Causal role of immune cells in diabetic nephropathy: a bidirectional Mendelian randomization study.

Background: Diabetic nephropathy (DN) stands as a pervasive chronic renal disease worldwide, emerging as the leading cause of renal failure in end-stage renal disease. Our objective is to pinpoint potential immune biomarkers and evaluate the causal effects of prospective therapeutic targets in the context of DN. Methods: We employed Mendelian randomization (MR) analysis to examine the causal associations between 731 immune cell signatures and the risk of DN. Various analytical methods, including inverse-variance weighted (IVW), MR-Egger, weighted median, simple mode, and weighted mode, were employed for the analysis. The primary analytical approach utilized was the inverse-variance weighted (IVW) method. To ensure the reliability of our findings, we conducted comprehensive sensitivity analyses to assess the robustness, heterogeneity, and presence of horizontal pleiotropy in the results. Statistical powers were also calculated. Ultimately, a reverse Mendelian randomization (MR) analysis was conducted to assess the potential for reverse causation. Results: After Benjamini & Hochberg (BH) correction, four immunophenotypes were identified to be significantly associated with DN risk: HLA DR on Dendritic Cell (OR=1.4460, 95% CI = 1.2904~1.6205, P=2.18×10-10, P.adjusted= 1.6×10-7), HLA DR on CD14+ CD16- monocyte (OR=1.2396, 95% CI=1.1315~1.3580, P=3.93×10-6, P.adjusted = 0.00143). HLA DR on CD14+ monocyte (OR=1.2411, 95% CI=1.12957~1.3637, P=6.97×10-6, P.adjusted=0.0016), HLA DR on plasmacytoid Dendritic Cell (OR=1.2733, 95% CI= 1.1273~1.4382, P= 0.0001, P.adjusted = 0.0183). Significant heterogeneity of instrumental variables was found in the four exposures, and significant horizontal pleiotropy was only found in HLA DR on Dendritic Cell. The bidirectional effects between the immune cells and DN were not supported. Conclusion: Our research illustrated the intimate association between immune cells and DN, which may contribute to a deeper understanding of the intricate mechanisms underlying DN and aid in the identification of novel intervention target pathways.

Hyperbaric oxygen therapy promotes the browning of white fat and contributes to the healing of diabetic wounds.

Non-healing wounds are one of the chronic complications of diabetes and have remained a worldwide challenge as one of the major health problems. Hyperbaric oxygen (HBO) therapy is proven to be very successful for diabetic wound treatment, for which the molecular basis is not understood. Adipocytes regulate multiple aspects of repair and may be therapeutic for inflammatory diseases and defective wound healing associated with aging and diabetes. Endothelial cell-derived extracellular vesicles could promote wound healing in diabetes. To study the mechanism by which HBO promotes wound healing in diabetes, we investigated the effect of HBO on fat cells in diabetic mice. A diabetic wound mouse model was established and treated with HBO. Haematoxylin and eosin (H&E) staining and immunofluorescence were used for the analysis of wound healing. To further explore the mechanism, we performed whole-genome sequencing on extracellular vesicles (EVs). Furthermore, we conducted in vitro experiments. Specifically, exosomes were collected from human umbilical vein endothelial cell (HUVEC) cells after HBO treatment, and then these exosomes were co-incubated with adipose tissue. The wound healing rate in diabetic mice treated with HBO was significantly higher. HBO therapy promotes the proliferation of adipose precursor cells. HUVEC-derived exosomes treated with HBO significantly promoted fat cell browning. These data clarify that HBO therapy may promote vascular endothelial cell proliferation and migration, and promote browning of fat cells through vascular endothelial cells derived exosomes, thereby promoting diabetic wound healing. This provides new ideas for the application of HBO therapy in the treatment of diabetic trauma.

The Prognostic Value of Sarcopenia and Myosteatosis in Biliary Tract Cancer After Palliative Treatment With Radiation-Emitting Metallic Stent.

