Objective To investigate the association of serum total testosterone(TT),free testosterone(FT),sex hormone-binding globulin(SHBG),and estradiol(E_2)with all-cause mortality rate(AMR)in males and to evaluate their predictive value. Methods Based on data from the National Health and Nutrition Examination Survey(NHANES)cycles(1999—2004 and 2013—2016),the relationships between different sex hormones and AMR was analyzed with Cox proportional hazards regression models. The dose-response relationships between different sex hormones and male AMR were assessed with restricted cubic splines(RCS). The predictive performances of different sex hormones for male AMR were compared with receiver operating characteristic(ROC)curves and the area under the curve(AUC). The survival differences across varying sex hormone levels were evaluated with Kaplan-Meier survival curves and log-rank tests. Results This study involved 3632 adult male participants with a median follow-up of 6.5 years,during which 320 AMR occurred(8.8%). Cox univariate analysis indicated that TT,FT and SHBG were risk factors for AMR(P＜0.001). Cox multivariate analysis revealed that FT and SHBG were independent risk factors for AMR(FT:HR=0.90,95%CI:0.86-0.94; SHBG:HR=1.01,95%CI:1.01-1.02). RCS revealed a U-shaped nonlinear relationship between TT,FT and AMR(P＜0.001); SHBG showed a positive dose-response relationship with AMR(P＜0.001). The AUCs of FT predicting the 5-year,10-year,and 15-year AMR were 0.78(95%CI:0.73-0.82),0.80(95%CI:0.76-0.84),and 0.84(95%CI: 0.80-0.88),respectively,significantly outperforming other indicators. Subgroup analysis revealed that FT was negatively correlated with male AMR,but this association was modulated by age,race,smoking status and diabetes status(P_(interaction)＜0.05). Kaplan-Meier survival analysis showed that different levels of TT and FT(Q1-Q4)were significantly positively correlated with survival rate(P＜0.001),while different levels of SHBG were significantly negatively correlated with survival rate,with patients in the Q4 group having the highest risk of death(P＜0.001). Conclusion Based on US NHANES,studies have shown that the FT and SHBG are independent risk factors for male AMR,and FT demonstrates greater predictive value for male AMR than TT.

Extracellular vesicles(EVs)are nanoscale membrane vesicles released by cells that carry bioactive molecules such as proteins and nucleic acids. They play a key role in intercellular communication. In recent years, they have shown significant potential in the diagnosis and treatment of corneal and ocular surface diseases. As diagnostic biomarkers, EVs derived from tears or other sources can reflect disease-specific characteristics, providing a basis for the early disease detection. In terms of therapy, mesenchymal stem cells(MSCs)-derived EVs deliver miRNAs to modulate inflammatory pathways, promote corneal epithelial repair, and inhibit fibrosis. Furthermore, as natural drug vehicles, EVs enable precise delivery of therapeutic agents and promote corneal wound healing. This review systematically summarizes the recent research advances in the application of EVs in the field.

Developing an intelligent agent for integrated traditional Chinese and western medicine diagnosis and treatment based on clinical practice guidelines is a key approach to advancing the standardization and intelligent deve-lopment of traditional Chinese medicine （TCM） and to supporting clinical decision-making. This paper argues for the necessity of building a knowledge base using guidelines as the sole data source， systematically identifies five core methodological challenges across the entire process， and proposes corresponding solutions. An ontology framework capable of distinguishing between TCM and western medicine concepts should be designed to address the difficulty of knowledge integration. A closed-loop "algorithm-based extraction-expert review" model is adopted to reduce data extraction errors. Expert consensus is incorporated to address decision gaps in specific clinical scenarios outlined in the guidelines， while a multi-stage， standardized output process for the AI system is established to eliminate model hallucinations. Furthermore， an evaluation framework reflecting clinical applicability is developed to enhance the AI system's accuracy and stability. Throughout the research process， it is essential to ensure the in-depth and continuous participation of multidisciplinary experts， strictly control the selection and quality evaluation of guidelines， and rely on the expert consensus method to address decision gaps in the knowledge base. Additionally， continuous validation and iterative optimization of intelligent agents are required to ensure the accuracy and stability of generated outputs. Limitations remain in the mechanisms for real-time knowledge synchronization in intelligent diagnostic and treatment systems， and further validation through large-scale real-world studies is warranted.

