1.Role of autophagy in treatment of paracetamol-induced liver injury
Guojing XING ; Lifei WANG ; Longlong LUO ; Xiaofeng ZHENG ; Chun GAO ; Xiaohui YU ; Jiucong ZHANG
Journal of Clinical Hepatology 2025;41(2):389-394
N-acetyl-p-aminophenol (APAP) is an antipyretic analgesic commonly used in clinical practice, and APAP overdose can cause severe liver injury and even death. In recent years, the incidence rate of APAP-induced liver injury (AILI) tends to increase, and it has become the second most common cause of liver transplantation worldwide. Autophagy is a highly conserved catabolic process that removes unwanted cytosolic proteins and organelles through lysosomal degradation to achieve the metabolic needs of cells themselves and the renewal of organelles. A large number of studies have shown that autophagy plays a key role in the pathophysiology of AILI, involving the mechanisms such as APAP protein conjugates, oxidative stress, JNK activation, mitochondrial dysfunction, inflammatory response and apoptosis. This article elaborates on the biological mechanism of autophagy in AILI, in order to provide a theoretical basis for the treatment of AILI and the development of autophagy regulators.
2.Role of mesenchymal stem cells and their exosomes in the treatment of drug-induced liver injury
Guojing XING ; Longlong LUO ; Lifei WANG ; Shunna WANG ; Xiaofeng ZHENG ; Lixia LU ; Jiucong ZHANG
Journal of Clinical Hepatology 2024;40(3):633-638
The incidence rate of drug-induced liver injury (DILI) is increasing year by year with unknown mechanisms, and the treatment methods for DILI mainly include drugs, liver support systems, and liver transplantation, all of which have certain limitations. Therefore, the search for safer and more effective treatment methods has become a research hotspot at present. Studies have shown that mesenchymal stem cells and their exosomes can alleviate liver injury by reducing liver inflammation, promoting hepatocyte proliferation and regeneration, inhibiting the apoptosis of hepatocytes, improving oxidative stress, and regulating immunity. This article briefly reviews the role of mesenchymal stem cells and their exosomes in the treatment of DILI, so as to provide a reference for further research.
3.Role of extracellular vesicles of different origins in the development and progression of hepatocellular carcinoma
Tingting SHI ; Runbing ZHANG ; Yang WU ; Yani ZHANG ; Lingling ZHU ; Chun GAO ; Jingjing JIANG ; Xiaofeng ZHENG ; Jiucong ZHANG
Journal of Clinical Hepatology 2024;40(6):1264-1268
Hepatocellular carcinoma(HCC)is the most common type of primary liver cancer and the third leading cause of cancer-related deaths,and it is a serious threat to human health and has become a clinical problem that needs to be solved urgently.Extracellular vesicles(EV)are membrane vesicles containing multiple components and play an important role in the development and progression of HCC.This article summarizes the effect of EVs of different origins on HCC and analyzes the mechanism of action of EV on HCC,so as to provide new perspectives for the diagnosis and treatment of HCC.
4.Mechanism of action of follicular helper T cells in autoimmune hepatitis
Longlong LUO ; Lifei WANG ; Guojing XING ; Ying ZHENG ; Lixia LU ; Chuyi LI ; Bin LI ; Jun MA ; Xiaohui YU ; Jiucong ZHANG
Journal of Clinical Hepatology 2024;40(7):1466-1469
Autoimmune hepatitis(AIH)is a type of chronic hepatitis caused by the attack of hepatocytes by the autoimmune system,and with the prolongation of disease course,it may gradually progress to liver cirrhosis and even hepatocellular carcinoma.Although great achievements have been made in the understanding and treatment of AIH,its etiology and pathogenesis still remain unclear.T cells play a crucial role in the development and progression of AIH,and by focusing on follicular helper T cells,this article elaborates on the research advances in follicular helper T cells in AIH,in order to provide new ideas and strategies for the clinical treatment of AIH.
