Causal relationship between atrial fibrillation and cognitive impairment:a Mendelian randomization study / 上海交通大学学报（医学版）

Objective·To investigate the causal relationship between atrial fibrillation(AF)and cognitive impairment.Methods·A two-sample Mendelian randomization(TSMR)analysis was used to assess the potential causality of AF on cognitive dysfunction.Single nucleotide polymorphisms(SNPs)strongly associated with AF were extracted as instrumental variables by using a dataset of a large-scale genome-wide association study(GWAS)on AF.The associations of SNPs with Alzheimer's disease dementia,Parkinson's disease dementia,vascular dementia,Lewy body dementia,frontotemporal dementia,undefined dementia,and overall cognitive function assessment were extracted separately from publicly available GWAS data on cognitive dysfunction.The inverse variance-weighted(IVW)method was used for the main analysis,and sensitivity analyses were conducted by using Cochran's Q test,MR-Egger regression,and leave-one-out method.To verify the robustness of the results,replicate analyses and meta-analyses were performed by using different GWAS data.Results·In the initial analysis,101 SNPs were extracted as instrumental variables from a meta-analysis of a genome-wide association study involving up to 1 030 836 individuals.The IVW analysis showed no evidence for causal associations between AF and dementia[dementia(OR=1.032;95％CI 0.973-1.094;P=0.290),Parkinson's disease dementia(OR=1.004;95％CI 0.780-1.291;P=0.977),vascular dementia(OR=1.123;95％CI 0.969-1.301;P=0.125),or unspecified dementia(OR=1.013;95％CI 0.910-1.129;P=0.807)].In the replication analysis,27 SNPs were extracted as instrumental variables from the FinnGen AF GWAS data,and the 1VW analysis were consistent with the initial analysis[cognitive function(OR=0.999;95％CI 0.982-1.016;P=0.874),Alzheimer's disease dementia(OR=0.977;95％CI 0.943-1.012;P=0.193),Lewy body dementia(OR=1.014;95％CI 0.898-1.145;P=0.826),or frontotemporal dementia(OR=0.996;95％CI 0.745-1.333;P=0.980)].Both Mendelian randomization analyses and meta-analyses showed no evidence of an association between genetically predicted AF and different types of dementia or overall cognitive function assessment.MR-Egger regression suggested no horizontal pleiotropy and leave-one-out analysis showed stable results after individually removing each SNP.Conclusion·No evidence of a causal relationship between AF and cognitive impairment was found.The associations observed in observational studies can be partially attributed to confounding factors such as shared biology or co-morbidities.

Comparison of new and old electrocardiographic algorithms of location diagnosis for outflow tract ventricular arrhythmias / 实用医学杂志

Objective To evaluate the accuracy of the new and old electrocardiographic algorithms for differentiating the origins of outflow tract ventricular arrhythmias. Methods The clinical data of 202 patients treated between 2010 and 2013 were retrospectively reviewed for the investigations of the four algorithms including the transitional zone index, the V2 transition ratio, V2 R-wave duration and R/S-wave amplitude indices and the Sv2/Rv3 index. Results Regardless of rotation, the V2 transition ratio had the highest sensitivity (93.5%), while the Sv2/Rv3 index had the highest specificity (93.8). The maximal area under the ROC curve of four was more than 0.8, while the transitional zone index had the minimal area (0.804) with statistical significance (P 0.05). Conclusion Regardless of rotation, the Sv2/Rv3 index has the highest specificity and equal diagnostic value, with equal diagnostic value of the V2 transition ratio and V2 R-wave duration and R/S-wave amplitude indices. Compared with other algorithms, the Sv2/Rv3 index is simple and can be a complement as well for the direction of ablation therapy.

Partial safety of Ad-HIF-1α-Trip gene transfection on a rabbit model of acute hind-limb ischemia / 实用医学杂志

Objective To investigate the partial safety of the recombinant adenovirus containing the triple-point mutants HIF-1αgene (Ad-HIF-1α-Trip)transfection in a rabbit model of hind limb ischemia. Methods After ligation of left femoral artery, 22 New Zealand whites rabbits were randomly divided into 3 groups: saline group(n=6), Ad-Null group(n=6) and Ad-HIF-1α-Trip group(n=10). After operation, saline, Ad-Null and Ad-HIF-1αwere injected intramuscularly respectively. The expression of transferred HIF-1αat mRNA level in the ischemic skeletal muscle and other important organs were detected by Real-time PCR 10 days after gene transfection. The body temperature, weight, blood, liver and renal function, as well as the myocardial enzymes were detected before operation, and on the 3th, 7th, 14th and 28th day after gene transfection, so that pathological changes could be observed. Results On the 10th day after gene transfection, obvious expressions of HIF-1αat mRNA level in the ischemic limb were found, but no expression in other important organs was detected in Ad-HIF-1α-Trip group. The blood routine, liver and renal function were all in the normal range (P > 0.05). No abnormalities were found in heart, liver, kidney, and lung HE transfection in Ad-HIF-1α-Trip group. Conclusion Single intramuscular injection of Ad-HIF-1α-Trip can be expressed obviously in the ischemic limb without detected damage of liver , cardiac and kidney.

