OBJECTIVE: Gastric cancer (GC) is one of the most common malignancies seen in clinic and requires novel treatment options. Morin is a natural flavonoid extracted from the flower stalk of a highly valuable medicinal plant Prunella vulgaris L., which exhibits an anti-cancer effect in multiple types of tumors. However, the therapeutic effect and underlying mechanism of morin in treating GC remains elusive. The study aims to explore the therapeutic effect and underlying molecular mechanisms of morin in GC. METHODS: For in vitro experiments, the proliferation inhibition of morin was measured by cell counting kit-8 assay and colony formation assay in human GC cell line MKN45, human gastric adenocarcinoma cell line AGS, and human gastric epithelial cell line GES-1; for apoptosis analysis, microscopic photography, Western blotting, ubiquitination analysis, quantitative polymerase chain reaction analysis, flow cytometry, and RNA interference technology were employed. For in vivo studies, immunohistochemistry, biomedical analysis, and Western blotting were used to assess the efficacy and safety of morin in a xenograft mouse model of GC. RESULTS: Morin significantly inhibited the proliferation of GC cells MKN45 and AGS in a dose- and time-dependent manner, but did not inhibit human gastric epithelial cells GES-1. Only the caspase inhibitor Z-VAD-FMK was able to significantly reverse the inhibition of proliferation by morin in both GC cells, suggesting that apoptosis was the main type of cell death during the treatment. Morin induced intrinsic apoptosis in a dose-dependent manner in GC cells, which mainly relied on B cell leukemia/lymphoma 2 (BCL-2) associated agonist of cell death (BAD) but not phorbol-12-myristate-13-acetate-induced protein 1. The upregulation of BAD by morin was due to blocking the ubiquitination degradation of BAD, rather than the transcription regulation and the phosphorylation of BAD. Furthermore, the combination of morin and BCL-2 inhibitor navitoclax (also known as ABT-737) produced a synergistic inhibitory effect in GC cells through amplifying apoptotic signals. In addition, morin treatment significantly suppressed the growth of GC in vivo by upregulating BAD and the subsequent activation of its downstream apoptosis pathway. CONCLUSION Morin suppressed GC by inducing apoptosis, which was mainly due to blocking the ubiquitination-based degradation of the pro-apoptotic protein BAD. The combination of morin and the BCL-2 inhibitor ABT-737 synergistically amplified apoptotic signals in GC cells, which may overcome the drug resistance of the BCL-2 inhibitor. These findings indicated that morin was a potent and promising agent for GC treatment. Please cite this article as: Wang Y, Sun XY, Ma FQ, Ren MM, Zhao RH, Qin MM, Zhu XH, Xu Y, Cao ND, Chen YY, Dong TG, Pan YF, Zhao AG. Morin inhibits ubiquitination degradation of BCL-2 associated agonist of cell death and synergizes with BCL-2 inhibitor in gastric cancer cells. J Integr Med. 2025; 23(3): 320-332.
Humans ; Flavonoids/therapeutic use* ; Stomach Neoplasms/pathology* ; Animals ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Cell Line, Tumor ; Apoptosis/drug effects* ; Cell Proliferation/drug effects* ; Ubiquitination/drug effects* ; Mice ; Drug Synergism ; Mice, Inbred BALB C ; Mice, Nude ; Xenograft Model Antitumor Assays ; Flavones

Objective To compare the diagnostic value of transabdominal intestinal ultrasound (IUS) and magnetic resonance enterography (MRE) for intestinal stenosis in inflammatory bowel disease (IBD). Methods A retrospective analysis was conducted on the imaging features of 51 IBD patients who underwent both IUS and MRE at Beijing Friendship Hospital,Capital Medical University,between January 2021 and February 2025.With endoscopy as the gold standard,the diagnostic performance of the two methods was compared. Results The sensitivity (84.2% vs. 52.6%,P=0.008) and accuracy (66.7% vs. 45.1%,P=0.035) of IUS for stenosis were higher than those of MRE.In the localization of stenosis,IUS demonstrated higher sensitivity than MRE for detecting stenosis in the terminal ileum (78.6% vs. 35.7%,P=0.070) and colorectum (86.7% vs. 53.3%,P=0.060).Furthermore,IUS showed higher diagnostic accuracy than MRE for terminal ileum stenosis (70.6% vs. 29.4%,P=0.039).The intestinal wall thickness[(8.2±2.7) mm vs. (10.3±3.8) mm;t=3.20,P=0.002)] and stenosis inner diameter[(3.0±1.6) mm vs. (4.3±1.8) mm;t=2.15,P=0.035] measured by IUS were lower than those measured by MRE,with a moderate level of consistency (ICC:0.19-0.53).In addition,IUS demonstrated a higher detection rate for mesenteric fat hypertrophy (70.6% vs. 27.5%,Kappa=0.27,P=0.005),whereas MRE was more sensitive in detecting lymphadenopathy (90.2% vs. 56.9%,Kappa=0.16,P=0.080). Conclusions IUS is superior to MRE in the diagnosis and localization sensitivity for intestinal stenosis in IBD.However,the two methods showcase poor consistency in detecting and quantitating some inflammatory signs.IUS can be used as a first-line screening method for diagnosing intestinal stenosis in IBD patients,while its clinical application should be combined with specific needs to optimize diagnosis.
