1.The Potential Role of Immune Checkpoint Molecules in the Pathogenesis of Autoimmune Hepatitis and in Targeted Therapy
Haixia LI ; Aiping TIAN ; Miao XUE ; Ziyi LI ; Xiaorong MAO
Medical Journal of Peking Union Medical College Hospital 2026;17(2):512-518
Autoimmune hepatitis (AIH) is a chronic, immune-mediated liver injury of unknown etiology. The onset of this disease involves the activation and recruitment of diverse immune and non-immune cells, which in turn trigger hepatic damage. Immune checkpoint molecules (ICM) are expressed on the surface of multiple cell types. By regulating cellular functional states, they help limit the intensity and duration of immune responses, thereby preventing excessive inflammation and tissue damage, and maintaining immune homeostasis. In AIH, however, this natural "braking" mechanism is impaired, leading to aberrant activation of both immune and non-immune cells and the breakdown of immune homeostasis. Consequently, ICM are likely to play a critical role in the pathogenesis of AIH. A deeper understanding of the function of ICM in AIH not onlyadvances our insight into the disease mechanism, but also suggests that targeting these molecules may represent a promising therapeutic strategy for the treatment of AIH.
2.WANG Xixing's Clinical Experience in Treating Immune Checkpoint Inhibitor-Related Pneumonitis Based on the Theory of "Cough Attributed to the Five Zang (脏) Organs"
Xue QI ; Xi YANG ; Xinyue WANG ; Dongxin ZHANG ; Yuxing MAO ; Yuankun HAN ; Wenbo ZHAI ; Boyang LYU ; Yifang LI ;
Journal of Traditional Chinese Medicine 2026;67(5):477-481
This paper summarizes Professor WANG Xixing's clinical experience in treating immune checkpoint inhibitor-related pneumonitis (CIP) based on the theory of "cough attributed to the five zang (脏) organs". Cough is a common predominant symptom of CIP. According to the theory of "cough attributed to the five zang organs", drug toxicity triggers cancer toxin, leading to disharmony among the five zang organs, and then lung failing to diffuse and govern descent as the core pathogenesis. Therefore, treatment should focus on harmonizing the five zang organs to restore the normal function of lung qi to diffuse and govern descent. In clinical practice, CIP can be classified into four syndrome patterns, including lung yin depletion, deficiency of both the lung and the spleen with phlegm-dampness, liver fire harassing the lung, and lung-kidney yin deficiency. Correspondingly, Chaimai Jinluo Runfei Decoction (柴麦金络润肺汤) is used to nourish yin and moisten the lung; Qigui Peitu Huayin Decoction (芪桂培土化饮汤) is used to fortify the spleen and tonify the lung, resolve dampness and dispel phlegm; Chaidan Shuyu Runjin Decoction (柴丹疏郁润金汤) is used to drain liver and clear the lung; and Dimai Jinshui Xiangsheng Decoction (地脉金水相生汤) is used to nourish the kidney and moisten the lung.
