ObjectiveTo analyze the output and efficiency of chronic disease management services for hypertension and diabetes in community health service institutions in Shanghai, to evaluate the allocation and efficiency of chronic disease management resources, and to provide references for improving the efficiency of chronic disease management in Shanghai’s communities. MethodsA total of 73 community health institutions from 15 districts of Shanghai were selected. Based on the chronic disease management resource data of community health institutions in 2019, 2021, and 2023, descriptive methods and the BCC model in Data Envelopment Analysis (DEA) were used to analyze the resource allocation, service output, and the efficiency of chronic disease management services in community health institutions in Shanghai. ResultsFrom 2019 to 2023, the indicators of resource allocation and service output of community health service institutions in Shanghai all showed upward trends. In terms of service efficiency, the average number of chronic disease patients managed by each health technician decreased from 237 to 231, and the number of patients served per 1 000 working hours decreased from 54 to 44. DEA efficiency analyses showed that the average overall efficiency increased from 0.867 in 2019 to 0.886 in 2021 and then decreased to 0.811 in 2023. The average technical efficiency decreased from 0.901 to 0.847, which was the main reason for the decline in overall efficiency. The average scale efficiency showed an initial increase followed by a decrease, rising from 0.961 in 2019 to 0.977 in 2021 and dropping back to 0.955 in 2023. The number of strong effective districts (overall efficiency=1.000) decreased from 6 in 2019 to 3 in 2023, and the efficiency differences between districts expanded. The range of overall efficiency widened from 0.622‒1.000 to 0.513‒1.000, indicating a decline in overall efficiency and an increase in inter-district heterogeneity. ConclusionFrom 2019 to 2023, the total volume of resource allocation and service output for chronic disease management in community health service institutions in Shanghai increased continuously. However, both the service output efficiency and the overall resource allocation efficiency declined, driven primarily by a decrease in technical efficiency, and accompanied by widening inter‑district disparities.

Objective To investigate the relationship between the expression levels of serum integrin αMβ2(ITG αMβ2)and gasdermin D(GSDMD)in patients with severe acute pancreatitis(SAP)complicated with acute respiratory distress syndrome(ARDS)and the severity of the disease and its value in predicting prognosis.Methods A total of 147 patients with SAP complicated with ARDS(ARDS group)admitted to the Department of Intensive Care Medicine of the Southwest Jiaotong University Affiliated Hospital(Chengdu Third People's Hospital)from August 2021 to October 2023 were selected.According to the oxygenation index(OI),they were divided into mild group(n=35),moderate group(n=46)and severe group(n=66).According to the 28-day prognosis,they were divided into death group(n=77)and survival group(n=70).Another 147 SAP patients without ARDS at the same time period were selected(non-ARDS group).The expression levels of serum ITG αMβ2 and GSDMD were detected by enzyme-linked immunosorbent assay.Spearman method was used to analyze the correlation between serum ITG αMβ2,GSDMD expression levels and OI in patients with SAP complicated with ARDS.Multivariate Logistic regression was used to analyze the factors of death in patients with SAP complicated with ARDS.Receiver operating characteristic(ROC)curve was used to analyze the value of serum ITG αMβ2,GSDMD expression levels in evaluating the death of patients with SAP complicated with ARDS.Results Compared with the non-ARDS group,the expression levels of serum ITG αMβ2(31.95±8.17 ng/L vs 53.33±12.22 ng/L)and GSDMD(2.25±0.55 ng/ml vs 4.39±1.18 ng/ml)in the ARDS group were increased,and the differences were statistically significant(t=17.637,19.899,all P<0.05).The expression levels of serum ITG αMβ2 and GSDMD in mild group,moderate group and severe group increased in turn,and the differences were statistically significant(F=163.069,194.028,all P<0.05).The expression levels of serum ITG αMβ2 and GSDMD were negatively correlated with OI in patients with SAP complicated with ARDS(r=-0.787,-0.778,all P<0.05).The 28-day mortality rate of 147 SAP patients with ARDS was 52.38%(77/147).Compared with the survival group,the expression levels of serum ITG αMβ2(46.96±10.28 ng/L vs 59.11±10.94 ng/L)and GSDMD(3.74±0.98 ng/ml vs 4.98±1.04 ng/ml)in the death group were increased,and the differences were statistically significant(t=6.920,7.415,all P<0.05).The number of extrapulmonary organ failure≥2,prolonged mechanical ventilation time,increased acute physiological and chronic health assessment II score,and increased ITG αMβ2.and GSDMD were independent risk factors for death in SAP patients complicated with ARDS(Wald χ2=4.297～13.536,all P<0.05),and increased OI was an independent protective factor(Wald χ2=8.346,P<0.05).The combined evaluation AUC of serum ITG αMβ2 and GSDMD expression levels results in a larger area under the curve(AUC)for mortality in SAP patients with ARDS compared to the individual evaluation of SAP complicated with ARDS,which was greater than serum ITG αMβ2 and GSDMD expression levels alone,and the differenes were statistically significant(Z=3.517,3.430,all P<0.05).Conclusion The increase of serum ITG αMβ2 and GSDMD expression levels is related to the progression and poor prognosis of patients with SAP complicated with ARDS.The combined monitoring of serum ITG αMβ2 and GSDMD expression levels has a high evaluation value for the risk of death in patients with SAP complicated with ARDS.

