Effects of Lifestyle Modification and Anti-diabetic Medicine on Prediabetes Progress: A Systematic Review and Meta-Analysis.

Background: Pre-diabetes is a risk factor for full-blown diabetes; it presents opportunities to prevent the actual diseases. It is therefore essential to identify effective preventive strategies, and to clarify the direction of future research. Methods: PubMed, Embase and Cochrane Central Register of Controlled Trials were searched using key terms (Supplementary Table 1). We applied network meta-analysis to multiple comparisons among various diabetic preventive strategies, including lifestyle and pharmacological interventions; traditional meta-analysis for the synthesis of basal metabolic changes after interventions; and trial sequential analysis for determinations as to whether analysis conclusions meet expectations. Results: We included 32 randomized controlled trials comprising 43,669 patients and 14 interventions in the meta-analysis. Both lifestyle modifications and anti-diabetic medications improved physical conditions, including weight loss, blood glucose, and blood pressure. Network meta-analysis suggested that the progression of diabetes could be delayed to varying degrees by lifestyle and pharmacological interventions, except for angiotensin-converting enzyme inhibitors, statins, sulfonylureas and vitamin D. The risk ratios (RR) [95% credible interval (CrI)] compared with control were: GLP-1RAs 0.28 (0.15, 0.50), Orlistat 0.33 (0.18, 0.55), TZM 0.33 (0.16, 0.63), TZD 0.39 (0.27, 0.53), LST 0.54 (0.32, 0.88), lifestyle 0.58 (0.49, 0.67), LSM 0.62 (0.45, 0.80), GI 0.66 (0.46, 0.88), SU 0.67 (0.40, 1.00), Vitamin D 0.91 (0.59, 1.40), ACEI 0.93 (0.62, 1.40), statins 1.20 (0.84, 1.60). Conclusions: In adults with pre-diabetes, firm evidence supports the notion that lifestyle modifications and metformin reduces the incidence of diabetes with an average of 20% relative risk reduction, while statins increase the relative risk 20%. We found that lifestyle modifications, promising long-term strategies involving three factors (nutrition, exercise, and weight loss) contribute to health by reducing BMI, body weight, waist and hip circumference, systolic and diastolic pressure, fasting, and 2-h postprandial blood glucose, total cholesterol and by increasing HDL. We made this determination using TSA, avoiding further waste of experimental resources.

Correction to: Systematic Review and Meta-Analysis of the Change in Ghrelin Levels After Roux-en-Y Gastric Bypass.

This article was initially published with incorrect copyright information. Upon publication of this correction, the copyright of this article changed to "The Author(s)." The original article has been corrected.

Systematic Review and Meta-analysis of the Change in Ghrelin Levels After Roux-en-Y Gastric Bypass.

BACKGROUND: Roux-en-Y gastric bypass (RYGB) is considered effective for weight loss and for treatment of many obesity-related metabolic diseases. Ghrelin is an essential orexigenic peptide that plays an indispensable role in controlling body weight and energy homeostasis of post-operative patients. This systematic review and meta-analysis aimed to investigate changes in the level of fasting total ghrelin following RYGB. METHODS: A systematic literature search of PubMed, EMBASE, and the Cochrane Library until April 2018 with keywords "ghrelin" and "gastric bypass" was performed in accordance with the MOOSE guidelines and PRISMA statement. Three reviewers independently selected the studies and extracted data. Quality assessment of the included studies was undergone. A random effects model was employed to calculate overall effect sizes. Subgroup analyses and meta-regression were subsequently performed. RESULTS: Sixteen studies with 325 patients were included. We found ghrelin levels had an increasing tendency (SMD = 0.30; 95% CI = 0.04 to 0.57) despite moderate heterogeneity (I2 = 58%). Subsequent subgroup analysis indicated that ghrelin levels decreased (SMD = - 0.49; 95% CI = - 0.98 to 0.00) in the short term (≤ 3 months) and increased (SMD = 0.46; 95% CI = 0.22 to 0.69) in the long term (> 3 months) after RYGB. Meta-regression showed that gastric pouch volume, alimentary limb length and biliopancreatic limb length were not associated with changes in ghrelin levels. CONCLUSION: Fasting total ghrelin levels decreased in the short term (≤ 3 months) and increased in the long term (> 3 months) after RYGB.

Expression of nerve growth factor carried by pseudotyped lentivirus improves neuron survival and cognitive functional recovery of post-ischemia in rats.

