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.

ObjectiveTo explore the protective effect and underlying mechanism of Gegen Qinliantang on cognitive function in db/db mice with diabetic cognitive impairment （DCI）. MethodsThirty-two 8-week-old male db/db mice were randomly assigned to the model group， dapagliflozin group （1.0 mg·kg^-1·d^-1）， low-dose Gegen Qinliantang group （6.24 g·kg^-1·d^-1）， and high-dose Gegen Qinliantang group （24.96 g·kg^-1·d^-1）. Eight db/m mice served as the normal group. All mice were administered the corresponding treatment once daily by gavage for 10 consecutive weeks. Body weight and fasting blood glucose （FBG） were dynamically monitored. The Morris water maze test was used to evaluate cognitive function. Hematoxylin-eosin （HE） staining and Nissl staining were used to observe pathological changes in the hippocampus. Enzyme-linked immunosorbent assay （ELISA） was employed to measure the levels of tumor necrosis factor-α （TNF-α） and interleukin-1β （IL-1β） in hippocampal tissue. Immunofluorescence double staining was used to detect the co-expression of M1 microglial marker CD16/32 and ionized calcium-binding adapter molecule 1 （IBA1） in the hippocampus. Western blot analysis was performed to detect the protein expression of postsynaptic density protein 95 （PSD-95）， synapsin （SYN）， nuclear factor-κB p65 （NF-κB p65）， and phosphorylated NF-κB p65 （p-NF-κB p65） in the hippocampus. ResultsCompared with the normal group， the model group showed significantly increased body weight and FBG levels （P<0.01）， significantly prolonged escape latency and reduced platform crossings in the Morris water maze test （P<0.01）， disordered arrangement of hippocampal neurons， nuclear pyknosis， increased neuronal necrosis， reduced Nissl bodies， decreased expression of synaptic proteins PSD-95 and SYN （P<0.01）， increased CD16/32⁺ /IBA1⁺ positive rate， elevated levels of TNF-α and IL-1β， and an increased p-NF-κB p65/NF-κB p65 ratio （P<0.01）. Compared with the model group， the dapagliflozin group exhibited significantly reduced FBG levels at weeks 5 and 10 （P<0.05， P<0.01） and increased body weight. The high-dose Gegen Qinliantang group showed significantly reduced FBG at week 10 （P<0.05）. Escape latency was significantly reduced on days 3 and 5 of the water maze test in the dapagliflozin group and on day 5 in the high-dose Gegen Qinliantang group （P<0.05）. Platform crossings were significantly increased in both the dapagliflozin group and the high-dose Gegen Qinliantang group （P<0.05）. Hippocampal pathological damage was alleviated to varying degrees in the dapagliflozin group and the low- and high-dose Gegen Qinliantang groups， with significantly increased expression of PSD-95 and SYN （P<0.01）. Further studies revealed that both low- and high-dose Gegen Qinliantang reduced hippocampal IL-1β levels and the CD16/32⁺/IBA1⁺ positive rate of microglia， while the high-dose group also significantly reduced hippocampal TNF-α levels and the p-NF-κB p65/NF-κB p65 （P<0.05， P<0.01）. ConclusionGegen Qinliantang can improve hyperglycemia， cognitive dysfunction， and synaptic damage in DCI， inhibit M1 polarization of microglia and neuroinflammation， and its mechanism may be related to the inhibition of NF-κB activation.

BACKGROUND: The contraction behaviors of cardiomyocytes (CMs), especially contraction synchrony, are crucial factors reflecting their maturity and response to drugs. A wider field of view helps to observe more pronounced synchrony differences, but the accompanied greater computational load, requiring more computing power or longer computational time. METHODS: We proposed a method that directly correlates variations in optical field brightness with cardiac tissue contraction status (CVB method), based on principles from physics and photometry, for rapid video analysis in wide field of view to obtain contraction parameters, such as period and contraction propagation direction and speed. RESULTS: Through video analysis of human induced pluripotent stem cell (hiPSC)-derived CMs labeled with green fluorescent protein (GFP) cultured on aligned and random nanofiber scaffolds, the CVB method was demonstrated to obtain contraction parameters and quantify the direction and speed of contraction within regions of interest (ROIs) in wide field of view. The CVB method required less computation time compared to one of the contour tracking methods, the LucasKanade (LK) optical flow method, and provided better stability and accuracy in the results. CONCLUSION This method has a smaller computational load, is less affected by motion blur and out-of-focus conditions, and provides a potential tool for accurate and rapid analysis of cardiac tissue contraction synchrony in wide field of view without the need for more powerful hardware.

