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 explore the potential mechanism of Benzo(K)fluoranthene(BkF)on male reproductive injury in mice by proteomics and metabolomics.Methods Twenty healthy and clean male Kunming mice(6 weeks old,18±2 g)were randomly divided into control group(corn oil group),low-,medium-and high-dose BkF groups(7.5,15.0 and 30.0 mg/kg),with 5 mice in each group.The corresponding agents were gavaged at a dose of 10 mL/kg,5 d per week,for 35 consecutive days.After modeling,the rats were fasted for 10 h,and then sperm samples and testicular tissues were harvested.Computer assisted sperm analysis(CASA)was used to detect and analyze semen parameters.HE staining was employed to observe the histopathological structure of the testicular tissue.Bioinformatics analysis was applied to analyze the differential protein pathways.Volcano plot were conducted to analyze the top 10 differentially expressed proteins(DEPs)in the control and high-dose BkF group.Liquid chromatography-tandem mass spectrometry(LC-MS/MS)untargeted metabolomics techniques were utilized to screen out differential metabolites.KEGG signaling pathway and KEGG annotation analyses and GO enrichment analysis were used to analyze the differential metabolites.Results Compared with the control group,the sperm number and motility of BkF-treated mice showed a decreased trend,with statistical differences(P＜0.05).Pathological observation showed that BkF treatment resulted in dilated seminal tubules and badly-arranged spermatogenic cells when compared with the control group.Proteomics analysis found that the protein levels of Spata46 and Rab5b were decreased,while those of Zscan21 and Aifm2 were increased(P＜0.01).Proteomic KEGG enrichment analysis showed that it was mainly involved in phagosome,protein export,ribosome and other pathways.GO enrichment analysis indicated that it was mainly involved in male meiosis I,histone acetylation,regulation of p53 signaling pathway,positive regulation of cell cycle,positive regulation of cell death and other signaling pathways.Metabonomics KEGG displayed that amino sugar and nucleotide sugar metabolism were most closely related to other metabolic pathways.Conclusion Proteomics and metabolomics analyses show that BkF exposure is associated with spermatogenesis,apoptosis and cell cycle,DNA damage,amino sugar and nucleotide sugar metabolism.

Objective To explore the mechanism of Zishen Jianpi Huayu Tablets(Corni Fructus,Notoginseng Radix et Rhizoma,Astragali Radix,Puerariae Lobatae Radix,Spatholobi Caulis,Rehmanniae Radix)in the treatment of diabetic retinopathy(DR)by means of network pharmacology and molecular docking technique,and verified by in vitro experiments.Methods The active components of Zishen Jianpi Huayu Tablets and their corresponding target proteins were screened using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and the BATMAN-TCM database.Drug target proteins were converted to their corresponding gene names through the UniProt database.DR-related targets were searched using"diabetic retinopathy"as a keyword in GeneCards,DrugBank,OMIM,and TTD databases.Common targets between the disease and the drug were identified using the Venny tool.These common targets were analyzed using the String database,a protein-protein interaction(PPI)network was constructed.Topological heterogeneity analysis was performed using Cytoscape 3.9.1 to select core targets and create a PPI network diagram.These common targets were entered into the Metascape database for Gene Ontology(GO)function analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis to identify potential action pathways.Molecular docking of the main active components and core targets was performed using Auto Dock tools software,followed by further experimental validation.The CCK-8 assay was used to assess the effect of Zishen Jianpi Huayu Tablet medicated serum on the cell viability of Human Retinal Microvascular Endothelial Cells(HRmECs)under high glucose conditions,and RT-qPCR was used to measure the expression of IL-1β,AKT1,VEGFA,and TP53 mRNA in HRmECs.Results(1)The effective components and corresponding target proteins of Zishen Jianpi Huayu Tablets were screened by Traditional Chinese Medicine System Pharmacology Database and Analysis Platform(TCMSP)and BATMAN-TCM database.The disease-related targets of DR were searched by GeneCards,OMIM and TTD databases.The use of VENNY platform for drug active components target and DR disease-related target to take intersection(common target),that is,Zishen Jianpi Huayu Tablets in the treatment of DR potential target.The network of"drugs-active components-common targets"was constructed to screen out the key active components of Zishen Jianpi Huayu Tablets in the treatment of DR.Import the common target into STRING database,obtain the PPI network relationship,and screen out the core target.Metascape platform was used to analyze the GO function and KEGG pathway enrichment of the common targets.The key active components and core targets were verified by Autodock 4 software for molecular docking.(2)The drug-containing serum and blank serum of Zishen Jianpi Huayu Tablets was prepared.Human retinal microvascular endothelial cells(HRmECs)were randomly divided into 5 groups:the control group(low-sugar DMEM medium+10%blank serum),high-glucose group(high-sugar DMEM medium+10%blank serum)and Zishen Jianpi Huayu Tablets containing low-,medium-and high-dose serum(high-sugar DMEM medium+10%low-,medium-and high-dose drug containing serum)were detected after 48 hours of culture.The proliferative activity of HRmECs cells was detected by CCK-8 method,and the mRNA expressions of IL-1β,AKT1,VEGFA and TP53 in HRmECs cells were detected by RT-qPCR method.Conclusion Zishen Jianpi Huayu Tablets may act on core targets such as IL-1β,IL-6 and VEGFA,as well as key pathways such as NF-κB signaling pathway,AGE-RAGE signaling pathway and PI3K-AKT pathway through various active components such as quercetin,kaempferol and rehmannia flavonoids,so as to play a therapeutic role in DR.

