Liver cancer is one of the most common malignant tumors in the digestive system and ranks sixth among newly diagnosed malignant tumors worldwide. Transforming growth factor-β （TGF-β） regulates cell differentiation， proliferation， apoptosis， and other physiological and pathological mechanisms and exerts cancer-suppressive and pro-cancerous dual effects in the process of tumor development. In recent years， with the continuous exploration of the mechanism of liver cancer， it has been found that the conversion of the cancer-suppressive effect into a pro-cancerous effect of this pathway plays a key role in the development of liver cancer. Traditional Chinese medicine （TCM） provides a unique perspective for the classification， diagnosis， and treatment of liver cancer with its comprehensive regulatory effects of multi-components， multi-targets， and multi-pathways. This paper summarized that the cancer-suppressive mechanisms of the TGF-β signaling pathway included promoting cancer cell cycle arrest， apoptosis， autophagy， et al， while the pro-cancerous mechanisms included promoting cancer cell proliferation， invasion and metastasis， immunosuppression， angiogenesis， et al. The TCM compounds intervening this pathway were sorted out， including Jianpi Huayu compound， Fuyang Baoyuan compound， Yipi Yanggan compound， Fuzheng Jiedu compound， compound Astragalus and Salvia， Biejia Jianwan， Dahuang Zhechong pill， and Qingxiang powder. The single TCMs mainly included Schizocapsa plantaginea， Dendrobii Caulis， Gleditsia sinensis， and Dracaena cochinchinensis. The active ingredients of TCM are mainly concentrated on flavonoids， alkaloids， glycosides， phenolics， terpenoids， polysaccharides， and other kinds of compounds. At the same time， it summarized that the liver cancer inhibition mechanism of TCM by regulating this pathway mainly included promoting apoptosis of liver cancer cells， blocking the cell cycle， and inhibiting liver cancer cell proliferation， migration， invasion， angiogenesis， immune escape， etc. The mechanism aims to give full play to the advantages of TCM and precisely regulate the TGF-β signal， thereby exerting positive anti-tumor effects， opening up a new direction for the precise targeted treatment of liver cancer， and providing a scientific basis and a new strategy for the application of TCM in the treatment of liver cancer.

Liver cancer is one of the most common malignant tumors in the digestive system and ranks sixth among newly diagnosed malignant tumors worldwide. Transforming growth factor-β （TGF-β） regulates cell differentiation， proliferation， apoptosis， and other physiological and pathological mechanisms and exerts cancer-suppressive and pro-cancerous dual effects in the process of tumor development. In recent years， with the continuous exploration of the mechanism of liver cancer， it has been found that the conversion of the cancer-suppressive effect into a pro-cancerous effect of this pathway plays a key role in the development of liver cancer. Traditional Chinese medicine （TCM） provides a unique perspective for the classification， diagnosis， and treatment of liver cancer with its comprehensive regulatory effects of multi-components， multi-targets， and multi-pathways. This paper summarized that the cancer-suppressive mechanisms of the TGF-β signaling pathway included promoting cancer cell cycle arrest， apoptosis， autophagy， et al， while the pro-cancerous mechanisms included promoting cancer cell proliferation， invasion and metastasis， immunosuppression， angiogenesis， et al. The TCM compounds intervening this pathway were sorted out， including Jianpi Huayu compound， Fuyang Baoyuan compound， Yipi Yanggan compound， Fuzheng Jiedu compound， compound Astragalus and Salvia， Biejia Jianwan， Dahuang Zhechong pill， and Qingxiang powder. The single TCMs mainly included Schizocapsa plantaginea， Dendrobii Caulis， Gleditsia sinensis， and Dracaena cochinchinensis. The active ingredients of TCM are mainly concentrated on flavonoids， alkaloids， glycosides， phenolics， terpenoids， polysaccharides， and other kinds of compounds. At the same time， it summarized that the liver cancer inhibition mechanism of TCM by regulating this pathway mainly included promoting apoptosis of liver cancer cells， blocking the cell cycle， and inhibiting liver cancer cell proliferation， migration， invasion， angiogenesis， immune escape， etc. The mechanism aims to give full play to the advantages of TCM and precisely regulate the TGF-β signal， thereby exerting positive anti-tumor effects， opening up a new direction for the precise targeted treatment of liver cancer， and providing a scientific basis and a new strategy for the application of TCM in the treatment of liver cancer.