Summarized the nursing experience of a patient with concurrent Nectriahaematococca infection after allogeneic hematopoietic stem cell transplantation. The nursing points included: implementing infection prevention and control measures to prevent the recurrence of severe infections. Provide goal oriented care measures to control skin infection symptoms. Provide preventive nursing interventions for fungal keratitis to prevent potential infections from occurring. Strengthen medication management and be vigilant against adverse drug reactions.Implementing multiple forms of psychological care to enhance confidence in disease treatment. After active treatment and meticulous care, the patient infection was controlled and successfully discharged on the 59th day after transplantation.

Purpose To analyze and discuss the clinicopathological,molecular pathological characteristics,as well as diagnostic and prognostic features of pleomorphic xanthoastrocytoma(PXA)according to the new WHO classifi-cation.Methods 79 cases of PXA were collected to analyze their pathological and clinical data.Immunohistochemis-try using the EnVision method was employed to detect the expression of CD34,ATRX,Rb,Olig-2,H3K27M,H3K27me3,IDH1 R132H,BRAF VE1 and Ki67.Sanger sequencing was used to detect mutations in H3F3A and IDH1/2.Fluorescence quantitative PCR was used to detect the BRAF V600E mutation and TERT promoter region al-terations.Fluorescence in situ hybridization(FISH)was used to detect CDKN2A and EGFR alterations.The relation-ship between clinical,pathological,molecular genetics data,and prognosis was analyzed.Results The patients'ages ranged from 9 to 69 years,with an average age of 36.4 years.Most tumors were located in the temporal lobe,frontal lobe and parietal lobe.Among the 79 cases,42 were classified as grade 2 PXA and 37 as grade 3 PXA.The tumor cells exhibited pleomorphic changes,with perivascular lymphocytic sheaths and eosinophilic bodies frequently ob-served.Grade 3 PXA exhibited more mitotic figures(average of 11.8/10 HPF),and was usually accompanied by nec-rosis,focal marginal infiltration and microvascular proliferation.Immunohistochemistry and molecular characteristics revealed frequent positivity for CD34,BRAF V600E mutation(68.1％),and CDKN2A homozygous deletion(36.8％)in PXA.Some cases showed TERT gene mutation and absent Rb expression.Univariate survival analysis in-dicated that necrosis,focal marginal infiltration,and CNS WHO grade were related to overall survival,while focal infil-tration and CNS WHO grade were the independent risk factors.Conclusion The prognosis of CNS WHO grade 3 PXA is wrose than that of grade 2 PXA.Accurate diagnosis of PXA requires the combination of the morphological features,immunohistochemical staining,and multiple molecular tests.

Ovarian cancer is the most lethal malignancy affecting the female reproductive system. Pharmacological inhibitors targeting CDK4/6 have demonstrated promising efficacy across various cancer types. However, their clinical benefits in ovarian cancer patients fall short of expectations, with only a subset of patients experiencing these advantageous effects. This study aims to provide further clinical and biological evidence for antineoplastic effects of a CDK4/6 inhibitor (TQB4616) in ovarian cancer and explore underlying mechanisms involved. Patient-derived ovarian cancer organoid models were established to evaluate the effectiveness of TQB3616. Potential key genes related to TQB3616 sensitivity were identified through RNA-seq analysis, and TRIM4 was selected as a candidate gene for further investigation. Subsequently, co-immunoprecipitation and GST pull-down assays confirmed that TRIM4 binds to hnRNPDL and promotes its ubiquitination through RING and B-box domains. RIP assay demonstrated that hnRNPDL binded to CDKN2C isoform 2 and suppressed its expression by alternative splicing. Finally, in vivo studies confirmed that the addition of siTRIM4 significantly improved the effectiveness of TQB3616. Overall, our findings suggest that TRIM4 modulates ubiquitin-mediated degradation of hnRNPDL and weakens sensitivity to CDK4/6 inhibitors in ovarian cancer treatment. TRIM4 may serve as a valuable biomarker for predicting sensitivity to CDK4/6 inhibitors in ovarian cancer.
Humans ; Female ; Ovarian Neoplasms/pathology* ; Animals ; Tripartite Motif Proteins/genetics* ; Mice ; Cyclin-Dependent Kinase 4/antagonists & inhibitors* ; Cell Line, Tumor ; Cyclin-Dependent Kinase 6/antagonists & inhibitors* ; Protein Kinase Inhibitors/pharmacology* ; Ubiquitin/metabolism* ; Xenograft Model Antitumor Assays ; Ubiquitination ; Antineoplastic Agents/pharmacology*

