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.

Objective To explore the diagnostic value of ultrasonography in ischiofemoral impinge-ment syndrome(IFI).Methods Fifty-six patients who underwent hip MRI with confirmed IFI diagnosis and completed ultrasonography examinations were enrolled as the IFI group,including 44 females and 12 males.Twenty healthy volunteers were concurrently recruited as the control group,consisting of 10 females and 10 males.The control group underwent ultrasonography examinations of bilateral hip joints,whiletheischialfemoralspace(IFS)andquadratusfemoristhickness(QFT)of both groups were measured and recorded.Then measurements were compared within(by laterality and gender)and between the two groups using independent-samples t-tests.Moreover,receiver operating characteristic adults,males exhibited significantly higher IFS and QFT values than females(P<0.05).Within the IFI group,males with affected hips had significantly higher IFS than females(P<0.05),while no sig-nificant differences were observed in QFT between different genders(P>0.05).Moreover,affected hips in the IFI group showed significantly narrower IFS and thicker QFT compared to both contralateral hips and the control group(P<0.001).In addition,the diagnostic cut-off values of IFS and QFT for ultrasound diagnosis of IFI were 22.93 mm and 16.48 mm,respectively.At these thresholds,the ar-eas under the curve(AUC)were 0.997 and 0.977,with sensitivities of 97.8%and 91.8%,and speci-ficities of 98.4%and 97.8%,respectively.Conclusion Ultrasound can serve as a reliable diagnostic technique for IFI,where narrowing of the IFS and thickening of the QFT should raise suspicion of this condition.

Cognitive impairment is one of the most common non-motor symptoms of Parkinson′s disease, which seriously affects the health and quality of life of patients. Therefore, it is particularly important to identify and predict the future cognitive decline of this population. Cognitive reserve can compensate for brain damage caused by aging and brain diseases, and reduce and delay cognitive decline, reflecting the different sensitivity of individuals to cognitive impairment. However, the specific relationship between the two is not fully understood. This paper mainly analyzes the concept, measurement method, genetics and functional imaging of cognitive reserve in Parkinson′s disease to further reveal the relationship between cognitive impairment and cognitive reserve in Parkinson′s disease.

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.

A brain-computer interface (BCI) based on motor imagery (MI) provides additional control pathways by decoding the intentions of the brain. MI ability has great intra-individual variability, and the majority of MI-BCI systems are unable to adapt to this variability, leading to poor training effects. Therefore, prediction of MI ability is needed. In this study, we propose an MI ability predictor based on multi-frequency EEG features. To validate the performance of the predictor, a video-guided paradigm and a traditional MI paradigm are designed, and the predictor is applied to both paradigms. The results demonstrate that all subjects achieved > 85% prediction precision in both applications, with a maximum of 96%. This study indicates that the predictor can accurately predict the individuals' MI ability in different states, provide the scientific basis for personalized training, and enhance the effect of MI-BCI training.
Humans ; Imagination/physiology* ; Electroencephalography/methods* ; Brain-Computer Interfaces ; Male ; Female ; Adult ; Young Adult ; Brain/physiology* ; Movement/physiology* ; Motor Activity/physiology* ; Psychomotor Performance/physiology*

This research study focuses on addressing the limitations of current neuropathic pain (NP) treatments by developing a novel dual-target modulator, E0199, targeting both Na_V1.7, Na_V1.8, and Na_V1.9 and K_V7 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 Na_V1.7, Na_V1.8, and Na_V1.9 channels with a particularly low half maximal inhibitory concentration (IC₅₀) for Na_V1.9 by promoting sodium channel inactivation, and also effectively increased K_V7.2/7.3, K_V7.2, and K_V7.5 channels, excluding K_V7.1 by promoting potassium channel activation. This dual action significantly reduced the excitability of dorsal root ganglion neurons and alleviated 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 therapeutic option for NP. This study introduces a promising direction for the future development of NP therapeutics.

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

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.

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.