Special feature of 1905 film network The Awakeing Age’s, yes, in recent years, the popular revolutionary historical film and television works, these actors all performed the same great man: Mao Zedong.They are all different in appearance, but why can they become so similar?

In addition to Chairman Mao, there are many heroic revolutionary heroes and great men’s images, which impressed everyone. How do different actors restore these revolutionary figures in their external images? Modeling and makeup design are indispensable.

"Film and television makeup is very different from our usual makeup. Film and television makeup is to complete the modeling task of the specified characters in the specified story and the specified plot. "

This issue of Behind the Scenes takes you into the movie "The Adaptation of Three Bays" to see Bai Lijun, a famous domestic film and television modeling expert and senior stylist of Bayi Film Studio, and reveals the film’s modeling and makeup design and the technical secrets of great people’s special makeup.

Revealing the Design of Three Bay Adaptations

Restore the clothing of the rebel army and the makeup of the soldiers of the workers and peasants revolutionary army

"Every little detail is exquisite and can’t be sloppy. After this comes out, the movie is real. "

In the program, Bai Lijun showed the audience the clothes of the rebel army designed in the film "Adaptation of Three Bays". The whole set of clothes included tops, breeches, belts, hats and red cloth armbands. "Zhou Enlai, He Long, Lu Deming and He Changgong all wore this kind of clothes." From the fabric, color and style to the detailed design of bags and buttons, they tried their best to restore the style of the clothes of that year.

In order to conform to the atmosphere of war, it is necessary to further make the clothes of the insurgents old when filming, such as adding some dust and blood.

Bai Lijun said, "There can be no falsehood, but it must be particularly true. When we make a historical film, we must understand that history and consult a lot of materials before we can shape the characters at that time. "

In addition to making old clothes, actors who play soldiers should also put on "war atmosphere makeup", which plays a vital role in all war movies. Without the rendering of these war atmosphere makeup, it is impossible to show the tragic war. "

The first step to create a war atmosphere makeup is to change the actor’s skin color and use a darker color to isolate him, showing the soldiers’ weather-beaten and dusty state on the battlefield.

The second step is to melt the wound, which is shown in detail by plasma made of special materials, which can be thick or thin.

The formula for making plasma includes a little white wine and red wine, a little brown sugar and a little food red. Bai Lijun said, "This kind of plasma has no harm at all, and it drops on the white shirt and is clean as soon as it is washed. This is the top secret recipe of our Bayi factory, and no one else can do it. "

The last step is to increase three-dimensional trauma, such as pasting "scars", deepening the color on the scars, turning bright red into cyan and purple, and making some scabbed scars. New injuries and old injuries exist at the same time, which enriches the overall effect and highlights the true state of soldiers injured in the war.

Bai Lijun said that the difficulty of making this makeup is that you can’t wear it when the movie changes scenes. "War atmosphere makeup is particularly difficult to pick up. This scar can’t be here today, and it will be there tomorrow. The blood left today is like this, and the blood left tomorrow is like that. "

Recalling the styling design of the film "Adapted from Three Bays", Bai Lijun revealed that it was raining all the time because it caught up with the rainy season during the location shooting, and a lot of atmosphere makeup melted as soon as it met water, which required them to constantly do makeup and makeup work in the rear, and encountered great difficulties.

How was Chairman Mao’s "Great Makeup" born?

Bai Lijun’s experience: Young makeup artists should pass the technical test.

In the category of film and television makeup, Bai Lijun thinks that it is the most difficult to make a great man’s special effect makeup. "The great man’s makeup requires a lot of technical content and is difficult, and it must have the makeup artist’s own design concept."

Bai Lijun was in charge of the first film with "Great Makeup" in Bayi Film Studio in 1982, which was also the second film starring the actor after becoming a special actor in Mao Zedong.

"Although Mr. Gu Yue looks like Chairman Mao, he doesn’t think his nose is similar enough." Bai Lijun used special makeup techniques to "shrink" Gu Yue’s nose, and at the same time strengthened the makeup effect of his nose, glued his eyes a little bigger, and affixed Chairman Mao’s signature mole, which made him closer to Chairman Mao’s appearance.

Later, in the series Armageddon and March, Chairman Mao in the film reached middle age, "his forehead became taller, his hairstyle changed, and his warts kept growing." According to the needs of the plot, according to the needs of different age groups, follow and adjust the shape. "

Nowadays, Mao Zedong’s special actors are led by the younger generation. Although the purpose of shaping Chairman Mao’s image as a great man remains unchanged, the performance style is changing, and the special effects technology of "Great Makeup" is constantly being updated and upgraded.

Bai Lijun said that the cosmetic material for making Chairman Mao’s "Great Makeup" headgear has been changed to imported high-definition yarn, and the material for "boils" has also been changed from latex to silicone rubber.

Especially in the production technology of headgear, it used to measure the size with a tape measure and make it on wood quinone. Since Gutian bugle, 3D scanning technology has been used to model it. "In the past, I was always afraid that the sideburns were not suitable, but now I have a head mold as the foundation, which is very accurate."

Bai Lijun began to learn modeling and makeup design from the model drama "The Red Lantern". At that time, she learned to hook a moustache and hooked more than 100 times the first time. After learning to hook a moustache, she learned to make a headgear.

"Just care about. Every one is very important. " Bai Lijun believes that every hair is very important whether making a beard or a headgear. If you don’t know these production methods, you can’t be a good makeup artist.

"You must work hard and learn this technology patiently. You can’t just order one from the outside and ask others to hook one. That’s not your creation. You have to do it yourself. This is a creative process. "

After 50 years in business, Bai Lijun said that she was proud that she had been doing this all her life. She reminded young makeup artists not to be eager for quick success and instant benefit, but to be down-to-earth. Even if the learning process is boring, they must learn the basic skills solidly and pass the exam. "Learning studio makeup may soon be a disciple, but film and television makeup is different, and it will take at least three or five years to understand."

The successful shooting of a film can’t be separated from the staff running around behind the scenes. Like directors, screenwriters, photographers, artists, recording and other positions, plastic makeup designers also hide behind the camera to help the actors shape their roles in the external image. Without them, the actors will lose their makeup and the "coat" of performance.

This group of behind-the-scenes heroes are unknown and worthy of respect. Bai Lijun also appealed to the audience: "I hope that when the film ends with subtitles, we must stick to the end. I hope that you can all see our names."

In most people’s cognition, only sallow and emaciated, short stature and skinny bones are malnutrition, while the 2016 Global Nutrition Report released recently believes that malnutrition should also include obesity, diabetes, heart disease, hyperlipidemia and other nutrition-related chronic diseases. Moreover, the global malnutrition problem is particularly serious, which has become the biggest factor causing the global disease burden.

Then, what exactly is malnutrition, why obesity and diabetes are also malnutrition, and how can people correctly supplement nutrition in life? The reporter interviewedYou Xiangmei, Director of Nutrition Department, No.117 Hospital of PLA.

The global malnutrition problem is severe.

According to the 2016 Global Nutrition Report, the global nutrition report conducted research in 129 countries and found that one out of every three people in the world was malnourished.

The World Food and Agriculture Organization reported in 2013 that 923 million people in the world were undernourished in 2007; The World Health Organization reported in 2013 that malnutrition is the leading cause of child death worldwide, accounting for 45% of all child deaths; The Cancer Nutrition and Support Committee of China Anti-Cancer Association reported that the malnutrition rate of cancer patients in China was as high as 67%.

Malnutrition can be divided into two types.

Director You introduced that malnutrition usually refers to malnutrition caused by insufficient intake, malabsorption or excessive loss of nutrients, but it may also include overnutrition caused by overeating or excessive intake of specific nutrients. In other words, malnutrition includes undernutrition and overnutrition.

There are three forms of malnutrition: energy deficiency malnutrition, protein deficiency malnutrition and mixed malnutrition. The causes of malnutrition are improper feeding in infancy; Poor eating habits; Some diseases affect appetite, hinder food digestion and absorption, and increase the consumption of the body.

There are two typical symptoms of malnutrition.

1 emaciation type

Short stature, emaciation, loss of subcutaneous fat, weakness and fatigue in children caused by serious shortage of thermal energy.

2 edema type

It is caused by the serious lack of protein, with edema all over, dry and atrophied skin, fragile hair, loss of appetite, large liver and frequent diarrhea.

Overnutrition is actually another "malnutrition symptom". Due to the improvement of living standards, people tend to choose meat or high-fat food, as well as exquisite and sweet food, and the intake of high-fiber food is too small, which leads to overnutrition.

Why do chronic diseases such as diabetes and heart disease belong to malnutrition?

