1.Safety and efficacy of argon-helium cryoablation combined with targeted therapy and anti-programmed death-1 monoclonal antibody in treatment of patients with unresectable hepatocellular carcinoma aged 60 years or older
Shujuan GONG ; Xiujuan CHANG ; Yan LIU ; Dong JI ; Yan CHEN ; Quanwei HE ; Yongping YANG
Journal of Clinical Hepatology 2026;42(3):629-638
ObjectiveTo investigate whether anti-programmed death-1 (PD-1) monoclonal antibody can enhance the efficacy and safety of argon-helium cryoablation combined with targeted therapy in patients with unresectable hepatocellular carcinoma (uHCC) aged 60 years or older. MethodsA retrospective analysis was performed for the clinical data of 124 patients with advanced uHCC aged 60 years or older who were treated at The Fifth Medical Center of Chinese PLA General Hospital from January 2013 to September 2024. After propensity score matching, 57 patients received cryoablation combined with targeted therapy (double combination group), while 57 received cryoablation combined with targeted therapy and anti-PD-1 monoclonal antibody (triple combination group). The indicators for efficacy assessment included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and the incidence rate of adverse events. The Mann-Whitney U test was used for comparison of continuous data between two groups, and the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. The Kaplan-Meier method was used to plot survival curves, and the Log-rank test was used for comparison between groups. A Cox proportional-hazards regression model analysis was used to investigate the influencing factors for survival prognosis. ResultsThe triple combination group had a significantly higher ORR than the double combination group (59.6% vs 29.8%, χ2=9.083, P=0.003), while there was no significant difference in DCR between the two groups (87.7% vs 77.2%, χ2=1.516, P=0.218), and compared with the double combination group, the triple combination group had significantly longer median PFS (9.1 months vs 4.8 months, χ2=7.813, P=0.005) and median OS (26.1 months vs 13.6 months, χ2=14.199, P<0.001). The multivariate Cox proportional-hazards regression model analysis showed that triple combination treatment was an independent influencing factor for PFS (hazard ratio [HR]=0.52, 95% confidence interval [CI]: 0.35 — 0.78, P=0.001) and OS (HR=0.32, 95%CI: 0.20 — 0.51, P<0.001). There was no significant difference in the incidence rate of adverse events between the two groups (P>0.05). ConclusionTriple combination treatment with argon-helium cryoablation, targeted therapy, and anti-PD-1 monoclonal antibody can significantly improve survival benefits in uHCC patients aged 60 years or older, with a controllable safety profile.
2.Mechanism of Taishan Panshisan in Inhibiting Oxidative Stress Injury of Trophoblast Cells by Regulating KEAP1/Nrf2/FoxO3 Signaling Pathway
Yangyang DUAN ; Xianglun JI ; Jiahong CHEN ; Jinghang YANG ; Xinyu XIAO ; Shutao CHEN ; Chaorui LIN ; Fan LIN ; Shu JIANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(10):12-22
ObjectiveTo explore the effect and mechanism of Taishan Panshi powder (TSPSP) on inhibiting oxidative stress injury in human chorionic trophoblast cells (HTR-8/SVneo), and to uelucidate the underlying mechanism of TSPSP in the treatment of spontaneous abortion (SA). MethodsGene differential analysis of SA was performed using the Gene Expression Omnibus (GEO) database and correlated with oxidative stress. Network pharmacology was employed to screen the active components of TSPSP, and a "Chinese medicine-component-target-disease" network was constructed to predict the mechanism of action of TSPSP. For in vitro validation experiments, HTR-8/SVneo cells were divided into blank group, model