Meta-analysis of postoperative antithrombotic therapy after left atrial appendage occlusion.

OBJECTIVE: This meta-analysis explored the safety and effectiveness of different anticoagulant regimens after left atrial appendage occlusion (LAAO). METHODS: Databases, such as PubMed, MEDLINE, EMBASE, Web of Science, and Cochrane Library, were searched to identify eligible studies according to the inclusion criteria. The incidences of events, including device-related thrombus (DRT) formation, stroke, systemic thromboembolism, bleeding, cardiovascular mortality, and all-cause mortality, were analyzed using R version 3.2.3. RESULTS: The screening retrieved 32 studies, including 36 study groups and 4,474 patients. The incidence of outcomes after LAAO was calculated via meta-analysis. In the subgroup analysis, the rates of DRT formation, cardiovascular mortality, and all-cause mortality were significantly different among different antithrombotic methods. Single antiplatelet therapy was associated with the highest rate of adverse events, followed by dual antiplatelet therapy (DAPT). Vitamin K antagonists (VKAs) and new oral anticoagulants (NOACs) carried lower rates of adverse events. CONCLUSIONS: Anticoagulant therapy had better safety and efficacy than antiplatelet therapy. Thus, for patients with nonabsolute anticoagulant contraindications, anticoagulant therapy rather than DAPT should be actively selected. NOACs displayed potential for further development, and these treatments might represent alternatives to VKAs in the future.

Prognostic value of endogenous and exogenous metabolites in liver transplantation.

Liver transplantation has been widely accepted as an effective intervention for end-stage liver diseases and early hepatocellular carcinomas. However, a variety of postoperative complications and adverse reactions have baffled medical staff and patients. Currently, transplantation monitoring relies primarily on nonspecific biochemical tests, whereas diagnosis of multiple complications depends on invasive pathological examination. Therefore, a noninvasive monitoring method with high selectivity and specificity is desperately needed. This review summarized the potential of endogenous small-molecule metabolites as biomarkers for assessing graft function, ischemia-reperfusion injury and liver rejection. Exogenous metabolites, mainly those immunosuppressive agents with high intra- and inter-individual variability, were also discussed for transplantation monitoring.

Individualized medication of digoxin based on the serum drug concentration and blood biochemical indexes.

Aim: The dose of digoxin is often difficult to be determined precisely. The aim of this study was to retrospectively investigate the effect of blood biochemical indexes on the serum concentration of digoxin. Materials & methods: We collected the data of hospitalized patients treated orally with digoxin in Nanjing Drum Tower Hospital (Nanjing, China) from 2016 to 2018. Descriptive statistics was used to analyze the patients' comprehensive condition. Results: A total of 425 patients were included in the study. Through analysis, nine factors were included in the regression model of the serum concentration of digoxin, and this regression model showed good predictive performance (r2 = 0.83138; p < 0.001). Conclusion: The regression model for the prediction of serum concentration of digoxin has clinical significance, and can provide research basis for individualized medication of digoxin.

Leptin -2548g/a gene polymorphism in association with antipsychotic-induced weight gain: a meta-analysis study.

BACKGROUND: The leptin -2548G/A (rs7799039) gene polymorphism has been implicated in susceptibility to antipsychotic-induced weight gain (AIWG), but study results are still controversial. The present meta-analysis was performed to investigate the relationship between the leptin -2548G/A gene polymorphism and AIWG. METHODS: Electronic databases were searched for eligible articles in English and Chinese and seven separate studies on the association of the leptin -2548G/A gene polymorphism with AIWG were analyzed. RESULTS: The meta-analysis involved 451 AIWG patients and 568 controls. The pooled odds ratio (OR) and their corresponding 95% confidence interval (CI) were calculated by a fixed or random effect. Overall, our meta-analysis suggests that the leptin -2548G/A gene polymorphism was not significantly associated with AIWG risk under various genetic models. But, in the subgroup analysis by ethnicity, significant association was found between leptin -2548A allele and the AIWG risk in Asian populations under additive, dominant, recessive, and homozygote genetic model. On the contrary, in European populations, the -2548A allele seemed to decrease the risk of AIWG when compared with the -2548G allele under various genetic models, even though they were not statistically significant. CONCLUSION: Our meta-analysis suggests that the correlation between leptin -2548G/A gene polymorphism and AIWG risk has significant racial differences.

CYP3A4/5 polymorphisms affect the blood level of cyclosporine and tacrolimus in Chinese renal transplant recipients.