Director You explained that people are no longer facing food shortage, but food quality problems. Many people think they are full, but in fact they are in a state of "latent hunger". They lack necessary trace elements, such as iron, vitamin A and iodine, so their health is not good. Many people suffer from diseases such as heart disease, stroke and diabetes due to long-term nutritional imbalance.

Furthermore, many people are getting less and less exercise, but they are eating more and more fast food or processed food, which is often too high in calories and lacks other nutrients.

　 　 　 　As we all know, infection is almost inevitable in plasma cell disorders (PCD). Although infection is not the diagnostic standard of PCD, it is a common complication of most patients, and it is also an important cause of morbidity and mortality of patients, especially the elderly and immunocompromised patients. In addition, the increasing use of immune-based therapeutic drugs in multiple myeloma may also have a negative impact on infection epidemiology and clinical outcome.

　 　 　 　According to statistics, the risk of infection in patients with multiple myeloma is 7 times higher than that in the general population; 10% patients died within 60 days after diagnosis, of which 45% were attributed to infection, and most of them occurred in elderly patients; 17% of multiple myeloma deaths are attributed to infection, and before the first-line treatment, the highest death rate was caused by infection (46%)1.

　 　 　 　In addition, infection, inflammation and pathogens also play an important role in the pathogenesis of plasma cell disease. Infectious cancer factors can be divided into direct carcinogens and indirect carcinogens. The former expresses viral oncogenes that directly contribute to carcinogenic transformation, while the latter causes cancer through chronic inflammation and acquired driven mutation. The mechanism of pathogen carcinogenesis includes pathogen as the direct carcinogen of PCD (oncogenic virus assists the occurrence of immunosuppressive cancers, such as Kaposi sarcoma and HHV8) and pathogen as the indirect carcinogen of PCD (chronic inflammation can enhance cell proliferation, and abnormal immune response to self-protein or infectious pathogens increases the risk of gene change and subsequent malignant transformation into dominant MM, Long-term antigen stimulation may also promote the genomic instability of MM by combining cytidine deaminase) and pathogens as regulators of PCD immune monitoring (Th17 cells secrete inflammatory cytokines, and promote the growth of plasma cells through IL-6-STAT3 signaling pathway and local activation of eosinophils; Intestinal flora may affect the response and toxicity of immunotherapy, and the principle is that immunosuppressants and broad-spectrum antibiotics can significantly change the composition of microbial flora.

　 　 　 　As mentioned earlier, infection is still the main cause of morbidity and mortality of patients with multiple myeloma due to the cumulative effect of disease, treatment and host-related factors. In view of the cumulative risk of infection in the whole course of disease, it is very important to prevent infection. At present, the best prevention strategies include vaccination against common pathogens, antibacterial prevention, infection management and immunoglobulin replacement for a small number of patients. But in general, there is no universally accepted infection prevention guideline for multiple myeloma.

　 　 　 　In view of this, the International Myeloma Association convened 36 experts from all over the world to jointly review the existing literature and guidelines, and solve the problems related to the infection risk and prevention of infectious complications of multiple myeloma under the emerging treatment background, including providing personalized infection treatment strategies for MM and providing suggestions for preventing infectious complications. The consensus statement was published in Lancet Haematology in February.

　

Panel1: Summary of key points and key suggestions for preventing infection in patients with multiple myeloma

Infection is still the main cause of death in patients with multiple myeloma. Risk factors include immunosuppression, treatment, age and complications (such as renal failure and weakness) of multiple myeloma.

The period with the highest risk of infection is the first 3 months after diagnosis and when treating relapsed/refractory multiple myeloma.

Patients with newly diagnosed multiple myeloma are more likely to prevent potential infections (such as Streptococcus pneumoniae or Haemophilus influenzae).

Most infections in patients with multiple myeloma are caused by viruses and bacteria: bacterial infections are most often manifested as pneumonia and bacteremia, while viral infections are usually manifested as seasonal viruses, especially influenza and herpes zoster.

If the risk of infection increases, levofloxacin can be considered for prevention (NCCN 2A level). Patients with seropositive herpes simplex virus and varicella-zoster virus (such as detection) can be given acyclovir for prevention. It is recommended that patients who receive proteasome inhibitors or targeted monoclonal antibodies, especially CD38 targeted monoclonal antibodies, use acyclovir for prevention (NCCN level 1). Trimethoprim-sulfamethoxazole can be reserve for patients at risk of pneumocystis Yersinia pneumonia, such as patients with relapsed/refractory myeloma or patients receiving large doses of dexamethasone (for example, ≥40 mg/ day, 4 days a week). For patients with sulfur allergy, alternative drugs such as dapsone (NCCN 2A grade) can be considered.

It is suggested that patients with multiple myeloma should be vaccinated with inactivated influenza vaccine (preferably with two doses of influenza vaccine, regardless of age) and inactivated streptococcus pneumoniae vaccine (PCV13) every year, and then with PPSV23(NCCN 2A level) every five years.

Only patients with multiple myeloma are recommended to be vaccinated with inactivated vaccine.

The ability to produce protective response after immunization depends on the immunosuppressive status of patients (such as disease load, remission status, cumulative immunosuppression of anti-tumor treatment) and vaccination time.

Conventional chemotherapy can significantly impair the response of patients with multiple myeloma to vaccination.

Vaccination at the early stage of the disease (such as MGUS or SMM), before the start of treatment or when it reaches remission can get the best protection.

Lenalidomide monotherapy can improve the response of patients with multiple myeloma to vaccination, provided that dexamethasone is not given at the same time. At present, the immune response after receiving new drugs (such as monoclonal antibody, panobinostat and Cellini) has not been determined.

After autologous hematopoietic stem cell transplantation, patients with multiple myeloma may lose immunity to the pathogens they were vaccinated against, and these patients should be vaccinated again 6-24 months after HSCT. The data show that it is safe and effective to inoculate recombinant herpes zoster vaccine after autologous HSCT. Therefore, it is recommended to inoculate recombinant herpes zoster vaccine after autologous HSCT (NCCN level 1).

It is suggested that the recombinant herpes zoster vaccine should be extended to all patients with multiple myeloma. It is suggested to continue to use varicella-zoster vaccine for prevention according to the indications, regardless of the vaccination status (NCCN 2b level).

It is suggested that patients with multiple myeloma should use passive immunization after being exposed to hepatitis A, chickenpox or measles (NCCN 2b).

It is suggested that close contacts of patients with multiple myeloma should be routinely vaccinated with inactivated vaccine, and patients should avoid close contact with live vaccine vaccinators as much as possible (NCCN 2A level).

Encourage the medical care and family members of patients with multiple myeloma to receive all designated immunization, especially seasonal influenza virus (NCCN 2A level).

Intravenous immunoglobulin is suitable for specific situations, such as life-threatening infection and IgG concentration below 400mg/dL with recurrent infection (NCCN 2A level).

For patients with multiple myeloma who go to infected epidemic areas, it is recommended to receive vaccines and antibacterial prevention at the destination, and consult infectious disease experts or medical institutions at the destination.

Risk factors of infection in patients with multiple myeloma

Disease factors

　 　 　 　Plasma cell diseases can increase the susceptibility of patients to viral and bacterial infections. The increased risk of infection in newly diagnosed patients with multiple myeloma is caused by the common global immune insufficiency paralysis in this patient, including the dysfunction of B cells in hypogammaglobulinemia, the destruction of global T cell diversity, and the significant changes in the functional activities of dendritic cells, natural killer cells and alternative complement pathways.

　 　 　 　Although rare at the time of seeing a doctor, neutropenia associated with bone marrow infiltration can also increase this risk. Of course, other related complications such as renal failure are also risk factors. The highest risk of infection is in the first 3 months after diagnosis and when treating recurrent or refractory multiple myeloma.

Therapeutic factors

Basic principles of treatment and infection of multiple myeloma

　 　 　 　The main therapeutic drugs for multiple myeloma are shown in Table 1. These treatments significantly improved the patient’s outcome, and transformed myeloma from a rapidly fatal disease to a chronic disease with multiple recurrences (usually successfully saved), but it also led to cumulative immunosuppression and increased risk of infection. For example, CD4 cell count drops sharply with the increase of chemotherapy cycle, which is closely related to opportunistic infection. Even so, the deep and lasting remission achieved by the combined regimen will generally lead to the reversal of immunosuppression and improvement of outcome.

　 　 　 　The immune status of patients with multiple myeloma is related to many factors, including the disease state and treatment stage (such as induction, remission vs first relapse vs relapse or refractory to multiple types and drugs), the degree of previous treatment (such as single drug vs multiline) and the intensity of treatment (such as triple induction vs autologous HSCT myeloablative regimen). In addition, continuous treatment can cause mild persistent immune suppression, which leads to an increase in the risk of infection. Immunomarkers can be used to determine whether there is cumulative immunosuppression.

glucocorticoid

　 　 　 　The cumulative dose of dexamethasone is an independent risk factor for infection, both during induction and at the time of recurrence. In addition, high-dose accumulation of glucocorticoids (for example, dexamethasone ≥40 mg/ day, 4 days per week) will increase the risk of opportunistic infections, including pneumocystis Yersinia.