3.Mechanistic study on alleviation of Schistosoma japonicum infection-induced hepatic damages by macrophage efferocytosis
Yuxin ZHANG ; Junyao SHEN ; Weijie XUE ; Chenxu MAO ; Ziling WANG ; Zhigang LEI ; Sha ZHOU ; Chuan SU
Chinese Journal of Schistosomiasis Control 2026;38(3):274-286
Objective To investigate the development, role, and regulatory mechanism of macrophage efferocytosis in the liver of hosts infected with Schistosoma japonicum. Methods The expression of efferocytosis-related gene like efferocytosis receptors, efferocytosis-related bridging molecules,“eat me” signal and “don’t eat me” signal was detected in the livers of patients and mice infected with S. japonicum in the Gene Expression Omnibus (GEO) database. Ten wild-type (WT) male mice (6 ~ 8 weeks old, weighing 20 ~ 25 g) were randomly divided into a Schistosoma japonicum infection (SJ) group and a normal control (NC) group, with 5 mice in each group. The efferocytosis of neutrophils and T cells by liver macrophages was detected in mice from SJ group and NC group using flow cytometry and immunofluorescence assay, respectively. The expression of efferocytosis-related Mer receptor tyrosine kinase (MerTK) and Axl receptor tyrosine kinase (Axl) proteins was determined in mouse liver tissues using Western blotting assay, and the proportion of MerTK+ macrophages and the average fluorescence intensity of macrophage MerTK were detected in mouse livers using flow cytometry. Changes in liver granulomas and fibrosis were observed in mice infected with S. japonicum following injection of efferocytosis inhibitors, and S. japonicum-infected mice without injection of efferocytosis inhibitors served as controls. Bone marrow-derived macrophages (BMDMs) were isolated from macrophage scavenger receptor class A (SR-A) conditional knockout (CKO) and wild-type (WT) mice, and changes in apoptotic neutrophils were detected in SR-A CKO mouse macrophages in vitro using flow cytometry. Then, BMDMs was divided into the WT mono-culture group, the WT and apoptotic neutrophils co-culture group, the SR-A CKO mono-culture group, and the SR-A CKO and neutrophils co-culture group, and the expression of MerTK and Axl was quantified in vitro using Western blotting and real-time quantitative PCR (RT-qPCR) assays during neutrophil efferocytosis. The efferocytosis of neutrophils and T cells by mouse liver macrophages was detected in the SR-A CKO SJ group and the WT SJ group using flow cytometry and immunofluorescence assay, and the expression of MerTK and Axl proteins was determined in mouse liver tissues in both groups using Western blotting. In addition, the proportion of MerTK+ macrophages and the average fluorescence intensity of macrophage MerTK were detected in mouse livers in both groups using flow cytometry. Results Data from the GEO database showed that the expression of some efferocytosis receptors and efferocytosis-related bridging molecules, and “eat me” and “don’t eat me” signals all appeared a tendency towards a rise in livers of patients and mice in the SJ group relative to the NC group, suggesting that S. japonicum infection-induced liver diseases may be associated with efferocytosis. Flow cytometry detected higher proportions of Ly6G+ cells [(13.13 ± 0.45)% vs. (6.48 ± 0.25)%; t = 22.30, P < 0.05] and CD3+ cells [(7.60 ± 0.33)% vs. (3.30 ± 0.42)%; t = 13.98, P < 0.05] in mouse liver macrophages in the SJ group than in the NJ group, and the expression of MerTK protein [(2.30 ± 0.14) vs. (1.14 ± 0.46); t = 4.19, P < 0.05], the mean fluorescence intensity of macrophages [(160.67 ± 15.28) vs. (94.50 ± 19.61); t = 4.81, P < 0.05], and the proportion of MerTK+ macrophages [(20.78 ± 4.17)% vs. (6.85 ± 0.39)%; t = 6.57, P < 0.05] were significantly higher in mouse liver tissues in the SJ group than in the NC group. The Axl expression was lower in mouse liver tissues in the SJ group than in the NC group [(1.25 ± 0.08) vs. (1.93 ± 0.37); t = 2.79, P < 0.05], and the area of granulomas around single eggs [(9.18 ± 1.81) × 104μm2 vs. (5.24 ± 1.35) × 104 μm2; t = 3.03, P < 0.05] and proportion of collagen fibers [(25.27 ± 3.99)% vs. (15.14 ± 4.02)%; t = 3.10, P < 0.05] were significantly greater in livers of S. japonicum-infected mice with injection of efferocytosis inhibitors than in mice without