1.Effect of Oral Sodium Butyrate on Skeletal Muscle Atrophy via The Gut-muscle Axis in Antibiotic-pretreated CT26 Tumor-bearing Mice and Its Mechanism
Shu-Ling ZHANG ; Jun-Wei WANG ; Shi-Liang HU ; Tu-Tu WANG ; Shun-Chang LI ; Jia FAN ; Jun-Zhi SUN
Progress in Biochemistry and Biophysics 2026;53(3):724-739
ObjectiveTo explore the effect of oral sodium butyrate on skeletal muscle atrophy in CT26 tumor mice through the gut microbiota-skeletal muscle axis and its potential mechanism. MethodsSixty SPF BALB/c male mice aged 8 weeks were randomly divided into a normal control group (NC, n=18) and a ABX-depleted group (ABX, n=42). The ABX mice were pretreated with a quadruple antibiotic cocktail via oral gavage (0.2 ml per administration, once daily, 6 d per week, for 2 weeks), whereas NC received an equal volume of sterile water. The quadruple antibiotic cocktail consisted of metronidazole (1 g/L), vancomycin (0.5 g/L), ampicillin (1 g/L), and gentamicin (1 g/L). Following successful pretreatment, six mice from each group were randomly selected for gut microbiota sequencing analysis and designated as the Abx group and the NC0 group, respectively. Theremaining mice in ABX were subcutaneously inoculated in the dorsum with 0.2 ml of CT26 cell suspension (at a cell density of 1×107/ml). Then these mice were randomly allocated into three subgroups: a control tumor bearing model group (0_NaB, n=12), a tumor-bearing model group receiving low-dose oral sodium butyrate (L_NaB, n=12), a tumor-bearing model group receiving high-dose oral sodium butyrate (H_NaB, n=12). And mice in NC were inoculated at the same site with 0.2 ml of normal saline. The administration dose for L_NaB was 0.3 g/(kg·d), that for H_NaB was 0.5 g/(kg·d), while NC and 0_NaB were given the same volume of normal saline (0.2ml per time, once daily, 6 d per week, for 4 weeks). The general condition of mice was monitored, and forelimb grip strength gastrocnemius muscle mass and its muscle fiber cross-sectional area were measured for each group. The structural changes in gut microbiota were assessed by 16S rRNA sequencing of cecal contents. Pathological alterations in the intestinal wall were examined via HE staining. Serum and gastrocnemius muscle levels of TNF‑α, IL-6, IL-1β, and LPS were quantified using ELISA. The protein expression of ZO-1 and occludin in the small intestine, as well as proteins associated with the TLR4/MyD88/NF-κB signaling pathway in the gastrocnemius muscle, were detected by Western blot analysis. Results(1) The alpha-diversity in Abx was significantly lower than that in NC0 (P<0.01), a significant decrease of the mass and muscle fiber cross-sectional area of the gastrocnemius (P<0.01), with the majority of gut microbiota being effectively depleted. (2) Compared with NC, the subcutaneous tumors of mice in 0_NaB were prominent, a significant increase of the mass and muscle fiber cross-sectional area of the gastrocnemius, accompanied by a significant decrease in body weight at the end of the 3th and 4th week (P<0.05), and a significant weakening of the forelimb grasping strength at the 5th and 6th week (P<0.01). Compared with 0_NaB, the tumor mass of mice in L_NaB and H_NaB showed a significant decreasing trend, and the grip strength of the forelimbs significantly increased at the 5th and 6th week (P<0.05, P<0.01). (3) Compared with 0_NaB, the Shannon and Observed species indices in α diversity of L_NaB and H_NaB were significantly increased (P<0.05). At the genus level, compared with 0_NaB, L_NaB exhibited a significant decrease in the relative abundance of Parasutterella (P< 0.01), while H_NaB showed significant reductions in the relative abundances of both Escherichia-Shigella and Parasutterella (P < 0.01). (4) Compared with 0_NaB, the small intestinal tissue structure in L_NaB and H_NaB was more intact, the infiltration of inflammatory cells was significantly reduced, and the capillaries were slightly dilated. The expression levels of ZO-1 and occludin proteins in L_NaB were significantly increased (P<0.01). (5) The LPS concentration in the gastrocnemius muscle and the protein expression levels of TLR4, MyD88, p-IκBα, and p-NF‑κB p65 in L_NaB and H_NaB were significantly lower than those in 0_NaB (P<0.05). The serum TNF‑α concentration in H_NaB and TNF-α concentration in the gastrocnemius muscle of the L_NaB and H_NaB were significantly lower than those in 0_NaB (P<0.05, P<0.01, P<0.01). ConclusionOral administration of NaB can improve gut microbiota α diversity, adjusting its composition, improving intestinal mucosal barrier function, reducing the LPS-induced pro-inflammatory response, and delaying skeletal muscle atrophy. The underlying mechanism may involve down regulation of TLR4/MyD88/NF-κB signaling in skeletal muscle.