OBJECTIVE: Both cyclosporine and tacrolimus display a narrow therapeutic index as well as high interindividual pharmacokinetic variability. We approached the effect of the CYP3A4*18B and CYP3A5*3 polymorphisms and haplotypes on the whole blood cyclosporine or tacrolimus concentration in Chinese renal transplant patients during the first month after transplantation. MATERIALS AND METHODS: A total of 83 recipients receiving tacrolimus or cyclosporine was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The whole blood concentration was measured by enzyme-multiplied immunoassay technique. RESULTS: Both CYP3A4*18B and CYP3A5*3 polymorphisms affected the tacrolimus dose-adjusted trough concentration (C0/D). The tacrolimus C0/D was higher in carriers of haplotype GG compared with the non-carriers. The cyclosporine dose-adjusted 2-hour post-dose concentrations (C2/D), dose-adjusted C0 + C2 ((C0 + C2)/D) and C2/C0 during Days 15 - 21 displayed significant difference among the three genotypes. Statistical difference was observed between CYP3A4*1/*1 and CYP3A4*18B/*18B groups and between CYP3A4*1/*18B and CYP3A4*18B/*18B groups, but no difference was detected between CYP3A4*1/*1 and CYP3A4*1/*18B groups. No difference was found in C0/D among the three genotypes of CYP3A4*18B polymorphism, and neither CYP3A5*3 polymorphisms nor CYP3A haplotype-derived genotypes affected the cyclosporine dose-adjusted concentration. CONCLUSIONS: Genetic polymorphisms of CYP3A5*3 and CYP3A4*18B may be partly responsible in large interindividual variability of cyclosporine and tacrolimus blood levels in Chinese renal transplant patients during the first month after transplantation. A patient carried combined genotype of CYP3A4*1/*1-CYP3A5* 3/*3 might require lower tacrolimus doses to achieve target concentration levels. Genotyping of CYP3A4*18B and CYP3A5*3 before transplantation is of benefit in determining a suitable initial dose for each patient.

Functional outcomes and health-related quality of life in fracture victims 27 months after the Sichuan earthquake.

OBJECTIVE: To evaluate functional outcomes, health-related quality of life and life satisfaction in fracture victims 27 months after the 2008 Sichuan earthquake. METHODS: A total of 390 earthquake survivors from 3 earthquake areas who sustained fractures were divided into early intervention, late intervention and control groups. Functional outcomes assessed included activities of daily living using the Modified Barthel Index and pain level with a visual analogue scale. Health-related quality of life was evaluated with the Medical Outcomes Study Short-Form 36 and life satisfaction using the Life Satisfaction Questionnaire. RESULTS: Activities of daily living and life satisfaction in the intervention groups were significantly improved compared with the control group. Health-related quality of life was higher in early intervention subjects compared with controls. Group differences in pain level were not significant. In addition, the early and late intervention groups did not differ significantly in any of the measured outcomes. Good performance of activities of daily living and widowed marital status predicted high health-related quality of life, while pain level was associated with worsened outcomes. Rehabilitation therapy, remunerative employment and female gender were predictors of improved life satisfaction. CONCLUSION: Clinical effectiveness of physical rehabilitation intervention was demonstrated in fracture earthquake victims.

[A modified rat model for infection-induced stone formation].

OBJECTIVE: To employ a newly modified rat model for infection-induced bladder stone formation. METHODS: 24 adult male Sprague Dawley rats were divided into 3 groups, model group (n=12), sham operation group (n=8) and control group (n=4). The surgical procedures were performed aseptically under anesthesia (25% Ultane 1.0 g/kg). The bladder in model group was exposed through a short lower midline abdominal incision, the puncture needle (G18) with guideline was inserted aseptically into bladder, a metal wire, which have been contaminated by the Proteus mirabilis, was put into the puncture canal, then implanted into the bladder lumen through the guideline. In the sham operated group the puncture needle (G18) with guideline was inserted into bladder without metal wire implanted into the bladder. There was no any operation in control group. The rats were sacrificed by excessive anesthesia at 21 days post challenge. The bladder were removed aseptically and inspected for evidence of urolithiasis. RESULTS: On Day 2 after surgery, two rats died in model group, no rats died in other groups. Twenty-one days after surgery, all of rats in model group developed various-sized bladder stones. There was no stone formation in sham operation group and control group. All stones were verified by infrared spectroscopy and optical crystallography. These stone were struvite stone. CONCLUSION: This model has a less trauma, faster recovery and excellent stone formation so that it may be used for the study of infection stone.

Genetic variant in glutathione peroxidase 1 gene is associated with an increased risk of coronary artery disease in a Chinese population.

