1.Application prospects of mitochondrial pyruvate carrier inhibitors in treatment of metabolic dysfunction-associated steatohepatitis
Journal of Clinical Hepatology 2026;42(4):938-942
Metabolic dysfunction-associated steatohepatitis (MASH) is a complex liver disease characterized by abnormal fat accumulation in the liver, accompanied by inflammation and hepatocyte injury, and it can gradually progress to liver fibrosis, liver cirrhosis, and even hepatocellular carcinoma. MASH has a complex pathogenesis involving multiple links such as insulin resistance, de novo lipogenesis (DNL), oxidative stress, and mitochondrial dysfunction. In recent years, mitochondrial pyruvate carrier (MPC) has attracted wide attention as a key molecular target for regulating lipid metabolism. This article systematically reviews the mechanism of action of MPC in MASH, with a focus on how inhibiting MPC expression regulates lipid synthesis and metabolism by reducing DNL production and modulating signaling pathways such as AMPK-ACC, thereby improving liver inflammation. In addition, this article discusses the potential application prospects of MPC inhibitors in MASH treatment, in order to provide new ideas for future clinical research on MASH management.
2.Elesclomol combined with Cu2 + induced cuproptosis in hepatoma cell lines PLC/PRF/5 and Huh-7
Qiaohui Ren ; Xinyue Zhu ; Wei Lv ; Yan Zang ; Lianzi Wang ; Xinyi Zhou ; Junxiao Yao ; Tao Li
Acta Universitatis Medicinalis Anhui 2025;60(8):1470-1477
Objective:
To investigate the inhibitory effect of Elesclomol (ES) + Cu2 + on the proliferation of human hepatoma cell lines PLC/PRF/5 and Huh-7 and its potential to induce Cuproptosis.
Methods:
Human hepatoma cell lines PLC/PRF/5 and Huh_7 cells were Cultured in vitro. ES solution , Cu2 + solution and copper chelating agent ammonium tetrathiomolybdate VI (ATTM) solution was treated separately or in combination. The effect of ES + Cu2 + on the survival rate of human hepatoma cell lines PLC/PRF/5 and Huh_7 cells and the effect of ES + Cu2 + on the survival rate after pretreatment with copper chelating agent ATTM were evaluated using CCK_8 kit. The cell death induced by ES + Cu2 + was detected by flow cytometry and the changes of ES + Cu2 + after pretreatment with copper chelating agent ATTM. The expression of Cuproptosis related proteins ATPase copper transporting beta (ATP7B) ,ferredoxin 1 (FDX1) , dihydrolipoamide s_acetyltransferase(DLAT) and superoxide dismutase 1 (SOD1) were detected by Western blot. The effect of ES + Cu2 + on cell proliferation and the reverse effect after ATTM pretreatment was detected by cell scratch assay.
Results:
The toxicity of ES + Cu2 + to human hepatocellular carcinoma cell lines PLC/PRF/5 and Huh_7 was significantly dose_dependent (P < 0. 05) . Compared with the control group , the combined application of ES and Cu2 + had a more significant inhibitory effect on hepatocellular carcinoma cells than ES or Cu2 + alone (P < 0. 05) , and copper chelating agent ATTM could reverse the inhibitory effect of ES + Cu2 + on hepatocellular carcinoma cells (P < 0. 05) . Flow cytometry results showed that compared with the control group , the proportion of cell death in PLC/PRF/5 and Huh_7 cells treated with ES + Cu2 + increased , while the proportion of cell death decreased after ATTM intervention (P < 0. 05) . The results of cell scratch test showed that the migration ability of PLC/PRF/5 and Huh_7 cells was decreased after ES + Cu2 + treatment , however, the addition of ATTM reversed the inhibitory effect of ES + Cu2 + on cell migration (P < 0. 05) . Compared with the control group , the expression levels of copper death related proteins ATP7B , FDX1 , DLAT and SOD1 decreased after ES + Cu2 + treatment , but the addition of ATTM reversed the expression trend of these proteins (P < 0. 05) .
Conclusion
The combination of ES and Cu2 + can effectively inhibit the proliferation and migration of PLC/PRF/5 and Huh_7 of hepatocellular carcinoma cells , and induce Cuproptosis , which provides a new strategy for the treatment of hepatocellular carcinoma.