ObjectiveTo investigate the incidence and influencing factors of posttraumatic stress disorder （PTSD） three months after a traffic accident， and to explore the role of social support and coping strategies. MethodsA total of 117 individuals exposed to trauma following road traffic accidents were recruited. General demographic and clinical information was collected within one week， and the hamilton anxiety rating scale （HAMA）， the hamilton depression rating scale-24 （HAMD-24）， the social support rating scale （SSRS）， and the simplified coping style questionnaire （SCSQ） were administered. A 3-month follow-up was subsequently conducted， during which PTSD symptoms were assessed using the post-traumatic stress disorder checklist for DSM-5 （PCL-5）. Participants were divided into a PTSD group and a non-PTSD group according to whether PTSD occurred. Between-group comparisons were performed using the Mann-Whitney U non-parametric test or the χ² test， as appropriate. Spearman correlation analysis was used to examine the associations between general characteristics and PCL-5 scores. Binary Logistic regression was applied to identify factors influencing PTSD， and receiver operating characteristic （ROC） curve analysis was conducted to evaluate the diagnostic value of the SCSQ and SSRS. ResultsDuring the 3-month follow-up of the 117 trauma-exposed individuals， 17 cases developed PTSD， with a higher proportion of females （70.59%）. Between-group comparisons showed that， compared with the PTSD group， the non-PTSD group had higher scores for positive coping， objective support， and subjective support （P<0.05）， and lower scores for negative coping， HAMA， HAMD， and PCL-5 （P<0.05）. Correlation analysis indicated that female gender， negative coping， and higher HAMA and HAMD scores were associated with greater PTSD severity. Logistic regression analysis demonstrated that educational level （OR=1.715， 95% CI： 1.020-2.883， P=0.042） and negative coping （OR=1.590， 95% CI： 1.003-2.522， P=0.048） were risk factors for PTSD， whereas objective support （OR=0.646， 95% CI： 0.451-0.925， P=0.017） was a protective factor. The ROC analysis showed that the total SCSQ score and its negative and positive coping dimensions， the total SSRS score and its subjective and objective support dimensions， as well as their combined use， all demonstrated good discriminative ability in distinguishing between the PTSD and non-PTSD groups. ConclusionThe results suggest that individuals who are female， with higher HAMA and HAMD scores after a motor vehicle accident， and those with lower social support and negative coping strategies， should be given particular attention. Early interventions for these individuals may reduce the incidence of PTSD.

Objective:Based on value orientation,it aimed to scientifically define the concept and connotation of accessibility to novel anticancer drugs,in order to deeply understand the nature and current status of the accessibility issues of novel anticancer drugs,and to provide a reference for the formulation and optimization of policies related to novel anticancer drugs.Methods:Data was collected through literature review and expert interviews,and the concept of drug accessibility was defined using the atomic diagram method.Results:The core images include"affordability","availability","high quality"and"patients".The concept of accessibility to novel anticancer drugs is defined as"the process of ensuring the sustainable supply,equitable access,affordability,and rational use of high-quality anticancer drugs to safeguard the realization of patient benefit goals."The connotation of the value orientation in policies on the accessibility of novel anticancer drugs is profoundly reflected in the multi-dimensional value-driven approach to ensure the ultimate benefit of patients,which includes quality,sustainability,equity,affordability,and rational use.Conclusion:The proposal of the concept and connotation of accessibility provides a theoretical basis for a deep understanding of the accessibility of novel anticancer drugs and offers valuable references for subsequent policy-making and practical operations.