Background: Radiation-emitting metallic stent (REMS) placement is increasingly used for malignant biliary obstruction (MBO) caused by unresectable biliary tract carcinoma (UBTC) in clinical practice. The study is aimed to evaluate the prognostic value of sarcopenia, myosteatosis, and their combination on overall survival (OS) in patients treated with REMS for UBTC. Methods: Patients diagnosed with UBTC who underwent REMS placement between January 2013 and May 2021 were included consecutively in this retrospective study. Sarcopenia and myosteatosis were defined based on skeletal muscle index (SMI) and skeletal muscle attenuation (SMA), respectively, which were measured by computer tomography (CT) images on the level of the third lumbar vertebral body before REMS placement. Patients were categorized into two groups by sex-specific cutoff value for sarcopenia and myosteatosis, and OS rates were compared between the groups. Univariate and multivariate cox regression analyses were used to assess factors associated with OS. Results: Data of 135 patients included were retrospectively reviewed and analyzed. Median OS was 7.17 months in total cohort. Patients in the sarcopenia group had significant poorer OS than those in the non-sarcopenia group (median: 3.23 vs. 11.60 months, p < 0.001). OS was shorter in patients with myosteatosis than those without myosteatosis (median: 4.40 vs. 9.17 months, p < 0.001). Sarcopenia (odds ratio [OR] = 9.61; 95% CI = 5.41-17.09; p < 0.001) and myosteatosis (OR = 1.70; 95% CI = 1.13-2.57; p = 0.012) were significantly associated with OS. Combining sarcopenia and myosteatosis (CSM) showed a better predictive accuracy in OS than either one (area under curves: CSM vs. sarcopenia = 0.760 vs. 0.698, p = 0.049; CSM vs. myosteatosis = 0.760 vs. 0.671, p = 0.006). Conclusion: Sarcopenia and myosteatosis are negative predictors of survival in patients who underwent REMS placement for UBTC. CSM seemed to show a better prognostic value than either sarcopenia or myosteatosis alone. They can be used preoperatively for risk evaluation.

Association between XRCC1 polymorphisms and glioma risk among Chinese population.

The pathogenesis of glioma remains largely unknown now. It has been suggested that the X-ray cross-complementing group 1 (XRCC1) gene may influence the capacity to repair DNA damage leading to an increased gliomas susceptibility. This study aimed to evaluate the relationship between XRCC1 polymorphisms and glioma risk. Genotypes were assessed in 368 Chinese glioma patients and 346 healthy controls. XRCC1 Arg194Trp (rs1799782), Arg280His (rs25489) and Arg399Gln (rs25487) and three additional polymorphisms were directly sequenced. The frequency of Arg280His A allele was significant lower in glioma group than in healthy controls [9.6 vs 16%, OR=0.60 (0.46-0.80), P<0.001]; the frequencies of GA or AA genotypes were different in two groups (16.6 vs 22.8%, 1.3 vs 4.7%). The frequency of Arg399Gln A allele was significant higher in glioma group than in healthy controls [38.7 vs 30.1%, OR=1.29 (1.11-1.49), P=0.001]; the frequencies of GA or AA genotypes were different in two groups (45.4 vs 38.2%, 16 vs 10.9%). This study demonstrates that the rs25489 (Arg280His) and Arg399Gln (rs25487) polymorphisms in XRCC1 gene might influence the risk of developing glioma in Chinese population.

[Release of gluteal muscle contracture by radiofrequency under arthroscopy].

OBJECTIVE: To evaluate the clinical therapeutic effect of the release of gluteal muscle contracture by radiofrequency under arthroscopy. METHODS: From January 2004 to April 2005, 86 patients with gluteal muscle contracture were treated by radiofrequency release under arthroscopy.The patients were followed-up for 6-18 months(mean=12.6 months). RESULTS: Getting carriage, squatting down while keeping their knees contacting, crossing leg test, and impact on movement were served as evaluation criteria. Of the 86 patients, 79 had excellent results, 5 good, and the rest 2 were acceptable. There was no recurrence at the last follow-up, and all the patients were satisfied. CONCLUSION: For gluteal muscle contracture, radiofrequency release under arthroscopy has minimally invasion, good results and quick recovery.