ObjectiveMigraine is a leading neurological disorder and the fourth most common cause of years lived with disability worldwide, affecting nearly 116 million individuals. Although pharmacological treatments are available, their efficacy is often limited by side effects and variable response rates. Repetitive transcranial magnetic stimulation (rTMS) over the dorsolateral prefrontal cortex (DLPFC) offers a safe, non-invasive alternative for migraine management. However, the neurophysiological mechanisms, particularly how rTMS modulates local cortical excitability and distributed pain-related circuits, remain poorly understood. Elucidating these mechanisms is essential for optimizing treatment protocols and improving clinical outcomes. MethodsThis study employed concurrent transcranial magnetic stimulation and electroencephalography (TMS-EEG) to investigate neuroplastic and neurocircuitry mechanisms of DLPFC-rTMS in migraine. Study 1 compared 30 migraineurs and 28 healthy controls to identify abnormalities in TMS-evoked potentials (TEPs) and significant current density (SCD) within sensory-discriminative regions including the primary somatosensory cortex (S1) and posterior insula (pINS), cognitive-affective regions including the anterior insula (aINS) and midcingulate cortex (MCC), and a descending modulatory region, the periaqueductal gray (PAG). Study 2 used a single-blind, crossover, sham-controlled design in 34 healthy participants. Each participant received both active (10 Hz, 80% RMT, 1 500 pulses) and sham DLPFC-rTMS in counterbalanced order. TMS-EEG and cold pain tolerance were assessed before and after each session. ResultsIn Study 1, migraineurs showed a significantly less negative N120 amplitude compared to healthy controls (P=0.027, Cohen’s d=0.60), indicating local intracortical disinhibition. No group differences were observed for N40, P60, or P180 components. At the source level, migraineurs exhibited significantly higher SCD in the S1, pINS, aINS, and MCC (allQ<0.05), but not in the ventroposterior thalamus (vpTHAL), mediodorsal thalamus (mdTHAL), or PAG. In Study 2, active rTMS significantly reduced SCD from pre- to post-stimulation in the S1, aINS, and MCC (all Q<0.05). Sham stimulation also reduced SCD in the S1 (Q<0.05) but not in the aINS or MCC. Although no significant group-level analgesic effect was observed between active and sham conditions (P=0.107), correlation analyses revealed that greater SCD reductions in the S1 and MCC were significantly associated with higher post-rTMS pain tolerance (R=-0.487 and -0.495, both Q<0.01) and larger improvements in pain tolerance(R=-0.487 and -0.451, both Q<0.05). No such correlations were found following sham stimulation, suggesting that the behavioural relevance of neural changes is specific to active rTMS. ConclusionThis study provides novel evidence that migraineurs exhibit both local neuroplastic abnormalities (reduced N120 amplitude) and hyperactivity in key pain-processing regions (S1, pINS, aINS, MCC). A single session of DLPFC-rTMS reduced hyperactivity in the aINS, MCC, and S1. Notably, greater reductions in the S1 and MCC were associated with improved pain tolerance. These findings identify distinct cortical circuitries, particularly within the cognitive-affective pain network, that may serve as potential biomarkers for optimizing rTMS treatment in migraine and other chronic pain conditions. Future studies should validate these results in patient populations experiencing spontaneous migraine attacks and explore multi-session or accelerated rTMS protocols.

