Secondary prevention of antithrombotic therapy in patients with stable cardiovascular disease at high ischemic risk: A network meta-analysis of randomized controlled trials.

Aims: Antithrombotic secondary prevention in stable cardiovascular disease (SCVD) patients at high ischemic risk remains unclear. We compared the efficacy and safety of aspirin monotherapy, clopidogrel monotherapy, ticagrelor monotherapy, rivaroxaban monotherapy, clopidogrel plus aspirin, ticagrelor plus aspirin, and rivaroxaban plus aspirin in the high-risk ischemic cohorts. Methods and results: Eleven randomized controlled trials were included (n = 111737). The primary outcomes were major cardiovascular and cerebrovascular events (MACEs) and major bleeding. A random effects model was used for frequentist network meta-analysis. Odds ratio (OR) and 95% credible intervals (CI) were reported as a summary statistic. Compared with aspirin monotherapy, rivaroxaban plus aspirin [OR 0.79 (95% CI, 0.69, 0.89)], ticagrelor plus aspirin [0.88 (0.80, 0.98)], clopidogrel plus aspirin [0.56 (0.41, 0.77)] were associated with a reduced risk of MACEs, but rivaroxaban monotherapy [0.92 (0.79, 1.07)], ticagrelor monotherapy [0.68 (0.45, 1.05)], and clopidogrel monotherapy [0.67 (0.43, 1.05)] showed no statistically significant difference. However, rivaroxaban monotherapy and all dual antithrombotic strategies increased the risk of major bleeding to varying degrees, with ticagrelor plus aspirin associated with the highest risk of major bleeding. The net clinical benefit favored clopidogrel or ticagrelor monotherapy, which have a mild anti-ischemic effect without an increase in bleeding risk. Conclusion: The present network meta-analysis suggests that clopidogrel or ticagrelor monotherapy may be recommended first in this cohort of SCVD at high ischemic risk. But clopidogrel plus aspirin or rivaroxaban plus aspirin can still be considered for use in patients with recurrent MACEs.

IL-10, IL-18 Gene Polymorphisms Might Influence Predisposition to Coronary Artery Disease in East Asians: A Meta-Analysis.

The results of already published studies regarding relationship between interleukin-10 (IL-10), interleukin-18 (IL-18) polymorphisms and predisposition to coronary artery disease (CAD) were still controversial. So the authors designed this meta-analysis to more precisely estimate relationship between IL-10, IL-18 polymorphisms and CAD by pooling the results of already published studies. The authors searched Pubmed, Embase, Web of Science and CNKI for already published studies. The authors used Review Manager to pool the results of already published studies. Thirty-four studies were pooled analyzed in this meta-analysis. The pooled meta-analyses results showed that IL-18 rs187238, IL-18 rs1946518 and IL-18 rs1946519 polymorphisms were all significantly associated with predisposition to CAD in the general population. We also detected similar significant results for IL-10 rs1800871, IL-10 rs1800896, IL-18 rs187238 and IL-18 rs1946518 polymorphisms in East Asians in further subgroup analyses. In conclusion, this meta-analysis suggested that IL-10 rs1800871, IL-10 rs1800896, IL-18 rs187238 and IL-18 rs1946518 polymorphisms might influence predisposition to CAD in East Asians.

Effects of the Antianginal Drugs Ranolazine, Nicorandil, and Ivabradine on Coronary Microvascular Function in Patients With Nonobstructive Coronary Artery Disease: A Meta-analysis of Randomized Controlled Trials.

