ObjectiveTo explore the protective effect of Shengxiantang on cardiac function and myocardial microvascular injury in rats with chronic heart failure （CHF）. MethodsThe CHF rat model was prepared by aortic arch constriction （TAC）. Of the 72 SD rats， 8 were randomly selected as the sham operation group， where the chest was opened without ligating the aortic arch. The 40 successfully modeled rats were randomly divided into the model group， the Shengxiantang low-， medium-， and high-dose groups （5.1， 10.2， 20.4 g·kg^-1）， and the trimetazidine group （6.3 mg·kg^-1）， with 8 rats in each group. Drug administration began 4 weeks after modeling. The administration groups received the corresponding drugs by gavage， while the sham operation and model groups were given the same amount of distilled water for 8 consecutive weeks. Echocardiography was used to assess cardiac function. Enzyme-linked immunosorbent assay （ELISA） was used to detect the levels of nitric oxide （NO）， endothelin （ET-1）， vascular endothelial growth factor （VEGF）， and von Willebrand factor （vWF）. Ultrastructural changes of microvessels were observed by transmission electron microscopy. Immunohistochemistry was used to detect the expression levels of ATP synthase subunit （ATP5D） and F-actin in myocardial tissue. Western blot was used to detect the expression levels of occludin， claudin， vascular endothelial cadherin （VE-Cadherin）， and zonula occludens-1 （ZO-1）. Microvessel density was measured by immunofluorescence staining. ResultsCompared with the sham operation group， the ejection fraction （EF） and left ventricular shortening fraction （FS） in the model group were significantly decreased （P<0.01）， while the left ventricular diastolic diameter （LVIDd）， left ventricular systolic diameter （LVIDs）， left ventricular end-diastolic posterior wall thickness （LVPWd）， left ventricular end-systolic posterior wall thickness （LVPWs）， left ventricular end-diastolic volume （LVVOLd）， and left ventricular end-systolic volume （LVVOLs） were significantly increased （P<0.01）. The levels of NO and VEGF were significantly decreased （P<0.01）， while the levels of ET-1 and vWF were significantly increased （P<0.01）. Under electron microscopy， the microvascular basement membrane was incomplete and the tight junctions were blurred. The expression levels of ATP5D， F-actin， occludin， claudin， ZO-1， and VE-Cadherin were significantly decreased （P<0.05， P<0.01）， and the relative density of microvessels was significantly reduced （P<0.05， P<0.01）. After intervention with Shengxiantang， the EF and FS of CHF rats significantly increased （P<0.01）， while the LVIDd， LVIDs， LVPWd， LVPWs， LVVOLd， and LVVOLs significantly decreased （P<0.01）. The levels of NO and VEGF significantly increased （P<0.01）， while the levels of ET-1 and vWF significantly decreased （P<0.01）. Under electron microscopy， the microvascular basement membrane was relatively complete and the tight junctions were more continuous. The expression levels of ATP5D， F-actin， occludin， claudin， ZO-1， and VE-Cadherin significantly increased （P<0.05， P<0.01）， and the relative density of microvessels significantly increased （P<0.01）. ConclusionShengxiantang can effectively improve the cardiac function of CHF rats， reduce microvascular endothelial injury， strengthen the connection between endothelial cells， and increase microvessel density， thereby protecting myocardial microvascular injury.