Humans ; Retrospective Studies ; Constriction, Pathologic/diagnostic imaging* ; Ultrasonography/methods* ; Magnetic Resonance Imaging/methods* ; Inflammatory Bowel Diseases/diagnostic imaging* ; Male ; Female ; Adult ; Middle Aged ; Intestines/diagnostic imaging* ; Sensitivity and Specificity

This study was aimed at understanding the antimicrobial resistance patterns,virulence characteristics,and phyloge-netic relationships of foodborne Listeria monocytogenes in Weifang.A total of 67 strains of Listeria monocytogenes were isolated from livestock,poultry meat,and clinical samples in Weifang between 2020 and 2023.The susceptibility of these isolates was determined through broth microdilution.Whole-genome sequencing and genetic characterization of these isolates were conducted.The 67 strains were divided into 12 STs,among which ST121,ST8,ST9,and ST87 predominated(76.12%).Eight groups of closely related strains were identified through cgMLST typing.Three Listeria pathogenicity islands and two genomic islands were identified in all strains:100%of the strains carried LIPI-1,5.97%carried LIPI-3,14.93%carried LIPI-4,2.99%carried LGI-2,and 4.48%of the strains carried LGI-3.No antibiotic resistance genes were found in any strains.All isolates were susceptible to ampicillin,penicillin,merope-nem,trimethoprim-sulfamethoxazole,and vancomycin.Five isolates were resistant to tetracycline,and three strains of ST87,one strain of ST8,one strain of ST224,and two strains of ST87 were simultaneously resistant to erythromycin.The tet(M)tetracycline re-sistance genes and msr(D)and mef(A)erythromycin resistance genes from three strains of ST87 and one strain of ST8 were carried by a phage similar to phi1605 in Erysipelothrix,with>95%identity.The tet(M)gene from the ST224 isolates was carried by a transposon similar to Tn5801_B15 in Enterococcus faecalis,with>95%identity.Drug-resistant strains of Listeria monocytogenes were found in livestock and poultry meat on sale in Weifang,particularly strains of type ST87 and ST224 simultaneously carrying highly pathogenic virulence islands,thus posing a threat to food safety and public health.These findings therefore warrant attention from relevant depart-ments and strengthened monitoring efforts.

Objective:To evaluate the clinical efficacy of transoral robotic surgery (TORS) in the treatment of malignant tongue base tumors.Methods:A multicenter study was conducted to collect and analyze the clinical data of patients with malignant tongue base tumors who underwent TORS at five otolaryngology-head and neck surgery centers in China, including Eye Ear Nose and Throat Hospital of Fudan University, Sun Yat-sen University Cancer Center, Tongji Hospital of Huazhong University of Science and Technology, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, and the First Affiliated Hospital of China Medical University between January 2017 and January 2023. Among the patients, 38 were males and 11 were females, with a mean age of 59.0±8.8 years. Baseline characteristics, complications, and follow-up data were compared between groups. Independent sample t-tests or Mann-Whitney U tests was used for comparisons of continuous variables; chi-square tests or Fisher′s exact tests was applied for categorical variables. Survival analysis was performed using the Kaplan-Meier method to calculate overall survival and disease-free survival, and differences between groups were compared using the log-rank test. Results:Among the 49 patients, 41 (83.7%) were diagnosed with squamous cell carcinoma (SCC), with a p16 positive rate of 51.2% (21/41). There were no statistically significant differences between the p16-positive group ( n=21) and the p16-negative group ( n=20) in age, sex, or postoperative bleeding (all P>0.05). However, there was a significant difference in TNM stage between the two groups ( χ2=14.556, P=0.020), with the p16-positive group predominantly in stage I (66.7%) and the p16-negative group primarily in stages Ⅲ and Ⅳ (40.0% and 30.0%, respectively). The postoperative tracheotomy rate was 30.6% (15/49), and the incidence of postoperative bleeding was 6.1% (3/49). The 1-year and 3-year overall survival rates were 98.0% and 92.5%, respectively, while, the 1-year and 3-year disease-free survival rates were 89.2% and 84.9%, respectively. No significant differences were observed between the p16-positive and p16-negative groups in 3-year overall survival (100% vs. 83.8%, χ2=1.093, P=0.518) or 3-year disease-free survival (68.2% vs. 88.9%, χ2=2.161, P=0.382). Conclusion:TORS for malignant tongue base tumors demonstrates high clinical safety and favorable oncological outcomes.

