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.

This study aims to explore the protective effect of Chaihu Jia Longgu Muli Decoction on rats with heart failure after myocardial infarction, and to clarify its possible mechanisms, providing a new basis for basic research on the mechanism of classic Chinese medicinal formula-mediated inflammatory response in preventing and treating heart failure induced by apoptosis after myocardial infarction. A heart failure model after myocardial infarction was established in rats by coronary artery ligation. The rats were divided into sham group, model group, and low, medium, and high-dose groups of Chaihu Jia Longgu Muli Decoction, with 10 rats in each group. The low-dose, medium-dose, and high-dose groups of Chaihu Jia Longgu Muli Decoction were given 6.3, 12.6, and 25.2 g·kg~(-1) doses by gavage, respectively. The sham group and model group were given an equal volume of distilled water by gavage once daily for four consecutive weeks. Cardiac function was assessed using color Doppler echocardiography. Myocardial pathology was detected by hematoxylin-eosin(HE) staining, apoptosis was measured by TUNEL assay, and mitophagy was observed by transmission electron microscopy. The levels of tumor necrosis factor-α(TNF-α), interleukin(IL)-1β, and N-terminal pro-B-type natriuretic peptide(NT-proBNP) in serum were detected by enzyme-linked immunosorbent assay(ELISA). The expression of apoptosis-related proteins B-cell lymphoma 2(Bcl-2), Bcl-2-associated X protein(Bax), and cleaved caspase-3 was detected by Western blot. Additionally, the expression of phosphorylated nuclear transcription factor-κB(NF-κB) p65(p-NF-κB p65)(upstream) and nuclear factor kappa B inhibitor alpha(IκBα)(downstream) in the NF-κB signaling pathway was assessed by Western blot. The results showed that compared with the sham group, left ventricular ejection fraction(LVEF) and left ventricular short axis shortening(LVFS) in the model group were significantly reduced, while left ventricular end diastolic diameter(LVEDD) and left ventricular end systolic diameter(LVESD) increased significantly. Myocardial tissue damage was severe, with widened intercellular spaces and disorganized cell arrangement. The apoptosis rate was increased, and mitochondria were enlarged with increased vacuoles. Levels of TNF-α, IL-1β, and NT-proBNP were elevated, indicating an obvious inflammatory response. The expression of pro-apoptotic factors Bax and cleaved caspase-3 increased, while the anti-apoptotic factor Bcl-2 decreased. The expression of p-NF-κB p65 was upregulated, and the expression of IκBα was downregulated. In contrast, the Chaihu Jia Longgu Muli Decoction groups showed significantly improved of LVEF, LVFS and decreased LVEDD, LVESD compared to the model group. Myocardial tissue damage was alleviated, and intercellular spaces were reduced. The apoptosis rate decreased, mitochondrial volume decreased, and the levels of TNF-α, IL-1β, and NT-proBNP were lower. The expression of pro-apoptotic factors Bax and cleaved caspase-3 decreased, while the expression of the anti-apoptotic factor Bcl-2 increased. Additionally, the expression of p-NF-κB p65 decreased, while IκBα expression increased. In summary, this experimental study shows that Chaihu Jia Longgu Muli Decoction can reduce the inflammatory response and apoptosis rate in rats with heart failure after myocardial infarction, which may be related to the regulation of the IκBα/NF-κB signaling pathway.
Animals ; Apoptosis/drug effects* ; Drugs, Chinese Herbal/administration & dosage* ; Rats ; Myocardial Infarction/physiopathology* ; Male ; NF-kappa B/genetics* ; Heart Failure/etiology* ; Rats, Sprague-Dawley ; Signal Transduction/drug effects* ; NF-KappaB Inhibitor alpha/genetics* ; Humans ; Tumor Necrosis Factor-alpha/genetics*