Cytotoxic chemotherapy

　 　 　 　Conventional chemotherapy drugs, such as cyclophosphamide, etoposide, cisplatin, anthracyclines, melphalan and bendamustine, can enhance the susceptibility of patients with multiple myeloma to infection by inducing neutropenia, T cell dysfunction and mucosal damage.

Autologous hematopoietic stem cell transplantation

　 　 　 　High-dose melphalan combined with autologous HSCT (the standard treatment of multiple myeloma) can cause severe neutropenia and gastrointestinal mucositis, thus making patients susceptible to severe infections (mainly bacterial infections). Long-term T cell immune deficiency after implantation is rare, but it can increase the risk of virus infection and pneumocystis acquisition and reactivation.

Proteasome inhibitor

　 　 　 　Bortezomib can deplete T cells and impair viral antigen presentation, and the incidence of reactivation of varicella-zoster virus is relatively high in seropositive patients, so the preventive treatment of acyclovir is very important (NCCN grade 1). Caffezomib and Isazomib are also powerful immunosuppressants and have the same risk of viral infection. EMN guidelines recommend stopping antiviral preventive treatment 6 weeks after stopping PI. The authors suggest that the duration of prevention should be adjusted according to the immunosuppressive status of patients and whether other immunosuppressants (such as glucocorticoids or monoclonal antibodies) that increase the risk of varicella-zoster virus are given subsequently.

immunomodulator

　 　 　 　Lenalidomide and pomadomide can cause neutropenia, especially when combined with monoclonal antibodies. Granulocyte colony stimulating factor does not seem to reduce the risk of infection during lenalidomide treatment, but it can be used intermittently to fight chronic neutropenia. Thalidomide alone will not increase the risk of infection in patients with newly diagnosed multiple myeloma unless it is combined with other immunosuppressants (especially dexamethasone).

monoclonal antibody

　 　 　 　Monoclonal antibodies are associated with severe lymphopenia, pneumonia, reactivation of viral infection (especially varicella zoster virus) and opportunistic infection (especially in patients with intensive pretreatment). Clinical neutropenia may occur when monoclonal antibody is used in combination with lenalidomide or pomadumide, so the dosage needs to be adjusted. The neutropenia rate of CD38-targeted monoclonal antibody was higher than that of elotuzumab.

Selinexor in Cellini.

May lead to neutropenia-related infections.

New immune drugs

　 　 　 　Methods of targeting mature antigens of B cells, such as cell therapy (e.g. chimeric antigen receptor T cells), bispecific T cell adapters and antibody drug conjugates (e.g. belanatmab mafodotin), will all lead to immunosuppression because of targeting antibody-producing B cells and plasma cells. Therefore, patients with multiple myeloma who receive this treatment may need immunoglobulin replacement therapy. In addition, these treatments can lead to neutropenia and bone marrow suppression, and in some cases preventive use of antibiotics, antiviral coverage and antifungal coverage are needed.

Inhibition of bone resorption therapy

　 　 　 　Most patients with multiple myeloma will use anti-bone resorption therapy to prevent bone diseases. Rarely infected mandible and maxilla lead to jaw necrosis. Poor oral hygiene, poor denture fit, advanced periodontal disease and recent alveolar surgery are the risk factors. If infection occurs in the case of jaw necrosis, it is suggested to start using broad-spectrum antibiotics active against anaerobic bacteria, including actinomycetes spp46 and drug-resistant Bacteroides fragilis, such as clindamycin, carbapenems or β -lactamases or β -lactamase inhibitors. If the response to antibiotics is slow or unsatisfactory, or osteomyelitis is suspected, it is suggested to biopsy the lesion through staining and culture. Limited debridement may be required at this time; However, for refractory multiple myeloma, surgical resection should be reserve.

Kyphoplasty and vertebroplasty

　 　 　 　Vertebral kyphoplasty and vertebroplasty are generally well tolerated and are essential to control the pain associated with multiple myeloma of the vertebral body. In rare cases, spondylitis caused by Gram-positive bacteria (such as Staphylococcus aureus) can develop and evolve into paravertebral abscess. It is suggested that antibacterial prevention should be used 24 hours before operation and during operation when planning such operations for patients with high risk of infection.

Host factor

　 　 　 　Multiple myeloma mainly affects elderly patients with aging immune system (age ≥65 years old), whose antibody responses to pneumococcal and influenza vaccines are reduced, and the possibility of clinically significant complications is increased.

What factors can predict early and severe infection in MM patients?

　 　 　 　A considerable number of newly diagnosed patients with multiple myeloma will die prematurely before they can benefit from effective treatment, and the main reason is infection. Predictors of early and severe infection in newly diagnosed patients with multiple myeloma include high tumor load (ISS score II–III), abnormal increase of IDH, poor physical fitness and renal insufficiency.

　 　 　 　The prognosis model developed in 2018 divided patients into high-risk (infection rate was 24% during tertiary treatment) and low-risk (infection rate was 7%). In addition, men and high tumor load (ISS scores II-III and IDH increased) were risk factors for pneumonia, while high tumor load (ISS scores II-III) and increased serum creatinine concentration could independently predict the risk of sepsis.

Immune reconstruction after successful treatment

　 　 　 　Effective control of multiple myeloma can usually improve immunity. Immune reconstruction after autologous HSCT may provide an opportunity window for vaccination that may produce protective response.

Infection spectrum of patients with multiple myeloma

　 　 　 　With the introduction of new therapy, the types, severity and time of infection complications in patients with multiple myeloma have changed, and the complications mostly occur in the first few months of induction therapy and reach the peak in 4-6 months. The pathogens are mainly Gram-positive bacteria (such as coagulase-negative Staphylococcus, Staphylococcus aureus, Streptococcus pneumoniae and Enterococcus faecalis) and Gram-negative bacteria (such as Haemophilus influenzae and Escherichia coli). In addition, tracheobronchitis and pneumonia caused by respiratory viruses (such as influenza and respiratory syncytial virus) are also common.

　 　 　 　Infection can reach its peak again during the treatment of recurrent diseases, so the immunity of patients with multiple myeloma is seriously damaged. In addition, the uncommon infections in patients with multiple myeloma include invasive pulmonary aspergillosis and viral infections, such as cytomegalovirus, hepatitis B virus (HBV) or hepatitis C virus (HCV) and parvovirus B19, and tuberculosis and other opportunistic infections are also rare.

Prevention and treatment strategies of multiple myeloma infection

　 　 　 　The key to reduce the burden of infection complications in patients with multiple myeloma is to carry out comprehensive staging in diagnosis and recurrence, so as to adjust individualized treatment strategies according to risks. Staging includes collecting clinical history (especially vaccination and past infection), checking physical health and evaluating the functional status of patients over 65 years old (that is, healthy, moderately healthy or weak).

　 　 　 　It is suggested to optimize the dose intensity in patients with high risk of severe infection (that is, high disease load or increased IDH) and clinically significant complications (especially renal insufficiency). In addition, it is suggested that the preventive strategies of immunosuppression state should be considered when using various previous treatment lines to treat recurrent patients, including vaccination against common pathogens (Table 2), paying attention to the time of vaccination (panel 2), and educating patients and nurses to take measures to reduce exposure to potential pathogen sources, including traveling (panel 3). In addition, it is suggested to carry out risk-adaptive antibacterial prevention in a small number of patients (Table 3), and consider immunoglobulin replacement and possible myeloid growth factor support. Careful monitoring during high immunosuppression therapy and after autologous HSCT may predict the risk and type of infection.

　

　

Panel 2: Vaccination Opportunity of Inactivated Vaccine for Multiple Myeloma Patients

MGUS, SMM or asymptomatic MM

These patients can respond to immunization.

Vaccination may be more effective for the following patients: MGUS with low concentration of M protein and SMM may need to be vaccinated repeatedly to be effective.

MM in need of treatment

MM status is related to insufficient immune response, and the precautions are as follows:

Inoculate as soon as possible

Vaccinate patients 14 days before starting treatment (preferred)

In partial remission (especially immune reconstruction)

Good remission is usually associated with immune reconstitution, with unaffected immunoglobulin returning to normal.

Inhibition of uninvolved immunoglobulin is a risk factor for insufficient response to repeated vaccination.

When the immunomodulator is used alone or in combination with proteasome inhibitor,

Immunomodulators alone or in combination with proteasome inhibitors are associated with increased possibility of serological response.

Maintenance therapy with a single immunomodulator (lenalidomide) can enhance immunity to some pathogens, but it will not enhance immunity when combined with dexamethasone.

