Trophoblast cells serve as the foundation for placental development. We analyzed published multiomics sequencing data and found that trophoblast cells highly expressed RRS1 compared to primitive endoderm and epiblast. We used HTR-8/SVneo cells for further investigation, and Western blot and immunofluorescence staining confirmed that HTR-8/SVneo cells highly expressed RRS1. RRS1 was successfully knocked down in HTR-8/SVneo cells using siRNA. Using IncuCyte S3 live-cell analysis system based on continuous live-cell imaging and real-time data, we observed that proliferation, migration, and invasion abilities were all significantly decreased in RRS1-knockdown cells. RNA-seq revealed that knockdown of RRS1 affected the gene transcription, and upregulated pathways in extracellular matrix organization, DNA damage response, and intrinsic apoptotic signaling, downregulated pathways in embryo implantation, trophoblast cell migration, and wound healing. Differentially expressed genes were enriched in diseases related to placental development. Consistent with these findings, human chorionic villus samples collected from spontaneous abortion cases exhibited significantly reduced RRS1 expression compared to normal controls. Our results highlight the functional importance of RRS1 in human trophoblasts and suggest that its deficiency contributes to early pregnancy loss.
Humans ; Trophoblasts/physiology* ; Cell Movement/genetics* ; Cell Proliferation/genetics* ; Female ; Pregnancy ; Abortion, Spontaneous/metabolism* ; Cell Line ; Placentation/genetics*

Objective:To examine the satisfaction and teaching effectiveness of Health Statistics among students majoring in Public Utility Administration,and to provide valuable insights for optimizing current teaching practices and enhancing teaching effectiveness.Methods:A survey questionnaire,specifically designed for this study,was administered to 56 students of grade 2021 majoring in Public Utility Administration in our school.The questionnaire covered topics such as the difficulty of teaching content,learning satisfaction,and the Student Evaluation of Educational Quality(SEEQ)scale.Results:Non-parametric testing was considered the most difficult knowledge point,and male students found statistical inference of quantitative data was the most challenging,while female students found non-parametric testing was the most difficult.In terms of satisfaction,the highest score was obtained for pre-class review,while the lowest score was given to improving learning interest in Rain Classroom.The overall score for teaching effectiveness,as measured by SEEQ,was good across seven dimensions.Teaching enthusiasm received the highest score(4.40±0.43),while homework volume received the lowest score(3.23±0.37).With the exception of homework grading,satisfaction was positively correlated with most dimensions of teaching effectiveness evaluation.Conclusions:Despite perceiving the course as generally difficult,students expressed high satisfaction and overall positive evaluation of teaching effectiveness.Therefore,it is recommended to actively explore new teaching reforms to cultivate well-rounded applied talents for public utilities.

Objective:By analyzing the curative cost of treatment for children in Beijing,it provided recommendations for further optimizing child health management policies in Beijing.Methods:The System of Health Accounts 2011(SHA 2011)was used to calculate the CCE of children in Beijing's medical institutions.Results:The CCE of children under the age of 15 in Beijing were 92.29 billion yuan,97.54 billion yuan,and 105.72 billion yuan in 2017-2019,with an average annual growth rate of 4.67%;the financing structure of children's CCE is dominated by family health expenditure,accounting for about 65%;children's outpatient and inpatient CCE primarily flew to secondary and tertiary hospitals;respiratory diseases account for the largest share of the disease categories of the CCE,with a share of 25.96%,followed by digestive diseases with a share of 10.26%.Conclusion:The financing structure needs to be optimized to lessen the financial burden of medical care on the families of child patients;the capacity of grass-roots pediatric services should be strengthened,and reasonably guide the flow of adolescent patients to institutions;financial investment should be increased for pre-pregnancy,prenatal screening and other preventive services.It needs to give careful consideration to children's safety education and encourage the implementation of children's commercial accidental injury insurance.

