1.Effect of astragaloside Ⅳ on a mouse model of carbon tetrachloride-induced liver fibrosis and its mechanism
Wanchun ZHU ; Jiahao QIU ; Yu CUI ; Yijing ZHANG ; Zhi SHANG ; Yueqiu GAO ; Lingying HUANG
Journal of Clinical Hepatology 2026;42(3):608-617
ObjectiveTo investigate the liver-protecting and anti-liver fibrosis effects of astragaloside Ⅳ (AS-Ⅳ) in vitro and in vivo, as well as its mechanism of action in intervention against liver fibrosis. MethodsIn the animal experiment, C57BL/6J mice were divided into control group, model group, low-dose AS-Ⅳ (20 mg/kg) group, and high-dose AS-Ⅳ (80 mg/kg) group. The mice were given intraperitoneal injection of carbon tetrachloride for 6 weeks to induce liver fibrosis, and since week 3 of injection, the mice in the low-dose AS-Ⅳ group and the high-dose AS-Ⅳ group were given AS-Ⅳ by gavage at a dose of 20 mg/kg and 80 mg/kg, respectively. The serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured after 4 weeks of administration, as well as the serum levels of hyaluronic acid (HA), laminin (LN), procollagen Ⅲ N-terminal peptide (PⅢNP), and collagen type Ⅳ (Col-Ⅳ). HE staining, picrosirius red staining, and Masson staining were used to observe liver histopathology and collagen deposition; RT-qPCR was used to measure the mRNA expression levels of Acta2, Col1a1, and Col3a1 in liver tissue, and Western blot was used to measure the protein expression levels of α-smooth muscle actin (α-SMA), collagen type Ⅲ (Col-Ⅲ), phosphatidylinositol 3-kinase (PI3K), phosphorylated PI3K (pPI3K), protein kinase B (Akt), and phosphorylated AKT (p-Akt) in liver tissue; transcriptome sequencing was performed for liver tissue to identify differentially expressed genes and perform a bioinformatics analysis. In the cell experiment, transforming growth factor-β (TGF-β) was used to induce the activation of LX-2 cells, and the PI3K inhibitor LY294002 and the PI3K activator 740 Y-P were used for intervention. The cells were divided into control group, model group, AS-Ⅳ group, LY294002 group, and AS-Ⅳ+740 Y-P group, and the cells were harvested after 36 hours of intervention. Changes in the protein expression levels of α-SMA, Col-Ⅲ, pPI3K/PI3K, and pAkt/Akt in LX-2 cells were measured, as well as changes in the relative mRNA expression levels of Acta2, Col1a1, and Col3a1. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups. ResultsIn the animal experiment, compared with the model group, the AS-Ⅳ treatment group had significant reductions in the serum levels of ALT, AST, HA, LN, PⅢNP, and Col-Ⅳ (all P<0.01), the mRNA expression levels of Acta2, Col1a1, and Col3a1 in liver tissue (all P<0.05), and the protein expression levels of α-SMA, Col-Ⅲ, pPI3K, and pAkt (Ser473) in liver tissue (all P<0.05). In the cell experiment, compared with the control group, the model group had significant increases in the protein expression levels of α-SMA, Col-Ⅲ, pPI3K, and pAkt (Ser473) after TGF-β induction (all P<0.05); compared with the model group, the AS-Ⅳ group had significant reductions in the protein expression levels of α-SMA, Col-Ⅲ, pPI3K, and pAkt (Ser473) (all P<0.05), and both the AS-Ⅳ group and the LY294002 group had significant reductions in the protein expression level of pPI3K and the relative mRNA expression levels of Acta2, Col1a1, and Col3a1 (all P<0.05). Compared with the AS-Ⅳ group, there were significant increases in the protein expression level of pPI3K and the relative mRNA expression levels of Acta2, col1a1, and Col3a1 after 740 Y-P intervention (all P<0.05). ConclusionAS-Ⅳ can inhibit hepatic stellate cell activation and improve liver fibrosis, possibly by inhibiting the PI3K/Akt signaling pathway.
