To thoroughly implement the strategic deployment outlined in the Opinions of the Central Committee of the Communist Party of China and the State Council on Promoting the Inheritance and Innovative Development of Traditional Chinese Medicine regarding research on dominant diseases of traditional Chinese medicine and to uphold the development philosophy of equal emphasis on traditional Chinese medicine and western medicine，the China Association of Chinese Medicine has fully played a leading academic role by systematically organizing and conducting a series of academic youth salons on clinical dominant diseases of traditional Chinese medicine. On September 13，2024，the 36^th Youth Salon on Clinical Dominant Diseases was successfully held in Nanjing，focusing on the advantages of traditional Chinese medicine and the integrative traditional Chinese medicine and western medicine in the diagnosis and treatment of erectile dysfunction （ED）. The conference brought together leading experts from traditional Chinese medicine，western medicine，and interdisciplinary fields，facilitating in-depth multidisciplinary discussions that led to key consensus on optimizing traditional Chinese medicine treatment protocols for ED，researching and developing new drugs of traditional Chinese medicine，and advancing interdisciplinary development in traditional Chinese medicine. This salon systematically sorted out the clinical strengths and distinctive features of traditional Chinese medicine in the diagnosis and treatment of ED. Based on current research foundations and clinical needs，it identified key directions for future scientific layout and scientific research tackling： （1） Standardization of syndrome differentiation system of traditional Chinese medicine for ED. （2） Optimization and standardization of intervention methods of integrated traditional Chinese medicine and western medicine. （3） High-quality clinical research guided by evidence-based medicine. （4） In-depth analysis of the pharmacological mechanisms of traditional Chinese medicine in the treatment of ED. （5） Clinical translation and application promotion of new drugs of traditional Chinese medicine. （6） Interdisciplinary integration and innovation in traditional Chinese medicine. For each research direction，key focus areas，expected objectives，and clinical value were further refined，along with the establishment of a scientifically sound priority funding level evaluation system. Therefore，building on the series of salons on the ED-focused dominant diseases of traditional Chinese medicine，this paper provides standardized guidance for clinical practice of traditional Chinese medicine in ED management，effectively contributing to the high-quality development of traditional Chinese medicine. It serves as a valuable reference for national scientific and technological strategic layout， research and development decision-making in new drugs of traditional Chinese medicine，research topic planning，and clinical guideline formulation.

The medicinal materials of Bawei Chenxiang Pills(BCPs) were extracted via three methods: reflux extraction by water, reflux extraction by 70% ethanol, and extraction by pure water following reflux extraction by 70% ethanol, yielding three extracts of ST, CT, and CST. The efficacy of ST(760 mg·kg~(-1)), CT(620 mg·kg~(-1)), and CST(1 040 mg·kg~(-1)) were evaluated by acute myocardial ischemia(AMI) and p-chlorophenylalanine(PCPA)-induced insomnia in mice, respectively. Western blot was further utilized to investigate their hypnosis mechanisms. The main chemical components of different extracts were identified by the UPLC-Q-Exactive-MS technique. The results showed that CT and CST significantly increased the ejection fraction(EF) and fractional shortening(FS) of myocardial infarction mice, reduced left ventricular internal dimension at end-diastole(LVIDd) and left ventricular internal dimension at end-systole(LVIDs). In contrast, ST did not exhibit significant effects on these parameters. In the insomnia model, CT significantly reduced sleep latency and prolonged sleep duration, whereas ST only prolonged sleep duration without shortening sleep latency. CST showed no significant effects on either sleep latency or sleep duration. Additionally, both CT and ST upregulated glutamic acid decarboxylase 67(GAD67) protein expression in brain tissue. A total of 15 main chemical components were identified from CT, including 2-(2-phenylethyl) chromone and 6-methoxy-2-(2-phenylethyl) chromone. Six chemical components including chebulidic acid were identified from ST. The results suggested that chromones and terpenes were potential anti-myocardial ischemia drugs of BCPs, and tannin and phenolic acids were potential hypnosis drugs. This study enriches the pharmacological and chemical research of BCPs, providing a basis and reference for their secondary development, quality standard improvement, and clinical application.
Animals ; Drugs, Chinese Herbal/isolation & purification* ; Mice ; Male ; Sleep Initiation and Maintenance Disorders/physiopathology* ; Humans ; Myocardial Infarction/drug therapy* ; Myocardial Ischemia/drug therapy*

