This study investigated the effects and underlying mechanisms of vanillic acid(VA) against cardiac fibrosis(CF) induced by isoproterenol(ISO) in mice. Male C57BL/6J mice were randomly divided into control group, VA group(100 mg·kg~(-1), ig), ISO group(10 mg·kg~(-1), sc), ISO + VA group(10 mg·kg~(-1), sc + 100 mg·kg~(-1), ig), ISO + dynamin-related protein 1(Drp1) inhibitor(Mdivi-1) group(10 mg·kg~(-1), sc + 50 mg·kg~(-1), ip), and ISO + VA + Mdivi-1 group(10 mg·kg~(-1), sc + 100 mg·kg~(-1), ig + 50 mg·kg~(-1), ip). The treatment groups received the corresponding medications once daily for 14 consecutive days. On the day after the last administration, cardiac functions were evaluated, and serum and cardiac tissue samples were collected. These samples were analyzed for serum aspartate aminotransferase(AST), lactate dehydrogenase(LDH), creatine kinase-MB(CK-MB), cardiac troponin I(cTnI), reactive oxygen species(ROS), interleukin(IL)-1β, IL-4, IL-6, IL-10, IL-18, and tumor necrosis factor-α(TNF-α) levels, as well as cardiac tissue catalase(CAT), glutathione(GSH), malondialdehyde(MDA), myeloperoxidase(MPO), superoxide dismutase(SOD), total antioxidant capacity(T-AOC) activities, and cytochrome C levels in mitochondria and cytoplasm. Hematoxylin-eosin, Masson, uranium acetate and lead citrate staining were used to observe morphological and mitochondrial ultrastructural changes in the cardiac tissues, and myocardial injury area and collagen volume fraction were calculated. Flow cytometry was applied to detect the relative content and M1/M2 polarization of cardiac macrophages. The mRNA expression levels of macrophage polarization markers [CD86, CD206, arginase 1(Arg-1), inducible nitric oxide synthase(iNOS)], CF markers [type Ⅰ collagen(Coll Ⅰ), Coll Ⅲ, α-smooth muscle actin(α-SMA)], and cytokines(IL-1β, IL-4, IL-6, IL-10, IL-18, TNF-α) in cardiac tissues were determined by quantitative real-time PCR. Western blot was used to detect the protein expression levels of Coll Ⅰ, Coll Ⅲ, α-SMA, Drp1, p-Drp1, voltage-dependent anion channel(VDAC), hexokinase 1(HK1), NOD-like receptor protein 3(NLRP3), apoptosis-associated speck-like protein(ASC), caspase-1, cleaved-caspase-1, gasdermin D(GSDMD), cleaved N-terminal gasdermin D(GSDMD-N), IL-1β, IL-18, B-cell lymphoma-2(Bcl-2), B-cell lymphoma-xl(Bcl-xl), Bcl-2-associated death promoter(Bad), Bcl-2-associated X protein(Bax), apoptotic protease activating factor-1(Apaf-1), pro-caspase-3, cleaved-caspase-3, pro-caspase-9, cleaved-caspase-9, poly(ADP-ribose) polymerase-1(PARP-1), and cleaved-PARP-1 in cardiac tissues. The results showed that VA significantly improved cardiac function in mice with CF, reduced myocardial injury area and cardiac index, and decreased serum levels of AST, CK-MB, cTnI, LDH, ROS, IL-1β, IL-6, IL-18, and TNF-α. VA also lowered MDA and MPO levels, mRNA expressions of IL-1β, IL-6, IL-18, and TNF-α, and mRNA and protein expressions of Coll Ⅰ, Coll Ⅲ, and α-SMA in cardiac tissues, and increased serum levels of IL-4 and IL-10, cardiac tissue levels of CAT, GSH, SOD, and T-AOC, and mRNA expressions of IL-4 and IL-10. Additionally, VA ameliorated cardiac pathological damage, inhibited myocardial cell apoptosis, inflammatory infiltration, and collagen fiber deposition, reduced collagen volume fraction, and alleviated mitochondrial damage. VA decreased the ratio of F4/80~+CD86~+ M1 cells and the mRNA expressions of CD86 and iNOS in cardiac tissue, and increased the ratio of F4/80~+CD206~+ M2 cells and the mRNA expressions of CD206 and Arg-1. VA also reduced protein expressions of p-Drp1, VDAC, NLRP3, ASC, caspase-1, cleaved-caspase-1, GSDMD, GSDMD-N, IL-1β, IL-18, Bad, Bax, Apaf-1, cleaved-caspase-3, cleaved-caspase-9, cleaved-PARP-1, and cytoplasmic cytochrome C, and increased the expressions of HK1, Bcl-2, Bcl-xl, pro-caspase-3, pro-caspase-9 proteins, as well as the Bcl-2/Bax and Bcl-xl/Bad ratios and mitochondrial cytochrome C content. These results indicate that VA has a significant ameliorative effect on ISO-induced CF in mice, alleviates ISO-induced oxidative damage and inflammatory response, and its mechanism may be closely related to the inhibition of Drp1/HK1/NLRP3 and mitochondrial apoptosis signaling pathways, suppression of myocardial cell inflammatory infiltration and collagen fiber deposition, reduction of collagen volume fraction and CollⅠ, Coll Ⅲ, and α-SMA expressions, thus mitigating CF.
Animals ; Isoproterenol/adverse effects* ; Male ; Mice ; Signal Transduction/drug effects* ; Vanillic Acid/administration & dosage* ; Dynamins/genetics* ; Mice, Inbred C57BL ; Fibrosis/genetics* ; Apoptosis/drug effects* ; Mitochondria/metabolism* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Myocardium/metabolism* ; Humans

