High-Sensitivity C-Reactive Protein and Ischemic Stroke in Patients with Nonalcoholic Fatty Liver Disease: A Prospective Study.

Background and Aims: Inflammation is involved in the pathophysiology of ischemic stroke. The aim of this prospective study was to evaluate the association of hs-CRP with incident ischemic stroke in patients with nonalcoholic fatty liver disease (NAFLD). Methods: A sample of 318 participants without previous strokes was included in this study. Hs-CRP levels and other potential confounding factors were measured at baseline. NAFLD was performed by abdominal ultrasound after excluding secondary causes for fat accumulation. According to baseline hs-CRP concentrations, participants were categorized into 3 groups: level 1 (<1.0 mg/L), level 2 (1.0 to <3.0 mg/L), and level 3 (≥3.0 mg/L). The outcome of interest was the first occurrence of an ischemic stroke. Cox proportional hazards models were used to analyze hazard ratios (HRs) and 95% confidence intervals (CIs) of incident ischemic stroke, after adjusting for potential confounders. Results: The mean age of 318 participants with NAFLD was 71.1 ± 6.7 years, and 55.3% of them were male. Among 318 individuals with NAFLD, 115 (36.2%) of them had an hs-CRP value <1 mg/L (level 1), 105 (33.0%) had an hs-CRP value between 1 and 3 mg/L (level 2), and 98 (30.8%) belonged to level 3 (hs-CRP ≥3 mg/L). Over a median of 5.60 years of follow-up, 47 incident ischemic stroke events were documented in 318 patients with NAFLD. After full adjustment for confounding factors, compared with participants in the level 1 group (hs-CRP<1.0 mg/L), the HRs of those in the level 2 group (1.0 to <3.0 mg/L) and the level 3 group (≥3.0 mg/L) were 1.77 (95% CI: 0.94-2.98) and 2.45 (95% CI: 1.37-5.77) for developing ischemic stroke, respectively. Conclusions: Elevated hs-CRP levels were associated with an increased risk of ischemic stroke among patients with NAFLD.

The LAC Score Indicates Significant Fibrosis in Patients With Chronic Drug-Induced Liver Injury: A Large Biopsy-Based Study.

Currently, there are no satisfactory noninvasive methods for the diagnosis of fibrosis in patients with chronic drug-induced liver injury (DILI). Our goal was to develop an algorithm to improve the diagnostic accuracy of significant fibrosis in this population. In the present study, we retrospectively investigated the biochemical and pathological characteristics of consecutive patients with biopsy-proven chronic DILI, who presented at our hospital from January 2013 to December 2017. A noninvasive algorithm was developed by using multivariate logistic regression, receiver operating characteristic (ROC) curves, and decision curve analysis (DCA) to diagnose significant fibrosis in the training cohort, and the algorithm was subsequently validated in the validation cohort. Totally, 1,130 patients were enrolled and randomly assigned into a training cohort (n = 848) and a validation cohort (n = 282). Based on the multivariate analysis, LSM, CHE, and APRI were independently associated with significant fibrosis. A novel algorithm, LAC, was identified with the AUROC of 0.81, which was significantly higher than LSM (AUROC 0.78), CHE (AUROC 0.73), and APRI (AUROC 0.68), alone. The best cutoff value of LAC in the training cohort was 5.4. When the LAC score was used to diagnose advanced fibrosis and cirrhosis stages, the optimal cutoff values were 6.2 and 6.7, respectively, and the AUROC values were 0.84 and 0.90 in the training cohort and 0.81 and 0.83 in the validation cohort. This study proved that the LAC score can contribute to the accurate assessment of high-risk disease progression and the establishment of optimal treatment strategies for patients with chronic DILI.

The effect of complicated febrile convulsion on hippocampal function and its antiepileptic treatment significance.

BACKGROUND: This study aimed to explore the effects of complex febrile seizures on hippocampal function and the significance of antiepileptic therapy. METHODS: A total of 150 children with complex febrile seizures admitted to our hospital from July 2017 to July 2020 were included in the study. The VPA group was given sodium valproate treatment; the LEV group was given levetiracetam treatment; and the observation group was given basic treatment. The efficacy of the patients was evaluated after medication. A complex febrile seizure young mouse model was constructed, and the hippocampal cell morphology and BCL-2 expression of the mice pups were analyzed. A Morris water maze was used to detect the changes in cognitive function of the young mice with complex febrile seizures. RESULTS: After treatment, the recurrence-free rate of the VPA group was significantly higher than that of the observation group (P=0.0045). After 1 month and 6 months, the improvement rate of EEG in VPA group was significantly higher than that in observation group (P<0.05). After treatment, the levels of BCL-2 in the VPA group and the LEV group decreased and were significantly lower than the observation group during the same period (P<0.05), and the M/C of the two groups was significantly higher than the observation group (P<0.05). The neuronal cells in the hippocampus of the young rats in the VPA group and the LEV group were regular, the matrix was more uniform, and nuclear pyknotic cells were occasionally seen. The pathological changes were less obvious than the model group, followed by the degree of pathological changes (0.92±1.31, 0.94±1.24). The incubation period of pups in the model group was significantly higher than that of the normal group, VPA group, and LEV group (P<0.05), and the number of crossing the station area was significantly less than that of the normal group, VPA group, and LEV group (P<0.05). CONCLUSIONS: Antiepileptic drugs are effective in preventing the recurrence of complicated febrile seizures (CFS), and the main mechanism may be related to the targeted regulation of BCL-2 on the apoptosis of the hippocampus in the nervous system.

MicroRNA-545 targets ZEB2 to inhibit the development of non-small cell lung cancer by inactivating Wnt/ß-catenin pathway.