Vein graft (VG) failure (VGF) is associated with VG intimal hyperplasia, which is characterized by abnormal accumulation of vascular smooth muscle cells (VSMCs). Most neointimal VSMCs are derived from pre-existing VSMCs via a process of VSMC phenotypic transition, also known as dedifferentiation. There is increasing evidence to suggest that ginger or its bioactive ingredients may block VSMC dedifferentiation, exerting vasoprotective functions; however, the precise mechanisms have not been fully characterized. Therefore, we investigated the effect of ginger on VSMC phenotypic transition in VG remodeling after transplantation. Ginger significantly inhibited neointimal hyperplasia and promoted lumen (L) opening in a 3-month VG, which was primarily achieved by reducing ferroptotic stress. Ferroptotic stress is a pro-ferroptotic state. Contractile VSMCs did not die but instead gained a proliferative capacity and switched to the secretory type, forming neointima (NI) after vein transplantation. Ginger and its two main vasoprotective ingredients (6-gingerol and 6-shogaol) inhibit VSMC dedifferentiation by reducing ferroptotic stress. Network pharmacology analysis revealed that 6-gingerol inhibits ferroptotic stress by targeting P53, while 6-shogaol inhibits ferroptotic stress by targeting 5-lipoxygenase (Alox5), both promoting ferroptosis. Furthermore, both ingredients co-target peroxisome proliferator-activated receptor gamma (PPARγ), decreasing PPARγ-mediated nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 1 (Nox1) expression. Nox1 promotes intracellular reactive oxygen species (ROS) production and directly induces VSMC dedifferentiation. In addition, Nox1 is a ferroptosis-promoting gene that encourages ferroptotic stress production, indirectly leading to VSMC dedifferentiation. Ginger, a natural multi-targeted ferroptotic stress inhibitor, finely and effectively prevents VSMC phenotypic transition and protects against venous injury remodeling.

Computational approaches, encompassing both physics-based and machine learning (ML) methodologies, have gained substantial traction in drug repurposing efforts targeting specific therapeutic entities. The human dopamine (DA) transporter (hDAT) is the primary therapeutic target of numerous psychiatric medications. However, traditional hDAT-targeting drugs, which interact with the primary binding site, encounter significant limitations, including addictive potential and stimulant effects. In this study, we propose an integrated workflow combining virtual screening based on weighted holistic atom localization and entity shape (WHALES) descriptors with in vitro experimental validation to repurpose novel hDAT-targeting drugs. Initially, WHALES descriptors facilitated a similarity search, employing four benztropine-like atypical inhibitors known to bind hDAT's allosteric site as templates. Consequently, from a compound library of 4,921 marketed and clinically tested drugs, we identified 27 candidate atypical inhibitors. Subsequently, ADMETlab was employed to predict the pharmacokinetic and toxicological properties of these candidates, while induced-fit docking (IFD) was performed to estimate their binding affinities. Six compounds were selected for in vitro assessments of neurotransmitter reuptake inhibitory activities. Among these, three exhibited significant inhibitory potency, with half maximal inhibitory concentration (IC₅₀) values of 0.753 μM, 0.542 μM, and 1.210 μM, respectively. Finally, molecular dynamics (MD) simulations and end-point binding free energy analyses were conducted to elucidate and confirm the inhibitory mechanisms of the repurposed drugs against hDAT in its inward-open conformation. In conclusion, our study not only identifies promising active compounds as potential atypical inhibitors for novel therapeutic drug development targeting hDAT but also validates the effectiveness of our integrated computational and experimental workflow for drug repurposing.

BACKGROUND: The contraction behaviors of cardiomyocytes (CMs), especially contraction synchrony, are crucial factors reflecting their maturity and response to drugs. A wider field of view helps to observe more pronounced synchrony differences, but the accompanied greater computational load, requiring more computing power or longer computational time. METHODS: We proposed a method that directly correlates variations in optical field brightness with cardiac tissue contraction status (CVB method), based on principles from physics and photometry, for rapid video analysis in wide field of view to obtain contraction parameters, such as period and contraction propagation direction and speed. RESULTS: Through video analysis of human induced pluripotent stem cell (hiPSC)-derived CMs labeled with green fluorescent protein (GFP) cultured on aligned and random nanofiber scaffolds, the CVB method was demonstrated to obtain contraction parameters and quantify the direction and speed of contraction within regions of interest (ROIs) in wide field of view. The CVB method required less computation time compared to one of the contour tracking methods, the LucasKanade (LK) optical flow method, and provided better stability and accuracy in the results. CONCLUSION This method has a smaller computational load, is less affected by motion blur and out-of-focus conditions, and provides a potential tool for accurate and rapid analysis of cardiac tissue contraction synchrony in wide field of view without the need for more powerful hardware.

The menopausal age is one of the important menopausal factors, and women of different menopausal ages have different risks of diabetes. This study reviewed the evidence from prospective studies on the association between the age at natural menopause and diabetes risk, both domestically and internationally, and presented its research design and main findings. Advanced menopause, especially premature and early menopause, will increase the risk of diabetes in postmenopausal women. The research on the influence of delayed menopause on the incidence of diabetes is still insufficient. Many factors may modify the association between menopausal age and the risk of diabetes.