Objective:To investigate the current status of self-regulatory fatigue in patients after hematopoietic stem cell transplantation (HSCT) and analyze its influencing factors.Methods:From March 2022 to September 2023, convenience sampling was used to select 161 HSCT patients who were hospitalized and followed up in the Hematology Department of a Class Ⅲ Grade A hospital in Jinan City. A survey was conducted on patients using the General Information Questionnaire, Self-Regulatory Fatigue Scale (SRF-S), Perceived Social Support Scale, Connor and Davidson Resilience Scale, and Medical Coping Modes Questionnaire. Pearson correlation was used to analyze the correlation between self-regulatory fatigue and perceived social support, psychological resilience, and medical coping styles in patients after HSCT. Multiple linear regression was used to analyze the influencing factors of self-regulatory fatigue in patients after HSCT.Results:A total of 161 questionnaires were distributed, and 156 valid questionnaires were collected, with an effective response rate of 96.89% (156/161). The total SRF-S score of 156 patients after HSCT was (49.06±6.62). Multiple linear regression analysis showed that the current work or life status, perceived social support, psychological resilience, avoidance and surrender coping styles were the influencing factors of self-regulatory fatigue in patients after HSCT ( P<0.05) . Conclusions:After HSCT, patients generally experience self-regulatory fatigue, and psychological distress needs improvement. Medical and nursing staff should regularly evaluate the self-regulatory fatigue of patients and develop targeted intervention measures based on influencing factors to reduce the degree of self-regulatory fatigue of patients, improve their prognosis and psychological state.

Objective:To explore the different categories of home-based functional exercise adherence in patients undergoing total knee arthroplasty (TKA), identify the influencing factors, and provide a reference for the development of personalized intervention strategies.Methods:A cross-sectional study was conducted using convenience sampling to select 320 patients who underwent unilateral primary TKA at The First Affiliated Hospital of Shandong First Medical University between November 2022 and January 2023. The Orthopedic Functional Exercise Compliance Scale, Rehabilitation Self-Efficacy Scale, and Social Support Rating Scale were used for data collection. Latent profile analysis was employed to identify the latent characteristics of home-based functional exercise adherence in TKA patients. Univariate analysis and logistic regression were used to explore the influencing factors among different subgroups.Results:A total of 320 questionnaires were distributed, with 307 valid responses, yielding a recovery rate of 95.94%. The 307 patients were classified into three latent profile categories based on their characteristics: low adherence group (29.32%, 90/307), moderate adherence group (46.58%, 143/307), and high adherence group (24.10%, 74/307). Logistic regression analysis revealed that the number of comorbidities, marital status, home rehabilitation environment, pain score, education level, social support, and rehabilitation self-efficacy were influencing factors for home-based exercise adherence in TKA patients ( P< 0.05) . Conclusions:Home-based functional exercise adherence in TKA patients can be categorized into three latent profiles. Healthcare providers should implement targeted interventions based on the specific characteristics of each patient, with a focus on those with low adherence, to enhance their compliance with home-based exercises.

