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 molecular mechanisms by which serum containing Gegen Qinlian Tang （GQT） inhibits glycolysis and enhances chemotherapy sensitivity in 5-fluorouracil （5-FU）-resistant colorectal cancer （CRC） cells based on the cyclin-dependent kinase 16 （CDK16）/MYC proto-oncogene （MYC） pathway. MethodsHCT-116/5-FU cells were treated with different concentrations （5%， 10%， 20%， 30%） of GQT-containing serum. Cell viability and 5-FU sensitivity were assessed using the cell counting kit-8 （CCK-8） assay， and the experimental concentrations of 5-FU and GQT for subsequent experiments were determined. Cell proliferation and apoptosis under individual 5-FU， GQT， and combined 5-FU + GQT treatments were evaluated using 5-ethynyl-2′-deoxyuridine （EDU） staining and annexin V-FITC/PI double staining， respectively. Glucose consumption， adenosine triphosphate （ATP） production， and lactate levels were measured by colorimetric assays. Expression levels of glycolysis-related proteins， CDK16， MYC， and phosphorylated MYC were detected by Western blot. Co-immunoprecipitation （CoIP） was used to examine the protein interaction between CDK16 and MYC， and cycloheximide （CHX） treatment was applied to assess the effect of CDK16 overexpression on MYC protein stability. ResultsCCK-8 assays showed that 2.5 mg·L^-1 5-FU significantly inhibited HCT-116 cell viability in a dose-dependent manner. In HCT-116/5-FU cells， significant inhibition was observed only at 5 mg·L^-1 5-FU （P<0.05）， which was used for model establishment. Compared with 5-FU alone， addition of 5% GQT-containing serum significantly suppressed HCT-116/5-FU cell viability （P<0.05）， with stronger inhibition at higher serum concentrations. Thus， 5% GQT-containing serum was used in subsequent experiments. Compared with the control group， 5-FU， GQT， and 5-FU + GQT treatments all significantly reduced cell proliferation （P<0.05） and increased apoptosis （P<0.01）. The 5-FU + GQT combination showed superior inhibition of proliferation compared with 5-FU or GQT alone （P<0.01）， accompanied by more pronounced reductions in glucose consumption， ATP production， and lactate generation （P<0.01）. Additionally， compared with control， 5-FU， and GQT groups， the 5-FU + GQT group exhibited stronger suppression of MYC and its phosphorylated forms （P<0.01） and greater inhibition of glycolytic enzymes， including hexokinase 2 （HK2）， 3-phosphoinositide-dependent protein kinase 1 （PDK1）， lactate dehydrogenase A （LDHA）， and pyruvate kinase M2 （PKM2） （P<0.01）. CDK16， MYC， and MYC phosphorylation expression levels were significantly downregulated in the 5-FU + GQT group compared with the 5-FU group （all P<0.01）. MYC protein stability decreased in a time-dependent manner in the 5-FU + GQT group （P<0.05）， which was rescued by CDK16 overexpression （P<0.05）. ConclusionGQT significantly enhances the sensitivity of HCT-116/5-FU cells to 5-FU， potentially by inhibiting CDK16 and thereby reducing MYC-mediated glycolysis.