By employing the analytic hierarchy process(AHP), the CRITIC method(a weight determination method based on indicator correlations), and the AHP-CRITIC hybrid weighting method, the weight coefficients of evaluation indicators were determined, followed by a comprehensive score comparison. The grey correlation analysis was then performed to analyze the results calculated using the hybrid weighting method. Subsequently, a backpropagation-artificial neural network(BP-ANN) model was constructed to predict the extraction process parameters and optimize the extraction process for Shenxiong Huanglian Jiedu Granules(SHJG). In the extraction process, an L_9(3~4) orthogonal experiment was designed to optimize three factors at three levels, including extraction frequency, water addition amount, and extraction time. The evaluation indicators included geniposide, berberine, ginsenoside Rg_1 + Re, ginsenoside Rb_1, ferulic acid, and extract yield. Finally, the optimal extraction results obtained by the orthogonal experiment, grey correlation analysis, and BP-ANN method were compared, and validation experiments were conducted. The results showed that the optimal extraction process involved two rounds of aqueous extraction, each lasting one hour; the first extraction used ten times the amount of added water, while the second extraction used eight times the amount. In the validation experiments, the average content of each indicator component was higher than the average content obtained in the orthogonal experiment, with a higher comprehensive score. The optimized extraction process parameters were reliable and stable, making them suitable for subsequent preparation process research.
Drugs, Chinese Herbal/analysis* ; Neural Networks, Computer

Non-small cell lung cancer(NSCLC) is the most common type of lung cancer worldwide, accounting for approximately 80%-85% of all lung cancer cases. Despite the clinical benefits of traditional treatments such as surgery, chemotherapy, and radiotherapy, challenges such as the high rate of postoperative recurrence and resistance of some patients to chemotherapy and targeted therapies limit their effectiveness, necessitating the exploration of more effective treatment options. In recent years, immunotherapy, especially immune checkpoint inhibitors(ICIs), has revolutionized NSCLC treatment and significantly improved the survival prognosis of some patients. However, the efficacy of immunotherapy is limited by tumor immune escape, drug resistance, and immune-related adverse events(irAEs), which have not been effectively addressed. Traditional Chinese medicine(TCM), as a traditional therapeutic approach, has shown unique advantages in NSCLC treatment, with studies indicating its ability to enhance immune responses, regulate immune checkpoints, and improve the tumor microenvironment(TME), thus boosting the efficacy of immunotherapy. Additionally, the multi-target and multi-pathway effects of TCM help mitigate the side effects of immunotherapy, further improving efficacy and safety. This review summarizes the latest research progress of TCM in NSCLC immunotherapy, focusing on the research results of TCM in enhancing the effect of immunotherapy by regulating immune cells, optimizing the immune microenvironment, and being applied with ICIs, etc. The latest research progress of TCM in alleviating irAEs is also elucidated. The aim is to provide theoretical support for the clinical application of TCM in the prevention and treatment of NSCLC and the research and development of new drugs and promote the optimization and development of combined immunotherapy and TCM treatment models.
Humans ; Carcinoma, Non-Small-Cell Lung/therapy* ; Lung Neoplasms/therapy* ; Immunotherapy/methods* ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional ; Animals ; Tumor Microenvironment/drug effects*

