Objective:To investigate the effect and molecular mechanism of miR-15a-5p regulation Wnt signaling pathway in PQ-induced pulmonary fibrosis.Methods:The PQ-induced 16HBE cell model was constructed, high-throughput miRNA chip and RT-qPCR were used to screen for miR-15a-5p with significant differences. The experimental groups were as follows: NC group (normal control);no special treatment; PQ group: 50 μmol/L PQ treated cells for 72 h; miR-15a-5p group: 16HBE stable cell lines transfected with miR-15a-5p overexpressing lentivirus; miR-15a-5p+PQ group: Stable cell lines were treated with 50 μmol/L PQ for 72 h. The expression of Wnt pathway-related genes Wnt3α and β-catenin, fibroblast marker genes Collagen I, Vimentin and α SMA, epithelial marker genes Occludin and CK18 were detected by RT-qPCR and Western blot. The mice model of PQ-induced pulmonary fibrosis was constructed, and the protein expression and lung tissue injury were detected by Western blot, HE staining and immunohistochemistry. Data were expressed as mean ± standard deviation, and independent sample t-test was used to analyze the data between the two groups. Results:The expressions of Wnt3α, β-catenin, fibroblast marker genes Collagen I, Vimentin and α SMA significantly up-regulated in cell injury models ( P<0.05), the epithelial cell marker genes Occludin and CK18 significantly down-regulated ( P<0.05), overexpression of miR-15a-5p could inhibit the expression of Wnt3α and alleviated the EMT induced by PQ. In animal models, Wnt3α, β-catenin, fibroblast marker genes Collagen I, Vimentin and α SMA significantly increased ( P<0.01), the structure of lung tissue was disordered and fibrosis occurred, overexpression of miR-15a-5p inhibited the expression of Wnt3α protein ( P<0.05) and ameliorated lung tissue injury. Conclusions:miR-15a-5p ameliorates PQ-induced lung injury by modulating the Wnt3α/β-catenin signaling pathway, thereby inhibiting the development of pulmonary fibrosis.

Objective:To explore the protective mechanism of Xuebijing injection (referred to as Xuebijing) on sepsis-associated acute respiratory distress syndrome (ARDS).Methods:① Animal experiments: 100 mice were randomly(random number) divided into 4 groups, including sham operation (Sham) group, cecal ligation and puncture (CLP) group, CLP+low-dose Xuebijing (L-XBJ) group, and CLP+high-dose Xuebijing (H-XBJ) group. The survival rate, lung histological changes, lung wet/dry (W/D) ratio, cell count and protein concentration in bronchoalveolar lavage fluids (BALF), inflammatory factors levels in serum, oxidative stress indicators, cell apoptosis, and key proteins of HIF-1α/p38 MAPK/NF-κB signaling pathway were measured. ② Cell experiments: Mouse alveolar macrophages (MH-S) were cultured in vitro and divided into 6 groups, including control (Con) group, lipopolysaccharide (LPS) group, LPS+L-XBJ group, and LPS+H-XBJ group, LPS+H-XBJ+ dimethyloxallyl glycine (DMOG, HIF-1α activator) group, LPS+H-XBJ+ 2-methoxyestradiol (2ME2, HIF-1α inhibitor) group. The effects of Xuebijing on inflammatory factors, oxidative stress, and cell apoptosis and their relationship with HIF-1α/p38 MAPK/NF-κB signaling pathway were detected.Results:Xuebijing increased the survival rate of mice with sepsis-associated ARDS, relieved lung tissue damage [lung injury score: CLP group (8.778±0.588), CLP+L-XBJ group (5.833±0.310), and CLP+H-XBJ group (4.750±0.246)], alleviated lung W/D ratio, and decreased pneumonia cell infiltration and protein exudation (all P<0.05). Additionally, Xuebijing treatment also diminished the expression of inflammatory factors (TNF-α, IL-1β, and IL-6), intracellular reactive oxygen species (ROS) accumulation, malondialdehyde (MDA) formation, superoxide dismutase (SOD) depletion, and cell apoptosis in LPS-induced MH-S cells and CLP-induced sepsis-associated ARDS mice (all P<0.05). Furthermore, mechanistic investigation further clarified the effects of Xuebijing on inflammation, oxidative stress, and cell apoptosis through the HIF-1α/p38 MAPK/NF-κB signaling pathway. Conclusions:Xuebijing can exert anti-inflammatory, anti-oxidative, and anti-apoptotic effects by suppressing the HIF-1α/p38 MAPK/NF-κB signaling pathway, thereby conferring protection against sepsis-associated ARDS.

