1.Clinical trial of cardiovascular protective effect of dapagliflozin on patients with HFpEF complicated with T2DM
Zuo-ling LIU ; Yun LING ; Ling-yan FANG
The Chinese Journal of Clinical Pharmacology 2025;41(1):11-15
Objective To explore the cardiovascular protective effect of dapagliflozin on patients with heart failure with preserved ejection fraction(HFpEF)complicated with type 2 diabetes mellitus(T2DM).Methods Patients with HFpEF complicated with T2DM were divided into treatment group and control group according to cohort method.The control group was given 0.5 g of metformin hydrochloride tablet orally twice a day,while the treatment group was given 10 mg of dapagliflozin tablet orally once a day on the basis of treatment in the control group.Patients in both groups were continuously treated for 6 months.The clinical efficacy after treatment and blood glucose indicators[fasting blood glucose(FBG),2 hours postprandial blood glucose(2 h PBG),glycosylated hemoglobin(HbA1 c)],echocardiographic left ventricular parameters[left ventricular ejection fraction(LVEF),left ventricular end-diastolic diameter(LVEDD),left ventricular remodeling index(LVRI),left ventricular mass index(LVMI)]and serum N-terminal pro-brain natriuretic peptide(NT-proBNP),serum myocardial fibrosis indicators[matrix metalloproteinase-9(MMP-9),tissue inhibitor of metalloproteinase-1(TIMP-1)]before and after treatment were compared between both groups,and the safety evaluation was performed.Results Seventy-five cases in treatment group and 72 cases in control group were included.After treatment,the total effective rates in treatment group and control group were 93.33%(70 cases/75 cases)and 81.94%(59 cases/72 cases),respectively(P<0.05).After treatment,the levels of FBG,2 h PBG,HbA1c,LVEF and LVEDD revealed no statistical differences between treatment group and control group(all P>0.05).After treatment,LVRI values in treatment group and control group were(2.17±0.41)and(2.54±0.46)g·mL-2;LAMI values were(102.47±10.32)and(113.84±15.52)g·m-2;serum NT-proBNP levels were(652.38±208.26)and(993.24±302.69)pg·mL-1;MMP-9 levels were(142.52±21.67)and(168.73±25.88)mg·L-1;TIMP-1 levels were(3.68±0.84)and(3.12±0.91)μg·L-1,respectively(all P<0.05).The total incidence rates of adverse reactions in treatment group and control group were 14.67%(11 cases/75 cases)and 12.50%(9 cases/72 cases),respectively(P>0.05).Conclusion Dapagliflozin can improve ventricular remodeling and enhance cardiac function in patients with HFpEF complicated with T2DM,and it has a significant cardiovascular protective effect.
2.Interpretation of"Standard for infection prevention and control in hemodialysis department(center)"WS/T854-2025
Yanyan WU ; Min DENG ; Huixue JIA ; Anhua WU ; Li ZUO ; Yunxi LIU ; Jiancheng ZHAO ; Jiansheng LIANG ; Yun YANG ; Ling LIN
Chinese Journal of Nosocomiology 2025;35(20):3045-3048
Hemodialysis patients exhibit compromised immune function and require long-term repeated vascular punctures as therapeutic approach,the risk of infection increases.Hospital-associated infection in hemodialysis de-partment(center)happens from time to time,which has already become a concern for the medical community,patients and social media.This paper outlines the task origin of China's"Standard for infection prevention and control in hemodialysis department(center)"(WS/T854-2025),the compilation basis and explanations for its key content,feasibility and implementation recommendations,as well as the clarifications on common issues encoun-tered during its promotion and enforcement.
