Genetically determined tobacco and alcohol use and risk of atrial fibrillation.

BACKGROUND: The causality between the use of alcohol and cigarettes and atrial fibrillation (AF) remains controversial. We conducted a Mendelian randomization (MR) study to evaluate the association of genetic variants related to tobacco and alcohol use with AF. METHODS: Single nucleotide polymorphisms (SNPs) related to smoking initiation (N = 374), age at initiation of regular smoking (N = 10), cigarettes per day (N = 55), and smoking cessation (N = 24) were derived from a genome-wide association studies (GWAS) of tobacco use (N = 1.2 million individuals). SNPs related to heavy alcohol use (N = 6) were derived from a GWAS of UK biobank (N = 125,249 individuals). The genetically matching instrumented variables were obtained from the GWAS of AF (N = 588,190 individuals). The estimates between tobacco and alcohol use and AF were combined by inverse-variance weighted (IVW), simple median, weighted median, MR-robust adjusted profile score method, MR-PRESSO, and multivariable MR. RESULTS: A total of 65,446 AF patients and 522,744 referents were included. In the IVW analysis, the odds ratio per one-unit increase of smoking initiation was 1.11 (95% CI, 1.06-1.16; P = 3.35 × 10-6) for AF. Genetically predicted age at initiation of regular smoking, cigarettes per day and smoking cessation were not associated with AF. The IVW estimate showed that heavy alcohol consumption increased AF risk (OR, 1.11; 95% CI, 1.04-1.18; P = 0.001). The results were consistent in complementary analyses and multivariable MR. CONCLUSION: Our MR study indicated that regular smoking was associated with increased risk of AF, no matter the age at initiation of regular smoking, or the number of cigarettes smoked per day. Genetically predicted heavy alcohol consumption increased the risk of AF.

Smoking and heart failure: a Mendelian randomization and mediation analysis.

AIMS: We performed a Mendelian randomization (MR) study to elucidate the associations of ever smoking, lifelong smoking duration, and smoking cessation with heart failure (HF) risk. METHODS AND RESULTS: We extracted genetic variants associated with smoking initiation, age at initiation of regular smoking, cigarettes per day, and smoking cessation from the genome-wide association study and Sequencing Consortium of Alcohol and Nicotine use (1.2 million individuals), as well as a composite lifetime smoking index from the UK Biobank (462 690 individuals). The associations between smoking phenotypes and HF were explored in the Heart Failure Molecular Epidemiology for Therapeutic Targets Consortium (47 309 cases; 930 014 controls) employing inverse variance-weighted meta-analysis and multivariable MR. The mediation effects of coronary artery disease and atrial fibrillation on smoking-HF risk were explored using mediation analysis. The odds ratios (ORs) for HF were 1.28 [95% confidence interval (CI), 1.22-1.36; P = 1.5 × 10-18 ] for ever regular smokers compared with never smokers and 1.25 (95% CI, 1.09-1.44; P = 1.6 × 10-3 ) for current smokers vs. former smokers. Genetic liability to smoking more cigarettes per day (OR, 1.37; 95% CI, 1.20-1.58; P = 6.4 × 10-6 ) and a higher composite lifetime smoking index (OR, 1.49; 95% CI, 1.31-1.70; P = 2.5 × 10-9 ) were associated with a higher risk of HF. The results were robust and consistent in all sensitivity analyses and multivariable MR after adjusting for HF risk factors, and their associations were independent of coronary artery disease and atrial fibrillation. CONCLUSIONS: Genetic liability to ever smoking and a higher lifetime smoking burden are associated with a higher risk of HF.

Genetic Liability to Depression and Risk of Coronary Artery Disease, Myocardial Infarction, and Other Cardiovascular Outcomes.

Background Observational studies have indicated that depression is associated with coronary artery disease (CAD) and myocardial infarction. Nevertheless, causal associations between depression and cardiovascular diseases remain controversial. Hence, we conducted a Mendelian randomization and mediation analysis to evaluate the associations of depression-related genetic variants with CAD and myocardial infarction. Methods and Results Summary statistics from genome-wide association studies of depression (807 553 individuals), and CAD (60 801 cases, including 43 676 with myocardial infarction, and 123 504 controls) were used. We pooled Mendelian randomization estimates using a fixed-effects inverse-variance weighted meta-analysis and multivariable Mendelian randomization. The mediation effects of potential cardiovascular risk factors on depression-CAD and myocardial infarction risk were investigated by using mediation analysis. We also explored the relationship of genetic liability to depression with heart failure, atrial fibrillation, and ischemic stroke. Genetic liability to depression was associated with higher CAD (odds ratio [OR], 1.14; 95% CI, 1.06-1.24; P=1.0×10-3) and myocardial infarction (OR, 1.21; 95% CI, 1.11-1.33; P=4.8×10-5) risks. Results were consistent in all sensitivity analyses. Type 2 diabetes mellitus and smoking demonstrated significant mediation effects. Furthermore, our Mendelian randomization analyses revealed that the genetic liability to depression was associated with higher risks of heart failure and small vessel stroke. Conclusions Genetic liability to depression is associated with higher CAD and myocardial infarction risks, partly mediated by type 2 diabetes mellitus and smoking. The potential preventive value of depression treatment on cardiovascular diseases should be investigated in the future.

