1.Construction and analysis of a sepsis model of rat after liver transplantation
Zhiwei XU ; Shubin ZHANG ; Qian LIU ; Yi ZHANG ; Yiming HUANG ; Pusen WANG ; Lin ZHONG
Organ Transplantation 2026;17(3):432-443
Objective To establish a stable and reliable sepsis model of rat after liver transplantation (LT) for clinical translational research and analyze its characteristics. Methods The "two-sleeve method" was used to establish the in situ LT model of SD rats, and the sepsis model was constructed through cecal ligation and puncture (CLP) at 3 d after the operation. SD rats were randomly divided into 3 groups: sham operation group (Sham group), LT group, and LT + CLP group, with 6 rats in each group. The changes in body weight, rectal temperature and survival rate were compared, and the sepsis score was used for evaluation. The levels of blood biochemical indicators [alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea (Urea), creatinine (Cr), creatine kinase (CK), lactate dehydrogenase (LDH)] and inflammatory factors [interleukin (IL)-1β, IL-6, IL-10, tumor necrosis factor (TNF)-α] in each group were detected, and the pathological changes and cell apoptosis in different organs were observed. Results Compared with the Sham group, the body weight of the LT group and LT + CLP group decreased (all P<0.05). The rectal temperature of the LT + CLP group showed a continuous downward trend after the operation, the sepsis score increased sharply after the operation, and the survival rate dropped to 16.7%, and the differences between the Sham group, LT group and LT + CLP group were statistically significant (all P<0.05). The levels of ALT, AST, Urea, Cr, CK, LDH, and serum IL-1β, IL-6, IL-10 and TNF-α in the LT + CLP group were higher than those in the Sham group and LT group rats within 72 hours after the operation(all P<0.05). The pathological examination of the LT + CLP group showed severe tissue structure destruction, necrosis and infiltration of inflammatory cells in multiple organs, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining showed an increased level of cell apoptosis in multiple organs. Conclusions Using liver transplantation combined with CLP, a stable animal model of liver transplantation infection is successfully established, which exhibits a high mortality rate, significant multi-organ damage and intense inflammatory response, providing an ideal animal model for transplantation infection research.
2.Role of innate immune mechanisms triggered by mitochondrial DNA release in metabolic dysfunction-associated fatty liver disease and targeted intervention strategies
Yu ZHOU ; Kaiyang LI ; Mei YANG ; Qi ZHAO ; Yiming ZHAO ; Fei ZHANG ; Qian WANG
Journal of Clinical Hepatology 2026;42(8):1960-1966
Metabolic dysfunction-associated fatty liver disease (MAFLD) is the most prevalent chronic liver disease worldwide, with a complex pathogenesis. Mitochondria play a pivotal role in this disease process, and studies have confirmed that mitochondrial dysfunction can exacerbate metabolic disorders and induce innate immune imbalance, while mitochondrial DNA (mtDNA) is the core molecule mediating these two pathological effects. After the abnormal release of mtDNA, it can be recognized by intracellular pattern recognition receptors, which in turn triggers innate immune responses and causes tissue damage, forming a pathological pathway of “mtDNA release-immune activation-tissue damage”. Currently, there is a lack of systematic reviews summarizing the mechanism of action of this pathway in different stages of MAFLD and the intervention strategies targeting this pathway. This article systematically reviews the core molecular mechanism of this pathway, its pathological role in the development and progression of MAFLD, and the current intervention strategies targeting this mechanism, in order to provide a theoretical basis for analyzing the pathogenesis of MAFLD and developing novel therapeutic strategies.