2.Effect and mechanism of Wnt5a knockdown on the efficacy of M1 bone marrow-derived macrophage in treatment of liver cirrhosis
Feifei XING ; Danyang WANG ; Xinrui ZHENG ; Yannan XU ; Shihao ZHANG ; Junyi ZHAN ; Wei LIU ; Gaofeng CHEN ; Jiamei CHEN ; Ping LIU ; Yongping MU
Journal of Clinical Hepatology 2026;42(3):618-628
ObjectiveTo observe the effect of M1 bone marrow-derived macrophages (M1-BMDM) with Wnt5a knockdown on liver fibrosis and regeneration in a rat model of liver cirrhosis, and to investigate its gain-of-function effect compared with unmodified M1-BMDM. MethodsPrimary bone marrow-derived macrophages were isolated from rats and were polarized to M1 phenotype to construct M1-BMDMWnt5a-KD cells. A rat model of liver cirrhosis induced by CCl4/2-AAF was established, and at the end of week 8, rats were randomly divided into model group, M1-BMDM group, M1-BMDM Wnt5a-knockdown empty vector group (M1-BMDMKD-EV group), and M1-BMDM Wnt5a-knockdown group (M1-BMDMWnt5a-KD group), with 6 rats in each group. On the first day of week 9, the rats in each group were given a single injection of the corresponding cells via the caudal vein, along with an intraperitoneal injection of a CCR2 inhibitor. Six rats without any treatment were used as normal control group. Samples were collected at the end of week 12 to assess liver histopathology, serum liver function parameters, hepatic stellate cell activation, and the expression levels of mature hepatocyte markers. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the model group, all cell treatment groups had significant alleviation of liver inflammatory response and significant reductions in the activities of alanine aminotransferase and aspartate aminotransferase (AST) in serum (all P<0.01), and the M1-BMDMWnt5a-KD group had a significantly lower serum level of AST than the M1-BMDM group (P<0.05). The semi-quantitative analysis based on immunohistochemical staining showed that compared with the model group, all cell treatment groups had a significant reduction in the percentage of CD68-positive area (all P<0.05), and compared with the M1-BMDMKD-EV group, the M1-BMDMWnt5a-KD group had a significant reduction in the percentage of CD68-positive area and a significant increase in the percentage of CD163-positive area (both P<0.05). Compared with the model group, all cell treatment groups had significant reductions in the mRNA expression levels of CD68 and tumor necrosis factor-α (all P<0.05) and the protein expression level of CD68 (all P<0.01); compared with the M1-BMDMKD-EV group, the M1-BMDMWnt5a-KD group had significant increases in the protein and mRNA expression levels of CD163 (both P<0.05), significant reductions in the protein and mRNA expression levels of CD68 (both P<0.05), and a significant reduction in the protein expression level of tumor necrosis factor-α (P<0.01). Sirius Red collagen staining and alpha-smooth muscle actin (α-SMA) immunohistochemical staining showed that compared with the model group, all cell treatment groups had significant alleviation of liver collagen deposition and α-SMA-positive area, with the most significant changes in the M1-BMDMWnt5a-KD group, and compared with the M1-BMDMKD-EV group, the M1-BMDMWnt5a-KD group had significantly smaller Sirius Red-positive area and α-SMA-positive area and a significantly lower content of hydroxyproline in liver tissue (all P<0.05). Compared with the M1-BMDMKD-EV group, the M1-BMDMWnt5a-KD group had significant reductions in the protein and mRNA expression levels of α-SMA and the mRNA expression level of COL-I and TGF-β (all P<0.05). Compared with the model group, all cell treatment groups had a significant increase in the protein expression level of HNF-4α in liver tissue (all P<0.05), and the M1-BMDMWnt5a-KD group had significantly higher protein and mRNA expression levels of HNF-4α and hepatocyte specific antigen than the M1-BMDMKD-EV group (both P<0.05). The M1-BMDMWnt5a-KD group had a significantly higher serum level of albumin than the M1-BMDMKD-EV group (P<0.01). Immunofluorescence co-staining showed that compared with the model group, all cell treatment groups had a significant increase in the number of cells stained positive for HNF and HNF-4α and Ki67 (all P<0.01), and the M1-BMDMWnt5a-KD group had a significantly higher number of such cells than the M1-BMDMKD-EV group (P<0.05). ConclusionInhibition of Wnt5a expression enhances the therapeutic effect of M1-BMDM on rats with liver cirrhosis induced by CCl4/2-AAF, which provides new ideas for enhancing the anti-cirrhotic effect of M1-BMDM through genetic modification.
