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.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.
3.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.
4.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.
5.Expression profiling of miRNAs in chrysotile-exposed lung epithelial cells
Jiarui HE ; Juan SONG ; Yujun WANG ; Xu ZHANG ; Jie YANG ; Tingting HUO ; Faqin DONG ; Jianjun DENG
Journal of Environmental and Occupational Medicine 2024;41(11):1277-1282
Background Chrysotile is widely used in construction and industry. Research has shown that it is associated with lung fibrosis in occupational groups, but the involvement of microRNAs (miRNAs) in chrysotile-induced lung fibrosis has been less well studied, and the specific mechanism is still unclear. Objective Using next-generation sequencing technology to analyze the effects of chrysotile exposure on the miRNAs expression profiles of human lung epithelial cells (BEAS-2B cells), to explore the variations of differentially expressed miRNAs and related signaling pathways, and to identify potential targets and molecular mechanisms of chrysotile-induced lung fibrosis. Methods Chrysotile was analyzed with a laser particle size analyzer and an X-ray diffractometer for particle size and physical phase. BEAS-2B cells were exposed to chrysotile for designed time sessions (12, 24, and 48 h) and doses (0, 50, 100, and 200 μg·mL−1). Cell viability was detected with a cell viability assay kit (CCK8); expression levels of Fibronectin, Collagen-Ⅰ, and α-smooth muscle actin (α-SMA) were detected by Western blot after exposure to 200 μg·mL−1 chrysotile for 24 h. Sample correlation and changes in miRNAs expression profiles between the chrysotile-exposed and the control groups were analyzed by next-generation sequencing technology. The target genes of differentially expressed miRNAs were predicted and subjected to Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Results The average particle size of the chrysotile dust sample used in this study was 3.58 μm, and the results of X-ray diffraction analysis confirmed the characteristic peaks of chrysotile. Compared with the control group, the chrysotile gradually inhibited the survival rate of BEAS-2B cells with increasing concentration and exposure time (P<0.01). The survival rates of the 50, 100, and 200 μg·mL−1 chrysotile-exposed cells after 12 h exposure were 83.88%±1.86%, 78.07%±3.97%, and 71.95%±2.99%, respectively; the survival rates after 24 h exposure were 77.41%±1.58%, 69.57%±2.23%, and 62.79%±3.65%, respectively; the survival rates after 48 h exposure were 74.31%±4.93%, 65.84%±2.71%, and 52.74%±6.31%, respectively. The Fibronectin, Collagen-Ⅰ, and α-SMA protein expression levels were elevated in the 200 μg·mL−1 chrysotile-exposed BEAS-2B cells (P <0.05). The results of principal component analysis showed that there were differences in the composition of the samples between the chrysotile exposure group and the control group, and a total of 163 differential miRNAs were screened, of which 79 were up-regulated and 84 were down-regulated. The results of GO analysis showed that the differential miRNAs were mainly associated with biological processes such as regulation of transcription by RNA polymerase II, regulation of DNA templated transcription, cellular differentiation, protein phosphorylation, lipid metabolism, and cell cycle, cellular components such as nucleus, cytomembrane, cytoskeleton, mitochondria, and endoplasmic reticulum, as well as molecular functions such as protein binding, metal ion binding, transferase activity, and DNA binding. The results of KEGG analysis revealed that the differential miRNAs were mainly enriched in cancer pathway, phosphatidylinositol 3-kinase/ protein kinase B (PI3K/AKT) pathway, Ras-associated protein 1 (Rap1) pathway, calcium pathway, cyclic guanosine monophosphate/ protein kinase G (cGMP-PKG) pathway, Hippo pathway, cyclic adenosine monophosphate (cAMP) pathway, and Ras pathway. Conclusion Chrysotile exposure could significantly inhibit BEAS-2B cell survival, elevate the expression of lung fibrosis-associated proteins, and induce differential miRNAs expression, affecting biological processes (such as lipid metabolism, protein phosphorylation, and cell cycle) and cell components (such as mitochondria and endoplasmic reticulum), and interfering with PI3K/AKT pathway, Hippo pathway, cAMP pathway, Rap1 pathway, and Ras pathway.
