Cancer has become a significant global public health issue， severely impacting public health and societal development. Despite advances in tumor treatment methods in recent years and a gradual decline in cancer mortality rates， drug-related adverse reactions and drug resistance remain substantial challenges. Traditional Chinese medicine （TCM） has demonstrated significant clinical efficacy in cancer treatment and small side effects， making it widely applied in the field of oncology. Xuefu Zhuyutang， derived from Yilin Gaicuo， is known for its abilities to invigorate blood circulation， dispel blood stasis， promote Qi flow， and alleviate pain. It was specifically formulated by the esteemed WANG Qingren of the Qing dynasty for the "blood stasis syndrome in the blood mansion" and is commonly used to treat Qi stagnation and blood stasis syndrome. Clinical studies have shown that Xuefu Zhuyutang， when combined with conventional Western medications， produces significant effects in the treatment of malignant tumors such as liver cancer， lung cancer， and cervical cancer. It substantially reduces the incidence of adverse reactions following Western treatments， including radiation esophagitis， radiation encephalopathy， radiation-induced oral mucositis， and edema. Additionally， it alleviates cancer-related pain and fever， blood hypercoagulability， and associated complications such as depression and anxiety， and also mitigates chemotherapy-induced side effects like hand-foot syndrome. Basic research has demonstrated its potential anti-tumor mechanisms， including the inhibition of Wnt/β-catenin signaling pathway activation， suppression of mitogen-activated protein kinase （MAPK） pathway activation， and anti-tumor angiogenesis. Pharmacological studies have revealed that its active components inhibit tumor cell proliferation and migration， induce tumor cell apoptosis， suppress tumor angiogenesis， enhance the cytotoxicity of natural killer cells against tumors， improve the tumor microenvironment， and regulate immune function. This paper reviewed the latest research progress on Xuefu Zhuyutang in the treatment of malignant tumors from four aspects： theoretical exploration， clinical studies， mechanisms of action， and pharmacological basis， aiming to provide insights and methods for the clinical diagnosis and treatment of malignant tumors.

Cancer has become a significant global public health issue， severely impacting public health and societal development. Despite advances in tumor treatment methods in recent years and a gradual decline in cancer mortality rates， drug-related adverse reactions and drug resistance remain substantial challenges. Traditional Chinese medicine （TCM） has demonstrated significant clinical efficacy in cancer treatment and small side effects， making it widely applied in the field of oncology. Xuefu Zhuyutang， derived from Yilin Gaicuo， is known for its abilities to invigorate blood circulation， dispel blood stasis， promote Qi flow， and alleviate pain. It was specifically formulated by the esteemed WANG Qingren of the Qing dynasty for the "blood stasis syndrome in the blood mansion" and is commonly used to treat Qi stagnation and blood stasis syndrome. Clinical studies have shown that Xuefu Zhuyutang， when combined with conventional Western medications， produces significant effects in the treatment of malignant tumors such as liver cancer， lung cancer， and cervical cancer. It substantially reduces the incidence of adverse reactions following Western treatments， including radiation esophagitis， radiation encephalopathy， radiation-induced oral mucositis， and edema. Additionally， it alleviates cancer-related pain and fever， blood hypercoagulability， and associated complications such as depression and anxiety， and also mitigates chemotherapy-induced side effects like hand-foot syndrome. Basic research has demonstrated its potential anti-tumor mechanisms， including the inhibition of Wnt/β-catenin signaling pathway activation， suppression of mitogen-activated protein kinase （MAPK） pathway activation， and anti-tumor angiogenesis. Pharmacological studies have revealed that its active components inhibit tumor cell proliferation and migration， induce tumor cell apoptosis， suppress tumor angiogenesis， enhance the cytotoxicity of natural killer cells against tumors， improve the tumor microenvironment， and regulate immune function. This paper reviewed the latest research progress on Xuefu Zhuyutang in the treatment of malignant tumors from four aspects： theoretical exploration， clinical studies， mechanisms of action， and pharmacological basis， aiming to provide insights and methods for the clinical diagnosis and treatment of malignant tumors.

Myosteatosis is one of the common complications in patients with end-stage liver disease, which is significantly associated with poor outcomes after liver transplantation. Currently, diagnostic criteria of myosteatosis have not been established, and CT is the most commonly used for diagnosis. The pathogenesis of myosteatosis is multifactorial, and the pathophysiological mechanisms linking it to end-stage liver disease are not fully understood. An increasing number of scholars have recognized that the severity of myosteatosis is closely related to its clinical consequences, but there are no effective treatment options available. This article reviews the pathophysiological mechanisms and diagnostic methods of myosteatosis, and its impact on the prognosis of liver transplant recipients, and discusses current treatment strategies to provide references for the perioperative management of liver transplant recipients.