Non-influenza respiratory tract infection in influenza season

Avoid immunization for the time being, because the response to the vaccine may not be sufficient, and the overall infection risk of patients with active multiple myeloma may increase.

During routine chemotherapy

Avoid vaccination until the disease is controlled, because the response of cancer patients may be insufficient, and the higher the load of multiple myeloma, the higher the risk of infection.

When high-dose myeloablative therapy combined with autologous HSCT

Avoid vaccination before autologous HSCT, because the response to the vaccine cannot be sufficient.

Patients were replanted 6-12 months after autologous HSCT, because patients would have severe humoral and cell-mediated immune deficiency after autologous HSCT, but the immune reconstruction was rapid.

The recovery of ?CD4 cell count is a marker of immune recovery.

Recurrent/Refractory Multiple Myeloma

Avoid immunization during active diseases, because the response to vaccines cannot be sufficient, especially in patients who have received several lines of treatment in the past.

Cumulative immunosuppression after extensive treatment can increase the net state of immunosuppression and the risk of severe infection.

The possibility of vaccine response decreases in descending order. There are no vaccine response data for monoclonal antibodies, Papi and Cellini.

　

Panel 3: Travel Notes for Patients with Multiple Myeloma

To evaluate the immune status, it is not recommended for patients with severe immune dysfunction to travel to potentially severe infection epidemic areas.

Update the patient’s immune status and verify the drug.

Patients are advised to use general protective measures, insect repellents, mosquito nets and protective clothing to minimize the risk of mosquito bite infection (such as malaria, dengue virus, Chikungunya fever, Zika virus and West Nile encephalitis) and ticks (such as Borrelia Lyme disease, tick-borne encephalitis and relapsing fever).

Provide relevant country-specific and region-specific vaccination according to the risk, including drugs against Neisseria meningitidis, hepatitis A virus and hepatitis B virus, and poliovirus.

Provide antibacterial prevention in specific countries and regions, including malaria and tuberculosis.

Provide antibiotics (such as fluoroquinolones or macrolides) that can be used for self-administration for persistent diarrhea with fever (> 48h), and actively encourage patients to seek medical treatment when the situation occurs.

Immunoglobulin seronegative and high-risk groups of hepatitis A virus infection should consider hepatitis A immunoglobulin, including those who go to areas where hepatitis A virus is prevalent.　

Educate patients and nursing staff as follows:

Understand specific risk areas, focusing on malaria and tuberculosis.

Avoid raw food, eat peelable fruits and vegetables, prevent travelers from diarrhea, and only drink bottled or boiled drinks.

Avoid bad cooking of meat

Avoid close contact or long-term contact with crowded tuberculosis patients and closed environments (such as hospitals or clinics); If you plan to travel, check for tuberculosis (skin or blood) before leaving and after returning home.

Avoid activities that increase the risk of fungal infection (such as digging) to prevent endemic fungal pneumonia.

Detection of infection

　 　 　 　Fever is regarded as the most important sign of infection in patients with multiple myeloma. Patients without fever should be highly suspicious, especially those receiving corticosteroids. It is suggested to obtain the vaccination history, past infection, virus serum status, disease status, recent treatment and related complications of patients to determine possible pathogenic pathogens, and of course, local epidemiology should also be considered.

　 　 　 　It is suggested that patients with febrile neutropenia and patients with infection should start empirical broad-spectrum antibiotic treatment when they are diagnosed and tested. In addition, it is suggested to choose drugs active against Streptococcus pneumoniae and Gram-negative pathogens, especially Escherichia coli and Pseudomonas aeruginosa. Antibacterials should be recommended according to clinical, imaging and microbiological results.

　 　 　 　Diagnostic tests of infection include complete blood cell count and classification, liver and kidney function examination, electrolyte examination and microscopic examination or culture of blood and other parts according to clinical indications. It is also recommended to obtain rapid pneumococcal antigen detection in urine, blood and cerebrospinal fluid samples when there are indications.

　 　 　 　For patients with respiratory manifestations, it is suggested to scan the chest and sinuses with CT, collect nasopharyngeal samples for respiratory pathogens detection, microscopic examination or culture of respiratory secretions, and detect Legionella urine antigen. For persistent fever with lung infiltration for more than 3-4 days, it is suggested to consider bronchoscopy combined with bronchoalveolar lavage or bronchial biopsy to determine conditional pathogens. Fungal infection markers, such as galactomannan and β-glucan, can be used when there are clinical indications.

　 　 　 　For abdominal symptoms and diarrhea, it is recommended to start using broad-spectrum antibiotics immediately. In addition, it is suggested that the infection of Clostridium difficile can be confirmed by stool samples. If it can be confirmed, it is suggested to add oral vancomycin because its activity is better than metronidazole. There is evidence that fidamycin is at least as effective as oral vancomycin for the confirmed Clostridium difficile infection, and may be related to the lower risk of recurrent infection, especially when it is used as extended pulse therapy for 25 days. Empirical treatment should be considered when severe colitis exists, especially when the infection index of Clostridium difficile is suspected to be high, until the diagnosis and detection results are obtained.

　 　 　 　It is suggested that the abdomen and pelvis should be scanned by CT to find severe focal signs and symptoms. According to local epidemiology, it is suggested to obtain PCR of fecal culture and intestinal pathogens, as well as other tests of intestinal parasites (such as Giardia and Cryptosporidium).

　 　 　 　If the fever persists and the cause is unknown, further diagnostic imaging examination is suggested to determine the existence, location and degree of infection. Once an infection cause is ruled out, other causes of fever diseases related to multiple myeloma should be considered, such as tumor fever, venous thromboembolism, adrenal insufficiency or implantation syndrome synchronized with bone marrow recovery after autologous HSCT. Other patients with stable clinical signs should consider non-infectious causes if their fever persists after the best exploration and antibacterial treatment. Tumor fever should be considered when the concentration of serum LDH and other markers of multiple myeloma in blood and urine increases abnormally. Fever associated with venous thromboembolism should be excluded by Doppler or ultrasound examination of limbs, ventilation or perfusion scanning or CT scanning, especially in patients at risk of venous thromboembolism, such as patients receiving immunomodulatory imide drugs or recombinant erythropoietin, patients with restraint (due to fracture or spinal cord compression) or patients with other known risk factors. Patients with fever of unknown origin should always consider drug-induced fever. Fever under the background of new immunization strategy may also be a symptom of cytokine release syndrome and should be treated appropriately.

Consider infection treatment according to the disease state and treatment period.

Newly diagnosed MM

　 　 　 　Because pneumococcus is a common pathogen when multiple myeloma is first diagnosed, it is suggested that pneumococcus vaccine should be inoculated as soon as possible (Table 2), and if there is fever or other infection, broad-spectrum antibacterial drugs active against pneumococcus should be given.

Induction treatment period of newly diagnosed MM

　 　 　 　A considerable proportion of newly diagnosed patients with multiple myeloma died in the first few months after diagnosis, mainly due to infection complications, so we should actively manage them by starting fast active drugs and treating complications related to multiple myeloma, such as renal failure. Levofloxacin can be considered for antibacterial prevention in the first 3 months of treatment, especially in patients with high risk of early infection, although its benefits are still unknown under the current triple and quadruple treatment strategies (NCCN 2A level). The benefits of using fluoroquinolones (such as levofloxacin) should be weighed, because these drugs are rarely associated with tendinopathy with rupture, especially Achilles tendon. The risk factors of tendinopathy include old age (> 60 years old), concomitant use of corticosteroids and renal insufficiency. Table 3 lists other antibacterial prevention suggestions according to disease stages and anti-tumor treatment types. The use of quinolones should be considered according to the degree and duration of neutropenia.

Autologous HSCT consolidation period

　 　 　 　Multiple myeloma patients with autologous HSCT are at risk of serious infection (mainly bacterial infection), so it is suggested to use antibacterial drugs to prevent it, and the immune deficiency after autologous HSCT may lead to clinically significant infection. It is recommended to monitor infection and prevent pneumocystis carinii for 3 months and prevent herpes simplex virus or varicella zoster virus for 1 year (NCCN 2A level) according to global guidelines. Antibacterial prevention is not a routine practice in all transplant centers around the world. Although its use reduces the incidence of fever and bloodstream infection, it does not translate into a reduction in mortality. Antibacterial prevention also needs to consider the risk of drug resistance.

Maintenance treatment period

Severe infection during maintenance treatment is mainly due to neutropenia, but the risk is low and the mortality rate is lower than 1%.

Treatment period of recurrent MM

　 　 　 　Patients with recurrent and refractory myeloma are at high risk of life-threatening broad-spectrum pathogen infection, including bacterial and viral infections (such as herpes simplex virus or varicella-zoster virus, cytomegalovirus, HBV and HCV). Fungal pneumonia, including invasive pulmonary aspergillosis and pneumocystis, may also occur.

