Objective:To analyze the association between healthcare workers mental health,institu-tional supplies and facilities,inter-organizational coordination during infectious disease outbreaks,and the healthcare institution resilience.Methods:An online questionnaire survey was conducted among the healthcare workforce from 146 institutions in Beijing from January 13,2023 to February 9,2023,and a total of 1 434 eligible respondents were included.The sample comprised 408 responses from tertiary hos-pitals,117 from secondary hospitals,and 909 from primary care institutions.The resilience indicator for healthcare institutions was defined as the degree to which medical services met patient demands,with in-fluencing factors including physical factors,such as material shortages and facility space adaptation or ex-pansion,organizational factors such as information sharing and patient referral,and psychological factors were evaluated using job satisfaction(extrinsic satisfaction,intrinsic satisfaction),burnout(emotional exhaustion,depersonalization,reduced personal accomplishment),and depression status.Ordered mul-ticlassification Logistic regression was used to examine the impact of various factors on the degree to which healthcare services met patient needs;additionally,demographic factors that might influence institutional resilience were controlled.Results:During the emergency response phase,93％of hospitals maintained the capacity to meet patient needs,though tertiary hospitals demonstrated significantly higher rates of service inadequacy(21.05％).Material shortages were reported across all institutions,with tertiary hos-pitals experiencing more frequent multi-item shortages.Inter-institutional collaboration patterns revealed substantial variation:87.50％of primary care facilities,42.86％of secondary hospitals,and 31.58％of tertiary hospitals.Healthcare workers across all levels reported mild depressive symptoms and moderate-to-severe burnout levels.Regression analysis showed high satisfaction(overall satisfaction β=0.04,ex-trinsic satisfaction β=0.06,and intrinsic satisfaction β=0.08),low degree of job burnout(emotional exhaustion β=-0.04,depersonalization β=-0.07 and reduced personal accomplishment β=0.01),low degree of depression(β=-0.06)were significantly associated with higher healthcare institution re-silience.In addition,material shortages were significantly associated with lower resilience,and renova-tion and expansion of treatment spaces,and information sharing,were all associated with higher resilience.Demographic factors(age,gender,marital status,educational background,etc.)had no sig-nificant impact on resilience.Conclusion:Mental health status significantly influences healthcare institu-tion resilience.As human resources constitute the core asset of healthcare institutions,strategic optimiza-tion of workforce allocation and psychological support interventions can effectively strengthen resilience.Moreover,healthcare institution resilience is positively impacted by orderly material supply chains,timely resource distribution,and adaptive reconfiguration of clinical spaces.Finally,facilitating information sharing also enhances institutional resilience.

Objective To elucidate the correlation between specific nucleocapsid(N)protein mutant of the SARS-CoV-2 B.1.1.7 variant and clinical stratification in COVID-19 patients,revealing their impact on N protein liquid-liquid phase separation(LLPS)and host innate immune response.Methods Based on whole-genome sequencing data of the SARS-CoV-2 B.1.1.7 lineage from the GISAID database,non-synonymous mutation sites significantly associated with mild/severe clinical phenotypes were screened.For high-frequency N protein mutant,IFN-β promoter transcriptional activity was quantitatively measured using a dual-luciferase reporter system.qPCR was used to detect the mRNA expression levels of interferon(IFN)-β,interleukin(IL)-6 and tumor necrosis factor(TNF)-α.LLPS characteristics were observed by confocal microscopy.The ubiquitination status of host MAVS was detected by Western blot assay.Results A total of 17 640 non-synonymous mutation sites were identified,among which 65 were associated with mild cases and 20 were related to severe cases,with a mutation frequency>1%.The N protein mutation sites associated with severe cases were D3L,M234I and R203K-G204R-T205I.N protein and the mutants NM234I,NR203K-G204R-T205I inhibited the promoter activity of IFN-β(P＜0.05).Compared to the wild type N protein,NR203K-G204R-T205I mutation significantly reduced the mRNA levels of IFN-β,IL-6 and TNF-α(P＜0.05),and altered the phase separation state by dispersing the formation of LLPS condensates.However,N mutant did not affect the ubiquitination modification of host MAVS.Conclusion N protein mutants of the SARS-CoV-2 B.1.1.7 variant can influence the clinical prognosis of COVID-19 patients by altering LLPS status and suppressing the innate immune responses.These finding provides a theoretical basis for the design of antiviral drugs targeting the N protein.