2.Wdr63 Deletion Aggravates Ulcerative Colitis Likely by Affecting Th17/Treg Balance and Gut Microbiota
Hao ZHU ; Meng-Yuan ZHU ; Yang-Yang CAO ; Qiu-Bo YANG ; Zhi-Peng FAN
Progress in Biochemistry and Biophysics 2025;52(1):209-222
ObjectiveUlcerative colitis is a prevalent immunoinflammatory disease. Th17/Treg cell imbalance and gut microbiota dysregulation are key factors in ulcerative colitis pathogenesis. The actin cytoskeleton contributes to regulating the proliferation, differentiation, and migration of Th17 and Treg cells. Wdr63, a gene containing the WD repeat domain, participates in the structure and functional modulation of actin cytoskeleton. Recent research indicates that WDR63 may serve as a regulator of cell migration and metastasis via actin polymerization inhibition. This article aims to explore the effect of Wdr63 deletion on Th17/Treg cells and ulcerative colitis. MethodsWe constructed Wdr63-/- mice, induced colitis in mice using dextran sulfate sodium salt, collected colon tissue for histopathological staining, collected mesenteric lymph nodes for flow cytometry analysis, and collected healthy mouse feces for microbial diversity detection. ResultsCompared with wild-type colitis mice, Wdr63-/- colitis mice had a more pronounced shortening of colonic tissue, higher scores on disease activity index and histological damage index, Treg cells decreased and Th17 cells increased in colonic tissue and mesenteric lymph nodes, a lower level of anti-inflammatory cytokine IL-10, and a higher level of pro-inflammatory cytokine IL-17A. In addition, WDR63 has shown positive effects on maintaining intestinal microbiota homeostasis. It maintains the balance of Bacteroidota and Firmicutes, promoting the formation of beneficial intestinal bacteria linked to immune inflammation. ConclusionWdr63 deletion aggravates ulcerative colitis in mice, WDR63 inhibits colonic inflammation likely by regulating Th17/Treg balance and maintains intestinal microbiota homeostasis.
3.Research of Subtype A Caused by New A Allele Mutation
Li-Ping ZOU ; Fang QIU ; Jian-Shuo LIU ; Zhi-Peng WU ; Feng-Qing ZHANG ; Ying ZHU
Journal of Experimental Hematology 2025;33(6):1765-1768
Objective:In order to clarify the ABO phenotype and genotype,and explore the molecular biological mechanism,serological detection,genotyping and gene sequencing were performed on an upper gastrointestinal hemorrhage patient with inconsistent forward and reverse ABO blood typing.Methods:ABO forward and reverse blood typing,H antigen identification,capillary centrifugation test and salivary substance detection were performed by classical serological method,moreover,polymerase chain reaction-sequence specific primer(PCR-SSP)was used for ABO genotyping,ABO gene 1-7 exons were sequenced by Sanger analysis in order to identify mutation.Results:Mixed field agglutination with anti-A,anti-AB and no agglutination with anti-A1 were appeared in the forward typing tests,agglutination with B cells but no agglutination with A1 cells and O cells were appeared in the reverse typing tests.3+agglutination strength was showed with anti-H.In capillary centrifugation experiment,erythrocyte after isolation in proximal part and distal end had same strength of agglutination with anti-A.Substances A and H were detected in saliva.The patient was assigned an A3 phenotype according to serological characteristics.Sequencing results of ABO gene 1-7 exons showed c.261delG,c.467C>T,c.865A>G,in which,865A>G was the first discovered mutation,and this new mutation had been submitted to GenBank with accession number PP187306.Conclusion:A novel site mutation c.865A>G is reported in this study,and this new mutation can result in a replacement of Met with Val at residue 289(p.Met289Val)and lead to an A3 phenotype.
4.Effect of Graft Composition on Viral Infection and Survival after Allogeneic Hematopoietic Stem Cell Transplantation
Fan LIU ; Shan WANG ; Qiu-Juan ZHU ; Tao WANG ; Wei-Wei TIAN ; Rong GONG ; Zhi-Lin GAO
Journal of Experimental Hematology 2025;33(6):1803-1808
Objective:To investigate the effect of infusing different doses of graft cells on viral infections and survival after allogeneic hematopoietic stem cell transplantation(allo-HSCT).Methods:Clinical data of 99 patients with hematological diseases who underwent allo-HSCT in Shanxi Bethune Hospital were retrospectively analysed.The proportion of mononuclear cells(MNC)was counted microscopically,the proportions and absolute counts of CD34+cells and lymphocyte subsets(including CD3+T,CD4+T,CD8+T,CD4+CD8+T,B,and NK cells)were detected by flow cytometry,and the infusion dose of each cell types was calculated.The patients were divided into high-dose group and low-dose group based on the median value of the infused cell dose.The effects of different doses of various graft cells on post-transplant viral infections(CMV,EBV,BKV)and survival were analyzed.Results:The low-dose MNC(<7.97 × 108/kg)and high-dose CD4+CD8+T cell(≥3.02 × 106/kg)groups had a higher Epstein-Barr virus(EBV)infection rate(P=0.031;P=0.020).The high-dose CD34+cell group and low-dose CD3+T,CD8+T and natural killer(NK)cell groups showed a trend toward higher EBV infection rates,but the differences were not statitsically significant(P>0.05).There was no significant difference in the rates of EBV infection between the high-dose and low-dose groups of CD4+T and B cells(P>0.05).Multivariate analysis revealed that the doses of MNC and CD4+CD8+T cells in the graft were independent factors influencing EBV infection(P=0.023;P=0.016).The doses of cells in the graft showed no significant impact on CMV and BKV infection,or patient survival(P>0.05).Conclusion:Infusing a lower dose of MNC and a higher dose of CD4+CD8+T cells increases the risk of EBV infection,but does not affect the survival outcome.
