Flap necrosis, the most prevalent postoperative complication of reconstructive surgery, is significantly associated with ischaemia–reperfusion injury. Recent research indicates that exosomes derived from bone marrow mesenchymal stem cells (BMSCs) hold potential therapeutic applications in several diseases. Traditionally, BMSCs are cultured under normoxic conditions, a setting that diverges from their physiological hypoxic environment in vivo. Consequently, we propose a method involving the hypoxic preconditioning of BMSCs, aimed at exploring the function and the specific mechanisms of their exosomes in ischaemia–reperfusion skin flaps. This study constructed a 3 × 6 cm² caudal superficial epigastric skin flap model and subjected it to ischaemic conditions for 6 h. Our findings reveal that exosomes from hypoxia-pretreated BMSCs significantly promoted flap survival, decrease MCP-1, IL-1β, and IL-6 levels in ischaemia–reperfusion injured flap, and reduce oxidative stress injury and apoptosis. Moreover, results indicated that Hypo-Exo provides protection to vascular endothelial cells from ischaemia–reperfusion injury both in vivo and in vitro. Through high-throughput sequencing and bioinformatics analysis, we further compared the differential miRNA expression profiles between Hypo-Exo and normoxic exosomes. Results display the enrichment of several pathways, including autophagy and mTOR. We have also elucidated a mechanism wherein Hypo-Exo promotes the survival of ischaemia–reperfusion injured flaps. This mechanism involves carrying large amounts of miR-421-3p, which target and regulate mTOR, thereby upregulating the expression of phosphorylated ULK1 and FUNDC1, and subsequently further activating autophagy. In summary, hypoxic preconditioning constitutes an effective and promising method for optimizing the therapeutic effects of BMSC-derived exosomes in the treatment of flap ischaemia–reperfusion injury.

Background: Osteoarthritis (OA) is a prevalent degenerative joint disease that causes disability and diminishes quality of life. The pathogenesis of OA remains poorly understood, creating an urgent need for biomarkers to aid research, diagnosis, and treatment. Methods: This study integrated transcriptome data from the GEO database with bioinformatics analyses to identify biomarkers associated with OA. The bioinformatics methods utilized include the Limma package, WGCNA, PPI network analysis, and machine learning algorithms. Genetic variants were used as instrumental variables to evaluate the potential causal impact of circulating white blood cell (WBC) counts on OA. Data sources encompassed the largest genome-wide analysis for OA and a comprehensive GWAS summary for circulating WBC counts. Four mendelian randomization (MR) methods were employed to investigate the genetic association, with a primary focus on findings from the inverse variance-weighted (IVW) method. Results: Total of 233 OA-related genes were identified, showing significant enrichment in pathways associated with WBC function. Key biomarkers, including CD4, CSF1R, and TYROBP, were upregulated in OA samples and exhibited strong diagnostic potential. MR analysis findings provided evidence of a genetic association between elevated neutrophil counts and a reduced risk of OA across sites (IVW: OR = 0.97, 95% CI 0.93–1.00, p = 0.047). Additionally, higher circulating WBC counts, particularly neutrophil counts, were associated with a suggestive decrease in hip OA (WBC IVW: OR = 0.94, 95% CI 0.89–0.99, p = 0.015; neutrophil IVW: OR = 0.93, 95% CI 0.88–0.99, p = 0.017). Conversely, reverse MR analysis found no evidence to support a genetic effect of OA on circulating WBC counts. Conclusion: Our findings suggest that elevated neutrophil counts may offer protective effects against OA, underscoring the interplay between the immune functions and OA pathogenesis. CD4, CSF1R, and TYROBP emerge as promising OA biomarkers, meriting further validation in prospective studies.