Objective To explore the basis of PERMA on the overall well-being and social support of elderly patients with maintenance hemodialysis(MHD).Methods A total of 60 elderly patients with MHD were selected from the blood purification center of a tertiary A hospital in Zhejiang Province from January to December 2022 as the study subjects.According to the different disease areas of the patients,they were randomly divided into an experimental group or a control group.Finally,30 patients were included in each group.The control group received routine care,and the experimental group received another 4-week bidirectional social support intervention based on the PERMA model.General well-being scale,social support rating scale,sleep duration,activity duration were used to evaluate the effect before intervention,4 weeks after intervention and 1 month after intervention.Results The results of repeated measurement ANOVA showed that there were statistically significant differences in general happiness score,social support score,sleep duration and activity duration in terms of time effect(P＜0.05),while there were statistically significant differences in general happiness score,social support score and sleep duration in terms of inter-group effect(P＜0.05).Social support score and sleep duration had statistically significant interac-tion effects(P＜0.05).Conclusion The bidirectional social support intervention based on well-being PERMA model can enhance the general well-being and social support level of elderly patients with MHD,and improve the sleep and activity status of elderly patients with MHD.

Objective To investigate the effect of Eriodictyol(ERI)on the development of metabolic dysfunction-associated steatotic liver disease by regulating the expression of ubiquitin A 52(UBA52)at both in vivo and in vitro levels.Methods A mouse metabolic dysfunction-associated steatotic liver disease model was established using a high-fat diet induction.The mice were randomly separated into the normal control group(normal group),the model group,the low-dose ERI group(ERI-L group,50 mg/kg ERI)and the high-dose ERI group(ERI-H group,100 mg/kg ERI),with 12 mice in each group.Oil red O staining was applied to observe lipid deposition in mouse liver tissue.HE staining was applied to observe pathological changes in mouse liver tissue.ELISA method was applied to detect serum levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),low-density lipoprotein cholesterol(LDL-C),total cholesterol(TC)and triglycerides(TG)in mice.The expression of UBA52 protein in liver was detected by Western blot assay.HepG2 cells were treated with 0.5 mmol/L oleic acid to induce an in vitro metabolic dysfunction-associated steatotic liver disease model.HepG2 cells were randomly divide into the control group,the oleic acid induced group,the low concentration ERI group(ERI low group,50 μmol/L ERI),the high concentration ERI group(ERI high group,100 μmol/L ERI),the high concentration ERI+si-NC group(ERI high+si-NC group,100 μmol/L ERI+transfected with si-NC)and the high concentration ERI+si-UBA52 group(ERI high+si-UBA52 group,100 μmol/L ERI+transfected with si-UBA52).Oil red O staining was applied to detect lipid deposition in HepG2 cells of each group.ELISA method was applied to detect the levels of TG,TC,SOD and MDA in HepG2 cells in each group.Immunoblotting was used to detect the expression levels of UBA52,p62 and autophagy related proteins in HepG2 cells.Results Compared with the normal group,serum levels of ALT,AST,LDL-C,TC,TG and the expression of UBA52 protein in liver tissue were increased in the model group(P＜0.05),and the lipid deposition in liver increased,pathological damage was severe,and the proportion of lipid deposition area and non-alcoholic fatty liver disease(NAFLD)activity score were also increased(P＜0.05).Changes in the corresponding indicators in the ERI-L group and the ERI-H group were opposite to those of the model group(P＜0.05),and the ERI-H group was even lower(P＜0.05).The lipid deposition in liver decreased