1.Effect of sodium-glucose cotransporter 2 inhibitor empagliflozin in alleviating uremic cardiomyopathy and related mechanism
Shi CHENG ; Yeqing XIE ; Wei LU ; Jiarui XU ; Yong YU ; Ruizhen CHEN ; Bo SHEN ; Xiaoqiang DING
Chinese Journal of Clinical Medicine 2025;32(2):248-258
Objective To investigate the effect of sodium-glucose cotransporter 2 inhibitor (empagliflozin, EMPA) on myocardial remodeling in a mouse uremic cardiomyopathy (UCM) model induced by 5/6 nephrectomy, through the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (PKB/AKT)/p65 signaling pathway. Methods The animals were divided into three groups: Sham group (n=6), UCM group (n=8), and UCM+EMPA group (n=8). A UCM model was established in C57BL/6N mice using the 5/6 nephrectomy. Starting from 5 weeks post-surgery, EMPA or a placebo was administered. After 16 weeks, blood pressure, serum creatinine, blood urea nitrogen, 24-hour urine glucose and urine sodium were measured. Cardiac structure and function were assessed by echocardiography. Hematoxylin-eosin (HE) staining and Masson trichrome staining were used to observe pathological changes in the heart and kidneys. Wheat germ agglutinin (WGA) staining was used to evaluate myocardial hypertrophy. The real-time quantitative PCR (RT-qPCR) was used to detect the expression levels of myocardial hypertrophy- and fibrosis-related mRNAs. Western blotting was used to detect the expression levels of PI3K, AKT and p65 in myocardial tissues. Results After 16 weeks, UCM group exhibited significantly higher blood pressure, serum creatinine, blood urea nitrogen than sham group (P<0.01); UCM+EMPA group exhibited lower blood pressure, serum creatinine, blood urea nitrogen, and higher 24 h urine sodium and glucose than UCM group (P<0.05). Echocardiographic results showed ventricular remodeling in the UCM group, evidenced by left ventricular wall thickening, left ventricular enlargement, increased left ventricular mass, and decreased systolic function (P<0.05); ventricular remodeling was alleviated (P<0.05), though there was no significant improvement in systolic function in UCM+EMPA group. HE and Masson stainings revealed myocardial degeneration, necrosis, and interstitial fibrosis in UCM group (P<0.01); the myocardial pathology improved with reduced collagen deposition in UCM+EMPA group (P<0.01). WGA staining confirmed myocardial hypertrophy in UCM group (P<0.01), while myocardial hypertrophy was alleviated in UCM+EMPA group (P<0.01). RT-qPCR results showed myocardial hypertrophy- and fibrosis-related genes (NPPA, NPPB, MYH7, COL1A1, COL3A1, TGF-β1) were upregulated in UCM group (P<0.05), but downregulated in UCM+EMPA group. Western blotting showed PI3K, p-AKT/AKT ratio, and p-p65/p65 ratio were increased in UCM group, but decreased in UCM+EMPA group (P<0.05). Conclusion EMPA can improve myocardial hypertrophy and fibrosis in the UCM mouse model, and it may play the role through inhibiting the PI3K/AKT/p65 signaling pathway.
2.A case of acute respiratory distress syndrome induced by inhalation of hydrogen chloride
Baobao FENG ; Jiarui XU ; Wei ZHANG ; Xingguo ZHANG
Chinese Journal of Industrial Hygiene and Occupational Diseases 2024;42(1):55-57
Poisoning induced by inhalation of hydrogen chloride has significant effects on the respiratory system. It can cause severe pulmonary edema and acute respiratory distress syndrome (ARDS) in the early stage, and even death in critical cases. As a novel treatment for ARDS, the efficacy of sivelestat sodium in infection-induced ARDS has been widely verified, but its application in ARDS caused by chemical poisoning is still scarce in literature. Here we report a case of ARDS induced by hydrogen chloride inhalation which was successfully treated with sivelestat sodium and conventional treatment.