OBJECTIVE: To screen out the key metabolites related to diabetic foot (DF) by integrating genome-wide association studies (GWAS) and metabolome genome-wide association studies (mGWAS). METHODS: The literature databases such as PubMed and China national knowledge infrastructure(CNKI), as well as genomics databases such as PAN UKBB, FinnGen, and IEU Open GWAS were systematically retrieved from database estobilishment to November 2024 on DF-related single nucleotide polymorphisms and genome-wide association studies. DF-single nucleotide polymorphism-metabolite network was constructed by mGWAS package and mGWAS-Explorer platform. The causal relationship between key factors was evaluated by two-sample Mendelian randomization. The genetic correlation between DF and 575 metabolites (source:IEU Open GWAS) was evaluated by linkage disequilibrium score regression. In vitro experiments were conducted to induce injury of human umbilical vein endothelial cells with 30 mM glucose and intervene with 20 μM γ-tocopherol. Changes in cell migration, scratch healing and tube formation function were detected. RESULTS: Twenty-senen literatures on single nucleotide polymorphism literatures and 3 studies on GWAS were included. Genetic analysis results showed DF-related single nucleotide polymorphisms were enriched in vascular endothelial dysfunction-related pathways (such as fluid shear stress and atherosclerosis). The results of metabolic network analysis screened out 19 associated metabolites, among which 12 such as γ -tocopherol and pyruvate had significant genetic correlations with DF. Mendelian randomization suggested matrix metalloproteinase-9(MMP-9) might be a potential driver of DF (β=0.658, P=0.063 8), and the occurrence of DF could reduce the level of high-density lipoprotein (β=-0.002, P=0.015 2). The results of in vitro experiments confirmed that γ -tocopherol could improve endothelial dysfunction induced by high glucose, specifically manifested as an increase in the number of cell migrations, improvement in the scratch healing rate, and recovery of tubule formation ability (P<0.05). CONCLUSION DF has a genetic basis centered on vascular endothelial dysfunction, and its occurrence can lead to further metabolic disorders. The key single nucleotide polymorphism loci integrated provided molecular markers for the risk stratification of foot ulcers in diabetic patients. In addition, γ -tocopherol has demonstrated clinical application potential as a therapeutic drug for DF by significantly improving the function of vascular endothelial cells in a high-glucose environment.
Humans ; Diabetic Foot/drug therapy* ; Polymorphism, Single Nucleotide ; Genome-Wide Association Study ; Genomics ; Metabolomics ; Metabolome

Chronic cerebral hypoperfusion leads to white matter injury (WMI), which plays a significant role in contributing to vascular cognitive impairment. While 13-docosenamide is a type of fatty acid amide, it remains unclear whether it has therapeutic effects on chronic cerebral hypoperfusion. In this study, we conducted bilateral common carotid artery stenosis (BCAS) surgery to simulate chronic cerebral hypoperfusion-induced WMI and cognitive impairment. Our findings showed that 13-docosenamide alleviates WMI and cognitive impairment in BCAS mice. Mechanistically, 13-docosenamide specifically binds to cannabinoid receptor 1 (CNR1) in oligodendrocyte precursor cells (OPCs). This interaction results in an upregulation of ubiquitin-specific peptidase 33 (USP33)-mediated CNR1 deubiquitination, subsequently increasing CNR1 protein expression, activating the phosphorylation of the AKT/mTOR pathway, and promoting the differentiation of OPCs. In conclusion, our study suggests that 13-docosenamide can ameliorate chronic cerebral hypoperfusion-induced WMI and cognitive impairment by enhancing OPC differentiation and could serve as a potential therapeutic drug.
Animals ; Oligodendrocyte Precursor Cells/metabolism* ; Mice ; Cell Differentiation/drug effects* ; Male ; Receptor, Cannabinoid, CB1/metabolism* ; Mice, Inbred C57BL ; Ubiquitin Thiolesterase/metabolism* ; Ubiquitination/drug effects* ; Carotid Stenosis/complications* ; Cognitive Dysfunction/drug therapy*

