ObjectiveTo understand the seropositivity of neutralizing antibodies (NAb) and low-level NAb against SARS-CoV-2 infection in the community residents, and to explore the impact of COVID-19 vaccination and SARS-CoV-2 infection on the levels of NAb in human serum. MethodsOn the ground of surveillance cohort for acute infectious diseases in community populations in Shanghai, a proportional stratified sampling method was used to enroll the subjects at a 20% proportion for each age group (0‒14, 15‒24, 25‒59, and ≥60 years old). Blood samples collection and serum SARS-CoV-2 NAb concentration testing were conducted from March to April 2023. Low-level NAb were defined as below the 25^th percentile of NAb. ResultsA total of 2 230 participants were included, the positive rate of NAb was 97.58%, and the proportion of low-level NAb was 25.02% (558/2 230). Multivariate logistic regression analysis indicated that age, infection history and vaccination status were correlated with low-level NAb (all P<0.05). Individuals aged 60 years and above had the highest risk of low-level NAb. There was a statistically significant interaction between booster vaccination and one single infection (aOR=0.38, 95%CI: 0.19‒0.77). Compared to individuals without vaccination, among individuals infected with SARS-CoV-2 once, both primary immunization (aOR=0.23, 95%CI: 0.16‒0.35) and booster immunization (aOR=0.12, 95%CI: 0.08‒0.17) significantly reduced the risk of low-level NAb; among individuals without infections, only booster immunization (aOR=0.28, 95%CI: 0.14‒0.52) showed a negative correlation with the risk of low-level NAb. ConclusionsThe population aged 60 and above had the highest risk of low-level NAb. Regardless of infection history, a booster immunization could reduce the risk of low-level NAb. It is recommended that eligible individuals , especially the elderly, should get vaccinated in a timely manner to exert the protective role of NAb.

Objective To explore the quantitative evaluation of integrity risk prevention and control in public hospitals,provide reference for improving the quality and efficiency of integrity risk prevention and control.Methods Self-designed"Inspection Standards for Integrity Risk Prevention and Control of Power Matters in Public Hospitals"was used to score and rate the power matters provided by each functional department/clinical department of West China Hospital of Sichuan University from three aspects:the clarity of power operation process,the accuracy of finding integrity risk points,the effectiveness of prevention and control measures.Results A total of 236 power matters of the hospital were inspected for integrity risk prevention and control,and according to the inspection criteria,57 items were rated as first grade,103 items were rated as second grade,and 76 items were rated as third grade,accounting for 24.15％,43.64％and 32.20％,respectively.The score for the special work of integrity risk prevention and control was 5.82±1.92 points,of which the process dimension score was 2.11±0.75 points,the risk points dimension score was 1.89±0.92 points,the prevention and control dimension score is 1.89± 0.79 points,which reflects the problems of unclear workflow,inaccurate finding of individual risk points,and unspecified prevention and control measures in some units.Conclusion Hospitals should focus on the concreteness,accuracy,salience and quantification in the long-term construction of integrity risk prevention and control from the aspects of thought,behavior,effectiveness and evaluation.

Background::With an increasing number of patients with hematological malignancies being treated with umbilical cord blood transplantation (UCBT), the correlation between immune reconstitution (IR) after UCBT and graft-versus-host disease (GVHD) has been reported successively, but reports on double-negative T (DNT) cell reconstitution and its association with acute GVHD (aGVHD) after UCBT are lacking.Methods::A population-based observational study was conducted among 131 patients with hematological malignancies who underwent single-unit UCBT as their first transplant at the Department of Hematology, the First Affiliated Hospital of USTC, between August 2018 and June 2021. IR differences were compared between the patients with and without aGVHD.Results::The absolute number of DNT cells in the healthy Chinese population was 109 (70-157)/μL, accounting for 5.82 (3.98-8.19)% of lymphocytes. DNT cells showed delayed recovery and could not reach their normal levels even one year after transplantation. Importantly, the absolute number and percentage of DNT cells were significantly higher in UCBT patients without aGVHD than in those with aGVHD within one year ( F = 4.684, P = 0.039 and F = 5.583, P = 0.026, respectively). In addition, the number of DNT cells in the first month after transplantation decreased significantly with the degree of aGVHD increased, and faster DNT cell reconstitution in the first month after UCBT was an independent protective factor for aGVHD (HR = 0.46, 95% confidence interval [CI]: 0.23-0.93; P = 0.031). Conclusions::Compared to the number of DNT cells in Chinese healthy people, the reconstitution of DNT cells in adults with hematological malignancies after UCBT was slow. In addition, the faster reconstitution of DNT cells in the early stage after transplantation was associated with a lower incidence of aGVHD.