ObjectiveTo explore the molecular mechanisms by which serum containing Gegen Qinlian Tang （GQT） inhibits glycolysis and enhances chemotherapy sensitivity in 5-fluorouracil （5-FU）-resistant colorectal cancer （CRC） cells based on the cyclin-dependent kinase 16 （CDK16）/MYC proto-oncogene （MYC） pathway. MethodsHCT-116/5-FU cells were treated with different concentrations （5%， 10%， 20%， 30%） of GQT-containing serum. Cell viability and 5-FU sensitivity were assessed using the cell counting kit-8 （CCK-8） assay， and the experimental concentrations of 5-FU and GQT for subsequent experiments were determined. Cell proliferation and apoptosis under individual 5-FU， GQT， and combined 5-FU + GQT treatments were evaluated using 5-ethynyl-2′-deoxyuridine （EDU） staining and annexin V-FITC/PI double staining， respectively. Glucose consumption， adenosine triphosphate （ATP） production， and lactate levels were measured by colorimetric assays. Expression levels of glycolysis-related proteins， CDK16， MYC， and phosphorylated MYC were detected by Western blot. Co-immunoprecipitation （CoIP） was used to examine the protein interaction between CDK16 and MYC， and cycloheximide （CHX） treatment was applied to assess the effect of CDK16 overexpression on MYC protein stability. ResultsCCK-8 assays showed that 2.5 mg·L^-1 5-FU significantly inhibited HCT-116 cell viability in a dose-dependent manner. In HCT-116/5-FU cells， significant inhibition was observed only at 5 mg·L^-1 5-FU （P<0.05）， which was used for model establishment. Compared with 5-FU alone， addition of 5% GQT-containing serum significantly suppressed HCT-116/5-FU cell viability （P<0.05）， with stronger inhibition at higher serum concentrations. Thus， 5% GQT-containing serum was used in subsequent experiments. Compared with the control group， 5-FU， GQT， and 5-FU + GQT treatments all significantly reduced cell proliferation （P<0.05） and increased apoptosis （P<0.01）. The 5-FU + GQT combination showed superior inhibition of proliferation compared with 5-FU or GQT alone （P<0.01）， accompanied by more pronounced reductions in glucose consumption， ATP production， and lactate generation （P<0.01）. Additionally， compared with control， 5-FU， and GQT groups， the 5-FU + GQT group exhibited stronger suppression of MYC and its phosphorylated forms （P<0.01） and greater inhibition of glycolytic enzymes， including hexokinase 2 （HK2）， 3-phosphoinositide-dependent protein kinase 1 （PDK1）， lactate dehydrogenase A （LDHA）， and pyruvate kinase M2 （PKM2） （P<0.01）. CDK16， MYC， and MYC phosphorylation expression levels were significantly downregulated in the 5-FU + GQT group compared with the 5-FU group （all P<0.01）. MYC protein stability decreased in a time-dependent manner in the 5-FU + GQT group （P<0.05）， which was rescued by CDK16 overexpression （P<0.05）. ConclusionGQT significantly enhances the sensitivity of HCT-116/5-FU cells to 5-FU， potentially by inhibiting CDK16 and thereby reducing MYC-mediated glycolysis.

ObjectiveTo construct a multifunctional liposomal delivery system by replacing cholesterol（Chol） in conventional liposomes with saikosaponin D（SSD） and modifying with poloxamer 407（P407） for co-delivery of curcumin（Cur）. The system was evaluated for in vivo tumor targeting and inhibitory effects on mouse subcutaneous solid tumors. MethodsSingle-factor and orthogonal tests combined with information entropy weighting were used to optimize the formulation process of the liposome with encapsulation efficiency and absolute Zeta potential as indexes， and validation studies and liposomal characterization were performed. A subcutaneous solid tumor model was established by injecting H22 hepatocellular carcinoma cells subcutaneously into the dorsal surface of the right forelimb of mice. DiR-loaded traditional Chol liposomes（P407-DiR-Chol-LPs， PDCL） and novel SSD-based liposomes（P407-DiR-SSD-LPs， PDSL） were prepared by the optimized formulation process， and tail vein injection was performed to investigate the impact of SSD on liposome tumor targeting with small animal in vivo imaging. Mice were randomly divided into eight groups， including blank group， model group， free doxorubicin（DOX） group（2 mg·kg^-1）， free Cur group（8 mg·kg^-1）， free SSD group（10 mg·kg^-1）， P407-Cur-Chol-LPs（PCCL） group， P407-SSD-LPs（PSL） group， and P407-Cur-SSD-Lps（PCSL） group. Treatments were administered intraperitoneally every other day for seven doses. Antitumor efficacy and biocompatibility were evaluated by monitoring body weight change， organ indices， tumor volume and mass， relative tumor proliferation rate（T/C）， and tumor growth inhibition rate（TGI）. Histopathological analysis of liver， kidney， and tumor tissues was performed using hematoxylin-eosin（HE） staining. Serum levels of aspartate aminotransferase（AST）， alanine aminotransferase （ALT）， blood urea nitrogen（BUN）， and creatinine（Crea）in mice were quantified by fully automated biochemical analyzer. ResultsOrthogonal test yielded optimal ratios of Cur， SSD， and P407 to soybean phosphatidylcholine（SPC） as 1∶25， 1∶20， and 1∶4. The optimized PCSL exhibited spherical morphology with a particle size of 179.15 nm， a Zeta potential of -47.25 mV， and an encapsulation efficiency of 96.40%. Its in vitro release profile conformed to first-order kinetics， demonstrating excellent storage stability and hemocompatibility. In vivo imaging revealed that the fluorescence signal in tumor tissues and the fluorescence intensity ratio between tumors and organs were significantly higher in the PDSL group than in the PDCL group（P<0.05， P<0.01）. Among the treatment groups， PCSL group showed superior efficacy over free Cur group， free SSD group， PCCL group， and PSL group， with TGI>40% and T/C<60%， indicating pronounced anti-hepatocellular carcinoma effects（P<0.05， P<0.01）. Histopathology and serum biochemistry indicated minimal hepatorenal toxicity and improved hepatic and renal function in PCSL-treated mice. ConclusionReplacing Chol with SSD in preparing multifunctional drug delivery systems not only stabilizes liposomes but also yields superior anti-hepatocellular carcinoma efficacy， achieving the effect of drug-excipient integration. Co-delivery of Cur via this system can be used for treating subcutaneous solid tumors in hepatocellular carcinoma， providing new insights and technical approaches for anti-hepatocellular carcinoma research and the meridian-guiding and messenger-directing theory in traditional Chinese medicine.