5.Research advances in the mechanism of action of nucleotide-binding oligomerization domain-like receptor protein 3 inflammasome in autoimmune hepatitis
Lifei WANG ; Longlong LUO ; Guojing XING ; Lixia LU ; Bin LI ; Jiucong ZHANG ; Xiaohui YU
Journal of Clinical Hepatology 2024;40(10):2092-2097
Autoimmune hepatitis(AIH)is chronic hepatitis caused by the attack of live cells by the immune system,and at present,the pathogenesis of AIH remains unclear.Inflammasomes are important components of innate immunity and are involved in a variety of pathophysiological processes.Studies have shown that inflammatory response associated with nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)plays an important role in the pathogenesis of AIH,which mainly mediates the release of proinflammatory factors and pyroptosis,thereby participating in the pathophysiological process of AIH.Therefore,the development and progression of AIH can be delayed by inhibiting the activation of NLRP3 inflammasomes,which provides new ideas for the prevention and treatment of AIH.
6.The mechanism of autophagy inducing drug resistance of hepatocellular carcinoma
Runbing ZHANG ; Tingting SHI ; Yang WU ; Jiucong ZHANG ; Xiaofeng ZHENG
Journal of Clinical Hepatology 2024;40(11):2315-2319
Treatment resistance of hepatocellular carcinoma(HCC)is an important factor restricting its treatment outcome.Autophagy is a process involving multiple steps and targets and is closely associated with the proliferation and apoptosis of tumor cells.At the same time,there is significant crosstalk between autophagy and tumor treatment resistance.Therefore,autophagy may be one of the key factors hindering tumor cell death after medical intervention.Transforming growth factor-β(TGF-β),epithelial-mesenchymal transition(EMT),and long non-coding RNA(lncRNA)are important factors leading to drug resistance of HCC.This article discusses the possible mechanism of TGF-β,EMT,and lncRNA mediating complex molecular networks and inducing drug resistance of HCC,in order to provide new ideas for improving the sensitivity of HCC treatment.
7.The role of tumor necrosis factor-α in the development and progression of hepatocellular carcinoma
Lingling ZHU ; Yani ZHANG ; Tingting SHI ; Yang WU ; Chun GAO ; Xiaohui YU ; Yujing HE ; Jiucong ZHANG
Journal of Clinical Hepatology 2024;40(11):2320-2325
Tumor necrosis factor-α(TNF-α)is involved in the regulation of multiple biological processes such as the proliferation,invasion,migration,and chemotherapy resistance of hepatocellular carcinoma(HCC)cells through TNF receptor-mediated signaling pathways.At the same time,TNF-α also plays a role in inducing the apoptosis of HCC cells.Some TNF-α inhibitors have been shown to inhibit the progression of HCC and prolong survival time.At present,the potential mechanism of action of TNF-α in HCC remains unclear,and exploration of the interaction between TNF-α and HCC can help to determine the potential therapeutic targets for HCC.This article summarizes the latest research advances in the mechanism of action of TNF-α in HCC and introduces the possibility of targeting TNF-α as a treatment method for HCC,in order to provide a theoretical basis for the prevention and treatment of liver cancer and drug research and development.