and the pathological damage was alleviated.Compared with the control group,the levels of TG,TC,MDA,the proportion of lipid droplet area and the expression of UBA52 protein were increased in HepG2 cells of the oleic acid-induced group,while the levels of SOD,p62 and LC3Ⅱ/LC3Ⅰ decreased(P＜0.05).Changes in the corresponding indicators of the low-concentration ERI group and the high-concentration ERI group were opposite to those of the oleic acid-induced group(P＜0.05),and the therapeutic effect of ERI on metabolic dysfuntion-associated steatotic liver disease was enhanced after knocking down the expression of UBA52.Conclusion ERI may slow down the progression of metabolic dysfuntion-associated steatotic liver disease by down-regulating the expression of UBA52 at both in vivo and in vitro levels.

Objective To investigate the effect of Eriodictyol(ERI)on the development of metabolic dysfunction-associated steatotic liver disease by regulating the expression of ubiquitin A 52(UBA52)at both in vivo and in vitro levels.Methods A mouse metabolic dysfunction-associated steatotic liver disease model was established using a high-fat diet induction.The mice were randomly separated into the normal control group(normal group),the model group,the low-dose ERI group(ERI-L group,50 mg/kg ERI)and the high-dose ERI group(ERI-H group,100 mg/kg ERI),with 12 mice in each group.Oil red O staining was applied to observe lipid deposition in mouse liver tissue.HE staining was applied to observe pathological changes in mouse liver tissue.ELISA method was applied to detect serum levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),low-density lipoprotein cholesterol(LDL-C),total cholesterol(TC)and triglycerides(TG)in mice.The expression of UBA52 protein in liver was detected by Western blot assay.HepG2 cells were treated with 0.5 mmol/L oleic acid to induce an in vitro metabolic dysfunction-associated steatotic liver disease model.HepG2 cells were randomly divide into the control group,the oleic acid induced group,the low concentration ERI group(ERI low group,50 μmol/L ERI),the high concentration ERI group(ERI high group,100 μmol/L ERI),the high concentration ERI+si-NC group(ERI high+si-NC group,100 μmol/L ERI+transfected with si-NC)and the high concentration ERI+si-UBA52 group(ERI high+si-UBA52 group,100 μmol/L ERI+transfected with si-UBA52).Oil red O staining was applied to detect lipid deposition in HepG2 cells of each group.ELISA method was applied to detect the levels of TG,TC,SOD and MDA in HepG2 cells in each group.Immunoblotting was used to detect the expression levels of UBA52,p62 and autophagy related proteins in HepG2 cells.Results Compared with the normal group,serum levels of ALT,AST,LDL-C,TC,TG and the expression of UBA52 protein in liver tissue were increased in the model group(P＜0.05),and the lipid deposition in liver increased,pathological damage was severe,and the proportion of lipid deposition area and non-alcoholic fatty liver disease(NAFLD)activity score were also increased(P＜0.05).Changes in the corresponding indicators in the ERI-L group and the ERI-H group were opposite to those of the model group(P＜0.05),and the ERI-H group was even lower(P＜0.05).The lipid deposition in liver decreased and the pathological damage was alleviated.Compared with the control group,the levels of TG,TC,MDA,the proportion of lipid droplet area and the expression of UBA52 protein were increased in HepG2 cells of the oleic acid-induced group,while the levels of SOD,p62 and LC3Ⅱ/LC3Ⅰ decreased(P＜0.05).Changes in the corresponding indicators of the low-concentration ERI group and the high-concentration ERI group were opposite to those of the oleic acid-induced group(P＜0.05),and the therapeutic effect of ERI on metabolic dysfuntion-associated steatotic liver disease was enhanced after knocking down the expression of UBA52.Conclusion ERI may slow down the progression of metabolic dysfuntion-associated steatotic liver disease by down-regulating the expression of UBA52 at both in vivo and in vitro levels.