Infection screening

　 　 　 　For relapsed/refractory MM with positive cytomegalovirus serum reaction, it is suggested to detect HBV (cytomegalovirus antigenemia or quantitative PCR) or circulating HBV DNA(NCCN 2B grade) before starting treatment. Patients with high suspicion suggest that serum Aspergillus galactomannan antigen should be tested before symptoms appear to detect invasive pulmonary aspergillosis. The effect of serum (1,3)-β-D- glucan on invasive pulmonary aspergillosis is not clear, but it may be a useful auxiliary means to diagnose pneumocystis disease.

　 　 　 　According to the patient’s serum status, HBV reactivation can lead to severe complications and death in patients with multiple myeloma, and usually occurs after autologous HSCT. In addition, HBV reactivation was rarely observed after treatment with CD38-targeted monoclonal antibody. It is suggested that patients should be managed according to their HBV serum status and the type and duration of immunosuppressive therapy (Table 3). It is suggested that antiviral prevention should be used for patients with HBV reactivation or high risk of disease, or early preemptive treatment should be used for patients with low risk. Only in the presence of clinically relevant diseases (such as cytopenia and cytomegalovirus diseases) can cytomegalovirus disease be treated.

　 　 　 　The effect of chronic HCV on the course of multiple myeloma is not very clear, but it is known that it will be reactivated after chemotherapy, and it may be necessary to reduce or stop taking drugs, but acute liver failure or death is not the outcome of chronic HCV infection. It is suggested that HCV serum status should be evaluated when multiple myeloma is diagnosed, and interferon α-free treatment schemes, such as direct antiviral drugs (such as sofebuvir, cimetivir and redipavir), should be used during the whole treatment period, and serum alanine aminotransferase and HCV viral load should be closely monitored.

Before stem cell mobilization, it is very important to monitor HCV viral load and treat infection. Chronic HCV infection may cause three-line hemocytopenia and lead to poor mobilization. Cancer patients may rarely lose HCV seropositivity, so it is suggested to measure HCV viral load when the patient’s serum status is unknown. It is recommended to seek help from infectious disease experts in complex situations.

vaccine

General principle of multiple myeloma vaccine

　 　 　 　Although the response to vaccination is usually very small, partial protection may still reduce the infection rate and hospitalization rate, but it should also be noted that the duration of benefit is unknown and may vary with vaccination time. Although the safety of most vaccines has not been tested in patients with multiple myeloma, inactivated vaccines such as influenza and pneumococcal vaccines are safe. Patients with multiple myeloma strongly recommend vaccination against Streptococcus pneumoniae and seasonal influenza virus, as well as vaccines necessary for local epidemiology (such as HBV). Splenectomy patients are also vaccinated against Haemophilus influenzae.

　 　 　 　It is suggested that patients with multiple myeloma should be vaccinated with pneumococcal vaccine, including one dose of pneumococcal conjugate vaccine (PCV13) and another dose of polysaccharide vaccine (PPS V23) at least 8 weeks later. If the patient has been vaccinated with PPSV23 before, it is recommended to be vaccinated with PCV13(NCCN 2A grade; Table 2). The protective titer of pneumococcus is unknown, which may vary according to serotype. If a breakthrough pneumococcal infection occurs after vaccination, it is suggested to try to identify the serotype of the strain to report the non-response to the vaccine (if possible). The purpose of serotype identification is to determine whether this serotype is included in the PCV13 vaccine-for example, patients vaccinated with PCV7 or PCV10. In this case, consider vaccination with PCV13 vaccine.

　 　 　 　Because the antibody response of pneumococcal vaccine may not be ideal, it may be useful to prolong antibiotic prevention in patients with recurrent pneumococcal infection and patients with invasive pneumococcal disease. Although penicillin G is the standard treatment, antibiotics based on strain sensitivity and local drug resistance patterns that have caused invasive pneumococcal diseases in the past can be used. Fluoroquinolones (such as levofloxacin), azithromycin or second-generation penicillin or cephalosporin are reasonable substitutes (NCCN 2B grade). (panel 1)。

　 　 　 　Vaccination against seasonal influenza virus is necessary because cancer patients are at increased risk of infection and death. It is suggested that patients with multiple myeloma be vaccinated with two doses of inactivated tetravalent influenza vaccine instead of standard vaccine, regardless of age (NCCN 2A level). The initial dose should be given as early as possible in the flu season, and the second high-dose booster vaccination should be carried out one month later. For patients with inactivated influenza vaccine in serious adverse events, two doses of recombination vaccines can be considered.

　 　 　 　It is generally recommended to vaccinate against HBV, especially for patients with high risk of virus infection (NCCN 2A level). Other potentially useful vaccines for patients with multiple myeloma include vaccines against Neisseria meningitidis, tetanus, diphtheria and pertussis, and inactivated poliovirus vaccines.

　 　 　 　Because of the increased risk of reactivation of varicella-zoster virus during the treatment of multiple myeloma, vaccination should be considered to reduce the risk of infection and post-herpetic neuralgia. It is suggested that patients with multiple myeloma should be vaccinated with recombinant herpes zoster vaccine instead of live herpes zoster vaccine, because it is safe (that is, non-live vaccine) and can provide higher and longer-lasting prevention of herpes zoster, thus preventing post-herpetic neuralgia (NCCN grade 1). However, even after vaccination, patients treated with proteasome inhibitors or CD38-targeted monoclonal antibodies should continue to receive acyclovir preventive treatment, because the degree of protection provided by vaccination is difficult to assess (NCCN 2A level). Specifically, patients with multiple myeloma have different immune responses and are highly dependent on their immune status, so they cannot be prevented by vaccination alone. For patients who have been vaccinated with live herpes zoster vaccine in the past, it is recommended to vaccinate with 2 doses of recombinant herpes zoster vaccine at least 8 weeks after vaccination.

　 　 　 　Generally speaking, due to the lack of safety or efficacy data, live vaccines are not recommended for patients with multiple myeloma. For patients with MGUS and SMM, considering their relatively healthy immune system, we can consider vaccination with live vaccine. Measles, mumps and rubella vaccines and live herpes zoster vaccine have been used after HSCT. If patients are in remission, they can be considered for use under certain circumstances.

Vaccination of non-immune close contacts

　 　 　 　Patients with multiple myeloma, especially those receiving treatment, may not be able to produce immune response to pathogens, and close contacts vaccinated with inactivated vaccine may also provide group immunity for patients. Therefore, according to vaccination history, age and exposure history, it is suggested that non-immune close contacts should be vaccinated with vaccines that are usually suitable for individuals with normal immune function, and it should be emphasized that inactivated vaccines (NCCN 2A level) should be used. Encourage the medical care and family members of patients with multiple myeloma to receive all designated immunization, especially seasonal influenza virus immunization.

Immunoglobulin substitution

　 　 　 　Immunoglobulin replacement can be administered intravenously, subcutaneously or intramuscularly. Intravenous immunoglobulin is recommended for patients with plateau multiple myeloma who have hypogammaglobulinemia and recurrent bacterial infection and have no response to pneumococcal immunization. However, immunoglobulin substitution supports the scarcity of contemporary data, high cost, limited availability and the possibility of complications (including acute renal failure and cardiovascular events). It is suggested that replacement therapy should be limited to patients with serum IgG concentration below 400 mg/dL and severe and recurrent infection caused by capsular bacteria (or other pathogens reasonably thought to be caused by hypogammaglobulinemia), even with antibacterial prevention and immunization (NCCN 2A level).

　 　 　 　Another potential consideration includes patients with insufficient antibody production, especially pneumococcal vaccine. Using immunoglobulin replacement therapy can only benefit patients infected with pathogens, which may respond according to the specific antibody titer against the target pathogen in intravenous immunoglobulin preparation; For example, it is used for infection caused by severe parvovirus B19 in patients with multiple myeloma.

　 　 　 　When planning to use intravenous immunoglobulin, it is necessary to evaluate the patient’s immune status and infection history (especially recurrent infection), and carry out laboratory examination of immune parameters (including specific antibody response) to determine the patients who can benefit from early intravenous immunoglobulin intervention.

　 　 　 　Immunoglobulin infusion is usually well tolerated, and most reactions are frequency dependent. But serious complications may also occur, including acute renal failure and rare cardiovascular events (such as myocardial infarction, stroke or venous thromboembolism). It is suggested to give standard preoperative medication to reduce the severity of infusion-related reactions, and to replenish water before infusion, especially in patients with hyperviscosity, risk factors of renal complications and receiving sucrose-containing preparations. It is suggested that intravenous immunoglobulin therapy should be started at a slow rate of 0.01 mL/kg/min and gradually increased to a maximum rate of 0.08 mL/kg/min according to the tolerance. If the serum IgA concentration cannot be detected, it is recommended to use intravenous immunoglobulin to remove IgA.

