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 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 relationship of changes in serum chromogranin A(CgA)and heat shock transcription factor 1(HSF1)levels with cardiac remodeling and myocardial injury in elderly patients with chronic heart failure(CHF).Methods A total of 165 elderly CHF patients admitted to our hospital from January 2019 to May 2022 were selected as the disease group,and according to NYHA classification,they were divided into Class Ⅰ(28 patients),Ⅱ(29 patients),Ⅲ(65 patients)and Ⅳ(43 patients)subgroups.Another 80 healthy individuals taking physical examination in our hospital during the same period were enrolled as the control group.The serum CgA and HSF1 levels were detected,and the indicators of cardiac remodeling and myo-cardial injury were collected at admission in the two groups.The correlation of serum CgA and HSF1 levels with cardiac remodeling and myocardial injury was determined with Pearson correla-tion analysis.During 1 year's follow-up,6 cases were lost,and the left 159 patients were divided into MACE group(51 cases)and non-MACE group(108 cases)according to whether MACE occurred.Univariate and multivariate logistic regression analyses were used to analyze the influen-cing factors of MACE,and ROC curve was plotted to analyze the predictive value of serum CgA and HSF1 levels for MACE.Results The disease group had significantly higher left ventricular mass index(LVMI),left ventricular end-systolic volume(LVESV),left ventricular posterior wall thickness(LVPWT),serum levels of CgA,cardiac troponin Ⅰ(cTnⅠ),creatine kinase isoenzyme(CK-MB)and N-terminal B-type natriuretic peptide precursor(NT-proBNP),and obviously lower HSF1 level and left ventricular ejection fraction(LVEF)when compared with the control group(P＜0.01).Pearson correlation analysis showed that serum CgA level was negatively correlated with LVEF and positively with LVMI,LVESV,LVPWT,and serum levels of cTnⅠ,CK-MB and NT-proBNP(P＜0.01);serum HSF1 level was positively correlated with LVEF and negatively with LVMI,LVESV,LVPWT,and serum cTnⅠ,CK-MB and NT-proBNP levels(P＜0.01).Multi-variate logistic regression analysis showed that CgA,HSF1,LVEF,LVMI,LVESV,LVPWT and cTnⅠ were influencing factors for MACE in elderly CHF patients(P＜0.05,P＜0.01).ROC curve analysis indicated that the cut-off value of CgA was 387.55 μg/L,the sensitivity was 74.51％,the specificity was 71.30％,and the AUC value was 0.802(95％CI:0.751-0.855);the cut-off value of HSF1 was 2.34 ng/L,the sensitivity was 74.51％,the specificity was 69.44％,and the AUC value was 0.760(95％CI:0.707-0.812).Conclusion In elderly CHF patients,serum levels of CgA and HSF1 are closely associated with cardiac remodeling and myocardial injury,and the two indicators can be used as prognostic indicators for MACE.

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: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: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: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: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: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.