Given that ovarian stimulation is vital for assisted reproductive technology (ART) and results in elevated serum estrogen levels, exploring the impact of elevated estrogen exposure on oocytes and embryos is necessary. We investigated the effects of various ovarian stimulation treatments on oocyte and embryo morphology and gene expression using a mouse model and estrogen-treated mouse embryonic stem cells (mESCs). Female C57BL/6J mice were subjected to two types of conventional ovarian stimulation and ovarian hyperstimulation; mice treated with only normal saline served as controls. Hyperstimulation resulted in high serum estrogen levels, enlarged ovaries, an increased number of aberrant oocytes, and decreased embryo formation. The messenger RNA (mRNA)‍-sequencing of oocytes revealed the dysregulated expression of lysine-specific demethylase 6b (Kdm6b), which may be a key factor indicating hyperstimulation-induced aberrant oocytes and embryos. In vitro, Kdm6b expression was downregulated in mESCs treated with high-dose estrogen; treatment with an estrogen receptor antagonist could reverse this downregulated expression level. Furthermore, treatment with high-dose estrogen resulted in the upregulated expression of histone H3 lysine 27 trimethylation (H3K27me3) and phosphorylated H2A histone family member X (γ-H2AX). Notably, knockdown of Kdm6b and high estrogen levels hindered the formation of embryoid bodies, with a concomitant increase in the expression of H3K27me3 and γ-H2AX. Collectively, our findings revealed that hyperstimulation-induced high-dose estrogen could impair the demethylation of H3K27me3 by reducing Kdm6b expression. Accordingly, Kdm6b could be a promising marker for clinically predicting ART outcomes in patients with ovarian hyperstimulation syndrome.
Female ; Mice ; Demethylation/drug effects* ; Embryonic Stem Cells ; Estrogens/administration & dosage* ; Gene Expression/drug effects* ; Histones/metabolism* ; Jumonji Domain-Containing Histone Demethylases/metabolism* ; Mice, Inbred C57BL ; Oocytes ; Ovary/drug effects* ; Reproductive Techniques, Assisted ; Animals

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ObjectiveTo analyze the epidemiological characteristics of clustered vomiting and diarrhea outbreaks in Minhang District of Shanghai, to identify the influencing factors of outbreak scale and duration of epidemic, and to provide scientific evidence for further strengthening surveillance early-warning efforts in key settings and for optimizing prevention and control measures. MethodsThe data for describing epidemiological characteristics of clustered vomitting and diarrhea outbreaks in Minhang District from 2018 to 2023 were collected, multivariable logistic regression models were applied to analyze the influencing factors for epidemic scale,and Spearman rank correlation analyses were applied to analyze the factors duration. ResultsA total of 136 clustered vomiting and diarrhea outbreaks were reported in Minhang District from 2018 to 2023, all occurring in school settings, with an overall attack rate of 0.90%. The outbreaks exhibited distinct seasonality, predominantly occurring from October to December (43.38%) and March to May (32.35%). The primary settings were preschools (45.59%) and elementary schools (44.12%), with students accounted for the majority of cases (99.48%). The predominant clinical manifestation was vomiting (90.44%), with person-to-person contact being the primary transmission route (98.53%). Norovirus genogroup Ⅱ was identified as the main pathogen (71.32%). Standardized terminal disinfection of outbreak sites (OR=0.39, 95%CI=0.20‒0.74) and effective isolation of affected classes (OR=0.23, 95%CI=0.09‒0.57) were significant protective factors for reducing outbreak scale. Both response time (r=0.64, P<0.001) and the number of case generations (r=0.71, P<0.001) showed positive correlations with outbreak duration. ConclusionSchools are the key settings for the prevention and control of clustered vomiting and diarrhea outbreaks in Minhang District, with peak occurring in autumn and spring. Early detection, timely reporting, and prompt response to outbreaks are crucial. Strengthening school-based surveillance systems and standardizing outbreak management protocols are of particular importance.

Objective It evaluates the high-quality development policies of public hospitals at the provincial level in China,and provides theoretical basis and countermeasures for formulating and optimizing the high-quality develop-ment policies of public hospitals.Methods The ROST CM 6.0 software was used to conduct text mining for 11 sample policies,and the Policy Modeling Consistency(PMC)index model was constructed to evaluate the sample policies quantitatively.Results The average PMC index of 11 sample policies included in the study was 7.16 points,of which 8 were excellent grades and 3 were qualified grades.The first-level variables X5 service system(0.82),X8 Party leadership(0.91)and X6 organization and operation(0.94)scored higher;X2 policy timeliness(0.52),X7 cultural construction(0.68)and X4 service capability(0.71)scored low.Conclusion The content of the high-quality develop-ment policy of public hospitals at the provincial level is basically in line with the national policy,and is relatively excel-lent in the aspects of organization and operation,service system and party leadership,etc.,but there are some weaknesses in the aspects of policy timeliness,cultural construction and service capacity,etc.,which can be op-timized and improved from the aspects of improving service capacity,supplementing long-term policies and strengthening hospital cultural construction.

