Identification of secretory pathway-related genes based on Random Forest algorithm to predict the prognosis and immunotherapy response of hepatocellular carcinoma.

BACKGROUND: The dysfunction of secretory pathways may represent biomarkers or therapeutic targets of cancer. The hepatocellular carcinoma (HCC) phenotype was studied in relation to the genes in the secretory pathway and to screen for a combination of genes that may be a viable therapeutic target for HCC and connected to the pathophysiological features of the tumor. METHODS: Using the HCC information from The Cancer Genome Atlas, somatic mutation and prognostic association analysis were performed on the secretory pathway genes. Based on prognostic genes in the secretory pathway, the samples were consensus clustered, and a Random Forest model was built. The clinical characteristics, tumor mutation burden, functional status and potential responses to immunotherapy and tumor suppressor medications of various subtypes and risk groups were discussed. RESULTS: Of the 84 genes for secretory pathway, 32 were prognostic genes related to HCC, which divided HCC into two categories: C1 and C2. By comparing the two types of HCC samples, it was found that the survival outcome of C1 was inferior, with stronger adaptive and innate immunity, but less sensitive to immunotherapy than C2. The constructed prognostic signature included seven of the 32 prognostic genes in the secretory pathway, which showed significant correlation with the prognosis, somatic mutation, biological pathway status, potential response to immunotherapy and sensitivity of 72 tumor suppressor drugs from different HCC cohorts, and had a feasible prognostic effect for 31 types of cancer and immunotherapy cohorts. CONCLUSIONS: In this study, HCC was divided into two molecular subtypes according to prognostic genes in the secretory pathway, and seven of them were combined into one signature, which produced significant results in evaluating the prognosis of different HCC cohorts, pan-cancer cohorts and immunotherapy cohorts, and had potential guiding significance for prophylactic immunotherapy in patients with HCC.

[Comparison of different methods for drug delivery via the lumbar spinal subarachnoid space in rats].

OBJECTIVE: To compare 3 commonly used methods for drug delivery via the lumbar spinal subarachnoid space in rats. METHODS: We compared the effects of 3 methods for drug delivery via the lumbar spinal subarachnoid space in Sprague Dawley rats, namely acute needle puncture, chronic catheterization via laminectomy, and non-laminectomized catheterization. Body weight changes of the rats were measured, and their general and neurological conditions were assessed after the surgeries. The motor function of the rats was examined using rota rod test both before and after the surgeries. Nociceptive tests were performed to assess nociception of the rats. HE staining was used to examine local inflammation caused by the surgeries in the lumbar spinal cord tissue, and lidocaine paralysis detection and toluidine blue dye assay were used to confirm the precision of drug delivery using the 3 methods. RESULTS: Both needle puncture and catheterization via laminectomy resulted in a relatively low success rate of surgery and caused neurological abnormalities, severe motor dysfunction, hyperalgesia, allodynia and local inflammation. Catheterization without laminectomy had the highest success rate of surgery, and induced only mild agitation, slight cerebral spinal fluid leakage, mild sensory and motor abnormalities, and minimum pathology in the lumbar spinal cord. Catheterization without laminectomy produced less detectable effects on the behaviors in the rats and was well tolerated compared to the other two methods with also higher precision of drug delivery. CONCLUSIONS: Catheterization without laminectomy is a safe, accurate and effective approach to lumbar drug delivery in rats.

Supplementation of enteral nutritional powder decreases surgical site infection, prosthetic joint infection, and readmission after hip arthroplasty in geriatric femoral neck fracture with hypoalbuminemia.

BACKGROUND: Nearly half of elderly patients with hip fracture were malnourished, indicated with a serum marker of hypoalbuminemia. Malnutrition was a risk factor for poor outcomes in geriatrics after hip replacement. The purpose of this study was to investigate if oral nutritional supplementation after the procedure in geriatrics with hypoalbuminemia was beneficial for outcomes. METHODS: A retrospective cohort study of older (≥ 65 years old) patients suffering femoral neck fracture and undergoing hip replacement with hypoalbuminemia was conducted. Outcomes were compared between patients with and without postoperative nutritional supplementation. RESULTS: There were 306 geriatric patients met the criteria. Following adjustment for baseline characteristics, patients with nutritional supplementation showed a lower grade of wound effusion with adjusted OR 0.57 (95% confidence interval (CI), 0.36 to 0.91, P < 0.05). And also a lower rate of surgical site infection (5.5% compared with 13.0% [adjusted OR 0.40, 95% CI, 0.17 to 0.91, P < 0.05]), periprosthetic joint infection (2.8% compared with 9.9% [adjusted OR 0.26, 95% CI, 0.08 to 0.79, P < 0.05]), and 30 days readmission (2.1% compared with 8.7% [adjusted OR 0.22, 95% CI, 0.06 to 0.79, P < 0.05]). The average total hospital stay was longer in patients without nutritional supplementation (10.7 ± 2.0 compared with 9.2 ± 1.8 days, P < 0.05). CONCLUSIONS: The data suggest that postoperative nutritional supplementation is a protective factor for surgical site infection, periprosthetic joint infection, and 30-days readmission in geriatric with hypoalbuminemia undergoing a hip replacement. Postoperative nutritional supplementation for these patients should be recommended.