Utilizing network pharmacology, molecular docking, and cellular experimental validation, this study delved into the therapeutic efficacy and underlying mechanisms of matrine in combating senescence. Databases were utilized to predict targets related to the anti-senescence effects of matrine, resulting in the identification of 81 intersecting targets for matrine in the treatment of senescence. A protein-protein interaction(PPI) network was constructed, and key targets were screened based on degree values. Gene Ontology(GO) function and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses were performed on the key targets to elucidate the critical pathways involved in the anti-senescence effects of matrine. Molecular docking was conducted between matrine and key targets. A senescence model was established using human umbilical vein endothelial cells(HUVECs) induced with hydrogen peroxide(H_2O_2). Following treatment with varying concentrations of matrine(0.5, 1, and 2 mmol·L~(-1)), cell viability was assessed by using the CCK-8. SA-β-galactosidase staining was employed to observe the positive rate of senescent cells. Flow cytometry was utilized to measure the apoptosis rate. Real-time quantitative PCR(RT-PCR) was utilized to measure the mRNA expression of apoptosis-related cysteine peptidase 3(CASP3), albumin(ALB), glycogen synthase kinase 3β(GSK3B), CD44 molecule(CD44), and tumor necrosis factor-α(TNF-α). Western blot was performed to detect the protein expression of tumor protein p53(p53), cyclin-dependent kinase inhibitor 1A(p21), cyclin-dependent kinase inhibitor 2A(p16), and retinoblastoma tumor suppressor protein(pRb) in the senescence signaling pathway, p38 protein kinase(p38), c-Jun N-terminal kinase(JNK), and extracellular regulated protein kinases(ERK) in the mitogen-activated protein kinase(MAPK) pathway, and phosphatidylinositol 3-kinase(PI3K) and protein kinase B(Akt) in the PI3K/Akt signaling pathway. The experimental results revealed that matrine significantly increased the viability of HUVECs(P<0.05), decreased the positive rate of senescent cells and the apoptosis rate(P<0.05), and reduced the mRNA expression levels of CASP3, ALB, GSK3B, CD44, and TNF-α(P<0.05). It also inhibited the protein expression of p53, p21, p16 and pRb in the senescence signaling pathway(P<0.05), upregulated the protein expression of p-PI3K/PI3K and p-Akt/Akt(P<0.05), and downregulated the protein expression of p-p38/p38, p-JNK/JNK, and p-ERK/ERK(P<0.05). Collectively, these findings suggest that matrine exerts an inhibitory effect on HUVECs senescence, and its mechanism involves the modulation of the senescence signaling pathway, MAPK pathway, and PI3K/Akt signaling pathway to suppress cell apoptosis and inflammation.
Humans ; Matrines ; Quinolizines/chemistry* ; Alkaloids/chemistry* ; Human Umbilical Vein Endothelial Cells/cytology* ; Cellular Senescence/drug effects* ; Network Pharmacology ; Molecular Docking Simulation ; Signal Transduction/drug effects* ; Protein Interaction Maps/drug effects* ; Cell Survival/drug effects* ; Apoptosis/drug effects* ; Drugs, Chinese Herbal/pharmacology*

AIM To investigate the promotional effects of esculin combined with bone marrow mesenchymal stem cells(BM-MSCs)transplantation on the repair of spinal cord injury(SCI)in rats.METHODS The rats were randomly divided into the sham operation group,the model group,the esculin group for gavage of 20 mg/kg esculin,the BM-MSCs group for tail vein injection of 1 mL of 1×106/mL BM-MSCs,and the combinaiton treatment group.The SCI rat model was established using Allen's method,followed by the 14 days consecutive corresponding drug administration starting from the 2nd day after modeling.On days 3,7 and 14 of drug administration,the rats had their hind limbs motor function evaluated by the BBB scoring;and their footprint experiment conducted on the 14th day after modeling.After 14 days of administration,the rats had their morphological changes of spinal cord tissue observed with HE staining and Nissl staining;their activities of SOD and GSH,and level of MDA in spinal cord tissue detected by kits;their expressions of MAP2,GAP43 and GFAP in spinal cord tissue detected by immunofluorescence;and their expressions of NQO-1,Nrf-2,Bcl-2 and Bax proteins in spinal cord tissue detected by Western blot.RESULTS Compared with the model group,the groups interved with esculin,or BM-MSCs,or the combination treatment showed improvements in hind limb function and spinal cord tissue morphology(P＜0.05);decreased MDA levels(P＜0.05);increased SOD and GSH activities(P＜0.05);increased MAP2 and GAP43 fluorescence intensity(P＜0.05);decreased GFAP fluorescence intensity(P＜0.05);increased NQO-1,Nrf-2 and Bcl-2 protein expressions(P＜0.05);and decreased Bax protein expression(P＜0.05).And the combination treatment group was observed with an even better effects(P＜0.05).CONCLUSION The combination of esculin and BM-MSCs transplantation can effectively improve the spinal cord tissue damage and hind limb function in SCI rats.This effect may be achieved by activating the Nrf-2/NQO-1 signaling pathway to inhibit oxidative stress response,thereby reducing neuronal apoptosis,blocking glial scar formation,and promoting stem cell differentiation to rebuild neurons.

