OBJECTIVE: To investigate the differential efficacy and safety profiles of oral mucosa (OM) grafts compared with acellular dermal matrix (ADM) grafts in the surgical management of long-segment urethral strictures. METHODS: A retrospective cohort study was conducted involving 27 patients who underwent graft urethroplasty for long-segment urethral strictures in Peking University First Hospital, spanning from May 2010 to September 2023. The patient cohort comprised 14 individuals who received OM grafts and 13 who underwent ADM grafts. The participants were stratified into two groups based on the type of grafts material utilized during surgery. The demographic and clinical baseline characteristics included an average age of (43.3±14.0) years in the OM group and (54.2±15.9) years in the ADM group. The mean body mass index (BMI) for the respective groups were (24.7±4.3) kg/m² for OM and (25.4±4.8) kg/m² for ADM. Etiological differences were noted, with idiopathic causes predominantly in the OM cohort and lichen sclerosus in the ADM cohort. RESULTS: The surgical interventions were successfully executed for all the patients. The median stricture length was 4.5 (2.5, 9.0) cm for the OM group and 5.0 (2.0, 14.0) cm for the ADM group (P=0.555). The median operative duration was 160 (71, 221) min for the OM group and 134 (112, 274) min for the ADM group (P=0.065). The catheterization durations was 1.5 (1.0, 6.0) months for the OM group and 3.0 (1.0, 3.0) months for the ADM group. The median postoperative follow-up duration was 12.5 (1.0, 170.0) months for the OM group and 59.0 (3.0, 142.0) months for the ADM group. The surgical success rates were 50.00% in the OM group and 53.85% in the ADM group. No statistically significant differences were observed in postoperative quality of life (QoL) or international prostate symptom score (IPSS) at the final follow-up. The stricture-free survival rates did not differ significantly (HR=0.875, 95%CI: 0.507-1.511, P=0.6). In terms of safety, three patients in the OM group experienced sexual dysfunction, and two had oral complications, whereas the ADM group had one case of postoperative infection. CONCLUSION The findings suggest that ADM grafts are comparable to OM grafts in terms of efficacy and safety for the treatment of long-segment urethral strictures, including complex cases attributed to lichen sclerosus. However, given the small sample size of this study, the above conclusions may have certain limitations. Larger cohort studies will be needed in the future to further validate these findings.
Humans ; Urethral Stricture/surgery* ; Acellular Dermis ; Mouth Mucosa/transplantation* ; Retrospective Studies ; Middle Aged ; Male ; Adult ; Treatment Outcome ; Skin Transplantation/methods* ; Aged

Objective:To evaluate the effect of TBK1 overexpression on hypoxia-reoxygenation (H/R) injury in isolated mouse cardiomyocytes subjected to high glucose and the relationship with mitochondrial autophagy.Methods:Normally cultured log-phase HL-1 mouse cardiomyocytes were inoculated in a 6-well plate at a density of 1×10 6 cells/ml and were divided into 4 groups ( n=10 each) using a random number table method: control group (group C), high glucose group (group HG), high glucose and H/R group (group HG+ H/R), and TBK1 overexpression group (group TBK1). The cells were incubated in culture medium with 1% fetal bovine serum and 1% double antibody for 24 h when the cell density reached 50%.When the cell density reached 80%, pcDNA3.1 (+ ) was used as a vector to achieve TBK1 overexpression.The cells were cultured with high glucose medium (33 mmol/L) for 24 h, exposed to 94% N 2+ 5% CO 2+ 1% O 2 for 24 h in an incubator at 37℃ followed by 12 h reoxygenation in an incubator containing 5% CO 2 at 37°C to establish the model of H/R injury to cardiomyocytes subjected to high glucose.After reoxygenation, CCK-8 assay was used to detect cell viability, the activity of lactic dehydrogenase (LDH) in supernatant was detected using LDH kit, mitochondrial contents were determined using Mito-Tracter green fluorescent probe, and the expression of TBK1 and mitophagy-related proteins PINK1, Parkin, LC3B and P62 was detected by Western blot. Results:Compared with group C, the cell viability was significantly decreased, the activity of LDH in supernatant was increased, mitochondrial contents were decreased, the expression of TBK1, PINK1, Parkin and LC3B was down-regulated, and the expression of P62 was up-regulated in HG group and HG+ H/R group ( P<0.05). Compared with group HG, the cell viability was significantly decreased, the activity of LDH in supernatant was increased, mitochondrial contents were decreased, the expression of TBK1, PINK1, Parkin and LC3B was down-regulated, and the expression of P62 was up-regulated in group HG+ H/R ( P<0.05). Compared with group HG+ H/R, the the cell viability was significantly increased, the activity of LDH in supernatant was decreased, mitochondrial contents were increased, the expression of TBK1, PINK1, Parkin and LC3B was up-regulated, and the expression of P62 was down-regulated in group TBK1 ( P<0.05). Conclusion:The mechanism by which TBK1 overexpression reduces the H/R injury is related to restoring mitophagy in isolated mouse cardiomyocytes subjected to high glucose.

Objective To evaluate the role of autophagy in Parkin over-expression-induced reduction of cardiac hypertrophy in diabetic rats.Methods Thirty-two healthy SPF male Sprague-Dawley rats,aged 2 months,weighing 200-230 g,were divided into 4 groups (n =8 each) using a random number table method:non-diabetes mellitus (DM) group (group Non-DM),DM group,DM plus AAV9-CMV-Parkin group (group DM+P) and DM puls AAV9-CMV-Parkin puls autophagy inhibitor 3-methyladenine (3-MA) group (group DM+P+MA).DM was induced by intraperitoneal streptozotocin (STZ) 60 mg/kg and confirmed by blood glucose level ＞16.7 mmol/L,and Parkin overexpression was achieved with adeno-associated virus serotype 9 as a vector.AAV9-CMV-Parkin 1 × 1012 mg/kg was injected into the tail vein at 3 weeks after STZ injection in group DM+P.In group DM+P+MA,AAV9-CMV-Parkin 1× 1012 mg/kg was injected into the tail vein at 3 weeks after STZ injection,and 3 weeks later 3-MA 15 mg/kg was injected into the tail vein,once a week for 6 weeks in total.Cardiac diastolic and systolic function was detected using Bmode ultrasonography.Cardiomyocytes were obtained for microscopic examination of the cross-sectional area (with a light microscope) and for determination of the expression of microtubule-associated protein 1 light chain 3,P62 and Parkin.Results Compared with group Non-DM,the cross-sectional area of cardiomyocytes was significantly increased,and the diastolic and systolic function was decreased in DM group (P＜0.05).Compared with group DM,the cross-sectional area of cardiomyocytes was significantly decreased,the diastolic and systolic function was improved,the expression of microtubule-associated protein 1 light chain 3 and Parkin in myocardial tissues was up-regulated,and the expression of P62 was down-regulated in group DM+P (P＜0.05).Compared with group MD+P,the cross-sectional area of cardiomyocytes was significantly increased,the diastolic and systolic function was decreased,the expression of microtubule-associated protein 1 light chain 3 was down-regulated,and the expression of P62 was up-regulated in group DM+P+MA (P＜0.05) Conclusion Autophagy is involved in Parkin over-expression-induced reduction of cardiac hypertrophy in diabetic rats.