3.Challenges and Recommendations for Implementing Key Technologies in Decentralized Clinical Trials of Traditional Chinese Medicine
Runze WANG ; Xuehan WEI ; Xiaoying CHEN ; Yingqian ZHANG ; Jin SUN ; Chunli LU
Journal of Traditional Chinese Medicine 2026;67(9):926-934
Traditional Chinese medicine (TCM) clinical trials face challenges such as low participant compliance, insufficient geographical coverage, and cost-effectiveness imbalances. Decentralized clinical trials (DCT), enabled by digital technology for remote data collection and monitoring, offer a new direction for TCM clinical trial research. This article systematically reviews three novel clinical trial design models. Combining the holistic concept and indivi-dualized treatment characteristics of TCM, it analyzes the challenges currently faced in TCM DCT practice, including the digitization and standardization of TCM theory, data security, privacy protection and patient engagement difficu-lties, insufficient ethical review and regulatory system adaptation, inadequate personnel training, and a shortage of interdisciplinary talent. Addressing these challenges, the article proposes methodological recommendations for DCT implementation that align with the principles of TCM diagnosis and treatment. These recommendations include promoting the intelligentization and standardization of TCM practices, constructing a full-chain data security and privacy protection system, improving the ethical framework and clarifying regulatory responsibilities, and cultivating and building interdisciplinary talent and capabilities, which provide theoretical and technical references for establishing standardized DCT practices in TCM.
4.Exploration on the Connotation and Application of the Three Aspects of "Dietary Inquiry" for "Appetite" "Eating Capacity" "Food Preference"
Chengxiang WANG ; Chen YANG ; Xueping ZHANG ; Xinxin HU ; Wei WEI ; Xiaolan SU
Journal of Traditional Chinese Medicine 2026;67(9):1017-1022
"Dietary inquiry" is a core component of the diagnostic system in traditional Chinese medicine (TCM), which can be divided into three aspects including appetite, eating capacity, and food preference. Abnormalities in appetite are mainly attributed to dysfunction of the mind and impaired regulatory mechanisms. Clinical inquiry should focus on hunger sensation and the willingness to eat voluntarily. Treatment should aim to soothe the liver, regulate the spleen, nourish and calm the mind. Abnormalities in eating capacity are related to disorders of qi movement and structural dysfunction, for which inquiry should focus on whether food descends smoothly and on postprandial reactions, and the corresponding treatment is descending qi, relieving fullness, and promoting bowel movement and digestion. Abnormalities in food preference arise from damage caused by the five flavors and imbalance of visceral qi, for which inquiry should focus on dietary preferences and whether eating brings comfort. It is important to distinguish between "stomach preference" and "oral preference", and treatment should carefully differentiate flavor tendencies and correct imbalances through appropriate dietary flavors. By refining the content of dietary inquiry, this study explores how different dimensions of eating status reflect the holistic concept and syndrome differentiation-based treatment in TCM, providing a reference for the clinical diagnosis and treatment of spleen and stomach diseases and related disorders.