AIM:To investigate the effects of overexpressing α-Klotho(KL)in RAW264.7 cells stimulated by oxidative stress on the proliferation, migration, tube-formation and tight junction of human umbilical vein endothelial cells(HUVECs).METHODS:RAW264.7 cells were categorized into control, 4-hydroxynonenal(4HNE), and 4HNE+KL groups, with F4/80 expression assessed via immunofluorescence staining. Three groups of conditional media were prepared for HUVECs and culture divided into Mø-NC, Mø-4HNE, and Mø-4HNE+KL groups. Cell proliferation was evaluated using CCK8 assay, while scratch test and Transwell assays were employed to measure cell migration. Additionally, tube-formation assay was conducted to assess cell tubule formation, and Western blot assay was utilized to detect the protein expression levels of Claudin 5, Occludin and ZO 1.RESULTS:The results of immunofluorescence staining showed that the fluorescence intensity of F4/80 of RAW264.7 cells in the 4HNE group was significantly enhanced compared with the control group, while that of F4/80 in the 4HNE+KL group was significantly decreased compared with the 4HNE group(all P<0.05). The CCK8 assay results revealed a significant increase in the proliferation of HUVECs in the Mø-4HNE group compared with the Mø-NC group. Conversely, the proliferation of the Mø-4HNE+KL group exhibited a significant decrease compared with that in the Mø-4HNE group(all P<0.01). The results of scratch test and Transwell assays demonstrated a significant increase in the migration of HUVECs in the Mø-4HNE group compared with the Mø-NC group, while the migration of the Mø-4HNE+KL group exhibited a significant decrease compared with the Mø-4HNE group(all P<0.01). In the tube-formation assay, it was observed that the number of tubes formed by HUVECs in the Mø-4HNE group was significantly increased compared with the Mø-NC group, while that of tubes formed in the Mø-4HNE+KL group was significantly decreased compared with the Mø-4HNE group(all P<0.01). Additionally, the Western blot results revealed a significant decrease in the relative expression levels of Claudin 5, Occludin, and ZO 1 in the Mø-4HNE group compared with the Mø-NC group. Conversely, in the Mø-4HNE+KL group, there was a significant increase in the relative expression levels of Claudin 5, Occludin, and ZO 1 compared to the Mø-4HNE group(all P<0.01).CONCLUSIONS: KL inhibits the proliferation, migration, and tube-formation of HUVECs while enhancing the tight junction by changing the activation state of macrophages in the diabetic oxidative stress environment.

Objective By studying the changes in the institutional distribution of curative care expenditure(CCE)of the elderly population before and after the comprehensive reform medical-pharmaceutical separation and linkage of medical consumption,it provided data reference for the next step of accurately optimizing the elderly patients flow.Methods A multi-stage stratified whole-group sampling survey was used to select the sample.A System of Health Accounts 2011 was used to calculate the CCE of elderly patients in medical institutions.Results The CCE of medical institutions for the elderly population in Beijing increased from 60.457 billion yuan to 797.54 billion yuan,with an average annual growth rate of 6.83%,the fastest growth rate of 24.04%for community-based health treat-ment center.The percentage of CCE in the community increased from 11.31%to 17.71%,while the percentage of CCE in tertiary hospitals decreased by 4.39 percentage points.The flow of CCE for outpatient patients was obviously opti-mized.Younger elderly outpatient patients are more willing to seek treatment in the community,but the flow di-rection of outpatient treatment for elderly patients is more optimized.The CCE fpr elderly outpatient patients with chronic diseases such as endocrine,nutritional and metabolic diseases and nervous system diseases have been substantially transferred to the community-based health center.Conclusion The reform has different impacts on the treatment of elderly patients with different genders,ages and diseases.It is necessary to strengthen the service capacity building of primary medical institutions,highlight the development characteristics of secondary hospitals,and accurately improve the hierarchical diagnosis and treatment system for elderly patients.