Objective To investigate the influencing factors of disease progression and prognosis in patients with large artery atherosclerotic(LAA)cerebral infarction and analyze the value of plasma cyclin-dependent kinase 9(CDK9)level in the diagnosis and treatment of LAA cerebral infarction.Methods Patients with acute cerebral infarction admitted to the Department of Neurology of the Affili-ated Hospital of Yangzhou University between March 1,2022,and November 20,2023,were select-ed.According to the diagnostic criteria,98 patients with acute LAA(LAA group)and 33 patients with acute small artery occlusion(SAO)cerebral infarction(SAO group)were selected.Additionally,40 healthy individuals matched for age and gender from the Health Examination Center were included as control group.Based on whether the condition of LAA cerebral infarction patients progressing,they were divided into progressive cerebral infarction(PCI)group(39 patients)and the non-pro-gressive cerebral infarction(NPCI)group(59 patients).During the 3-month follow-up period,6 patients from the 98 LAA cerebral infarction patients were lost.According to the modified Rankin Scale(mRS)score at 90 days of follow-up,patients were divided into good prognosis group(mRS score≤2,59 patients)and poor prognosis group(mRS score＞2,33 patients).Fasting lipid in-dices[total cholesterol(TC),triglyceride(TG),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),glucose(GLU),glycated hemoglobin(HbA1c),and homocysteine(Hey)]were collected on the second day after admission.The National Institutes of Health Stroke Scale(NIHSS)was used to assess the degree of neurological impairment in cerebral infarction patients.Enzyme-linked immunosorbent assay(ELISA)was used to measure plasma CDK9 levels in different groups;factors influencing disease progression in patients with acute LAA cerebral infarction were explored;and receiver operating characteristic curves were plotted to evalu-ate the predictive value of CDK9 in patients with acute LAA cerebral infarction.Results Compared with the control group,the LAA group had lower HDL-C level and higher CDK9 level(P＜0.05).The LAA group had a higher proportion of diabetes history,larger infarction volume,higher NIHSS score at admission,and higher CDK9 level compared with the SAO group(P＜0.05).Binary Logistic regression analysis showed that diabetes history and plasma CDK9 levels were influencing factors for LAA cerebral infarction.There were statistically significant differences in the proportion of diabetes history,HbA1c,random GLU,and CDK9 levels between the NPCI and PCI groups(P＜0.05).Diabetes history and plasma CDK9 levels were influencing factors for disease progression in patients with acute LAA cerebral infarction.The area under the ROC curve for CDK9 in predicting acute LAA cerebral infarction was 0.854 5(95％CI,0.794 1 to 0.9148).When the CDK9 level was 602.1 ng/L,the Youden index was maximum(0.604),with a corresponding sensitivity of 0.849 and specificity of 0.755.The NIHSS score,infarction volume,and plasma CDK9 level were higher in the poor prognosis group compared with the good prognosis group(P＜0.01).Correlation analysis showed a positive correlation between mRS scores and CDK9 levels(r=0.485,P＜0.01).Conclusion Plasma CDK9 levels are significantly elevated,and is an influencing factor.It is positively correlated with disease progression and poor prognosis in acute cerebral infarction and has certain predictive value for the progression of LAA cerebral infarction.