Objective To analyze the association between lifestyle and the risk of type 2 diabetes(T2D)among adult residents.Methods The data was sourced from the Shanghai Suburban Adult Cohort and Biobank.A total of 42 096 adult residents who had not developed T2D were recruited from four districts of Shanghai(Songjiang,Jiading,Minhang,and Xuhui)between 2016 and 2019.The follow-up ended on Feb 28,2023.A structured questionnaire was used to collect information on six lifestyle-related items,including smoking,alcohol consumption,BMI,waist circumference(WC),physical activity,and diet.The unhealthy lifestyle scores(UHLS)were calculated by counting the number of all the unhealthy lifestyle items,with a range of 0-6.New-onset T2D events diagnosed by physicians were obtained through the medical information system.Cox proportional hazards regression model and restricted cubic spline model were utilized to evaluate the association between unhealthy lifestyles and the risk of T2D incidence.Results About 28.1%of the participants led 4-6 unhealthy lifestyles.A total of 1 752 new T2D cases were identified during 218 513.4 person-years of follow-up.Analysis of single unhealthy lifestyle showed that abnormal WC(HR=1.5,95%CI:1.4-1.7)and abnormal BMI(HR=1.3,95%CI:1.2-1.5)were associated with an increased risk of T2D.Compared with individuals with a UHLS of 0-1,those with a UHLS of 3 and 4-6 had 30%(95%CI:1.1-1.6)and 50%(95%CI:1.2-1.8)higher risks of T2D,respectively.Each additional unhealthy lifestyle was associated with a 10%increase in T2D incidence risk(HR=1.1,95%CI:1.1-1.2).Conclusion The risk of T2D in adult residents increases with the cumulative number of unhealthy lifestyles.Adult residents with abnormal WC or BMI,or have three or more unhealthy lifestyles accumulated,will increase the risk of new-onset T2D.

The scientific research and innovation capabilities of medical students are intrinsically linked to the sustained and high-quality development of national healthcare initiatives.Cultivating outstanding medi-cal students with independent scientific capabilities and innovative consciousness is a critical component in the education and training of high-level medical professionals.Our investigation revealed that within the imperfections of the cultivating model,some faculty and students at medical schools have an insufficient understanding of scientific research and innovation and lack motivation for engaging in such activities,which hinder the progression of scientific research activities.Consequently,we initiated a teaching practice and exploratory study on the"tutorial system"aimed at fostering medical students'scientific research and innovation abilities.Based on the principle of"research informing teaching,teaching and research advan-cing together,"this study implements a"tutorial system"coordinated by tutors,supplemented by graduate and undergraduate student mentors,to cultivate innovative thinking,stimulate interest in scientific re-search,and enhance practical and research skills among medical students.Through collaborative efforts within"scientific research innovation teams,"various educational methods—including preliminary re-search,in-class and extracurricular activities,intra-group and inter-group interactions,and theoretical and practical applications—are employed to improve and strengthen the cultivation of medical students'scientif-ic research and innovation abilities.This study aims to provide valuable references for optimizing medical education management systems and enhancing the quality of medical student training.

Aim To investigate the regulatory effects and underlying mechanisms of 4-methoxybenzyl alcohol(4-MBA),an active ingredient of Gastrodia elata,on hepatic cholesterol metabolism.Methods Acute hy-perlipidemia mouse models were established via egg yolk emulsion induction,and hyperlipidemia rat models were constructed using a high-fat diet.Serum and he-patic total cholesterol(TC),triglycerides(TG),low-density lipoprotein cholesterol(LDL-C),and high-den-sity lipoprotein cholesterol(HDL-C)levels were quan-tified via enzymatic assays.Hepatic histopathological changes were evaluated through hematoxylin-eosin(HE)and Oil Red O staining.Interactions between 4-MBA and key cholesterol metabolism targets were sim-ulated using molecular docking.mRNA and protein ex-pression levels of LDL receptor(LDLR),proprotein convertase subtilisin/kexin type 9(PCSK9),liver X receptor α(LXRα),peroxisome proliferator-activated receptor γ(PPARγ),ATP-binding cassette transporter G1(ABCG1),and cholesterol 7α-hydroxylase(CYP7A1)were assessed using quantitative polymer-ase chain reaction(qPCR)and immunohistochemis-try.Results In acute hyperlipidemic mice,4-MBA administration significantly reduced serum TG and LDL-C levels while elevating HDL-C(P＜0.05).Hy-perlipidemic rats exhibited decreased serum TG and LDL-C,increased HDL-C(P＜0.01),reduced hepatic LDL-C(P＜0.01),and elevated hepatic HDL-C(P＜0.01).Although TC levels showed a downward trend,the difference lacked statistical significance.He-patic lipid accumulation and steatosis were alleviated.Upregulated mRNA and protein expression of LDLR,PPARγ,LXRα,and ABCG1(P＜0.01),alongside downregulated PCSK9(P＜0.05),were observed.Conclusion 4-MBA modulates cholesterol metabolism primarily via the LDLR/PCSK9 pathway to enhance cholesterol uptake and the PPARγ-LXRα-CYP7A1/ABCA1 axis to promote cholesterol utilization and ef-flux.

