1.Role of endoplasmic reticulum stress-mediated DEAD-box helicase 3 X-linked in a mouse model of concanavalin A-induced immune-mediated liver injury
Zhenzhen PAN ; Ling XU ; Xianru ZHU ; Zihao FAN ; Yaling CAO ; Yinkang MO ; Sai YAN ; Feng REN
Journal of Clinical Hepatology 2026;42(1):134-142
ObjectiveTo investigate the role of DEAD-box helicase 3 X-linked (DDX3X) in immune-mediated liver injury (ILI), and to clarify its mechanism by regulating endoplasmic reticulum stress (ERS)-dependent apoptotic pathway and its association with the clinical progression of hepatitis B. MethodsMice were given injection of concanavalin A (ConA) via the caudal vein to establish a model of ILI, PBS (control group) and different concentrations of ConA were injected into the tail vein of hepatocyte-specific DDX3X-knockout mice (DDX3XΔHep and DDX3X-flox mice (DDX3Xfl/fl), respectively.. The log-rank survival analysis, measurement of the serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), and HE staining of liver tissue were performed to assess liver injury, and qRT-PCR and Western Blot were used to measure the mRNA and protein expression levels of glucose-regulated protein 78 (GRP78), CCAAT/enhancer-binding protein homologous protein (CHOP), and DDX3X in liver tissue. Intraperitoneal injection of 4-phenylbutyric acid (4-PBA, 100 mg/kg) was performed to inhibit ERS. Serum samples (n=30) and liver tissue samples (n=6) were collected from healthy controls, chronic hepatitis B (CHB) patients, and hepatitis B virus-associated liver failure (HBV-LF) patients; ELISA was used to measure the serum level of DDX3X, and qRT-PCR/Western Blot was used to analyze the expression of targets in liver tissue. 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. ResultsCompared with the control group of mice, the expression of DDX3X in the liver of mice induced by ConA was significantly increased after liver injury (P<0.05), and hepatocyte-specific DDX3X knockout increased the 72-hour survival rate of mice by 55% (compared with 20% in the DDX3Xfl/fl group), with significant reductions in the serum levels of ALT and AST (P<0.000 1) and the expression levels of the ERS markers GRP78 and CHOP (P<0.05). After ERS was inhibited by 4-PBA, there was alleviation of liver injury (with reductions in ALT and AST, P <0.001) and a reduction in DDX3X expression (P<0.01). The analysis of clinical samples showed that the mRNA and protein expression levels of liver DDX3X in CHB patients and HBV-LF patients were significantly higher than those in healthy controls (all P<0.01), and there was a significant increase in the serum level of DDX3X in HBV-LF patients (P<0.000 1). ConclusionDDX3X exacerbates ILI by regulating the ERS-dependent apoptotic pathway (GRP78/CHOP), and its expression is associated with the progression of hepatitis B. Therefore, it can be used as a potential therapeutic target.
2.Expert Consensus on Clinical Application of Qidong Yixin Oral Liquid
Changkuan FU ; Xiaochang MA ; Mingjun ZHU ; Yue DENG ; Hongxu LIU ; Mingxue ZHANG ; Ying CHEN ; Yan ZHOU ; Ling ZHANG ; Jianhua FU ; Wei YANG ; Yu'er HU ; Ming CHEN ; Yanming XIE ; Yuanyuan LI
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(4):147-158
The prescription of Qidong Yixin oral liquid is derived from the experience of national medical master Ren Jixue in treating viral myocarditis (VMC). It has the functions of tonifying Qi, nourishing the heart,calming the mind, and relieving palpitations. It is used to treat VMC and angina pectoris of coronary heart disease caused by deficiency of both Qi and Yin. However,the understanding of its efficacy evidence, advantageous aspects, dosage and administration, and medication safety remains insufficient in clinical practice. Therefore,the development of the Expert Consensus on the Clinical Application of Qidong Yixin Oral Liquid (hereinafter referred to as consensus) was initiated. Consensus strictly followed the process and methods of the expert consensus on the clinical application of Chinese patent medicines of the China Association of Chinese Medicine,successively completing multiple tasks such as the consensus project initiation,determination of clinical problems,evidence search and evaluation,formation of recommendation opinions and consensus suggestions,solicitation of opinions,peer review, submission for review and release, and so on. Consensus formed a total of 10 recommendation opinions and 12 consensus suggestions,clarifying the clinical positioning,efficacy advantages,syndrome differentiation,dosage and administration,combination therapy,timing of medication,adverse reactions,contraindications, and precautions of Qidong Yixin oral liquid,indicating that it has good clinical advantages and safety in the treatment of VMC and angina pectoris of coronary heart disease,providing norms and references for physicians to safely and rationally apply Qidong Yixin oral liquid. Consensus was reviewed and approved for release by the Standardization Office of the China Association of Chinese Medicine on December 23, 2024. Standard number:GSCACM-376-2024.