3.Performance of aortic annulus diameter in diagnosis of T2DM with concomitant coronary heart disease
Jiarui LI ; Xuan LIU ; Haifeng XU
Journal of Army Medical University 2024;46(14):1647-1652
Objective To investigate the performance of a common echocardiographic(ECG)indicator,aortic annulus diameter,in the diagnosis of type 2 diabetes mellitus(T2DM)complicated with coronary heart disease(CHD).Methods A cross-sectional study was conducted on the patients undergoing coronary angiography in Department of Cardiovascular Medicine of Affiliated Hospital of Xuzhou Medical University from October 1,2022 to October 31,2023.A total of 440 patients were included into a training set,including 217 with confirmed T2DM combined with CHD(T2DM-CHD group)and 223 patients with simple T2DM(control group).In a ratio of 7:3,another 187 patients were selected and assigned into a validation group,including 91 T2DM-CHD patients and 96 T2DM patients.Their general clinical data and ECG indicators were collected,and the relationships of ECG indicators and coexistence of T2DM-CHD were analyzed.Receiver operating characteristic curve(ROC)was plotted to identify the best predictor for the coexistence with area under the curve(AUC),and the cutoff values and their accuracies in diagnosis were further determined and verified.Results Among all ECG indicators,only aortic sinus and aortic annulus diameter showed statistical differences between the T2DM-CHD group and the control group(P<0.05).Significant correlations were observed between the above 2 indicators and the diagnostic types of the 2 groups(P<O.05).The AUC value of aortic annulus diameter in predicting diagnostic types was 0.920(P<0.01),with a sensitivity of 0.819 and a specificity of 0.843,and the cutoff value was 23.00 mm,which had an accuracy of 90.37%.Conclusion Aortic annulus diameter is a pivotal predictor for identifying T2DM-CHD patients.The T2DM patients with aortic ring diameter<23.00 mm are more common with concomitant CHD.
4.Analysis of factors influencing the approval of national natural science foundation projects in hospitals and construction of prediction models
Ri LI ; Yanli GAO ; Jiarui QU ; Hang XU ; Zhijun LUN
Modern Hospital 2024;24(6):840-843
Objective Explore effective strategies for hospitals to manage the National Natural Science Foundation of China.Methods A retrospective analysis was conducted on the population characteristics of a certain tertiary comprehensive hospital's National Natural Science Foundation project application and approval from 2016 to 2022.Single factor analysis and bi-nary multivariate logistic regression analysis were used to analyze the factors that affect the approval of the National Natural Sci-ence Foundation project,and a function prediction model was established.Results A total of 1 098 applicants were collected in this study,including 653 young project applicants and 178 approved,445 general project applicants and 114 approved;Multi fac-tor logistic results show that in youth programs,the younger the age,the doctor's degree,scientific research posts,the experi-ence of studying abroad,the average impact factor of publishing SCI papers as the first/corresponding author is 3-5 points Appli-cants who have published SCI papers as the first/corresponding author with an average impact factor of more than 5 points,pub-lished SCI papers in four districts as the first/corresponding author,presided over national level and academic level topics are more likely to be approved by the Youth Program of the National Natural Science Foundation of China;Among general programs,applicants who have doctoral degree,overseas study experience,published Zone 1and Zone 2 SCI essays,and presided over na-tional projects as the first/corresponding author are more likely to be approved as general programs of the National Natural Science Foundation of China.The area under the AUC curve of the youth project regression prediction model is 0.860,and the area under the AUC curve of the surface project regression prediction model is 0.838.The model has high predictive value.Conclusion Hospitals should strengthen policy guidance,increase economic investment,encourage applicants to carry out preliminary work layout,focus on talent cultivation,and comprehensively promote the effective management of the National Natural Science Foun-dation of the hospital.
5.The role of circadian clock-controlled mitochondrial dynamics in nonalcoholic fatty liver disease
Ce ZHANG ; Jiarui MIAO ; Xu FAN
Journal of Clinical Hepatology 2024;40(8):1670-1676
Nonalcoholic fatty liver disease(NAFLD)is a disease closely associated with metabolic abnormalities and is currently one of the most common chronic liver diseases.Mitochondria are highly dynamic organelles involved in a variety of metabolic and bioenergetic pathways in the liver,and they respond to environmental changes in a highly dynamic manner through mitochondrial dynamics.The circadian clock is able to modulate mitochondrial dynamics,making it exhibit rhythmic changes.In case of circadian rhythm disorders,mitochondrial dynamics loses rhythmicity,and mitochondria are unable to respond to changing energy demands in different environments,leading to the development and progression of NAFLD.This article summarizes the important role of circadian clock-controlled mitochondrial dynamics in the etiology of NAFLD.
6.Development of a national health standard:Guideline for pediatric transfusion
Rong HUANG ; Qingnan HE ; Mingyan HEI ; Minghua YANG ; Xiaofan ZHU ; Jun LU ; Xiaojun XU ; Tian-Ming YUAN ; Rong ZHANG ; Xu WANG ; Jinping LIU ; Jing WANG ; Zhili SHAO ; Mingyi ZHAO ; Jia GUO ; Xiny-In WU ; Jiarui CHEN ; Qirong CHEN ; Rong GUI ; Yongjian GUO
Chinese Journal of Blood Transfusion 2024;37(7):839-844
Children and adults differ significantly in physiology,biochemistry and immune function,which leads to sig-nificant differences in blood transfusion strategies between children and adults.To guide the clinical transfusion practice of pediatric patients and improve the prognosis of children,the National Health Commission organized the formulation and re-lease of the health industry standard Guideline for Pediatric Transfusion(WS/T 795-2022).This paper will briefly introduce some concepts that help understand of the Standard and the preparation process of the Standard,and explain and interpret the preparation of the"scope","general provisions"and"factors to consider"of the Standard,hoping to contribute to the understanding and implementation of the Standard.