Oral squamous cell carcinoma (OSCC) is a common head and neck malignancy. Approximately 50% to 60% of patients with OSCC are diagnosed at a locally advanced stage (clinical staging III-IVa). Even with comprehensive and sequential treatment primarily based on surgery, the 5-year overall survival rate remains below 50%, and patients often suffer from postoperative functional impairments such as difficulties with speaking and swallowing. Programmed death receptor-1 (PD-1) inhibitors are increasingly used in the neoadjuvant treatment of locally advanced OSCC and have shown encouraging efficacy. However, clinical practice still faces key challenges, including the definition of indications, optimization of combination regimens, and standards for efficacy evaluation. Based on the latest research advances worldwide and the clinical experience of the expert group, this expert consensus systematically evaluates the application of PD-1 inhibitors in the neoadjuvant treatment of locally advanced OSCC, covering combination strategies, treatment cycles and surgical timing, efficacy assessment, use of biomarkers, management of special populations and immune related adverse events, principles for immunotherapy rechallenge, and function preservation strategies. After multiple rounds of panel discussion and through anonymous voting using the Delphi method, the following consensus statements have been formulated: 1) Neoadjuvant therapy with PD-1 inhibitors can be used preoperatively in patients with locally advanced OSCC. The preferred regimen is a PD-1 inhibitor combined with platinum based chemotherapy, administered for 2-3 cycles. 2) During the efficacy evaluation of neoadjuvant therapy, radiographic assessment should follow the dual criteria of Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and immune RECIST (iRECIST). After surgery, systematic pathological evaluation of both the primary lesion and regional lymph nodes is required. For combination chemotherapy regimens, PD-L1 expression and combined positive score need not be used as mandatory inclusion or exclusion criteria. 3) For special populations such as the elderly (≥ 70 years), individuals with stable HIV viral load, and carriers of chronic HBV/HCV, PD-1 inhibitors may be used cautiously under the guidance of a multidisciplinary team (MDT), with close monitoring for adverse events. 4) For patients with a poor response to neoadjuvant therapy, continuation of the original treatment regimen is not recommended; the subsequent treatment plan should be adjusted promptly after MDT assessment. Organ transplant recipients and patients with active autoimmune diseases are not recommended to receive neoadjuvant PD-1 inhibitor therapy due to the high risk of immune related activation. Rechallenge is generally not advised for patients who have experienced high risk immune related adverse events such as immune mediated myocarditis, neurotoxicity, or pneumonitis. 5) For patients with a good pathological response, individualized de escalation surgery and function preservation strategies can be explored. This consensus aims to promote the standardized, safe, and precise application of neoadjuvant PD-1 inhibitor strategies in the management of locally advanced OSCC patients.

ObjectiveTo investigate the changing trends of the incidence rate， prevalence rate， mortality rate， and disability-adjusted life years （DALYs） of benign hepatobiliary and pancreatic diseases among people aged 15 — 39 years in China in 1990 — 2021. MethodsThe data of 2021 Global Burden of Disease Study were downloaded to obtain the epidemiological data of liver fibrosis/chronic liver disease， benign gallbladder/biliary tract diseases， and pancreatitis among people aged 15 — 39 years in China， and estimated annual percentage change （EAPC） was calculated to assess the changing trends of incidence， prevalence， mortality， and DALY rates. The Bayesian age-period-cohort model was used to predict the incidence and mortality rates from 2022 to 2030. ResultsIn 2021， there were 10 448 778 new cases of benign hepatobiliary and pancreatic diseases among the individuals aged 15 — 39 years in China， which was increased by 3.8% compared with the data in 1990， while the numbers of prevalent cases， deaths， and DALYs were reduced by 20.4%， 59.6%， and 50.2%， respectively. In 2021， the age-standardized incidence rates of liver fibrosis/chronic liver disease， benign gallbladder/biliary tract diseases， and pancreatitis were 1 104.40/100 000， 1 045.05/100 000， and 16.64/100 000， respectively； the age-standardized prevalence rates were 20 592.37/100 000， 2 364.85/100 000， and 9.43/100 000， respectively； the age-standardized mortality rates were 1.61/100 000， 0.04/100 000， and 0.18/100 000， respectively. From 1990 to 2021， there was a tendency of increase in the age-standardized incidence rate of liver fibrosis/chronic liver disease （EAPC=0.43， 95% confidence interval ［CI］： 0.23 — 0.63）， and there was also a tendency of increase in the age-standardized incidence and prevalence rates of benign gallbladder/biliary tract diseases （incidence rate： EAPC=1.07， 95%CI： 0.91 — 1.24； prevalence rate： EAPC=0.75， 95%CI： 0.59 — 0.89）， while there was a tendency of reduction in the age-standardized mortality rate of all three disease categories. Predictions for 2022 — 2030 indicated a potential reduction in the incidence rate of benign gallbladder/biliary tract diseases and an increase in the incidence rate of pancreatitis. ConclusionThere has been an overall upward trend in the incidence rate of liver fibrosis/chronic liver disease and gallbladder/biliary tract diseases over the past three decades， and it is needed to pay attention to the disease burden of benign hepatobiliary diseases among the people aged 15 — 39 years in China.