3.Mechanism of Paeoniflorin Regulating TLR4/NF-κB-IRS1 Inflammation-insulin Signaling Axis to Improve Metabolic Dysfunction Associated Fatty Liver Disease Combined with Insulin Resistance
Luyu LI ; Yiming FAN ; Wenlong YU ; Yiteng ZHANG ; Yaorui HU ; Huanxin DING ; Chuxuan LIU ; Xin JIN ; Hongyu ZHANG ; Qian XU ; Guangyong ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(21):146-156
ObjectiveTo investigate the therapeutic effect of paeoniflorin on metabolic dysfunction-associated fatty liver disease (MASLD) combined with insulin resistance (IR), and to elucidate its regulatory mechanisms on the Toll-like receptor 4 (TLR4)/nuclear transcription factor (NF)-κB-insulin receptor substrate 1 (IRS1) inflammation-insulin signaling axis. MethodsMASLD mouse model was established using a 60% high-fat diet. Mice were randomly assigned to a normal control group, a MASLD model group, and paeoniflorin groups (low dose: 25 mg·kg-1·d-1, medium dose: 50 mg·kg-1·d-1, high dose: 100 mg·kg-1·d-1), receiving intragastric administration for consecutive 12 weeks. Concurrently, a palmitic acid/oleic acid (PA/OA)-induced lipid deposition model was established in HepG2 cells. Cell counting kit-8 (CCK-8) assay was performed to determine the optimal concentrations of PA/OA and paeoniflorin for intervention. Mice body weight, liver index, and serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglycerides (TG), and total cholesterol (TC) were measured. Fasting blood glucose (FBG) and fasting insulin (FINS) levels were measured, and the homeostatic model assessment of insulin resistance (HOMA-IR) was calculated, while an oral glucose tolerance test (OGTT) was performed to evaluate glucose metabolism. Hematoxylin and eosin (HE) staining was used to observe pathological changes and inflammatory cell infiltration in liver tissue, and oil red O staining was used to evaluate lipid droplet deposition in liver tissue and HepG2 cells. Potential targets were screened using network pharmacology and molecular docking. Western blot analysis was performed to detect the expression of HSP90AA1, TLR4, p-NF-κB p65, p-IRS1, and p-Akt proteins in liver tissue and HepG2 cells. ResultsCompared with the normal control group, mice in the MASLD model group exhibited significantly increased body weight, liver index, and serum levels of ALT, AST, TG, and TC, as well as markedly elevated FBG, FINS, and HOMA-IR, and impaired glucose tolerance (P<0.01). HE staining revealed marked hepatic steatosis and inflammatory cell infiltration, while oil red O staining showed a significant increase in lipid droplet deposition. Compared with the MASLD model group, after intervention with various doses of paeoniflorin, the increase in body weight and liver index was reduced, serum ALT, AST, TG, and TC levels decreased, and FBG, FINS, and HOMA-IR were significantly lowered, with glucose tolerance markedly improved (P<0.05, P<0.01), showing a certain dose-dependent trend. HE and oil red O staining results showed a marked reduction in hepatic steatosis and lipid deposition. In vitro experiments demonstrated that, compared with the control group, PA/OA treatment significantly induced increased lipid deposition in HepG2 cells. Compared with the model group, paeoniflorin intervention significantly reduced intracellular lipid droplets, and lipid deposition showed a dose-dependent decreasing trend. Mechanism studies indicated that, compared with the normal control group, the MASLD model group exhibited significantly elevated expression of TLR4, HSP90AA1, and p-NF-κB p65, while p-IRS1 (Ser307) expression was elevated and p-Akt (Ser473) expression was reduced (P<0.01). Compared with the model group, the expression of the aforementioned proteins was significantly reversed in all treatment groups following intervention (P<0.05, P<0.01). ConclusionPaeoniflorin significantly alleviates lipid deposition and insulin resistance in MASLD mice. Its mechanism of action may involve targeting HSP90AA1, TLR4, and NF-κB1 to regulate the TLR4/NF-κB-IRS1 inflammation-insulin signaling axis. This regulation suppresses inflammatory responses and restores insulin signaling, thereby ameliorating abnormalities in glucose and lipid metabolism.