PURPOSE: The goal of this study was to investigate the effects of the antianginal drugs ranolazine, nicorandil, and ivabradine on coronary microvascular function. METHODS: Electronic scientific databases were searched for randomized trials investigating the effects of antianginal drugs on coronary microvascular function. Primary outcomes were changes in the coronary flow reserve (CFR), index of microvascular resistance (IMR), and myocardial perfusion reserve index (MPRI). The secondary outcome was the Seattle Angina Questionnaire scores. The standardized mean difference or weighted mean difference (WMD) (95% CI) served as a summary statistic. FINDINGS: The antianginal drugs ranolazine, nicorandil, and ivabradine did not increase the CFR compared with the control drugs (standardized mean difference, 0.39; 95% CI, -0.08 to 0.85; P = 0.10). Ranolazine did not increase the global MPRI compared with the control drugs (weighted mean difference [WMD], 0.11; 95% CI, -0.06 to 0.29; P = 0.21). However, in the subgroups with a baseline CFR <2.5 or a global MPRI <2, ranolazine increased the global MPRI (WMD, 0.19; 95% CI, 0.10 to 0.27; P < 0.0001). In addition, the subendocardial midventricular MPRI (mid-subendocardial MPRI) was improved after ranolazine treatment (WMD, 0.12; 95% CI, 0.03 to 0.20; P = 0.007). Moreover, nicorandil significantly reduced the IMR compared with the control drugs (WMD, -7.63; 95% CI, -11.82 to -3.44; P = 0.0004). In addition, ranolazine and ivabradine improved 3 of the 5 Seattle Angina Questionnaire scores. IMPLICATIONS: Ranolazine improved the global MPRI in patients with definite coronary microvascular dysfunction and the mid-subendocardial MPRI with suspicious coronary microvascular dysfunction, and nicorandil reduced the IMR. In addition, ranolazine and ivabradine reduced angina. Moreover, it is possible that the IMR and mid-subendocardial MPRI are more sensitive than the CFR and global MPRI for evaluating coronary microvascular function.

Effects of mitochondrial ATP-sensitive potassium channel activation (nicorandil) in patients with angina pectoris undergoing elective percutaneous coronary interventions: A meta-analysis of randomized controlled trials.

AIMS: Nicorandil, which is a mitochondrial ATP-sensitive potassium channel opener, is believed to improve perioperative myocardial injury (PMI) in patients undergoing percutaneous coronary intervention (PCI), but recent studies have shown that nicorandil treatment did not improve functional and clinical outcomes in patients with angina pectoris who underwent elective PCI. We performed a meta-analysis to investigate the protective effect of nicorandil on perioperative injury in patients with angina pectoris who underwent elective PCI. METHODS: The Medline, EMBASE, and Cochrane databases were searched for randomized clinical trials examining the effects of nicorandil. Two investigators independently selected suitable trials, extracted data, and assessed trial quality. RESULTS: Seven studies of patients undergoing elective PCI, comprising a total of 979 patients, were included in this review. The results showed that nicorandil did not reduce the levels of markers of myocardial injury (standardized mean difference [SMD] 0.31 [95%CI -0.6, 1.22] for creatine kinase-MB [CK-MB] and 1.29 [95%CI -2.18, 4.76] for troponin I [TNI]), perioperative complications (relative risk [RR] 0.91 [95%CI 0.46-1.81]), target vessel revascularization (RR 0.79 [95%CI 0.50-1.25]) or major adverse cardiac events (MACE) (RR 0.83 [95%CI 0.49-1.43]). Nicorandil did reduce the corrected TIMI frame count (SMD-0.30 [95%CI -0.52, -0.09]). CONCLUSION: Although nicorandil did not reduce the overall incidence of perioperative complications and the incidence of major adverse cardiac events (MACE) in patients with angina pectoris who underwent elective PCI, it could still improve no reflow and slow coronary flow.

A novel quartz crystal microbalance sensor array based on molecular imprinted polymers for simultaneous detection of clenbuterol and its metabolites.

For the rapid and robust detection of both parent clenbuterol (CLB) and its metabolites in swine urine samples, a novel quartz crystal microbalance (QCM) sensor array for CLB detection based on molecularly imprinted polymers (MIPs) was developed in this investigation. At first, clenbuterol and the structural analogs of its metabolites, 4-Aminohippuric acid (AHA) and 4-hydroxymandelic acid (HMA), were chosen as molecular templates. Through computational molecular modeling, the optimum ratio between the functional monomer and molecular template was selected. The surface imprinting method was applied to modify QCM electrode surface to graft a thin MIP film. The grafting polymer was characterized by Fourier-transformed infrared spectrometry (FTIR) and atomic force microscopy (AFM), respectively. After then, an array system composed of three sensors was employed to test the responses with different solutions and the principal component analysis (PCA) was adopted to analyze the corresponding data. As a result, for the designed sensor to clenbuterol, a linear equation y=100.07x-722.96 (R2=0.9928) was found between the sensor frequency shift ΔF and negative logarithm of clenbuterol concentration (-lgC). The limitation of detection (LOD) was 3.0ng/mL, which is lower than the Codex Alimentarius Commission regulations residue limit 10µg/L. The corresponding data of the three template solutions were analyzed by PCA, obtaining 100% recognition. The result demonstrated the feasibility that the developed method could be applied to detect whether the livestock was feed with CLB nutrient redistribution agent by checking the urine samples.