Objective:To explore changes in brain activity in patients with post-traumatic stress disorder(PTSD).Methods:A total of 40 participants involved in car accidents were included,and functional magnetic reso-nance imaging(fMRI)scans were collected within one week.Anxiety,depression,and personality assessments were conducted with the Hamilton Anxiety Scale(HAMA),Hamilton Depression Scale(HAMD),and Eysenck Person-ality Scale for Adult(EPQ).After two months,a second fMRI scan was conducted,and a PTSD diagnosis was made.Participants were divided into a trauma-exposed group(n=23)and a PTSD group(n=17)based on wheth-er they developed PTSD.Changes in brain functional activity between the trauma-exposed group and the PTSD group were compared using the percentage of amplitude fluctuation(perAF)method.Results:Compared to the trauma-exposed group,the PTSD group showed a decreased perAF value in the left hippocampus at 1 week,and de-creased perAF values in the right mid-cingulate gyrus and left postcentral gyrus at 2 months(P＜0.05).When comparing the PTSD group at different times,the perAF values in the left middle temporal gyrus and left medial su-perior frontal gyrus decreased at 2 months(P＜0.05).Correlation analysis revealed that PCL-5 scores were posi-tively correlated with EPQ Psychoticism(r=0.32,P=0.041),HAMA(r=0.35,P＜0.05),and HAMD(r=0.34,P＜0.05).Regression analysis found that higher scores of EPQ psychoticism(OR=11.79)and HAMA(OR=1.62)were risk factors for post-accident PTSD,while higher scores of EPQ extraversion(OR=0.32)were pro-tective factors.Conclusion:It suggests that patients with post-traumatic stress disorder may show decreased activity in the right middle cingulate cortex,left postcentral gyrus,left middle temporal gyrus,and left medial superior fron-tal gyrus within two months after the traumatic event.

Objective:Based on value orientation,it aimed to scientifically define the concept and connotation of accessibility to novel anticancer drugs,in order to deeply understand the nature and current status of the accessibility issues of novel anticancer drugs,and to provide a reference for the formulation and optimization of policies related to novel anticancer drugs.Methods:Data was collected through literature review and expert interviews,and the concept of drug accessibility was defined using the atomic diagram method.Results:The core images include"affordability","availability","high quality"and"patients".The concept of accessibility to novel anticancer drugs is defined as"the process of ensuring the sustainable supply,equitable access,affordability,and rational use of high-quality anticancer drugs to safeguard the realization of patient benefit goals."The connotation of the value orientation in policies on the accessibility of novel anticancer drugs is profoundly reflected in the multi-dimensional value-driven approach to ensure the ultimate benefit of patients,which includes quality,sustainability,equity,affordability,and rational use.Conclusion:The proposal of the concept and connotation of accessibility provides a theoretical basis for a deep understanding of the accessibility of novel anticancer drugs and offers valuable references for subsequent policy-making and practical operations.

Objective To analyze the policy texts related to pediatric medications in China over the past decade,to explore the deficiencies in existing policy formulation from the perspective of stakeholders,and to propose reasonable optimization suggestions based on the current situation.Methods Collecting national-level policies related to pediatric drugs in China from 2013 to 2023,a two-dimensional policy analysis framework of"Policy tools-Stakeholder"were established.And the content analysis method was used to code,categorize,and statistically analyze the policy texts.Results A total of 54 pediatric drug policies were included in the analysis.In terms of policy tools,a total of 197 policy codes were formed,with environmental tools being the most prevalent with 92 codes(46.70％),primarily consisting of regulatory management tools(28 codes,30.43％).This was followed by supply-oriented tools with 53 codes(26.90％),mainly focused on the issuance of technical guidelines(21 codes,39.62％).Demand-oriented tools accounted for the least with 52 codes(26.40％),with inter-departmental collaboration tools having the highest proportion(17 codes,32.69％).In the dimension of stakeholders,a total of 223 policy codes were formed,with the government having the highest number of codes at 133(59.64％),followed by medical institutions with 56 codes(25.11％).The proportions for medical personnel,pharmaceutical companies,and patients were similar,with 14 codes(6.28％),11 codes(4.93％),and 9 codes(4.04％),respectively.Conclusions Pediatric drugs face challenges with policy tools where supply-oriented tools,particularly those providing financial support,suffer from insufficient policy depth and customization.The demand-oriented tools have a low proportion,leading to structural imbalance and underutilized effectiveness;the environment-oriented tools focus more on regulation than incentives,restricting the accessibility of pediatric drugs;the potential of multiple stakeholders is not fully activated,and there is a lack of policies centered around pediatric patients.To address these issues,supply-oriented policy tools need to establish a diversified financial support model and clearly define the scope of coverage.Demand-oriented policy tools require further adjustments to the catalog,procurement upgrades,and international collaborative research to reshape the pediatric drug security system.Environmental policy tools should enhance economic support,strengthen intellectual property rights,and implement targeted education to build a development ecosystem for pediatric drugs.Regarding stakeholders,it is essential to strengthen multi-stakeholder collaboration and optimize pediatric drug policy tools with a patient-centered approach.