Icaritin(ICT)is an 8-isopentenylflavonoid,which is the main effective component of the tra-ditional Chinese medicine Epimedium.Previously,we found that Icaritin inhibits the growth of glioblasto-ma(GBM)cells.Herein we aim to study the in vivo anti-GBM effectiveness of Icaritin and explore its mechanism.The results of MTT assay,flow cytometry,comet assay and cellular immunofluorescence as-say in vitro showed that ICT inhibited the proliferation of four kinds of GBM cells,U87,U251,U118 and A172,induced early apoptosis(P＜0.001)and late apoptosis(P＜0.05)in U87 cells,induced DNA damage in U87 cells,and blocked the growth of U87 cells at the G0/G1 phase(P＜0.0001)in a concen-tration-time-dependent manner.In vivo subcutaneous tumor transplantation tumor experiments showed that feeding 200 mg/kg(P＜0.01)and 400 mg/kg(P＜0.001)ICT had a significant inhibitory effect on the growth of GBM subcutaneous tumors,and had no significant toxic effects on heart,liver,spleen,lung and kidney tissues.The results of network pharmacological analysis,molecular docking and cellular thermodynamic experiments showed that there were 26 possible target proteins between ICT and GBM,a-mong which the expression of p53 in GBM tissues was significantly(P＜0.001)higher than in normal tis-sues,and the binding energy of ICT and p53 was lower;cellular thermodynamic experiments verified that ICT significantly enriched the level of p53 in the living cells of GBM,which indicated that ICT could tar-get p53.The expression of key proteins in the DNA damage repair and apoptosis-associated FOXO signa-ling pathway was detected by ICT.The results showed that the expression of ATR(P＜0.01),P53(P＜0.001),P21(P＜0.05)and γ-H2AX(P＜0.05)was up-regulated,whereas the expression of Cyc-lin E1(P＜0.01),E2F1(P＜0.05),CDK2(P＜0.01),Rb(P＜0.001),p-Rb(P＜0.0001)and WRN(P＜0.0001)expression were down-regulated.There was no significant change in the expres-sion of FOXO 1 in the FOXO pathway or a significant down-regulation of its phosphorylation level.This study demonstrated that ICT could effectively inhibit the growth of GBM cells in vivo.It targets p53 to regulate the DNA damage repair pathway and FOXO signaling pathway to induce GBM cell cycle arrest and apoptosis.

Objective To summarize and analyze the clinicopathological characteristics,imaging manifestations,treatment and prognosis of anaplastic lymphoma kinase(ALK)-positive histiocytosis(APH)involving the central nervous system(CNS),so as to enhance understanding of this rare disease.Methods A retrospective analysis was conducted on 5 cases of CNS-involved APH diagnosed in Huashan Hospital,Fudan University between 2019 and 2023.Clinical,imaging and pathological data were collected,and supplemented by immunohistochemical staining(IHC),fluorescence in situ hybridization(FISH)and high-throughput sequencing for auxiliary diagnosis and molecular characterization.The findings were summarized and integrated with previous literature for a comprehensive analysis.Results All five patients were male,with a mean age of 27.6 years,in which 2 cases exhibited multi-system involvement,while 3 cases exhibited single system involvement.Imaging revealed multiple intracranial lesions in multi-system cases and solitary lesions in single system cases,with well-defined boundaries and homogeneous enhancement.Histologically,tumor cells were intermingled with lymphocytes,displaying an alternating"light and dark"pattern in 1 case.Granuloma-like structures were observed in 4 cases,along with frequent nuclear grooves,indentations and convolutions.Tumor cells usually infiltrated surrounding tissues.IHC demonstrated that tumors expressed histiocytic markers(CD68/CD163)and ALK predominantly expressed in the cytoplasm.FISH confirmed ALK gene rearrangements in all patients,while high-throughput sequencing identified KIF5B-ALK fusions in 2 cases.All single system CNS cases achieved complete remission after surgical resection with or without adjuvant chemotherapy/ALK inhibitors.Among multi-system cases,one achieved partial remission,and one experienced relapse and progression.Conclusion CNS APH is prone to preoperative misdiagnosis.Its histopathological features,ALK immunohistochemical expression,and ALK gene fusions are critical for diagnosis.Patients with single system involvement demonstrate overall superior outcomes compared to multi-system cases.Total resection is effective for localized disease,while multi-system cases require systemic therapy.Multidisciplinary collaboration is crucial for precise diagnosis and treatment.