The specific function of microRNA-545 (miR-545) has been reported to regulate the development of human cancers. However, the effect of miR-545 is still unclear in non-small cell lung cancer (NSCLC). Hence, this study explored the molecular mechanism of miR-545 in NSCLC. The expression levels of miR-545 and ZEB2 were measured through reverse transcription-quantitative polymerase chain reaction (RT-qPCR) assay. The protein expression was detected by western blotting. Dual luciferase assay was applied to evaluate the relationship between miR-545 and zinc finger E-box-binding homeobox 2 (ZEB2). MTT and Transwell assays were used to investigate the function of miR-545 in NSCLC. The expression of miR-545 was decreased in NSCLC tissues. The overexpression of miR-545 suppressed the migration, invasion and proliferation of NSCLC cells. Furthermore, ZEB2 was a direct target gene of miR-545. The knockout of ZEB2 suppressed the development of NSCLC. miR-545 inhibited the progression of NSCLC through targeting ZEB2. Moreover, miR-545 repressed the development of NSCLC via blocking EMT and Wnt/ß-catenin pathway. In conclusion, miR-545 inhibited the progression of NSCLC through targeting ZEB2 and blocking EMT and Wnt/ß-catenin pathway.

The Effect of Puerarin on Carotid Intima-media Thickness in Patients With Active Rheumatoid Arthritis: ARandomized Controlled Trial.

PURPOSE: Cardiovascular and diabetic complications are the main causes of death in patients with rheumatoid arthritis (RA). Puerarin has potential protective effects against subclinical atherosclerosis and insulin resistance, but the clinical evidence is still not sufficient to draw definitive conclusions. Therefore, we performed the clinical trial to assess the effect of puerarin on carotid intima-media thickness (CIMT) in RA. METHODS: This is an open, controlled, randomized, and parallel-group comparison study of 119 patients with a definite diagnose of active RA. All 119 consecutive patients with RA receiving routine antirheumatic care were randomized to receive treatment with (n = 60; 16 males and 44 females; mean age, 52.97 years; 95% CI, 49.78-56.15 years) or without (n = 59; 17 males and 42 females; mean age, 54.05 years; 95% CI, 50.03-58.07 years) 400mg of puerarin. The effects of both interventions on CIMT, homeostasis model assessment of insulin resistance (HOMA-IR) value, and possible adverse events were assessed and compared at entry, 12 weeks, and 24 weeks. The collected data were processed and assessed using ANCOVA, paired t test, repeated-measure ANOVA, one-way ANOVA, Pearson's χ2 test, Fisher exact test, Kaplan-Meier survival analysis, Pearson correlation, and LOESS (locally weighted smoothing) regression analysis. FINDINGS: No significant adverse effects occurred concerning the use of puerarin, and both interventions were generally well tolerated in all the patients. A tiny but significant decrease of CIMT was observed in puerarin-treated patients at 24 weeks (-0.003 mm; 95% CI, -0.005 to -0.001vs 0.019 mm; 95% CI, -0.002 to 0.040; P < 0.001). At 24 weeks, insulin resistance was indicated with more pronounced improvement in the puerarin group versus the control group (homeostasis model assessment, -0.40; 95% CI, -0.47 to -0.33vs -0.05; 95% CI, -0.08 to -0.01; P < 0.001). Correlation analysis indicated an interaction between the parallel reductions in CIMT and insulin resistance in the puerarin group (r = 0.878, P < 0.001) but not in the control group. IMPLICATIONS: In the study, 24 weeks of treatment with 400mg of puerarin exerted a significant effect against CIMT progression in patients with active RA, which may be associated with the improvement of insulin resistance. Puerarin holds promise as a drug candidate for the prevention and treatment of cardiometabolic comorbidities in patients with active RA. However, more strictly designed trials, such as double-blind and placebo-controlled trials, are still required. ClinicalTrials.gov identifier: NCT02254655.

Correlations among Helicobacter pylori infection and the expression of cyclooxygenase-2 and vascular endothelial growth factor in gastric mucosa with intestinal metaplasia or dysplasia.

BACKGROUND AND AIMS: To examine the rate of Helicobacter pylori infection and the expression of cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF) in gastric mucosa with intestinal metaplasia or dysplasia, and explore their correlations in precancerous gastric lesions. METHODS: A total of 172 patients were included in the study. H. pylori infection was evaluated by hematoxylin-eosin and modified Giemsa staining. The expression of COX-2 and VEGF proteins was detected by immunohistochemistry. RESULTS: The rates of H. pylori infection in gastric mucosal dysplasia (DYS), intestinal metaplasia in gastric mucosa (IM), chronic atrophic gastritis (CAG) and chronic superficial gastritis (CSG) patients were significant differences (P = 0.001). The average optical density (AOD) values of COX-2 staining in CSG, CAG, IM and DYS patients were 13.81 +/- 5.53, 45.28 +/- 21.44, 73.67 +/- 26.02 and 91.23 +/- 45.11, respectively, with significant differences among CSG, CAG and IM patients (P = 0.037, 0.001 and 0.047 for CSG vs CAG, CSG vs IM and CAG vs IM, respectively). The expression level of VEGF in DYS patients was significantly higher than those in other patients (P = 0.001, 0.001 and 0.001 for DYS vs CSG, DYS vs CAG and DYS vs IM, respectively). The expression levels of COX-2 in H. pylori-positive IM, CAG and DYS patients were significantly higher than those in H. pylori-negative counterparts (P = 0.043, 0.009, 0.001, respectively). Additionally, the expression level of COX-2 was positively correlated with that of VEGF with the aggravation of gastric mucosal lesions (r = 0.640, P = 0.006). CONCLUSION: H. pylori infection might be able to induce the expression of COX-2 in precancerous gastric lesions, which in turn upregulates the expression of VEGF.