Objective To analyze the policy texts related to pediatric medications in China over the past decade,to explore the deficiencies in existing policy formulation from the perspective of stakeholders,and to propose reasonable optimization suggestions based on the current situation.Methods Collecting national-level policies related to pediatric drugs in China from 2013 to 2023,a two-dimensional policy analysis framework of"Policy tools-Stakeholder"were established.And the content analysis method was used to code,categorize,and statistically analyze the policy texts.Results A total of 54 pediatric drug policies were included in the analysis.In terms of policy tools,a total of 197 policy codes were formed,with environmental tools being the most prevalent with 92 codes(46.70％),primarily consisting of regulatory management tools(28 codes,30.43％).This was followed by supply-oriented tools with 53 codes(26.90％),mainly focused on the issuance of technical guidelines(21 codes,39.62％).Demand-oriented tools accounted for the least with 52 codes(26.40％),with inter-departmental collaboration tools having the highest proportion(17 codes,32.69％).In the dimension of stakeholders,a total of 223 policy codes were formed,with the government having the highest number of codes at 133(59.64％),followed by medical institutions with 56 codes(25.11％).The proportions for medical personnel,pharmaceutical companies,and patients were similar,with 14 codes(6.28％),11 codes(4.93％),and 9 codes(4.04％),respectively.Conclusions Pediatric drugs face challenges with policy tools where supply-oriented tools,particularly those providing financial support,suffer from insufficient policy depth and customization.The demand-oriented tools have a low proportion,leading to structural imbalance and underutilized effectiveness;the environment-oriented tools focus more on regulation than incentives,restricting the accessibility of pediatric drugs;the potential of multiple stakeholders is not fully activated,and there is a lack of policies centered around pediatric patients.To address these issues,supply-oriented policy tools need to establish a diversified financial support model and clearly define the scope of coverage.Demand-oriented policy tools require further adjustments to the catalog,procurement upgrades,and international collaborative research to reshape the pediatric drug security system.Environmental policy tools should enhance economic support,strengthen intellectual property rights,and implement targeted education to build a development ecosystem for pediatric drugs.Regarding stakeholders,it is essential to strengthen multi-stakeholder collaboration and optimize pediatric drug policy tools with a patient-centered approach.

AIM:To explore the central mechanisms by which metformin(Met)attenuates insulin resistance in high-fat diet(HF)-fed rats.METHODS:Forty healthy male Sprague-Dawley rats were randomly divided into 4 groups:normal chow(NC)group,HF group,HF+Met group,and HF+Met+SHU9119[melanocortin 4 receptor(MC4R)antagonist]group,with 10 rats per group.Treatments with HF and Met lasted for 12 weeks,while SHU9119 was injected for the last 10 d.Skeletal muscle AMP-activated protein kinase(AMPK)and silent information regulator 1(SIRT1)ex-pression and activity were measured,along with mitochondria oxidative stress markers,mitochondrial function and quanti-ty.Systemic and skeletal muscle insulin sensitivity were assessed using the average glucose infusion rate from 60 to 120 min(GIR60-120)and 2-deoxyglucose uptake(DGU)during hyperinsulinemic-euglycemic clamp.RESULTS:The rats in HF group exhibited significantly reduced expression and activity of AMPK/SIRT1 in skeletal muscles(P<0.05).More-over,mitochondrial oxidative stress markers,reactive oxygen species(ROS)and malondialdehyde(MDA),were marked-ly elevated(P<0.05),and the activity of antioxidant enzymes glutathione peroxidase(GPX)and manganese superoxide dismutase(MnSOD)was significantly decreased in HF group(P<0.05).There was also a notable decline in the activity of citrate synthase(P<0.05),a marker of mitochondrial oxidative capacity,and the copy number of mitochondrial DNA in HF group.These changes were correlated with significantly decreased GIR60-120 and DGU(P<0.05).Notably,Met treat-ment(HF+Met)restored the AMPK/SIRT1 expression and activity,improved mitochondrial function,and reduced oxida-tive stress,leading to improved insulin sensitivity(P<0.05).However,these beneficial effects of Met were reversed by the MC4R antagonist SHU9119 in HF+Met+SHU9119 group.CONCLUSION:Treatment with Met enhances skeletal muscle AMPK/SIRT1 expression and activity,reverses mitochondrial dysfunction,and improves insulin resistance in HF-fed rats.These effects might be mediated through the activation of hypothalamic MC4R.