Effects of a triple mutant hypoxia-inducible factor-1α on proliferation and vascular endothelial growth factor expression in human microvascular endothelial cells / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effects of a recombinant adenovirus-mediated triple mutant hypoxia-inducible factor-1α (HIF-1α) on the proliferation and vascular endothelial growth factor (VEGF) expression in human microvascular endothelial cells (hMVECs).</p><p><b>METHODS</b>The adenovirus vector of the triple mutant HIF-1α (Ad-HIF-1α(564/402/803)), adenovirus vector of wild-type HIF-1α (Ad-HIF-1α(nature)), Ad-lacZ and Ad-Null were amplified in HEK293A cells, and the adenoviruses were purified and titrated. Dual luciferase reporter assay system was employed to detect the transcriptional activities of wild-type and triple mutant HIF-1α. After infection of the hMVECs with the adenoviruses, the cellular protein expressions of HIF-1α and VEGF were detected using Western blotting, and the cell proliferation was assessed by MTS assay.</p><p><b>RESULTS</b>The transcriptional activity of the triple mutant HIF-1α was significantly higher than that of wildtype HIF-1α in the infected hMVECs (P<0.001). The protein levels of HIF-1α and VEGF in cells infected with Ad-HIF-1α(564/402/803) were significantly higher than those in cells infected with other adenoviruses, and HIF-1α dose-dependently up-regulated VEGF protein expression. The absorbance was significantly higher in Ad-HIF-1α(564/402/803) group than in the other groups (P<0.01) on the third and fifth days after infection.</p><p><b>CONCLUSION</b>The recombinant adenovirus-mediated triple mutant HIF-1α expression is stable under normoxic condition. The triple mutant HIF-1α can up-regulate the expression of VEGF protein in hMVECs to promote the cell proliferation.</p>

Contrast induced nephropathy after percutaneous coronary intervention: risk factors and preventive strategy / 老年心脏病学杂志（英文版）

Objective To analyze the risk factors and clinical outcome of contrast induced nephropathy (CIN) in patients with coronary artery disease (CAD) after percutaneous coronary intervention (PCI) and discuss its prevention.Methods Fifty-four patients with CIN among 729 patients who received PCI were retrospectively studied and the related risk factors,cardiovascular events and preventive strategy were analyzed.Results CIN was strongly associated with pre-procedure chronic renal failure,diabetes mellitus and large-dose contrast.The incidence of cardiac mortality and major adverse cardiac events 1 year after PCI in CIN group was higher than that in group without CIN.Conclusion Chronic renal failure,diabetes mellitus and dosage of contrast agent were three independent risk factors of CIN.CIN could affect the patients' prognosis.A well overall perioperative management of CAD patients following PCI,especially hydration therapy,is the most important strategy for prevention of CIN .

Effect of PD on the activity of protein kinase c of vascular smooth muscle cells / 中国药理学通报

Aim To study the influence of PD on the activity of PKC(protein kinase C) of VSMC during ischemia and hypoxia.Methods The hypoxia model was made by drawing off the oxygen of an enclosed acryl glass box and ischemia model was made by low sugar culture medium. Then the activity of PKC was measured by ?-scintillation counting instrument.Results It was found that the activity of PKC of cytoplasm in VSMC in ischemia and hypoxia situation increased (vs normal group P0.05 ).Conclusion PD can reverse the PKC activities induced by ischemia and hypoxia. It may be one of the mechanisms of PD to have antishock effect.

Effect of polydatin on protein kinase C activity of myocardial cells in ischemia and hypoxia / 中国药理学通报

Aim To explore the mechanism of polydatin (PD) treating shock through investigating influence of PD in protein kinase C (PKC) activity of myocardial cells when myocardial cells are treated by ischemia and hypoxia. Methods The hypoxia model was set up by drawing off the oxygen of an enclosed acryl glass box and ischemia model by low sugar culture medium.The activity of PKC was measured by ?-scintillation counter. Results The activity of PKC of myocardial cells cytoplasm in normal situation after the cells were treated by PD decreased(vs normal group P0.05). Conclusion PD antagonizes the damage by reversing the PKC activities, which is associated with the anti-shock effect of PD.