ObjectiveTo explore the protective effect of Shengxiantang on cardiac function and myocardial microvascular injury in rats with chronic heart failure （CHF）. MethodsThe CHF rat model was prepared by aortic arch constriction （TAC）. Of the 72 SD rats， 8 were randomly selected as the sham operation group， where the chest was opened without ligating the aortic arch. The 40 successfully modeled rats were randomly divided into the model group， the Shengxiantang low-， medium-， and high-dose groups （5.1， 10.2， 20.4 g·kg^-1）， and the trimetazidine group （6.3 mg·kg^-1）， with 8 rats in each group. Drug administration began 4 weeks after modeling. The administration groups received the corresponding drugs by gavage， while the sham operation and model groups were given the same amount of distilled water for 8 consecutive weeks. Echocardiography was used to assess cardiac function. Enzyme-linked immunosorbent assay （ELISA） was used to detect the levels of nitric oxide （NO）， endothelin （ET-1）， vascular endothelial growth factor （VEGF）， and von Willebrand factor （vWF）. Ultrastructural changes of microvessels were observed by transmission electron microscopy. Immunohistochemistry was used to detect the expression levels of ATP synthase subunit （ATP5D） and F-actin in myocardial tissue. Western blot was used to detect the expression levels of occludin， claudin， vascular endothelial cadherin （VE-Cadherin）， and zonula occludens-1 （ZO-1）. Microvessel density was measured by immunofluorescence staining. ResultsCompared with the sham operation group， the ejection fraction （EF） and left ventricular shortening fraction （FS） in the model group were significantly decreased （P<0.01）， while the left ventricular diastolic diameter （LVIDd）， left ventricular systolic diameter （LVIDs）， left ventricular end-diastolic posterior wall thickness （LVPWd）， left ventricular end-systolic posterior wall thickness （LVPWs）， left ventricular end-diastolic volume （LVVOLd）， and left ventricular end-systolic volume （LVVOLs） were significantly increased （P<0.01）. The levels of NO and VEGF were significantly decreased （P<0.01）， while the levels of ET-1 and vWF were significantly increased （P<0.01）. Under electron microscopy， the microvascular basement membrane was incomplete and the tight junctions were blurred. The expression levels of ATP5D， F-actin， occludin， claudin， ZO-1， and VE-Cadherin were significantly decreased （P<0.05， P<0.01）， and the relative density of microvessels was significantly reduced （P<0.05， P<0.01）. After intervention with Shengxiantang， the EF and FS of CHF rats significantly increased （P<0.01）， while the LVIDd， LVIDs， LVPWd， LVPWs， LVVOLd， and LVVOLs significantly decreased （P<0.01）. The levels of NO and VEGF significantly increased （P<0.01）， while the levels of ET-1 and vWF significantly decreased （P<0.01）. Under electron microscopy， the microvascular basement membrane was relatively complete and the tight junctions were more continuous. The expression levels of ATP5D， F-actin， occludin， claudin， ZO-1， and VE-Cadherin significantly increased （P<0.05， P<0.01）， and the relative density of microvessels significantly increased （P<0.01）. ConclusionShengxiantang can effectively improve the cardiac function of CHF rats， reduce microvascular endothelial injury， strengthen the connection between endothelial cells， and increase microvessel density， thereby protecting myocardial microvascular injury.

Metabolic dysfunction-associated steatohepatitis (MASH), a severe type of metabolic dysfunction-associated steatotic liver disease (MASLD), is a leading etiology of end-stage liver disease worldwide, posing significant health and economic burdens. microRNA-320 (miR-320), a ubiquitously expressed and evolutionarily conserved miRNA, has been reported to regulate lipid metabolism; however, whether and how miR-320 affects MASH development remains unclear. By performing miR-320 in situ hybridization with RNAscope, we observed a notable downregulation of miR-320 in hepatocytes during MASH, correlating with disease severity. Most importantly, miR-320 downregulation in hepatocytes exacerbated MASH progression as demonstrated that hepatocyte-specific miR-320 deficient mice were more susceptible to high-fat, high-fructose, high-cholesterol diet (HFHC) or choline-deficient, amino acid-defined, high-fat diet (CDAHFD)-induced MASH compared with control littermates. Conversely, restoration of miR-320 in hepatocytes ameliorated MASH-related steatosis and fibrosis by injection of adeno-associated virus 8 (AAV8) carrying miR-320 in different types of diet-induced MASH models. Mechanistic studies revealed that miR-320 specifically regulated fibroblast growth factor 1 (FGF1) production in hepatocytes by inhibiting regulator factor X1 (RFX1) expression. Notably, knockdown of Rfx1 in hepatocytes mitigated MASH by enhancing FGF1-mediated AMPK activation. Our findings underscore the therapeutic potential of hepatic miR-320 supplementation in MASH treatment by inhibiting RFX1-mediated FGF1 suppression.