5.Single-center analysis of unplanned reoperation case after liver transplantation
Zhi CHEN ; Qingqing DAI ; Fan HUANG ; Guobin WANG ; Xiaojun YU ; Ruolin WU ; Liujin HOU ; Zhenghui YE ; Xinghua ZHANG ; Wei WANG ; Xiaoping GENG ; Hongchuan ZHAO
Organ Transplantation 2026;17(3):452-459
Objective To analyze the main causes and risk factors of unplanned reoperation after liver transplantation. Methods The clinical data of 242 liver transplant recipients in the First Affiliated Hospital of Anhui Medical University from January 2015 to December 2024 were retrospectively analyzed. According to whether unplanned reoperation was performed during the same hospitalization after surgery, the recipients were divided into the reoperation group (n=36) and the non-reoperation group (n=206). The preoperative, intraoperative and postoperative data of the two groups, as well as donor and graft-related data, were compared to analyze the risk factors of unplanned reoperation after liver transplantation and the survival status of the two groups. Results Among the 242 liver transplant recipients, 36 underwent unplanned reoperations, with a total of 54 procedures including various laparotomies, endoscopic and interventional surgeries, among which there were 20 laparotomies, 18 endoscopic surgeries and 16 interventional surgeries. The most common cause of unplanned reoperation was biliary complications (20 times), followed by vascular complications (17 times). Compared with the non-reoperation group, the reoperation group had longer graft cold ischemia time, higher postoperative fatality rate of recipients, longer length of stay in the intensive care unit and postoperative hospital stay, and higher total hospitalization costs (all P<0.05). The incidence of unplanned reoperation was higher in recipients who underwent split liver transplantation (P<0.05). Multivariate analysis showed that intraoperative blood loss ≥1 000 mL, positive culture of graft perfusate and split liver transplantation were independent risk factors for unplanned reoperation (all P<0.05). The postoperative 7-day, 1-month, 3-month and 6-month survival rates of recipients in the reoperation group and the non-reoperation group were 100% vs. 98.1%, 88.9% vs. 94.2%, 69.4% vs. 90.8% and 66.7% vs. 90.8%, respectively, and the postoperative survival rate of recipients in the reoperation group was lower than that in the non-reoperation group (P<0.05). Conclusions The main causes of unplanned reoperation after liver transplantation are biliary complications, vascular complications, abdominal incision infection and intra-abdominal hemorrhage. Intraoperative massive blood loss, positive culture of graft perfusate and split liver transplantation are the risk factors associated with unplanned reoperation after liver transplantation.
6.Challenges and Recommendations for Implementing Key Technologies in Decentralized Clinical Trials of Traditional Chinese Medicine
Runze WANG ; Xuehan WEI ; Xiaoying CHEN ; Yingqian ZHANG ; Jin SUN ; Chunli LU
Journal of Traditional Chinese Medicine 2026;67(9):926-934
Traditional Chinese medicine (TCM) clinical trials face challenges such as low participant compliance, insufficient geographical coverage, and cost-effectiveness imbalances. Decentralized clinical trials (DCT), enabled by digital technology for remote data collection and monitoring, offer a new direction for TCM clinical trial research. This article systematically reviews three novel clinical trial design models. Combining the holistic concept and indivi-dualized treatment characteristics of TCM, it analyzes the challenges currently faced in TCM DCT practice, including the digitization and standardization of TCM theory, data security, privacy protection and patient engagement difficu-lties, insufficient ethical review and regulatory system adaptation, inadequate personnel training, and a shortage of interdisciplinary talent. Addressing these challenges, the article proposes methodological recommendations for DCT implementation that align with the principles of TCM diagnosis and treatment. These recommendations include promoting the intelligentization and standardization of TCM practices, constructing a full-chain data security and privacy protection system, improving the ethical framework and clarifying regulatory responsibilities, and cultivating and building interdisciplinary talent and capabilities, which provide theoretical and technical references for establishing standardized DCT practices in TCM.