group, TSPSP-containing serum 2.5%, 5%, 10% groups, and nuclear factor E2-related factor 2 (Nrf2) inhibitor group (ML385, 30 μmol·L-1). Except for the blank group, other groups were stimulated with 150 μmol·L-1 H2O2 for 3 h to establish a cell oxidative stress injury model. After successful modeling, the blank group and model group were given 10% blank serum, each TSPSP-containing serum group was treated with the corresponding concentration of drug-containing serum, and the Nrf2 inhibitor group was additionally given 30 μmol·L-1 ML385 on the basis of 10% TSPSP-containing serum. All groups of cells were continuously cultured under the above conditions for 24 h, and then samples were collected for subsequent detection. Cell viability in each group was detected by CCK-8 assay. Cell migration rate was detected by scratch test. The contents of malondialdehyde (MDA), Fe2+, and Glutathione (GSH) were detected by enzyme-linked immunosorbent assay (ELISA). Intracellular reactive oxygen species (ROS) level was detected by a fluorescent probe (DCF-DA). The protein and mRNA expression levels of Kelch-like ECH-associated protein 1 (KEAP1), Nrf2, and forkhead box protein O3 (FoxO3) in cells were detected by immunofluorescence (IF) and real-time quantitative polymerase chain reaction (Real-time PCR). The protein expression levels of KEAP1, Nrf2, FoxO3, Glutathione peroxidase 4 (GPX4), and superoxide dismutase (SOD) in cells were detected by Western blot. ResultsThe GSE76862 and GSE22490 datasets were obtained from the GEO database. Differential gene analyses showed that the KEAP1, Nrf2, and FoxO3 genes were all associated with the disease. After matching with the oxidative stress pathway, nine significantly differential pathways were identified (P<0.05), among which three contained the target genes Nrf2 and FoxO3. A total of 246 active ingredient targets of TSPSP and 2 804 SA-related targets were obtained through network pharmacology, and 154 potential action targets were obtained after taking the intersection. Topological analysis showed that targets such as KEAP1 and Nrf2 exhibited high degree values. GO and KEGG enrichment analyses indicated that the intersection targets were mainly involved in oxidative stress response, FOXO and MAPK signaling pathways, etc. In in vitro experiments, compared with the blank group, the cell viability in the model group was significantly decreased (P<0.01). Compared with the model group, the cell viability in each TSPSP-containing serum group was significantly increased (P<0.01). Compared with the 10% TSPSP-containing serum group, the cell viability in the ML385 group decreased to approximately 70% (P<0.01). Compared with the blank group, the model group showed significantly increased contents of MDA, Fe2+, and ROS, decreased GSH expression (P<0.01), significantly reduced cell migration rate (P<0.01), and increased protein and mRNA expression levels of KEAP1 and FoxO3 (P<0.01), while decreased protein and mRNA expression levels of Nrf2, GPX4, and SOD (P<0.01). Compared with the model group, each TSPSP-containing serum group showed significantly decreased contents of MDA, Fe²⁺, and ROS, increased GSH expression (P<0.01), significantly increased migration rate (P<0.01), significantly decreased protein and mRNA expression levels of KEAP1 and FoxO3 (P<0.05, P<0.01), and significantly increased protein and mRNA expression levels of Nrf2, GPX4, and SOD (P<0.05, P<0.01). Compared with the 10% TSPSP-containing serum group, the ML385 group showed reversed trends in all indicators (P<0.05, P<0.01). ConclusionTSPSP can inhibit H2O2-induced oxidative stress injury of trophoblast cells, and its mechanism of action may be related to the drug activating the KEAP1/Nrf2/FoxO3 signaling pathway.