Objective:To investigate the safety and therapeutic effect of split liver transplantation (SLT) in clinical application.Methods:This is a retrospective case-series study. The clinical data of 203 consecutive SLT, 79 living donor liver transplantation (LDLT) and 1 298 whole liver transplantation (WLT) performed at the Third Affiliated Hospital of Sun Yat-sen University from July 2014 to July 2023 were retrospectively analyzed. Two hundred and three SLT liver grafts were obtained from 109 donors. One hundred and twenty-seven grafts were generated by in vitro splitting and 76 grafts were generated by in vivo splitting. There were 90 adult recipients and 113 pediatric recipients. According to time, SLT patients were divided into two groups: the early SLT group (40 cases, from July 2014 to December 2017) and the mature SLT technology group (163 cases, from January 2018 to July 2023). The survival of each group was analyzed and the main factors affecting the survival rate of SLT were analyzed. The Kaplan-Meier method and Log-rank test were used for survival analysis.Results:The cumulative survival rates at 1-, 3-, and 5-year were 74.58%, 71.47%, and 71.47% in the early SLT group, and 88.03%, 87.23%, and 87.23% in the mature SLT group, respectively. Survival rates in the mature SLT group were significantly higher than those in the early SLT group ( χ2=5.560, P=0.018). The cumulative survival rates at 1-, 3- and 5-year were 93.41%, 93.41%, 89.95% in the LDLT group and 87.38%, 81.98%, 77.04% in the WLT group, respectively. There was no significant difference among the mature SLT group, the LDLT group and the WLT group ( χ2=4.016, P=0.134). Abdominal hemorrhage, infection, primary liver graft nonfunction,and portal vein thrombosis were the main causes of early postoperative death. Conclusion:SLT can achieve results comparable to those of WLT and LDLT in mature technology liver transplant centers, but it needs to go through a certain time learning curve.

Objective:To analyze the influence mechanism of primary physicians'salary satisfaction on the turnover tendency,explore the moderating role of professional identity,and to provide a basis for enhancing the stability of the primary care physician workforce.Methods:The questionnaire survey method was used to study the salary satisfaction,professional identity and turnover ten-dency among 298 primary care doctors in the main urban area of Wuhan,and 284 valid questionnaires were obtained.The data were statistically analyzed.Results:The propensity to leave scores of primary care physicians aged 40 to 50 years,with bachelor's de-gree and 11 to 15 years of work were(3.01±0.87),(3.02±0.90),and(3.03±0.86),respectively,with high were high turnover tendency;primary care physicians'salary satisfaction and professional identity had a negative effect on the propensity to leave(P＜0.001);and professional identity had a negative effect on the salary satisfaction and turnover tendency(P＜0.001).Conclusion:Primary physicians'propensity to leave is more pronounced in the high-quality human capital group,with moderate security but in-sufficient incentives for pay;higher levels of professional identity reduce the relationship between pay satisfaction and propensity to leave.

Objective:To analyze the influence mechanism of primary physicians'salary satisfaction on the turnover tendency,explore the moderating role of professional identity,and to provide a basis for enhancing the stability of the primary care physician workforce.Methods:The questionnaire survey method was used to study the salary satisfaction,professional identity and turnover ten-dency among 298 primary care doctors in the main urban area of Wuhan,and 284 valid questionnaires were obtained.The data were statistically analyzed.Results:The propensity to leave scores of primary care physicians aged 40 to 50 years,with bachelor's de-gree and 11 to 15 years of work were(3.01±0.87),(3.02±0.90),and(3.03±0.86),respectively,with high were high turnover tendency;primary care physicians'salary satisfaction and professional identity had a negative effect on the propensity to leave(P＜0.001);and professional identity had a negative effect on the salary satisfaction and turnover tendency(P＜0.001).Conclusion:Primary physicians'propensity to leave is more pronounced in the high-quality human capital group,with moderate security but in-sufficient incentives for pay;higher levels of professional identity reduce the relationship between pay satisfaction and propensity to leave.