Uveal melanoma(UM)is the most common primary intraocular malignancy in adults, characterized by high invasiveness and unique metastatic biological features. Although local treatments(such as proton beam therapy and brachytherapy)can effectively control the primary lesion, approximately 50% of patients eventually develop distant metastasis, with the liver being the primary target organ(occurring in 90% of cases). This highlights a paradigm shift in treatment focus from mere local control to systemic prevention and management. For metastatic UM(mUM), current treatment strategies encompass biomarker-guided molecular targeted therapy, immunotherapy(including Tebentafusp, vaccines, and oncolytic virus therapy), and liver-directed therapy. Focusing on the synergy between local and systemic prevention and control, this article systematically elaborates on the precision local treatment for primary UM, the decision-making pathway for systemic treatment of metastatic UM based on molecular subtyping, the integration of local and systemic therapies for liver metastases, and the translational value of nanomedicine in addressing therapeutic bottlenecks. It provides insights for optimizing clinical management of mUM and developing novel therapeutic strategies.

To evaluate the therapeutic effect of a modified Devine procedure with a subcutaneous sliding fixation method for the treatment of congenital concealed penis, we retrospectively selected 45 patients with congenital concealed penises who were admitted to General Hospital of Ningxia Medical University (Yinchuan, China) between September 2020 and November 2023. In all cases, the penis was observed to be short, and retracting the skin at the base revealed a normal penile body, which immediately returned to its original position upon release. All patients underwent the modified Devine procedure with subcutaneous sliding fixation and completed a 12-week postoperative follow-up. A statistically significant increase in penile length was observed postoperatively, with the median length increasing from 4.0 (interquartile range [IQR]: 3.5-4.8; 95% confidence interval [CI]: 3.9-4.4) cm to 8.0 (IQR: 7.8-8.0; 95% CI: 7.7-7.9) cm, with P < 0.001. The parents were satisfied with the outcomes, including increased penile length, improved hygiene, and enhanced esthetics. Except for mild foreskin edema in all cases, no complications (such as infections, skin necrosis, or penile retraction) were observed. The edema was resolved within 4 weeks after the operation. This study demonstrates that the modified Devine procedure utilizing the subcutaneous sliding fixation method yields excellent outcomes with minimal postoperative complications, reduced penile retraction, and high satisfaction rates among patients and their families.
Humans ; Male ; Penis/abnormalities* ; Retrospective Studies ; Urologic Surgical Procedures, Male/methods* ; Treatment Outcome ; Child ; Plastic Surgery Procedures/methods*