Bone marrow mesenchymal stem cells ameliorated kidney fibrosis by attenuating TLR4/NF-κB in diabetic rats.

Diabetic nephropathy (DN) is a chronic inflammatory complication of diabetes mellitus, which becomes the most common cause of end-stage renal disease (ESRD). Recently, bone marrow mesenchymal stem cells (BMSCs) are considered as a promising therapy for DN. However, the protective mechanism of BMSCs on DN remains unclear. This study was done to explore the effect of a bone marrow stromal cell (BMSCs) transplant on DN rats and rat glomerular mesangial cells in high-glucose concentration. Diabetic rats were induced by a single intraperitoneal injection of streptozotocin (STZ) 65 mg/kg, then 4 × 106 BMSCs were transplanted in diabetic rats as the treatment group. Six weeks after BMSCs transplantation, blood serum creatinine (Scr) and blood urea nitrogen (BUN) were used to test renal function. Renal pathological examination was observed by HE staining, Masson staining, PAS staining and immunohistochemistry. The results demonstrated that BMSCs could dramatically improve renal function and collagen accumulation by reducing Scr, BUN, collagen I and IV expression and histopathological abnormalities in the diabetic kidneys. Furthermore, BMSCs could significantly attenuate the expression of TLR4/NF-κB and MCP-1 in vitro and in vivo (P < 0.05, vs diabetic groups). This study reported a novel finding that BMSCs play a protective role in inhibition of inflammatory and fibrotic cytokines by down-regulating TLR-4/NF-κB expression under diabetic condition.

Does chronic obstructive pulmonary disease relate to poor prognosis in patients with lung cancer?: A meta-analysis.

BACKGROUND: Nowadays, there is growing recognition that chronic obstructive pulmonary disease (COPD) may have influence on lung cancer. However, coexisted COPD related to prognosis of lung cancer is still elusive. We conducted this meta-analysis to examine the association between COPD and 5-year overall survival (OS) and postoperative pulmonary complications of patients with lung cancer. METHODS: A comprehensive computer-based online search was conducted using PubMed, Embase, Medline, and the Cochrane Library for articles published before September 30, 2017. We identified 29 eligible studies, which included 70,111 patients in the related literature. RESULTS: Twenty-two of the 29 studies provided hazard ratio for OS (1.18, 95% confidence interval: 1.11-1.25; P < .001), it suggested that the presence of COPD indicated poor survival for the patients with lung cancer. In subgroup analysis, the relationship between COPD and OS occurrence remained statistically prominent in the subgroups stratified by study designs, COPD diagnosis timing, lung cancer surgery, cancer stage, and origins of patients. The presence of COPD increased the risk of bronchopleural fistula, pneumonia, prolonged air leakage, and prolonged mechanical ventilation. CONCLUSIONS: The present meta-analysis suggested that coexisting COPD is associated with poor survival outcomes in patients with lung cancer and higher rates of postoperative pulmonary complications.

Bone marrow mesenchymal stem cells (BMSCs) improved functional recovery of spinal cord injury partly by promoting axonal regeneration.

Spinal cord injury (SCI) disrupts the spinal cord and results in the loss of sensory and motor function below the lesion site. The treatment of SCI became a challenge because the injured neurons fail to axon regenerate and repair after injury. Promoting axonal regeneration plays a key role in the treatment strategies for SCI. It would meet the goal of reconstruction the injured spinal cord and improving the functional recovery. Bone marrow mesenchymal stem cells (BMSCs) are attractive therapeutic potential cell sources for SCI, and it could rebuild the injured spinal cord through neuroprotection, neural regeneration and remyelinating. Evidence has demonstrated that BMSCs play important roles in mediating axon regeneration, and glial scar formation after SCI in animal experiments and some clinical trials. We reviewed the role of BMSCs in regulating axon regeneration and glial scar formation after SCI. BMSCs based therapies may provide a therapeutic potential for the injured spinal cord by promoting axonal regeneration and repair.

Sentinel lymph node mapping in endometrial cancer: a systematic review and meta-analysis.

Endometrial cancer is the most frequent tumor in the female reproductive system, while the sentinel lymph node (SLN) mapping for diagnostic efficacy of endometrial cancer is still controversial. This meta-analysis was conducted to evaluate the diagnostic value of SLN in the assessment of lymph nodal involvement in endometrial cancer. Forty-four studies including 2,236 cases were identified. The pooled overall detection rate was 83% (95% CI: 80-86%). The pooled sensitivity was 91% (95% CI: 87-95%). The bilateral pelvic node detection rate was 56% (95% CI: 48-64%). Use of indocyanine green (ICG) increased the overall detection rate to 93% (95% CI: 89-96%) and robotic-assisted surgery also increased the overall detection rate to 86% (95% CI: 79-93%). In summary, our meta-analysis provides strong evidence that sentinel node mapping is an accurate and feasible method that performs well diagnostically for the assessment of lymph nodal involvement in endometrial cancer. Cervical injection, robot-assisted surgery, as well as using ICG, optimized the sensitivity and detection rate of the technique. Sentinel lymph mapping may potentially leading to a greater utilization by gynecologic surgeons in the future.