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.

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 analyze the risk factors of pulmonary embolism complications following laparoscopic bile duct exploration.Methods The data of 201 cases undergoing laparoscopic bile duct exploration from June 2002 to December 2014 were retrospectively analyzed.Fourteen risk factors of pulmonary cmbolism complications were evaluated by univariate analysis using no conditional binary Logistic regression.Results 23 patients developed pulmonary embolism complications (11.4％).Age (≥60y),Diabetes mellitus,coronary heart disease,history of cerebral infarction,preoperative shock,time of operation,ambulation after operation (≥3 d) were significant risk factors of pulmonary embolism complications (P ＜0.05).Multivariate Logistic regression analysis identified diabetes mellitus,coronary heart disease,history of cerebral infarction,time of operation,ambulation after operation (≥ 3 d) as independent risk factors of pulmonary embolism complications (P ＜ 0.05).Conclusions Diabetes mellitus,coronary heart disease,history of cerebral infarction,time of operation,ambulation after operation (≥ 3 d) are independent risk factors for pulmonary embolism complications following laparoscopic bile duct exploration.

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.

ObjectiveTo analysis the different types of bacteria in patients with a varying severity of acute cholangitis.Methods241 patients who presented with actue cholangitis between Jan 2008 to Oct 2011 to our hospital were retrospectively studied.These patients were divided into three groups according to the Tokyo Guideline.The bile specimens were obtained intraoperatively.The parameters were compared by SPSS 16.0 package program for statistical analysis.Results75.1 percent of the patients were positive for bacteria in the bile.There were 241 strains of bacterium which included 139 Gram-positive bacteria,99 Gram-negative bacteria and 6 strains of microzyme.Escherichia coli,Enterococcus faecalis,Enterococcus casseliflavus,Pseudomonas aeruginosa and Klebsiella species were the most frequently isolated bacteria.The positive rates for bacteria were significantly different between patients with mild and severe cholangitis (P＜0.05).There was no significant difference between patients with moderate and mild cholangits (P=0.141),or moderate and severe cholangitis (P=0.647).Gram-negative bacteria were more common than Gram- positive bacteria in patients with moderate and severe acute cholangitis (P＜0.05).In patients with moderate and severe acute cholangitis,there was more patients with multiple and mixed bacterial infection.ConclusionsEscherichia coli and Enterococcus species were more common in patients with acute cholangitis.The positive rate of bacteria in the bile in severe acute cholangitis was higher than that in mild acute cholangitis.In patients with moderate and severe cholangitis,Gram-negative bacterial infections and multiple and mixed bacterial infections were more common.