OBJECTIVES: To investigate the clinical features of children with STAT gene mutations, and to explore corresponding immunotherapy strategies. METHODS: A retrospective analysis was performed for the clinical data of 10 children with STAT gene mutations who were admitted to the Department of Pediatrics of the First Affiliated Hospital of Guangzhou Medical University, from October 2015 to October 2024. Exploratory immunotherapy was implemented in some refractory cases, and the changes in symptoms, imaging manifestations, and cytokine levels were assessed after treatment. RESULTS: For the 10 children, the main clinical manifestations were recurrent rash since birth (7/10), cough (8/10), wheezing (5/10), expectoration (4/10), and purulent nasal discharge (4/10). Genotyping results showed that there was one child with heterozygous loss-of-function (LOF) mutation in the STAT1 gene, four children with heterozygous LOF mutation in the STAT3 gene, and five children with heterozygous gain-of-function (GOF) mutation in the STAT3 gene. Two children with LOF mutation in the STAT3 gene showed decreased interleukin-6 levels and improved clinical symptoms and imaging findings after omalizumab treatment. Three children with GOF mutation in the STAT3 gene achieved effective disease control after treatment with methylprednisolone (0.5 mg/kg per day). Two children with GOF mutation in the STAT3 gene received treatment with JAK inhibitor and then showed some improvement in symptoms. CONCLUSIONS STAT gene mutation screening should be considered for children with recurrent rash and purulent respiratory tract infections. Targeted immunotherapy may improve prognosis in patients with no response to conventional treatment.
Humans ; Male ; Immunotherapy ; Female ; Child, Preschool ; Child ; Gain of Function Mutation ; Retrospective Studies ; Infant ; Loss of Function Mutation ; STAT Transcription Factors/genetics*

Objective： The aim of this study is to explore the predictive value of biparametric magnetic resonance imaging(bpMRI)for pelvic lymph node metastasis in prostate cancer patients with PSA≤20 μg/L and establish a nomogram. Methods： The imaging data and clinical data of 363 patients undergoing radical prostatectomy and pelvic lymph node dissection in the First Affiliated Hospital of Nanjing Medical University from July 2018 to December 2023 were retrospectively analyzed. Univariate analysis and multivariate logistic regression were used to screen independent risk factors for pelvic lymph node metastasis in prostate cancer, and a nomogram of the clinical prediction model was established. Calibration curves were drawn to evaluate the accuracy of the model. Results： Multivariate logistic regression analysis showed extrocapusular extension (OR=8.08,95%CI=2.62－24.97, P<0.01), enlargement of pelvic lymph nodes (OR=4.45,95%CI=1.16－17.11,P=0.030), and biopsy ISUP grade(OR=1.97,95%CI=1.12－3.46, P=0.018)were independent risk factors for pelvic lymph node metastasis. The C-index of the prediction model was 0.834, which indicated that the model had a good prediction ability. The actual value of the model calibration curve and the prediction probability of the model fitted well, indicating that the model had a good accuracy. Further analysis of DCA curve showed that the model had good clinical application value when the risk threshold ranged from 0.05 to 0.70.Conclusion： For prostate cancer patients with PSA≤20 μg/L, bpMRI has a good predictive value for the pelvic lymph node metastasis of prostate cancer with extrocapusular extension, enlargement of pelvic lymph nodes and ISUP grade≥4.
Humans ; Male ; Prostatic Neoplasms/diagnostic imaging* ; Lymphatic Metastasis ; Retrospective Studies ; Nomograms ; Prostate-Specific Antigen/blood* ; Lymph Nodes/pathology* ; Pelvis ; Predictive Value of Tests ; Prostatectomy ; Lymph Node Excision ; Risk Factors ; Magnetic Resonance Imaging ; Logistic Models ; Middle Aged ; Aged

The innate immune sensor NLRP3 inflammasome overactivation is involved in the pathogenesis of ulcerative colitis. PGAM5 is a mitochondrial phosphatase involved in NLRP3 inflammasome activation in macrophages. However, the role of PGAM5 in ulcerative colitis and the mechanisms underlying PGAM5 regulating NLRP3 activity remain unknown. Here, we show that PGAM5 deficiency ameliorates dextran sodium sulfate (DSS)-induced colitis in mice via suppressing NLRP3 inflammasome activation. By combining APEX2-based proximity labeling focused on PGAM5 with quantitative proteomics, we identify NEK7 as the new binding partner of PGAM5 to promote NLRP3 inflammasome assembly and activation in a PGAM5 phosphatase activity-independent manner upon inflammasome induction. Interfering with PGAM5-NEK7 interaction by punicalagin inhibits the activation of the NLRP3 inflammasome in macrophages and ameliorates DSS-induced colitis in mice. Altogether, our data demonstrate the PGAM5-NEK7 interaction in macrophages for NLRP3 inflammasome activation and further provide a promising therapeutic strategy for ulcerative colitis by blocking the PGAM5-NEK7 interaction.