Post-exposure prevention of immunosuppressed MM patients

　 　 　 　 Immunoglobulin prevention may have protective effect on patients with multiple myeloma who are immunosuppressed after exposure to chickenpox, herpes zoster and hepatitis A (NCCN 2B grade). Serious diseases after exposure to herpes zoster, especially chickenpox, are very high, so it is very important to determine the risk level. The infectious stage begins 1-2 days before the rash occurs, so patients can appear several days after exposure. Except the recipients of autologous HSCT, all immunocompromised patients with a history of chickenpox infection can be considered immune. For patients with no history of varicella infection, risk assessment includes determining the susceptibility and exposure duration of patients. Risk factors include recent use of proteasome inhibitors, previous vaccination against varicella, severe immunosuppression, and close face-to-face or indoor contact for more than 1 hour. Post-exposure prevention depends on varicella-zoster immunoglobulin, ideally within 96 hours after exposure, but the benefit can be extended to 10 days. If immunoglobulin of varicella-zoster is not easily available, it is recommended to use acyclovir after exposure. The typical incubation period of chickenpox is 14-16 days. However, since the immunoglobulin of varicella zoster may prolong the incubation period, it is recommended to monitor the evidence of varicella for up to 28 days after exposure in the recipients of this therapy.

　 　 　 　For patients with multiple myeloma who travel to areas where hepatitis A virus is prevalent, it is recommended to give 0.02 mL/kg of hepatitis A immunoglobulin within 2 weeks of travel, and give the initial dose of hepatitis A vaccine. It is recommended to give a dose of hepatitis A immunoglobulin to patients with known exposure.

　 　 　 　For patients who have not been vaccinated against HBV or whose anti-HBV titer is less than 10 IU/L after vaccination, it is suggested to use tenofovir or entecavir for prevention to avoid the need for HBV immunoglobulin.

　 　 　 　Patients may occasionally need tetanus immunoglobulin 138 or human rabies immunoglobulin 139 after specific high-risk exposure. For patients at risk of respiratory syncytial virus infection in virus season, it is not recommended to use intravenous immunoglobulin or palizumab, that is, humanized monoclonal antibody against respiratory syncytial virus F glycoprotein.

Myeloid growth factor

　 　 　 　Prophylactic granulocyte macrophage colony stimulating factor (granulocyte colony stimulating factor is better) is recommended for patients without fever, and the risk of fever and neutropenia in these patients is at least 20%(NCCN 2A grade). The decision on whether to use granulocyte colony stimulating factor to prevent treatment delay (such as treatment delay related to lenalidomide) should be considered individually. Chronic neutropenia occasionally needs the support of growth factors.

references

1. Jessica Caro, Marc Braunstein, Louis Williams, et al. Inflammation and infection in plasma cell disorders: how pathogens shape the fate of patients. Leukemia . 2022 Feb 2. doi: 10.1038/s41375-021-01506-9.

2. Noopur S Raje, Elias Anaissie,Shaji K Kumar, et al.Consensus guidelines and recommendations for infection prevention in multiple myeloma: a report from the International Myeloma Working Group. Lancet Haematol . 2022 Feb; 9(2):e143-e161. doi: 10.1016/S2352-3026(21)00283-0

　　Building a new development pattern is an original achievement of great theoretical and practical significance in the supreme leader’s economic thought. In April, 2020, General Secretary of the Supreme Leader proposed at the meeting of the Central Financial and Economic Committee to build a new development pattern with the domestic big cycle as the main body and the domestic and international double cycles promoting each other. The Fifth Plenary Session of the 19th CPC Central Committee systematically expounded the construction of a new development pattern, and the 20th CPC National Congress made important strategic arrangements to accelerate the construction of a new development pattern and focus on promoting high-quality development. Recently, during the second collective study in the Political Bureau of the Communist Party of China (CPC) Central Committee, General Secretary of the Supreme Leader made a profound exposition and put forward clear requirements on speeding up the construction of a new development pattern and enhancing the security initiative of development, which provided a powerful ideological motivation and scientific action guide for opening up a new look with confidence on the new journey.

　　Building a new development pattern is related to the overall situation and has far-reaching influence.

　　Building a new development pattern is a strategic decision based on achieving the goal of the second century, overall development and security, and a strategic deployment to grasp the initiative of future development, which is of great and far-reaching significance for building a socialist modernization power in an all-round way and promoting the great rejuvenation of the Chinese nation with Chinese modernization.

　　First, focusing on coordinating the "two overall situations" is related to achieving the goal of the second century as scheduled. At present, we are closer, more confident and capable of achieving the goal of the great rejuvenation of the Chinese nation than at any time in history. At the same time, the world’s unprecedented changes in a hundred years have accelerated its evolution, and the global economic map and governance pattern are facing reshaping. We are now in a time when it is more urgent to wander in the middle of a boat and steeper when people reach the middle of a mountain road. It is a time when it is more difficult and more dangerous to advance, but if you don’t advance, you will retreat and have to enter. It is a strategic choice to realize China’s economic modernization to put the development foothold at home, smooth the domestic big cycle and promote the mutual promotion of domestic and international double cycles. Only by speeding up the construction of a new development pattern, stabilizing the basic economic disk, and promoting the effective improvement of quality and reasonable growth of quantity can we continuously enhance the viability, competitiveness, development and sustainability of China’s economy and successfully achieve the goal of building a socialist modern power in an all-round way.

　　Second, focusing on expanding domestic demand as a whole and deepening supply-side structural reform is related to consolidating the foundation of China’s economic development. China has a super-large domestic market, the most complete industrial system, perfect supporting capacity and rich human resources. Building a new development pattern is conducive to cultivating a complete domestic demand system, improving the adaptability and flexibility of the supply structure, making the supply system better adapt to the changes in the demand structure, and achieving a leap to a high level of supply and demand balance. Only by accelerating the construction of a new development pattern, organically combining the implementation of the strategy of expanding domestic demand with deepening the structural reform on the supply side, forming a higher level dynamic balance of demand pulling supply and supply creating demand, and realizing a virtuous circle of the national economy, can we continuously improve the quality of economic development, consolidate the foundation of economic development, cross the important barrier of economic development in big countries, and continuously enhance China’s economic strength, scientific and technological strength and comprehensive national strength.

　　Third, focusing on overall development and security is related to enhancing the security and stability of development. At present, the epidemic situation in the century has a far-reaching impact, the anti-globalization trend is on the rise, unilateralism and protectionism are obviously rising, the recovery of the world economy is weak, local conflicts and turmoil are frequent, global geopolitical and security risks are increasing, and the uncertainty and instability of China’s development external environment are obviously rising. Strengthening the security and stability of development has become a top priority. Only by speeding up the construction of a new development pattern, breaking through the blocking point of the national economic cycle, coping with the instability of the international cycle with the reliability of the domestic big cycle, realizing the self-reliance of high-level science and technology, and improving the quality and level of the domestic and international double cycle, can we firmly hold the bottom line of safe development and ensure the stability and far-reaching development of China’s economic giant.

　　Fourth, focusing on coordinating international cooperation and competition is related to firmly grasping the initiative in future development. At present, the pattern of international economic cycle is accelerating reconstruction, the global division of labor system is deeply adjusted, and the competition is becoming increasingly fierce. Accelerating the construction of a new development pattern is an active choice to reshape China’s new advantages in international cooperation and competition based on the characteristics of super-large-scale economies. Only by speeding up the construction of a new development pattern, participating in the international division of labor more effectively, actively participating in shaping the supply chain value chain of the international industrial chain, and improving the global resource allocation ability in the cooperative competition, can we reach a broad consensus, carry out in-depth cooperation, cultivate and enhance China’s new advantages in international cooperation and competition, and win the strategic initiative in the open development.

　　Building a new development pattern, making solid progress and achieving results

　　Under the scientific guidance of the supreme leader’s economic thought, we have taken the initiative to build a new development pattern, the ideological consensus has been continuously condensed, the ability level has been continuously improved, the work foundation has been continuously consolidated, the policy system has been continuously improved, the leading role of the domestic grand cycle has been further strengthened, and the benign interaction and mutual promotion between the domestic and international double cycles have accelerated, effectively supporting the stable, healthy and sustainable development of China’s economy and laying a solid foundation for achieving high-quality development.