The NOD-like receptor protein 3 (NLRP3) inflammasome is essential in innate immune-mediated inflammation, with its overactivation implicated in various autoinflammatory, metabolic, and neurodegenerative diseases. Pharmacological inhibition of NLRP3 offers a promising treatment strategy for inflammatory conditions, although no medications targeting the NLRP3 inflammasome are currently available. This study demonstrates that clioquinol (CQ), a clinical drug with chelating properties, effectively inhibits NLRP3 activation, resulting in reduced cytokine secretion and cell pyroptosis in both human and mouse macrophages, with a half maximal inhibitory concentration (IC₅₀) of 0.478 μM. Additionally, CQ mitigates experimental acute peritonitis, gouty arthritis, sepsis, and colitis by lowering serum levels of interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α). Mechanistically, CQ covalently binds to Arginine 335 (R335) in the NACHT domain, inhibiting NLRP3 inflammasome assembly and blocking the interaction between NLRP3 and its component protein. Collectively, this study identifies CQ as an effective natural NLRP3 inhibitor and a potential therapeutic agent for NLRP3-driven diseases.

The NOD-like receptor protein 3(NLRP3)inflammasome is essential in innate immune-mediated inflammation,with its overactivation implicated in various autoinflammatory,metabolic,and neurode-generative diseases.Pharmacological inhibition of NLRP3 offers a promising treatment strategy for in-flammatory conditions,although no medications targeting the NLRP3 inflammasome are currently available.This study demonstrates that clioquinol(CQ),a clinical drug with chelating properties,effec-tively inhibits NLRP3 activation,resulting in reduced cytokine secretion and cell pyroptosis in both human and mouse macrophages,with a half maximal inhibitory concentration(IC50)of 0.478 μM.Additionally,CQ mitigates experimental acute peritonitis,gouty arthritis,sepsis,and colitis by lowering serum levels of interleukin-1β(IL-1β),IL-6,and tumor necrosis factor-α(TNF-α).Mechanistically,CQ covalently binds to Arginine 335(R335)in the NACHT domain,inhibiting NLRP3 inflammasome assembly and blocking the interaction between NLRP3 and its component protein.Collectively,this study identifies CQ as an effective natural NLRP3 inhibitor and a potential therapeutic agent for NLRP3-driven diseases.

Objective:To analyze the clinical characteristics of 18 patients with Brucella melitensis infection (abbreviated as brucellosis) in Xinjiang Uygur Autonomous Region (abbreviated as Xinjiang). Methods:A retrospective analysis was conducted on the medical records of 18 patients diagnosed with Brucella melitensis infection by blood culture at the First Affiliated Hospital of Shihezi University from March 2023 to March 2024, including general information, epidemiological characteristics, clinical manifestations, laboratory test results, etc. Results:Among the 18 patients with sheep brucellosis, 14 patients were aged 45-59 years old and 13 patients were male, with 13 cases having a clear history of contact with cattle and sheep. The main clinical manifestations were fever (18 cases), bone and joint pain (5 cases), and fatigue (5 cases). Laboratory test results confirmed all 18 cases as Brucella melitensis infection (AMOS-PCR), with one case originating from cattle. Laboratory tests showed that 12 patients had elevated lactate dehydrogenase (LDH) levels. Correlation analysis revealed, there was a positive association between aspartate aminotransferase (AST) and LDH ( r = 0.84, P < 0.001); a positive correlation between the number of affected systems and the percentage of neutrophils (N%, r = 0.73, P = 0.001); a positive correlation between the duration of medication and the number of affected systems ( r = 0.82, P < 0.001) and N% ( r = 0.75, P = 0.001); and a negative correlation between treatment duration and lymphocyte percentage (LYM%, r =-0.76, P = 0.001). Conclusions:The main source of Brucella melitensis infection in Xinjiang is sheep, and contact with cattle can also cause Brucella melitensis infection. Brucella melitensis patients are more common in middle-aged males. The clinical manifestations are diverse and atypical; N% and LYM% are correlated with the number of affected systems.