Objective:To investigate the comorbidity status of hypertension, diabetes, and dyslipidemia (the"three diseases") among residents aged≥40 in Liaoning Province, and to explore the correlation between the comorbidity and cardiovascular disease mortality.Methods:This investigation was a prospective cohort study. From February 2017 to March 2019, a multi-stage stratified cluster random sampling method was used to carry out a baseline survey of 18 758 permanent residents aged≥40 years in Liaoning Province. Demographic information and history of hypertension, diabetes, and dyslipidemia were collected and followed up every year. Death was mainly identified by linkage to the Population Death Information Registration Management System. Cox proportional hazard regression model was used to analyze the association between the comorbidity of the "three diseases" and cardiovascular disease mortality risk.Results:A total of 18 758 residents aged≥40 in Liaoning Province were included, with an age of (60.3±9.9) years and 7 325 males (39.1%). The comorbidity rate of hypertension, diabetes, and dyslipidemia was 6.7% (1 256/18 758), and the standardized prevalence rate was 5.4%. The comorbidity rate increased with age (P<0.001), which was higher in women than in men, and more significant in urban areas than in rural areas (all P<0.001). The comorbidity of "three diseases" accounted for 39.3% (1 256/3 198), 18.7% (1 256/6 710), and 11.8% (1 256/10 653) in patients with diabetes, dyslipidemia, and hypertension, respectively. With a follow-up of (4.3±0.6) years, 463 people died of cardiovascular disease. The mortality rate of cardiovascular disease in the comorbidity of hypertension, diabetes, and dyslipidemia was 8.74/1 000 person-years. After adjusting potential confounders, Cox proportional hazard regression model analysis showed that compared with normal individuals, the hazard ratio of cardiovascular disease mortality in patients with the "three diseases" was 2.55 (95% CI: 1.63-3.99). Conclusion:The prevalence of comorbidity of hypertension, diabetes, and dyslipidemia among residents aged≥40 in Liaoning Province was relatively high, and the risk of cardiovascular disease mortality in patients with the "three diseases" was increased.

Objective:To investigate the prevalence of diabetes in the elderly aged ≥60 years in Liaoning Province from 2017 to 2019 and analyze the impact of blood glucose control on all-cause mortality and cardiovascular disease (CVD) mortality.Methods:A survey was conducted in the elderly aged ≥60 years in Liaoning from 2017 to 2019 to collect the information about the prevalence of diabetes and other chronic diseases in the diabetes patients. The mortality of the enrolled subjects was investigated in September 2023. Cox proportional hazards regression models were used to estimate the association between blood glucose control in the elderly with diabetes and the risks of all-cause mortality and CVD mortality.Results:The crude prevalence of diabetes in the elderly aged ≥60 years was 20.2% (2 014/9 958) in Liaoning from 2017 to 2019, and the standardized prevalence rate was 19.9%. The prevalence rates of hypertension, dyslipidemia, and overweight/obesity in the diabetes patients were 77.0%, 51.7%, and 67.5% respectively. The median follow-up time was 5.5 years, and the all-cause mortality and CVD mortality rates in the diabetes patients were 244.3/10 000 person-years and 142.9/10 000 person-years, respectively. The results of the Cox proportional hazards regression model analysis showed that compared with non-diabetic individuals, diabetes patients had an increased risk of all-cause mortality by 1.68 times [hazard ratio ( HR)=1.68, 95% CI: 1.44-1.94] and an increased risk of CVD mortality by 1.56 times ( HR=1.56, 95% CI: 1.29-1.89). The differences in risks of all-cause mortality and CVD mortality between the diabetes patients with normal fasting blood glucose and glycated hemoglobin levels and people without diabetes were not significant (all P>0.05). The failure to meet either the FPG or HbA1c target increased the risk of all-cause mortality (all P<0.05). For individuals who failed to meet the HbA1c target, there was an increased risk of CVD mortality (all P<0.05). Conclusions:The comorbidity rate of chronic diseases was higher in the elderly with diabetes than in the elderly without diabetes in Liaoning. Elderly diabetes patients can benefit from good blood glucose control.

Objective:By analyzing the curative cost of treatment for children in Beijing,it provided recommendations for further optimizing child health management policies in Beijing.Methods:The System of Health Accounts 2011(SHA 2011)was used to calculate the CCE of children in Beijing's medical institutions.Results:The CCE of children under the age of 15 in Beijing were 92.29 billion yuan,97.54 billion yuan,and 105.72 billion yuan in 2017-2019,with an average annual growth rate of 4.67%;the financing structure of children's CCE is dominated by family health expenditure,accounting for about 65%;children's outpatient and inpatient CCE primarily flew to secondary and tertiary hospitals;respiratory diseases account for the largest share of the disease categories of the CCE,with a share of 25.96%,followed by digestive diseases with a share of 10.26%.Conclusion:The financing structure needs to be optimized to lessen the financial burden of medical care on the families of child patients;the capacity of grass-roots pediatric services should be strengthened,and reasonably guide the flow of adolescent patients to institutions;financial investment should be increased for pre-pregnancy,prenatal screening and other preventive services.It needs to give careful consideration to children's safety education and encourage the implementation of children's commercial accidental injury insurance.