4.Mechanism of Paeoniflorin Regulating TLR4/NF-κB-IRS1 Inflammation-insulin Signaling Axis to Improve Metabolic Dysfunction Associated Fatty Liver Disease Combined with Insulin Resistance
Luyu LI ; Yiming FAN ; Wenlong YU ; Yiteng ZHANG ; Yaorui HU ; Huanxin DING ; Chuxuan LIU ; Xin JIN ; Hongyu ZHANG ; Qian XU ; Guangyong ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(21):146-156
ObjectiveTo investigate the therapeutic effect of paeoniflorin on metabolic dysfunction-associated fatty liver disease (MASLD) combined with insulin resistance (IR), and to elucidate its regulatory mechanisms on the Toll-like receptor 4 (TLR4)/nuclear transcription factor (NF)-κB-insulin receptor substrate 1 (IRS1) inflammation-insulin signaling axis. MethodsMASLD mouse model was established using a 60% high-fat diet. Mice were randomly assigned to a normal control group, a MASLD model group, and paeoniflorin groups (low dose: 25 mg·kg-1·d-1, medium dose: 50 mg·kg-1·d-1, high dose: 100 mg·kg-1·d-1), receiving intragastric administration for consecutive 12 weeks. Concurrently, a palmitic acid/oleic acid (PA/OA)-induced lipid deposition model was established in HepG2 cells. Cell counting kit-8 (CCK-8) assay was performed to determine the optimal concentrations of PA/OA and paeoniflorin for intervention. Mice body weight, liver index, and serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglycerides (TG), and total cholesterol (TC) were measured. Fasting blood glucose (FBG) and fasting insulin (FINS) levels were measured, and the homeostatic model assessment of insulin resistance (HOMA-IR) was calculated, while an oral glucose tolerance test (OGTT) was performed to evaluate glucose metabolism. Hematoxylin and eosin (HE) staining was used to observe pathological changes and inflammatory cell infiltration in liver tissue, and oil red O staining was used to evaluate lipid droplet deposition in liver tissue and HepG2 cells. Potential targets were screened using network pharmacology and molecular docking. Western blot analysis was performed to detect the expression of HSP90AA1, TLR4, p-NF-κB p65, p-IRS1, and p-Akt proteins in liver tissue and HepG2 cells. ResultsCompared with the normal control group, mice in the MASLD model group exhibited significantly increased body weight, liver index, and serum levels of ALT, AST, TG, and TC, as well as markedly elevated FBG, FINS, and HOMA-IR, and impaired glucose tolerance (P<0.01). HE staining revealed marked hepatic steatosis and inflammatory cell infiltration, while oil red O staining showed a significant increase in lipid droplet deposition. Compared with the MASLD model group, after intervention with various doses of paeoniflorin, the increase in body weight and liver index was reduced, serum ALT, AST, TG, and TC levels decreased, and FBG, FINS, and HOMA-IR were significantly lowered, with glucose tolerance markedly improved (P<0.05, P<0.01), showing a certain dose-dependent trend. HE and oil red O staining results showed a marked reduction in hepatic steatosis and lipid deposition. In vitro experiments demonstrated that, compared with the control group, PA/OA treatment significantly induced increased lipid deposition in HepG2 cells. Compared with the model group, paeoniflorin intervention significantly reduced intracellular lipid droplets, and lipid deposition showed a dose-dependent decreasing trend. Mechanism studies indicated that, compared with the normal control group, the MASLD model group exhibited significantly elevated expression of TLR4, HSP90AA1, and p-NF-κB p65, while p-IRS1 (Ser307) expression was elevated and p-Akt (Ser473) expression was reduced (P<0.01). Compared with the model group, the expression of the aforementioned proteins was significantly reversed in all treatment groups following intervention (P<0.05, P<0.01). ConclusionPaeoniflorin significantly alleviates lipid deposition and insulin resistance in MASLD mice. Its mechanism of action may involve targeting HSP90AA1, TLR4, and NF-κB1 to regulate the TLR4/NF-κB-IRS1 inflammation-insulin signaling axis. This regulation suppresses inflammatory responses and restores insulin signaling, thereby ameliorating abnormalities in glucose and lipid metabolism.