Objective:To analyze the clinical characteristics of 18 patients with Brucella melitensis infection (abbreviated as brucellosis) in Xinjiang Uygur Autonomous Region (abbreviated as Xinjiang). Methods:A retrospective analysis was conducted on the medical records of 18 patients diagnosed with Brucella melitensis infection by blood culture at the First Affiliated Hospital of Shihezi University from March 2023 to March 2024, including general information, epidemiological characteristics, clinical manifestations, laboratory test results, etc. Results:Among the 18 patients with sheep brucellosis, 14 patients were aged 45-59 years old and 13 patients were male, with 13 cases having a clear history of contact with cattle and sheep. The main clinical manifestations were fever (18 cases), bone and joint pain (5 cases), and fatigue (5 cases). Laboratory test results confirmed all 18 cases as Brucella melitensis infection (AMOS-PCR), with one case originating from cattle. Laboratory tests showed that 12 patients had elevated lactate dehydrogenase (LDH) levels. Correlation analysis revealed, there was a positive association between aspartate aminotransferase (AST) and LDH ( r = 0.84, P < 0.001); a positive correlation between the number of affected systems and the percentage of neutrophils (N%, r = 0.73, P = 0.001); a positive correlation between the duration of medication and the number of affected systems ( r = 0.82, P < 0.001) and N% ( r = 0.75, P = 0.001); and a negative correlation between treatment duration and lymphocyte percentage (LYM%, r =-0.76, P = 0.001). Conclusions:The main source of Brucella melitensis infection in Xinjiang is sheep, and contact with cattle can also cause Brucella melitensis infection. Brucella melitensis patients are more common in middle-aged males. The clinical manifestations are diverse and atypical; N% and LYM% are correlated with the number of affected systems.

Objective:To investigate the clinical effect of magnetic stimulation combined with moxibustion on mild to moderate overactive bladder(OAB)and sexual function in women.Methods:We enrolled 80 female patients with mild to moderate OAB in this study and equally randomized them into a control and an experimental group,the former treated by magnetic stimulation and the latter by magnetic stimulation combined with moxibustion,both for 8 weeks.We obtained from the patients their OAB syndrome scores(OABSS),72-hour urination diary(72-h UD)scores,International Consultation on Incontinence Questionnaire-Overactive Bladder(ICIQ-OAB)scores and female sexual function indexes(FSFI),and compared them between the two groups before and after interven-tion.Results:A total of 77 patients completed the study,37 in the control and 40 in the experimental group.There were no statisti-cally significant differences in the baseline data between the two groups(P＞0.05).Compared with the baseline,the experimental group showed significant improvement after treatment in the OABSS(7.54±1.12 vs 4.46±0.96),72-h urine volume([126.40±46.04]vs[216.63±38.26]ml),urination frequency(15.55±3.21 vs 8.03±1.40),ICIQ-OAB score(10.25±1.15 vs 6.32±1.07)and FSFI(20.00±12.40 vs 33.30±21.00)(all P＜0.05),even more significantly than in the control group(OABSS:4.46±0.96 vs 5.59±0.90;72-h urine volume:[216.63±38.26]vs[173.41±15.55]ml;urination frequency:8.03±1.40 vs 9.90±1.49;ICIQ-OAB score:6.32±1.07 vs 7.89±0.77;FSFI:33.30±21.00 vs 30.40±10.40)(all P＜0.01).Conclu-sion:Magnetic stimulation combined with moxibustion can improve the symptoms of mild to moderate overactive bladder and improve sexual function in females.

Objective:To explore whether thiotert treatment can inhibit proliferation and induce apoptosis in myelodysplastic syndromes(MDS)cells.Methods:CCK-8 assay was used for determining the cytotoxicity of thiotert to MDS cell line SKM-1 and the reversal effect of GSH,NAC,and Z-VAD-FMK on thiotert-induced inhibition of cell viability.EdU assay was deployed to detect the cell proliferation ability.Intracellular reactive oxygen species(ROS)was measured by flow cytometry after DCFH-DA staining.The expression of DNA damage-and apoptosis-related proteins was detected by Western blot.Results:Thiotert treatment significantly suppressed the cell viability and proliferation ability in SKM-1 cells.A large amount of ROS generation and markedly elevated C-PARP,C-Caspase 3,and γ-H2AX were observed after thiotert administration,while BCL-2 was significantly decreased.In addition,GSH,NAC,and Z-VAD-FMK were able to mitigate the cytotoxicity of thiotert on SKM-1 cells.Conclusion:Thiotert can promote MDS cell apoptosis by mediating ROS production and pro-apoptotic proteins expression.