3.Investigations into the Mechanism of Phycocyanin in Modulating the Wip1/p53 Pathway to Induce Apoptosis in Human Hepatocellular Carcinoma HepG2 Cells
Yun-Xi JIA ; Da HUO ; Chao YAO ; Min LI ; Fu-Ling LIU ; Hong YUAN ; Hui-Ting XUE ; Rui-Ping HU
Chinese Journal of Biochemistry and Molecular Biology 2025;41(5):741-752
Hepatocellular carcinoma(HCC)is difficult to detect in its early stages and current treatment methods are associated with significant side effects and a high risk of developing drug resistance.This study aims to investigate the effect of phycocyanin(PC)on the apoptosis of human HCC HepG2 cells and its potential mechanism.HepG2 cells were treated with PC at concentrations of 0.1,0.25,0.5,1,2.5,5,and 10 μg/mL for 12 h,and with 10 μg/mL PC and 2.5 μmol/L Wip1 inhibitor(Wip1i)alone or in combination for 12 and 24 h,respectively.Cell proliferation levels were assessed using the CCK-8 cell proliferation-toxicity assay kit.Apoptosis levels were measured by Annexin V-FITC/Propidium Iodide double staining combined with flow cytometry.TMT(Tandem Mass Tag)proteomics quantitative technol-ogy was applied to analyze differential protein expression.Western blotting was used to detect the expres-sion levels of Wip1,p53,and phosphorylated-p53(Ser15)proteins.The CCK-8 assay revealed that PC effectively inhibited HepG2 cell proliferation in a concentration-dependent manner,with a half-maximal inhibitory concentration(IC50)of 19.37 μg/mL.Flow cytometry results showed that PC significantly in-duced apoptosis,with an apoptosis rate of 30.40%.Quantitative proteomics analysis indicated that PC induced activation of the p53 pathway.The CCK-8 assay showed that Wip1i enhanced the cytotoxic effect of PC on HepG2 cells.Western blotting confirmed that PC inhibited Wip1 expression,induced p53 pro-tein phosphorylation,and promoted the expression of total p53 protein.Additionally,Wip1i further en-hanced PC-mediated activation of the p53 pathway,increasing the expression of p53 and pP53(S15).In conclusion,PC may induce apoptosis by inhibiting the activity of the p53 negative regulator Wip1,thereby promoting apoptosis through the Wip1/p53 pathway.
4.Quantitative evaluation and driving path exploration on the level of the tripartite system reform in China
Ling-yun GUO ; Liu-jie FU ; Yong-yi GUAN ; Liang-ru ZHOU ; Qiu-ying ZHENG ; Rui-feng LI
Chinese Journal of Health Policy 2025;18(3):9-17
Objective:To quantitatively evaluate the level of the three medical linkage in China from 2009 to 2022,explore the influencing factors and driving paths of the three medical linkage in China,and provide a new perspective for promoting the development of the three medical linkage.Methods:An optimized coupling coordination degree model was used to calculate the coupling coordination degree between the trinity healthcare systems and different binary systems within the systems in 31 provinces of China(excluding Hong Kong,Macao and Taiwan),and the Fuzzy-set Qualitative Comparative Analysis method was used to explore the condition configurations of multi-factor-driven three medical linkage.Results:From 2009 to 2022,the coupling coordination degree between the trinity healthcare systems in each province of China generally showed an increasing trend year by year.Among the binary systems,the overall coordinated development situation between the medical and medical insurance systems was the best and the regional development was the most balanced.The coupling coordination degree gap between the trinity healthcare system and the internal binary systems among provinces gradually widened,and the multi-polarization trend intensified.The paths to promote high-level three medical linkage can be summarized into two types:internal and external balanced development type(H1)and government-led type(H2,H3),among which the H1 path with per capita GDP and health expenditure as core conditions was the most common.Conclusion:It is suggested to enhance institutional and technological innovation,and integrate resources through a cross-departmental collaboration mechanism and digital technology.Provinces should select high-level optimization paths by leveraging regional endowments to narrow the regional development gap.Meanwhile,under the impetus of high-level policies,the protection and supervision system continues to improve,thereby promoting the three medical linkage.