5.Cost-effectiveness and mortality risk impact on elderly health management of essential public health services:A case study in Henan Province
Zhi-ping GUO ; Rong-mei LIU ; Neng-guang DAI ; Yi LI ; Tong JIN ; Qiu-ping ZHAO ; Hao SHI ; Chun-rong BAO ; Yan-qing MIAO
Chinese Journal of Health Policy 2025;18(11):17-24
Objective:To evaluate the cost-effectiveness and impact on mortality of health management services for the elderly aged 65 years and older in national essential public health service project.Methods:Based on the data of county-level medical institutions in Henan Province from 2019 to 2024,the Random Forest Method was used to construct a counterfactual framework to predict the hospitalization expenses under the unmanaged scenario,and then the cost-benefit ratio(BCR)and net income were calculated.Time-dependent Cox proportional hazards model was used to evaluate the effect of health management on all-cause mortality and cardiovascular and cerebrovascular disease mortality in the elderly.Results:A total of 962 955 elderly patients were included,451 119(46.85%)were included in the management group.The average hospitalization cost of the management group was significantly lower than that of the non-management group(P<0.05).Except for 2020-2021,BCRS in 2019 and 2022-2024 were 6.34,2.05,4.45 and 6.60,respectively.The risk of all-cause death was reduced by 76.96%,and the risk of cardiovascular and cerebrovascular death was reduced by 75.57%in the elderly patients included in the management group compared with those not included in the management group.Suggestions:It is necessary to establish a health outcomes-based evaluation system and promote the transformation and upgrading of the service model from single chronic disease management to"integrated health services with multi-disease management".
6.Impact of Ticagrelor vs. Clopidogrel in Patients With Acute Coronary Syndrome Undergoing Left Main Percutaneous Coronary Intervention
Miaohan QIU ; Xuehan ZHI ; Haiwei LIU ; Zhenyang LIANG ; Bin WANG ; Kai XU ; Shaoyi GUAN ; Geng WANG ; Xiaozeng WANG ; Yingyan MA ; Quanmin JING
Cardiology Discovery 2025;05(1):39-46
Objective::There is limited evidence regarding the choice of P2Y 12 receptor inhibitors as a component of dual antiplatelet therapy in patients with left main (LM) disease undergoing percutaneous coronary intervention (PCI). This study aimed to evaluate long-term clinical outcomes of ticagrelor- vs. clopidogrel-based dual antiplatelet therapy strategy in acute coronary syndrome (ACS) patients undergoing LM PCI. Methods::This is a post-hoc analysis from a prospective, single-center, real-world PCI registry. A total of 1,163 patients discharged post-ACS who underwent LM PCI and received ticagrelor or clopidogrel between March 2016 and March 2019 were included in the study. The primary endpoint was ischemic events at 12 months, including cardiac death, myocardial infarction, or stroke. Secondary outcomes included all-cause death and Bleeding Academic Research Consortium types 2, 3, and 5, and types 3 and 5 bleeding. Propensity score matching was used to adjust for bias due to confounders between the 2 groups.Results::The ticagrelor and clopidogrel groups comprised 529 (45.49%) and 634 (54.51%) patients, respectively. During the follow-up period, the rate of ischemic events was significantly lower with ticagrelor than with clopidogrel before (1.32% (7/529) vs. 3.63% (23/634), P = 0.013,6) and after propensity score matching (1.41% (6/425) vs. 4.00% (17/425), P = 0.020,1). The rates of all-cause death, Bleeding Academic Research Consortium-defined type 2, 3, and 5 bleeding, and type 3 and 5 bleeding were similar between the ticagrelor group and clopidogrel group before or after propensity score matching adjustment (all P > 0.05). Conclusion::Among patients with ACS undergoing LM PCI, ticagrelor use was associated with ischemic events benefit without excessive risk of bleeding at 12 months compared with clopidogrel.
