[摘 要] 目的：探究西贝素通过调控Cyclin D1介导的CDK4/6-Rb-E2F1信号轴对人胃腺癌细胞（AGS）的增殖抑制效果及其分子机制。方法：利用不同浓度的西贝素处理AGS和人正常胃黏膜上皮细胞（GES-1），通过CCK-8检测和结晶紫染色实验确定西贝素的最适抑制剂量和作用时间；采用划痕实验和Transwell迁移实验与侵袭实验检测西贝素对AGS细胞迁移与侵袭能力的影响；利用流式细胞术和WB检测西贝素对AGS细胞周期及细胞周期相关蛋白表达的影响；利用质粒过表达Cyclin D1，并通过WB检测、结晶紫染色实验、划痕实验和Transwell迁移实验与侵袭实验进一步明确西贝素的抑制机制；构建AGS移植瘤裸鼠模型，采用免疫荧光染色法和免疫组化检测Cyclin D1、CDK4、CDK6、Rb、p-Rb、E2F1的表达水平。结果：与对照组相比，西贝素药物浓度为100 μg/mL时，对GES-1细胞的增殖无影响（P > 0.05），但能够显著性抑制AGS细胞增殖、迁移和侵袭能力（P < 0.01），并诱导AGS细胞周期G0/G1期阻滞，显著抑制周期相关蛋白Cyclin D1、CDK4、CDK6、p-Rb、E2F1的表达水平（P < 0.05或P < 0.01）；Cyclin D1过表达能够显著降低西贝素对AGS细胞的抑制效果（P < 0.05或P < 0.01）；荷瘤裸鼠实验结果显示，西贝素能够抑制AGS移植瘤的增殖，影响肿瘤组织中Cyclin D1、CDK4、CDK6、p-Rb、E2F1的表达（P < 0.01）。结论：西贝素可能通过下调Cyclin D1介导的CDK4/6-Rb-E2F1信号轴活化抑制AGS增殖。

ObjectiveTo investigate the present situation of input, output, outcome and impact of all registered community-based rehabilitation stations in Inner Mongolia in China, and analyze how the input predict the output, outcome and impact. MethodsFrom March 1st to April 30th, 2025, a questionnaire survey was conducted on all registered community-based rehabilitation stations in Inner Mongolia, covering four dimensions: input, output, outcome and impact. A total of 1 365 questionnaires were distributed. The input included four items: laws and policies, human resources, equipment and facilities, and rehabilitation information management. The output included two items: technical paths and benefits/effectiveness. The outcome included three items: coverage rates, rehabilitation interventions and functional results. The impact included two items: health and sustainability. Each item contained several questions, all of which were described in a positive way. Each question was scored from one to five. A lower score indicated that the situation of the community-based rehabilitation station was more in line with the content described in the question. Regression analysis was performed using the total score of each item of input dimension as independent variables, and the total scores of the output, outcome and impact dimensions as dependent variables. ResultsA total of 1 262 valid questionnaires were collected. The mean values of input, output, outcome and impact of community-based rehabilitation stations were 1.827 to 1.904, with coefficient of variation of 45.892% to 49.239%. The regression analysis showed that, rehabilitation information management, human resources, and laws and policies significantly predicted the output dimension (R² = 0.910, P < 0.001). Meanwhile, all four items in the input dimension predicted both the outcome (R² = 0.850, P < 0.001) and impact dimensions (R² = 0.833, P < 0.001). ConclusionInput, output, outcome and impact of the community-based rehabilitation stations in Inner Mongolia were generally in line with the content of the questions, although some imbalances were observed. Additionally, the input of community-based rehabilitation stations could significantly predict their output, outcome and impact.

The prescription of Qidong Yixin oral liquid is derived from the experience of national medical master Ren Jixue in treating viral myocarditis （VMC）. It has the functions of tonifying Qi， nourishing the heart，calming the mind， and relieving palpitations. It is used to treat VMC and angina pectoris of coronary heart disease caused by deficiency of both Qi and Yin. However，the understanding of its efficacy evidence， advantageous aspects， dosage and administration， and medication safety remains insufficient in clinical practice. Therefore，the development of the Expert Consensus on the Clinical Application of Qidong Yixin Oral Liquid （hereinafter referred to as consensus） was initiated. Consensus strictly followed the process and methods of the expert consensus on the clinical application of Chinese patent medicines of the China Association of Chinese Medicine，successively completing multiple tasks such as the consensus project initiation，determination of clinical problems，evidence search and evaluation，formation of recommendation opinions and consensus suggestions，solicitation of opinions，peer review， submission for review and release， and so on. Consensus formed a total of 10 recommendation opinions and 12 consensus suggestions，clarifying the clinical positioning，efficacy advantages，syndrome differentiation，dosage and administration，combination therapy，timing of medication，adverse reactions，contraindications， and precautions of Qidong Yixin oral liquid，indicating that it has good clinical advantages and safety in the treatment of VMC and angina pectoris of coronary heart disease，providing norms and references for physicians to safely and rationally apply Qidong Yixin oral liquid. Consensus was reviewed and approved for release by the Standardization Office of the China Association of Chinese Medicine on December 23， 2024. Standard number：GSCACM-376-2024.