3.Analysis of stroke-related risk factors among urban community residents:A case-control study based on propensity score matching
Qianwei REN ; Siyi ZHOU ; Xinyue JIN ; Fuzhen GUO ; Zhongjun GUAN
Journal of Capital Medical University 2025;46(3):520-526
Objective To analyze stroke-related risk factors and their impact on urban community residents in Beijing,focusing on chronic diseases,psychological health,and quality of life,to provide evidence for community screening and intervention strategies.Methods Data were collected from residents aged 50+in 19 communities by using questionnaires and a WeChat App.Propensity score matching(PSM)balanced baseline characteristics.Logistic regression(univariate and stepwise)and mediation effect analysis were conducted by using SPSS and R.Results After PSM,87 stroke cases and 348 controls showed balanced baseline characteristics.The stroke group had higher chronic disease prevalence and lower psychological and quality of life scores.Hypertension increased stroke risk(P=0.002).Cognitive-12 Scale(Cog-12)was positively,and European Quality of Life-5 Dimensions(EQ-5D)negatively,associated with stroke(P<0.001).Hypertension mediated stroke risk through Cog-12 and EQ-5D,with EQ-5D contributing 26.72%.Conclusion In this urban community study,stroke prevention should focus on managing chronic diseases,improving cognitive health and quality of life,and addressing psychological health.Digital tools can enhance follow-up and assessment,optimizing community-based stroke management strategies.
4.Characteristics of gut microbiota in elderly patients with severe pneumonia
Steven YU ; Hao ZHOU ; Juan JIANG ; Xinyue HU ; Tiao LI ; Yuanyuan LI
Chinese Journal of Infection Control 2025;24(3):361-371
Objective To summarize and analyze the main clinical characteristics,feature and composition changes of gut microbiota in elderly patients with severe pneumonia,and to further explore the potential correlation between the gut characteristics and the etiology of severe pneumonia in elderly patients.Methods Patients with severe pneu-monia admitted to the respiratory intensive care unit of a tertiary teaching hospital in Changsha were selected as the research subjects.Patients aged ≥65 years were assigned to the elderly severe pneumonia group,while those aged<65 years were assigned to the non-elderly severe pneumonia group.Based on clinical characteristics and pathogen detection of lower respiratory secretion,the elderly severe pneumonia group was further divided into a pulmonary bacterial infection group and a pulmonary fungal infection group.The pulmonary bacterial infection group was sub-divided into Gram-positive bacteria group and Gram-negative bacteria group based on Gram-staining results.Clinical data of patients were collected,and fecal specimens within 24 hours after admission were obtained for 16S rRNA se-quencing.Differences in gut microbiota characteristics between two groups of patients were compared,and the cor-relation between clinical characteristics of patients in the elderly severe pneumonia group and the abundance of dif-ferential microbiota was analyzed.Subsequently,the gut microbiota characteristics of elderly patients in severe pneumonia group infected by different pathogens were analyzed.Results Gut microbiota analysis showed no signifi-cant statistical differences in α-and β-diversity indicices between patients in the elderly and non-elderly severe pneu-monia groups(both P>0.05).Linear discriminant analysis effect size(LEFSe)analysis indicated that,compared with patients in the non-elderly severe pneumonia group,the relative abundance of opportunistic pathogens,inclu-ding Pseudomonadales,Moraxellaceae,and Acinetobacter,was significantly higher in patients in the elderly severe pneumonia group(all P<0.05).Some differential gut microbiota in two groups of patients were correlated with clinical indicators in patients in the elderly severe pneumonia group(all P<0.05).β-diversity analysis(principal co-ordinate analysis)combined with Anosim analysis revealed that in patients in elderly severe pneumonia group,there was significant differences in gut colony structures between patients in the bacterial and fungal infection groups(R=0.149,P=0.02).Compared with the fungal infection group,patients in bacterial infection group showed a signifi-cantly reduced abundance of probiotics,including Verrucomicrobiales and Collinsella,and opportunistic pathogens such as Akkermansia(all P<0.05).Conclusion Elderly patients with severe pneumonia have a dysregulated gut microbiota with significantly increased abundance of pathogenic bacteria compared with non-elderly patients.Differ-ential gut microbiota of two groups of patients are correlated with some infection-related and organ function indica-tors in elderly patients with severe pneumonia.Compared with elderly patients with severe fungal pneumonia,those with severe bacterial pneumonia have significant differences in gut colony structures and a notably reduction in probi-otics abundance.