injection of efferocytosis inhibitors. The in vitro efferocytosis efficiency of BMDMs [(32.83 ± 3.17)% vs. (45.43 ± 2.34)%; t = 5.54, P < 0.05], and the proportions of Ly6G+ [(9.37 ± 0.48)% vs. (13.13 ± 0.72)%; t = 7.50, P < 0.05] and CD3+ cells [(4.95 ± 0.17)% vs. (7.64 ± 0.50)%; t = 8.87, P < 0.05] in liver macrophages post-infection with S. japonicum were significantly lower in SR-A CKO mice than in WT mice, and the expression of MerTK protein [(0.65 ± 0.25) vs. (1.96 ± 0.69); t = 3.10, P < 0.05], the average fluorescence intensity of macrophages [(138.33 ± 8.39) vs. (160.67 ± 15.28); t = 3.03, P < 0.05] and the proportion of MerTK+ macrophages [(13.17 ± 5.01)% vs. (22.63 ± 2.06)%; t = 3.56, P < 0.05] were significantly lower in mouse liver tissues in the SR-A CKO SJ group than in the WT group. Western blotting detected no significant difference in the Axl protein expression in mouse liver tissues between the SR-A CKO SJ group and the WT SJ group [(0.48 ± 0.07) vs. (0.68 ± 0.30); t = 1.09, P > 0.05]. There were significant differences in the relative MerTK mRNA and protein expression during efferocytosis of BMDMs among the WT monoculture group, the WT and apoptotic neutrophils co-culture group, the SR-A CKO mono-culture group, and the SR-A CKO and neutrophils co-culture group (F = 9.41 and 40.68, both P values < 0.05). In addition, there was a significant difference in the relative Axl mRNA expression during efferocytosis of BMDMs among the four groups (F = 13.62, P < 0.05); however, no significant difference was seen in the relative Axl protein expression (F = 1.27, P > 0.05). Conclusions Efferocytosis of liver macrophages is seen in mice infected with S. japonicum and inhibits liver fibrosis. SR-A may up-regulate the efficiency of macrophage efferocytosis through regulating the expression of efferocytosis receptors.
4.Clinical and epidemiological characteristics of influenza A (H3N2) cases in Tangshan City in 2023 - 2025
Xiaojing SONG ; Jing SUN ; Lichao MAO ; Xue' ; er BAI ; Xin ZHOU ; Da LI ; Lei QIN
Journal of Public Health and Preventive Medicine 2026;37(5):82-86
Objective To analyze the clinical and epidemiological characteristics of influenza A(H3N2) in Tangshan City, Hebei Province, from 2023 to 2025, and to provide a scientific basis for precise prevention and control of local influenza. Methods The influenza-like cases and influenza outbreak cases in the influenza surveillance sentinel hospitals in Tangshan City from January 2023 to December 2025 were included in this study. The clinical characteristics and epidemic characteristics of H3N2 influenza patients were analyzed by descriptive epidemiological methods and chi-square test. Results A total of 11 567 influenza case samples were tested in the study, with a positive rate of 9.34% (1 080/11 567). Influenza A (H3N2) remained the predominant circulating subtype throughout the study period. January 2023 to February 2023 marked the tailing end of the previous season’s H3N2. Then, a minor peak dominated by H1N1 occurred from March to June, and H3N2 circulated again from October to December, peaking in December. From September 2024 to December 2024, H1N1 and H3N2 circulated concurrently, with H3N2 as the dominant strain, peaking in January of the following year. From March 2025 to September 2025, influenza activity remained at low level, and activity began to rise in October, with H1N1 peaking in November before declining, and H3N2 becoming the dominant strain in December. H3N2 mainly occurred in the 5-14 years old group. Cases in the 0–4-year-old group were primarily characterized by gastrointestinal symptoms, with high fever being common. Cases in the 5–59-year-old group were primarily characterized by systemic and respiratory symptoms, with better clinical outcomes. Cases aged 60 and older exhibited the highest rates of hospitalization, severe illness, and incidence of complications. Conclusion From 2023 to 2025, the influenza virus in Tangshan City, Hebei Province is dominated by influenza A (H3N2). The epidemic is characterized by a peak incidence during autumn and winter, co-circulation with H1N1, and fluctuations during the peak period. It is necessary to pay attention to the clinical management and prevention and control of influenza A (H3N2) in infants and the elderly.