3.Subchronic systemic toxicity of disposable plasma virus-inactivated blood transfusion sets
Qiu-jin QU ; Ling-xiao SUN ; Xiao-fei WANG ; Fu-yu ZHU ; Guo-xi CHE ; Jing XU ; Xiao-yan WANG ; Nai-shui HAN ; Xiao-xia SUN ; Chun-xia QIAO
Chinese Medical Equipment Journal 2025;46(10):29-35
Objective To evaluate the subchronic systemic toxicity of disposable plasma virus-inactivated blood transfusion sets using hydroxyethyl starch(HES)130/0.4 sodium chloride injection as an extraction medium.Methods Firstly,40 Sprague Dawley(SD)rats including 20 male and 20 female ones were seleted and randomly enrolled into a sample group and a control group by sex,with 20 ones in each group.Secondly,instead of plasma HES 130/0.4 sodium chloride injection was used to leach disposable plasma virus-inactivated blood transfusion sets to prepare the test solution by simulating clinical application such as lighting,adsorption and filtration and storage.Finally,the test solution and HES 130/0.4 sodium chloride injection were injected into the tail vein of the SD rats at a dose of 20 mL/kg for 28 d in the sample group and in the control group respectively,and the subchronic systemic toxicity of disposable plasma virus-inactivated blood transfusion sets and the feasibility of using HES 130/0.4 sodium chloride injection as the extraction medium to assess their subchronic systemic toxicity were evaluated with clinical observation,body mass monitoring,clinical pathology examination,gross necropsy and histopathology examination.Results The sample group and control group had no significant differences in mortality rates,clinical observation results,body mass,gross necropsy results,hematological and coagulation examination results and organ weight(all P>0.05);blood biochemical examinations showed the male rats in the sample group had the cholesterol(CHO)values higher while the creatinine(CR)values lower than those in the control group,with the differences being statistically significant(both P<0.05)and the two indexes within the range of the laboratory's historical reference data,and other blood biochemical indexes were not significantly different(all P>0.05);the sample group had the spleen weight-to-body mass ratios of the female rates lower significantly than those in the control group(P<0.05),and the ratios of other organ weight to body mass had significant differences(all P>0.05);histopathology examination showed slight pathological changes in liver,spleen and kidney of female rats and in spleen and kidney of male rats in the sample group,and the female and male rats in the control group had similar pathological changes found in the sample group,which might be caused by HES metabolites.Conclusion Disposable plasma virus-inactivated blood transfusion sets prove to have no significant subchronic systemic toxicity,and its feasible to use HES 130/0.4 sodium chloride injection as the extraction medium to evaluate the subchronic systemic toxicity of disposable plasma virus-inactivated blood transfusion sets.[Chinese Medical Equipment Journal,2025,46(10):29-35]
4.Effects of alcoholism on nonalcoholic fatty liver disease
Hao-qing ZHU ; Yan-ling WU ; Ji-xing NAN ; Li-hua LIAN
Chinese Pharmacological Bulletin 2025;41(7):1227-1230
NAFLD is the most prevalent chronic liver disease,which has become a world public health issue and the incidence rate is also showing an increasing trend.A series of liver disea-ses,such as simple fatty liver disease,NASH,liver cirrhosis,liv-er failure and liver cancer,can be collectively referred to as NAFLD.Through the study of numerous factors that influence the production of NAFLD,it has been found that the main patho-logical mechanism is excessive synthesis of fat,which is difficult to be transported into the blood,causing massive lipid accumula-tion.Alcohol has a direct damaging effect on liver and will in-hibit the breakdown of liver fat,eventually forming AFLD.How-ever,it is still controversial whether alcohol has a synergistic effect on NAFLD onset.This article provides a review on the effect of alcohol intake on NAFLD and its potential mechanisms of action.
5.Molecular characteristics and advances in drug therapy of ovarian clear cell carcinoma
Yue TAN ; Yan XU ; Zhi-ling ZHU
Fudan University Journal of Medical Sciences 2025;52(3):450-457
Ovarian clear cell carcinoma(OCCC)typically exhibited high-grade atypia and aggressive chemotherapy resistance,leading to poor prognosis,necessitating continuous exploration of novel therapeutic approaches to enhance patient survival and quality of life.In recent years,with the in-depth study of the biological behavior and molecular characteristics of OCCC,unique molecular features of OCCC were discovered,making it a potential molecular target for personalized biotherapy,with the prospect of improving treatment efficacy and patient prognosis.An increasing number of clinical trials focused on exploring the driver mutations and molecular characteristics of recurrent OCCC in the hope of finding more precise and effective treatment modalities.This article provided a comprehensive review of the molecular characteristics of OCCC and advances in drug therapy.