5.Optimization Study of Rat Models for Sequelae of Pelvic Inflammatory Disease
Zhen LIU ; Wei-ling WANG ; Yun-cheng MA ; Yu-xi WANG ; Yuan TIAN ; Qian LI ; Xiao-zhu WANG ; Xiao-yao LIU ; Mei JIANG ; Wen-hui XU ; Jian GAO ; Ting WANG
Progress in Modern Biomedicine 2025;25(12):1921-1930
Objective:To establish a stable rat model of sequelae of pelvic inflammatory disease(SPID)with clinical characteristics,and to provide a reliable experimental model for the study of the pharmcological effect and mechanism of SPID.Methods:Twenty-four 7-week-old SD rats were divided into sham operation group,model-A(108 cfu/mL mixed bacterial solution,0.2 mL),model-B(109 cfu/mL mixed bacterial solution 0.2 mL),and model-C(108 cfu/mL E.coli 0.2 mL).The weight of the rat's uterine was weighed and the uterine index was calculated.The automatic hematology analyzer was used to detect the blood routine;hematoxylin-eosin staining(HE)and masson staining were used to detect uterine pathlogical changes in rats.Enzyme-linked immunosorbent assay(ELISA)was used to detect interleukin-1β(IL-1β),interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)in rat uterine tissue homogenates.Western blot was used to detect the expression of proteins related to NF-κB signaling pathway.Results:Compared with the sham operation group,the uterine index of model-A,model-B,and model-C were significantly increased(P<0.05,P<0.01).The levels of WBC and NE in the model-A increased significantly(P<0.01).The level of LY in model-B decreased significantly(P<0.01).The levels of IL-1β,TNF-α in model-A,model-B,and model-C were significantly increased(P<0.01).The levels of IL-6 in model-A and model-B were significantly increased(P<0.05,P<0.01).The collagen volume fraction of model-A and model-B were significantly increased(P<0.01).Mechanism study indicates that the expression levels of p-IKKβ/IKKβ,p-IκBα/IκBα and p-p65/p65 in model-A were significantly increased(P<0.01),and the expression levels of IκBα/β-actin were significantly decreased(P<0.01).The expression level of p-IKKβ/IKKβ in model-B was significantly increased(P<0.01).Conclusions:A stable rat model of SPID that conforms to clinical characteristics can be successfully constructed by combining 0.2 mL of mixed bacterial solution with a concentration of 108 cfu/mL and mechanical injury.This modeling method intervened in the expression of the NF-κB inflammatory signaling pathway.
6.Application of"integration of four dimensions"teaching mode in the un-dergraduate compulsory education on"Healthcare-associated Infection Control"based on KANO model
Ling ZENG ; Xiuhua KANG ; Minyu LIU ; Yun ZHOU ; Tianxin XIANG ; Na CHENG
Chinese Journal of Infection Control 2025;24(6):800-807
Objective To investigate the application of the"integration of four dimensions(mainline teaching-on-line course-medical case-mind map)"teaching mode in the undergraduate compulsory teaching course"Health-care-associated Infection Control",and provide reference for further improving the design of undergraduate compul-sory course on infection control.Methods A questionnaire survey on undergraduate students' satisfaction for com-pulsory course"Healthcare-associated Infection Control"was conducted using KANO model.A total of 4 dimen-sions and 21 quality indicators were set up.KANO attribute classification,satisfaction degree,and importance coef-ficients etc.were analyzed,and curriculum design was optimized.Results The overall questionnaire reliability Cronbach's a coefficient was 0.915,and the validity analysis Kaiser-Meyer-Olkin(KMO)measure of sampling adequacy value was 0.867.Among the 21 quality indicators,12 were charismatic attributes,which accounted for the largest proportion(57.14%)of the total indicators.Most quality indicators received high student satisfaction ratings.The indicators with the highest satisfaction coefficients were"playing teaching videos in class"(4.73),along with"in-tegrating typical healthcare-associated infection cases into the curriculum for relevant teaching""maintaining a relax-ed and pleasant teaching atmosphere",and"humorous and witty teaching style of the teacher"(all scoring 4.71).Four important but currently with low satisfaction indicators were"combining course content with utilitarian exam preparation""adopting a completely offline teaching format""adopting relatively strict assessment methods",and"reflecting differentiation based on difficulty coefficient in final assessment".Conclusion This course has achieved certain efficacy in undergraduate compulsory education,but there is still room for improvement in the setting of cur-riculum assessment methods.In the future,the course system should be integrated,the assessment mode of combi-ning theory and practice should be optimized,and course improvement and innovation should be promoted.