6.Antioxidant activity of water extract from bamboo stems and its protective effect on t-BHP induced oxidative damage in Caco-2 cells
Xin YUAN ; Yunlong HUANG ; Xiaomin XIE ; Zihan ZHONG ; Jiarui CHEN ; Cuiyu BAO ; Xu YANG ; Ping MA
Journal of Public Health and Preventive Medicine 2024;35(6):50-54
Objective To investigate the antioxidant activity of bamboo stem extracts and the therapeutic effect of bamboo stem water extract on oxidative inflammation induced by tert butyl hydroperoxide (t-BHP) in human colon adenocarcinoma cells (Caco-2). Methods In this study, ABTS, DPPH, and FRAP assays were used to determine the extracellular antioxidant activity of petroleum ether extract, ethyl acetate extract, n-butanol extract, 95% ethanol extract, and distilled water extract from bamboo stems. The human intestinal Caco-2 cell line was used as the model cell, and t-BHP was selected as the oxidative stress modeling agent. The CCK-8 assay was used to detect cell viability and the optimal oxidative damage concentration of t-BHP. The content of MDA, 8-OHdG, TNF-α and IL-1β were detected to assess antioxidant stress effect. Results The five extracts of bamboo all had certain antioxidant activity, among which the water extract of bamboo stem had the best comprehensive antioxidant activity with high cell viability in Caco-2 cells. The optimal modeling concentration of t-BHP was 200 μMol/L. The water extract of bamboo stem significantly reduced the content of oxidative stress related biomarkers and inflammatory factors in Caco-2 cells induced by t-BHP. Conclusion The stem extracts of bamboo in Xianning City have strong in vitro antioxidant activity. Among them, the water extract of bamboo stem has a protective effect on t-BHP induced oxidative damage in Caco-2 cells, suggesting that the water extract possesses a potential to be developed as new antioxidant products for clinical prevention and treatment of oxidative damage related diseases.
7.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.
8.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.
9.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.
10.Relationship of miR-126 and miR-325 in serum and vitreous with the severity of proliferative vitreoretinopathy
Xin TANG ; Zhiming LIU ; Ningda XU ; Jiarui LI ; Lyuzhen HUANG
International Eye Science 2024;24(3):351-355
AIM: To explore the relationship of miR-126 and miR-325 in serum and vitreous with the severity of proliferative vitreoretinopathy(PVR).METHODS: A total of 100 cases(100 eyes)with PVR who were treated in our hospital from October 2019 to October 2022 were selected and retrospectively studied. They were divided into a mild group(42 eyes)and a severe group(58 eyes)according to the degree of retinopathy, and another 30 cases(30 eyes)that underwent vitrectomy without retinopathy due to eye trauma in our hospital during the same period were selected as the control group. Fluorescence quantitative PCR was used to detect the expression levels of miR-126 and miR-325 in serum and vitreous; ELISA was used to detect the levels of transforming growth factor β(TGF-β), platelet-derived growth factor(PDGF), vascular endothelial growth factor(VEGF), and tumor necrosis factor α(TNF-α)in serum and vitreous; and Pearson's method was used to analyze the correlation between the serum and vitreous levels of miR-126 and miR-325 correlated with the levels of TGF-β, PDGF, VEGF, and TNF-α; Logistic multifactorial analysis was used to analyze the influencing factors for the occurrence of severe PVR.RESULTS: Compared with the control group, miR-126 levels in serum and vitreous of PVR patients were decreased and lower in the severe PVR group than in the mild PVR group(both P<0.05); miR-325 levels were increased and higher in the severe PVR group than in the mild PVR group(both P<0.05). TGF-β, PDGF, VEGF, and TNF-α levels in serum and vitreous were increased in the severe PVR group compared to the mild PVR group(all P<0.05). The miR-126 levels in serum and vitreous of patients with PVR were negatively correlated with miR-325, TGF-β, VEGF, TNF-α, and PDGF levels(all P<0.05), and miR-325 was positively correlated with TGF-β, VEGF, TNF-α, and PDGF levels(all P<0.05). Logistic regression analysis showed that miR-325, TGF-β, PDGF, and TNF-α were all independent risk factors for the development of severe PVR in serum and vitreous, and miR-126 was an independent protective factor for the development of severe PVR in serum and vitreous(P<0.05).CONCLUSION: With the aggravation of PVR, miR-126 expression in serum and vitreous decreased while miR-325 expression increased and correlated with TGF-β, TNF-α, VEGF, and PDGF.


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