Objective To explore the predictive factors of recurrence of chronic suppurative otitis media(CSOM)after otoendoscopic surgery,and construct a risk quantified nomogram model.Methods The clinical data of 485 patients with CSOM who underwent otoendoscopic surgery in our hospital from February 2021 to February 2023 were retrospectively analyzed.The patients were divided into the recurrence group and the non-recurrence group according to the recurrence situation during the follow-up period.The clinical data of patients between the two groups were compared,and the predictive factors of postoperative recurrence were analyzed by Cox regression method.A risk quantified nomogram model was constructed based on these predictive factors.The predictive efficiency of the model was verified by receiver operating characteristic(ROC)curve,and the calibration degree of the model was verified by Hosmer-Lemeshow goodness of fit analysis,and the clinical net benefit of the model was evaluated by decision curve analysis(DCA)method.Results Follow-up ranged from 6 to 39 months,with a median of 21(11,32)months,the postoperative recurrence rate was 14.64%(71/485).Combined with recurrent upper respiratory tract infections(HR=3.019,95%CI:1.609 to 5.664),combined with chronic rhinosinusitis(HR=2.428,95%CI:1.529 to 3.856),combined with adenoid hypertrophy(HR=2.214,95%CI:1.381 to 3.551),middle ear risk index(MERI)score(HR=2.863,95%CI:1.445 to 5.675),the seven-item eustachian tube dysfunction questionnaire(ETDQ-7)score(HR=2.679,95%CI:1.505 to 4.765)and inadequate drainage of the surgical cavity(HR=2.373,95%CI:1.503 to 3.746)were the risk factors for postoperative recurrence(P<0.05).A risk quantified nomogram model of recurrence after otoendoscopic surgery in CSOM patients was constructed based on the predictive factors of Cox regression analysis,among them the risk value ranges of patients who combined with recurrent upper respiratory tract infections,combined with chronic rhinosinusitis,combined with adenoid hypertrophy,MERI score,ETDQ-7 score,and inadequate drainage of the surgical cavity were 0 to 65 points,0 to 56 points,0 to 52 points,0 to 76 points,0 to 64 points,and 0 to 76 points,respectively.The area under the curve of ROC,sensitivity and specificity of the model for predicting postoperative recurrence were 0.928(95%CI:0.875 to 0.948),85.92%and 88.89%,respectively.There was no significant difference between the predicted probability of postoperative recurrence and the actual probability(P>0.05).The threshold probability of postoperative recurrence predicted by the model in the range of 4%to 92%could obtain clinical net benefit.Conclusion The predictive factors of recurrence after otoendoscopic surgery in CSOM patients include combined with recurrent upper respiratory tract infections,combined with chronic rhinosinusitis,combined with adenoid hypertrophy,MERI score,ETDQ-7 score and inadequate drainage of the surgical cavity,the risk quantified nomogram model based on these factors is highly effective in predicting postoperative recurrence.

Purpose: The genomic characteristics of uterine sarcomas have not been fully elucidated. This study aimed to explore the genomic landscape of the uterine sarcomas (USs). Materials and Methods: Comprehensive genomic analysis through RNA-sequencing was conducted. Gene fusion, differentially expressed genes (DEGs), signaling pathway enrichment, immune cell infiltration, and prognosis were analyzed. A deep learning model was constructed to predict the survival of US patients. Results: A total of 71 US samples were examined, including 47 endometrial stromal sarcomas (ESS), 18 uterine leiomyosarcomas (uLMS), three adenosarcomas, two carcinosarcomas, and one uterine tumor resembling an ovarian sex-cord tumor. ESS (including high-grade ESS [HGESS] and low-grade ESS [LGESS]) and uLMS showed distinct gene fusion signatures; a novel gene fusion site, MRPS18A–PDC-AS1 could be a potential diagnostic marker for the pathology differential diagnosis of uLMS and ESS; 797 and 477 uterine sarcoma DEGs (uDEGs) were identified in the ESS vs. uLMS and HGESS vs. LGESS groups, respectively. The uDEGs were enriched in multiple pathways. Fifteen genes including LAMB4 were confirmed with prognostic value in USs; immune infiltration analysis revealed the prognositic value of myeloid dendritic cells, plasmacytoid dendritic cells, natural killer cells, macrophage M1, monocytes and hematopoietic stem cells in USs; the deep learning model named Max-Mean Non-Local multi-instance learning (MMN-MIL) showed satisfactory performance in predicting the survival of US patients, with the area under the receiver operating curve curve reached 0.909 and accuracy achieved 0.804. Conclusion USs harbored distinct gene fusion characteristics and gene expression features between HGESS, LGESS, and uLMS. The MMN-MIL model could effectively predict the survival of US patients.