Objective To explore the effects of dapnetin's regulation of STING/TBK1/IRF3 signaling pathway on immune inflammatory response in sepsis rats.Methods In this study,80 male Sprague Dawley(SD)rats were selected and randomly divided into four groups,20 rats in the sham-operation group,the remaining 60 mice with sepsis were constructed according to cecal ligation puncture(CLP)method and were intraperitoneally injected with different doses of dapnetin.They were divided into no-dapnetin model group(0 mg/kg),low-dose group(2.5 mg/kg),and high-dose group(5 mg/kg),with 20 mice in each group.The model group and sham-operation group were intraperitoneally injected with 0.1％DMSO.The survival rate of rats in each group after 72 h of CLP modeling was observed.Lung,kidney,liver and spleen tissues were collected for histopathological analysis.Serum inflammatory factors(TNF-α,IL-6,and IL-1β)were detected by ELISA,T lymphocyte subsets in peripheral blood were detected by flow cytometry,and STING/TBK1/IRF3 signaling pathway protein expression was detected by Western blotting.Results Compared with sham-operation group,the survival rate of rats in model group was reduced(P＜0.05),each organ tissue injury was significant,serum inflammatory factors(TNF-α,IL-6,and IL-1β)levels were increased(P＜0.05),CD4+ratio and CD4+/CD8+ratio in peripheral blood were decreased(P＜0.05),while CD8+ratio and Th1/Th2 ratio were increased(P＜0.05),the protein expressions of STING,p-TBK1/TBK1 and p-IRF3/IRF3 were downregulated(P＜0.05).Compared with the model group,dapnetin in high-dose group improved the survival rate of rats(P＜0.05),the injury of all organs and tissues was reduced,and the level of serum inflammatory factors was decreased(P＜0.05),CD4+ratio and CD4+/CD8+ratio in peripheral blood were increased(P＜0.05),while CD8+ratio and Th1/Th2 ratio were decreased(P＜0.05),the protein expressions of STING,p-TBK1/TBK1 and p-IRF3/IRF3 were increased(P＜0.05).Conclusion Dapnetin can improve the immune inflammatory response of sepsis rats by regulating STING/TBK1/IRF3 signaling pathway.

Objective:To determine the karyotype of a patient with mosaicism complex structural aberration of chromosome 18.Methods:A male patient with a 2-year history of infertility presented at the Center of Reproductive Medicine of the Third Hospital of Peking University in October 2019 was selected as the study subject. Clinical data of the patient was collected. Peripheral blood sample was taken for chromosomal karyotyping, copy number variation (CNV) analysis and fluorescence in situ hybridization (FISH) assay. Semen sample was taken for single sperm CNV analysis. Results:The patient was found to have a karyotype of mos 47, XY, del(18)(q21q23), + r(18)(q21q23)[84]/46, XY, del(18)(q21q23)[9]/48, XY, del(18)(q21q23), + r(18)(q21q23)×2[6]/47, XY, del(18)(q21q23), + r(18)(q21q23×2)[1]. ish 47, XY, del(18)(q21q23), + r(18)(q21q23)[84]/46, XY, del(18)(q21q23)[9]/48, XY, del(18)(q21q23), + r(18)(q21q23)×2[6]/47, XY, del(18)(q21q23), + r(18)(q21q23×2)[1]del(18)(q21q23)( D18Z1+, 18p+, 18q+, WCP18+ ), r(18)(q21q23)(WCP18+ ), r(18)(q21q23×2)(WCP18+ ). No pathogenic CNV was identified. Sequencing of 20 single sperms showed that 1 sperm was normal, 1 had yielded no result, 9 had harbored del(18q), 7 had harbored dup(18q)×2, and 2 had harbored dup(18q)×3. The dup/del fragments had both spanned approximately 33 Mb. Conclusion:It is rare for carriers of complex structural and numerical abnormalities of chromosome 18 to have a normal phenotype. Based on the accurate cytogenetic and molecular analyses and the single sperm CNV analysis, the influence of the aberrant karyotype on the gametogenesis may be evaluated.