As the understanding of the pathogenic mechanisms of gastric cancer deepens and the identification of gastric cancer driver genes advances,drugs targeting gastric cancer driver genes have been applied in clinical practice.Among them,trastuzumab,as the first targeted drug for gastric cancer,effectively inhibits the proliferation and metastasis of tumor cells by targeting overexpressed human epidermal growth factor receptor 2(HER2).Trastuzumab has become the standard treatment for HER2-positive gastric cancer patients.Ramucirumab,on the other hand,inhibits tumor angiogenesis by targeting vascular endothelial growth factor receptor 2(VEGFR2)and has been used as second-line therapy for advanced gastric cancer patients.In addition,bemarituzumab targets overexpressed fibroblast growth factor receptor 2(FGFR2),while zolbetuximab targets overexpressed claudin 18.2(CLDN18.2),significantly extending progression-free survival and overall survival in patients with gastric cancer in clinical trials.This article reviews the roles of tumor driver genes in the progression of gastric cancer,and the treatment strategies for gastric cancer primarily based on targeting HER2,VEGF,FGFR2,CLDN18.2 and MET.This provides a reference for clinical application of targeted therapy for gastric cancer.

Objective : To investigate the effect of sinomenine on proliferation and migration of multiple myeloma (MM) cells by regulating STAT3 and NF-κB signaling pathway． Methods : The cultured U266 cells were treated with different concentrations of sinomenine (0，0．5，1，2 mmol / L) ．The control group was added DMSO with 0．5% concentration．CCK-8 assay was used to detect the proliferation of U266 cells．Flow cytometry was used to detect the apoptosis of U266 cells．Western blot assay was used to detect the expression levels of apoptosis-related proteins， STAT3 and NF-κB signaling pathway proteins in the each group. Results : Compared with CON group，the apopto- sis of U266 cells increased after Sinomenine treatment，the proliferation was inhibited ; B lymphoma-2 (Bcl-2) mye- loid and cell leukemia-1 (Mcl-1) expression level decreased ; activated Caspase-3 (cleaved Caspase-3) and PARP (Cleaved Caspase-3) expression levels increased ; the activity of STAT3 and NF-κB signaling pathway decreased. Conclusion Sinomenine can down-regulate the activity of STAT3 and NF-κB signaling pathway，promote the apop- tosis of U266 cells and inhibit the proliferation of U266 cells.

Objective:To investigate the risk factors of early neurological deterioration (END) in patients with minor ischemic stroke caused by large vessel occlusion (LVO) and the impact of rescue endovascular thromboectomy (REVT) on clinical outcomes of patients with END at discharge.Methods:Consecutive patients with acute minor ischemic stroke caused by LVO within 24 h of onset in the Third Affiliated Hospital, Soochow University from January 2021 to March 2023 were retrospectively enrolled. Minor ischemic stroke was defined as baseline National Institute of Health Stroke Scale (NIHSS) score ≤5 at admission. END was defined as an increase of ≥4 in the NIHSS score within 24 h after the best medical management. The modified Rankin Scale was used to evaluate the clinical outcomes of patients with END at discharge. 0-2 was defined as a good outcome. Multivariate logistic regression analysis was used to identify the independent risk factors for END and the impact of REVT on clinical outcomes in patients with END. Results:A total of 75 patients with minor ischemic stroke caused by LVO were included, of which 31 (41.3%) developed END and 13 (41.9%) underwent REVT after END. Multivariate logistic regression analysis showed that internal carotid artery occlusion was an independent risk factor for END (odds ratio 4.304, 95% confidence interval 1.213-15.270; P=0.024), and REVT was an independent protective factor for good outcomes in patients with END (odds ratio 0.068, 95% confidence interval 0.006-0.774; P=0.030). Conclusions:The incidence of END is higher in patients with minor ischemic stroke caused by LVO, and internal carotid artery occlusion is an independent risk factor for the occurrence of END. Providing REVT after END may improve the clinical outcomes of patients with END at discharge.

Objective:To analyze the features of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) co-infected with other common respiratory pathogens among coronavirus disease 2019 (COVID-19) patients in Shanghai City, and to provide a reference for scientific prevention and control of COVID-19 and other respiratory infectious diseases.Methods:Descriptive epidemiological approaches were used to analyze the data of COVID-19 reported cases in Shanghai City from January 2020 to February 2021 in the information system of Chinese Disease Prevention and Control. Clinical data of the participants were collected, and their SARS-CoV-2 nucleic acid-positive respiratory specimens were collected at the time of illness onset or admission. Multiplex reverse transcription-polymerase chain reaction (RT-PCR) was performed to detect the 22 respiratory pathogens. Independent-samples t test was used for statistical analysis. Results:Of the 272 patients with COVID-19, 15(5.5%) had co-infection of SARS-CoV-2 with other respiratory pathogens, all of which were double infection. There were three cases infected with enterovirus/rhinovirus, two of each with adenovirus, human metapneumovirus and coronavirus NL63/HKU1, and one of each with coronavirus 229E, influenza A virus H1N1, parainfluenza virus 1 and respiratory syncytial virus B. Two cases infected with Mycoplasma pneumoniae. Among the 272 COVID-19 patients, 212(77.9%) had fever, 117(43.0%) had cough, 46(16.9%) had fatigue, and 35(12.9%) had sore throat. The white blood cell count of co-infection cases was higher than that of non-co-infection cases ((6.8±1.7)×10 9/L vs (5.3±1.6)×10 9/L), and the difference was statistically significant ( t=3.09, P=0.008). Conclusions:There is a certain proportion of co-infection of SARS-CoV-2 with other respiratory pathogens among the COVID-19 cases in Shanghai City, mainly viral pathogens, especially enterovirus/rhinovirus. A rational combination of drugs was recommended to improve the cure rate. Surveillance of acute respiratory infection should be further strengthened as well.