7.Outcome of low molecular weight heparin combined with continuous renal replacement therapy for severe acute pancreatitis
Yi ZHOU ; Wei-zhi CHEN ; Lin QIU ; Wei-di WANG
Journal of Regional Anatomy and Operative Surgery 2025;34(10):871-875
Objective To investigate the outcome of low molecular weight heparin combined with continuous renal replacement therapy(CRRT)in the treatment of severe acute pancreatitis.Methods The clinical data of 84 patients with severe acute pancreatitis admitted to our hospital from June 2022 to December 2023 were collected,and the patients were divided into the CRRT group and the combination group according to their treatment methods,with 42 cases in each group.The patients in the CRRT group were treated with CRRT,while those in the combination group were treated with CRRT and low molecular weight heparin.The serum levels of pancreatitis markers,inflammatory factors,serum intercellular adhesion molecules-1(ICAM-1)and high mobility group proteins B1(HMGB1)and acute physiology and chronic health status evaluation Ⅱ(APACHE Ⅱ)scores were compared between the two groups,the symptom improvement time of patients were recorded,and the curative effect of patients were evaluated.Results The serum levels of amylase(S-AMY),pancreatic lipase(LPS),urinary amylase(U-AMY),C-reactive protein(CRP),ICAM-1 and HMGB1,and APACHE Ⅱ scores after treatment in the two groups were significantly lower than those before treatment,and the combination group was lower than the CRRT group(P<0.05).After treatment,the disappearance time of abdominal pain and abdominal bloating,the recovery time of defecation,and the disappearance time of fever in the combination group were all significantly shorter than those in the CRRT group(P<0.05).The combination group had a significantly higher overall effective rate of treatment than the CRRT group(P<0.05).Conclusion Low molecular weight heparin combined with CRRT is effective for on the treatment of severe acute pancreatitis,which can significantly reduce the levels of pancreatitis markers,inflammatory factors,serum ICAM-1 and HMGB1,effectively improve clinical symptoms,and shorten the time for symptom improvement.
8.Clinical trail of vericiguat combined with sacubitril valsartan sodium in the treatment of patients with heart failure with reduced ejection fraction
Miao-jun WANG ; Shi-ping XU ; Xiao-jin PAN ; Zhi-dong YE ; Yu-fang LIAN ; Jun QIU ; Shao-tang LU ; Sheng-jie ZHOU
The Chinese Journal of Clinical Pharmacology 2025;41(1):6-10
Objective To observe the clinical efficacy and safety of vericiguat tablets combined with sacubitril valsartan sodium(Sac/Val)tablets in the treatment of patients with heart failure with reduced ejection fraction(HFrEF).Methods The HFrEF patients were divided into control group and treatment group according to the cohort method.The control group was treated with Sac/Val tablets 200 mg per time,bid,orally.On the basis of control group,the treatment group was treated with vericiguat tablets 2.5 mg per time,qd,taken with meal.Two groups were treated for 3 months.The clinical efficacy,left ventricular ejection fraction(LVEF),left ventricular end-diastolic dimension(LVEDD)and end-systolic diameter(LVESD),levels of high sensitivity C-reactive protein(hs-CRP),interleukin-6(IL-6),nitric oxide(NO),N-terminal pro-brain natriuretic peptide(NT-proBNP),blood urea nitrogen(BUN)and serum creatinine(SCr),and safety were compared between the two groups.During follow-up,the heart failure rehospitalization rates and major adverse cardiovascular events were compared between the two groups.Results Treatment group was enrolled 53 patients,control group was enrolled 53 patients.After treatment,the total effective rates of treatment and control groups were 94.34%(50 cases/53 cases)and 81.13%(43 cases/53 cases)with statistical significant difference(P<0.05).After treatment,the LVEF of treatment and control groups were(48.02±5.20)%and(43.02±4.33)%,the LVEDDs were(52.85±6.30)and(55.63±6.88)mm,the LVESDs were(41.64±6.40)and(44.22±5.85)mm,the levels of hs-CRP were(10.22±2.63)and(14.60±2.98)mg L-1,the levels of IL-6 were(14.48±2.40)and(17.36±2.52)pg·mL-1,the levels of NO were(102.60±20.16)and(92.16±16.33)μmol·L-1,the levels of NT-proBNP were(898.74±102.20)and(1315.60±182.64)ng·L-1,the levels of BUN were(12.02±2.28)and(13.45±2.33)mmol·L-1,the levels of SCr were(82.22±5.89)and(85.64±6.03)μmol·L-1,the heart failure rehospitalization rates were 5.66%and 13.21%,respectively;the differences were statistical significant between two groups(all P<0.05).The adverse drug reactions of treatment group were hyperkalemia,hypotension,renal dysfunction,dizziness and headache,while those in control group were renal dysfunction,hyperkalemia,and hypotension.The major adverse cardiovascular events of treatment group were angina pectoris and acute myocardial infarction,while those in control group were angina pectoris,acute myocardial infarction and atrial fibrillation.The incidences of total adverse drug reactions in treatment and control groups were 13.21%and 7.55%,the incidences of major adverse cardiovascular events were 5.66%and 13.21%,respectively,without statistically significant differences(all P>0.05).Conclusion Vericiguat tablets combined with Sac/Val tablets have a definitive clinical efficacy in the treatment of HFrEF patients,which can improve cardiac and endothelial function,reduce inflammatory response and readmission times,without increasing the incidences of adverse drug reactions.