5.Advances in traditional Chinese medicine treatment of liver fibrosis in metabolic associated fatty liver disease
Zhijia ZHOU ; Xinyue LI ; Chao ZHENG ; Xuehua SUN
Journal of Clinical Hepatology 2025;41(10):1968-1974
Metabolic associated fatty liver disease (MAFLD) has become one of the most prevalent chronic liver disease worldwide, and its progression to liver fibrosis is a key influencing factor for prognosis and the risk of complications. In recent years, novel drugs, such as selective thyroid hormone receptor-β agonists, glucagon-like peptide-1 receptor agonists, and fibroblast growth factor 21 analogs, have shown preliminary efficacy in the treatment of MAFLD-related liver fibrosis; however, such drugs have limited overall effectiveness, and there is still a lack of ideal therapeutic strategy to address the disease across its different stages. Traditional Chinese medicine (TCM), with its characteristics of multiple targets and systemic regulation, has shown unique advantages in this field. This article systematically reviews the basic and clinical research on the anti-fibrotic mechanisms of compound TCM prescriptions and their active components in recent years, focusing on the key processes including hepatic stellate cell activation, lipid metabolism disorders, oxidative stress, immune inflammation, and gut-liver axis dysfunction. Meanwhile, it is pointed out that there are still certain issues in current research, including ambiguities in the clarification of mechanisms, a lack of standardized evaluation systems, and the need to improve the quality of clinical evidence. Future research should emphasize the standardization and quality control of TCM herbal preparations and integrate emerging technologies, such as omics analysis, organoid models, and real-world data, to advance TCM intervention of MAFLD-related liver fibrosis toward well-defined mechanisms, clear therapeutic pathways, and robust scientific evidence. TCM is expected to play a vital role in the multi-dimensional targeted intervention and stage-specific management of MAFLD-related liver fibrosis, in order to provide new perspectives and comprehensive solutions for the precise treatment of chronic liver diseases.
6.Establishment of an in vitro model for Erastin and RSL3-induced ferroptosis in hepatocellular carcinoma
Xinyue Zhu ; Qiaohui Ren ; Yan Zang ; Xinyi Zhou ; Junxiao Yao ; Lianzi Wang ; Xudong Sha ; Tao Li
Acta Universitatis Medicinalis Anhui 2025;60(4):611-618
Objective:
To establish anin vitromodel of ferroptosis induced by Erastin and RAS-selective lethal 3(RSL3) in hepatoma cells, and to provide theoretical basis for the development of novel therapeutic strategies for HCC.
Methods:
Hepatoma cells(HCCLM3, HepG2, Hep3B, Huh7 and PLC/PRF/5) in logarithmic growth phase were treated with Erastin(0-40 μmol/L) and RSL3(0-10 μmol/L) at double concentrations respectively. After 24 h, CCK-8 method was used to detect cell viability, draw growth curve, calculate IC50, and HCC cells sensitive to inducers were selected for follow-up experiments. The effect of inducer on the state of hepatoma cells was observed under light microscope, and immunoblotting and flow cytometry were used to verify whether the ferroptotic modelin vitrowas successfully constructed.
Results:
Huh7, Hep3B and HepG2 cells were sensitive to Erastin and RSL3, but HCCLM3 and PLC/PRF/5 were insensitive to Erastin and RSL3. When the concentration of Erastin and RSL3 reached the maximum, the survival rate was still above 65%. Huh7, Hep3B and HepG2 cells were selected for subsequent experiments. Compared with the control group, the expression of Glutathione peroxidase 4(GPX4), a ferroptotic marker, was down-regulated in a concentration-dependent manner. In Huh7, Hep3B and HepG2 cells, lipid reactive oxygen species(ROS) levels significantly increased after 24 h treatment with 10 μmol/L and 20 μmol/L Erastin, respectively; in Huh7 cells, lipid ROS levels significantly increased after 24 h treatment with 0.5 μmol/L and 1 μmol/L RSL3, respectively; in Hep3B and HepG2 cells, lipid ROS levels significantly increased after 24 h treatment with 1 μmol/L and 2 μmol/L RSL3, respectively, compared with control group.
Conclusion
Huh7, Hep3B and HepG2 cells are highly sensitive to Erastin and RSL3. Huh7, Hep3B and HepG2 cells treated with 10 μmol/L Erastin for 24 h are good models for simulating ferroptosis induced by Erastinin vitro, Huh7 cells treated with 0.5 μmol/L RSL3 for 24 h and Hep3B and HepG2 cells treated with 1 μmol/L RSL3 for 24 h are good models for simulating ferroptosis induced by RSL3in vitro.