3.Mechanism of Taishan Panshisan in Inhibiting Oxidative Stress Injury of Trophoblast Cells by Regulating KEAP1/Nrf2/FoxO3 Signaling Pathway
Yangyang DUAN ; Xianglun JI ; Jiahong CHEN ; Jinghang YANG ; Xinyu XIAO ; Shutao CHEN ; Chaorui LIN ; Fan LIN ; Shu JIANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(10):12-22
ObjectiveTo explore the effect and mechanism of Taishan Panshi powder (TSPSP) on inhibiting oxidative stress injury in human chorionic trophoblast cells (HTR-8/SVneo), and to uelucidate the underlying mechanism of TSPSP in the treatment of spontaneous abortion (SA). MethodsGene differential analysis of SA was performed using the Gene Expression Omnibus (GEO) database and correlated with oxidative stress. Network pharmacology was employed to screen the active components of TSPSP, and a "Chinese medicine-component-target-disease" network was constructed to predict the mechanism of action of TSPSP. For in vitro validation experiments, HTR-8/SVneo cells were divided into blank group, model group, TSPSP-containing serum 2.5%, 5%, 10% groups, and nuclear factor E2-related factor 2 (Nrf2) inhibitor group (ML385, 30 μmol·L-1). Except for the blank group, other groups were stimulated with 150 μmol·L-1 H2O2 for 3 h to establish a cell oxidative stress injury model. After successful modeling, the blank group and model group were given 10% blank serum, each TSPSP-containing serum group was treated with the corresponding concentration of drug-containing serum, and the Nrf2 inhibitor group was additionally given 30 μmol·L-1 ML385 on the basis of 10% TSPSP-containing serum. All groups of cells were continuously cultured under the above conditions for 24 h, and then samples were collected for subsequent detection. Cell viability in each group was detected by CCK-8 assay. Cell migration rate was detected by scratch test. The contents of malondialdehyde (MDA), Fe2+, and Glutathione (GSH) were detected by enzyme-linked immunosorbent assay (ELISA). Intracellular reactive oxygen species (ROS) level was detected by a fluorescent probe (DCF-DA). The protein and mRNA expression levels of Kelch-like ECH-associated protein 1 (KEAP1), Nrf2, and forkhead box protein O3 (FoxO3) in cells were detected by immunofluorescence (IF) and real-time quantitative polymerase chain reaction (Real-time PCR). The protein expression levels of KEAP1, Nrf2, FoxO3, Glutathione peroxidase 4 (GPX4), and superoxide dismutase (SOD) in cells were detected by Western blot. ResultsThe GSE76862 and GSE22490 datasets were obtained from the GEO database. Differential gene analyses showed that the KEAP1, Nrf2, and FoxO3 genes were all associated with the disease. After matching with the oxidative stress pathway, nine significantly differential pathways were identified (P<0.05), among which three contained the target genes Nrf2 and FoxO3. A total of 246 active ingredient targets of TSPSP and 2 804 SA-related targets were obtained through network pharmacology, and 154 potential action targets were obtained after taking the intersection. Topological analysis showed that targets such as KEAP1 and Nrf2 exhibited high degree values. GO and KEGG enrichment analyses indicated that the intersection targets were mainly involved in oxidative stress response, FOXO and MAPK signaling pathways, etc. In in vitro experiments, compared with the blank group, the cell viability in the model group was significantly decreased (P<0.01). Compared with the model group, the cell viability in each TSPSP-containing serum group was significantly increased (P<0.01). Compared with the 10% TSPSP-containing serum group, the cell viability in the ML385 group decreased to approximately 70% (P<0.01). Compared with the blank group, the model group showed significantly increased contents of MDA, Fe2+, and ROS, decreased GSH expression (P<0.01), significantly reduced cell migration rate (P<0.01), and increased protein and mRNA expression levels of KEAP1 and FoxO3 (P<0.01), while decreased protein and mRNA expression levels of Nrf2, GPX4, and SOD (P<0.01). Compared with the model group, each TSPSP-containing serum group showed significantly decreased contents of MDA, Fe²⁺, and ROS, increased GSH expression (P<0.01), significantly increased migration rate (P<0.01), significantly decreased protein and mRNA expression levels of KEAP1 and FoxO3 (P<0.05, P<0.01), and significantly increased protein and mRNA expression levels of Nrf2, GPX4, and SOD (P<0.05, P<0.01). Compared with the 10% TSPSP-containing serum group, the ML385 group showed reversed trends in all indicators (P<0.05, P<0.01). ConclusionTSPSP can inhibit H2O2-induced oxidative stress injury of trophoblast cells, and its mechanism of action may be related to the drug activating the KEAP1/Nrf2/FoxO3 signaling pathway.