Objective:To conduct quantitative evaluation on the revise requirements of Specifications of Air Sampling for Hazardous Substances Monitoring in the Workplace (GBZ 159-2004) , clarify the problems and suggestions during its implementation for improvement, and provide a basis for the revision of the standard.Methods:From April to September 2021, stratified convenient sampling method was adopted and semi-open questionnaire was used to investigate the occupational health personnel in CDC, occupational prevention and control institutes, employers, third-party technical service institutions and universitie. The entropy weight of each index and the score based on entropy weight of GBZ 159 were calculated. Spearman rank correlation analysis was used to describe the correlation between the two indexes and radar chart was drawn for comprehensive evaluation.Results:A total of 151 questionnaires were received from the respondents, of which 147 were valid, with an effective recovery rate of 97.35%, involving 29 provinces, autonomous regions and municipalities. The median G scores of the necessity and urgency of GBZ 159 revision based on entropy weight were 2.84 and 3.17, respectively, and the difference was statistically significant ( M=-25.50, P<0.001) . The trend of the score G of necessity and urgency based on entropy weight was basically the same for all secondary items ( rs=0.9998, P<0.001) , and the score G of urgency based on entropy weight was higher than that of necessity. The highest score G of necessity and urgency based on entropy weight was "3.13 long time sampling", which were 7.56 and 8.23 respectively. This was followed by "3.12 short time sampling", which were 7.19 and 7.13 respectively. Conclusion:GBZ 159 has encountered some new problems and challenges in the implementation process, and some of its technical indicators have been out of line with the actual practice of occupational health at present. These are the two items that urgently needs to be revised and improved, such as "3.13 long time sampling" and "3.12 short time sampling" and other items need to be revised and improved.

Objective:To study and compare the occupational exposure limits (OELs) of coal dust between China and foreign countries, understand the OEL of coal dust in China, and provide data and basis for revising the OEL of coal dust in China.Methods:In August 2023, by searching the official websites of limits setting institutions in relevant countries and regions at home and abroad, collecting and sorting out the OELs of coal dust issued by 10 limit setting institutions in 6 countries and the background information of the formulation, and conducting specific analysis on the classification, limit level and formulation principles of coal dust OEL in each country/institution.Results:In China and Japan, the total dust and respirable dust of coal dust OEL were established respectively, while in other countries, only the time-weighted average concentration (TWA) of respirable coal dust exposure was established. The TWA prescribed by China's Notional Health Commission, the United States Occupational Safety and Health Administration (OSHA) , the United States Mining Safety and Health Administration (MSHA) and the Australian Safety Work Bureau when the SiO 2 content was less than 5% were 5, 2.4, 2 and 3 mg/m 3 respectively. China GBZ 2.1-2019 sets the limit of 2.5 mg/m 3 for respirable coal dust with SiO 2 content less than 10%. The TWA set by the American Conference of Government Industrial Hygienists (ACGIH) and the South African Department of Mines and Energy (DME) for anthracite coal were 0.4 and 0.8 mg/m 3, respectively, and bituminous coal or lignite were 0.9 and 1.8 mg/m 3, respectively. The respirable coal dust TWA set by the National Institute for Occupational Safety and Health (NIOSH) in the United States was 1 mg/m 3, and the TWA set by the New Zealand Work Safety Authority was 3 mg/m 3. Conclusion:At present, the OEL of coal dust in China is at a relatively loose level, and it is suggested to further explore the possibility of revising coal dust OEL.

Systematically evaluate the implementation of Specifications of Air Sampling for Hazardous Substances Monitoring (GBZ 159-2004) , so as to provide technical basis for the future standard revision. The semi-structured interview method was used to interview the industry experts from centers for disease control and prevention, occupational disease prevention and control hospitals/institutes, employers, third-party technical service institutions and universities, and the induction method was used to refine the topics and relevant suggestions. Some technical indicators of GBZ 159 are not suitable for the current actual work of occupational health, and need to be revised and improved urgently. The revised GBZ 159 should comply with the current situation of China's industrial development and the development of occupational health testing equipment in the new era, and improve the relevant technical requirements of sampling quality control.