Hematologic malignancies, including leukemia, lymphoma, and multiple myeloma, are hazardous diseases characterized by the uncontrolled proliferation of cancer cells. Dysregulated cell cycle resulting from genetic and epigenetic abnormalities constitutes one of the central events. Importantly, cyclin-dependent kinases (CDKs), complexed with their functional partner cyclins, play dominating roles in cell cycle control. Yet, efforts in translating CDK inhibitors into clinical benefits have demonstrated disappointing outcomes. Recently, mounting evidence highlights the emerging significance of WEE1 G2 checkpoint kinase (WEE1) to modulate CDK activity, and correspondingly, a variety of therapeutic inhibitors have been developed to achieve clinical benefits. Thus, WEE1 may become a promising target to modulate the abnormal cell cycle. However, its function in hematologic diseases remains poorly elucidated. In this review, focusing on hematologic malignancies, we describe the biological structure of WEE1, emphasize the latest reported function of WEE1 in the carcinogenesis, progression, as well as prognosis, and finally summarize the therapeutic strategies by targeting WEE1.
Humans ; Protein-Tyrosine Kinases/physiology* ; Hematologic Neoplasms/drug therapy* ; Cell Cycle Proteins/antagonists & inhibitors* ; Nuclear Proteins/antagonists & inhibitors* ; Cyclin-Dependent Kinases ; Molecular Targeted Therapy ; Animals

Objective To investigate serum levels of food intake inhibitory factor-1(Nesfatin-1)and Klotho and their predictive value for secondary mild cognitive impairment(MCI)in elderly patients with type 2 diabetes mellitus(T2DM).Methods A total of 118 elderly patients with T2DM diagnosed and treated in the hospital from April 2023 to March 2024 were selected as the T2DM group,and they were divided into the non-MCI group(n=71)and the MCI group(n=47)according to the Montreal Cognitive Assessment(Mo-CA)scale.In addition,110 healthy people in the same hospital during the same period were selected as the control group.The clinical data of the patients were collected.Serum Nesfatin-1 and Klotho levels were detec-ted by enzyme-linked immunosorbent assay.Spearman and Pearson correlation analysis were used to analyze the correlation of serum Nesfatin-1 and Klotho levels with MoCA score and related clinical indicators in elder-ly patients with T2DM.Multivariate Logistic regression analysis was used to analyze the influencing factors for secondary MCI in elderly patients with T2DM.Receiver operating characteristic(ROC)curve was used to evaluate the predictive value of serum Nesfatin-1 and Klotho levels for secondary MCI in elderly patients with T2DM.Results Compared with control group,the serum levels of Nesfatin-1 and Klotho were significantly decreased in T2DM group(P<0.05).The serum levels of Nesfatin-1 and Klotho in MCI group were signifi-cantly lower than those in non-MCI group(P<0.05).Compared with the non-MCI group,the levels of fast-ing plasma glucose(FPG),insulin resistance index(HOMA-IR),reactive oxygen species(ROS)and C-reac-tive protein(CRP)were significantly increased in the MCI group(all P<0.05),and were negatively correla-ted with serum Nesfatin-1 and Klotho levels(all P<0.05).The serum levels of Nesfatin-1 and Klotho were positively correlated with MoCA score(P<0.05).Increased levels of FPG and ROS and decreased levels of Nesfatin-1 and Klotho were risk factors for secondary MCI in T2DM patients(P<0.05).The area under the curve of serum Nesfatin-1,Klotho and their combination for predicting secondary MCI in T2DM patients was 0.803,0.829 and 0.932,respectively.The combined prediction of serum nesfatin-1 and Klotho was better than each index alone(Zcombined-Nesfatin-1=3.421,P=0.001,Zcombined-Klotho=2.980,P=0.003).Conclusion The serum lev-els of Nesfatin-1 and Klotho are decreased in T2DM patients,which are significantly correlated with secondary MCI in T2DM patients,and both of them have high predictive value for secondary MCI in T2DM patients.