Background: Accumulating evidence has shown that patients with inflammatory bowel disease (IBD) have liver function abnormalities and are susceptible to liver diseases. However, the existence of a causal relationship between IBD and liver function or disease remains unclear.Methods: A two-sample Mendelian randomization (MR) analysis was performed using genetic associations from publicly available genome-wide association studies (GWAS). These associations encompass ulcerative colitis (UC), Crohn’s disease (CD), liver function traits, and liver disease phenotypes. The liver function traits comprised hepatic biochemistries, percent liver fat, and liver iron content from the UK Biobank. Furthermore, the liver disease phenotypes included cholelithiasis, non-alcoholic fatty liver disease (NAFLD), primary sclerosing cholangitis (PSC), and primary biliary cholangitis (PBC) in cohorts of European ancestry. The primary estimation used the inverse-variance weighted method, with GWAS of C-reactive protein (CRP) in the UK Biobank serving as a positive control outcome.Results: Genetically predicted UC is causally associated with decreased levels of albumin (ALB) and liver iron content, while genetically predicted CD is causally associated with increased levels of alkaline phosphatase (ALP). Moreover, genetically predicted UC or CD increases the risk of PSC, and CD increases the risk of PBC. Neither UC nor CD causally increases the risk of cholelithiasis and NAFLD.Conclusion: UC affects the levels of ALB and liver iron content, while CD affects the levels of ALP. Both UC and CD increase the risk of PSC, and CD increases the risk of PBC.

Accumulating evidence has indicated an increased risk of acute pancreatitis in individuals with inflammatory bowel disease (IBD); however, the establishment of a clear and direct causal connection between IBD and acute pancreatitis remains uncertain. Utilizing genetic data from publicly accessible genome-wide association studies (GWAS), we conducted a 2-sample MR analysis to identify the associations between IBD, ulcerative colitis (UC), Crohn disease (CD), and acute pancreatitis risk. Rigorous quality control steps ensured the selection of eligible single nucleotide polymorphisms (SNPs) with strong associations to IBD. The primary estimation used the inverse-variance weighted method. We also assessed heterogeneity, potential pleiotropy, and conducted sensitivity analyses. The direction of causality was confirmed using the Steiger test. The MR analysis showed that IBD increased the risk of acute pancreatitis (IVW: OR = 1.032, 95% CI: 1.006–1.06, P = .015). Among the subgroup of IBD, CD (IVW: OR = 1.034, 95% CI: 1.008–1.06, P = .007) indicates a significant increase in the risk of acute pancreatitis compared to UC (IVW: OR = 1.02, 95% CI: 0.99–1.051, P = .189). The MR analysis assessing the association between CD and acute pancreatitis showed no evidence of heterogeneity or horizontal pleiotropy. Likewise, the leave-one-out (LOO) method indicated no significant influence of any individual SNP on the overall findings. In addition, the Steiger direction test revealed that CD was the cause for increased risk of acute pancreatitis, but not vice versa. In summary, this research pioneers in proposing a causal relationship between CD and acute pancreatitis among the European population.

Background and Aims: The increasing prevalence of Crohn's disease (CD) and ulcerative colitis (UC)—the two main forms of inflammatory bowel disease (IBD)—has made these conditions a growing concern in global public health. While IBD primarily impacts the gastrointestinal tract, emerging evidence suggests its extraintestinal effects, especially on the respiratory system. The correlation between the lungs and the gastrointestinal system has drawn attention to the potential pulmonary complications in IBD patients. The causal link between IBD and lung function or related disease remains inconclusive.Methods: Leveraging publicly available genome‐wide association study (GWAS) data sets, we performed a two‐sample Mendelian randomization analysis to investigate potential links between ulcerative colitis, Crohn's disease, and various aspects of lung function or respiratory illness. Through meticulous quality control measures, we pinpointed SNPs with robust associations to UC and CD. The inverse‐variance weighted method was our primary analytic approach. Additionally, we evaluated heterogeneity, explored potential pleiotropy, and performed sensitivity tests.Results: We conducted an analysis using GWAS data obtained from the European population, identifying 54 and 77 SNPs for association studies related to lung function and disease in UC and CD, respectively. The results from the MR analysis revealed that neither UC nor CD exhibited a discernible impact on lung function, encompassing metrics such as total lung volume, forced vital capacity, forced expiratory volume in the first second, the forced vital capacity/forced expiratory volume in the first second ratio, and peak expiratory flow. Additionally, neither UC nor CD demonstrated an elevated risk of idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease, or pulmonary cancer. In contrast, CD presented a heightened risk of asthma compared to UC.Conclusion: CD has been associated with a higher risk of developing asthma in the European population.

INPLASY202210009 Safety and Efficacy of overlap esophagojejunostomy During Totally Laparoscopic Total Gastrectomy: A Systematic Review and Meta Analysis Keywords: Laparoscopy; Gastrectomy; Esophaoj…