Objective:To investigate the effects of the interaction between ubiquitin-specific peptidase 22 (USP22) and hepatitis B virus X protein (HBx) on the protein level and the biological function of HBx.Methods:The interactions between HBx and USP22 were analyzed by GST pull-down, co-immunoprecipitation assay and confocal laser scanning assay. USP22 recombinant plasmids or specific siRNA were transiently co-transfected with HBx plasmids. Western blot were used to detect the protein level of HBx. The half-life and degradation pathway of HBx in the transfected cells treated with cycloheximide (CHX) or proteasome inhibitor MG132 were detected. In vivo ubiquitination assay was used to detect the ubiquitination of HBx with USP22 overexpression. Moreover, dual-luciferase reporter assay and colony formation assay were used to analyze the effects of USP22 on the biological function of HBx. Results:USP22 could interact with HBx in vivo and in vitro. USP22 significantly increased the stability of HBx and inhibited the proteasome-mediated degradation of HBx protein by reducing the ubiquitination of HBx, thereby enhancing the biological function of HBx. Conclusions:USP22 inhibited HBx protein degradation through ubiquitin-dependent proteasome pathway, thus enhancing the stability and biological function of HBx.

This article summarizes and analyzes the reported synthetic routes of brivudine in patent and literature.2′-Deoxyuridine was employed as starting material, affording brivudine through iodization, heck coupling, hydrolysis, decarboxylation, bromination and recrystallization.After optimization of reaction conditions of each step, a synthetic route suitable for industrial production was achieved with simple synthetic process, high yield and excellent purity.

Objective:To evaluate the effect of hierarchical diagnosis and treatment model of childhood bronchial asthma in Shanghai Pudong New Area.Methods:According to the principle of proximity, children aged 6 months-17 years who were diagnosed with bronchial asthma at Shanghai Children′s Medical Center from July 2016 to May 2017 were divided into two cohorts: the specialized hospital group and the community hospital group.Twelve months of treatment and follow-up were conducted.The asthma control level, Childhood Asthma Control Test (C-ACT) score, medication adherence and health economic indicators were collected.Results:A total of 524 children were included for data analysis and divided into the specialized hospital group (300 cases) and the community hospital group (224 cases). According to the Global Initiative for Asthma(GINA) criteria, there was no statistical difference in monthly asthma control level between the two groups (all P>0.05). In the 12 th month, the well-controlled rate of the specialized hospital group increased by 12.4% ( P<0.01), and that of the community hospital group increased by 22.9% ( P= 0.015). According to the C-ACT criteria, there was no statistical difference in the monthly well-controlled rate between the two groups (all P>0.05), and the rate maintained an upward trend.The rates of patients with good compliance in the specialized hospital group and the community hospital group at the 12 th month of hierarchical diagnosis and treatment were 78.3%(235/300 cases) and 75.0%(168/224 cases), respectively, and the difference was not statistically significant ( P=0.370). After 12 months of hierarchical diagnosis and treatment, the number of asthma attacks were 1.0 and 2.0 ( P=0.269), and the hospitalization rates for asthma were 3.0%(9/300 cases) and 4.9%(11/224 cases), respectively in the specialized hospital group and the community hospital group, and the diffe-rence was not statistically significant ( P=0.259); the number of respiratory infections in the specialized hospital group (2.0 times) was lower than that in the community hospital group (3.0 times), and the total cost of treatment in the community hospital group (2 471.5 Yuan) was lower than that in the specialized hospital group (3 445.5 Yuan), and the difference was statistically significant ( Z=-3.308, -3.336, all P<0.01). Twelve months after hierarchical diagnosis and treatment, the number of asthma attacks, the number of respiratory infections and the hospitalization rate for asthma in the two groups were all lower than those in the first 12 months of hierarchical diagnosis and treatment, and the difference was statistically significant (all P<0.01). Conclusions:Hierarchical diagnosis and treatment model of childhood asthma in Shanghai Pudong New Area can improve asthma control level, C-ACT score and asthma medication adherence, and enhance health economic benefits, thus it′s an effective way to manage childhood asthma.