6.Site-specific mutation and immunogenicity of Mannheimia varigena TbpB
Zhihao YAN ; Yuhong ZHU ; Jian SHI ; Xingyi MA ; Ling GAN ; Jianhua GUO
Chinese Journal of Veterinary Science 2025;45(5):954-962
Mannheimia varigena(M.varigena)is a significant pathogen causing bovine respiratory disease.Transferrin binding protein B(TbpB)is a lipoprotein directly exposed to the outer mem-brane of the cell,which is not only involved in the bacterial iron metabolism pathway,but also an important virulence factor.This study aims to lay the groundwork for developing novel subunit vaccines by conducting site-directed mutagenesis on M.varigena TbpB binding-related residues and evaluating their immunogenicity.Based on whole-genome sequencing of a bovine M.varigena i-solate,its iron uptake pathway was predicted.Key amino acid residues of M.varigena TbpB that play a role for binding to bovine transferrin(bTf)was identified by bioinformatics.We constructed two M.varigena TbpB mutants(Y205A and Y258A)and assessed their bTf binding activity and immunogenicity through dot blot assays and mouse immunization studies.Dot blot assays result showed that the Y258A mutation caused TbpB to lose its ability to bind to bTf.Mouse immuniza-tion studies showed that,compared to wild-type TbpB,the mutants of TbpB induced higher levels of specific antibodies.In challenge experiments,mice immunized with mutant TbpB exhibited high-er survival rates.These results demonstrate that site-directed mutagenesis can enhance the immu-nogenicity of TbpB.This study provides a novel approach for developing new subunit vaccines a-gainst M.varigena.
7.The effect of LCN2-mediated EGFR phosphorylation on inflammatory injury in human fallopian tube epi-thelial cells
Yaqiong XIA ; Yue ZHU ; Chengcheng JIANG ; Hongping TAN ; Yan ZHANG ; Ling LIU
The Journal of Practical Medicine 2025;41(14):2174-2182
Objective To investigate the regulatory effect of lipocalin 2(LCN2)on epidermal growth factor receptor(EGFR)phosphorylation and its impact on inflammatory damage in human fallopian tube epithelial cells.Methods Human fallopian tube epithelial cells were isolated and a lipopolysaccharide(LPS)intervention was applied to establish an in vitro cell model.The cells were randomly assigned into the following groups:a blank control group(Control),a model group(Model),experimental groups(Model+si-LCN2 or Model+oe-LCN2),and negative control groups(Model+si-NC or Model+oe-NC).Changes in cell viability,apoptosis rates,inflam-matory levels,as well as the expression of EGFR mRNA,LCN2,EGFR,p-EGFR,and the ratio of p-EGFR/EGFR proteins were evaluated.Results Compared to the Model group,the Model+si-LCN2 group exhibited enhanced cell viability,a reduced apoptosis rate,and decreased expression of inflammatory factors(P<0.05).Immunopre-cipitation analysis confirmed a direct interaction between LCN2 and EGFR.In comparison with the Model group,the Model+oe-LCN2 group demonstrated elevated levels of p-EGFR and the p-EGFR/EGFR ratio(P<0.05),while no significant change was observed in total EGFR expression(P>0.05).Conclusion Inhibition of LCN2-mediated EGFR phosphorylation enhances cell viability,reduces apoptosis,and mitigates inflammatory responses,thereby ameliorating LPS-induced inflammatory injury in human fallopian tube epithelial cells.
