N6-Methyladenosine (m6A) modification is a crucial post-transcriptional regulatory mechanism and the most abundant and highly conserved RNA epigenetic modification in eukaryotes. Previous studies have indicated the involvement of m6A modification in various tissue regeneration processes, including liver regeneration. Vir-like m6A methyltransferase associated protein (VIRMA) is an m6A methyltransferase with robust methylation capability. However, its role in liver regeneration remains poorly understood. In this study, we generated liver-specific Virma knockout mice using the Cre-loxP system and investigated the biological functions of VIRMA in liver regeneration using both the Associating Liver Partition and Portal vein Ligation for Staged Hepatectomy (ALPPS) mouse model and the carbon tetrachloride (CCl₄) mouse model. The expression level of VIRMA was rapidly up-regulated after ALPPS surgery and gradually down-regulated during liver repair. Virma deficiency significantly impaired liver regeneration capacity and disrupted cell cycle progression. Methylated RNA immunoprecipitation sequencing (MeRIP-seq) analysis revealed that Shq1 is an effective downstream target of VIRMA-mediated m6A modification. The upregulation of Shq1 enhanced the proliferation ability of cells, which was attenuated by the specific AKT inhibitor ipatasertib. Supplementation of Shq1 in vivo alleviated the liver cell proliferation inhibition caused by Virma deficiency. Furthermore, the m6A-binding protein heterogeneous nuclear ribonucleoprotein a2b1 (HNRNPA2B1) enhanced the mRNA stability of Shq1. Mechanistically, Virma deficiency resulted in decreased m6A modification on Shq1 mRNA, leading to reduced binding ability of m6A-binding protein HNRNPA2B1 with Shq1, thereby decreasing the mRNA stability of Shq1 and reducing its protein expression level. Downregulation of Shq1 inhibited the PI3K/AKT pathway, thereby suppressing cell proliferation and cell cycle progression, ultimately impeding liver regeneration. In summary, our results demonstrate that VIRMA plays a critical role in promoting liver regeneration by regulating m6A modification, providing valuable insights into the epigenetic regulation during liver regeneration.

Objective:To investigate the effects of radiofrequency technology combined with electrical stimulation biofeedback training on stress urinary incontinence in female patients.Methods:This is a prospective study that included 360 female patients with stress urinary incontinence who visited the Department of Gynecology and Obstetrics at Lianyungang Maternal and Child Health Hospital from June 2021 to June 2023. The patients were divided into three groups using a random number table method: a radiofrequency treatment group ( n = 120, treated with radiofrequency technology), an electrical stimulation treatment group ( n = 120, treated with electrical stimulation biofeedback training), and a combined treatment group ( n = 120, treated with a combination of radiofrequency technology and electrical stimulation biofeedback training). The clinical efficacy of the three groups was evaluated. Before and after treatment, a 1-hour pad test and urine test were conducted. The Incontinence Questionnaire-Urinary Incontinence Short Form was used to assess the surface electromyography values of the pelvic floor muscles in patients across the three groups. Results:The effective treatment rate in the combined treatment group was 87.50% (105/120), which was significantly higher than the rates in the radiofrequency treatment group (69.17%, 83/120) and the electrical stimulation treatment group (71.67%, 86/120) ( χ2 = 13.05, P < 0.05). After treatment, the 1-hour pad test showed that the urine leakage amounts and the Incontinence Questionnaire-Urinary Incontinence Short Form scores for the combined treatment group were (1.14 ± 0.16) g and (4.15 ± 0.48), respectively. In comparison, the values in the radiofrequency treatment group were (3.04 ± 0.42) g and (8.66 ± 0.89), while in the electrical stimulation treatment group they were (3.01 ± 0.39) g and (8.78 ± 0.91). Differences among the three groups were statistically significant ( F = 1 024.37, 1 354.96, all P < 0.05). After treatment, the surface electromyography values during the rapid contraction, sustained contraction, and endurance contraction phases for the combined treatment group were (31.97 ± 3.24) μV, (27.01 ± 3.02) μV, and (20.05 ± 2.11) μV, respectively. For the radiofrequency treatment group, the values were (27.85 ± 2.72) μV, (21.63 ± 2.39) μV, and (15.14 ± 1.63) μV, while the electrical stimulation treatment group showed values of (27.93 ± 2.75) μV, (22.04 ± 2.41) μV, and (15.39 ± 1.67) μV. Differences among the three groups were also statistically significant ( F = 78.49, 156.43, 278.16, all P < 0.05). Conclusions:Radiofrequency technology combined with electrical stimulation biofeedback training can substantially improve pelvic floor muscle strength and reduce urinary incontinence symptoms in female patients with stress urinary incontinence.