ObjectiveThis paper aims to conduct a secondary analysis of a randomized controlled trial on the treatment of myelodysplastic syndrome （MDS） with deficiency of both the spleen and kidney and blockage of toxin and blood stasis with an arsenic-containing traditional Chinese medicine compound， by applying the mixed model for repeated measure （MMRM） and the method of stratified composite outcome with win ratio. The analysis includes the assessment of hematological efficacy and the composite outcome evaluation of adverse reactions， so as to more comprehensively assess the therapy of this regimen. MethodsThe MMRM and win ratio methods were used to evaluate the efficacy of a prospective，multi-center，double-blind，randomized controlled study. The blood routine （hemoglobin concentration，neutrophil count， and platelet count） and biochemical indexes （aspartate aminotransferase，alanine aminotransferase，serum creatinine，and serum ferritin） of the patients were detected at the time of enrollment and at the end of each course of treatment in the laboratory department of Xiyuan Hospital. The patients' syndromes at the time of enrollment and after treatment were recorded and scored according to the therapy standard of traditional Chinese medicine for diseases and syndromes. MMRM was used to analyze the blood routine indexes of the experimental group and the control group. This method has the advantages of high data reliability and dynamic efficacy under intervention and time. The win ratio method was used to evaluate the composite outcome of traditional Chinese medicine syndrome scores and biochemical indexes according to the priority and to verify the clinical safety of arsenic-containing traditional Chinese medicine compound. ResultsThe results of MMRM analysis showed that the hemoglobin concentration of patients in the group with arsenic-containing traditional Chinese medicine compound increased significantly compared with that before treatment in the group，while that in the placebo group decreased significantly （P<0.01）. When compared with that after treatment in the placebo group，the hemoglobin concentration of patients in the group with arsenic-containing traditional Chinese medicine compound increased significantly，and the mean difference of least squares （LS） was statistically significant （P<0.01）. When compared with those before treatment in the group，there were no statistically significant differences in the neutrophil count and platelet count in both groups. After treatment，there were no statistically significant differences in the neutrophil count， platelet count， and the mean difference of LS between the two groups. The analysis results of win ratio showed that the group with arsenic-containing traditional Chinese medicine compound had a significant advantage in the comparison of composite outcomes，with a win ratio （95% CI） of 2.01 （1.24-3.27） （P<0.01），and that the possibility of "winning" in terms of safety was 2.01 times that of the placebo group. The safety advantage of the group with arsenic-containing traditional Chinese medicine compound mainly came from the traditional Chinese medicine syndrome scores，renal function indexes， and iron reserve capacity indexes，and the number of winning times was less than that of losing times in the comparison of liver function outcomes. ConclusionThe MMRM analysis proves that the arsenic-containing traditional Chinese medicine compound can significantly improve the hemoglobin concentration of patients with myelodysplastic syndrome with refractory cytopenia and multilineage dysplasia （MDS-RCMD） of the type of deficiency of both the spleen and kidney and blockage of toxin and blood stasis. This conclusion is not interfered with by time trends and individual relationships and methodologically improves the credibility of the therapy of the arsenic-containing traditional Chinese medicine compound in treating MDS. Four outcomes are evaluated by the win ratio method，namely traditional Chinese medicine syndromes，liver function，renal function， and iron reserve capacity，proving that the arsenic-containing traditional Chinese medicine compound has the comprehensive advantages of improving the survival quality of the patients and reducing adverse reactions. The win ratio outcome provides clear comparative indexes for the evaluation of adverse reactions，making it easier for regulatory authorities，medical staff， and patients to understand the safety of the arsenic-containing traditional Chinese medicine compound in clinical application.