The anatomic study of clival screw fixation for the craniovertebral region.

PURPOSE: To study the anatomic parameters related to clival screw and establish reference data concerning the craniovertebral fixation technique. METHODS: Morphometric measurement of the clivus and the surrounding anatomic structures were obtained on 41 dry bone specimens. Then, 2-D CT reconstruction of the craniovertebral region of 30 patients (19 men and 11 women, ranging in age from 20-64 years with an average age of 38.8 years) were performed to measure the safety range for a 3.5-mm screw placement. Nine entry points were evaluated. Finally, one male fresh cadaver specimen (age 46 years) was dissected to observe the craniovertebral region. RESULTS: The clivus faces the basilar artery, the V ~ XII cranial nerves, the pons, and ventral medulla oblongata at its intracranial surface. The longitudinal diameter of extracranial clivus was 25.87 ± 2.64 mm. The narrowest diameter of the clivus was 12.84 ± 1.08 mm, the distance between the left and right hypoglossal canal was 32.70 ± 2.09 mm at its widest part. The distance between the left and right structures, the maximum value was 49.31 ± 4.16 mm at carotid canal, the minimum value was 16.54 ± 2.04 mm at the occipital condyle. The measurement of clival screws placement simulation via 2-D CT reconstruction images shows the maximum upper insertion angle of three components the optimal entry points, the candidate points, the limit entry points was 130.19°, 125.23° and 85.72°, and the total mean screw length was 7.57, 10.13 and 15.6 mm at the vertical entry angle, respectively. CONCLUSIONS: Clival screw placement is a viable option for craniovertebral fixation. There is a safe scope for the screw length and angle of the screw placement. And, these parameters obtained in the present study will be helpful for anyone contemplating the use of clival screw fixation.

[Correlation between ethambutol-resistance and embB gene mutation in Mycobacterium tuberculosis].

OBJECTIVE: To analyze the characteristics of embB gene mutation in ethambutol-resistant Mycobacterium tuberculosis (M. TB) strains isolated from patients in Xi'an for establishing a rapid method to detect the mutation of embB gene in M. TB. METHODS: The embB gene of 104 Mycobacterium tuberculosis isolates was detected by PCR-Single Strand Conformation Polymorphism (PCR-SSCP) and PCR-Restriction Fragment Length Polymorphism (PCR-RFLP). RESULTS: Taking strain H37Rv as a control, the SSCP and RFLP profiles of embB of 35 drug-sensitive strains in 104 Mycobacterium tuberculosis isolates were normal. The display of SSCP profiles in 39 of 69 (56.52%) ethambutol-resistant isolates and the display of RFLP profiles in 19 of 69 (27.54%) ethambutol-resistant isolates were abnormal. CONCLUSION: The EMB-resistance of M. TB strains isolated from patients in Xi'an is related to the mutation of embB gene, PCR-SSCP and PCR-RFLP are sensitive methods for detecting ethambutol-resistance of M. tuberculosis.

Comparative research of the thin transverse sectional anatomy and the multislice spiral CT on Pterygopalatine Fossa.