Objective To investigate the relationship between the expression levels of serum integrin αMβ2(ITG αMβ2)and gasdermin D(GSDMD)in patients with severe acute pancreatitis(SAP)complicated with acute respiratory distress syndrome(ARDS)and the severity of the disease and its value in predicting prognosis.Methods A total of 147 patients with SAP complicated with ARDS(ARDS group)admitted to the Department of Intensive Care Medicine of the Southwest Jiaotong University Affiliated Hospital(Chengdu Third People's Hospital)from August 2021 to October 2023 were selected.According to the oxygenation index(OI),they were divided into mild group(n=35),moderate group(n=46)and severe group(n=66).According to the 28-day prognosis,they were divided into death group(n=77)and survival group(n=70).Another 147 SAP patients without ARDS at the same time period were selected(non-ARDS group).The expression levels of serum ITG αMβ2 and GSDMD were detected by enzyme-linked immunosorbent assay.Spearman method was used to analyze the correlation between serum ITG αMβ2,GSDMD expression levels and OI in patients with SAP complicated with ARDS.Multivariate Logistic regression was used to analyze the factors of death in patients with SAP complicated with ARDS.Receiver operating characteristic(ROC)curve was used to analyze the value of serum ITG αMβ2,GSDMD expression levels in evaluating the death of patients with SAP complicated with ARDS.Results Compared with the non-ARDS group,the expression levels of serum ITG αMβ2(31.95±8.17 ng/L vs 53.33±12.22 ng/L)and GSDMD(2.25±0.55 ng/ml vs 4.39±1.18 ng/ml)in the ARDS group were increased,and the differences were statistically significant(t=17.637,19.899,all P<0.05).The expression levels of serum ITG αMβ2 and GSDMD in mild group,moderate group and severe group increased in turn,and the differences were statistically significant(F=163.069,194.028,all P<0.05).The expression levels of serum ITG αMβ2 and GSDMD were negatively correlated with OI in patients with SAP complicated with ARDS(r=-0.787,-0.778,all P<0.05).The 28-day mortality rate of 147 SAP patients with ARDS was 52.38%(77/147).Compared with the survival group,the expression levels of serum ITG αMβ2(46.96±10.28 ng/L vs 59.11±10.94 ng/L)and GSDMD(3.74±0.98 ng/ml vs 4.98±1.04 ng/ml)in the death group were increased,and the differences were statistically significant(t=6.920,7.415,all P<0.05).The number of extrapulmonary organ failure≥2,prolonged mechanical ventilation time,increased acute physiological and chronic health assessment II score,and increased ITG αMβ2.and GSDMD were independent risk factors for death in SAP patients complicated with ARDS(Wald χ2=4.297～13.536,all P<0.05),and increased OI was an independent protective factor(Wald χ2=8.346,P<0.05).The combined evaluation AUC of serum ITG αMβ2 and GSDMD expression levels results in a larger area under the curve(AUC)for mortality in SAP patients with ARDS compared to the individual evaluation of SAP complicated with ARDS,which was greater than serum ITG αMβ2 and GSDMD expression levels alone,and the differenes were statistically significant(Z=3.517,3.430,all P<0.05).Conclusion The increase of serum ITG αMβ2 and GSDMD expression levels is related to the progression and poor prognosis of patients with SAP complicated with ARDS.The combined monitoring of serum ITG αMβ2 and GSDMD expression levels has a high evaluation value for the risk of death in patients with SAP complicated with ARDS.