7.Exploration on the Connotation and Application of the Three Aspects of "Dietary Inquiry" for "Appetite" "Eating Capacity" "Food Preference"
Chengxiang WANG ; Chen YANG ; Xueping ZHANG ; Xinxin HU ; Wei WEI ; Xiaolan SU
Journal of Traditional Chinese Medicine 2026;67(9):1017-1022
"Dietary inquiry" is a core component of the diagnostic system in traditional Chinese medicine (TCM), which can be divided into three aspects including appetite, eating capacity, and food preference. Abnormalities in appetite are mainly attributed to dysfunction of the mind and impaired regulatory mechanisms. Clinical inquiry should focus on hunger sensation and the willingness to eat voluntarily. Treatment should aim to soothe the liver, regulate the spleen, nourish and calm the mind. Abnormalities in eating capacity are related to disorders of qi movement and structural dysfunction, for which inquiry should focus on whether food descends smoothly and on postprandial reactions, and the corresponding treatment is descending qi, relieving fullness, and promoting bowel movement and digestion. Abnormalities in food preference arise from damage caused by the five flavors and imbalance of visceral qi, for which inquiry should focus on dietary preferences and whether eating brings comfort. It is important to distinguish between "stomach preference" and "oral preference", and treatment should carefully differentiate flavor tendencies and correct imbalances through appropriate dietary flavors. By refining the content of dietary inquiry, this study explores how different dimensions of eating status reflect the holistic concept and syndrome differentiation-based treatment in TCM, providing a reference for the clinical diagnosis and treatment of spleen and stomach diseases and related disorders.
8.Research progress on the prevention and treatment of drug-induced myocardial injury related to anti-tumor therapy with Chinese traditional medicine
Yanan GU ; Guoping LI ; Wei ZHANG ; Dingfang CAI ; Xiaolin WANG
Chinese Journal of Clinical Medicine 2026;33(2):330-338
With the widespread application of chemotherapy, immunotherapy, and targeted therapy, cardiotoxicity associated with anti-tumor treatment has gained increasing attention. Drug-induced cardiac injury can significantly impact patients’ quality of life and may even limit the overall efficacy of anti-tumor therapy. The underlying mechanisms include oxidative stress, inflammatory responses, mitochondrial dysfunction, apoptosis, and immune dysregulation. Owing to multitarget effects, low toxicity, and holistic regulatory properties, Chinese traditional medicines have demonstrated considerable potential in cardioprotection. This review summarizes the principal mechanisms of drug-induced myocardial injury related to anti-tumor therapy and highlights recent advances in the prevention and treatment of cardiotoxicity using Chinese medical formulae, such as compound danshen dripping pills, nuanxinkang, qili qiangxin capsules, and shengmai powder, as well as their bioactive constituents. The cardioprotective effects of these agents are discussed in terms of their antioxidative, anti-inflammatory, immunomodulatory, and mitochondrial-protective actions. Furthermore, it highlights certain traditional medicines that exhibit unique advantages in synergistic cardioprotective and anti-tumor therapy. Future efforts should focus on well-designed, systematic clinical studies to facilitate the translational application of integrated Chinese and Western medicine in cardio-oncology.
9.Long-term survival outcomes and prognostic factors following radical resection of pancreatic body and tail cancer:a retrospective analysis of 992 patients
Dong XU ; Yang WU ; Kai ZHANG ; Nan LYU ; Qianqian WANG ; Pengfei WU ; Jie YIN ; Baobao CAI ; Guodong SHI ; Jianzhen LIN ; Yazhou WANG ; Lingdi YIN ; Zipeng LU ; Min TU ; Jianmin CHEN ; Feng GUO ; Jishu WEI ; Junli WU ; Wentao GAO ; Cuncai DAI ; Yi MIAO ; Kuirong JIANG
Chinese Journal of Surgery 2026;64(1):46-54