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.

Background Air pollution is a major environmental factor threatening respiratory health. Different pollutants exhibit varying degrees of lag effects on respiratory diseases, and synergistic effects may exist among multiple pollutants. There is an urgent need to identify the key air pollutants influencing respiratory diseases and their interactive effects at specific lags. Objective To identify key pollutants affecting hospital admissions for respiratory diseases, to analyze their lag effect characteristics, and to quantify the impact of multi-pollutant synergistic effects on respiratory disease admissions. Methods Daily air pollution data, meteorological data, and respiratory disease hospitalization records were collected from multiple national monitoring stations in Hefei City from 2019 to 2024. A two-stage analytical framework was employed. First, a distributed lag model (DLM) was used to construct pollutant lag matrices, followed by least absolute shrinkage and selection operator (LASSO) regression to select key variables among fine particulate matter (PM_2.5), sulfur dioxide (SO₂), nitrogen dioxide (NO₂), carbon monoxide (CO), and ozone (O₃). Second, a generalized additive model (GAM) was established, incorporating product interaction terms and excess relative risk (ERI) to quantitatively assess synergistic effects among the selected pollutants. Results Through LASSO regression, 24 pollutant lag terms with non-zero coefficients were identified, among which NO₂, PM_2.5, and SO₂ accounted for 66.7% of the total positive effects and exhibited distinct lag patterns. Exposure to NO₂ showed acute risk, with a relative risk of 1.040 (95%CI: 1.023, 1.057) at lag0. Conversely, PM_2.5 and SO₂ exhibited delayed effects, with peak impacts observed at lag7 (RR=1.012, 95%CI: 1.0002, 1.024) and lag3 (RR=1.015, 95%CI: 1.0004, 1.03), respectively. Short-term NO₂ exposure (lag0–1) exhibited a significant positive interaction with medium-term PM_2.5 exposure (lag4–7). When both pollutants coexisted at high exposure levels, the combined health risk exceeded the sum of their independent effects by 4.40%. Stratified analysis showed that the interaction effects of pollutants were higher in females (ERI=5.00%), children (<18 years, ERI=5.50%), and older adults (≥65 years, ERI=3.90%)Conclusion There are significant lag heterogeneity and synergistic mechanisms in the health effects of air pollution in Hefei. It is recommended to implement real-time early warning responses for NO₂, prioritize medium-to-long-term management for PM_2.5 and SO₂, and adopt coordinated emission reduction measures when NO₂ and PM_2.5 concentrations rise simultaneously. Concurrently, enhanced health protection should be provided for sensitive populations such as women, children, and the elderly.