7.Agitation of TGR5 by INT-777 protected hypoxic-ischemic encephalopathy in neonatal rats
Rong-jie LIU ; Qin CHEN ; Ying XIONG ; Zhao-yun WANG ; Chang-ling CHEN ; Qin ZHANG ; Mao-qiong CHEN ; Zhan-hui FENG ; Lan YE
Chinese Pharmacological Bulletin 2025;41(6):1085-1090
Aim To investigate the neuroprotective effect of Takeda G protein-coupled receptor-5(TGR5)activated by INT-777 on hypoxic-ischemic encephalop-athy(HIE)in neonatal rats.Methods Seven-day-old SD rats were randomly divided into the sham opera-tion group(Sham,S),model group(HIE,G),INT-777 low-dose(L),medium-dose(M),and high-dose(H)groups.The modified Rice-Vanucci method was used to construct the HIE model and Intranasal admin-istration 1 h after modeling.Short-term neurobehavioral tests were performed 48 h after modeling to evaluate the neurological function of neonatal rats,TTC staining was used to determine the volume of cerebral infarction,dry and wet specific gravity was used to determine the brain water content,ferrous ion kit was used to deter-mine the brain ferrous ion content,HE staining was used to observe the pathological damage of brain tis-sue,Nissl staining was used to observe the loss of Nissl substance,Transmission electron microscopy(TEM)was used to observe the mitochondrial morphological changes of cortical neurons,and Western blot was em-ployed to detect the expression of ferroptosis-related proteins TFR1 and GPX4.Results Compared with group S,group G had increased short-term neurobehav-ioral test consumption time,higher scores,increased cerebral infarct volume,brain water content,and brain ferrous iron content,significant brain tissue damage on the affected side,severe loss of Nissl substance,smaller neuronal mitochondria,decreased mitochondrial cris-tae,and increased expression of TFR1 and reduced ex-pression of GPX4.Compared with group G,the INT-777 administration group had a shorter consumption time for short-term neurobehavioral tests,lower scores,the cerebral infarction volume,brain water content,and brain ferrous ion content decreased,the brain tissue damage on the affected side was reduced,and there was insignificant loss of Nissl substance,larger neuronal mi-tochondrial volume,increased mitochondrial cristae,re-duced expression of TFR1,and increased expression of GPX4.Conclusions INT-777 agonist TGR5 has a protective effect against hypoxic-ischemic encephalopa-thy in neonatal rats,and its mechanism of action may be related to the inhibition of neuronal ferroptosis.
8.Construction of a prediction model for seroma after endoscopic thyroid-ectomy by breast approach
Sheng-fei YANG ; Yun-da ZHANG ; Ming LIU ; Shi-ran QIAN ; Shu-xiong LI ; Man ZHANG ; Meng-ling WEI ; Dong-wei LI
Chinese Journal of Current Advances in General Surgery 2025;28(5):337-342
Objective:To explore the prognostic factors of seroma after endoscopic thyroidectomy by breast ap-proach,and construct a nomogram to predict the possibility of cervical seroma.Methods:Data of patients undergoing endoscopic thyroid surgery in Dongguan Tungwah Hospital from January 2022 to May 2024 and Dongguan Songshan Lake Tungwah Hospital from May 2023 to August 2024 were retrospectively analyzed,and 1493 patients meeting the in-clusion criteria were selected.Among them,there were 1048 patients in Dongguan Tungwah Hospital as the training co-hort,1015 patients without seroma group and 33 patients with seroma group.There were 445 patients in Dongguan Songshan Lake Tungwah Hospital as the verification cohort,including 424 patients without seroma and 21 patients with seroma.Multivariate logistic regression analysis was used to obtain relevant independent prognostic factors,and R soft-ware established a nomogram model.Calibration curves,Hosmer-Lemeshow goodness of fit,ROC curves were used to evaluate the calibrability of the nomogram model,and clinical utility was assessed by clinical decision curves.Results:Multivariate logistic regression analysis showed that central lymph node dissection,diabetes,hyperthyroidism,and nod-ule size were independent prognostic factors related to seroma.Based on the prognostic factors,the nomogram of se-roma after ETBA was constructed.The calibration curves of the training and the verification group were in good agree-ment with the observed results,and the Hosmer-Lemeshow goodness of fit test was good,with the training cohort P=0.244 and the verification cohort P=0.803.The ROC curve of the training cohort showed that the area under the curve was 0.810(95%CI:0.740~0.879),and the ROC curve of the verification cohort showed that the area under the curve was 0.815(95%CI:0.722~0.909).Conclusion:The nomogram model based on the relevant prognostic factors ob-tained by multivariate logistic regression analysis has a good prediction effect on the seroma after ETBA,and can provide reasonable and individualized treatment plan for patients.