Objective To make a comprehensive analysis of the index of benefit and medical service ability of disease,and provide references for the operation management of public hospital based on disease.Methods TOPSIS was used to compre-hensively evaluate the income contribution,income structure,daily income,the proportion of operation/grade 4 operation,DRG-CMI and other indexes.According to the Boston matrix,two-dimensional quadrant analysis was carried out to determine the dominant diseases in the operation management.Results Twelve main diseases in a hospital specialty were analyzed,and the comprehensive scores of two dimensions of benefit and medical service ability were formed.According to the scores,a two-dimen-sional quadrant map was drawn,and the characteristics of diseases in each quadrant were summarized to identify the dominant diseases that contribute greatly to the economic operation and technical difficulty evaluation of the specialty.Conclusion The combined application of TOPSIS and Boston matrix in specialty operation analysis can help public hospital to realize the classifica-tion management of disease balancing benefit and difficulty,so as to optimize the disease structure and improve the utilization rate of medical resources.

Objective To investigate the effect of glycine N-methyl transferase (GNMT)on intrauterine adhesion (IUA)fibrosis and its related mechanism.Methods In vivo experiment:A total of 36 healthy female SD rats (SPF grade,6～8 weeks old and weighing from 180～220 g)were subjected in this study.IUA model of SD rats and IUA model of GNMT overexpressed rats were established.RT-qPCR and immunofluorescence assay were applied to detect GNMT expression level in normal uterus and model group.RT-qPCR and Western blotting were used to detect the mRNA and protein levels of fibrosis-related molecules and the activation of TGF-β1/Smad3 signaling pathway in each group.The number of endometrial glands in each group was observed by HE staining.Masson staining was used to analyze the severity of endometrial fibrosis in each group.In vitro experiment:transformed human endometrial stromal cells (THESCs)fibrotic phenotype model was constructed using TGF-β1,and THESCs stably transfected with GNMT overexpression lentvirus were treated with TGF-β1.RT-qPCR and Western blotting were used to detect the mRNA and protein expression of fibrosis-related molecules.The expression of TGF-β1/Smad3 signaling pathway was detected by Western blotting.TGF-β1/Smad3 signaling pathway was activated by TGF-β1/Smad signaling pathway activator (SRI-011381),and the expression of TGF-β1/Smad3 signaling pathway and key molecular proteins of fibrosis phenotype was measured with Western blotting.Results In vivo experiment,the mRNA and protein expression levels of GNMT were significantly decreased in the IUA rats than the control rats (P<0.05).Overexpression of GNMT decreased the mRNA and protein levels of fibrosis related molecules,Collagen Ⅰ,Collagen Ⅲ and FN in the IUA rats (P<0.05),and decreased the phosphorylation levels of TGF-β1 and its downstream Smad3 protein (P<0.05).HE and Masson staining showed that overexpression of GNMT could increase the number of endometrial glands and reduce the severity of fibrosis in the IUA rats (P<0.05).In vitro experiments:overexpression of GNMT decreased the mRNA and protein levels of Collagen Ⅰ,Collagen Ⅲ and FN associated with fibrotic phenotype of THESCs (P<0.05),and reduced the phosphorylation level of Smad3 protein,downstream of TGF-β1 (P<0.05).After activation of TGF-β1/Smad3 signaling pathway,the protein levels of TGF-β1/Smad3 signaling pathway and downstream fibrosis phenotype molecules,Collagen Ⅲ and FN,were significantly decreased in the LV-GNMT+SRI-011381 group.Conclusion Overexpression of GNMT can inhibit endometrial fibrosis by regulating TGF-β1/Smad3 signaling pathway,thus achieving therapeutic effect on IUA.