8.Subchronic systemic toxicity of disposable plasma virus-inactivated blood transfusion sets
Qiu-jin QU ; Ling-xiao SUN ; Xiao-fei WANG ; Fu-yu ZHU ; Guo-xi CHE ; Jing XU ; Xiao-yan WANG ; Nai-shui HAN ; Xiao-xia SUN ; Chun-xia QIAO
Chinese Medical Equipment Journal 2025;46(10):29-35
Objective To evaluate the subchronic systemic toxicity of disposable plasma virus-inactivated blood transfusion sets using hydroxyethyl starch(HES)130/0.4 sodium chloride injection as an extraction medium.Methods Firstly,40 Sprague Dawley(SD)rats including 20 male and 20 female ones were seleted and randomly enrolled into a sample group and a control group by sex,with 20 ones in each group.Secondly,instead of plasma HES 130/0.4 sodium chloride injection was used to leach disposable plasma virus-inactivated blood transfusion sets to prepare the test solution by simulating clinical application such as lighting,adsorption and filtration and storage.Finally,the test solution and HES 130/0.4 sodium chloride injection were injected into the tail vein of the SD rats at a dose of 20 mL/kg for 28 d in the sample group and in the control group respectively,and the subchronic systemic toxicity of disposable plasma virus-inactivated blood transfusion sets and the feasibility of using HES 130/0.4 sodium chloride injection as the extraction medium to assess their subchronic systemic toxicity were evaluated with clinical observation,body mass monitoring,clinical pathology examination,gross necropsy and histopathology examination.Results The sample group and control group had no significant differences in mortality rates,clinical observation results,body mass,gross necropsy results,hematological and coagulation examination results and organ weight(all P>0.05);blood biochemical examinations showed the male rats in the sample group had the cholesterol(CHO)values higher while the creatinine(CR)values lower than those in the control group,with the differences being statistically significant(both P<0.05)and the two indexes within the range of the laboratory's historical reference data,and other blood biochemical indexes were not significantly different(all P>0.05);the sample group had the spleen weight-to-body mass ratios of the female rates lower significantly than those in the control group(P<0.05),and the ratios of other organ weight to body mass had significant differences(all P>0.05);histopathology examination showed slight pathological changes in liver,spleen and kidney of female rats and in spleen and kidney of male rats in the sample group,and the female and male rats in the control group had similar pathological changes found in the sample group,which might be caused by HES metabolites.Conclusion Disposable plasma virus-inactivated blood transfusion sets prove to have no significant subchronic systemic toxicity,and its feasible to use HES 130/0.4 sodium chloride injection as the extraction medium to evaluate the subchronic systemic toxicity of disposable plasma virus-inactivated blood transfusion sets.[Chinese Medical Equipment Journal,2025,46(10):29-35]
9.Effectiveness of a modified puncture method in hemodialysis patients with difficult internal fistula
Ling JIANG ; Yanhua ZHU ; Yan YU ; Hongyan WEI
Chinese Journal of Modern Nursing 2025;31(19):2648-2651
Objective:To explore the effectiveness of a modified puncture method in hemodialysis patients with difficult internal fistula.Methods:From January 2022 to October 2023, patients with difficult internal fistula undergoing dialysis at the Blood Purification Center of Qingdao Municipal Hospital were selected for the study using the convenience sampling method. According to the hemodialysis time, patients dialyzed on Mondays, Wednesdays, and Fridays were included in the conventional group, and patients dialyzed on Tuesdays, Thursdays, and Saturdays were included in the experimental group, with 56 cases in each group. Internal fistula puncture was performed in the conventional group using the traditional puncture method and in the experimental group using the modified puncture method. The success rate of one-time puncture of internal fistula and the injury rate of internal fistula were compared between the two groups of patients.Results:The success rate of one-time puncture of internal fistula in the experimental group was higher than that in the conventional group, with a statistical difference ( P<0.05). The injury rate of the internal fistula vessel of the experimental group was lower than that of the conventional group, and the difference was statistically significant ( P<0.05) . Conclusions:Modified puncture methods have a positive effect on increasing the success rate of a one-time puncture of the internal fistula and decreasing the rate of internal fistula injuries in patients with difficult internal fistula.
10.Analysis of 281 cases of adverse reactions of drug-induced liver injury
Ling FAN ; Qinhua GU ; Yan WU ; Xiaojing ZHU
China Modern Doctor 2025;63(11):50-53
Objective To explore characteristics of patients with drug-induced liver injury(DILI),suspected drugs and outcomes,and to provide reference for clinical standard use of drugs and reduce adverse reactions of DILI.Methods Retrospective analysis of adverse drug reactions of 281 patients with DILI in Suzhou Hospital of Integrated Traditional Chinese and Western Medicine from 2016 to 2023.Age,sex,severity,clinical manifestations,clinical classification,Roussel Uclaf causality assessment method(RUCAM)score,injury degree,combination,disease type,suspected drugs and outcomes of patiengs were statistically analyzed.Results Among 281 patients with DILI,there were 83 general ADRs cases and 198 serious ADRs cases.In terms of clinical manifestations,main manifestations were yellow skin sclera,poor appetite,fatigue and so on.In terms of injury degree,156 cases suffered mild liver injury,121 cases suffered moderate liver injury,and 4 cases suffered severe liver injury.There were 164 cases of combined drug use and 117 cases of single drug use.The top diseases of patients were tumor,respiratory disease,tuberculosis infection and so on.Among the suspected drugs,the top three drugs were Chinese medicine,anti-tumor drugs and anti-tuberculosis drugs in order,and there were significant differences between different types of suspected drugs and whether they were used in combination(P<0.05).There were significant differences in clinical classification and effectiveness(P<0.05).Conclusion Chinese medicine,anti-tumor drugs and anti-tuberculosis drugs are relatively easy to cause DILI.The type of liver cell damage,combination of drugs,types of diseases,and underlying diseases all affect the occurrence of DILI.

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