Isoflavones which mainly distributed in leguminous plants have plenty of health benefits.Isoflavone synthase(IFS)is a membrane-associated cytochrome P450 enzyme(CYP450)which carries out the unique aryl-ring migration and hydroxylation.So far,few crystal structures of plant P450s have been obtained.We determined the crystal structure of IFS from Medicago truncatula at 1.9 ? by MAD method using a selenomethionine substituted crystal and conducted molecular docking and mutagenesis study.The structure of IFS complexed with imidazole exhibits the helix Ⅰa-loop-helix Ⅰβ motif which cor-responds to helix Ⅰ of other P450s.Compared with structures of common P450s,IFS/imidazole structure contains an extra domain,i.e.,the γ-domain.The structure reveals a homodimer in which the γ-domain of one molecule interacts with the β-domain of another.The plane of heme group makes an angle of ap-proximately 40° with the helix Ⅰa-loop-helix Ⅰβ motif.Molecular docking combined with mutagenesis study suggested that Trp-128 and Asp-300 might play important roles in substrate binding and recogni-tion.Phe-301,Ser-303 and Gly-305 from the helix Ⅰa-loop-helix Ⅰβ motif may play important roles in the aryl-ring migration.These novel structural features reveal insights into the unique reaction mechanism of IFS and provide a basis for engineering IFS in leguminous crops for health purpose.

Isoflavones which mainly distributed in leguminous plants have plenty of health benefits.Isoflavone synthase(IFS)is a membrane-associated cytochrome P450 enzyme(CYP450)which carries out the unique aryl-ring migration and hydroxylation.So far,few crystal structures of plant P450s have been obtained.We determined the crystal structure of IFS from Medicago truncatula at 1.9 ? by MAD method using a selenomethionine substituted crystal and conducted molecular docking and mutagenesis study.The structure of IFS complexed with imidazole exhibits the helix Ⅰa-loop-helix Ⅰβ motif which cor-responds to helix Ⅰ of other P450s.Compared with structures of common P450s,IFS/imidazole structure contains an extra domain,i.e.,the γ-domain.The structure reveals a homodimer in which the γ-domain of one molecule interacts with the β-domain of another.The plane of heme group makes an angle of ap-proximately 40° with the helix Ⅰa-loop-helix Ⅰβ motif.Molecular docking combined with mutagenesis study suggested that Trp-128 and Asp-300 might play important roles in substrate binding and recogni-tion.Phe-301,Ser-303 and Gly-305 from the helix Ⅰa-loop-helix Ⅰβ motif may play important roles in the aryl-ring migration.These novel structural features reveal insights into the unique reaction mechanism of IFS and provide a basis for engineering IFS in leguminous crops for health purpose.

support the diagnosis.The treatment of PHCC is mainly based on surgery.Due to the characteristics of intact capsule,surgical resection is relatively easy and the cure rate is higher than that of ordinary hepatocellular carcinoma,and the postoperative survival rate is relatively ideal.For unresectable PHCC,palliative treatment based on transcatheter arterial chemoembolization can be used.This article reviews the progress on diagnosis and treatment of PHCC in order to provide reference for clinical practice.