Objective:To explore the clinical application value of transoral robotic surgery (TORS) in the treatment of tonsil squamous cell carcinoma (TSCC).Methods:A retrospective analysis was conducted. The clinical data of 157 TSCC patients were collected who received TORS at five medical centers, namely, the Sun Yat-sen University Cancer Center, Sun Yat-sen Memorial Hospital, Eye Ear Nose and Throat Hospital of Fudan University, the First Affiliated Hospital of China Medical University, and Tongji Hospital of Tongji Medical College, from January 1 2017 to July 31 2022. There were 130 males and 27 females, aged 24-85 years. All patients were followed-up at least for 2 years (2-year group), among them, 99 patients had a follow-up of 3 years (3-year group). The overall survival (OS), progression-free survival (PFS), clinical stage, human papillomavirus (HPV) infection status were analyzed. SPSS 25.0 and SAS 9.4 were used for statistical analysis.Results:The OS and PFS of the 2-year group were 91.7% and 87.9%, respectively. The OS and PFS of the 3-year group were 85.9% and 82.8%, respectively. The prognosis of patients with locally early-stage was better than that of locally advanced patients, with the OS of 94.4% for T1-2 vs. 78.0% for T3 ( P=0.005) and the PFS of 91.2% for T1-2 vs. 75.0% for T3 ( P=0.011) in the 2-year group; the OS of 91.1% for T1-2 vs. 65.0% for T3 ( P=0.004) and the PFS of 88.6% for T1-2 vs. 60.0% for T3 ( P=0.002) in the 3-year group; and also, the OS of 90.0% for stage Ⅰ-Ⅱ vs. 79.5% for stage Ⅲ-Ⅳ ( P=0.204) and the PFS of 86.7% for stage Ⅰ-Ⅱ vs. 76.9% for stage Ⅲ-Ⅳ ( P=0.188) in the 3-year group. The prognosis of HPV-positive TSCC patients was better than that of HPV-negative patients in the 3-year group, with the OS of 90.9% for HPV-positive vs. 80.5% for HPV-negative ( P=0.045) and the PFS of 90.9% for HPV-positive vs. 75.6% for HPV-negative ( P=0.047). The average time of postoperative tracheal cannula indwelling was 25.1 days. The indwelling rate and average indwelling time of the postoperative nasogastric tube were 94.3% (148/157) and 8.5 days, respectively. Conclusion:TORS has outstanding survival benefits for TSCC patients. HPV-positive TSCC patients have a better prognosis than HPV-negative patients. TORS treatment of TSCC patients has advantages in postoperative recovery and quality of life.