4.Pre-operative risk assessment of hepatocellular carcinoma recurrence in liver transplant recipients by non-invasive detection of pre-existing genetic lesions
Suqin YANG ; Sunbin LING ; Jianhua LI ; Yan WANG ; Jiapei WANG ; Qiwei HUANG ; Fanming LIU ; Yiqi ZHUANG ; Yingyu ZHENG ; Rui WANG ; Zhe YANG ; Xiaoping ZHENG ; Kai WANG ; Zhikun LIU ; Jun CHEN ; Jianguo WANG ; Haiyang XIE ; Lin ZHOU ; Leiming CHEN ; Guoqiang CAO ; Dandan CHEN ; Junfang JI ; Bin ZHAO ; Chao JIANG ; Di LU ; Xuyong WEI ; Hangjin JIANG ; Qiaonan SHAN ; Hengbo SHI ; Yong-Zhen XU ; Shusen ZHENG ; Zhengxin WANG ; Shengda LIN ; Xiao XU
Clinical and Molecular Hepatology 2026;32(2):884-903
Background/Aims:
Liver transplantation (LT) following total hepatectomy is a life-saving treatment for hepatocellular carcinoma (HCC). The HCC recurrence after LT hinders the effectiveness of the procedure. The objective of this study is to develop a pre-operative risk stratification model based on a liquid biopsy.
Methods:
We conducted a comprehensive multi-omics study of 260 HCC patients from three centers, including clinical data, low-coverage whole-genome sequencing of cell-free DNA (cfDNA) from plasma, as well as whole-exome, single-nucleus RNA, and spatial transcriptomics from matched tumor and non-tumor tissues.
Results:
We identified cfDNA-derived copy number alteration (CNA) signatures associated with post-transplant recurrence. By integrating cfDNA-derived CNA profiles with single-cell transcriptomic data, we traced recurrence-associated cfDNA to a distinct subpopulation of malignant cells within the primary tumor. These cells were embedded in a pro-metastatic microenvironment of specialized endothelial subtypes and cancer-associated fibroblasts. Notably, most recurrence-associated lesions were detectable in cfDNA prior to liver transplantation (LT). Building on these insights, we developed the ZJU Criteria based on CNA fragments and tumor markers, a pre-LT risk prediction tool that integrates conventional clinical factors with cfDNA-derived CNA signatures, and validated it using internal and independent external cohorts.
Conclusion
Our findings suggest that post-transplant recurrence commonly originates from advanced subclones that emerge late during tumor evolution. The ZJU Criteria provides an accurate, non-invasive strategy that significantly improves pre-LT risk stratification and clinical decision-making for patients with HCC.
5.PD-L1 and TGF-β cooperatively regulate tumor immune escape: mechanisms and advances in dual-targeting therapy
Qianqian HE ; Yanli YANG ; Han ZHANG ; Zheyu CHEN ; Puzhong JI
Chinese Journal of Clinical Medicine 2026;33(3):533-543
While programmed cell death ligand 1 (PD-L1) inhibitors have yielded breakthroughs in tumor therapy, their efficacy is constrained by the heterogeneity of the tumor microenvironment and multiple immunosuppressive pathways. In recent years, research has revealed that transforming growth factor-β (TGF-β) synergistically drives tumor cell immune escape with PD-L1 via pathways such as metabolic reprogramming, epithelial-mesenchymal transition, and SOX family factors. Currently, various PD-L1/TGF-β bispecific antibodies (bsAbs) have exhibited promising therapeutic potential in early-phase clinical trials, yet they still confront challenges related to toxicity and drug resistance. This article systematically reviews the mechanisms by which PD-L1 and TGF-β synergistically regulate tumor immune escape, summarizes the clinical research progress of bsAbs, and discusses strategies for novel drug design and biomarker development, with the aim of offering new insights for the development of combined tumor immunotherapy strategies.
6.Adhering to the purpose of academic journal establishment, and fulfilling the mission of scientific journals: discipline construction of digestive surgery in the new era
Peng JIANG ; Jiahong DONG ; Jia FAN ; Qiang LI ; Xiujun CAI ; Minhua ZHENG ; Jiafu JI ; Yinmo YANG ; Hui CAO ; Yajin CHEN ; Guoxin LI ; Guoyue LYU ; Leida ZHANG ; Min CHEN
Chinese Journal of Digestive Surgery 2025;24(8):1022-1026
On the occasion of the 110th Anniversary of the establishment of the Chinese Medical Association, the third conference of the Fourth Editorial Board of Chinese Journal of Digestive Surgery, and the Second Elite Group of Chinese Journal of Digestive Surgery, was successfully held in Kunming on July 4, 2025. This conference systematically summarizes the development experience of the journal over the past 20 years from three aspects: the role of ecological construction of thought in the discipline construction of digestive surgery, the display of the latest academic achievements in the field of digestive surgery, the development difficulties, and breakthrough paths of the discipline, and strategically plans the path of discipline construction in the new era.
