Objectives:To investigate the effect of non-optimal temperature exposure during pregnancy on the risk for preterm birth and identify the susceptible exposure window. At the same time, the interaction between non-optimal temperature and pollutants exposure during pregnancy on preterm birth was analyzed, in order to provide strong clues for the influence of non-optimal temperature exposure during pregnancy on the risk for preterm birth.Methods:A total of 1 852 pregnant women were recruited from September 2021 to June 2023 in Fujian Provincial Maternal and Child Health Care Center. Questionnaire survey was conducted, and their health records were analyzed. The permanent address of each pregnant woman was matched with Fifth Generation European Centre for Medium-Range Weather Forecasts Atmospheric Reanalysis of the Global Climate and a geo-statistical combination model based on satellite remote sensing data collection, then follow-up for pregnancy outcome was conducted. Distributed lag nonlinear model was used to assess the association between exposure to non-optimal temperature during pregnancy and the risk for preterm birth and a multiplicative interaction model was used to assess the interaction between exposure to pollutants and non-optimal temperatures during pregnancy on the risk for preterm birth.Results:After adjusting for potential confounders such as maternal age, occupation, Gross Domestic Product of the region, pre-pregnancy preconception BMI, newborn sex, the weekly susceptibility windows of extreme low temperature ( P1, P3, P5) were week 1-22 , and the weekly susceptibility windows of extreme high temperature ( P95, P97, P99) were week 27 and week 32-36. Extreme low temperature [ P1 ( OR=1.147, 95% CI: 1.041-1.265), P5 ( OR=1.284, 95% CI: 1.035-1.501)] and extreme high temperature [ P97 ( OR=1.146, 95% CI: 1.039-1.263), P99 ( OR=1.216, 95% CI: 1.099-1.345)] exhibited multiplicative interaction with PM 2.5. Conclusions:Exposure to non-optimal temperature during pregnancy was associated with an increased risk for preterm birth. The susceptible exposure windows of extreme low temperature were mainly in early and mid-pregnancy, and the susceptible exposure windows of extreme high temperature were mainly in late-pregnancy. Exposure to non-optimal temperatures and pollutants during pregnancy was associated with an increased risk for preterm birth.

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.

Objectives:To investigate the effect of non-optimal temperature exposure during pregnancy on the risk for preterm birth and identify the susceptible exposure window. At the same time, the interaction between non-optimal temperature and pollutants exposure during pregnancy on preterm birth was analyzed, in order to provide strong clues for the influence of non-optimal temperature exposure during pregnancy on the risk for preterm birth.Methods:A total of 1 852 pregnant women were recruited from September 2021 to June 2023 in Fujian Provincial Maternal and Child Health Care Center. Questionnaire survey was conducted, and their health records were analyzed. The permanent address of each pregnant woman was matched with Fifth Generation European Centre for Medium-Range Weather Forecasts Atmospheric Reanalysis of the Global Climate and a geo-statistical combination model based on satellite remote sensing data collection, then follow-up for pregnancy outcome was conducted. Distributed lag nonlinear model was used to assess the association between exposure to non-optimal temperature during pregnancy and the risk for preterm birth and a multiplicative interaction model was used to assess the interaction between exposure to pollutants and non-optimal temperatures during pregnancy on the risk for preterm birth.Results:After adjusting for potential confounders such as maternal age, occupation, Gross Domestic Product of the region, pre-pregnancy preconception BMI, newborn sex, the weekly susceptibility windows of extreme low temperature ( P1, P3, P5) were week 1-22 , and the weekly susceptibility windows of extreme high temperature ( P95, P97, P99) were week 27 and week 32-36. Extreme low temperature [ P1 ( OR=1.147, 95% CI: 1.041-1.265), P5 ( OR=1.284, 95% CI: 1.035-1.501)] and extreme high temperature [ P97 ( OR=1.146, 95% CI: 1.039-1.263), P99 ( OR=1.216, 95% CI: 1.099-1.345)] exhibited multiplicative interaction with PM 2.5. Conclusions:Exposure to non-optimal temperature during pregnancy was associated with an increased risk for preterm birth. The susceptible exposure windows of extreme low temperature were mainly in early and mid-pregnancy, and the susceptible exposure windows of extreme high temperature were mainly in late-pregnancy. Exposure to non-optimal temperatures and pollutants during pregnancy was associated with an increased risk for preterm birth.