Objective:To investigate the efficacy and feasibility of transoral robotic surgery (TORS) for resection of tumors in the parapharyngeal spaces.Methods:The clinical data of 57 patients who underwent TORS for parapharyngeal space tumors from September 2018 to February 2024 were retrospectively analyzed. These patients were treated at five medical institutions: The First Affiliated Hospital of China Medical University, Eye & ENT Hospital of Fudan University, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, and Sun Yat-sen University Cancer Center. The patients were 28 males and 29 females, aged 17-77 years (median age, 47 years). The pathological types, locations, and sizes of the tumors, operation time, intraoperative bleeding volumes, postoperative hospital stays, and postoperative complications were evaluated. The data were analyzed using SPSS 27.0 software.Results:Postoperative pathological examination revealed 11 types of benign tumors. Among 57 cases, 27 cases had their tumors in the prestyloid spaces, predominantly with pleomorphic adenoma ( n=17), and 30 cases in the retrostyloid spaces, predominantly with schwannoma ( n=22). The tumor volumes ranged from 0.6 to 130.1 cm3, the intraoperative bleeding volumes ranged from 5 to 1 000 ml, the operation time ranged from 20 to 390 min, and the postoperative hospital stays ranged from 2 to 25 days. The total costs for individual cases were 36 000-100 000 yuan, with the highest cost in the case suffering from cerebrovascular accident. Four patients(7.0%) had tracheotomy and 36(63.2%) had nasogastric tube placement. Among the 57 patients, 5 had postoperative cavity effusion, 2 had wound dehiscence, 2 had cerebrovascular accidents, 1 had Horner syndrome, and 2 had other complications. The patients were followed up for 1-67 months, with only 1 patient with intracranial and extracranial communication relapsed. Conclusion:TORS is a safe and feasible approach for treating parapharyngeal space tumors, offering advantages such as minimal invasiveness, reduced blood loss, and faster recovery. It is suitable for parapharyngeal space tumors of various pathological types and locations. The postoperative complications are manageable, with favorable long-term follow-up results and low recurrence rates.

Objective:To explore the correlation between skeletal muscle mass and strength with metabolic syndrome in children.Methods:This cross-sectional study was conducted involving 383 children aged 10 to 15 years who visited the Department of Child Health Care, Children′s Hospital of Nanjing Medical University from June 2021 to December 2022. Their height, weight, waist circumference, body composition, grip strength and blood pressure were measured. Relative skeletal muscle mass, muscle-to-fat ratio, and grip strength-to-body weight index were calculated. The levels of fasting blood glucose, lipids and insulin were tested. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. Children were divided into the metabolic syndrome group and the non-metabolic syndrome group. Independent t test or Mann-Whitney U test etc. was used to compare the difference between groups. Spearman correlation analysis and binary Logistic regression were used to investigate the correlation between skeletal muscle mass and strength and metabolic syndrome. The area under the curve (AUC) of receiver operating characteristic (ROC) curve was used to compare the accuracy of the index of skeletal muscle in predicting metabolic syndrome in children. Results:Among the 383 children, 282 (73.6%) were male, at the age of 11.4 (10.6, 12.5) years. There were 216 children (56.4%) diagnosed with obesity and 90 children (23.5%) diagnosed with metabolic syndrome. Relative skeletal muscle mass, muscle-to-fat ratio, and grip strength-to-body weight index of the metabolic syndrome group were all lower than those in the non-metabolic syndrome group (all P<0.001). After adjusting for sex and age, relative skeletal muscle mass, muscle-to-fat ratio, and grip strength-to-body weight index were all negatively correlated with body mass index ( r=-0.84, -0.38, -0.63), waist circumference ( r=-0.76, -0.36, -0.70), systolic blood pressure ( r=-0.42, -0.21, -0.38), diastolic blood pressure ( r=-0.33, -0.18, -0.24), triglycerides ( r=-0.29, -0.13, -0.23), fasting insulin ( r=-0.28, -0.20, -0.29), and HOMA-IR ( r=-0.26, -0.18, -0.26) (all P<0.05), and positively correlated with high-density lipoprotein cholesterol ( r=0.38, 0.13, 0.31, all P<0.01). After adjusting for sex and age, high relative skeletal muscle mass, high muscle-to-fat ratio, and high grip strength-to-body weight index all decreased the risks of metabolic syndrome ( OR=0.80, 0.55, 0.90), obesity ( OR=0.53, 0.64, 0.82), hypertension ( OR=0.86, 0.58, 0.92), low high-density lipoprotein cholesterol ( OR=0.83, 0.62, 0.92), hypertriglyceridemia ( OR=0.88, 0.78, 0.96). After adjusting for sex and age, high relative skeletal muscle mass and high grip strength-to-body weight index all decreased the risks of hyperglycemia ( OR=0.93 and 0.95, all P<0.05). ROC curve analysis showed that the relative skeletal muscle mass, muscle-to-fat ratio, and grip strength-to-body weight index all had good predictive accuracy of metabolic syndrome in children (AUC=0.79, 0.71, 0.76), with optimal cutoff values of 40%, 1.2, and 35%, respectively. Conclusions:High relative skeletal muscle mass, high muscle-to-fat ratio, and high grip strength-to-body weight index are all protective factors for metabolic syndrome in children. Regular measurement of skeletal muscle mass and grip strength can aid in the early identification and prevention of obesity and metabolic syndrome during childhood .