AIM: To explore a method to obtain sub-millimeter data of the thin transverse section of the pterygopalatine fossa (PPF), and to study the thin transverse sectional anatomy of the adult pterygopalatine fossa and its communicating structure for providing anatomic gist for the imaging diagnosis and minimal invasive operation when PPF diseased. MATERIAL AND METHODS: Two heads of adult cadaver without macroscopic trauma (four sides of PPF) were selected to observe. Images of 0.6 mm-thick multi-planar construction (MPR) were obtained with multislice spiral CT (MSCT) based on the superior orbitomeatal line. Then, the specimens were sliced into 0.1 mm serial section on the transverse plane with the computerized milling machine, the figures were taken with digital camera and the sectional data were stored in the computer. Lastly, the thin transversal section of PPF was investigated and compared with multislice spiral CT images acquired by MPR technique to explore and discuss the anatomy of the thin transverse section of the internal structure of PPF. RESULTS: PPF was divided into four portions: infrapterygopalatine portion, pterygopalatine ganglionic one, suprapterygopalatine one and roof of PPF according to the structural characteristics of the transverse section of PPF. The infrapterygopalatine portion communicated laterally with the infratemporal fossa through the pterygomaxillary fissure and communicated downwards with the oral cavity via palatine greater and lesser canals. The pterygopalatine ganglion was shown clearly in the pterygopalatine ganglionic portion, and its dimensions were 3.91x1.92 mm at the best layer. In the suprapterygopalatine portion, the sphenopalatine foramen and artery were obviously shown on the medial wall, while the palatovaginal canal and artery, the pterygoid canal and artery, and the foramen rotundum and maxillary nerve were shown from the inferiomedial to laterosuperior on the posterior wall. The vomerovaginal canal and artery were located at the slightly superior portion of the medial side of the palatovaginal canal. CONCLUSION: Figures of thin transverse section and multislice spiral CT have highly consistency for the display of PPF. Both of them can correctly identify the micro-structure, the complex relationship of the connectivity and the spatial localization in the narrow space of PPF. It can provide reference gist for the imaging diagnosis and minimal invasive operation.

[Cloning and expression of human keratin 8 gene cDNA in E.coli].

AIM: To clone and express human keratin 8 gene cDNA in E.coli. METHODS: Human cytokeratin 8 gene cDNA was amplified by RT-PCR from genomic RNA of human cell line 7721. The amplified cytokeratin 8 gene cDNA was cloned into pMD18-T vector. Then, the CK8 cDNA was amplified by PCR from recombinant plasmid pMD18-CK8, and was subcloned into pET-28a(+) expression vector. The recombinant plasmid pET-28a-CK8 DNA was transformed into E.coli DH5alpha strain. RESULTS: Human cytokeratin 8 gene cDNA was cloned, and the recombinant plasmid pMD18-CK8 was transformed into E.coli. The CK8 cDNA was subcloned into E.coli DH5alpha strain, and successfully expressed in E.coli. CONCLUSION: Human cytokeratin 8 gene cDNA is cloned, and successfully expressed in E.coli, which lay the foundation of further study on the CK8 biological properties and functions.

Detection of human papillomavirus type 16 DNA in formalin-fixed, paraffin-embedded tissue specimens of gastric carcinoma.

OBJECTIVES: Human papillomavirus type 16 (HPV16) is regarded as one of the important tumor-related viruses, which are known to have a role in cervical carcinoma; however, there are few reports on HPV16 in gastric carcinoma (GC). Our study aimed to investigate the relationship between HPV16 and the occurrence of GC. METHODS: Liquid PCR (LPCR) and in-situ PCR (ISPCR) methods were carried out to detect the HPV16 oncogene E6 cell-type-specific enhancer in the long control region of HPV16 in 40 GCs and corresponding gastric adjacent normal mucosa (GANM). The patients were from Shaanxi Province in China; Helicobacter pylori (Hp) was detected by immunohistochemistry and by hematoxylin and eosin staining in their gastric tissues. RESULTS: The HPV16 E6 gene was detected in 37.5% (15/40) of the GCs and 5% (2/40) of the GANMs with LPCR, as was the cell-type-specific enhancer; however, the positive rate of E6 was 27.5% (11/40) in GCs and 0% (0/40) in GANMs, respectively, with ISPCR. HPV16 DNA was mainly located in the nucleus of gastric glandular epithelium cells. The infection rate of HPV16 DNA in GCs was higher than that in GANMs (P=0.0004), and the HPV16 had no statistical correlations with sex, age, invasion, grading or lymph node metastasis (P>0.05). The infection rate of HPV16 in cardiac GCs was significantly higher than that in noncardiac ones (P=0.0136), and HPV16 had no correlation with Hp in GCs (P=0.0829). Receiver operator characteristic curve analysis indicated that there was no statistical difference between the LPCR and ISPCR methods in our study through optimizing parameters in ISPCR procedures (P=0.768). CONCLUSIONS: These findings suggested that HPV16 can infect gastric glandular epithelium cells and that viral infection might play a role in the occurrence of GCs independent of or without the cooperation of an Hp infection.