AIMS: Nerve growth factor (NGF) has been reported to prevent neuronal damage and contributes to the functional recovery in animal brain injury models and human ischemic disease as well. We aimed to investigate a potential therapeutic effect of NGF gene treatment in ischemic stroke and to estimate the functional recovery both at the cellular and cognitive levels in an ischemia rat model. METHODS: After microinjection of pseudolentivirus-delivered ß-NGF into an established ischemic stroke model in rats (tMCAO), we estimated neuronal cell apoptosis with TUNEL labeling and neurogenesis by cell proliferation marker Ki67 staining in both ischemic core and penumbra of striatum. Furthermore, we used behavioral functional tests, Morris water maze performance, to evaluate cognitive functional recovery in vivo and propose a potential underlying mechanism. RESULTS: We found that pseudolentivirus-mediated delivery of ß-NGF gene into the brain induced high expression in striatum of the infarct core area after ischemia in rats. The ß-NGF overexpression in the striatal infarction core after ischemia not only improved neuronal survival by reducing cell apoptosis and increasing cell proliferation, but also rescued cognitive functional impairment through upregulation of GAP-43 protein expression in tMCAO rat model of ischemia. CONCLUSION: This study demonstrates a potential ß-NGF gene therapy by utilization of pseudolentivirus in ischemia and indicates future applications of NGF gene treatment in ischemic patients.

Circular RNA Expression Profiles Alter Significantly after Traumatic Brain Injury in Rats.

Circular RNAs (circRNAs) are involved in a variety of diseases. However, the roles of circRNAs in traumatic brain injury (TBI) remain unknown. In this study, circRNA microarray was used to profile the altered circRNAs in the rat hippocampus following TBI. A total of 192 circRNAs were observed to be differentially expressed (fold change [FC] ≥1.5 and p < 0.05) after TBI, including 98 upregulated and 94 downregulated. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that many messenger RNAs (mRNAs) transcribed from the host genes of altered circRNAs were implicated in brain damage and neural regeneration. CircRNA/microRNA (miRNA) interaction was predicted using Arraystar's homemade miRNA target prediction software based on TargetScan and miRanda. Thus, our studies have demonstrated altered circRNA expression pattern in the rat hippocampus after TBI, which may play important roles in post-TBI physiological and pathological processes. These findings may provide not only a new direction for studying the molecular mechanisms underlying TBI but also a new possibility for the treatment of TBI by modulating circRNAs.

Coronary artery aneurysm combined with other multiple aneurysms at multiple locations: A case report and systematic review.

BACKGROUND: Coronary artery aneurysm (CAA) with concomitant aneurysms at multiple sites is quite unusual and rare. The characteristics and the etiology of this phenomenon are unknown. METHODS: Herein, we present a case with right coronary aneurysm with concomitant abdominal aorta as well as right renal artery aneurysm. A systematic review of the literatures regarding CAA with other coexisting aneurysms at multiple locations was also conducted on Medline and Embase databases. RESULTS: A total of 76 patients (male gender: 58; age: 37.4 ±â€Š26.5) including the present case were included in the final study. The most common etiology of CAA with multiple aneurysms was Kawasaki (43.3%) and atherosclerotic disease (16.4%). CAA was the most frequently found at the right coronary artery (62.7%), following, left anterior descending (51%), left main (43.1%), and left circumflex (35.3%). The most common concomitant aneurysms were abdominal aorta (52.6%) and iliac artery (50%). In addition, 60.5% of the patients had an involved bilateral peripheral artery. CONCLUSION: CAA with coexisting systemic aneurysms in multiple sites is quite rare. And it usually involves multiple aneurysms at the coronary and bilateral peripheral arteries simultaneously. Currently, there are no general consensus regarding the clinical characteristics, diagnostic method, and treatment of these cases.

Predictors and outcome of acute kidney injury after transcatheter aortic valve implantation: a systematic review and meta-analysis.