ObjectiveTo investigate the mechanism of modified Si Junzitang and Shashen Maidong Tang ［Yiqi Yangyin Jiedu prescription （YQYYJD）］ in enhancing the sensitivity of cisplatin in epidermal growth factor receptor tyrosine kinase inhibitor （EGFR-TKI）-resistant lung adenocarcinoma cells based on aerobic glycolysis. MethodsThe effects of different concentrations of YQYYJD （0， 2， 3， 4， 5， 6， 7， 8 g·L^-1） and cisplatin （0， 3， 6， 9， 12， 15， 18， 21， 24， 27 mg·L^-1） on the proliferation and activity of PC9/GR cells were detected by the cell counting kit-8 （CCK-8） assay after 24 hours of intervention. The half-maximal inhibitory concentration （IC₅₀） for PC9/GR cells was calculated to determine the concentrations used in subsequent experiments. PC9/GR cells were divided into blank group （complete medium）， YQYYJD group （5 g·L^-1）， cisplatin group （12 mg·L^-1）， and combined group （YQYYJD 5 g·L^-1 + cisplatin 12 mg·L^-1）. After 24 hours of intervention， cell viability was measured using CCK-8 assay. Cell proliferation was assessed by colony formation assay， and cell migration was evaluated by scratch and Transwell assays. Glucose consumption， lactate production， and adenosine triphosphate （ATP） levels were measured by colorimetric assays. The expression levels of glycolysis-related proteins， including hexokinase 2 （HK2）， phosphofructokinase P （PFKP）， pyruvate kinase M2 （PKM2）， lactate dehydrogenase A （LDHA）， glucose transporter 1 （GLUT1）， and monocarboxylate transporter 4 （MCT4）， were determined by Western blot. ResultsBoth YQYYJD and cisplatin inhibited the viability of PC9/GR cells in a concentration-dependent manner. The IC₅₀ of PC9/GR cells for YQYYJD and cisplatin were 5.15 g·L^-1 and 12.91 mg·L^-1， respectively. In terms of cell proliferation， compared with the blank group， the cell survival rate and the number of colonies formed in the YQYYJD group， cisplatin group， and combined group were significantly decreased （P<0.01）. Compared with the YQYYJD and cisplatin groups， the combined group showed a further significant reduction in cell survival rate and colony formation （P<0.01）. In terms of cell migration， compared with the blank group， the cell migration rate and the number of cells passing through the Transwell membrane in the YQYYJD group， cisplatin group， and combined group were significantly decreased （P<0.01）. Compared with the YQYYJD and cisplatin groups， the combined group exhibited a further significant reduction in cell migration rate and the number of cells passing through the Transwell membrane （P<0.01）. In terms of glycolysis， compared with the blank group， glucose consumption， lactate production， and ATP levels in the YQYYJD group， cisplatin group， and combined group were significantly decreased （P<0.01）. Compared with the YQYYJD and cisplatin groups， the combined group showed a further significant reduction in glucose consumption， lactate production， and ATP levels （P<0.05）. Compared with the blank group， the protein expression levels of HK2， PFKP， PKM2， and LDHA in the YQYYJD， cisplatin， and combined groups were significantly decreased （P<0.01）. The combined group showed a further significant reduction in the expression levels of these proteins compared with the YQYYJD and cisplatin groups （P<0.01）. No significant differences were observed in the protein expression levels of GLUT1 and MCT4 among the groups. ConclusionYQYYJD can synergistically inhibit the proliferation and migration of PC9/GR cells and enhance their sensitivity to cisplatin. The mechanism may be related to the downregulation of the expression of glycolysis-related rate-limiting enzymes， including HK2， PFKP， PKM2， and LDHA， thereby inhibiting glycolysis.

BACKGROUND:Nerve growth factor is a protein that induces nerve growth and regulates biological behaviors such as proliferation and differentiation of mesenchymal stem cells. OBJECTIVE:To investigate the promoting effect of nerve growth factor on chondrogenic differentiation of bone marrow mesenchymal stem cells. METHODS:Rabbit bone marrow mesenchymal stem cells were isolated and cultured,and nerve growth factor was transfected into bone marrow mesenchymal stem cells by lentiviral transfection.The effects of nerve growth factor on the proliferation,migration,hypertrophic differentiation,and chondrogenic differentiation of bone marrow mesenchymal stem cells were detected by CCK-8 assay,cell scratch assay,alizarin red staining,and western blot assay,using the transfected null-loaded virus as control.To further investigate the promoting effect of nerve growth factor on the chondrogenic differentiation of bone marrow mesenchymal stem cells,interleukin 1β was added in bone marrow mesenchymal stem cells transfected with empty virus and nerve growth factor for 14 days.The expression of proteins related to chondrogenic differentiation and hypertrophic differentiation was detected by western blot assay. RESULTS AND CONCLUSION:(1)CCK-8 assay results showed that nerve growth factor had no significant effect on the proliferation of bone marrow mesenchymal stem cells.(2)Compared with the control group,overexpression of nerve growth factor enhanced the migration ability of the cells,and the expression of cartilage-associated proteins type II collagen and SOX9 was up-regulated(P<0.05),while the expression of hypertrophic-associated proteins type X collagen and Runx2 was down-regulated(P<0.05).(3)Compared with the empty virus+interleukin 1β group,the expression of cartilage-associated proteins type II collagen and Sox9 was up-regulated(P<0.05),and the expression of hypertrophy-associated proteins type X collagen and Runx2 was down-regulated after overexpression of nerve growth factor(P<0.05).(4)The results indicated that nerve growth factor could promote the chondrogenic differentiation of bone marrow mesenchymal stem cells.