Objective By population survey,to explore the epidemiological characteristics of gastric precancerous lesions in Lishui District of Nanjing and provide objective basis for the prevention and treatment of early gastric cancer.Methods From July 2021 to December 2022,21 977 patients who received endoscopy and/or 13C-UBT in Lishui District People's Hospital and 6 medical community units in Nanjing City were retrospectively analyzed for demography characteristics,detection rate of gastric precancerous lesions,and H.Pylori infection rate.Results(1)590 cases of gastric precancerous lesions were detected(detection rate 2.68%);(2)The total detection rate of precancerous lesions and three pathological types in males were all higher than those in females(all P<0.001);(3)The minimum age for the total detection rate of precancerous lesions in males and the mini-mum age for each pathological type were lower than in females(P<0.001,0.009,0.005,0.002);(4)The popu-lation total H.pylori infection rate was 23.10%,the H.pylori infection rate in patients with precancerous lesions was higher than that in non-precancerous lesions(P<0.001),both H.pylori infection rate of male and female in precancerous lesions were all higher than those of non-precancerous lesions of the same sex(all P<0.001),in addition,the H.pylori infection rate of male whether in precancerous or non-precancerous lesions was higher than that of female(all P<0.001);(5)The precancerous lesions detection rate in male,female,and the overall age range of 20～29 to 70～79 years is positively correlated with age growth(P<0.001),and rapidly decreases after the age of 79,the of H.pylori infection rate was also positively correlated with age growth(P<0.001),and the trend of age change(P<0.001)was parallel to the precancerous lesions detection rate.Conclusions The detec-tion rate of gastric precancerous lesions in this region is above the average level in China;the total H.pylori infec-tion rate is at a relatively low level in China;the H.pylori infection rate is parallel to the age trend of the detection rate of gastric precancerous lesions,and increases with age.

Objective To investigate the causal relationship between gut microbiota and pigmented villonodular synovitis using Mendelian randomization analysis.Methods We conducted a two-sample Mendelian randomization analysis to investigate the causal relationship between 211 gut microbiome taxa and pigmented villonodular synovitis based on GWAS summary data,with inverse variance weighted(IVW)analysis as the primary result and the other methods as supplementary analyses.The reliability of the results was tested using Cochran's Q test,MR-Egger regression,MR-PRESSO method and conditional Mendelian randomization analysis(cML-MA).Results The increased abundance of Barnesiella(OR=3.12,95%CI:1.15-8.41,P=0.025)and Rumatococcaceae UCG010(OR=4.03,95%CI:1.19-13.68,P=0.025)may increase the risk of pigmented villous nodular synovitis,and elevated abundance of Lachnospiraceae(OR=0.33,95%CI:0.12-0.91,P=0.032),Alistipes(OR=0.16,95%CI:0.05-0.53,P=0.003),Blautia(OR=0.20,95%CI:0.06-0.61,P=0.005),and Lachnospiraceae FCS020 group(OR=0.38,95%CI:0.15-0.94,P=0.036)and Ruminococcaceae UCG014(OR=0.36,95%CI:0.14-0.94,P=0.037)were all associated with a reduced risk of pigmented villonodular synovitis,which were supported by the results of sensitivity analyses.Reverse Mendelian randomization analysis did not reveal any inverse causal association.Conclusion Increased abundance of specific intestinal microorganisms is associated with increased or decreased risks of developing hyperpigmented villonodular synovitis,and gut microbiota plays an important role in the pathogenesis of this disease.

Objective To investigate the diagnostic value of fecal microRNA-92a(miR-92a)and serum car-cinoembryonic antigen(CEA),carbohydrate antigen 199(CA199)and vascular endothelial growth factor(VEGF)in patients with colon cancer.Methods A total of 77 patients with colon cancer admitted to the First Affiliated Hospital of Air Force Medical University from January 2020 to August 2022 were selected as the co-lon cancer group,including 19 patients who underwent laparoscopic radical resection of colon cancer and were followed up for 6 months after surgery.Another 70 healthy subjects were selected as the control group and 81 patients with other digestive system tumors were selected as the other digestive system tumors group.Real-time fluorescence quantitative PCR was used to detect the level of fecal miR-92a,electrochemiluminescence was used to detect the levels of serum CEA and CA199,and chemiluminescence was used to detect the level of serum VEGF.The receiver operating characteristic(ROC)curve was used to analyze the diagnostic value of miR-92a,CEA,CA199 and VEGF in colon cancer.Results The positive rate of fecal miR-92a in colon cancer group was significantly higher than that in other digestive system tumors group and control group(P＜0.001).The serum levels of CEA,CA199 and VEGF in colon cancer group were significantly higher than those in control group(P＜0.05).The positive rate of miR-92a and the levels of serum CEA,CA199 and VEGF in colon cancer patients were significantly lower at 6 months after surgery than those before surgery(P＜0.05).ROC curve analysis showed that the combined detection of CEA,CA199,VEGF and miR-92a had the largest area under the curve(AUC,0.901),sensitivity(77.9％)and specificity(91.3％).When miR-92a+CEA was combined,the AUC was 0.899,the sensitivity was 77.9％,and the specificity was 92.8％.Conclusion The detection of miR-92a,CEA,CA199 and VEGF has important value in the diagnosis of colon cancer.The combined detection of miR-92a and CEA can improve the sensitivity and specificity of the diagno-sis of colon cancer,and has a certain value in the prognosis of patients with colon cancer.