Objective To explore the high-quality development path of tertiary public hospitals and provide scientific reference for deepening the reform of public hospitals.Methods Based on SPO theory,it constructed an analytical framework for the high-quality development of tertiary public hospitals,collected data of a quarterly monitoring in-dex for the performance assessment and high-quality development of tertiary public hospitals in a certain province in 2023,and analysed 73 tertiary public hospitals participating in the performance assessment as the object of analy-sis,and adopted the fuzzy-set Qualitative Comparative Analysis to explore different condition sets of high-quality de-velopment of tertiary public hospitals and reveal the path of high-quality development of public hospitals.Results High-quality development is the result of multi-factor interaction.Four configurations were identified to promote the high-quality development of tertiary public hospitals:service quality-technology-driven path,service quality-driven path,comprehensive service-driven path,and service quality-benefit-driven path.Quality safety and functional orientation were found to be the core elements in promoting high-quality development of public hospitals.Conclusion Hospitals at all levels should strengthen the guidance of party building,combine with the actual functional positioning,take quality and safety as the core,and optimize the combination conditions of technical level,personnel structure,service process,and cost control.It is essential to clarify the development strategy of hospitals,implement the dynamic concept,and realize the high-quality development of public hospitals.

Objective To empirically analyze the status quo of high-quality development of public hospitals in S Province,provides reference for promoting high-quality development of public hospitals.Methods SPSS 26.0 soft-ware and text analysis method were used to process the high-quality development monitoring data of tertiary public hospitals in S Province,and the qualitative interview results obtained by field investigation were comprehensively ana-lyzed.Results In terms of capacity improvement,public hospitals actively take measures such as the construction of medical union and the reform of payment methods to improve their capacity.Specialized hospitals and maternity and child care hospitals need to be improved in some indicators.In terms of structural optimization,the quality of medi-cal services is high in all regions.The proportion of medical service revenue and the proportion of high-grade surgery still need to be increased.In terms of innovation and efficiency improvement,the application level of electronic medi-cal records has made remarkable progress in various regions.There are differences in the funding of scientific re-search projects.In terms of cultural cohesion,patient satisfaction was higher.There is improvement room in the satisfaction of medical staff.Conclusion Third-level public hospitals in S province have achieved certain results in high-quality de-velopment,but there are still problems,such as the need to further integrate party building work with hospital busi-ness work,the lack of connection between performance incentive and performance evaluation index system,and the need to improve the satisfaction of medical staff.It is necessary to solve the problem and improve the quality and efficiency of medical service.

Objective To sort out and quantitatively evaluate the policies of"Internet+Nursing Service",and provide reference for the formulation and improvement of policies.Methods It uses ROST CM 6.0 software to mine the text data of 6"Internet+Nursing service"policies,constructs Policy Modeling Consistency(PMC)index model,and uses 9 first-class variables and 43 second-class variables to quantitatively evaluate the"Internet+Nursing service"policies.Results Among the 6 policies,1 policies were of good grade,5 policies were of acceptable grade,and the mean value of PMC index was 6.40,which was at the level of qualified or above,with higher scores on the primary variables X7 policy tools(0.95),X1 policy nature(0.92)and X9 policy evaluation(0.83),and lower scores on X8 incentive methods(0.63),X2 issuing organizations(0.58),and X5 policy timeliness(0.25).Conclusion The construction of the policy framework of"Internet+Nursing Service"in China is in the exploratory stage,and there is still room for improvement.It is recommended to improve the continuity and standardization of"Internet+Nursing Service"through rational planning of policy timing,comprehensive implementation of division of labour and coordination,and adoption of diversified incentives,etc.,so as to facilitate the high-quality development of public hospitals.