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.

BACKGROUND: One of the most important treatment modalities for non-small cell lung cancer (NSCLC) is immune checkpoint inhibitor. Nevertheless, a small percentage of patients do not respond well to these therapies, highlighting the significance of identifying important CD8+ T cell subsets for immunotherapy and creating trustworthy biomarkers. The purpose of this study is to assess the potential utility of TIM3+CD8+ T cells as new biomarkers by examining their expressions in various areas of the NSCLC tumor microenvironment. METHODS: Based on biopsy techniques, tumor tissue samples were obtained from patients with NSCLC and categorized into tumor central and non-central regions. Using flow cytometry, the infiltration of TIM3+CD8+ T cells and the surface expression of programmed cell death 1 (PD-1) on these cells were examined, and their correlations with the effectiveness of immunotherapy were assessed. RESULTS: The non-central region of tumor tissues had considerably larger infiltration of TIM3+CD8+ T lymphocytes compared to the non-central region (P<0.0001). This pattern was found in both subgroups with tumor diameters ≥3 cm or <3 cm (P<0.01). In comparison to TIM3-CD8+ T cells, TIM3+CD8+ T cells showed higher levels of PD-1 (P<0.001), with more PD-1+TIM3+CD8+ T cells invading the non-central region (P<0.01). Clinical responders to immunotherapy had considerably lower infiltration levels of TIM3+CD8+ T cells in the tumor non-central region compared to non-responders, with lower levels correlated with better clinical outcomes (P<0.01), while no correlation was identified in the tumor central region (P>0.05). According to reciever operating characteristic (ROC) curve analysis, TIM3+CD8+ T cells in the tumor non-central region had an area under the curve (AUC) of 0.9375 for predicting the effectiveness of immunotherapy, which was considerably higher than that of TIM3+CD8+ T cells in the tumor central region and programmed cell death ligand 1 (PD-L1) [tumor proportion score (TPS)]. CONCLUSIONS In the tumor microenvironment of NSCLC, TIM3+CD8+ T cells show regional distribution patterns. The expression of this cell population in the non-central region of the tumor microenvironment may be a biomarker for predicting the effectiveness of immunotherapy.
Humans ; Carcinoma, Non-Small-Cell Lung/metabolism* ; Lung Neoplasms/metabolism* ; Hepatitis A Virus Cellular Receptor 2/immunology* ; Tumor Microenvironment/immunology* ; CD8-Positive T-Lymphocytes/metabolism* ; Male ; Female ; Middle Aged ; Aged ; Adult ; Programmed Cell Death 1 Receptor/metabolism* ; Immunotherapy ; Clinical Relevance

Objective:To investigate the effects of Bushen Jianpi formula(BSJP)in mediating the inhibitory effects of farnesoid X receptor(FXR)on cancer cachexia(CC)induced by hepatocellular carcinoma AH-130 cells in a rat model and its underlying mechanism.Methods:A liver cancer cachexia rat model was established by intraperitoneal injection of AH-130 cells.The rats were divided into five groups:blank control,model control,CDCA(FXR agonist),BSJP,and BSJP+CDCA groups.After modelling,the rats were treated with CDCA,BSJP,or their combination for consecutive 16 days,and their body weights were measured weekly.At the end of the experiment,the rats were sacrificed,and abdominal aortic blood,feces,and brown adipose tissues from the epididymal,inguinal,and scapular regions were collected.Liquid chromatography-mass spectrometry(LC-MS)was used to detect the composition and content of bile acids in serum and feces of rats.WB and qPCR were used to detect the expression of FXR,Wnt family member 10b(Wnt10b),β-catenin,and uncoupling protein 1(UCP-1)in the ileum,brown adipose,and white adipose tissues of rats.Results:Compared with the blank control group,the body mass of the rats in the model group was significantly reduced(P<0.01);compared with the model control group,the body mass of the rats in CDCA,BSJP and BSJP+CDCA groups all increased(P<0.01).Compared with the blank control group,the epididymal,inguinal,scapular,and total brown adipose tissue mass were all elevated in the model control group(all P<0.05);compared with the model control group,the brown fat mass in the inguinal and epididymis regions of the rats decreased significantly in all treatment groups(P<0.05),but this decrease was not significant in the scapular region(P>0.05);besides,the total brown fat mass decreased notably in all treatment groups compared to the model control group(all P<0.01).LC-MS analysis showed that the composition and content of bile acids in the serum and feces of rats were altered in all groups.qPCR and WB results confirmed that,compared to the model group,BSJP and BSJP+CDCA promoted the mRNA and protein expression of FXR in the ileum,brown adipose,and white adipose tissues of rats(all P<0.05),and decreased the mRNA and protein expression of Wnt10b,β-catenin,UCP-1(all P<0.05).Conclusion:The BSJP formula can inhibit hepatocellular carcinoma cell AH-130-induced cachexia in rats,alleviating the associated body weight loss and brown adipose tissue formation.The mechanism may involve the regulation of FXR and the inhibition of the expression of Wnt10b,β-catenin,and UCP-1 in brown adipose tissue through the Wnt signaling pathway.