AIMS: The aim of this systematic review and meta-analysis was to investigate the predictors and outcome of acute kidney injury (AKI) after transcatheter aortic valve implantation (TAVI). METHODS AND RESULTS: There were 35 articles recruiting 13,256 patients included in our study. Hypertension (odds ratio [OR] 1.92, 95% CI: 1.44 to 2.56), diabetes mellitus (OR 1.33, 95% CI: 1.20 to 1.47), peripheral artery disease (OR 1.28, 95% CI: 1.14 to 1.45) and a left ventricular ejection fraction <40% (OR 1.50, 95% CI: 1.19 to 1.88) were identified as significant independent predictors of AKI. In addition to the aforementioned comorbidities, procedure-related/post-TAVI factors such as transapical access (OR 1.68, 95% CI: 1.44 to 1.97), major bleeding (OR 1.82, 95% CI: 1.37 to 2.40) and transfusion (OR 1.30, 95% CI: 1.12 to 1.51) were also associated with a higher risk of AKI. Importantly, the risk of short-term all-cause death increased progressively with the aggravating severity of AKI (OR, 30 days: stage 1: 3.41; stage 2: 4.0; stage 3: 11.02; one year: stage 1: 1.95; stage 2: 2.82; stage 3: 7.34), as determined by a univariate analysis. After eliminating confounders, AKI remained linked to a higher risk for both short-term (30 days: HR 2.12, 95% CI: 1.59 to 2.83) and long-term (≥3 years: HR 1.37, 95% CI: 1.27 to 1.48) all-cause mortality. CONCLUSIONS: The reason for the occurrence of AKI was multifactorial, including baseline characteristics, procedure-related and post-TAVI factors. It appeared that even stage 1 AKI exerted detrimental effects on survival within one year, and AKI was also independently linked to mortality beyond three years.

Meta-Analysis of the Effectiveness and Safety of Transcatheter Aortic Valve Implantation Without Balloon Predilation.

Evidence regarding the safety and feasibility of transcatheter aortic valve implantation without balloon predilation (BP) is scarce. A literature search of PubMed, EMBASE, CENTRAL, and major conference proceedings was performed from January 2002 to July 2015. There were 18 studies incorporating 2,443 patients included in the present study. No differences were observed in the baseline characteristics between patients without BP (no-BP) and with BP. Compared with BP, no-BP had a shorter procedure time (no-BP vs BP, 124.2 vs 138.8 minutes, p = 0.008), used less-contrast medium (no-BP vs BP, 126.3 vs 156.3 ml, p = 0.0005) and had a higher success rate (odds ratio [OR] 2.24, 95% CI 1.40 to -3.58). In addition, no-BP was associated with lower incidences of permanent pacemaker implantation (OR 0.45, 95% CI 0.3 to 0.67), grade 2 or greater paravalvular leakage (OR 0.55, 95% CI 0.37 to 0.83), and stroke (OR 0.57, 95% CI 0.32 to 1.0). Furthermore, no-BP was associated with a 0.6-fold decreased risk for 30-day all-cause mortality (OR 0.60, 95% CI 0.39 to 0.92). However, the difference in the risk for permanent pacemaker implantation, grade 2, or higher aortic regurgitation, stroke was noted to be significant only in the subgroup of the CoreValve-dominating studies. In conclusion, no-BP before transcatheter aortic valve implantation was not only safe and feasible but was also associated with fewer complications and short-term mortality in selected patients especially using self-expandable valve.

Causes of Death Following Transcatheter Aortic Valve Replacement: A Systematic Review and Meta-Analysis.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) is an effective alternative to surgical aortic valve replacement in patients at high surgical risk. However, there is little published literature on the exact causes of death. METHODS AND RESULTS: The PubMed database was systematically searched for studies reporting causes of death within and after 30 days following TAVR. Twenty-eight studies out of 3934 results retrieved were identified. In the overall analysis, 46.4% and 51.6% of deaths were related to noncardiovascular causes within and after the first 30 days, respectively. Within 30 days of TAVR, infection/sepsis (18.5%), heart failure (14.7%), and multiorgan failure (13.2%) were the top 3 causes of death. Beyond 30 days, infection/sepsis (14.3%), heart failure (14.1%), and sudden death (10.8%) were the most common causes. All possible subgroup analyses were made. No significant differences were seen for proportions of cardiovascular deaths except the comparison between moderate (mean STS score 4 to 8) and high (mean STS score >8) -risk patients after 30 days post-TAVR (56.0% versus 33.5%, P=0.005). CONCLUSIONS: Cardiovascular and noncardiovascular causes of death are evenly balanced both in the perioperative period and at long-term follow-up after TAVR. Infection/sepsis and heart failure were the most frequent noncardiovascular and cardiovascular causes of death. This study highlights important areas of clinical focus that could further improve outcomes after TAVR.

Design, synthesis, and evaluation of 3-aryl-4-pyrrolyl-maleimides as glycogen synthase kinase-3ß inhibitors.

A series of 3-aryl-4-pyrrolyl-maleimides were designed, synthesized, and evaluated for their glycogen synthase kinase-3ß (GSK-3ß) inhibitory activity. Most compounds exhibited potent activity against GSK-3ß. Among them, compounds 11a, 11c, 11h, 11i, and 11j significantly reduced Aß-induced Tau hyperphosphorylation, showing the inhibition of GSK-3ß at the cellular level. Structure-activity relationships were discussed based on the experimental data obtained.