Objective:To analyze the factors affecting the laxity of Oddi sphincter in patients with common bile duct stones prior to common bile duct exploration.Methods:Clinical data of 101 patients with common bile duct stones undergoing common bile duct exploration at Wenzhou Central Hospital from January 2020 to June 2024 were retrospectively analyzed, including 38 males and 63 females, aged (68.6±13.3) years. All patients underwent common bile duct exploration with choledochoscopy. The size, shape, and patency of the papillary opening at the lower end of Oddi sphincter were observed to classify the sphincter function into Grades 1 to 4. The morphology of the papillary opening at the lower end of common bile duct was defined as narrowed, normal, oversized, and relaxed, respectively. Univariate and multivariate logistic regression analysis were conducted to identify the influencing factors of the laxity of Oddi sphincter.Results:Among the 101 patients, there were two cases (2.0%) classified as Grade 1 of Oddi sphincter function, 40 (39.6%) classified as Grade 2, 43 (42.6%) classified as Grade 3, and 16 (15.8%) classified as Grade 4. Under choledochoscopy, the Oddi sphincter function was classified into Grades 1 to 3 (stenosis, normal and oversized, included in the control group, n=85). Grade 4 was included in the laxity group ( n=16). The proportion of endoscopic retrograde cholangiopancreatography (ERCP) history, preoperative level of alanine aminotransferase, preoperative common bile duct diameter, preoperative maximum diameter of common bile duct stones, and preoperative bile duct gas accumulation in the laxity group were all higher than those in the control group (all P<0.05). Multivariate logistic regression analysis showed that patients with larger preoperative common bile duct diameter ( OR=12.993, 95% CI: 1.913-88.263), larger preoperative maximum diameter of common bile duct stones ( OR=6.238, 95% CI: 1.266-30.730), and a history of ERCP ( OR=8.119, 95% CI: 1.125-58.584) had a higher risk of preoperative Oddi sphincter laxity (all P<0.05). Conclusion:History of ERCP, diameter of common bile duct, and maximum diameter of common bile duct stones are risk factors for the laxity of Oddi sphincter prior to common bile duct exploration in patients with common bile duct stones.

Objective:To investigate the effects of radiofrequency technology combined with electrical stimulation biofeedback training on stress urinary incontinence in female patients.Methods:This is a prospective study that included 360 female patients with stress urinary incontinence who visited the Department of Gynecology and Obstetrics at Lianyungang Maternal and Child Health Hospital from June 2021 to June 2023. The patients were divided into three groups using a random number table method: a radiofrequency treatment group ( n = 120, treated with radiofrequency technology), an electrical stimulation treatment group ( n = 120, treated with electrical stimulation biofeedback training), and a combined treatment group ( n = 120, treated with a combination of radiofrequency technology and electrical stimulation biofeedback training). The clinical efficacy of the three groups was evaluated. Before and after treatment, a 1-hour pad test and urine test were conducted. The Incontinence Questionnaire-Urinary Incontinence Short Form was used to assess the surface electromyography values of the pelvic floor muscles in patients across the three groups. Results:The effective treatment rate in the combined treatment group was 87.50% (105/120), which was significantly higher than the rates in the radiofrequency treatment group (69.17%, 83/120) and the electrical stimulation treatment group (71.67%, 86/120) ( χ2 = 13.05, P < 0.05). After treatment, the 1-hour pad test showed that the urine leakage amounts and the Incontinence Questionnaire-Urinary Incontinence Short Form scores for the combined treatment group were (1.14 ± 0.16) g and (4.15 ± 0.48), respectively. In comparison, the values in the radiofrequency treatment group were (3.04 ± 0.42) g and (8.66 ± 0.89), while in the electrical stimulation treatment group they were (3.01 ± 0.39) g and (8.78 ± 0.91). Differences among the three groups were statistically significant ( F = 1 024.37, 1 354.96, all P < 0.05). After treatment, the surface electromyography values during the rapid contraction, sustained contraction, and endurance contraction phases for the combined treatment group were (31.97 ± 3.24) μV, (27.01 ± 3.02) μV, and (20.05 ± 2.11) μV, respectively. For the radiofrequency treatment group, the values were (27.85 ± 2.72) μV, (21.63 ± 2.39) μV, and (15.14 ± 1.63) μV, while the electrical stimulation treatment group showed values of (27.93 ± 2.75) μV, (22.04 ± 2.41) μV, and (15.39 ± 1.67) μV. Differences among the three groups were also statistically significant ( F = 78.49, 156.43, 278.16, all P < 0.05). Conclusions:Radiofrequency technology combined with electrical stimulation biofeedback training can substantially improve pelvic floor muscle strength and reduce urinary incontinence symptoms in female patients with stress urinary incontinence.