5.Interpretation and Implementation Paths of Specification for Quality Control in Traditional Chinese Medicine Clinical Trials
Haoling ZHANG ; Yanling GAO ; Guanhua REN ; Panbo QIU ; Yiming WANG ; Qingna LI ; Zhenzhen QIAN ; Guoyuan ZHANG ; Xinyue DAI ; Leping WANG ; Rui GAO
Journal of Traditional Chinese Medicine 2026;67(20):2173-2178
Specification for Quality Control in Traditional Chinese Medicine Clinical Trials(GB/T 47336-2026) is the first national standard in the field of clinical research on traditional Chinese medicine (TCM), aims to address the core issue that the quality shortcomings of current TCM clinical research restrict the transformation of achievements and international recognition. Through the interpretation of the core contents of this standard, including its scope of application, graded quality control system, TCM-specific quality control requirements, implementation and responsible entities, responsibilities of quality control personnel, formulation of quality control plans, critical nodes of quality control, and quality control archive management, it is believed that the promotion and implementation of this standard are of great significance for improving the standard system of TCM clinical research, enhancing research quality, optimizing the quality management model, and promoting the internationalization process of TCM. Meanwhile, the implementation paths for the standard are discussed, including carrying out pilot applications in institutions, establishing publicity, implementation, and training mechanisms, encouraging multi-party collaborative supervision, and setting up implementation feedback mechanisms. On this basis, the challenges that may be encountered during implementation, such as resource input pressure, difficulties in implementing TCM-specific quality control, and a relative shortage of interdisciplinary composite talents, are sorted out, and corresponding strategies are proposed, which can provide references for relevant researchers and practitioners.
6.Development of Core Outcome Set for Clinical Research on Vitiligo Treated with Uyghur Medicine
Qian HUANG ; Xinfeng GUO ; Lihong YANG ; Genghang CHEN ; Wufuer TUERSON ; Yiming Maimaiti TURSUNTAI ; Abuduwayiti JULAITI ; Zhijian LI ; Shaonan LIU
Journal of Guangzhou University of Traditional Chinese Medicine 2025;42(10):2595-2602
Objective To develop a core outcome set(COS)for treatment of progressive vitiligo in Uyghur medicine,and to standardize the selection and reporting of outcome measures in relevant studies.Methods Based on the existing core outcome domain set of randomized controlled trials for vitiligo,additional outcome indicators reflecting the advantages and characteristics of Uyghur medical treatment were developed.Specific indicators for Uyghur medical treatment of progressive vitiligo were collected through literature review and semi-structured questionnaire surveys,and then a list of indicators were formed.The Delphi survey and consensus meetings were used to select core indicators.Results A total of 54 studies were included,and 86 questionnaires were collected.Through literature review and questionnaire surveys,a list of 28 indicators were obtained.After two rounds of Delphi survey and one consensus meeting,12 outcome indicators in 7 domains were finally determined,including vitiligo lesion area,repigmentation,disease control time,maintenance of repigmentation,recurrence rate,immune indicators,psychological health,patients' quality of life,adverse events,adverse reaction incidence,liver and kidney function monitoring,and Uyghur medicine syndrome differentiation of mucus.Additionally,some measurement tools for certain indicators were recommended.Conclusion The development of the COS for vitiligo treatment in Uyghur medicine helps to comprehensively evaluate the efficacy of Uyghur medicine,and will provide a model for establishing efficacy evaluation methods that conform to the characteristics of ethnic minority medicine.
7.Iatrogenic risks and countermeasures of smart healthcare for chronic diseases
Yiming HU ; Haotian WU ; Yang LIU ; Dong CHEN ; Yaqiang WANG ; Qian ZHOU ; Xueqing YANG ; Liling CHEN ; Xiangjun YIN ; Jing WU
Chinese Journal of Hospital Administration 2025;41(3):234-238
Smart healthcare plays an important role in easing the strain on medical resources and improving the continuity of chronic disease management. This study analysed the iatrogenic risks from the intrinsic attributes and the external environment of smart healthcare, including doctor-patient conflict risk, technical operation risk, information leakage risk, humanistic absence risk, legal risk, regulatory risk and ethical risk. Based on the " structure process result" model, suggestions were proposed to optimize the construction of a smart healthcare platform for chronic diseases, improve the legal system and industry standards, strengthen talent cultivation and capacity building, establish an integrated regulatory system, and regularly evaluate the effectiveness of chronic disease management. These suggestions provided references for creating a healthy, orderly, and safe smart healthcare environment for chronic disease patients.
