Osteoporosis and osteoarthritis: a bi-directional Mendelian randomization study.

OBJECTIVE: To investigate the causal relationship between low bone mineral density (BMD) and osteoarthritis (OA) using Mendelian randomization (MR) design. METHODS: Two-sample bi-directional MR analyses were performed using summary-level information on OA traits from UK Biobank and arcOGEN. Sensitivity analyses including MR-Egger, simple median, weighted median, MR pleiotropy residual sum, and outlier approaches were utilized in conjunction with inverse variance weighting (IVW). Gene ontology (GO) enrichment analyses and expression quantitative trait locus (eQTL) colocalization analyses were used to investigate the potential mechanism and shared genes between osteoporosis (OP) and OA. RESULTS: The IVW method revealed that genetically predicted low femoral neck BMD was significantly linked with hip (ß = 0.105, 95% CI: 0.023-0.188) and knee OA (ß = 0.117, 95% CI: 0.049-0.184), but not with other site-specific OA. Genetically predicted low lumber spine BMD was significantly associated with OA at any sites (ß = 0.048, 95% CI: 0.011-0.085), knee OA (ß = 0.101, 95% CI: 0.045-0.156), and hip OA (ß = 0.150, 95% CI: 0.077-0.224). Only hip OA was significantly linked with genetically predicted reduced total bone BMD (ß = 0.092, 95% CI: 0.010-0.174). In the reverse MR analyses, no evidence for a causal effect of OA on BMD was found. GO enrichment analysis and eQTL analysis illustrated that DDN and SMAD-3 were the most prominent co-located genes. CONCLUSIONS: These findings suggested that OP may be causally linked to an increased risk of OA, indicating that measures to raise BMD may be effective in preventing OA. More research is required to determine the underlying processes via which OP causes OA.

Study of the Intersegmental Veins Between S5 and S8 Based on 3D Reconstruction.

BACKGROUND: Anatomic resection (AR) is a surgical method for treating hepatocellular carcinoma, and identifying intersegmental planes between segments 5 (S5) and 8 (S8) remains challenging. This study aims to find reliable intersegmental veins (IVs) between them as anatomical landmarks using 3D reconstruction analysis. METHODS: We retrospectively evaluated 57 patients who underwent multidetector-row CT scans from September 2021 to January 2023. The portal vein watershed of S5 and S8 and hepatic veins were reconstructed using 3D reconstruction analysis software. We counted and analyzed the IVs running within the intersegmental plane between S5 and S8, examined their features, and analyzed the location of the junctions between IVs and middle hepatic veins (MHVs). RESULTS: Among the 57 patients, 43 patients (75.4%) had IVs between S5 and S8. Most patients (81.4%) had a single IV joining the MHV, while 13.9% had two IVs, one joining the MHV and the other joining the right hepatic vein (RHV). The majority of IV-MHV junctions were found in the lower part of the MHVs. The most clearly identifiable junctions between the IVs and MHVs occurred slightly below the midpoint of the horizontal planes of the second hepatic portal and the center of the gallbladder bed. CONCLUSION: Our study identified IVs between S5 and S8 in the liver as potential anatomical landmarks during AR for hepatocellular carcinoma surgery. We found three types of IVs and provided insights on how to locate their junctions with MHVs for easier surgical navigation. However, individual anatomical variations must be considered, and preoperative 3D reconstruction and personalized surgical planning are crucial for success. More research with larger sample sizes is needed to validate our findings and establish the clinical significance of these IVs as landmarks for AR.

Daifan San intervenes in forkhead box P3 and the interleukin (IL)-23/IL-17A signaling pathway to help prevent and treat primary biliary cirrhosis.

OBJECTIVE: To investigate the mechanism by which Daifan San (DFS) prevents and treats primary biliary cirrhosis (PBC) via the forkhead box P3 (FoxP3) and interleukin (IL)-23/IL-17A signaling pathways. METHODS: Ninety C57BL/6 mice were randomly divided into the control, model, DFS low-dose, DFS middle-dose, DFS high-dose and ursodeoxycholic acid (UDCA) groups (n = 15 per group). A mouse model of PBC was induced using polyinosinic polycytidylic acids (poly I:C). Lymphocyte subset expression in the peripheral blood was analyzed via flow cytometry. The inflammatory cytokines and antimitochondrial autoantibody (AMA) levels were detected via enzyme-linked immunosorbent assays. The expressions and location of type I collagen, type III collagen, cytokeratin 19 and FoxP3 in the liver tissue were evaluated via immunohistochemistry. FoxP3, IL-23 and IL-17 expressions in the peripheral blood and liver tissue were evaluated via real-time polymerase chain reaction and western blotting. RESULTS: IL-17, IL-23, IL-8, IL-33, TNF-a, and AMA expressions were significantly increased in the model group and decreased in the DFS and UDCA groups. Conversely, Treg cell and FoxP3 expressions were significantly decreased in the model group and increased in the DFS and UDCA groups. The IL-23/IL-17A signaling pathway was closely correlated with chronic inflammation of the bile duct in PBC and functional deletion of Treg cells, leading to reduced FoxP3 levels and mediating the loss of tolerance in PBC. CONCLUSION: DFS may delay the occurrence and relieve the symptoms of PBC by downregulating IL-23/IL-17A signaling pathway expression and upregulating FoxP3 expression.