Objective:To analyze the factors affecting the laxity of Oddi sphincter in patients with common bile duct stones prior to common bile duct exploration.Methods:Clinical data of 101 patients with common bile duct stones undergoing common bile duct exploration at Wenzhou Central Hospital from January 2020 to June 2024 were retrospectively analyzed, including 38 males and 63 females, aged (68.6±13.3) years. All patients underwent common bile duct exploration with choledochoscopy. The size, shape, and patency of the papillary opening at the lower end of Oddi sphincter were observed to classify the sphincter function into Grades 1 to 4. The morphology of the papillary opening at the lower end of common bile duct was defined as narrowed, normal, oversized, and relaxed, respectively. Univariate and multivariate logistic regression analysis were conducted to identify the influencing factors of the laxity of Oddi sphincter.Results:Among the 101 patients, there were two cases (2.0%) classified as Grade 1 of Oddi sphincter function, 40 (39.6%) classified as Grade 2, 43 (42.6%) classified as Grade 3, and 16 (15.8%) classified as Grade 4. Under choledochoscopy, the Oddi sphincter function was classified into Grades 1 to 3 (stenosis, normal and oversized, included in the control group, n=85). Grade 4 was included in the laxity group ( n=16). The proportion of endoscopic retrograde cholangiopancreatography (ERCP) history, preoperative level of alanine aminotransferase, preoperative common bile duct diameter, preoperative maximum diameter of common bile duct stones, and preoperative bile duct gas accumulation in the laxity group were all higher than those in the control group (all P<0.05). Multivariate logistic regression analysis showed that patients with larger preoperative common bile duct diameter ( OR=12.993, 95% CI: 1.913-88.263), larger preoperative maximum diameter of common bile duct stones ( OR=6.238, 95% CI: 1.266-30.730), and a history of ERCP ( OR=8.119, 95% CI: 1.125-58.584) had a higher risk of preoperative Oddi sphincter laxity (all P<0.05). Conclusion:History of ERCP, diameter of common bile duct, and maximum diameter of common bile duct stones are risk factors for the laxity of Oddi sphincter prior to common bile duct exploration in patients with common bile duct stones.

The management of antibiotic-resistant, bacterial biofilm infections in skin wounds poses an increasingly challenging clinical scenario. Pseudomonas aeruginosa infection is difficult to eradicate because of biofilm formation and antibiotic resistance. In this study, we identified a new benzothiazole derivative compound, SN12 (IC₅₀ = 43.3 nmol/L), demonstrating remarkable biofilm inhibition at nanomolar concentrations in vitro. In further activity assays and mechanistic studies, we formulated an unconventional strategy for combating P. aeruginosa-derived infections by targeting the two-component (Gac/Rsm) system. Furthermore, SN12 slowed the development of ciprofloxacin and tobramycin resistance. By using murine skin wound infection models, we observed that SN12 significantly augmented the antibacterial effects of three widely used antibiotics-tobramycin (100-fold), vancomycin (200-fold), and ciprofloxacin (1000-fold)-compared with single-dose antibiotic treatments for P. aeruginosa infection in vivo. The findings of this study suggest the potential of SN12 as a promising antibacterial synergist, highlighting the effectiveness of targeting the two-component system in treating challenging bacterial biofilm infections in humans.