Objectives:Accounting Total Health Expenditure(THE)in 2023,analyzing the changes of health financing in China since 2015,summarizing the main problems and challenges faced by health financing in China at present,and putting forward policy suggestions to improve health financing.Methods:Health expenditure accounting methods by financing source and by health provider were applied,and the change of total health expenditure in China is analyzed through the index analysis of time series.Results:THE in 2023 in China was 9 057.58 billion yuan,an increase of 6.77%over the previous year,accounting for 7.00%of GDP,and per capi-ta health expenditure was 6 425.32 yuan.The proportion of government health expenditure in THE decreased to 26.66%,the propor-tion of social health expenditure increased to 46.01%,and the proportion of household Out-of-Pocket(OOP)rebounded to 27.33%.Conclusions:The total scale of health expenditure in China continues to grow,but the growth rate slows down,and the stability and sustainability of health financing need to be strengthened.It is necessary to speed up the construction of a government investment mechanism based on health priority development,improve the social health insurance system,guide the rational resource allocation,and reduce the burden of medical treatment for residents.

Objective To elucidate the correlation between specific nucleocapsid(N)protein mutant of the SARS-CoV-2 B.1.1.7 variant and clinical stratification in COVID-19 patients,revealing their impact on N protein liquid-liquid phase separation(LLPS)and host innate immune response.Methods Based on whole-genome sequencing data of the SARS-CoV-2 B.1.1.7 lineage from the GISAID database,non-synonymous mutation sites significantly associated with mild/severe clinical phenotypes were screened.For high-frequency N protein mutant,IFN-β promoter transcriptional activity was quantitatively measured using a dual-luciferase reporter system.qPCR was used to detect the mRNA expression levels of interferon(IFN)-β,interleukin(IL)-6 and tumor necrosis factor(TNF)-α.LLPS characteristics were observed by confocal microscopy.The ubiquitination status of host MAVS was detected by Western blot assay.Results A total of 17 640 non-synonymous mutation sites were identified,among which 65 were associated with mild cases and 20 were related to severe cases,with a mutation frequency>1%.The N protein mutation sites associated with severe cases were D3L,M234I and R203K-G204R-T205I.N protein and the mutants NM234I,NR203K-G204R-T205I inhibited the promoter activity of IFN-β(P＜0.05).Compared to the wild type N protein,NR203K-G204R-T205I mutation significantly reduced the mRNA levels of IFN-β,IL-6 and TNF-α(P＜0.05),and altered the phase separation state by dispersing the formation of LLPS condensates.However,N mutant did not affect the ubiquitination modification of host MAVS.Conclusion N protein mutants of the SARS-CoV-2 B.1.1.7 variant can influence the clinical prognosis of COVID-19 patients by altering LLPS status and suppressing the innate immune responses.These finding provides a theoretical basis for the design of antiviral drugs targeting the N protein.

BACKGROUND:With the continuous advancement of medical technology,stem cell therapy has been used to treat a variety of diseases,including amyotrophic lateral sclerosis. OBJECTIVE:To review the research progress of stem cell therapy for amyotrophic lateral sclerosis,and prospect the development trend of this field. METHODS:PubMed,China National Knowledge Infrastructure(CNKI),and WanFang Data were searched for articles published from 1995 to 2024 using the key words"amyotrophic lateral sclerosis,mesenchymal stem cells,neural stem/progenitor cells,pluripotent stem cells."A total of more than 1 700 articles were retrieved,and 58 articles were finally included in this review. RESULTS AND CONCLUSION:Amyotrophic lateral sclerosis is a neurodegenerative disease that affects lower motor neurons in the brainstem and spinal cord and upper motor neurons in the motor cortex.The related research of stem cells in the treatment of amyotrophic lateral sclerosis has become a research hotspot.In this review,we summarize the application of different types of stem cells in amyotrophic lateral sclerosis research,including mesenchymal stem cells,neural stem progenitor cells,and induced pluripotent stem cells,and evaluate the key points of preclinical research such as stem cell source,cell volume,stem cell modification methods,and drug delivery routes,which lays the foundation for the future application of stem cell therapy.