9.Risk prevention and control and quality efficiency improvement of medical equipment procurement
Quan-quan LI ; Ming QIU ; Shu-ying LI ; Xin-yi HUANG ; Yu ZHENG ; Zhi-ling WANG ; Ke MA
Chinese Medical Equipment Journal 2025;46(3):81-85
Objective To investigate the impact of risk prevention and control on the quality efficiency of medical equipment procurement.Methods The medical equipment procurement projects with enhanced risk prevention measures during 2023(119 items)were assigned to an observation group,while those without strengthened risk control during 2022(118 items)were enrolled into a control group.The two groups were compared in terms of bid failure/rejection rates,procurement completion cycles(including procurement execution cycle and total procurement cycle)and procurement satisfaction.Statistical analysis was performed using SPSS 20.0 software.Results The observation group demonstrated significantly lower bid failure/rejection rates when compared with the control group(≥2 occurrences:5.88%vs.15.25%,P<0.05).The procurement execution cycle was notably shorter in the observation group((69.16±78.65)d vs.(97.67±49.84)d,P<0.05),though no significant difference was observed in total procurement cycle(P>0.05).The observation group behaved better significantly than the control group in procurement efficiency,equipment performance,procedural compliance and post-purchase service satisfaction(all P<0.05).Conclusion Risk prevention and control measures in medical equipment procurement effectively reduce bid failure/rejection risks while enhancing procurement quality efficiency.[Chinese Medical Equipment Journal,2025,46(3):81-85]
10.Development and reliability and validity testing of the questionnaire on rotavirus vaccination behavioral and social drivers
Yuting LIAO ; Xiaodong SUN ; Zhuoying HUANG ; Huakun LYU ; Zhiguo WANG ; Binbing WANG ; Jiaxi DU ; Yaqiong LIANG ; Jiangshun WAN ; Zhi LI ; Jing QIU ; Fang HUANG ; Juan LI ; Xiang GUO
Chinese Journal of Preventive Medicine 2025;59(11):1883-1888
Objective:To construct a questionnaire to measure parents′ behavioral and social drivers (BeSD) in administering rotavirus vaccine to their children, and to test the reliability and validity of the questionnaire.Methods:A questionnaire was constructed to investigate the BeSD of rotavirus vaccination among parents based on the WHO BeSD questionnaire. A survey was conducted among parents of children aged 0-3 years old in vaccination clinics from 15 community health service centers in Nanjing City of Jiangsu Province, Yuhuan and Kaihua Counties of Zhejiang Province, Anqing City of Anhui Province, and Yangpu District of Shanghai City from April to May in 2024. Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were used to analyze the reliability (internal consistency reliability, combination reliability and split half reliability) and validity (structural validity, convergence validity and discriminative validity) of the questionnaire.Results:A total of 850 questionnaires were collected, of which 614 were valid, with an effective response rate of 72.20%. The EFA resulted in the refinement of the rotavirus vaccine BeSD questionnaire from 37 to 35 items (including 24 core items), and suggested a five-factor structure including the perceptions of vaccine, confidence in vaccine, social process of vaccination, motivation for vaccination, and practical problems of vaccination. The cumulative variance contribution rate reached 56.27%. The CFA confirmed an ideal five-factor model fit (GFI=0.82,CFI=0.86,PNFI=0.67,RMSEA=0.07). The AVE of each dimension was greater than 0.50. The AVE square root of each dimension of the questionnaire was greater than its correlation coefficient. The Cronbach′s α coefficient of the total questionnaire was 0.79.Conclusion:The developed BeSD questionnaire of rotavirus vaccine has good reliability and validity, and can be used to measure parents′ behavioral and social factors in administering rotavirus vaccine to their children.

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