7.Research progress in roles of fibroblast activation in tissue fibrosis,autoimmune diseases and tumor disease
Xin GU ; Yujiao XU ; Jiarui SUN ; Yunyao LIU ; Lei QIANG
Chinese Journal of Pharmacology and Toxicology 2024;38(3):200-211
Fibroblasts are stromal cells widely distributed in tissues and organs throughout the body.Fibroblasts are involved in the synthesis and remodelling of the extracellular matrix.Fibroblasts participate in physiopathological processes such as tissue damage repair,inflammatory responses and immune regulation.Large numbers of activated fibroblasts have been found in fibrosis,autoimmune diseases and tumor lesions.Activated fibroblasts participate in tissue fibrosis and influence the tumor microenvi-ronment mainly by secreting collagen and fibronectin.They also secrete a variety of inflammatory and growth factors that play an immunomodulatory role in autoimmunity and tumors.In recent years,it has been found that modulating fibroblast activation can effectively delay the development of these diseases,and that targeting fibroblast activation biomarkers can assess the development and treatment of these diseases.Therefore,the use of fibroblast-targeted drugs and therapeutic tools is expected to achieve new breakthroughs in the clinical management of fibrosis,autoimmune diseases and tumors.
8.Survey and analysis on fertility status of female employees aged 22-35 years by industries
Changyan YU ; Jiarui XIN ; Ming XU ; Zhenxia KOU ; Wenlan YU ; Meibian ZHANG ; Xuefei LI
Journal of Environmental and Occupational Medicine 2024;41(4):397-402
Background As the population ages, there has been a growing focus on the decline in fertility. Research has identified age and fertility history as the primary influencing factors. Nevertheless, there is a deficiency in fundamental data regarding the fertility status among different industries. Objective To investigate the fertility status and influencing factors among female workers aged 22-35 years in different industries. Methods From July 2020 to February 2021, a cross-sectional survey was conducted using a staged sampling approach. This survey specifically targeted 22-35-year-old married female workers with a history of pregnancy in industries such as education, healthcare, finance, and telecommunications, totaling 22903 participants. The survey encompassed industry, demographic characteristics, pregnancy history, time to pregnancy (TTP), and other influencing factors. The influencing factors of decline in fertility were identified by chi-square test and Cox proportional hazards regression. Subsequent industry-specific Cox proportional hazards regression models were used to compared fertility decline patterns across a spectrum of industries after selected influencing factors were adjusted. Results Among the 22903 respondents, 19194 valid questionnaires were collected, with a valid recovery rate of 83.8%. The cumulative pregnancy rates (CRP) of 1-6 months and 1-12 months for the 22-35-year-old female workers were 67.23% and 91.33% respectively. The multivariate analysis showed that region, age, education level, personal annual income, housework time, coping style, gravidity, parity, and spontaneous abortion were influencing factors of fertility decline (P<0.05). Female workers with ≥3 gravidities and ≥2 spontaneous abortions had a higher risk of fertility decline, with hazard ratios (HR) and associated 95% confidence interval (95%CI) of 0.633 (0.582, 0.688) and 0.785 (0.670, 0.921) respectively (P<0.01). Compared to the education industry, the healthcare and finance industries showed a higher risk of fertility decline, with HR (95%CI) values of 0.876 (0.834, 0.920) and 0.909 (0.866, 0.954), respectively (P<0.05). These two HR (95%CI) values remained statistically significant [0.899 (0.852, 0.948) and 0.882 (0.833, 0.934) respectively, P<0.05)] after further adjustment with nine influencing factors such as region and age. Conclusion Regions, age, education level, personal annual income, housework time, coping style, pregnancy and childbirth times, and natural abortion times are influencing factors of fertility decline in female workers. Compared to the education industry, the healthcare and finance industries have a higher risk of declining fertility.