7.Value of Red Blood Cell Distribution Width Combined With BISAP Score in Early Prediction of Severe Acute Pancreatitis
Xian TU ; Yan LIU ; Chunyan YANG ; Yan SHEN ; Yiqing WANG ; Deqiong CHEN ; Qi JI ; Qingming WU
Chinese Journal of Gastroenterology 2025;30(1):9-15
Background:The incidence and mortality rates of severe acute pancreatitis(SAP)have been increasing year by year.Therefore,early and rapid identification,along with timely intervention in the progression of acute pancreatitis(AP),is of particular importance.Aims:To explore the value of red blood cell distribution width(RDW)combined with BISAP score in the early prediction of SAP.Methods:A total of 561 AP patients admitted from January 2019 to December 2021 at the General Hospital of the Central Theater Command of the PLA were enrolled and divided into SAP group and non-SAP group according to the disease severity.Venous blood samples were collected within 24 hours of admission.The relevant clinical data,laboratory indices,BISAP score,and MCTSI score were compared between the two groups.Logistic regression analysis was used to identify the risk factors for SAP.Spearman correlation coefficient was employed to assess the correlation of these risk factors with the severity of AP,as well as the correlation of RDW with BISAP score and MCTSI score.The predictive values of these risk factors for SAP were evaluated by ROC curve analysis.Results:Compared with the non-SAP group,the prevalence of hypertension,length and cost of hospital stay,neutrophil count(NEUT),neutrophil-to-lymphocyte ratio(NLR),RDW,serum potassium,aspartate transaminase(AST),blood urea nitrogen(BUN),serum creatinine(SCr),BISAP score and MCTSI score were significantly increased in the SAP group(all P<0.05),while the lymphocyte count(LYM),serum calcium and albumin(ALB)were significantly decreased(all P<0.05).RDW(OR=1.582,95%CI:1.066-2.348,P=0.023),SCr(OR=1.018,95%CI:1.001-1.035,P=0.040),BISAP score(OR=6.210,95%CI:3.121-12.356,P<0.001),and MCTSI score(OR=2.917,95%CI:2.160-3.939,P<0.001)were the independent risk factors for SAP.RDW(rs=0.320,P<0.001),SCr(rs=0.103,P=0.015),BISAP score(rs=0.516,P<0.001),and MCTSI score(rs=0.512,P<0.001)were positively correlated with the severity of AP.Moreover,RDW was positively correlated with BISAP score(rs=0.428,P<0.001)and MCTSI score(rs=0.408,P<0.001).ROC curve analysis revealed that the areas under the ROC curve of RDW,SCr,BISAP score,MCTSI score,and combination of RDW and BISAP score for predicting SAP were 0.753,0.581,0.889,0.888,and 0.905,respectively.Conclusions:RDW,SCr,BISAP score,and MCTSI score are the independent risk factors for SAP.RDW combined with BISAP score can enhance the predictive value for SAP.
8.The role of probiotics in prevention and treatment of heat stroke through modulation of the gut microbiota
Jian-Yao YOU ; Lei LI ; Yi-Tong GONG ; Yang-Yang CAO ; Ji-Kuai CHEN ; Shuo-Gui XU
Parenteral & Enteral Nutrition 2025;32(5):304-309
In recent years,the incidence of heat-related diseases has been on a steady upward trend,which is closely associated with environmental factors such as climate change and air pollution.Exposure to a hot environment and/or strenuous physical activities can progress to heat stroke(HS),an acute disease that can lead to death.Current research indicates that gut injury occupies the most crucial initiating position in the pathophysiological changes and pathogenesis of HS.Probiotics can reduce the incidence and mortality of HS through maintaining the health of the gut microbiota,regulating the intestinal immune system,and other effects.In addition,the gut microbiota can construct axis systems to interact with multiple organs such as the liver,lungs,and brain,which is of great significance for alleviating the damage to distant organs caused by HS.This paper reviews the regulation of the gut microbiota by probiotics to improve the intestinal heat tolerance ability and barrier function,aiming to provide references for the prevention and treatment of heat stroke in clinical practice.