8.Influencing Factors of Overall Survival of Elderly Patients with Hepatocellular Carcinoma and Construction of Prediction Model of Prognosis Nomogram:A Population-Based Study
Yang WU ; Tian LI ; Tingting SHI ; Lingling ZHU ; Yani ZHANG ; Peipei GUO ; Runbing ZHANG ; Shunna WANG ; Chun GAO ; Xiaohui YU ; Jiucong ZHANG
Cancer Research on Prevention and Treatment 2024;51(9):756-763
Objective To explore the independent risk factors that affect the overall survival(OS)of elderly patients with hepatocellular carcinoma(HCC,≥60 years old)and build a nomogram prediction model.Methods Clinical data of all elderly patients with HCC from the SEER database from 2005 to 2020 were downloaded from SEER database.In accordance with the inclusion and exclusion criteria,the screened patients were randomly assigned to a training group(70%)and a validation group(30%).The independent risk factors of elderly patients with HCC were determined by univariate and multivariate Cox regression analyses and further validated by Kaplan-Meier survival analysis.On the basis of the determined variables,nomograms were developed and verified to predict the OS of elderly patients with HCC at 6,12,and 24 months.The consistency index(C index),calibration curve,receiver's operating characteristic(ROC)curve,and area under curve(AUC)were used to evaluate the prediction efficiency and discrimination ability of the prediction model,and decision curve analysis(DCA)was used to evaluate the potential clinical application value of the nomogram.Results A total of 1134 elderly patients with HCC were included,with 793 in the training group and 341 in the validation group.Seven variables,including age,clinical grade,clinical stage,M stage,tumor size classification,and radiotherapy,were identified as independent prognostic factors of this population.The constructed nomogram shows excellent prediction performance,with C indices of 0.745 in the training group and 0.704 in the validation group.The AUC values of the training group at 6,12,and 24 months were 0.785,0.788,and 0.798,respectively,and those of the validation group were 0.780,0.725,and 0.607,respectively.The calibration curve shows good consistency from the predicted survival probability to the actual probability.The ROC curve and DCA show that the nomogram proposed in this study has good prediction ability.Conclusion Age,clinical grade,clinical stage,M stage,tumor size classification,and radiotherapy are important influencing factors for the survival of elderly patients with HCC.The prediction model of prognosis nomogram constructed in this study has good predictive value,and it can be used to predict the OS of elderly patients with HCC,which could be helpful for individualized survival assessment and clinical management of these patients.
9.Research progress in immunotherapy and targeted therapy for gastric cancer and esophagogastric junction cancer
Yang WU ; Tian LI ; Runbing ZHANG ; Tingting SHI ; Chun GAO ; Xiaofeng ZHENG ; Jiucong ZHANG
Journal of International Oncology 2024;51(9):595-600
Gastric cancer and esophagogastric junction cancer (EGJC) are one of the world 's most common types of malignant tumors. Traditional treatment methods mainly include radiotherapy, chemotherapy, and surgery, but the patients ' prognosis is limited. In recent years, with the development in treatment methods, immunotherapy and targeted therapy are gradually recognized as the first-line treatment methods. In immunotherapy, nivolumab and pabolizumab have shown clear efficacy in patients with programmed deathligand 1 positive, while other immunotherapies (such as tumor vaccine, engineered T cells, and non-specific immunomodulators) are still being tested or developed. In addition, targeted therapy has only shown comparatively large therapeutic potential in certain specific populations or in second-line treatment. For instance, tratuzumab has a clear curative effect on patients with positive human epidermal growth factor receptor 2, but has suboptimal efficacy in patients with amplification of other molecular targets. An in-depth discussion of the research progress of immunotherapy and targeted therapy in gastric cancer and EGJC will help to improve the prognosis of patients and provide a reference for accurate treatment of tumors.
10.Research progress on the role of interleukin-6 in tumor immune checkpoint inhibitor therapy
Zhu LINGLING ; Zhang YANI ; Shi TINGTING ; Yu XIAOHUI ; Zhang JIUCONG
Chinese Journal of Clinical Oncology 2024;51(11):585-589
Immune checkpoint inhibitors(ICI),an immunotherapy,have an important role in the treatment of various cancers.However,ICIs induce several immune-related adverse events(irAEs).Interleukin(IL)-6 is an important inflammatory factor that promotes cancer progres-sion and modulates the clinical application of ICIs through various mechanisms.Herein,we postulate possible mechanisms that are involved in the ICI-regulatory effects mediated by the expression of the cytokine interleukin-6(IL-6),elucidate the effect of IL-6 on checkpoint-block-ade therapy and irAEs,and summarize the role of IL-6 signaling-targeted interventions in ICIs efficacy and irAEs management.

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