Nonalcoholic fatty liver disease (NAFLD) is a clinicopathological syndrome of abnormal lipid deposition in the liver mediated by nonalcohol intake. The Gexia Zhuyu decoction, a classic traditional Chinese medicine compound, is widely used in the clinical treatment of NAFLD. However, its specific efficacy and underlying mechanisms have not been elucidated yet. This study aimed to quantitatively evaluate the efficacy of the Gexia Zhuyu decoction using pharmacodynamics and to explore its molecular mechanisms in conjunction with proteomics. High-fat diets and methionine choline-deficient diets were used to induce various NAFLD progression stages in mouse models. The effects of oral Gexia Zhuyu decoction administration on NAFLD were evaluated by measuring the serum and liver indicators of the treated mice before and after drug intervention and by comparing the changes in liver tissue. Liver TRPM4 mRNA and protein levels were measured using reverse transcription-polymerase chain reaction and Western blotting, respectively. Experimental data showed that serum ALT, AST, and liver triglyceride (TG) levels in each disease stage group of drug intervention mice decreased, and high-density lipoprotein (HDL) and superoxide dismutase (SOD) levels increased. Liver TG levels decreased after drug intervention in the liver fibrosis mice, but serum TG levels increased. Furthermore, cellular fatty changes, inflammatory changes, and fibrous tissue proliferation were all relieved. The TRPM4 protein and mRNA levels in the liver tissue were decreased, and the microRNA (miRNA)-24 expression was increased. The Gexia Zhuyu decoction has a clear therapeutic effect at each stage of NAFLD. It likely acts by altering miRNA-24 expression and regulating the target TRPM4 protein pathway to achieve NAFLD treatment.
Lung adenocarcinomas have diverse genetic and morphological backgrounds and are usually classified according to their distinct oncogenic mutations (or so-called driver mutations) and histological subtypes (the de novo classification proposed by the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society [IASLC/ATS/ERS]). Although both these classifications are essential for personalized treatment, their integrated clinical effect remains unclear. Therefore, we analyzed 981 lung adenocarcinomas to detect the potential correlation and combined effect of oncogenic mutations and histological subtype on prognosis. Analysis for oncogenic mutations included the direct sequencing of EGFR, KRAS, HER2, BRAF, PIK3CA, ALK, and RET for oncogenic mutations/rearrangements, and a rereview of the IASLC/ATS/ERS classification was undertaken. Eligible tumors included 13 atypical adenomatous hyperplasia/adenocarcinoma in situ, 20 minimally invasive adenocarcinomas, 901 invasive adenocarcinomas, 44 invasive mucinous adenocarcinomas, and three other variants. The invasive mucinous adenocarcinomas had a lower prevalence of EGFR mutations but a higher prevalence of KRAS, ALK, and HER2 mutations than invasive adenocarcinomas. Smoking, a solid predominant pattern, and a mucinous component were independently associated with fewer EGFR mutations. The ALK rearrangements were more frequently observed in tumors with a minor mucinous component, while the KRAS mutations were more prevalent in smokers. In addition, 503 patients with stage I-IIIA tumors were analyzed for overall survival (OS) and relapse-free survival. The stage and histological pattern were independent predictors of relapse-free survival, and the pathological stage was the only independent predictor for the OS. Although patients with the EGFR mutations had better OS than those without the mutations, no oncogenic mutation was an independent predictor of survival. Oncogenic mutations were associated with the novel IASLC/ATS/ERS classification, which facilitates a morphology-based mutational analysis strategy. The combination of these two classifications might not increase the prognostic ability, but it provides essential information for personalized treatment.
AbstractObjectives: Early nutrition after acute ischemic stroke is crucial. We explored early enteral nutrition for stroke patients and evaluated changes in blood indicators as a predictor of stroke prognosis. Methods:All hospitalized stroke patients receiving enteral nutrition were included in the study. We retrospectively collected the protein, energy, fat, and carbohydrate values for 7 days after admission. Serum albumin, total protein, and hemoglobin values were reviewed at admission and at one week. The main outcome indicators were the Modified Rankin Score, Barthel Index, and Quality of Life at 3 months. Results:A total of 354 patients (mean age, 70.7 years; 59.0% male) were included. The change in serum albumin at day 7 relative to at admission was positively correlated with the Quality of Life score (p=0.001), the Barthel Index (p=0.004), and the modified Rankin Score (p=0.029). The change in total protein at day 7 relative to at admission was positively correlated with the Quality of Life score (p=0.002), the Barthel Index (p=0.001), and the modified Rankin score (p=0.011). The change in hemoglobin values at day 7 relative to at admission was positively correlated with the Barthel Index (p=0.037 but not with the Quality of Life score (p=0.237) or the modified Rankin score (p=0.730). Conclusions:Improved nutrition-related blood indicators one week after admission were independently associated with good stroke outcomes. Nutritional support for acute ischemic stroke patients during the early hospitalization stage appears to be advisable.
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