Objective To screen metabolic core genes in colon cancer based on machine learning algorithms and analyze their functional mechanisms.Methods Data were obtained from The Cancer Genome Atlas(TCGA)database and the Gene Expression Omnibus(GEO)database.The TCGA co-hort included 375 tumor samples and 32 adjacent normal tissue samples,while the GSE39582 cohort comprised 419 tumor samples.Univariate Cox regression analysis combined with random forest,sup-port vector machine recursive feature elimination(SVM-RFE),and least absolute shrinkage and selec-tion operator(LASSO)regression algorithms were employed to screen for metabolic core genes.Re-ceiver operating characteristic(ROC)curves were plotted,and the area under the curve(AUC)was used to evaluate the predictive efficacy of the core genes.Real-time fluorescent quantitative polymerase chain reaction(qRT-PCR)and immunohistochemistry(IHC)methods were adopted to detect the ex-pression of the core genes.The core genes were knocked down to explore their roles in colon cancer.Results Three core genes,namely CPT2,SCP2 and NR3C2,were screened based on machine learning algorithms.According to the comparison results of the AUCs of the ROC curves,NR3C2 exhibited the best predictive efficacy.qRT-PCR detection results showed that NR3C2 mRNA was lowly ex-pressed in colon cancer cell lines;IHC detection results revealed that NR3C2 was lowly expressed in colon cancer tissues.Knocking down NR3C2 significantly promoted the proliferation and migration of colon cancer cells.Conclusion NR3C2 is identified as a core metabolic inhibitory gene in colon cancer by cross-applying three machine learning algorithms,which may provide a new strategy for metabolic targeted therapy.

Myocardial ischemia-reperfusion injury （MIRI） is a major complication following coronary revascularization. Studies indicate that its pathophysiological mechanisms of MIRI are closely associated with oxidative stress， iron overload， inflammatory responses， and lipid peroxidation. Oxidative stress refers to an imbalance in redox homeostasis under pathological conditions， characterized by the abnormal accumulation of reactive oxygen species （ROS）， which disrupts the dynamic balance between pro-oxidant systems and antioxidant defense networks. In recent years， traditional Chinese medicine （TCM） has demonstrated unique advantages in the prevention and treatment of MIRI due to its multi-target and multi-pathway antioxidant properties. Research reveals that TCM primarily exerts protective effects against oxidative stress-induced MIRI by regulating signaling pathways such as nuclear factor erythroid 2-related factor 2 （Nrf2）， adenosine monophosphate-activated protein kinase （AMPK）， phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt）， nuclear factor kappa-B （NF-κB）， Janus kinase 2/signal transducer and activator of transcription 3 （JAK2/STAT3）， and protein kinase C beta Ⅱ/nicotinamide adenine dinucleotide phosphate oxidase 2/reactive oxygen species （PKCβⅡ/NOX2/ROS）. This article reviews recent literature on TCM monomers， compound formulas， and their active components， which alleviate oxidative stress to prevent and treat MIRI by modulating the aforementioned signaling pathways. It summarizes a concise overview of the molecular mechanisms by which oxidative stress-related signaling pathways lead to MIRI， discusses how TCM regulates these pathways to reduce oxidative stress-induced MIRI， and explores clinical application prospects and research challenges， aiming to provide a theoretical reference for the research and clinical management of MIRI.

OBJECTIVE: To observe the clinical efficacy of Qihuang needle therapy for autism spectrum disorder (ASD) children with sleep disorder. METHODS: A total of 60 ASD children with sleep disorder were randomly divided into an observation group and a control group, 30 cases in each group. Both groups were treated with structured education intervention, 60 min each time, once a day, 6 times a week. Qihuang needle therapy was applied at Yintang (GV24⁺), Baihui (GV20) and bilateral Jueyinshu (BL14), Xinshu (BL15) in the observation group, multi-direction needling was delivered and without needle retaining. The treatment was given 2 times a week, each treatment was delivered at interval of 2 days at least. Behavioral intervention was adopted in the control group. Treatment for consecutive 12 weeks was required in both groups. Before and after treatment, the scores of children's sleep habits questionnaire (CSHQ), the autism behavior checklist (ABC), the childhood autism rating scale (CARS), and the childhood autism behavior scale (CABS) were observed in the two groups. RESULTS: After treatment, the scores of CSHQ, ABC, CARS and CABS were decreased compared with those before treatment (P<0.01), and the above scores in the observation group were lower than those in the control group (P<0.05). CONCLUSION Qihuang needle therapy can effectively treat ASD with sleep disorder, improve the core symptoms of ASD and the sleep quality.
Humans ; Autism Spectrum Disorder/physiopathology* ; Male ; Female ; Child ; Sleep Wake Disorders/physiopathology* ; Child, Preschool ; Acupuncture Therapy ; Acupuncture Points ; Treatment Outcome ; Sleep ; Needles