Objective·To establish a transgenic zebrafish line Tg(amh:mCherry)for studying gonadal development and related diseases,and to trace and analyze the developmental process of zebrafish gonads.Methods·A recombinant transgenic expression vector pTol2-amh-mCherry was constructed by using the upstream promoter sequence of the zebrafish anti-Müllerian hormone(amh)gene coding region and the gene coding sequence of the red fluorescent protein,and was validated by using Sanger sequencing.The recombinant transgenic expression vector and mRNA of Tol2 transposase were co-microinjected into zebrafish embryos,and fluorescent zebrafish were selected by using fluorescence microscope to screen for a stable inherited transgenic zebrafish line Tg(amh:mCherry).In situ hybridization was used to detect whether the location of the fluorescence signals was consistent with the location of endogenous expression of amh.The red fluorescence of transgenic zebrafish from generation F3 was observed by fluorescence microscopy,and the process of gonadal development was tracked and analyzed.Results·The recombinant transgenic expression vector pTol2-amh-mCherry was successfully constructed,and a stable inherited F3 generation transgenic zebrafish line Tg(amh:mCherry)was successfully established.The results of in situ hybridization showed that the location of the red fluorescence signals in the transgenic zebrafish Tg(amh:mCherry)was consistent with the location of endogenous expression of amh.Through observation and analysis of the fluorescence of transgenic zebrafish from F3 generation,five developmental patterns of zebrafish gonads were found.Conclusion·The successful construction of Tg(amh:mCherry)transgenic zebrafish line facilitates the tracer analysis of zebrafish gonadal development,which provides a better experimental model for the study of gonad-related diseases.

Objective·To establish a transgenic zebrafish line Tg(amh:mCherry)for studying gonadal development and related diseases,and to trace and analyze the developmental process of zebrafish gonads.Methods·A recombinant transgenic expression vector pTol2-amh-mCherry was constructed by using the upstream promoter sequence of the zebrafish anti-Müllerian hormone(amh)gene coding region and the gene coding sequence of the red fluorescent protein,and was validated by using Sanger sequencing.The recombinant transgenic expression vector and mRNA of Tol2 transposase were co-microinjected into zebrafish embryos,and fluorescent zebrafish were selected by using fluorescence microscope to screen for a stable inherited transgenic zebrafish line Tg(amh:mCherry).In situ hybridization was used to detect whether the location of the fluorescence signals was consistent with the location of endogenous expression of amh.The red fluorescence of transgenic zebrafish from generation F3 was observed by fluorescence microscopy,and the process of gonadal development was tracked and analyzed.Results·The recombinant transgenic expression vector pTol2-amh-mCherry was successfully constructed,and a stable inherited F3 generation transgenic zebrafish line Tg(amh:mCherry)was successfully established.The results of in situ hybridization showed that the location of the red fluorescence signals in the transgenic zebrafish Tg(amh:mCherry)was consistent with the location of endogenous expression of amh.Through observation and analysis of the fluorescence of transgenic zebrafish from F3 generation,five developmental patterns of zebrafish gonads were found.Conclusion·The successful construction of Tg(amh:mCherry)transgenic zebrafish line facilitates the tracer analysis of zebrafish gonadal development,which provides a better experimental model for the study of gonad-related diseases.