Small splint external fixation,due to its advantages of low cost,good breathability,easy adjustability,and sufficient flexibility,has been widely used in clinical practice for fracture patients after manual reduction.Compared to plaster external fixation,small splint fixation is associated with fewer cases of pressure ulcers,but the ulcers still occur clinically.This article analyzes the causes of splint-associated pressure ulcers in fracture patients,and introduced the preventive measures and practice experience of Foshan traumatology and bone-setting practitioners in managing such complications.Their preventive strategies include the gentle and bone-following manipulations of pushing skin and squeezing bone,proper shaping of splints,use of soft cotton padding,appropriate tightness in bandage wrapping,and elevation of the affected limb to promote venous return.For patients suffering pressure ulcers,the external application of traumatic medicated yellow oil gauze combined with medicated yellow water gauze for wet compress has shown efficacy.These approaches provide valuable clinical references for reducing the incidence of splint-related pressure ulcers and for guiding the management of pressure ulcers.

Objective:To analyze the association between healthcare workers mental health,institu-tional supplies and facilities,inter-organizational coordination during infectious disease outbreaks,and the healthcare institution resilience.Methods:An online questionnaire survey was conducted among the healthcare workforce from 146 institutions in Beijing from January 13,2023 to February 9,2023,and a total of 1 434 eligible respondents were included.The sample comprised 408 responses from tertiary hos-pitals,117 from secondary hospitals,and 909 from primary care institutions.The resilience indicator for healthcare institutions was defined as the degree to which medical services met patient demands,with in-fluencing factors including physical factors,such as material shortages and facility space adaptation or ex-pansion,organizational factors such as information sharing and patient referral,and psychological factors were evaluated using job satisfaction(extrinsic satisfaction,intrinsic satisfaction),burnout(emotional exhaustion,depersonalization,reduced personal accomplishment),and depression status.Ordered mul-ticlassification Logistic regression was used to examine the impact of various factors on the degree to which healthcare services met patient needs;additionally,demographic factors that might influence institutional resilience were controlled.Results:During the emergency response phase,93％of hospitals maintained the capacity to meet patient needs,though tertiary hospitals demonstrated significantly higher rates of service inadequacy(21.05％).Material shortages were reported across all institutions,with tertiary hos-pitals experiencing more frequent multi-item shortages.Inter-institutional collaboration patterns revealed substantial variation:87.50％of primary care facilities,42.86％of secondary hospitals,and 31.58％of tertiary hospitals.Healthcare workers across all levels reported mild depressive symptoms and moderate-to-severe burnout levels.Regression analysis showed high satisfaction(overall satisfaction β=0.04,ex-trinsic satisfaction β=0.06,and intrinsic satisfaction β=0.08),low degree of job burnout(emotional exhaustion β=-0.04,depersonalization β=-0.07 and reduced personal accomplishment β=0.01),low degree of depression(β=-0.06)were significantly associated with higher healthcare institution re-silience.In addition,material shortages were significantly associated with lower resilience,and renova-tion and expansion of treatment spaces,and information sharing,were all associated with higher resilience.Demographic factors(age,gender,marital status,educational background,etc.)had no sig-nificant impact on resilience.Conclusion:Mental health status significantly influences healthcare institu-tion resilience.As human resources constitute the core asset of healthcare institutions,strategic optimiza-tion of workforce allocation and psychological support interventions can effectively strengthen resilience.Moreover,healthcare institution resilience is positively impacted by orderly material supply chains,timely resource distribution,and adaptive reconfiguration of clinical spaces.Finally,facilitating information sharing also enhances institutional resilience.

Objectives:Accounting Total Health Expenditure(THE)in 2023,analyzing the changes of health financing in China since 2015,summarizing the main problems and challenges faced by health financing in China at present,and putting forward policy suggestions to improve health financing.Methods:Health expenditure accounting methods by financing source and by health provider were applied,and the change of total health expenditure in China is analyzed through the index analysis of time series.Results:THE in 2023 in China was 9 057.58 billion yuan,an increase of 6.77%over the previous year,accounting for 7.00%of GDP,and per capi-ta health expenditure was 6 425.32 yuan.The proportion of government health expenditure in THE decreased to 26.66%,the propor-tion of social health expenditure increased to 46.01%,and the proportion of household Out-of-Pocket(OOP)rebounded to 27.33%.Conclusions:The total scale of health expenditure in China continues to grow,but the growth rate slows down,and the stability and sustainability of health financing need to be strengthened.It is necessary to speed up the construction of a government investment mechanism based on health priority development,improve the social health insurance system,guide the rational resource allocation,and reduce the burden of medical treatment for residents.