8.Clinical efficacy of single-port laparoscopy combined with GnRH agonist in the treatment of deep infiltrating endometriosis and its influence on prognosis
Xiaoqian WANG ; Yuanyuan PENG ; Yiming ZHANG ; Qingyun PAN ; Xiaoqian ZHANG ; Yan LI ; Qian LIU
China Journal of Endoscopy 2025;31(10):40-47
Objective To explore the clinical efficacy of single-port laparoscopy combined with gonado-tropin-releasing hormone agonist(GnRH agonist)in the treatment of deep infiltrating endometriosis and its influence on serum circATRNL1 levels,and analyze its predictive value for patient prognosis.Methods 220 patients with deep infiltrating endometriosis from June 2021 to October 2023 were enrolled as study subjects and divided into an experimental group(n=110)and a control group(n=110)according to different surgical methods.The experimental group received single-port laparoscopy surgery combined with GnRH agonist treatment,while the control group only received single-port laparoscopy surgery.The changes in circATRNL1 expression level before and after treatment between the two groups were compared,the short-term efficacy and long-term prognosis of the two groups were evaluated.Spearman correlation analysis was conducted to explore the relationship between circATRNL1 expression levels after treatment and long-term prognosis.All patients were regrouped based on whether they relapsed during follow-up into a relapse group(n=42)and a non-relapse group(n=178).The circATRNL1 levels before and after treatment were compared between the two groups,and the predictive value of circATRNL1 expression levels after treatment for long-term relapse after treatment in patients with endometriosis was analyzed using a receiver operating characteristic curve(ROC curve).Results After treatment,the serum circATRNL1 levels in the experimental group was significantly lower than that in the control group,the difference was statistically significant(P<0.05).The postoperative pain VAS score of the experimental group was significantly lower than that of the control group,and the quality of life was significantly better than that of the control group,the recurrence rate was significantly lower than that of the control group,and the differences were statistically significant(P<0.05).The pregnancy rate of the experimental group was higher than that of the control group,and the postoperative dysmenorrhea rate was lower than that of the control group,but the differences were not statistically significant(P>0.05).Spearman correlation analysis showed that circATRNL1 expression levels after treatment was positively correlated with relapse among long-term prognosis indicators(r=0.290,P<0.05),but had no significant correlation with pregnancy rate(r=0.060,P>0.05).Compared to patients in the non-relapse group,the relapse group had significantly higher serum circATRNL1 expression levels after treatment,the difference was statistically significant(P<0.05).ROC curve analysis showed that the area under the curve(AUC)for serum circATRNL1 expression levels in predicting long-term postoperative relapse in patients with endometriosis after treatment was 0.746,with a sensitivity of 64.29%and a specificity of 82.02%,indicating good predictive value.Conclusion The treatment regimen combining single-port laparoscopy with GnRH agonist can significantly reduce patients'pain levels,improve their quality of life,and decrease the recurrence rate.Furthermore,this combined therapy also notably decreases serum circATRNL1 levels.The serum circATRNL1 expression levels have good predictive value for the long-term recurrence of deep-infiltrating endometriosis patients post-surgery.