Percutaneous coronary intervention(PCI),as one of the primary approaches for revascularization,still faces complications such as restenosis,myocardial ischemia-reperfusion injury and no-reflow/slow-flow phenomena,with no currently effective interventions ensuring long-term efficacy.Based on Li Dongyuan's theory that"fire and original qi cannot coexist",this article inherited Academician Chen Keji's academic perspective on"toxin-stasis pathogenesis"and the hemodynamic characteristics of coronary arteries to propose a"four-stage pathological progression"in post-PCI patients,namely spleen-stomach impairment-original qi deficiency-endogenous yin-fire-toxin-stasis accumulation.It emphasized that the heart vessels rely on qi and blood for nourishment and patency for function,elucidated the therapeutic rationale of Danggui Buxue Decoction,and presented the self-formulated Yixin Hemai Prescription,modified through syndrome differentiation,and performed simultaneous reinforcement and dredging,in order to provide diagnosis and treatment ideas for coronary heart disease after PCI treated with TCM.

This research study focuses on addressing the limitations of current neuropathic pain(NP)treatments by developing a novel dual-target modulator,E0199,targeting both Nav1.7,Nay1.8,and Nay1.9 and Kv7 channels,a crucial regulator in controlling NP symptoms.The objective of the study was to synthesize a compound capable of modulating these channels to alleviate NP.Through an experimental design involving both in vitro and in vivo methods,E0199 was tested for its efficacy on ion channels and its therapeutic potential in a chronic constriction injury(CCI)mouse model.The results demonstrated that E0199 significantly inhibited Nav1.7,Nav1.8,and Nav1.9 channels with a particularly low half maximal inhibitory concentration(ICs0)for Nay1.9 by promoting sodium channel inactivation,and also effectively increased Kv7.2/73,Kv7.2,and Kv7.5 channels,excluding Kv7.1 by promoting potassium channel acti-vation.This dual action significantly reduced the excitability of dorsal root ganglion neurons and alle-viated pain hypersensitivity in mice at low doses,indicating a potent analgesic effect without affecting heart and skeletal muscle ion channels critically.The safety of E0199 was supported by neurobehavioral evaluations.Conclusively,E0199 represents a ground-breaking approach in NP treatment,showcasing the potential of dual-target small-molecule compounds in providing a more effective and safe thera-peutic option for NP.This study introduces a promising direction for the future development of NP therapeutics.

Addressing the challenge of traditional physical/semi physical simulation methods being difficult to achieve full process and full element simulation of extravehicular activities,virtual reality technology is utilized to break through the limitations of physical environments and establish a virtual reality simulation system for extravehicular activities.Based on the application characteristics of space station extravehicular activity engineering,with the goal of improving system practicality and usability,integrating the visual immersion of virtual images,the ontology of real operation,and the consistency of virtual and real space perception,a three-dimensional scene simulation,multi-mode joystick interaction paradigm,continuous operation actions simulation of extravehicular operations,and interactive operation virtual/real space consistency method that were proposed and designed for the realistic visual perception and extravehicular operation.The system has been successfully applied to astronaut training,program validation,joint exercise,and flight control support for sixteen extravehicular activities from SZ-12 to SZ-18.The results showed that the complete reproduction of the static/dynamic realistic comprehensive scene was achieved on the ground for the human-machine operation in the entire process of extravehicular activity,and the system is an essential and important means of ground simulation for extravehicular activity.