9.Effects of Radix Angelica sinensis and Radix Hedysari ultrafiltration on ionizing radiation-induced damage in RAW264.7 Macrophages and the mechanisms
Ling-yun WANG ; Rui WANG ; Hua-qing XI ; Guo-ci LU ; Xing XU ; Kai LIU
Chinese Pharmacological Bulletin 2025;41(9):1700-1711
Aim To investigate the protective effects and potential mechanisms of Radix Angelica sinensis and Radix Hedysari ultrafiltrate(RAS-RH)on X-ray-induced cellular damage in Raw264.7 macrophages.Methods An integrated approach combining network pharmacology,molecular docking,and bioinformatics a-nalysis was employed to predict therapeutic targets and signaling pathways of RAS-RH in coronary heart dis-ease(CHD).Subsequent in vitro validation was per-formed using an X-ray(6 Gy)-induced macrophage in-jury model with four experimental groups:control,radi-ation-only model,and three RAS-RH-treated groups at varying concentrations.Cell viability was assessed by CCK-8 assay,apoptosis by flow cytometry with Annexin V-FITC/PI staining,mitochondrial membrane potential by JC-1 fluorescence,and inflammatory cytokine levels(IL-1 β,IL-6,IL-18,TNF-α)by ELISA.Molecular mechanisms were investigated through Western blot and qRT-PCR analyses of TLR4/NLRP3/Caspase-1 sig-naling pathway components and Bcl-2 family proteins.Results Network pharmacology revealed RAS-RH's multi-target action on apoptosis and inflammation-relat-ed pathways,particularly NF-κB and Bcl-2 signaling.Molecular docking identified strong binding affinities between RAS-RH components and TLR4/NLRP3 pro-teins.In vitro studies demonstrated that RAS-RH treat-ment significantly improved cell viability(P<0.01),reduced apoptosis(P<0.01),restored mitochondrial membrane potential(P<0.05),and attenuated radia-tion-induced ultrastructural damage including mem-brane disruption and cytoplasmic vacuolization.ELISA showed marked suppression of pro-inflammatory cyto-kines(P<0.01).Transmission electron microscopy(TEM)analysis revealed that RSA-RH ameliorated pyroptosis-associated ultrastructural alterations,inclu-ding plasma membrane disruption and cytoplasmic vac-uolization.Protein and gene expression analyses con-firmed downregulation of TLR4/NLRP3/Caspase-1 pathway and modulation of Bcl-2/Bax ratio.Conclu-sion RAS-RH exerts radioprotective effects through dual regulation of pyroptosis and apoptosis pathways,suggesting its potential as an adjuvant therapy for radia-tion-induced cardiovascular complications in CHD pa-tients.
10.Clinical trial of cardiovascular protective effect of dapagliflozin on patients with HFpEF complicated with T2DM
Zuo-ling LIU ; Yun LING ; Ling-yan FANG
The Chinese Journal of Clinical Pharmacology 2025;41(1):11-15
Objective To explore the cardiovascular protective effect of dapagliflozin on patients with heart failure with preserved ejection fraction(HFpEF)complicated with type 2 diabetes mellitus(T2DM).Methods Patients with HFpEF complicated with T2DM were divided into treatment group and control group according to cohort method.The control group was given 0.5 g of metformin hydrochloride tablet orally twice a day,while the treatment group was given 10 mg of dapagliflozin tablet orally once a day on the basis of treatment in the control group.Patients in both groups were continuously treated for 6 months.The clinical efficacy after treatment and blood glucose indicators[fasting blood glucose(FBG),2 hours postprandial blood glucose(2 h PBG),glycosylated hemoglobin(HbA1 c)],echocardiographic left ventricular parameters[left ventricular ejection fraction(LVEF),left ventricular end-diastolic diameter(LVEDD),left ventricular remodeling index(LVRI),left ventricular mass index(LVMI)]and serum N-terminal pro-brain natriuretic peptide(NT-proBNP),serum myocardial fibrosis indicators[matrix metalloproteinase-9(MMP-9),tissue inhibitor of metalloproteinase-1(TIMP-1)]before and after treatment were compared between both groups,and the safety evaluation was performed.Results Seventy-five cases in treatment group and 72 cases in control group were included.After treatment,the total effective rates in treatment group and control group were 93.33%(70 cases/75 cases)and 81.94%(59 cases/72 cases),respectively(P<0.05).After treatment,the levels of FBG,2 h PBG,HbA1c,LVEF and LVEDD revealed no statistical differences between treatment group and control group(all P>0.05).After treatment,LVRI values in treatment group and control group were(2.17±0.41)and(2.54±0.46)g·mL-2;LAMI values were(102.47±10.32)and(113.84±15.52)g·m-2;serum NT-proBNP levels were(652.38±208.26)and(993.24±302.69)pg·mL-1;MMP-9 levels were(142.52±21.67)and(168.73±25.88)mg·L-1;TIMP-1 levels were(3.68±0.84)and(3.12±0.91)μg·L-1,respectively(all P<0.05).The total incidence rates of adverse reactions in treatment group and control group were 14.67%(11 cases/75 cases)and 12.50%(9 cases/72 cases),respectively(P>0.05).Conclusion Dapagliflozin can improve ventricular remodeling and enhance cardiac function in patients with HFpEF complicated with T2DM,and it has a significant cardiovascular protective effect.

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