5.Association Between Perioperative Troponin Management and Major Adverse Cardiac Events in Elderly Patients with Colorectal Cancer
Xue LOU ; Chuyi ZHANG ; Jiaojie XUE ; Zhichong CHEN ; Shiyao CHENG ; Weijie ZENG ; Mao OUYANG
Journal of Sun Yat-sen University(Medical Sciences) 2026;47(4):594-600
ObjectiveTo investigate the association between perioperative troponin elevation and the occurrence of major adverse cardiac events (MACE) in elderly patients with colorectal cancer, and to provide evidence for optimizing perioperative management strategies. MethodsA total of 268 elderly patients aged 70 years and above who underwent colorectal cancer surgery were retrospectively enrolled. They were divided into a conventional management group (87 cases) and a standardized management group (181 cases) according to the perioperative management strategy. Binary logistic regression analysis was used to identify the independent influencing factors for the occurrence of major adverse cardiac events. P-value ≤ 0.05 was considered statistically significant. ResultsAmong the 268 patients, the overall incidence of perioperative major adverse cardiac events was 4.5% (12/268). The total incidence of major adverse cardiac events in the conventional management group was 8.0% (7/87), which was significantly higher than that in the standardized management group (2.8%, 5/181;P=0.05). Specifically, the incidences of myocardial infarction, heart failure, and death in the conventional management group were markedly higher than those in the standardized management group (8.0% vs. 2.2%, 4.6% vs. 0.6%, 4.6% vs. 0.6%, all P<0.05), while no significant difference was observed in the incidence of cardiogenic shock between the two groups (1.1% vs. 1.1%, P>0.05). Postoperative troponin elevation was significantly associated with the occurrence of perioperative major adverse cardiac events except for cardiogenic shock (including total cardiovascular events, myocardial infarction, heart failure, and death) (all P<0.05), and it was identified as a strong independent risk factor for perioperative major adverse cardiac events in these patients. ConclusionCompared with conventional management, standardized perioperative troponin management can significantly reduce the risks of myocardial infarction, heart failure, and death, and also exhibits a potential protective trend against cardiogenic shock. Postoperative troponin elevation is a strong independent risk factor for the occurrence of perioperative major adverse cardiac events.
6.Repurposing drugs for the human dopamine transporter through WHALES descriptors-based virtual screening and bioactivity evaluation
Ding LUO ; Zhou SHA ; Junli MAO ; Jialing LIU ; Yue ZHOU ; Haibo WU ; Weiwei XUE
Journal of Pharmaceutical Analysis 2025;15(8):1916-1925
Computational approaches,encompassing both physics-based and machine learning(ML)methodolo-gies,have gained substantial traction in drug repurposing efforts targeting specific therapeutic entities.The human dopamine(DA)transporter(hDAT)is the primary therapeutic target of numerous psychi-atric medications.However,traditional hDAT-targeting drugs,which interact with the primary binding site,encounter significant limitations,including addictive potential and stimulant effects.In this study,we propose an integrated workflow combining virtual screening based on weighted holistic atom localization and entity shape(WHALES)descriptors with in vitro experimental validation to repurpose novel hDAT-targeting drugs.Initially,WHALES descriptors facilitated a similarity search,employing four benztropine-like atypical inhibitors known to bind hDAT's allosteric site as templates.Consequently,from a compound library of 4,921 marketed and clinically tested drugs,we identified 27 candidate atypical inhibitors.Subsequently,ADMETlab was employed to predict the pharmacokinetic and toxi-cological properties of these candidates,while induced-fit docking(IFD)was performed to estimate their binding affinities.Six compounds were selected for in vitro assessments of neurotransmitter re-uptake inhibitory activities.Among these,three exhibited significant inhibitory potency,with half maximal inhibitory concentration(IC50)values of 0.753 μM,0.542 μM,and 1.210 μM,respectively.Finally,molecular dynamics(MD)simulations and end-point binding free energy analyses were con-ducted to elucidate and confirm the inhibitory mechanisms of the repurposed drugs against hDAT in its inward-open conformation.In conclusion,our study not only identifies promising active compounds as potential atypical inhibitors for novel therapeutic drug development targeting hDAT but also validates the effectiveness of our integrated computational and experimental workflow for drug repurposing.