Objective:Through imaging analysis, the association between the degree of paravertebral muscle fat infiltration (fat infiltration, FI), trabecular bone score (TBS) and the fracture risk of postmenopausal osteoporosis (OP) patients was explored.Methods:A retrospective selection was made of 110 postmenopausal female patients diagnosed with OP at Jiangnan Hospital Affiliated to Zhejiang Chinese Medical University from Mar. 2023 to Mar. 2024. Additionally, healthy postmenopausal individuals who underwent physical examinations during the same period were included in the healthy postmenopausal group. The levels of paravertebral muscle FI and TBS in the two groups were compared. Postmenopausal patients with OP were followed up for one year, and the incidence of fractures in the patients was analyzed by Kaplan-Meier curve. The patients were divided into the fracture group ( n=29) and the non-fracture group ( n=81). The clinical data of the two groups of patients at admission were compared. Binary Logistic regression was used to analyze the independent risk factors for fractures in patients. Spearman was used to analyze the correlation of fracture risk within one year among FI, TBS and postmenopausal OP patients. ROC was used to evaluate the predictive value of each independent risk factor. Results:The proportion of severe paraverteal muscle FI in the postmenopausal OP group was significantly higher than that in the healthy physical examination group (multifisis FI, erector spinae FI, psoas major muscle FI, χ2=14.96, 17.17, 16.08, all P=0.00), and the lumbar TBS level was significantly lower (t=4.52, P=0.00). The Kaplan-Meier curve indicated that the degree of paravertebral muscle FI affected the incidence of fractures in patients ( χ2=14.58, P=0.00), and the level of lumbar TBS also affected the incidence of fractures in patients ( χ2=6.02, P=0.01). The bone mineral density (BMD), cross-sectional area of the multifidus muscle (CSA), erectus spinae muscle area (CSA), and psoas major muscle area (CSA) of patients in the fracture group were significantly lower than those in the non-fracture group ( t=10.72, 3.40, 3.46, 2.12). P=0.00, 0.00, 0.00, 0.04), while the indicators of TNF-α, IL-6 and PCT were higher than those in the non-fracture group ( t=4.11, 4.96, 5.48, all P=0.00). Binary Logistic regression analysis showed that high-level BMD ( OR=0.52, 95%CI: 0.27-0.77, P=0.01) and TBS ( OR=0.68, 95 %CI: 0.48-0.93 ,P=0.02) were protective factors for fractures in postmenopausal patients with OP. Multifidus FI ( OR=1.73, 95 %CI: 1.48-1.98, P=0.03), erector spinae FI ( OR=1.25, 95%CI:1.10-1.50, P=0.01), and psoas major FI ( OR=1.96, 95 %CI: 1.71-2.21, P=0.03) is the risk factor. Spearman analysis indicated that the paravertebral muscle FI of patients at the first diagnosis of OP was positively correlated with the risk of fracture within one year after diagnosis ( r=0.88, 0.91, 0.82, P=0.01, 0.01, 0.02), while the BMD and TBS values were negatively correlated ( r=-0.92, -0.77, P=0.00, 0.02). ROC showed that the values of multifidus FI, erector spinae FI, psoas major FI, BMD and TBS at admission all had good predictive efficacy for fractures within one year in patients [area under the ROC curve (AUC) =0.88, 0.84, 0.86, 0.73, 0.82]. Moreover, the predictive efficiency of the joint model is higher (AUC=0.89) . Conclusions:Higher BMD and TBS levels protect against fractures in postmenopausal OP patients ( OR=0.523-0.675), while severe paraspinal muscle FI (multifidus: OR=1.726; erector spinae: OR=1.248; psoas: OR=1.961) increases risk. The combined model shows excellent predictive value (AUC=0.890), serving as effective clinical warning indicators for fracture risk assessment.

Hepatocellular carcinoma(HCC)is the most common type of liver cancer and a leading cause of cancer-related deaths worldwide.While early detection significantly improves prognosis,patients with alpha-fetoprotein-negative hepatocellular carcinoma(ANHCC)often face diagnostic challenges due to the lack of reliable biomarkers.This review systematically explores the potential of various circulating biomarkers in the early diagnosis of ANHCC,including AFP-L3,PIVKA-Ⅱ,lymphocyte-to-monocyte ratio,exosomes,circulating cell-free DNA(cfDNA),circulating tumor cells,osteopontin,paraoxonase 1,autoantibodies,and RNA-related biomarkers.The combined use of these markers,particularly AFP-L3 and PIVKA-Ⅱ,demonstrates enhanced diagnostic accuracy and specificity compared to single markers.Emerging evidence also highlights the diagnostic potential of exosomes,cfDNA,and RNA markers due to their non-invasive nature and high stability.Despite promising results,further large-scale,multicenter studies are needed to validate these findings,address challenges such as standardization of detection methods,and elucidate underlying mechanisms.These advances are anticipated to significantly improve early detection and personalized management of ANHCC.