Objective:To investigate the efficacy and prognostic survival of pembrolizumab combined with apatinib and chemotherapy in the treatment of human epidermal growth factor receptor-2 (HER2)-negative advanced gastric cancer.Methods:Patients with HER2-negative advanced gastric cancer were selected from December 2019 to December 2022 as the study subjects. Forty-five patients who received chemotherapy therapy (fluorouracil+cisplatin) were randomly collected and included in control group, and 52 patients who were treated with pembrolizumab combined with apatinib were randomly selected and enrolled as observation group. The difference in short-term efficacy was compared. The levels of serum tumor markers and immune function (CD3 +, CD4 +, CD8 +, CD4 +/CD8 +) were recorded. The long-term efficacy and adverse reactions of patients were compared. Measurement data conforming to the normal distribution were expressed as xˉ± s, and the mean comparison between groups was performed by independent sample t test. Chi-square test was used to compare the rate or composition ratio among enumeration data. P<0.05 was considered statistically significant. Results:At 6 months after treatment, the disease control rate in observation group was significantly higher than that in control group (78.85% (41/52) vs 57.78% (26/45)) ( χ2=5.01, P=0.025), but there was no statistical significance in objective response rate between groups (36.54% (19/52) vs 24.45% (11/45)) ( χ2=1.65, P=0.199). The levels of pepsinogen I, tissue polypeptide specific antigen, carcinoembryonic antigen, carbohydrate antigen 199 and CD8 + in both groups were reduced after treatment, and the levels were lower in observation group than those in control group ( t=6.06, 6.78, 4.68, 11.21, 3.45, all P<0.001). The levels of CD3 +, CD4 + and CD4 +/CD8 + were enhanced significantly in the two groups, and the observation group had higher levels after treatment ( t values were 2.10, 3.74, and 5.19; P values were 0.028, <0.001, and <0.001). After 1 year of follow-up, the survival rate in observation group with 59.62% (31/52) was significantly higher than 37.78% (17/45) in control group ( χ2=4.60, P=0.032). The progression-free survival time ((10.22±1.62) months vs (8.13±1.57) months, t=6.43, P<0.001) and overall survival time ((11.62±1.84) months vs (9.73±1.71) months, t=5.21, P<0.001) in observation group were significantly longer compared to control group. There were no statistical differences in the incidence rates of bone marrow suppression ( χ2=1.92, P=0.165), hand-foot syndrome ( χ2=3.47, P=0.062), gastrointestinal reaction ( χ2=0.32, P=0.574), hypertension ( χ2=0.94, P=0.333) and proteinuria ( χ2=2.39, P=0.122) between the two groups. Conclusion:Compared with chemotherapy, pembrolizumab combined with apatinib shows good short-term efficacy and long-term efficacy in patients with HER2-negative advanced gastric cancer.

Objective To investigate the effect and clinical efficacy of dapagliflozin on homocysteine(Hcy),uric acid(UA),and cystatin C(Cys C)in elderly patients with type 2 diabetes mellitus(T2DM)complicated by nephropathy and hypertension.Methods A total of 292 patients diag-nosed with T2DM nephropathy and hypertension admitted to our hospital between December 2022 and June 2023 were retrospectively recruited,and based on their medication regimens,they were divided into dapagliflozin group(147 cases)and control group(145 cases).After all of them were followed up for 3 months,the serum levels of Hcy,UA,cys C,urinary microalbumin/urinary creatinine ratio(UACR),estimated glomerular filtration rate(eGFR),and other metabolism-related indicators were measured and compared before and after treatment.Pearson correlation analysis was used to determine the correlation between Hcy and UA,while logistic regression analysis was employed to identify risk factors for proteinuria among the patients with T2DM ne-phropathy and hypertension.Results After treatment,the BMI,SBP,DBP,FBG,glycosylated Hb,TC,TG,LDL-C,UA,Cys C,Hcy,insulin resistance index(HOMA-IR),and UACR were all decreased in comparison to their levels before treatment(P＜0.05).Dapagliflozin treatment resul-ted in more significant declines in BM1,FBG,LDL-C,UA,Cys C,Hcy,HOMA-IR,and UACR when compared with the control group(P＜0.05,P＜0.01).Pearson correlation analysis revealed that the relationship between Hcy and UA was positively correlated across the entire population(r=0.560,P＜0.01),as well as among males(r=0.510,P＜0.01)and females(r=0.640,P＜0.01).Multivariate logistic regression analysis identified female gender,diabetic peripheral neu-ropathy,TC,eGFR,and Hcy ≥15 μmol/L as independent risk factors for proteinuria among eld-erly patients with T2DM nephropathy and hypertension(P＜0.05,P＜0.01).Conclusion Dapa-gliflozin,a novel antidiabetic agent,may offer further renal protection by lowering Hcy and UA levels in patients with T2DM nephropathy and hypertension.It can potentially decelerate the pro-gression of proteinuria and improve patient's outcomes.

Chronic pancreatitis(CP)is a progressive fibroinflammatory disease characterized by destruction of pancreatic aci-nar cells,infiltration of inflammatory cells,activation of pancreatic stellate cell(PSC),and pancreatic fibrosis.Autophagy partici-pates in the maintenance of cell homeostasis.Recent studies have shown that autophagy closely related to the occurrence and develop-ment of CP.However,several autophagy types in the pancreatic microenvironment play different roles in the progression of CP.The autophagy of acinar cells has a"double-edged sword"effect.PSC autophagy is positively correlated with its activation,while the role of autophagy of inflammatory cells is still unclear.This study focused on some key cells in the CP microenvironment and explored the role and mechanism of autophagy in the progression of CP.