Background::Although overnight fasting is recommended prior to endoscopic retrograde cholangiopancreatography (ERCP), the benefits and safety of high-carbohydrate fluid diet (CFD) intake 2 h before ERCP remain unclear. This study aimed to analyze whether high-CFD intake 2 h before ERCP can be safe and accelerate patients’ recovery.Methods::This prospective, multicenter, randomized controlled trial involved 15 tertiary ERCP centers. A total of 1330 patients were randomized into CFD group ( n = 665) and fasting group ( n = 665). The CFD group received 400 mL of maltodextrin orally 2 h before ERCP, while the control group abstained from food/water overnight (>6 h) before ERCP. All ERCP procedures were performed using deep sedation with intravenous propofol. The investigators were blinded but not the patients. The primary outcomes included postoperative fatigue and abdominal pain score, and the secondary outcomes included complications and changes in metabolic indicators. The outcomes were analyzed according to a modified intention-to-treat principle. Results::The post-ERCP fatigue scores were significantly lower at 4 h (4.1 ± 2.6 vs. 4.8 ± 2.8, t = 4.23, P <0.001) and 20 h (2.4 ± 2.1 vs. 3.4 ± 2.4, t= 7.94, P <0.001) in the CFD group, with least-squares mean differences of 0.48 (95% confidence interval [CI]: 0.26–0.71, P <0.001) and 0.76 (95% CI: 0.57–0.95, P <0.001), respectively. The 4-h pain scores (2.1 ± 1.7 vs. 2.2 ± 1.7, t = 2.60, P = 0.009, with a least-squares mean difference of 0.21 [95% CI: 0.05–0.37]) and positive urine ketone levels (7.7% [39/509] vs. 15.4% [82/533], χ2 = 15.13, P <0.001) were lower in the CFD group. The CFD group had significantly less cholangitis (2.1% [13/634] vs. 4.0% [26/658], χ2 = 3.99, P = 0.046) but not pancreatitis (5.5% [35/634] vs. 6.5% [43/658], χ2 = 0.59, P = 0.444). Subgroup analysis revealed that CFD reduced the incidence of complications in patients with native papilla (odds ratio [OR]: 0.61, 95% CI: 0.39–0.95, P = 0.028) in the multivariable models. Conclusion::Ingesting 400 mL of CFD 2 h before ERCP is safe, with a reduction in post-ERCP fatigue, abdominal pain, and cholangitis during recovery.Trail Registration::ClinicalTrials.gov, No. NCT03075280.

Objective To investigate the causal relationship between gut microbiota and pigmented villonodular synovitis using Mendelian randomization analysis.Methods We conducted a two-sample Mendelian randomization analysis to investigate the causal relationship between 211 gut microbiome taxa and pigmented villonodular synovitis based on GWAS summary data,with inverse variance weighted(IVW)analysis as the primary result and the other methods as supplementary analyses.The reliability of the results was tested using Cochran's Q test,MR-Egger regression,MR-PRESSO method and conditional Mendelian randomization analysis(cML-MA).Results The increased abundance of Barnesiella(OR=3.12,95%CI:1.15-8.41,P=0.025)and Rumatococcaceae UCG010(OR=4.03,95%CI:1.19-13.68,P=0.025)may increase the risk of pigmented villous nodular synovitis,and elevated abundance of Lachnospiraceae(OR=0.33,95%CI:0.12-0.91,P=0.032),Alistipes(OR=0.16,95%CI:0.05-0.53,P=0.003),Blautia(OR=0.20,95%CI:0.06-0.61,P=0.005),and Lachnospiraceae FCS020 group(OR=0.38,95%CI:0.15-0.94,P=0.036)and Ruminococcaceae UCG014(OR=0.36,95%CI:0.14-0.94,P=0.037)were all associated with a reduced risk of pigmented villonodular synovitis,which were supported by the results of sensitivity analyses.Reverse Mendelian randomization analysis did not reveal any inverse causal association.Conclusion Increased abundance of specific intestinal microorganisms is associated with increased or decreased risks of developing hyperpigmented villonodular synovitis,and gut microbiota plays an important role in the pathogenesis of this disease.