BACKGROUND:Repetitive trans-spinal magnetic stimulation(rTSMS)can inhibit inflammatory responses following spinal cord injury.rTSMS applies magnetic field stimulation to the spinal cord region to modulate neuronal excitability and synaptic transmission,thereby promoting plasticity and repair of the nervous system. OBJECTIVE:To observe the effects of rTSMS on the Toll-like receptor 4(TLR4)/nuclear factor(NF)-κB/NLRP3 signaling pathway after spinal cord injury and explore its mechanism in promoting motor function recovery. METHODS:Male C57BL/6J mice,SPF grade,were randomly divided into sham surgery group,spinal cord injury group,and rTSMS group.The latter two groups of mice were anesthetized and the T9 vertebral plate was removed using rongeur forceps to expose the spinal cord,and the spinal cord was clamped using a small aneurysm clip for 20 seconds to establish the spinal cord injury model.Mice in the rTSMS group underwent a 21-day rTSMS intervention starting on day 1 after spinal cord injury.The stimulation lasted 10 minutes per day,5 days per week with an interval of 2 days.Basso Mouse Scale scores were used to assess motor function recovery in mice after spinal cord injury at 1,3,7,14,and 21 days after spinal cord injury.Western blot was employed to detect the expression of AQP4,apoptotic factors Bax,Bcl-2,CL-Caspase-3,inflammatory factors tumor necrosis factor-α,interferon-γ,interleukin-6,interleukin-4,and the TLR4/NF-κB/NLRP3 signaling pathway related proteins in the injured spinal cord.Oxidative stress assay kit was used to measure the activity of superoxide dismutase,glutathione peroxidase,and malondialdehyde content at the site of spinal cord injury.Immunofluorescence staining was performed to detect the expression of neuronal nuclei(NeuN). RESULTS AND CONCLUSION:The Basso Mouse Scale score in the rTSMS group was significantly higher than that in the spinal cord injury group(P<0.05).Compared with the spinal cord injury group,the rTSMS group showed a reduction in spinal cord water content.The expression of AQP4 protein,malondialdehyde content,and expression of Bax,Bcl-2,CL-Caspase-3,tumor necrosis factor-α,interferon-γ,interleukin-6,and TLR4/NF-κB/NLRP3 signaling pathway related proteins were all decreased in the rTSMS group,while the activities of superoxide dismutase and glutathione peroxidase,as well as the expression of Bcl-2,interleukin-4,and NeuN,were all increased(P<0.05).These results suggest that rTSMS downregulates the expression of proteins related to the TLR4/NF-κB/NLRP3 signaling pathway,alleviating symptoms after spinal cord injury such as spinal cord edema,oxidative stress,apoptosis,and inflammation,exerting neuroprotective effects,and thereby promoting the recovery of hindlimb motor function after spinal cord injury.

The global distribution of medical resources is uneven and organ shortages are becoming increasingly serious. ASEAN countries have been working hard to explore and promote local organ transplantation in order to alleviate the serious imbalance between organ donation and organ transplantation needs. However, the development of cadaveric organ donation varies among ASEAN countries, and the cadaveric organ donation rate in most countries is generally low. Since 1991, China and ASEAN have evolved from dialogue to strategic cooperation, then to a community with a shared future, and further to a comprehensive strategic partnership, all demonstrating broad prospects for cooperation. This article analyzes the current situation and challenges of organ donation and transplantation in ASEAN countries, combining field visits and its own experience, and proposes strategies for strengthening international cooperation, optimizing policy environment, enhancing technical capabilities, and increasing public awareness in the field of organ donation and transplantation under the China-ASEAN development strategy framework. The aim is to build a more equitable, efficient, and sustainable organ donation and transplantation system, contributing to the realization of global public health security and a community of common health for mankind.