Objective:To understand the major cognition, major choice motivation and the relationship between the two of medical students, and provide references and suggestions for the selection of talents in various majors of medical schools and the effective development of enrollment work.Methods:This study selected undergraduates of Batch 2019 from Peking University Health Science Center as the survey objects, conducted a questionnaire survey on their major cognition, major choice motivation and influencing factors, and used principal component analysis and Spearman rank correlation analysis.Results:The study found that the major cognition scores of 640 undergraduates of Batch 2019 from Peking University Health Science Center were clinical medicine (3.24±0.89) > stomatology (2.89±1.00) > basic medicine (2.66±1.02) > pharmacy (2.54±0.97) > preventive medicine (2.29±0.93) > nursing medicine (2.21±0.99) > medical laboratory (1.98±0.95) > medical English (1.95±0.93). Six major motivation factors for professional choice were school and professional strength, professional learning and job prospects, own factors, Peking University sentiments and the influence of others, medical factors, school policies, and the contribution rates were 34.60%, 12.97%, 7.42%, 6.00%, 5.59% and 5.37%, respectively. Major cognition scores and major choice motivation factors were positively correlated with each other to some extent.Conclusions:At present, students' major cognition level of medical majors still has a large room for improvement, and the motivational factors of major choice are more complicated, among which "the school and professional strength" and "the prospects of study and work" are important factors. Medical schools should focus on strengthening major publicity, improving students' major cognition, attracting aspiring students to apply for medical majors from many aspects, and improving the training quality of medical professionals.

The seventy-two grid palm technique is an important theoretical source of traditional Chinese medicine hand diagnosis. Starting from the ecological medical model， we analyse the seventy-two grid palm technique， and believe that its diagnosis of human body integrates biological， ecological， psychological， social and other factors， and each factor is based on physiological and pathological theories， and its external social interpretation of the nature of the human body is inseparable from health state. It is proposed that the seventy-two grid palm technique should be integrated with the ecological and natural viewpoints based on the biomedical models or bio-psycho-social medical models， and the research should be conducted from the perspective of the ecological medical model， in order to promote the development of hand diagnosis.

Objective:To study the prevalence of body dysmorphic disorder (BDD) in patients with plastic and cosmetic by performing meta-analysis.Methods:We searched, collected and screened the published studies on the prevalence of BDD in population with cosmetic surgery at home and abroad, and conducted a meta-analysis to calculate the prevalence of BDD in this population. The literatures were screened strictly according to the inclusion and exclusion criteria, and the quality of the included studies was evaluated with reference to AHRQ scale. Cochrane Q test was used to analyze the heterogeneity among the studies. If there was no heterogeneity, the fixed effect model was used for the pooled analysis of effect size. If there was heterogeneity, the random effect model was used for the pooled analysis of effect size, and the potential sources of heterogeneity were tested by meta regression, and subgroup analysis was performed. Sensitivity analysis was performed to test the stability of the result. Funnel plot was used to determine whether publication bias existed.Results:Thirteen articles were finally included in the meta-analysis, including 4 Chinese articles and 9 English articles, with a total sample size of 3 366 cases. A total of 435 cases of BDD were detected. The AHRQ scores of the 13 articles were greater or equal to 4 points. Heterogeneity test showed that there was a high degree of heterogeneity among the 13 studies, so the random effect model was used for pooled analysis of effect size. The results showed that the prevalence rate of BDD in population with plastic surgery was 13% (95% CI 9% - 18%). Sensitivity analysis shows that the result calculated by the random effect model are stable and reliable. Meta regression analysis showed that the difference of surgical site was one of the reasons for heterogeneity. Thirteen articles were divided into two groups according to patients with rhinoplasty and plastic surgery in other parts, and meta-analysis was conducted respectively. There were 3 articles in rhinoplasty group and 10 articles in other part of the plastic surgery. The result showed that the prevalence of BDD was 29% (95% CI 24% - 35%) in rhinoplasty group and 9% (95% CI 8% -10%) group with plastic surgery in other parts. Funnel plot analysis showed that there was no publication bias in this study. Conclusions:About 9% of the people with cosmetic surgery suffer from BDD, and the prevalence of BDD in the people seeking nasal plastic surgery can be as high as 29%. Plastic surgeons should pay special attention to this kind of people in clinical work, and use appropriate screening tools to identify them, so as to provide more scientific diagnosis and treatment plan for patients. Aesthetic plastic surgeons should pay attention to the evaluation of patients’ psychological state in clinical work.