OBJECTIVE To investigate the effect and mechanism of action of KRT8 small interfering RNA(si-KRT8)in exosomes derived from patient serum with hypopharyngeal carcinoma on chemosensitivity to 5-fluorouracil(5-FU)in human pharyngeal squamous cell carcinoma FaDu cell line.METHODS The cancerous tissues of hypopharyngeal cancer patients and The serum,cancerous tissues and paracancerous tissues of drug-resistant patients after treatment were collected.A 5-FU-resistant cell line of FaDu(FaDu/R)was constructed for subsequent experiments.Exosomes were isolated from patient serum by ultrafast gradient centrifugation,identified using transmission electron microscopy and Western blot(WB)techniques.si-KRT8 was encapsulated into exosomes(Exosome@si-KRT8)using electroporation technology and subsequently used to treat cells.Real-time fluorescence quantitative PCR(RT-qPCR)and WB were used to detect the expression levels of KRT8 in different tissues,exosomes after electroporation of si-KRT8,and FaDu cells,respectively.Cell counting kit-8(CCK-8),terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay,migration invasion technique and WB were used to detect the effects of Exosome@si-KRT8 on viability,apoptosis,and epithelial-mesenchymal transition of FaDu/R cells.RESULTS The expression level of KRT8 in drug-resistant tissues of hypopharyngeal carcinoma and FaDu/R cells was elevated compared with that in paraneoplastic tissues,cancer tissues and normal FaDu cells(t=15.79,P＜0.01).Isolated patient serum exosomes showed a double membrane structure and expressed both CD63 and TSG101 proteins,and KRT8 expression in exosomes was decreased after electro-transfection with si-KRT8(t=6.70,P＜0.01).Exosome@si-KRT8 inhibited KRT8 protein expression levels in FaDu/R cells(t=123.50,P＜0.01).Compared with the 5-FU group and the 5-FU+Exosome group,Exosome@si-KRT8 was able to inhibit the viability of FaDu/R cells(t=17.07,P＜0.01),promote the level of apoptosis in FaDu/R cells,and inhibit the expression of drug-resistance-associated proteins in FaDu/R cells(P-gp:t=103.20,MDR1:t=238.60,P＜0.01),and Exosome@si-KRT8 was able to suppress the expression of metastasis of FaDu/R cells(t=42.30,t=122.00,P＜0.01)and promoted the expression of E-cadherin while inhibiting the expression level of N-cadherin(t=130.80,t=83.90,P＜0.01).CONCLUSION Serum-derived exosome encapsulation of si-KRT8 enhances chemosensitivity of hypopharyngeal carcinoma cells and its mechanism of action may be related to inhibition of epithelial-mesenchymal transition.

Objective:To delve deeply into the dynamic trajectories of cell subpopulations and the communication network among immune cell subgroups during the malignant progression of glioblastoma(GBM),and to endeavor to unearth key risk biomarkers in the GBM malignancy progression,so as to provide a more profound understanding for the treatment and prognosis of this disease by integrating tran-scriptomic data and clinical information of the GBM patients.Methods:Utilizing single-cell sequencing data analysis,we constructed a cell subgroup atlas during the malignant progression of GBM.The Mono-cle2 tool was employed to build dynamic progression trajectories of the tumor cell subgroups in GBM.Through gene enrichment analysis,we explored the biological processes enriched in genes that significant-ly changed with the malignancy progression of GBM tumor cell subpopulations.CellChat was used to identify the communication network between the different immune cell subgroups.Survival analysis helped in identifying risk molecular markers that impacted the patient prognosis during the malignant pro-gression of GBM.This methodological approach offered a comprehensive and detailed examination of the cellular and molecular dynamics within GBM,providing a robust framework for understanding the disease's progression and potential therapeutic targets.Results:The analysis of single-cell sequencing data identified 6 different cell types,including lymphocytes,pericytes,oligodendrocytes,macrophages,glioma cells,and microglia.The 27 151 cells in the single-cell dataset included 3 881 cells from the pa-tients with low-grade glioma(LGG),10 166 cells from the patients with newly diagnosed GBM,and 13 104 cells from the patients with recurrent glioma(rGBM).The pseudo-time analysis of the glioma cell subgroups indicated significant cellular heterogeneity during malignant progression.The cell interaction analysis of immune cell subgroups revealed the communication network among the different immune sub-groups in GBM malignancy,identifying 22 biologically significant ligand-receptor pairs across 12 key bio-logical pathways.Survival analysis had identified 8 genes related to the prognosis of the GBM patients,among which SERPINE1,COL6A1,SPP1,LTF,C1S,AEBP1,and SAA1L were high-risk genes in the GBM patients,and ABCC8 was low-risk genes in the GBM patients.These findings not only provided new theoretical bases for the treatment of GBM,but also offered fresh insights for the prognosis assessment and treatment decision-making for the GBM patients.Conclusion:This research comprehensively and pro-foundly reveals the dynamic changes in glioma cell subpopulations and the communication patterns among the immune cell subgroups during the malignant progression of GBM.These findings are of significant im-portance for understanding the complex biological processes of GBM,providing crucial new insights for precision medicine and treatment decisions in GBM.Through these studies,we hope to provide more ef-fective treatment options and more accurate prognostic assessments for the patients with GBM.