Objective:To analyze the influence mechanism of primary physicians'salary satisfaction on the turnover tendency,explore the moderating role of professional identity,and to provide a basis for enhancing the stability of the primary care physician workforce.Methods:The questionnaire survey method was used to study the salary satisfaction,professional identity and turnover ten-dency among 298 primary care doctors in the main urban area of Wuhan,and 284 valid questionnaires were obtained.The data were statistically analyzed.Results:The propensity to leave scores of primary care physicians aged 40 to 50 years,with bachelor's de-gree and 11 to 15 years of work were(3.01±0.87),(3.02±0.90),and(3.03±0.86),respectively,with high were high turnover tendency;primary care physicians'salary satisfaction and professional identity had a negative effect on the propensity to leave(P＜0.001);and professional identity had a negative effect on the salary satisfaction and turnover tendency(P＜0.001).Conclusion:Primary physicians'propensity to leave is more pronounced in the high-quality human capital group,with moderate security but in-sufficient incentives for pay;higher levels of professional identity reduce the relationship between pay satisfaction and propensity to leave.

Objective:To analyze the influence mechanism of primary physicians'salary satisfaction on the turnover tendency,explore the moderating role of professional identity,and to provide a basis for enhancing the stability of the primary care physician workforce.Methods:The questionnaire survey method was used to study the salary satisfaction,professional identity and turnover ten-dency among 298 primary care doctors in the main urban area of Wuhan,and 284 valid questionnaires were obtained.The data were statistically analyzed.Results:The propensity to leave scores of primary care physicians aged 40 to 50 years,with bachelor's de-gree and 11 to 15 years of work were(3.01±0.87),(3.02±0.90),and(3.03±0.86),respectively,with high were high turnover tendency;primary care physicians'salary satisfaction and professional identity had a negative effect on the propensity to leave(P＜0.001);and professional identity had a negative effect on the salary satisfaction and turnover tendency(P＜0.001).Conclusion:Primary physicians'propensity to leave is more pronounced in the high-quality human capital group,with moderate security but in-sufficient incentives for pay;higher levels of professional identity reduce the relationship between pay satisfaction and propensity to leave.

Objective:To analyze the influence mechanism of primary physicians'salary satisfaction on the turnover tendency,explore the moderating role of professional identity,and to provide a basis for enhancing the stability of the primary care physician workforce.Methods:The questionnaire survey method was used to study the salary satisfaction,professional identity and turnover ten-dency among 298 primary care doctors in the main urban area of Wuhan,and 284 valid questionnaires were obtained.The data were statistically analyzed.Results:The propensity to leave scores of primary care physicians aged 40 to 50 years,with bachelor's de-gree and 11 to 15 years of work were(3.01±0.87),(3.02±0.90),and(3.03±0.86),respectively,with high were high turnover tendency;primary care physicians'salary satisfaction and professional identity had a negative effect on the propensity to leave(P＜0.001);and professional identity had a negative effect on the salary satisfaction and turnover tendency(P＜0.001).Conclusion:Primary physicians'propensity to leave is more pronounced in the high-quality human capital group,with moderate security but in-sufficient incentives for pay;higher levels of professional identity reduce the relationship between pay satisfaction and propensity to leave.

Objective:To analyze the influence mechanism of primary physicians'salary satisfaction on the turnover tendency,explore the moderating role of professional identity,and to provide a basis for enhancing the stability of the primary care physician workforce.Methods:The questionnaire survey method was used to study the salary satisfaction,professional identity and turnover ten-dency among 298 primary care doctors in the main urban area of Wuhan,and 284 valid questionnaires were obtained.The data were statistically analyzed.Results:The propensity to leave scores of primary care physicians aged 40 to 50 years,with bachelor's de-gree and 11 to 15 years of work were(3.01±0.87),(3.02±0.90),and(3.03±0.86),respectively,with high were high turnover tendency;primary care physicians'salary satisfaction and professional identity had a negative effect on the propensity to leave(P＜0.001);and professional identity had a negative effect on the salary satisfaction and turnover tendency(P＜0.001).Conclusion:Primary physicians'propensity to leave is more pronounced in the high-quality human capital group,with moderate security but in-sufficient incentives for pay;higher levels of professional identity reduce the relationship between pay satisfaction and propensity to leave.