Objective:To study the prevalence of body dysmorphic disorder (BDD) in patients with plastic and cosmetic by performing meta-analysis.Methods:We searched, collected and screened the published studies on the prevalence of BDD in population with cosmetic surgery at home and abroad, and conducted a meta-analysis to calculate the prevalence of BDD in this population. The literatures were screened strictly according to the inclusion and exclusion criteria, and the quality of the included studies was evaluated with reference to AHRQ scale. Cochrane Q test was used to analyze the heterogeneity among the studies. If there was no heterogeneity, the fixed effect model was used for the pooled analysis of effect size. If there was heterogeneity, the random effect model was used for the pooled analysis of effect size, and the potential sources of heterogeneity were tested by meta regression, and subgroup analysis was performed. Sensitivity analysis was performed to test the stability of the result. Funnel plot was used to determine whether publication bias existed.Results:Thirteen articles were finally included in the meta-analysis, including 4 Chinese articles and 9 English articles, with a total sample size of 3 366 cases. A total of 435 cases of BDD were detected. The AHRQ scores of the 13 articles were greater or equal to 4 points. Heterogeneity test showed that there was a high degree of heterogeneity among the 13 studies, so the random effect model was used for pooled analysis of effect size. The results showed that the prevalence rate of BDD in population with plastic surgery was 13% (95% CI 9% - 18%). Sensitivity analysis shows that the result calculated by the random effect model are stable and reliable. Meta regression analysis showed that the difference of surgical site was one of the reasons for heterogeneity. Thirteen articles were divided into two groups according to patients with rhinoplasty and plastic surgery in other parts, and meta-analysis was conducted respectively. There were 3 articles in rhinoplasty group and 10 articles in other part of the plastic surgery. The result showed that the prevalence of BDD was 29% (95% CI 24% - 35%) in rhinoplasty group and 9% (95% CI 8% -10%) group with plastic surgery in other parts. Funnel plot analysis showed that there was no publication bias in this study. Conclusions:About 9% of the people with cosmetic surgery suffer from BDD, and the prevalence of BDD in the people seeking nasal plastic surgery can be as high as 29%. Plastic surgeons should pay special attention to this kind of people in clinical work, and use appropriate screening tools to identify them, so as to provide more scientific diagnosis and treatment plan for patients. Aesthetic plastic surgeons should pay attention to the evaluation of patients’ psychological state in clinical work.

The Continuing Education Department of Chinese Medical Association has undertaken and participated in a number of tasks for the training of primary health care personnel in recent years. It has been recognized that the main measures to promote the development of primary continuing medical education including four aspects: national policies provide the direction of the development; medical progress is the output of the primary continuing medical education; the combination of multiple measures is a good way to carry out the primary continuing medical education; and technical means are the support of the development. Through understanding and grasping such factors as the national policies, medical development, education level, and technical conditions, and actively thinking about the relevant countermeasures, we can steadily and rapidly continue to promote the healthy development of continuing medical education at the grassroots level.