Objective:Through imaging analysis, the association between the degree of paravertebral muscle fat infiltration (fat infiltration, FI), trabecular bone score (TBS) and the fracture risk of postmenopausal osteoporosis (OP) patients was explored.Methods:A retrospective selection was made of 110 postmenopausal female patients diagnosed with OP at Jiangnan Hospital Affiliated to Zhejiang Chinese Medical University from Mar. 2023 to Mar. 2024. Additionally, healthy postmenopausal individuals who underwent physical examinations during the same period were included in the healthy postmenopausal group. The levels of paravertebral muscle FI and TBS in the two groups were compared. Postmenopausal patients with OP were followed up for one year, and the incidence of fractures in the patients was analyzed by Kaplan-Meier curve. The patients were divided into the fracture group ( n=29) and the non-fracture group ( n=81). The clinical data of the two groups of patients at admission were compared. Binary Logistic regression was used to analyze the independent risk factors for fractures in patients. Spearman was used to analyze the correlation of fracture risk within one year among FI, TBS and postmenopausal OP patients. ROC was used to evaluate the predictive value of each independent risk factor. Results:The proportion of severe paraverteal muscle FI in the postmenopausal OP group was significantly higher than that in the healthy physical examination group (multifisis FI, erector spinae FI, psoas major muscle FI, χ2=14.96, 17.17, 16.08, all P=0.00), and the lumbar TBS level was significantly lower (t=4.52, P=0.00). The Kaplan-Meier curve indicated that the degree of paravertebral muscle FI affected the incidence of fractures in patients ( χ2=14.58, P=0.00), and the level of lumbar TBS also affected the incidence of fractures in patients ( χ2=6.02, P=0.01). The bone mineral density (BMD), cross-sectional area of the multifidus muscle (CSA), erectus spinae muscle area (CSA), and psoas major muscle area (CSA) of patients in the fracture group were significantly lower than those in the non-fracture group ( t=10.72, 3.40, 3.46, 2.12). P=0.00, 0.00, 0.00, 0.04), while the indicators of TNF-α, IL-6 and PCT were higher than those in the non-fracture group ( t=4.11, 4.96, 5.48, all P=0.00). Binary Logistic regression analysis showed that high-level BMD ( OR=0.52, 95%CI: 0.27-0.77, P=0.01) and TBS ( OR=0.68, 95 %CI: 0.48-0.93 ,P=0.02) were protective factors for fractures in postmenopausal patients with OP. Multifidus FI ( OR=1.73, 95 %CI: 1.48-1.98, P=0.03), erector spinae FI ( OR=1.25, 95%CI:1.10-1.50, P=0.01), and psoas major FI ( OR=1.96, 95 %CI: 1.71-2.21, P=0.03) is the risk factor. Spearman analysis indicated that the paravertebral muscle FI of patients at the first diagnosis of OP was positively correlated with the risk of fracture within one year after diagnosis ( r=0.88, 0.91, 0.82, P=0.01, 0.01, 0.02), while the BMD and TBS values were negatively correlated ( r=-0.92, -0.77, P=0.00, 0.02). ROC showed that the values of multifidus FI, erector spinae FI, psoas major FI, BMD and TBS at admission all had good predictive efficacy for fractures within one year in patients [area under the ROC curve (AUC) =0.88, 0.84, 0.86, 0.73, 0.82]. Moreover, the predictive efficiency of the joint model is higher (AUC=0.89) . Conclusions:Higher BMD and TBS levels protect against fractures in postmenopausal OP patients ( OR=0.523-0.675), while severe paraspinal muscle FI (multifidus: OR=1.726; erector spinae: OR=1.248; psoas: OR=1.961) increases risk. The combined model shows excellent predictive value (AUC=0.890), serving as effective clinical warning indicators for fracture risk assessment.

Background: Obesity and chronic pain are related in both directions, according to earlier observational research.This research aimed to analyze the causal association between obesity and chronic pain at the genetic level, as well as to assess whether common factors mediate this relationship. Methods: This study used bidirectional two sample Mendelian randomization (MR) technique to analyze the association between obesity and chronic pain. Obesity's summary genome-wide association data were obtained from European ancestry groups, as measured by body mass index (BMI), waist-to-hip ratio, waist circumference (WC), and hip circumference (HC), genome-wide association study data for chronic pain also came from the UK population, including chronic pain at three different sites (back, hip, and headache), chronic widespread pain (CWP), and multisite chronic pain (MCP). Secondly, a two-step MR and multivariate MR investigation was performed to evaluate the mediating effects of several proposed confounders. Results: The authors discovered a link between chronic pain and obesity. More specifically, a sensitivity analysis was done to confirm the associations between greater BMI, WC, and HC with an increased risk of CWP and MCP.Importantly, the intermediate MR results suggest that education levels and smoking initiation may mediate the causal relationship between BMI on CWP, with a mediation effect of 23.08% and 15.38%, respectively. Conclusions The authors’ findings demonstrate that the importance of education and smoking in understanding chronic pain’s pathogenesis, which is important for the primary prevention and prognosis of chronic pain.

To summarise the clinical experience of Professor TONG Xiaolin in treating prediabetes combined with overweight or obesity using the method of relieving depression and reducing turbidity. It is believed that prediabetes belongs to the category of "spleen-heat syndrome" in traditional Chinese medicine， and its core pathogenesis is center fullness with internal heat， while obesity is the initiating factor for exacerbating center fullness and internal heat， therefore， it is of great significance to reduce the risk of diabetes by interrupting the transformation between overweight， obesity and glucose metabolism abnormality. It is proposed that the main pathogenesis of prediabetes combined with overweight or obesity is qi depression and turbidity obstruction in middle jiao， with qi depression as the root and turbidity obstruction as the cause， forming a treatment idea with the method of relieving depression and reducing turbidity as the core. In clinic， Dahuang Huanglian Xiexin Decoction （大黄黄连泻心汤） is used as the basic prescription， with a primary focus on directing the turbid downward， supplemented by regulating qi， which embodies the concept of "promoting movement through descent， then figuring out the root of spleen-heat syndrome. Furthermore， the treatment is flexibly modified based on the patient's deficiency-excess syndrome to ensure individualized therapy.