9.Construction and application of pediatric diagnosis and treatment island in a tertiary hospital
Kaiyang GENG ; Hesheng CHANG ; Li ZHANG ; Chen WANG ; Liming YANG ; Ming ZHANG ; Ting WANG ; Zhili JI
Chinese Journal of Hospital Administration 2025;41(6):491-494
Establishing a one-stop diagnosis and treatment mode centered on patients and linked by diseases is of great significance for optimizing the medical process and improving the medical experience. In March 2024, a tertiary hospital integrated pediatric outpatient and emergency resources, established a pediatric diagnosis and treatment island through reasonable department settings, strengthened talent team construction, optimized diagnosis and treatment processes, and established supporting guarantee mechanisms. It was officially put into use in June of the same year, providing one-stop diagnosis and treatment services for children and achieving the goal of " not leaving the island for minor illnesses and not leaving the hospital for major illnesses". Before the operation of island (January May 2024), the complaint rate and waiting time for pediatric outpatient and emergency department were 39 cases per 100 000 patients and 15 to 30 minutes, respectively; After operation (June August 2024), the complaint rate and waiting time decreased to 17 cases per 100 000 people and 10 to 20 minutes respectively; The average monthly comprehensive income of outpatient and emergency departments increased by 33%. The pediatric diagnosis and treatment island mode could assist in the sustainable high-quality development of pediatrics in hospital, and provide references for optimizing outpatient and emergency department management in other tertiary public hospitals. In the future, we should further enrich the service content of the island and strengthen information technology construction.
10.Current status of cleaning and disinfection of medical bedding items in public medical institutions of Liangshan ethnic minority area
Shixia WANG ; Xiaoli JI ; Juan WANG ; Yun CHEN ; Shimei WANG ; Fumei TU ; Kexin YANG ; Jiaguo CHENG
Chinese Journal of Nosocomiology 2025;35(18):2837-2841
OBJECTIVE To investigate the current status of cleaning and disinfection of medical bedding items in public medical institutions of Liangshan ethnic minority area and analyze the risk of infections so as to provide ba-ses for optimizing the infection control strategies in the ethnic minority area.METHODS On the basis of question-naire survey,onsite sampling method and bacterial isolation and identification technique,a cross-sectional survey was conducted for the current status of cleaning and disinfection of medical bedding items in 15 different grades of public medical institutions of Liangshan ethnic minority area by stratified random sampling method from Sep.2021 to Sep.2023.RESULTS A total of 66 valid questionnaire were recycled,and 540 bedding item samples were col-lected.Totally 93.33%of the medical institutions relied on laundries for centralized cleaning of the medical bed-ding items.The implementation rates of management items such as policy formulation(100.00%)and pre-job training were remarkably higher in the tertiary hospitals than in the secondary and primary hospitals(allP<0.05).There were no significant differences in the qualified rates of surveillance of microbiological indexes for the medical bedding items among the medical institutions,the qualified rate of surveillance of microbiological inde-xes was highest(71.30%)in the general hospitals and was lowest(61.11%)in the infectious diseases specialized hospital.The qualified rate of surveillance of microbiological indexes was lowest(3.33%)in pediatrics department or internal medicine department,and it raised most remarkably(80.00%)after the disinfection,and there was significant difference(x2=36.274,P<0.001).CONCLUSIONS The current status of disinfection of the medical bedding items is not optimistic in the medical institutions of Liangshan ethnic minority area.There are the prob-lems such as imperfect system,insufficient equipment and absence of personnel training.It is necessary to com-plete the execution and supervision system for cleaning and disinfection standards,increase the cleaning facilities,promote the use of antibacterial textile and bring in smart management system so as to improve the cleaning and disinfection quality and reduce the risk of hospital-associated infections.

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