BACKGROUND: Glutathione peroxidase 1 (GPX1), the key antioxidant enzyme in vascular endothelial cells, has been shown to exert a protective effect against the presence of coronary artery disease (CAD). The 198Pro/leu variant, located at codon 198 of GPX1 gene, has recently been linked to cardiovascular disease, but data were inconsistent. We investigated the association between the occurrence of CAD and the 198Pro/leu variant in a Chinese population. METHODS: A total of 265 unrelated CAD patients and 265 age- and sex-matched control subjects were recruited in this study. The GPX1 198Pro/leu genotype was determined using polymerase chain reaction-restriction fragment length polymorphism. RESULTS: Compared to the 198Pro/Pro carriers, subjects with the variant genotypes (198Pro/leu and 198Leu/leu) had a significantly higher risk of CAD (adjusted OR=2.02, 95%CI=1.27-3.22). In stratified analyses, the variant genotypes were significantly associated with increased CAD risk in subjects <64 y (adjusted OR=2.41, 95%CI=1.16-4.98), males (adjusted OR=1.86, 95%CI=1.09-3.18) and non-smokers (adjusted OR=2.40, 95%CI=1.15-5.01). However, no significant association was observed between this variant and the severity of CAD. CONCLUSION: These data provide evidence that GPX1 198Pro/leu variant genotypes are significantly associated with CAD risk in this Chinese population.

Protective effect of an endothelial lipase gene variant on coronary artery disease in a Chinese population.

The aim of the present study was to assess the influence of the endothelial lipase (EL) gene 584C/T variant, which results in a change at codon 111 of the EL gene from threonine to isoleucine, on the risk of coronary artery disease (CAD) in a Chinese population. The study population consisted of 265 CAD patients and 265 age- and sex-matched control subjects. The T allele frequency was significantly lower among CAD patients than among control subjects (18.3% vs. 29.8%; P < 0.001). In both the CAD and control groups, the T allele carriers had higher high density lipoprotein cholesterol (HDL-C) levels than homozygote C allele carriers. In a multiple logistic regression model adjusted for age, sex, body mass index, smoking, hypertension, diabetes, hyperlipidemia, and low density lipoprotein cholesterol, a significantly decreased risk of developing CAD was found in subjects carrying a variant CT or TT genotype (odds ratio = 0.496, 95% confidence interval = 0.341-0.723; P < 0.001), and the significance persisted after further adjustment for HDL-C. In conclusion, our observation that the EL 584T allele was associated with protection from CAD in this Chinese population replicates the findings in a Japanese study, which found a similar association of this allele with acute myocardial infarction, independent of HDL-C levels.

A polymorphism in the resistin gene promoter and the risk of coronary artery disease in a Chinese population.

OBJECTIVE: Resistin, a novel adipocyte-derived peptide, has been linked to the pathogenesis of atherosclerosis. Recently, -420C>G, a variant located in the promoter region of the resistin gene (RETN) was identified. The aim of this study was to investigate the association between this RETN-420C>G polymorphism and the risk of coronary artery disease (CAD). DESIGN: A hospital-based case-control study. PATIENTS: A total of 225 CAD patients and 225 age- and sex-matched control subjects. MEASUREMENTS: Genotyping was performed by polymerase chain reaction (PCR) and restriction enzyme analysis to detect the presence of the RETN-420C>G polymorphism. RESULTS: The frequencies of RETN-420C>G genotypes in the CAD group were significantly different from those in the control group (P = 0.024). Subjects with the variant genotypes (CG and GG) had a 62% increased risk of CAD compared to CC carriers [adjusted odds ratio (OR) = 1.62, 95% confidence interval (CI) = 1.09-2.41, P = 0.016]. However, there were no significant differences between the genotypes with respect to weight, body mass index (BMI) and lipid profiles in CAD patients, and no significant association was found between the RETN-420C>G polymorphism and the severity of CAD. CONCLUSIONS: Our data suggest that the RETN-420C>G polymorphism might be associated with an increased risk of CAD in a Chinese population.

Preproghrelin Leu72Met polymorphism in Chinese subjects with coronary artery disease and controls.

BACKGROUND: Ghrelin, a novel endogenous ligand for the growth hormone secretagogue receptor, is considered to exert a protective effect against atherosclerosis. The Leu72Met (+408C>A) polymorphic variant of the preproghrelin, the gene for the ghrelin precursor, has been linked to obesity, diabetes and metabolic syndrome. However, it is unclear whether this polymorphism is associated with coronary artery disease (CAD). METHODS: We conducted a case-control study with 317 CAD patients and 323 controls to investigate the potential association of the Leu72Met polymorphism with the occurrence of CAD and CAD-related phenotypes in Chinese population. RESULTS: No significant difference in the Leu72Met genotype frequency was observed between CAD patients and controls (P=NS). The Leu72Met polymorphism was not associated with hypertension, diabetes, dyslipidemia, the number of diseased vessels, plasma total cholesterol, triglyceride, high density lipoprotein cholesterol, low density lipoprotein cholesterol or fasting glucose levels in CAD patients. However, among CAD patients, those with variant genotypes (Leu72Met and Met72Met) had lower BMI (24.4+/-0.3 kg/m(2)) than Leu72Leu carriers (25.4+/-0.2 kg/m(2), adjusted P=0.033). CONCLUSION: Our data indicate that the preproghrelin Leu72Met polymorphism is not associated with CAD in Chinese population. However, the Leu72Met variant is associated with BMI among CAD patients.