Objective:To investigate the survival outcomes and prognostic factors in patients undergoing radical resection for pancreatic body and tail cancer.Methods:A retrospective case series study was conducted on 992 patients who underwent radical resection for pancreatic body and tail cancer at the Pancreatic Center of the First Affiliated Hospital of Nanjing Medical University from January 2016 to June 2024. In this study, 577 (58.2%) were male and 415 (41.8%) were female,with an age of (65±9) years (range: 26 to 86 years). Follow-up continued until June 2024. Survival rates were estimated using the Kaplan-Meier method,and prognostic factors were identified using univariate and multivariate Cox proportional hazards models.Results:Among 992 patients,open surgery was the predominant approach (89.1%, 884/992), and radical antegrade modular pancreatosplenectomy (RAMPS) was performed in 317 patients (32.0%). Combined organ resection,venous resection,and arterial resection were performed in 23.5%, 9.3%,and 11.2% of patients,respectively. The rates of R0, R1-1 mm, and R1-direct resections were 49.8% (494/992),41.5% (412/992), and 8.7% (86/992),respectively. Stage ⅡB was the most common TNM stage (32.2%,319/992). A total of 801 patients (80.8%) received adjuvant chemotherapy. The median follow-up period was 32.0(8.8) months(range:3.2 to 105.3 months),during which 508 patients (51.2%) died. The overall median survival (OS) was 26.4 months,with 1-,3-, and 5-year survival rates of 79.0%,40.0%, and 29.0%, respectively. In the recent five years (from 2020 to 2024), the median OS improved significantly to 34.1 months compared to 20.0 months from 2016 to 2019 ( P<0.01). Histological subtype analysis showed that the median OS time was 26.7 months for pancreatic ductal adenocarcinoma (PDAC, n=855),58.9 months for invasive intraductal papillary mucinous carcinoma (IPMC, n=32),and 15.7 months for adenosquamous carcinoma of pancreas (ASCP, n=73) ( P=0.001). Among PDAC patients, adjuvant chemotherapy significantly improved survival (29.1 months vs. 14.4 months, P<0.01);in IPMC patients, adjuvant chemotherapy also extended survival (65.7 months vs. 58.9 months, P=0.047). Although ASCP patients receiving chemotherapy had a longer median OS time than those without (18.8 months vs. 8.9 months),the difference was not statistically significant ( P=0.151). Multivariate Cox regression analysis in PDAC patients indicated that adjuvant chemotherapy, R0 resection, T stage,N stage,and tumor differentiation were independent prognostic factors ( P<0.01). The median OS time by TNM stage was:not reached for stage ⅠA, 51.6 months for ⅠB, 25.5 months for ⅡA, 23.7 months for ⅡB, 23.0 months for Ⅲ, and 14.4 months for Ⅳ. The median OS time for R0,R1-1 mm,and R1-direct resections was 34.1,24.7,and 15.7 months,respectively ( P<0.01). Conclusion:Adjuvant chemotherapy,R0 resection,tumor stage,and differentiation are independent prognostic factors for pancreatic body and tail cancer.
10.Molecular Mechanisms of Salvia Miltiorrhiza and Its Active Ingredients against Colorectal Cancer: A Review
Jianing GUO ; Xiaochen NI ; Kaiyuan ZHANG ; Wei FAN ; Chuhang WANG ; Chao XU ; Jianbo HUANG ; Tao JIANG ; Guangji ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(4):307-314
Colorectal cancer (CRC) is one of the most common cancers, with its incidence ranking high among cancers. It stands as the second leading cause of cancer-related death worldwide. In the early stages, CRC lacks specific symptoms, and most patients are diagnosed at advanced stages, making it a major research focus in the field of gastrointestinal tumors. Currently, clinical CRC treatments face several common challenges, including high surgical risks, frequent metastasis and recurrence, drug resistance, and significant side effects from chemotherapy and radiation therapy. With the development and application of traditional Chinese medicine (TCM), it has been found that TCM and its active ingredients can effectively inhibit CRC cell proliferation, invasion, migration, and angiogenesis, and promote apoptosis and autophagy, thereby slowing the progression of CRC. This has become a key focus of CRC treatment research. Salvia Miltiorrhiza has multiple pharmacological effects, including activating blood circulation to dispel blood stasis, unlocking meridians to relieve pain, clearing heat to calm irritability, and cooling blood to reduce abscesses. It contains a variety of chemical components, including diterpenoids, phenolic acids, flavonoids, polysaccharides, nitrogen-containing compounds, steroids, and lactone compounds. This review summarized the molecular mechanisms of Salvia miltiorrhiza and its active ingredients in the treatment of CRC. It is found that these ingredients exert anti-CRC effects through various molecular mechanisms, including cell cycle arrest, promotion of apoptosis, inhibition of cell invasion and migration, induction of autophagy, suppression of tumor angiogenesis, and remodeling of the tumor microenvironment. The review aims to provide new insights for the drug development and clinical application of Salvia miltiorrhiza in CRC treatment.

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