Objective To analyze the association between lifestyle and the risk of type 2 diabetes(T2D)among adult residents.Methods The data was sourced from the Shanghai Suburban Adult Cohort and Biobank.A total of 42 096 adult residents who had not developed T2D were recruited from four districts of Shanghai(Songjiang,Jiading,Minhang,and Xuhui)between 2016 and 2019.The follow-up ended on Feb 28,2023.A structured questionnaire was used to collect information on six lifestyle-related items,including smoking,alcohol consumption,BMI,waist circumference(WC),physical activity,and diet.The unhealthy lifestyle scores(UHLS)were calculated by counting the number of all the unhealthy lifestyle items,with a range of 0-6.New-onset T2D events diagnosed by physicians were obtained through the medical information system.Cox proportional hazards regression model and restricted cubic spline model were utilized to evaluate the association between unhealthy lifestyles and the risk of T2D incidence.Results About 28.1%of the participants led 4-6 unhealthy lifestyles.A total of 1 752 new T2D cases were identified during 218 513.4 person-years of follow-up.Analysis of single unhealthy lifestyle showed that abnormal WC(HR=1.5,95%CI:1.4-1.7)and abnormal BMI(HR=1.3,95%CI:1.2-1.5)were associated with an increased risk of T2D.Compared with individuals with a UHLS of 0-1,those with a UHLS of 3 and 4-6 had 30%(95%CI:1.1-1.6)and 50%(95%CI:1.2-1.8)higher risks of T2D,respectively.Each additional unhealthy lifestyle was associated with a 10%increase in T2D incidence risk(HR=1.1,95%CI:1.1-1.2).Conclusion The risk of T2D in adult residents increases with the cumulative number of unhealthy lifestyles.Adult residents with abnormal WC or BMI,or have three or more unhealthy lifestyles accumulated,will increase the risk of new-onset T2D.

Hypothermia is a clinical syndrome characterized by core body temperature<35℃,caused by significant heat loss from body surface in cold environment.As a systemic cold injury,it can be lethal if treatment is delayed.Emergent diagnosis and treatment of hypothermia are expected to improve the prognosis of patients.In 2005,the U.S.Army Research Institute of Environmental Medicine(USARIEM)issued guidelines for the prevention and management of cold injuries,but there has been no corresponding standard in China.Therefore,Emergency Branch of Chinese Medical Rescue Association,Emergency Medical Equipment Society of China Association of Medical Equipment,Integrated Rehabilitation Medical Branch of Chinese Medical Rescue Association,and Pre-Hospital Emergency Care Working Committee of Chinese Aging Well Association jointly developed the Chinese Expert Consensus on Emergent Treatment of Hypothermia(2025 edition).The consensus covers the pathophysiology,etiology and epidemiology,diagnosis and severity grading,prehospital treatment,and in-hospital treatment of hypothermia,including 15 recommendations in total,aiming to provide guidance for the relevant clinical rescue work.

The scientific research and innovation capabilities of medical students are intrinsically linked to the sustained and high-quality development of national healthcare initiatives.Cultivating outstanding medi-cal students with independent scientific capabilities and innovative consciousness is a critical component in the education and training of high-level medical professionals.Our investigation revealed that within the imperfections of the cultivating model,some faculty and students at medical schools have an insufficient understanding of scientific research and innovation and lack motivation for engaging in such activities,which hinder the progression of scientific research activities.Consequently,we initiated a teaching practice and exploratory study on the"tutorial system"aimed at fostering medical students'scientific research and innovation abilities.Based on the principle of"research informing teaching,teaching and research advan-cing together,"this study implements a"tutorial system"coordinated by tutors,supplemented by graduate and undergraduate student mentors,to cultivate innovative thinking,stimulate interest in scientific re-search,and enhance practical and research skills among medical students.Through collaborative efforts within"scientific research innovation teams,"various educational methods—including preliminary re-search,in-class and extracurricular activities,intra-group and inter-group interactions,and theoretical and practical applications—are employed to improve and strengthen the cultivation of medical students'scientif-ic research and innovation abilities.This study aims to provide valuable references for optimizing medical education management systems and enhancing the quality of medical student training.