7.Relationship between insomnia symptoms combined with executive function impairment and depressive symptoms among adolescents in regions with different economic development levels
Mengfei ZHOU ; Xinyue MA ; Yuting WANG ; Qi ZHU ; Yanrui JIANG ; Qingmin LIN ; Fan JIANG
Chinese Journal of Pediatrics 2025;63(7):765-771
Objective:To investigate the current status of insomnia symptoms and executive function (EF) impairments among adolescents from regions with different economic development levels, and to analyze their relationship with depressive symptoms, so as to provide clues for improved depressive symptoms screening practices.Methods:This population-based cross-sectional study employed a multistage, stratified cluster random sampling method. During November 2017 to January 2018 and December 2018 to January 2019, a total of 2 495 adolescents aged 11 to 18 years were selected from Shanghai, representing a highly developed economic region, and 2 704 adolescents aged 11 to 18 years were selected from Shangrao city, Jiangxi province, representing a less developed economic region. The depressive symptoms were assessed using the short version of the 21-item depression, anxiety, and stress scale, based on which participants were categorized into groups with or without depressive symptoms. Insomnia symptoms and EF impairments were measured using a self-designed insomnia scale and the behavior rating inventory of executive function, respectively. Participants were further classified into 4 subgroups: neither insomnia nor EF impairment, EF impairment only, insomnia only, and comorbid insomnia and EF impairment. Chi-square test was used to compare the differences in basic information of adolescents from different regions. Multivariate Logistic regression models were applied to examine the associations between insomnia, EF impairment, and their combination with depressive symptoms as well as the differences in gender and school-stage among each subgroup.Results:A total of 2 305 adolescents were recruited from Shanghai (1 192 boys and 1 113 girls, 1 266 junior high school students and 1 039 senior high school students) and 2 250 adolescents from Shangrao (1 126 boys and 1 124 girls, 1 146 junior high school students and 1 104 senior high school students). The numbers of adolescents with depressive symptoms, insomnia symptoms and EF impairment in Shanghai were 460 adolescents (20.0%), 907 adolescents (39.3%), and 411 adolescents (17.8%), respectively, all of which were fewer than those in Shangrao, which were 616 adolescents (27.4%), 1 251 adolescents (55.6%), and 524 adolescents (23.3%), respectively (all P<0.001). In Shanghai, the numbers of adolescents with EF impairment only, insomnia only, and comorbid insomnia and EF impairment were 219 adolescents (9.5%), 670 adolescents (29.1%), and 237 adolescents (10.3%), respectively. And in Shangrao, the corresponding numbers were 193 adolescents (8.6%), 865 adolescents (38.4%), and 386 adolescents (17.2%), respectively. Compared to adolescents in Shanghai with neither EF impairment nor insomnia, the risk of depressive symptoms was all higher in adolescents with EF impairment only, insomnia only, and comorbid EF impairment-insomnia ( OR=2.86, 6.48, 20.10; 95% CI 1.57-5.22, 5.09-8.26, 13.66-29.58; all P<0.01). Similar results were observed in adolescents in Shangrao ( OR=3.22, 4.82, 10.91; 95% CI 1.66-6.28, 3.09-7.51, 7.26-16.40; all P<0.01). The analysis of gender and educational stage differences showed that, compared to the group neither EF impairment nor insomnia, the risk of depressive symptoms all higher in the groups with EF impairment only, insomnia only (all P<0.05), and comorbid EF impairment-insomnia, and the risk in comorbid EF impairment-insomnia group was the highest (all P<0.05). Conclusions:Compared with adolescents in regions with underdeveloped economies, those in economically developed regions had lower rates of insomnia, EF impairment, and depression. Both insomnia and EF impairment significantly increase the risk of depressive symptoms. Their coexistence confers the highest risk and therefore warrants particular attention for prevention and intervention efforts.
8.Interpretation of the group standard of " Humanistic Caring Management Standards for Patients in the Operating Room"
Ruiying YU ; Xinyue MIAO ; Qingmin ZHANG ; Yilan LIU ; Shujie GUO ; Huiling LI ; Guo CHEN ; Chunlan ZHOU ; Ting LIU ; Shuhua DENG ; Hongzhen XIE ; Yu CHENG ; Yinglan LI ; Yanlan MA ; Xia XIN ; Yanjin LIU ; Yongyi CHEN ; Gendi LU ; Xiaoqin GAN ; Feng XU ; Zuwei XIA ; Li HE ; Qinqin CHEN ; Fukang ZHANG ; Songmei WU ; Yi LI ; Wenjuan ZHOU
Chinese Journal of Hospital Administration 2025;41(7):512-517
Humanistic caring for patients in the operating room refers to providing the whole process of caring medical services for patients in the operating room. In order to standardize humanistic caring services for patients in the operating room of medical institutions, improve the comprehensive service level of the operating room, and enhance the surgical experience of patients, the Chinese Association for Life Care released the group standard " Humanistic Caring Management Standards for Patients in the Operating Room" in December 2023. This article interpreted the basic requirements for humanistic caring of patients in the operating room, the environment and facilities for humanistic caring, the procedures and measures for humanistic caring, and the quality management framework, aiming to assist administrators and clinical practitioners across various levels of medical institutions in accurately understanding and effectively implementing the standard, and to provide essential textual reference and practical guidance for promoting the application of the standard.