OBJECTIVE To study the therapeutic effect of Hongqi Shenmai Drink on heart failure(HF)after acute myocardial in-farction(AMI)with qi-yin deficiency and blood stasis,and its regulatory effect on serum secretory phosphoprotein 1(SPP1)in AMI-HF patients.METHODS Seventy-six patients with AMI-HF of qi-yin deficiency and blood stasis type were enrolled in this study from three centers:Affiliated Hospital of Integrated Traditional and Western Medicine,Nanjing University of Chinese Medicine;Hangzhou Xiaoshan Hospital of Traditional Chinese Medicine;and Changzhou Hospital of Traditional Chinese Medicine.They were randomly di-vided into a traditional Chinese medicine(TCM)group and a control group,with 38 patients in each group.During the treatment period,4 patients in the TCM group and 3 patients in the control group dropped out.The control group received conventional Guideline-directed medical therapy(GDMT),while the TCM group received GDMT plus Hongqi Shenmai Drink.The treatment course for both groups was 12 weeks.The TCM syndrome scores of the two groups of patients were compared before and after treatment,and the clini-cal efficacy and readmission rate were assessed.Echocardiography was used to assess cardiac structure and function.ELISA was used to detect changes in serum SPP1,N-terminal pro-brain natriuretic peptide(NT-proBNP),interleukin-1β(IL-1β),type Ⅰ collagen α1(COL1α1),and matrix metalloproteinase 9(MMP9)levels.The 6-minute walk test(6MWT)was used to assess exercise tolerance,and the Minnesota living with heart failure questionnaire(MLHFQ)was used to assess patients'quality of life.Adverse reactions were monitored in both groups during treatment.RESULTS After treatment,the TCM syndrome scores of both groups decreased signifi-cantly(P<0.01),with the TCM group showing a significantly lower score than the control group(P<0.01).The total effective rate of TCM clinical efficacy in the TCM group was superior to that in the control group(P<0.05),and the readmission rate in the TCM group was significantly lower than that in the control group(P<0.01).Left ventricular end diastolic diameter(LVEDD),left ventricular end-systolic diameter(LVESD),left ventricular ejection fraction(LVEF),6MWT,and MLHFQ scores improved in both groups(P<0.01),with the TCM group showing superior improvement compared to the control group(P<0.05,P<0.01).Serum levels of NT-proBNP,IL-1β,COL1α1,and MMP9 decreased in both groups(P<0.05,P<0.01).Serum SPP1 levels were significantly decreased in the TCM group(P<0.01),and serum levels of NT-proBNP,IL-1β,COL1α1,and MMP9 in the TCM group were significantly lower than those in the con-trol group(P<0.01).The change in SPP1(ΔSPP1)showed a negative correlation with the change in the cardiac function ΔLVEF(r=-0.42,P<0.01),and a positive correlation with the myocardial fibrosis marker ΔCOL1α1(r=0.58,P<0.01)and the matrix degradation marker ΔMMP9(r=0.51,P<0.01).There was no significant difference in adverse reaction rates between the two groups during treat-ment(P>0.05).CONCLUSION Hongqi Shenmai Drink combined with GDMT can effectively improve clinical symptoms and cardiac function in patients with AMI-HF of qi-yin deficiency and blood stasis type,with good safety.Its mechanism may be related to the in-hibition of SPP1-mediated inflammation-fibrosis pathway and the downregulation of IL-1β,COL1α1,and MMP9 expression.