7.Application of Micro-lecture Combined with Workshop Education Mode in Home Chinese Medicine Retention Enema for Pa-tients with Ulcerative Colitis
Xue YING ; Xue ZHANG ; Junyan MAO
Journal of Zhejiang Chinese Medical University 2025;49(6):775-781
[Objective]To investigate the application effect of micro-lecture combined with workshop education mode in home Chinese medicine retention enema for patients with ulcerative colitis(UC).[Methods]Eighty patients with UC who needed home Chinese medicine retention enema of Compound Qingdai Enema in Zhejiang Provincial Hospital of Chinese Medicine from June 2022 to June 2024 were selected and randomly divided into control group and experimental group,40 cases in each group.Control group received the routine health education,while experimental group received micro-lecture combined with workshop education mode.The scores of Chinese medicine retention enema and satisfaction with nursing were evaluated in the two groups within 1 day after intervention.The clinical intestinal symptoms,quality of life,anxiety and depression scores of patients were evaluated before intervention and 6 months after intervention.[Results]After the intervention of micro-lecture combined with workshop mode,the theoretical score of Chinese medicine retention enema in experimental group was(98.35±0.80),the operational score was(92.48±3.86),the nursing satisfaction score was(96.93±1.70),the quality of life score was(176.11±21.11),the anxiety score was(34.56±5.69),and the depression score was(33.41±5.69).In control group,the theoretical score was(92.02±2.01),the operational score was(80.05±3.07),the nursing satisfaction score was(92.40±2.12),the quality of life score was(161.29±20.56),the anxiety score was(42.31±5.33),and the depression score was(41.63±5.12).The scores of theoretical and operational assessment,nursing satisfaction,each item of clinical intestinal symptoms,quality of life,anxiety and depression in experimental group were significantly higher than those in control group(P<0.05).[Conclusion]Compared with conventional health education,the micro-lecture combined workshop education mode can improve the cognition and operation level of home Chinese medicine retention enema in patients with UC,reduce the anxiety and depression levels of patients,promote the relief of clinical intestinal symptoms,improve quality of life and nursing satisfaction.
8.The reduction of reproductive function of male zebrafish caused by high-fat diet:A molecular basis study
Zhenghong DU ; Fei MAO ; Xue ZHAO ; Shuo WANG ; Yongjun WAN ; Chengyu ZHANG ; Peng DUAN ; Dahu ZHANG
National Journal of Andrology 2025;31(11):963-971
Objective To investigate the effects and mechanisms of high-fat diet(HFD)-induced obesity on male ze-brafish reproductive function.Methods Adult male zebrafish were divided into normal diet(ND)group and HFD group.Growth and metabolic conditions were evaluated by measuring body weight,body length,BMI,organ index,and glucose/lipid lev-els.Reproductive capacity was assessed via sperm concentration,motility,fertilization rate,and testosterone levels.Testicular tissues from both of groups were subjected to transeriptomic sequencing(RNA-seq).And qRT-PCR was used to validate the expression of genes.Results Compared to male zebrafish in ND group,the ones in HFD group exhibited hepatic steatosis and glucose/lipid meta-bolic disorders(P<0.05).Testicular structural disorganization,along with reduced testosterone levels,decreased gonadosomatic in-dex,and impaired sperm concentration and motility occurred in HFD group(P<0.05).GO analysis revealed that differentially ex-pressed genes were enriched in spermatogenesis and ciliary system,while KEGG analysis highlighted metabolic related pathways(pu-rine metabolism,thyroid hormone synthesis,mTOR signaling)and cell adhesion molecules.Twenty key differentially expressed genes were validated by qRT-PCR,which confirmed the reliability of RNA-Seq results.Conclusion Impairment of reproductive function induced by HFD in zebrafish may be associated with three regulatory mechanisms including ciliary system,metabolic dysregulation,and aberrant cell adhesion molecule signaling.This study provides mechanistic insights and identifies potential therapeutic targets for clinical management of diet-associated infertility.