Objective To analyze the specific reasons for the suspension and termination of domestic medical device clinical trial projects.Based on the analysis results,provide reference suggestions and improvement measures for all parties in-volved in the trials.Methods Data collection method was used to collect samples of domestic medical device clinical trials,and visits were made to multiple medical institutions.For projects that were suspended or terminated,specific reasons were obtained through on-site interviews with research teams and clinical trial institution staff,reviewing"Project Suspension/Termination Let-ters"stored in the investigator's folder,and telephone consultations with clinical research associates(CRAs)of the projects.A contract research organization(CRO)commercial company was also visited,and specific reasons for project suspension or termi-nation were obtained through on-site interviews or telephone consultations with project managers,CRA-related personnel,etc.Descriptive analysis was used to summarize the reasons for suspension and termination and their rates.Results Statistical analy-sis showed that the suspension and termination rate of medical device clinical trials in China was 17.30％,with a rate of 16.04％in samples collected from medical institutions and 21.30％in samples collected from CRO companies.The reasons leading to the overall suspension and termination of domestic medical device clinical trials included sponsor strategy adjustments,medical insti-tution or research team issues,product or design defects,switching to registration using data from similar products,trial result-re-lated factors,third-party service provider issues,other reasons,safety-related factors,pandemic reasons,regulatory updates,and difficulties in obtaining informed consent.Conclusion The reasons for the suspension and termination of domestic medical de-vice clinical trial projects are complex and diverse,with a statistical analysis showing a rate of 17.30％in China.

Breast cancer is the most prevalent malignancy among women worldwide.In recent years,immune checkpoint inhibitors(ICIs)have emerged as a promising therapeutic strategy across different molecular subtypes of breast cancer,demonstrating significant clinical potential.This review systematically summarized the progress and clinical applications of ICIs in hormone receptor-positive(HR-positive),human epidermal growth factor receptor 2-overexpressing(HER2-positive),and triple-negative breast cancer(TNBC).In HR-positive breast cancer,the KEYNOTE-756 and CheckMate 7FL trials demonstrated that ICIs combined with neoadjuvant chemotherapy significantly improved the pathological complete response(pCR)rate,with greater benefits observed in programmed cell death-ligand 1(PD-L1)-positive patients.Furthermore,the PROMENADE study indicated that estrogen receptor(ER)-low HER2-negative breast cancer patients achieved a pCR rate closer to that of TNBC rather than HR-positive breast cancer following ICIs treatment.In metastatic HR-positive breast cancer,the SACI-IO and DOLAF studies suggested that ICIs combined with antibody-drug conjugates(ADC)or poly(ADP-ribose)polymerase(PARP)inhibitors may provide clinical benefits for specific subgroups of patients.For HER2-positive breast cancer,the Keyriched-1 and Neo-PATH studies revealed that ICIs combined with anti-HER2 therapy might improve pCR rates in HR-negative/HER2-positive patients.However,the Impassion-050 and KATE2 trials failed to demonstrate widespread clinical benefits of ICIs in HER2-positive breast cancer.In TNBC,long-term follow-up data from the KEYNOTE-522 study showed that ICIs combined with neoadjuvant chemotherapy not only improved pCR rates but also conferred long-term survival benefits.Additionally,the Impassion-130,KEYNOTE-355,and TORCHLIGHT studies confirmed that ICIs combined with chemotherapy prolonged both progression-free survival(PFS)and overall survival(OS)in PD-L1-positive advanced TNBC patients.Meanwhile,treatment strategies combining ICIs with anti-angiogenic therapy,PARP inhibitors and ADCs have demonstrated promising efficacy in TNBC(SPARK and BEGONIA trial).Currently,ICIs combined with chemotherapy remains the primary treatment approach,while combination strategies involving ICIs with anti-HER2 therapy,endocrine therapy,ADCs,and anti-angiogenic therapy are actively being explored.However,challenges remain,including complex resistance mechanisms,heterogeneous treatment responses,and the management of immune-related adverse events.Future research should focus on refining patient stratification strategies and developing more precise combination therapies to improve long-term survival outcomes for breast cancer patients.