　　First, consumer demand continues to be released. In recent years, by improving consumption capacity, improving consumption conditions and creating consumption scenarios, China’s consumption potential has been released rapidly, and the traction and driving effect of consumption on the economic cycle has continued to emerge. China has become the second largest consumer market in the world, and the total retail sales of social consumer goods will reach 44 trillion yuan in 2022. The consumption structure has been accelerated and upgraded, and mass consumption such as automobiles is in the ascendant. Service consumption is accelerating expansion and upgrading, and new consumer demand such as online consumption and green consumption is effectively stimulated. During the Spring Festival of 2023, the sales revenue of consumer-related industries in China increased by 12.2% year-on-year, the domestic tourism revenue increased by 30% year-on-year, and the movie box office exceeded 6.7 billion yuan, ranking second in the box office of China Film History during the Spring Festival. While consumer demand continues to be released, China’s consumer prices have maintained a stable trend. In the past 10 years, the increase in consumer prices has stabilized at a low level of around 2%, creating good conditions for expanding consumption.

　　Second, effective investment continues to expand. Focusing on high-quality development and comprehensively improving quality and efficiency, China’s total investment has continued to grow steadily and the investment structure has continued to be optimized. In 2022, when the investment in real estate development decreased by 10% year-on-year, China’s fixed assets investment increased by 5.1% year-on-year, exceeding 57 trillion yuan, of which the investment in manufacturing industry increased by 9.1% year-on-year and the investment in high-tech manufacturing industry increased by 22.2% year-on-year, achieving a double improvement in investment scale and quality. Investment in infrastructure construction has been promoted in an orderly manner, major projects such as Wudongde and Baihetan Hydropower Station have been put into operation, and major projects such as sichuan-tibet railway and "Counting East and Calculating West" have been fully implemented, which has played a leading role in the economic cycle. Driven by the reform of investment and financing system, the investment environment has been continuously optimized and investment confidence has been further enhanced.

　　Third, science and technology have taken solid steps towards self-reliance. China’s scientific and technological strength is moving from quantitative accumulation to qualitative leap, from point breakthrough to system capability improvement. The overall strength of science and technology has been significantly enhanced, and the ranking of global innovation index has been continuously improved, ranking 11th in the world in 2022. The investment in science and technology has greatly increased. The total social R&D expenditure has exceeded 3 trillion yuan, ranking second in the world, and the R&D intensity has increased to 2.55%, which is close to the national average of the Organization for Economic Cooperation and Development (OECD). The strategy of rejuvenating the country through science and education and strengthening the country through talents has been solidly promoted, and the total number of R&D personnel ranks first in the world. The innovation platform system has been continuously improved, the construction of the State Key Laboratory has been accelerated, and Beijing, Shanghai and Guangdong-Hong Kong-Macao Greater Bay Area rank among the top 10 global science and technology clusters. The reform of the science and technology system has been deepened, and the innovation system and mechanism have been accelerated. Take the initiative to design and take the lead in launching international large-scale scientific plans and large-scale scientific projects, and establish a science and technology partnership plan. The "circle of friends" for scientific and technological innovation and open cooperation is growing.

　　Fourth, the modern industrial system is becoming more and more perfect. The pace of high-end development, digital empowerment and green transformation of China’s industries has accelerated, and the industrial basic capacity and industrial modernization level have improved rapidly. In 2022, the added value of high-tech manufacturing and equipment manufacturing increased by 7.4% and 5.6% respectively, which played a leading role in the transformation and upgrading of manufacturing industry. With the rapid development of digital economy, industrial digitalization and digital industrialization are accelerating. Industrial Internet has been applied to 45 categories of national economy, covering R&D, design, manufacturing and marketing services. The "green content" of industrial development has been significantly improved, and green industry has become a new kinetic energy for economic growth. The total installed capacity of renewable energy exceeds 1.2 billion kilowatts. The new energy automobile industry ushered in explosive growth, and its production and sales volume ranked first in the world for eight consecutive years.

　　Fifth, the pace of coordinated development between urban and rural areas has accelerated. Consolidate and expand the achievements of poverty alleviation and effectively link with rural revitalization, the two-way flow of urban and rural factors is smoother, and the income gap between urban and rural residents continues to narrow. The strategy of coordinated regional development, major regional strategies and the strategy of main functional areas have been solidly promoted, the carrying capacity of areas with economic development advantages such as central cities and urban agglomerations has been further enhanced, and the regional economic layout with complementary advantages and high-quality development has been accelerated. In 2022, the GDP of nine cities in Beijing-Tianjin-Hebei, Yangtze River Delta and Guangdong-Hong Kong-Macao Greater Bay Area Mainland reached 49.5 trillion yuan, exceeding 40% of the national total, which played an important role in the national economic ballast and high-quality development power source. The effect of comprehensive management of ecological environment in large rivers has been further manifested. The urbanization construction with the county as an important carrier has been carried out in a solid way, and a series of policy systems of "1+N+X" have taken shape.

　　Sixth, the construction of a unified national market was accelerated. The basic market system has been continuously improved, and the opinions of speeding up the construction of a unified national market have been issued. The negative list system for market access has been fully implemented and updated, and the reform of the commercial system has been continuously implemented. The institutional transaction costs of business entities have been continuously reduced, and the reform of "separation of licenses" has been fully covered, which has accelerated the cleaning up and abolition of various regulations and practices that hinder the unified national market and fair competition. The pace of market-oriented allocation of factors has been obviously accelerated, the reform of stock issuance and registration system has been fully implemented, the unified urban and rural construction land market has been accelerated, and the reform of household registration system has been continuously promoted. Significant progress has been made in the construction of modern circulation system, the national backbone circulation network has been gradually improved, and the ratio of total social logistics costs to GDP has been declining.

　　Seventh, the high level of opening up has achieved remarkable results. In the face of a more complicated and severe external environment, China’s foreign trade has shown great resilience and vitality, and the domestic and international double-cycle linkage effect has been continuously enhanced. The scale of trade has reached a new level. In 2022, China’s total trade in goods reached a record high, reaching 42.1 trillion yuan, maintaining its position as the world’s largest trade country in goods for six consecutive years; The total trade in services was about 6 trillion yuan, up 12.9% year-on-year. The trade structure continued to be optimized, the proportion of general trade increased steadily, the export of capital-intensive and technology-intensive products increased rapidly, and the export of high value-added services increased strongly. In the context of global cross-border investment downturn, China’s foreign investment has grown against the trend, and the actual use of foreign capital has increased from $144.37 billion in 2020 to $189.13 billion in 2022. The Regional Comprehensive Economic Partnership Agreement (RCEP) came into effect, the leading role of innovation demonstration in the Pilot Free Trade Zone has been continuously enhanced, and the construction of Hainan Free Trade Port has been accelerated. The international trains are connected to China Unicom in many directions, and the trains in China and Europe continue to grow. In 2022, 16,000 trains will be opened and 1.6 million TEUs will be sent, and the trains in the new land and sea channel in the west will grow rapidly. Especially during the epidemic, the China-Europe train, as an important stable channel to smooth the trade of goods between Asia and Europe, has become an important achievement and highlight of building the "Belt and Road".

　　Eighth, the ability of safe development has been significantly enhanced. Faced with the increase of uncertainties and unpredictable factors in the international development environment and the increasing fluctuation of global primary product supply, China insists on overall development and safety, pays special attention to primary product production based on itself, and responds to the uncertainty of external environment with the certainty of stable domestic supply. Firmly hold the red line of 1.8 billion mu of cultivated land, and the grain output has reached more than 1.3 trillion Jin for eight consecutive years. The domestic energy production support capacity has been continuously enhanced, and a diversified clean power supply system has been vigorously developed. In 2022, the production of major energy products such as kerosene, gas and electricity in industrial enterprises above designated size has maintained growth, and the dependence on foreign countries for oil and gas has declined. We will make overall plans to make up short boards and forge long boards, implement industrial base reconstruction projects and strengthen manufacturing chains to make up chains, and the resilience and competitiveness of the supply chain of the industrial chain will continue to improve. After the outbreak, relying on a complete industrial system, strong mobilization organization and industrial transformation ability, China quickly formed a strong production and supply capacity of epidemic prevention and control materials in a relatively short period of time, and the industrial chain supply chain showed strong resilience in the stress test of epidemic impact.

　　To build a new development pattern, we must deepen our understanding and highlight the key points

　　All great achievements are the result of continuous struggle, and all great undertakings need to be promoted in the future. Summing up experience and deepening understanding are important magic weapons for continuing struggle. In practice, we feel more deeply the great strategic significance of building a new development pattern for building a socialist modern power in an all-round way, and more deeply understand the great practical significance of building a new development pattern for coping with the great changes that have never happened in a century.