Objective To explore the mechanism by which Sestrin2(SESN2)regulates autophagy activity of chondrocytes by mediating mammalian rapamycin target protein complex 1(mTORC1)signaling pathway.Methods The normal chondrocytes were treated with interleukin-1 β(IL-1β)to establish an osteoarthritis(OA)chondrocyte model,which was divided into the control group and the IL-1 β-treated group.Real-time quantitative PCR(qPCR)and Western blot were used to detect the expression levels of matrix metalloproteinase 13(MMP13),type Ⅱ collagen(COL2A1)and SESN2 in the two groups.The cell models of the chondrocyte overexpression SESN2 group and knockdown SESN2 group were obtained via cell transfection technology,and the expression levels of SESN2 in each group were detected by qPCR while those of SESN2,MMP13,COL2A1,mTORC1 pathway-related proteins and autophagy-related proteins in each group were detected by Western blot.The effects of SESN2 on cell proliferation and migration were detected by CCK-8 and cell scratch assay.Results(1)The expression level of MMP13 in the IL-1 β-treated group was significantly up-regulated,while the expression levels of COL2A1 and SESN2 were significantly decreased.(2)Compared with the control group,the expressions of p-mTORC1,ribosomal protein S6 kinase 1(S6K1),and MMP13 protein in OA chondrocytes in the overexpression group were significantly down-regulated,while the expressions of adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)and chondroprotective gene COL2A1 were significantly increased,and the expression level of Beclin-1 and the ratio of microtubule associated protein 1 light chain 3-Ⅱ(LC3-Ⅱ)/(LC3-Ⅰ)were increased.Meanwhile,overexpression of SESN2 could up-regulate the proliferation and migration of chondrocytes,but the results were opposite after knockdown of SESN2.Conclusion SESN2 can enhance autophagy,proliferation and migration of chondrocytes by inhibiting mTORC1 pathway,which has provided data for revealing the pathogenesis of OA and exploring new therapeutic methods.

Objective To investigate the value of peripheral blood soluble interleukin-2 receptor(sIL-2R),CD4+lymphocyte percentage/CD8+lymphocyte percentage ratio(hereinafter referred to as CD4+/CD8+)and tumor necrosis factor-α(TNF-α)in evaluating the efficacy of chemotherapy in elderly patients with newly treated active pulmonary tuberculosis.Methods A total of 102 elderly patients with newly treated active tu-berculosis admitted to the hospital from December 2019 to December 2022 were enrolled in the study as the observation group,and 102 healthy people aged 60 and older who underwent physical examination in the hos-pital during the same period were enrolled as the control group.The levels of sIL-2R,TNF-α and CD4+/CD8+in peripheral blood were compared between the two groups,and the correlations between sIL-2R,TNF-α and CD4+/CD8+were analyzed.The observation group was treated with 2HRZE/4HR anti-tuberculosis treatment regimen.The levels of sIL-2R,TNF-α and CD4+/CD8+in peripheral blood of patients with different efficacy before treatment,1 month and 6 months after treatment in the observation group were compared.The correla-tion between sIL-2R,CD4+/CD8+,TNF-α levels and therapeutic effect was analyzed.The receiver operating characteristic(ROC)curve was used to analyze the efficacy of indicators in evaluating the efficacy of chemo-therapy in elderly patients.Results The levels of sIL-2R and TNF-α in the observation group were higher than those in the control group,while CD4+/CD8+was lower than that in the control group,and the differ-ences were statistically significant(P＜0.05).In the observation group,sIL-2R and TNF-α were negatively correlated with CD4+/CD8+(P＜0.05),sIL-2R was positively correlated with TNF-α(P＜0.05).After 1 month and 6 months of treatment,the levels of sIL-2R and TNF-α in patients with apparent efficacy were low-er than those in patients with efficacy,and the latter were lower than those in patients with no effect,while the CD4+/CD8+in patients with apparent efficacy was higher than that in patients with efficacy,and the latter was higher than that in patients with no efficacy,and the differences were statistically significant(P＜0.05).The levels of sIL-2R and TNF-α were negatively correlated with the efficacy(P＜0.05),and CD4+/CD8+was positively correlated with the efficacy(P＜0.05).ROC curve analysis showed that the area under the curve(AUC)of sIL-2R,CD4+/CD8+,and TNF-α used in combination to assess efficacy was significantly greater than the AUCs of the single indicators used in the assessment at each time point of treatment(P＜0.05),and the AUC of the combination of the indicators was greater after 6 months of treatment than after 1 month of treatment(P＜0.05).Conclusion The levels of sIL-2R,CD4+/CD8+and TNF-α are closely related to the ef-ficacy of chemotherapy in elderly patients with newly treated active pulmonary tuberculosis,and the combina-tion of the above indicators has certain reference value in evaluating the efficacy of chemotherapy in patients.