9.Clinical study of Hewei Jiangni Formula in patients with non-erosive gastroesophageal reflux disease and cold-heat complex syndrome
Shuangyuan ZHANG ; Hanqing CHEN ; Junxiang LI ; Tangyou MAO ; Lei SHI ; Zhengdao LIN ; Chuchu XUE ; Xiaohong LI
Journal of Beijing University of Traditional Chinese Medicine 2025;48(8):1107-1114
Objective To observe and analyze the clinical efficacy of Hewei Jiangni Formula in treating patients with non-erosive gastroesophageal reflux disease(NERD)and cold-heat complex syndrome and explore its regulatory mechanism on visceral hypersensitivity.Methods Sixty patients with NERD and cold-heat complex syndrome diagnosed at the Gastroenterology Clinic of Dongfang Hospital,Beijing University of Chinese Medicine from January 2021 to Decemer 2023,were randomly divided into the Hewei Jiangni Formula group and omeprazole group,with 30 patients per group.The Hewei Jiangni Formula group was treated with Hewei Jiangni Formula and omeprazole enteric-coated tablets placebo,whereas the omeprazole group was treated with omeprazole enteric-coated tablets and Hewei Jiangni Formula placebo.The treatment period was scheduled to last for 8 weeks.The primary outcome indicators(Gastroesophageal Reflux Disease Quality of Life Questionnaire(GERD-Q)scale score:response rate,total score,and single symptom score)and secondary outcome indicators(traditional Chinese medicine clinical scores scale)were recorded before and after treatment in both groups.Ten healthy individuals were recruited from the Physical Examination Center of Dongfang Hospital,Beijing University of Chinese Medicine,as the healthy control group.The expression levels of mast cell tryptase(MCT),protease-activated receptor 2(PAR2),transient receptor potential vanilloid 1(TRPV1),substance P(SP),calcitonin gene-related peptide(CGRP),5-hydroxytryptamine(5-HT),and 5-hydroxytryptamine 3 receptor(5-HT3R)were recorded.These indicators were then used for the following comparisons:the NERD patients vs.the healthy group before treatment;the Hewei Jiangni Formula group vs.the omeprazole group after treatment;the intra-group comparisons within both NERD groups.Changes in serum levels of these indicators were observed before and after treatment in both NERD groups.Results According to the GERD-Q scores before and after treatment,the effective rate was 90.00%in the Hewei Jiangni Formula group and 86.67%in the omeprazole group,with no significant differences.Both groups exhibited improved symptoms of heartburn,regurgitation,upper abdominal pain,and sleep disorders caused by heartburn or regurgitation(P<0.05);however,neither group exhibited significantly improved nausea(P>0.05).Before treatment,MCT,PAR2,TRPV1,SP,CGRP,5-HT,and 5-HT3R expression levels in both NERD groups were significantly higher than those in the healthy control group(P<0.05).After treatment with Hewei Jiangni Formula or omeprazole enteric-coated tablets,the expression levels of these indicators decreased in both groups(P<0.05).The omeprazole group was superior to Hewei Jiangni Formula in reducing 5-HT3R expression(P<0.05).Conclusion Hewei Jiangni Formula significantly improves the symptoms of patients with NERD and cold-heat complex syndrome,with efficacy comparable to that of omeprazole enteric-coated tablets.It is superior to omeprazole in improving symptoms of spleen yang deficiency,such as loss of appetite,fatigue,borborygmus with loose stools,and cold extremities.Hewei Jiangni Formula reduces MCT,PAR2,TRPV1,SP,CGRP,5-HT,and 5-HT3R expression levels,regulates related signaling pathways,and alleviates visceral hypersensitivity.
10.Research progress of γδ T cells in head and neck squamous cell carcinoma
Lu RUONAN ; Mao XINHUI ; Xue JIYAO ; Zheng YIJING ; Huang LIANG ; Dou YUTING ; Gui YUN ; Shi YI
Chinese Journal of Clinical Oncology 2025;52(4):193-197
Head and neck squamous cell carcinoma(HNSCC)is a highly prevalent malignancy with poor prognosis.Treatment strategies to date have achieved limited success in significantly improving overall survival rates.γδ T cells,a unique subset of immune cells in the tumor microenvironment,can link adaptive and innate immune functions.While γδ T cells can effectively recognize and eliminate HNSCC tumor cells,certain subsets of these cells can secrete interleukin-17,contributing to tumor progression.Nevertheless,due to their remarkable cyto-toxic activity,γδ T cells have been identified as promising candidates for antitumor immunotherapy.This article reviews the biological back-ground of γδ T cells,their role in tumor immunity in HNSCC,and recent advances in γδ T cell immunotherapy,aiming to provide new in-sights into HNSCC diagnosis and treatment.


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