　　First, we must firmly grasp the key of smooth circulation. The key to building a new development pattern lies in the unimpeded economic cycle. If there are blocking points and breakpoints in the process of economic cycle, the cycle will be blocked, which will be manifested as the decline of growth rate, the increase of unemployment, the accumulation of risks, the imbalance of international payments, etc., and will be manifested as overcapacity, the decline of enterprise benefits, and the decline of residents’ income, etc. We must solve the blocking problems of production, distribution, exchange, consumption and other links in the domestic macro-cycle, strive to break the local small cycle, smooth the domestic macro-cycle, make overall plans to expand domestic demand and deepen the supply-side structural reform, improve the adaptability between supply and demand, and effectively enhance the endogenous motivation and stability of the domestic macro-cycle. At the same time, according to the change of comparative advantage, we should dynamically adjust the key areas and methods of China’s participation in international circulation, strive to improve the quality and level of international circulation, form an interactive relationship in which supply and demand match each other and domestic circulation and international circulation promote each other, and constantly promote a virtuous circle of the national economy that goes round and round and spirals.

　　Second, we must correctly grasp the dialectical relationship between internal and external circulation. It is necessary to realize that both internal and external circulation promote each other and cannot be neglected, whether it is coordinating development and security or participating in international competition and cooperation. In the process of building a new development pattern, we must take the domestic macro-cycle as the main body, constantly strengthen the leading role of the domestic macro-cycle, persist in putting the development of the country and the nation on the basis of our own strength, and enhance our ability and confidence to cope with various risk challenges with a solid domestic basic disk. At the same time, we must unswervingly implement the basic national policy of opening to the outside world and create a new open economic system at a higher level. To realize domestic and international double-cycle mutual promotion and common progress, it is necessary to give full play to the demand advantage of super-large-scale market and the supply advantage of complete industrial system, attract and gather high-end global resource elements, form a gravitational field for global resource elements, attract and utilize foreign capital more vigorously, and also go out steadily to strengthen overseas investment services, supervision and risk prevention and control.

　　Third, we must adhere to the problem-oriented and systematic concept. Adhering to the problem-oriented and systematic concept is an important methodology of the supreme leader’s economic thought. To build a new development pattern by adhering to the problem orientation, we should focus on major risk challenges, identify key links in key areas, work hard from unblocking blocking points, promoting advantages, filling shortcomings and strong and weak items, and strive to turn crises into opportunities and create conditions to improve the quality and level of economic cycles. Adhering to the concept of system to build a new development pattern, we must realize that the economic system is a complete and continuous whole in time and space, and it is a complex system that is interrelated and constantly moving. We should strengthen forward-looking thinking, overall planning, strategic layout and overall promotion, strengthen policy coordination and cooperation, drive the overall promotion with key breakthroughs, achieve key breakthroughs with overall promotion, and strive to achieve the combination of overall and local, gradual and breakthrough.

　　Fourth, we must guard against misunderstanding and action deviation. Building a new development pattern is a complex systematic project, and there are still some misunderstandings and action deviations in practice, which must be corrected in time. In understanding, we should not only avoid one-sided understanding that only emphasizes internal circulation or external circulation, but also avoid misunderstanding that the long-term task of building a new development pattern is regarded as a short-term emergency measure, and also avoid understanding self-reliance and self-improvement of science and technology as small and comprehensive repeated construction behind closed doors. In action, we should prevent ourselves from fighting each other, only consider the small market in this region and engage in our own small cycle, and also prevent selfish departmentalism. We think that building a new development pattern has little to do with our own departments, and we can’t form a joint effort if we only care about our own "one acre and three points".

　　Resolutely unify understanding and action with the decision-making and deployment of the CPC Central Committee.

　　Report to the 20th CPC National Congress of the Party pointed out that a new development pattern should be formed by 2035. We must profoundly understand and accurately grasp the decision-making arrangements of the CPC Central Committee, and with more firm ideological consciousness, hard work, precise and pragmatic policy measures, effectively incorporate the work in this field in this region into the construction of a new development pattern, make efforts to smooth the domestic economic cycle, promote the benign interaction between domestic and international double cycles, and effectively enhance the security and initiative of development.

　　First, accelerate the formation of a complete domestic demand system and form a higher level of dynamic balance. Adhere to the strategic starting point of expanding domestic demand, expand the domestic demand system according to the whole chain of production, distribution, circulation, consumption and investment reproduction, break through the difficulties that restrict the economic cycle, such as insufficient effective supply capacity, large income distribution gap, low modernization of circulation system, imperfect consumption system and mechanism, and investment structure still needs to be optimized, and strive to expand consumer demand with income support, investment demand with reasonable return, and financial demand with principal and debt constraints. Focus on tapping the potential of domestic demand, promoting consumption upgrading and expanding investment space. Efforts will be made to optimize the market structure, improve the market mechanism, stimulate market vitality, enhance market resilience, further enlarge and strengthen the domestic market, and continuously improve the attractiveness and allocation capacity of global resource elements.

　　The second is to speed up the pace of self-reliance and self-improvement in science and technology and shape the new advantages of domestic and international double circulation. Improve the new national system, strengthen the national strategic scientific and technological strength, promote the construction of international and regional scientific and technological innovation centers as a whole, and enhance the overall efficiency of the national innovation system. Deepen the reform of the scientific and technological system, strengthen the dominant position of enterprises in scientific and technological innovation, form a basic system to support innovation, optimize the allocation of innovative resources at home and abroad, strengthen basic research, implement a number of forward-looking and strategic national major scientific and technological projects in frontier fields such as artificial intelligence, quantum information and brain science, and speed up the conquest of "stuck-neck" technologies in important fields. We will promote the effective linkage between the strategy of rejuvenating the country through science and education, the strategy of strengthening the country through talents and the strategy of innovation-driven development, and promote the work of educational science and technology talents as a whole with the guidance of high-level science and technology self-reliance, so as to realize the deep integration of innovation chain’s industrial chain capital chain talent chain.

　　The third is to accelerate the construction of a modern industrial system and enhance the status of a global manufacturing center. Focus on the real economy, solidly promote new industrialization, and accelerate the construction of a manufacturing power, a quality power, a space power, a transportation power, a network power and a digital China. Actively promote short-board industries to supplement the chain, advantageous industries to extend the chain, traditional industries to upgrade the chain, and emerging industries to build the chain. Accelerate the development of high-end, intelligent and green manufacturing. We will promote the development of strategic emerging industries and foster a number of new growth engines such as information technology, artificial intelligence, biotechnology, new energy, new materials, high-end equipment and environmental protection. Build a high-quality and efficient new service industry system, promote the deep integration of modern service industry with advanced manufacturing industry and modern agriculture, and promote the deep integration of digital economy and real economy. Build a modern infrastructure system. Strengthen the security of grain, energy resources and important industrial chain supply chains.

　　Fourth, solidly promote the coordinated development of urban and rural areas and expand the vast and deep circulation space. Solidly promote the major strategic deployment of urban and rural areas, enhance the integrity and coordination of development, and provide multi-gradient growth, diversified development and strong and resilient urban and rural regional power support for building a new development pattern. We will further implement the rural revitalization strategy, accelerate the construction of an agricultural power, accelerate the pace of agricultural and rural modernization, further promote the new urbanization with people as the core, promote the integrated development of urban and rural areas, smooth the urban-rural economic cycle, and improve the coverage of the domestic macro-cycle. Establish and improve the cross-regional linkage development mechanism, improve the regional cooperation and interest adjustment mechanism, optimize the layout of major productive forces, focus on improving the power source function of Beijing-Tianjin-Hebei, Yangtze River Delta and Guangdong-Hong Kong-Macao Greater Bay Area to lead high-quality development, strengthen the support capacity of major agricultural products producing areas, key ecological functional areas, energy-rich areas and border areas, promote the deep integration and development of regional coordinated development strategies, major regional strategies and major functional areas strategies, and build a regional economic layout and land space system with complementary advantages and high-quality development.

　　Fifth, comprehensively deepen reform and opening up and enhance the dynamic vitality of internal and external circulation. Promote the market-oriented reform of land, labor, capital, technology, data and other factors, promote the independent and orderly flow of factors, and improve the efficiency of factor allocation. Open up the key blocking points that restrict the economic cycle and speed up the construction of a unified national market with high efficiency, standardization, fair competition and full opening. Strengthen the construction of business environment, improve the basic system of market economy such as property rights protection, market access, fair competition and social credit, and strengthen anti-monopoly and anti-unfair competition. We will steadily expand the institutional opening of rules, regulations, management and standards, innovate the development mechanism of service trade, accelerate the construction of Hainan Free Trade Port, and implement the strategy of upgrading the Pilot Free Trade Zone. Promote the high-quality development of the "Belt and Road" and expand new space for cooperation in the fields of health, green, digital and innovation. We will promote the stable scale and excellent structure of foreign trade and increase investment in key countries and manufacturing industries.

　　(Author Shi Yulong is the director of the Economic Thought Research Center of the Supreme Leader. Source: Economic Daily)