9.Effect of calumenin on metastasis and invasion of gastric cancer and prognosis of patients
Zhixiang REN ; Jiajia LIU ; Zhongyi QIN ; Junjie WANG ; Yiming ZHENG ; Bin WANG ; Feng QIAN
Journal of Army Medical University 2025;47(5):435-442
Objective To investigate the expression of calumenin(CALU)in gastric cancer and its effect on metastasis and invasion of gastric cancer,and analyze its relationship with the prognosis of gastric cancer patients.Methods The Cancer Genome Atlas(TCGA)database was used to analyze the expression level of CALU in gastric cancer and its impact on patient prognosis.A total of 102 pairs of gastric cancer and paracancerous tissue samples were collected from 189 gastric cancer patients who underwent partial gastrectomy in First Affiliated Hospital of Army Medical University from January 2018 to December 2022.The expression of CALU in gastric cancer and paracancerous tissues was detected by immunohistochemical assay,and the relationship of its expression with clinicopathological parameters was statistically analyzed.After gastric cancer cells with CALU knockdown and overexpression were constructed,and the efficiencies of knockdown and overexpression were evaluated by Western blotting as well as RT-qPCR.Transwell assay was applied to determine the effect of CALU on the migration and invasion abilities of gastric cancer cells.Results Bioinformation analysis found that CALU was significantly highly expressed in gastric cancer tissues(P<0.05),and its expression level was negatively correlated with the prognosis of patients(P<0.05).Immunohistochemical results showed that the expression level of CALU was obviously highly in gastric cancer tissues than the paracancerous tissues(P<0.01),and its level was positively correlated with the depth of infiltration(P<0.01),lymph node metastasis(P<0.01),and TNM stage(P<0.05).Statistical analysis revealed that the clinical data of 102 patients showed that CALU expression was positively correlated with the TNM stage(P=0.021)and T stage(P<0.001)and N stage(P=0.028).CALU knockdown significantly inhibited the migration and invasion abilities of gastric cancer cells(P<0.01),while over-expression obtained the opposite results.Conclusion CALU is highly expressed in gastric cancer tissues and promotes metastasis and invasion of gastric cancer and thus leads to poor prognosis in patients.
10.Over 20-year Follow-up Result of Total Knee Arthroplasty for Knee Arthropathy: A Single Center Cohort Study
Yiming XU ; Mingwei HU ; Wei ZHU ; Muyang YU ; Jin LIN ; Jin JIN ; Wenwei QIAN ; Bin FENG ; Xisheng WENG
Medical Journal of Peking Union Medical College Hospital 2025;16(1):35-41
To evaluate long-term survival and clinical outcomes of patients with knee osteo-arthritis undergoing total knee arthroplasty (TKA) through long-term follow-up. This study was based on a previous cohort study that had completed follow-up. We retrospectively collected clinical data of patients with knee arthropathy (including knee osteoarthritis and knee rheumatoid arthritis) who received the first TKA operation in Peking Union Medical College Hospital from 1993 to 2002 and were followed up for more than 20 years, and conducted a unified follow-up on them in November 10, 2024 (the last follow-up). Kaplan-Meier curve was used to evaluate the survival rate. Hospitals for special surgery (HSS) scores and joint range of motion (ROM) were compared before surgery, 10 years after surgery and at the last follow-up to evaluate the clinical efficacy of TKA. Likert scale was used to evaluate patient satisfaction at the last follow-up. A total of 226 patients (246 knees) received their first TKA in Peking Union Medical College Hospital from 1993 to 2002 and were followed up for more than 10 years. Among them, 104 patients (131 knees) were included in the study at the last follow-up, including 21 patients (24 knees) with prosthesis in place, 18 patients (18 knees) who underwent reoperation for various reasons, and 65 patients (89 knees) who died from non-TKA surgical causes. Up to the last follow-up, there were 29 patients (35 knees) with an average follow-up of more than 20 years, and 12 patients (16 knees) completed HSS score, ROM measurement and patient satisfaction evaluation. Kaplan-Meier curve showed that the 10-year, 15-year, 20-year, and 25-year survival rates were 93.6%, 92.4%, 89.8%, and 71.8%, respectively. The HSS score at the last follow-up was lower than that at 10- year postoperative follow-up[(84.69±11.03) scores TKA treatment for knee arthropathy has high long-term prosthesis survival rate, significant improvement of knee joint function and high patient satisfaction.

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