Objective:To investigate the clinical efficacy of electrical stimulation, biofeedback, and radiofrequency therapy in combination for the treatment of pelvic floor dysfunction.Methods:A total of 144 patients with pelvic floor dysfunction who received treatment in Lianyungang Maternal and Child Health Hospital from June 2020 to June 2022 were included in this prospective randomized controlled study. They were randomly assigned to undergo electrical stimulation combined with biofeedback (electrical stimulation group, n = 48), treatment with a novel radiofrequency technique (radiofrequency therapy group, n = 48), or electrical stimulation, biofeedback, and treatment with a novel radiofrequency technique (combined group, n = 48). Pelvic floor dysfunction, stress urinary incontinence, and pelvic floor myofascial pain were compared among the three groups. Pelvic organ prolapse quantification was compared among the three groups before and after treatment. Quality of life was evaluated. Results:The effective rates of treatment against pelvic floor dysfunction, stress urinary incontinence, and pelvic floor myofascial pain in the combined group were 95.83% (46/48), 97.92% (47/48), and 93.75% (45/48), respectively, which were significantly higher than 79.17% (38/48), 79.17% (38/48), 77.08% (37/48) in the radiofrequency group, and 75.00% (36/48), 77.08% (37/48), 72.92% (35/48) in the electrical stimulation group ( χ2 = 8.40, 9.77, 7.66, all P < 0.05). After treatment, the severity of pelvic organ prolapse in the combined group was significantly milder than that in the novel radiofrequency technique group and electrical stimulation group (both P < 0.05). The scores of the pelvic floor dysfunction questionnaire and urinary incontinence questionnaire in the combined group were significantly lower than those in the radiofrequency therapy group and the electrical stimulation group (both P < 0.05). Conclusion:Electrical stimulation, biofeedback, and radiofrequency therapy in combination can greatly strengthen the muscle strength of the pelvic floor, relieve urinary incontinence, reduce pelvic floor myofascial pain, and improve the quality of life of patients with pelvic floor dysfunction.

Objective:To establish a headspace solid phase microextraction-gas chromatography method for determination of n-Butyl alcohol in urine.Methods:In October 2019, the n-butyl alcohol in urine was extracted with a polydimethylsiloxane/divinylbenzene (PDMS/DVB) solid-phase microextraction head. The conditions of salt amount, extraction temperature, extraction time and desorption time were optimized. The separation was performed on HP-5 (30 m×0.32 mm×0.25 μm) capillary column and detected with flame ionization detector. The quantification was based on the external standard curve.Results:The linear relationship of n-butyl alcohol in urine was good in the range of 0.04-3.00 mg/L, the correlation coefficient was 0.999, the detection limit of the method was 0.04 mg/L, the recovery was 77.4%-102.8%, the intra-run precision was 3.67%-8.11%, and the inter-assay precision was 4.94%-6.90%.Conclusion:The method has simple operation, high concentration efficiency and high sensitivity, and it is suitable for the determination of n-butyl alcohol in urine of occupational exposure to n-butyl alcohol.

Objective:To establish a headspace solid phase microextraction-gas chromatography method for determination of n-Butyl alcohol in urine.Methods:In October 2019, the n-butyl alcohol in urine was extracted with a polydimethylsiloxane/divinylbenzene (PDMS/DVB) solid-phase microextraction head. The conditions of salt amount, extraction temperature, extraction time and desorption time were optimized. The separation was performed on HP-5 (30 m×0.32 mm×0.25 μm) capillary column and detected with flame ionization detector. The quantification was based on the external standard curve.Results:The linear relationship of n-butyl alcohol in urine was good in the range of 0.04-3.00 mg/L, the correlation coefficient was 0.999, the detection limit of the method was 0.04 mg/L, the recovery was 77.4%-102.8%, the intra-run precision was 3.67%-8.11%, and the inter-assay precision was 4.94%-6.90%.Conclusion:The method has simple operation, high concentration efficiency and high sensitivity, and it is suitable for the determination of n-butyl alcohol in urine of occupational exposure to n-butyl alcohol.

Objective To compare the effects between percutaneous transhepatic gallbladder drainage (PTGD) plus delayed laparoscopic cholecystectomy (LC) in comparison with emergency LC for elderly patients with acute cholecystitis.Methods From June 2011 to December 2014,the clinical data of elderly patients with acute cholecystitis receiving PTGD plus LC and emergency LC were retrospectively studied.Results In this study 38 patients received PTGD plus LC,59 patients received emergency LC.Patients in PTGD + LC group had longer operative time (67 ± 14) min and higher conversion rate (5 cases)than those in LC group (51 ± 13) min,1 case (t =5.741,x2 =5.057,P ＜ 0.05),but had quicker bowel function recovery time (24.5 ±6.4) h,shorter hospital stay (4.2 ± 1.8) d,less complications (3 cases)than those inLC group (27±5.2) h,(6.2±1.9) d,17 cases (t =2.11,t=5.165,x2 =6.18,P＜0.05).Conclusions Percutaneous transhepatic gallbladder drainage plus delayed cholecystectomy is safe for elderly patients with acute cholecystitis.