Response to pioglitazone in non-alcoholic fatty liver disease patients with vs. without type 2 diabetes: A meta-analysis of randomized controlled trials.

Background: Pioglitazone is considered a potential therapy for non-alcoholic fatty liver disease (NAFLD). However, different effects of pioglitazone on NAFLD have been demonstrated in diabetic and non-diabetic patients. Herein, a meta-analysis of randomized, placebo-controlled trials was carried out to indirectly compare pioglitazone in NAFLD patients with vs. without type 2 diabetes. Methods: Randomized controlled trials (RCTs) of pioglitazone vs. placebo involving NAFLD patients with or without type 2 diabetes/prediabetes collected from databases were enrolled into this analysis. Methodological quality was employed to evaluate the domains recommended by the Cochrane Collaboration. The analysis covered the changes in histology (fibrosis, hepatocellular ballooning, inflammation, steatosis), liver enzymes, blood lipids, fasting blood glucose (FBS), homeostasis model assessment-IR (HOMA-IR), weight and body mass index (BMI) before and after treatment, and adverse events. Results: The review covered seven articles, with 614 patients in total, of which three were non-diabetic RCTs. No difference was found in patients with vs. without type 2 diabetes in histology, liver enzymes, blood lipids, HOMA-IR, weight, BMI, and FBS. Moreover, no significant difference was revealed in adverse effects between NAFLD patients with diabetes and without DM, except the incidence of edema that was found to be higher in the pioglitazone group than in the placebo group in NAFLD patients with diabetes. Conclusions: Pioglitazone could exert a certain effect on alleviating NAFLD, which was consistent between non-diabetic NAFLD patients and diabetic NAFLD patients in improving histopathology, liver enzymes, and HOMA-IR and reducing blood lipids. Furthermore, there were no adverse effects, except the incidence of edema which is higher in the pioglitazone group in NAFLD patients with diabetes. However, large sample sizes and well-designed RCTs are required to further confirm these conclusions.

Exploration of a new method for Photoshop-assisted endoscopic ultrasound to distinguish gastrointestinal stromal tumor and leiomyoma.

BACKGROUND: Gastrointestinal stromal tumors (GISTs) and leiomyomas (GILs) are difficult to be distinguished by endoscopic ultrasound (EUS). Photoshop software combined with EUS has limitations in distinguishing GIST and GIL by detecting gray values. Therefore, the research aims to explore the new method by Photoshop in distinguishing the features of GISTs from GILs. METHODS: Patients who underwent EUS and were confirmed as GIST and GIL pathologically were included. The images of EUS were analyzed by Photoshop software. The mean gray value of tumor (Tmean), muscularis propria (Mmean), submucosa (Smean), water (Wmean) and TSD that originated from the same image, were calculated one by one. Then the ratio of the mean gray value of tumor to muscularis propria (TMratio), submucosa (TSratio), and water (TWratio) were calculated, respectively. RESULTS: Four hundred seventy-two patients (239 GILs and 233 GISTs) were enrolled in this study retrospectively. All the tumors were located in the stomach. Tmean and TSD were significantly higher in GISTs than in the GILs group (63.10 ± 23.29 vs. 57.70 ± 22.67, p = .011; 26.24 ± 8.99 vs. 24.30 ± 8.26, p = .015). TMratio, TSratio, and TWratio were also significantly higher in GISTs group (0.97 ± 0.37 vs. 0.81 ± 0.28, p < .001; 0.42 ± 0.14 vs. 0.38 ± 0.12, p < .001; 2.65 ± 1.36 vs. 2.16 ± 1.02, p < .001). The AUC of Tmean was 0.952 (95% CI 0.897-1.000), which can better distinguish GIST from GIL; the sensitivity was 0.900, the specificity was 0.975, and the Youden Index was 0.875, and the cutoff was 79.64. The AUCs of TMratio, TSratio, and TWratio were 0.917 (95% CI 0.844-0.991), 0.897 (95% CI 0.812-0.981), and 0.929 (95% CI 0.8870-0.987), respectively. The aforementioned data was verified in the clinical cases of known results, including 40 GISTs and 40 GILs. The sensitivity of Tmean, TMratio, TSratio, and TWratio for diagnosis of GIL was 97.5%, 82.5%, 95%, and 97.5%, respectively. And they were 62.5%, 95%, 80%, and 92.5% for GIST. CONCLUSION: The application of Photoshop combined with EUS to detect the gray value and standard deviation has a specific value in distinguishing GIST from GIL, but with some deviation. Applying the gray value ratio also has great discrimination significance and can avoid the differences in operation from different instrument and equipment personnel. Therefore, it is worthy of clinical promotion in the future.

Rapamycin Attenuates Anxiety and Depressive Behavior Induced by Helicobacter pylori in Association with Reduced Circulating Levels of Ghrelin.

Background: Helicobacter pylori (H. pylori) infection is closely associated with depression and development of neuroinflammation. The aim of this study is to explore the relationship between H. pylori, depression, and circulating levels of ghrelin. Methods: Mice were randomly divided into three groups: healthy control group (gavaged sterile saline and injected with saline, n = 8); H. pylori+saline group (gavaged H. pylori and injected with saline, n = 8); and H. pylori+rapa group (gavaged H. pylori and injected with rapamycin, n = 8). Open field test (OFT), sucrose preference test (SPT), forced swim test (FST), and tail suspension test (TST) were used for anxiety and depressive behavior test. Western blotting was utilized to assess mTOR, p-mTOR, and GSMD expression, and serum ghrelin levels were estimated using ELISA. Results: In the OFT, the control mice moved more and exhibited a increase in crossing number relative to the H. pylori+saline mice (all P < 0.05). Increased quantity of fecal boli can be indicative of increased anxiety and emotionality of the subject animal. H. pylori+saline mice exhibited an increase in fecal boli when compared to control mice and H. pylori+rapa mice (P < 0.05). H. pylori infected mice decreasing the expression of ghrelin. The protein levels of p-mTOR/mTOR in the gastric antrum mTOR signaling activation and low-level ghrelin in H. pylori-infect mice compared to those in control mice (all P <0.001). Compared with single H. pylori infection, mTOR inhibitors increased the ghrelin secretion of H. pylori infection to a certain extent (P < 0.05). The protein levels of GSDMD expression significantly increase in hippocampus of H. pylori-infected mice (P < 0.001). Rapamycin treatment inhibited expression of GSDMD in H. pylori-infected mice (P < 0.05). Conclusions: H. pylori infection is associated with increased expression of mTOR and decreased circulating levels of ghrelin. Elevated pyroptosis in the brain and anxiety- and depressed-like behaviors occur when ghrelin levels are suppressed.