9.Efficacy comparison between tenofovir disoproxil fumarate versus tenofovir alafenamide fumarate treatment in chronic hepatitis B patients with high viral load
Chenxia ZHANG ; Diwen SHI ; Xinyue CHEN ; Yaping DAI ; Yan QI ; Xueshi ZHOU ; Yuanwang QIU
Chinese Journal of Infectious Diseases 2025;43(9):530-536
Objective:Comparative efficacy and safety profiles of tenofovir disoproxil fumarate (TDF) versus tenofovir alafenamide fumarate (TAF) in chronic hepatitis B (CHB) patients with high viral load.Methods:CHB patients with high viral load (hepatitis B virus (HBV) DNA>7 lg IU/mL) receiving TDF ( n=155) or TAF ( n=157) monotherapy were included between December 1st, 2022 and December 1st, 2023, to compare the rates of undetectable HBV DNA (<20 IU/mL), the alanine transaminase (ALT) normalization rate, hepatitis B e antigen (HBeAg) seroconversion rate, renal function and lipid profiles at 48 weeks of treatment. The statistical analysis was performed by the two independent samples t test, Mann-Whitney U test, chi-square test or Fisher′s exact probability test. Results:At week 48 of treatment, the TDF group achieved significantly higher HBV DNA undetectability rates (49.03%(76/155) vs 29.30%(46/157)) and greater mean reduction ((6.05±0.81) lg IU/mL vs (5.57±1.02) lg IU/mL) than the TAF group ( χ2=12.75, t=-4.65, both P<0.001). The ALT normalization rate of patients in the TDF and TAF groups were 77.19%(88/114) and 72.50%(87/120), and HBeAg seroconversion rates were 4.00%(6/150) and 2.67%(4/150), respectively, with no statistically significant differences between the two groups (all P>0.05). The differences in the changes and abnormal rates of serum creatinine and estimated glomerular filtration rate between the two groups of patients were not statistically significant (both P>0.05). The magnitude of decrease (0.15(-0.02, 0.38) mmol/L vs 0.06(-0.06, 0.20) mmol/L) and abnormal rate (27.73%(33/119) vs 16.39%(20/122)) in high-density lipoprotein cholesterol in the TDF group was higher than those in the TAF group, while the increases in low-density lipoprotein cholesterol (-0.09(-0.39, 0.25) mmol/L vs 0.05(-0.31, 0.42) mmol/L), total cholesterol (TC) (-0.23(-0.75, 0.23) mmol/L vs 0.08(-0.35, 0.57) mmol/L), and triglyceride (-0.12(-0.40, 0.06) mmol/L vs 0.00(-0.19, 0.24) mmol/L), as well as the abnormal rate of TC (4.31%(5/116) vs 15.75%(20/127)), in the TDF group were lower than those in the TAF group ( Z=-3.19, χ2=4.51, Z=2.17, Z=4.09, Z=3.71, χ2=8.59, all P<0.05). Conclusion:TDF demonstrated superior efficacy and better safety profiles compared to TAF in high viral load CHB patients.
10.Current status of research on the impairment of natural killer cell function caused by hepatitis B virus infection
Xinyue ZHU ; Yufu ZHOU ; Shiguo ZHU
Chinese Journal of Hepatology 2025;33(3):300-306
Hepatitis B is a global health problem caused by hepatitis B virus (HBV) infection, with approximately 240 million people worldwide being hepatitis B surface antigen positive. However, existing antiviral therapies can only control HBV replication and cannot eliminate it, thereby seriously affecting the disease's prognosis. Immunotherapy has received widespread attention in recent years due to its long-lasting effects and safety profile. As one of the innate immune cells, natural killer cells play an important role in targeting HBV-infected cells and completely eliminating HBV infection. Natural killer cells can not only directly recognize and kill virus-infected cells but also regulate adaptive immune responses by secreting the cytokine interferon gamma. This article aims to review the regulatory relationship between natural killer cells and HBV-infected cells, research progress of natural killer cell-based immunotherapy targeting HBV infection, and explore the impact of natural killer cells on the occurrence and development of hepatocellular carcinoma in order to provide some enlightenment for improved treatment of HBV infection.


Result Analysis
Print
Save
E-mail