A polymorphism in the resistin gene promoter is related to increased C-reactive protein levels in patients with coronary artery disease.

BACKGROUND: Resistin, a novel adipocyte-derived peptide, has been linked to inflammatory process and coronary artery disease (CAD). The -420C>G polymorphism located in the resistin gene (RETN) promoter has recently been suggested to play a potential role in proinflammatory conditions (e.g., atherogenesis). However, whether this polymorphism has any effect on the inflammatory process in patients with stable CAD is unclear. METHODS: The RETN -420C>G polymorphism was determined by using PCR-restriction fragment length polymorphism. Plasma lipid profiles, glucose and high-sensitivity C-reactive protein (hs-CRP) were measured in fasting state. RESULTS: Patients with variant genotypes (CG+GG) had significantly higher levels of hs-CRP than CC carriers (adjusted p<0.001). In addition, the variant genotypes were observed to be independently associated with higher hs-CRP levels (>3 mg/L, p=0.004). However, no association was found between this polymorphism and plasma lipids or glucose levels. CONCLUSION: Our data suggest that the RETN -420C-to-G variant is associated with increased CRP levels in patients with stable CAD, suggesting that the RETN -420C>G polymorphism may be potentially involved in the inflammatory component of atherogenesis through an enhanced production of CRP.

Endothelin-converting enzyme-1b C-338A polymorphism is associated with the increased risk of coronary artery disease in Chinese population.

BACKGROUND: Endothelin-converting enzyme-1 (ECE-1), the key enzyme responsible for endothelin-1 generation, has been linked to coronary artery disease (CAD). Recently, a genetic polymorphism (ECE-1b C-338A) located in ECE-1 gene promoter was identified. However, it is unclear whether this polymorphism is associated with the risk of CAD. METHODS: We conducted a study with CAD patients and controls matched by age and sex to examine the prevalence of ECE-1b C-338A polymorphism in CAD. RESULTS: The frequencies of ECE-1b-338CC, CA, and AA genotypes in cases (40.1%, 42.2%, and 17.7%) were significantly different from those of controls (50.6%, 40.5%, and 8.9%, chi2=9.989, P=0.007). Subjects with the variant genotypes (CA+ AA) had a 58% increased risk of CAD relative to CC carriers (adjusted OR=1.58, 95% CI=1.07-2.32). Furthermore, the adjusted OR of AA genotype for CAD was 2.33 (95% CI=1.25-4.35). In stratified analyses, the A allele was significantly associated with increased risk of CAD in female (adjusted OR=2.86, 95% CI=1.40-5.84) and subjects with age >or= 64 y (adjusted OR=2.96, 95% CI=1.73-5.08). Moreover, the frequency of patients with variant genotypes increased gradually from single- to triple-vessel disease although without statistical significance (P=0.069 for trend). CONCLUSION: Our results suggested that ECE-1b-338C to A variant might be associated with increased risk of CAD in Chinese population.

Inhibitive effect of genistein on hypoxia-induced basic fibroblast growth factor expression in human retinal pigment epithelium cells.

AIM: The time course changes of basic fibroblast growth factor (bFGF) expression induced by hypoxia and the effects of genistein on hypoxia-induced bFGF expression in the human retinal pigment epithelium (RPE) cells were studied. METHODS: The bFGF mRNA expression was examined by reverse transcription polymerase chain reaction. The bFGF protein expression was detected by Western blot. RESULTS: Hypoxia significantly increased bFGF mRNA expression. The maximal level detected at 24 h was approximately two times that at the start of treatment. With pretreatment of genistein (10, 20, 50, 100, and 200 microM) for 30 min, the elevated expression of bFGF mRNA was suppressed in a concentration-dependent manner. bFGF mRNA expression was reduced to 30.4% by 200 microM of genistein when compared with that untreated with genistein. Hypoxia treatment also remarkably increased the expression of bFGF protein. At 24 h after hypoxia, when the highest expression of bFGF protein was observed, it was approximately two times as much as that at the start of treatment. Genistein (10, 20, 50, 100, and 200 microM) could also suppress bFGF protein expression in a concentration-dependent manner. The highest suppression was observed when exposed to 200 microM of genistein, which was 43% of control. CONCLUSIONS: These results suggested that suppression of bFGF expression in RPE cells might partly account for the inhibitive effect of genistein on retinal neovascularization in vivo.