9.Role of exosome-derived miRNA-21-5p/Smad7 in quartz dust-induced pulmonary fibrosis in rats
Yang LU ; Xiaohui DING ; Tiantian WANG ; Mengtong XU ; Jiarui HAO ; Wenjing LI ; Jing SONG
Journal of Environmental and Occupational Medicine 2024;41(8):861-866
Background Quartz dust cannot be degraded in the lungs, and inhalation of a large amount of quartz dust in the occupational production process will lead to the occurrence of pulmonary fibrosis, and then develop into silicosis. In recent years, studies have found that exosomes may be involved in the pathogenesis of fibrotic diseases by carrying microribonucleic acid (miRNA), but the mechanism of their actions in silicosis still needs to be studied. Objective To investigate the role of exosome-derived miRNA-21-5p/mothers against decapentaplegic homolog 7 (Smad7) in quartz dust-induced pulmonary fibrosis in rats. Methods Twenty-four healthy male SD rats were randomly divided into four groups (six rats in each group): control 4-week group, control 16-week group, quartz 4-week group, and quartz 16-week group. At the beginning of the experiment, 1 mL of quartz suspension (50 mg·mL−1) and 1 mL of normal saline were injected into the trachea of rats in the quartz group and the control group, respectively, by means of one-time non-exposure intratracheal dust staining. Alveolar lavage was performed at the 4th and 16th weeks after dust staining, the exosomes in lavage solution were extracted by polyethylene glycol (PEG) precipitation, morphological identification was conducted by transmission electron microscopy (TEM), particle size of exosomes was detected by nano-tracking analysis (NTA), and the marker proteins CD9 and CD63 of exosomes were detected by Western blotting (WB). The expression of miRNA-21-5p in exosomes was determined by reverse transcription polymerase chain reaction (RT-PCR). The degree of lung tissue injury and fibrosis was observed by hematoxylin-eosin staining (HE) and Masson staining. The collagen content of lung tissue was detected by hydroxyproline (HYP) method. The expression of Smad7 protein in lung tissue was detected by WB. Results The results of pathological staining showed that compared with the control group, lung inflammatory cell infiltration, alveolar wall thickening, and collagen increase were observed after 4 weeks of dusting, and collagen deposition and silicon nodules appeared after 16 weeks of dusting. Compared with the control group, the expression level of HYP in the lung tissue of the quartz group was increased after 4 weeks and 16 weeks of dust staining (P<0.05). Transmission electron microscopy showed that exosomes were saucer-shaped, and the average particle size of exosomes was 95.8 nm by NTA. Positive expression of exosome marker proteins CD9 and CD81 was found by WB. Compared with the control group, the expression of exosome-derived miRNA-21-5p in alveolar lavage fluid in the quartz group increased in the 4th week and the 16th week (P<0.05), and the expression of Smad7 protein in lung tissue decreased (P<0.05). Conclusion Exosome-derived miRNA-21-5p and Smad7 may be involved in the mechanism of quartz dust-induced pulmonary fibrosis in rats.
10.Analysis of N6-methyladenosine methylation and N6-methyladenosine RNA binding protein 1 in rats with subchronic aluminum exposure
DING Xiaohui ; LU Yang ; HAO Jiarui ; WANG Tiantian ; XU Mengtong ; SONG Jing
Journal of Preventive Medicine 2024;36(9):825-828
Objective:
To explore the effects of subchronic aluminum exposure on the level of N6-methyladenosine (m6A) methylation and the expression of N6-methyladenosine RNA binding protein 1 (YTHDF1) in the hippocampus of rats.
Methods:
Twenty-four healthy male SD rats were randomly divided into the control group (normal saline), the low dose group [10 μmol/kg Al(mal)3], the medium dose group [20 μmol/kg Al(mal)3] and the high dose group [40 μmol/kg Al(mal)3], with 6 rats in each group. The Al(mal)3 solution was administered via intraperitoneal injection on alternate days for 90 days. Escape latency, target quadrant dwell time and platform crossing times were tested to evaluate the learning and memory ability of the rats by the Morris water maze test after exposure. The brain tissue was weighted and the brain-to-body weight ratio was calculated after euthanasia. The level of m6A methylation and the expression of YTHDF1 were determined by enzyme-linked immunosorbent assay and western blot assay, respectively.
Results:
All rats survived during aluminum exposure period. The brain-to-body weight ratios of the control group and the low, medium and high dose groups were (0.46±0.06)%, (0.44±0.04)%, (0.49±0.06)% and (0.51±0.07)%, respectively, with no statistically significant differences (P>0.05). The escape latency of rats in the high dose group was longer than that in control and low group during the third to fifth day (both P>0.05). The escape latency of rats in all groups was shortened with the increase of training days (P<0.05). The target quadrant dwell time of rats in low, medium and high dose groups were lower than that in control group, and the platform crossing times of rats in high dose group were lower than that in control group (all P<0.05). The methylation level of m6A and expression level of YTHDF1 in hippocampus of rats in medium and high dose groups was higher than that in control group (both P<0.05).
Conclusion
The learning and memory impairment caused by subchronic aluminum exposure may be related to the increase of m6A methylation level and the decrease of YTHDF1 expression.


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