Objective:To investigate the correlation between fluid-attenuated inversion recovery (FLAIR) vascular hyperintensities (FVHs) and outcomes after endovascular mechanical thrombectomy (EMT) in patients with anterior circulation large vessel occlusive stroke.Methods:Using " Nanjing First Hospital Stroke Database" , consecutive patients with anterior circulation large vessel occlusive stroke received EMT treatment from June 2015 to December 2018 were enrolled retrospectively. Before EMT treatment, the distal FVH grade and the American Society of Intervention and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN/SIR) collateral circulation grade were evaluated. The modified Rankin Scale was used to evaluate the functional outcome of patients at 3 months after onset, and 0-2 was defined as a good outcome. Spearman correlation analysis was used to analyze the correlation between the distal FVH grade and the ASITN/SIR collateral circulation grade. Multivariate logistic regression analysis was used to identify the independent predictors of the outcomes. Results:A total of 117 patients with acute anterior circulation large vessel occlusive stroke were enrolled, aged 70.74±12.50 years, 72 (61.5%) were male. The baseline National Institutes of Health Stroke Scale (NIHSS) score was 13.73±4.91. Seventy-four patients (63.2%) had a good outcome and 43 (36.8%) had a poor outcome. The distal FVH grade was grade 0 in 8 cases (6.84%), grade 1 in 34 cases (29.06%), and grade 2 in 75 cases (64.10%). Compared with the distal FVH low-grade group (grade 0-1), the high-grade group (grade 2) had a higher ASITN/SIR collateral circulation grade ( P<0.001) and lower baseline National Institutes of Health Stroke Scale (NIHSS) score ( P=0.026). Spearman correlation analysis showed that the distal FVH grade was significantly positively correlated with the ASITN/SIR collateral circulation grade ( r=0.620, P<0.001). Multivariate logistic regression analysis showed that the high distal FVH grade (odds ratio [ OR] 0.336, 95% confidence interval [ CI] 0.128-0.879; P=0.026) was independently associated with the good outcomes, while the higher baseline NIHSS score ( OR 1.036, 95% CI 0.988-1.229; P=0.048) and symptomatic cerebral hemorrhage ( OR 5.597, 95% CI 1.052-29.761; P=0.043) were independently associated with the poor outcomes. Conclusion:The distal FVHs can reflect the state of collateral circulation. The high grade of distal FVHs is associated with the good outcomes after EMT in patients with anterior circulation large vessel occlusive stroke.

Objective: To investigate the effect of the time from onset to recanalization on the outcomes after endovascular treatment (EVT) in patients with acute stroke due to posterior circulation large vessel occlusion. Methods: From May 2015 to May 2019, patients with acute ischemic stroke due to posterior circulation large vessel occlusion receiving EVT in the Department of Neurology, Nanjing First Hospital, Nanjing Medical University were enrolled retrospectively. According to the modified Rankin Scale (mRS) score at 90 d after procedure, they were divided into good outcome group (≤2) and poor outcome group (>2). Demographic and clinical data were compared between the two groups. Multivariate logistic regression analysis was used to determine the independent correlation between the time from onset to recanalization and the outcomes. Results: A total of 64 patients with acute ischemic stroke due to posterior circulation large vessel occlusion treated by EVT were enrolled in this study. There were 50 males (78.0%) and 14 females (22.0%). The age was 67.52±10.30 years. The National Institutes of Health Stroke Scale (NIHSS) score was 22.04±4.17, and the time from onset to recanalization was 370.53±78.59 min. Thirty-one patients (48.0%) were in the good outcome group and 33 (52.0%) were in the poor outcome group. There were significant differences in baseline NIHSS score, systolic blood pressure, time from onset to revascularization, and the proportions of patients with tandem lesion and symptomatic intracranial hemorrhage between the two groups (all P<0.05). Multivariate logistic regression analysis showed that the longer time from onset to recanalization (odds ratio [OR] 1.317, 95% confidence interval [CI] 1.001-3.034; P=0.041) and symptomatic intracranial hemorrhage (OR 4.207, 95% CI 1.931-10.761; P=0.004) were the independent predictors of poor outcomes, while the lower baseline NIHSS score (OR 0.302, 95% CI 0.056-0.743; P=0.047) was the independent protective factor of poor outcomes. Conclusions The longer time from onset to recanalization is an independent risk factor for poor outcomes after EVT in patients with acute ischemic stroke caused by posterior circulation large vessel occlusion.