Coronary artery disease (CAD) causes more than 700,000 deaths each year in China. Previous genome-wide association studies (GWAS) in populations of European ancestry identified several genetic loci for CAD, but no such study has yet been reported in the Chinese population. Here we report a three-stage GWAS in the Chinese Han population. We identified a new association between rs6903956 in a putative gene denoted as C6orf105 on chromosome 6p24.1 and CAD (P = 5.00 × 10⁻³, stage 2 validation; P = 3.00 × 10⁻³, P = 1.19 × 10⁻⁸ and P = 4.00 × 10⁻³ in three independent stage 3 replication populations; P = 4.87 × 10⁻¹², odds ratio = 1.51 in the combined population). The minor risk allele A of rs6903956 is associated with decreased C6orf105 mRNA expression. We report the first GWAS for CAD in the Chinese Han population and identify a SNP, rs6903956, in C6orf105 associated with susceptibility to CAD in this population.

Pancreatic cancer has one of the highest mortality rates of all cancer types. Fatty acid synthase (FASN) is a multifunctional protein homodimer that can convert acetyl coenzyme A (CoA) and malonyl-CoA into palmitate, thus regulating lipogenesis. FASN overexpression has also been shown to cause resistance to gemcitabine, a chemotherapy treatment for pancreatic cancer; however, the mechanism by which this happens is unclear. Analysis of gene expression of FASN and pyruvate kinase M2 (PKM2) in pancreatic cancer was performed using Oncomine microarray gene expression datasets, which demonstrated that FASN and PKM2 were upregulated in pancreatic cancer compared with normal tissue. Specifically, it was demonstrated that FASN enabled the upregulation of PKM2 expression at the mRNA and protein levels, increasing the glucose consumption rate in pancreatic cancer cells. The present study also revealed that decreased levels of FASN reduced resistance to gemcitabine treatment, which was induced by PKM2 overexpression in pancreatic ductal adenocarcinoma cells. Therefore, FASN may represent a novel therapeutic target in pancreatic cancer.

Background The efficacy and safety of pharmacological thromboprophylaxis in patients with intracerebral hemorrhage (ICH) remains unclear. Methods A literature search was performed to collect studies comparing the effect of thromboprophylaxis in patients with ICH. The primary endpoints were deep vein thrombosis (DVT), pulmonary embolism (PE), and hematoma expansion or rebleeding. A meta-analytic approach was employed to estimate the relative risk (RR) by fitting fixed-effects (FE) and random-effects (RE) models. Results A total of 28 studies representing 3,697 hospitalized patients with ICH were included. Thromboprophylaxis was initiated within 4 days following hospital presentation and continued for 10 to 14 days in most of studies. Compared with control, thromboprophylaxis was associated with a reduced risk of DVT (47/1,399 [3.4%] vs. 202/1,377 [14.7%]; FE: RR, 0.24; 95% CI, 0.18–0.32; RE: RR, 0.27; 95% CI, 0.19–0.39) as well as PE (9/953 [0.9%] vs. 37/864 [4.3%]; FE: RR, 0.33; 95% CI, 0.19–0.57; RE: RR, 0.37; 95% CI, 0.21–0.66). Thromboprophylaxis was not associated with increased risk of hematoma expansion or rebleeding (32/1,319 [2.4%] vs. 37/1,301 [2.8%]; FE: RR, 0.75; 95% CI, 0.48–1.18; RE: RR, 0.80; 95% CI, 0.49–1.30) or mortality (117/925 [12.6%] vs. 139/904 [15.4%]; FE: RR, 0.82; 95% CI, 0.65–1.03; RE: RR, 0.83; 95% CI, 0.66–1.04). Conclusion Thromboprophylaxis was effective in preventing DVT and PE without increasing the risk of hematoma expansion or bleeding among ICH patients. Future studies should explore the long-term effects of thromboprophylaxis in this population, particularly on the functional outcomes.

Purpose. To investigate the alternation in cerebral and ocular blood flow velocity (BFV) in patients of carotid stenosis (CS) with or without contralateral carotid occlusion (CO) early after carotid endarterectomy (CEA). Patients and Methods. Nineteen patients underwent CEA for ≥50% CS. Fourteen patients had the unilateral CS, and five patients had the ipsilateral CS and the contralateral CO. Transcranial Doppler (TCD) and Color Doppler Imaging (CDI) were performed before and early after CEA. Results. In patients with unilateral CS, significant improvements in BFV were observed in anterior cerebral artery (ACA) and middle cerebral artery (MCA) on the ipsilateral side after CEA. In patients of ipsilateral CS and contralateral CO, significant improvements in BFV were observed in the ACA and MCA not only on the ipsilateral side but also on the contralateral side postoperatively. The ipsilateral ophthalmic artery (OA) retrograde flows in two patients were recovered to anterograde direction following CEA. The BFV in short posterior ciliary artery (SPCA) of the ipsilateral side significantly increased postoperatively irrespective of the presence of contralateral CO. Conclusions. CEA improved cerebral anterior circulation hemodynamics especially in patients of unilateral CS and contralateral CO, normalized the OA reverse flow, and increased the blood perfusion of SPCA.

Background: Bone marrow-derived mesenchymal stem cells (BMSCs) have been proved to be capable of differentiating into endothelial cells (ECs), however, the differentiation efficiency is rather low. Sonic hedgehog (Shh), an important factor in vascular development and postnatal angiogenesis, exerted promotional effect on new vessel formation in the ischemic animal models. Therefore, the current study aims to investigate whether Shh could induce the endothelial differentiation of BMSCs both in vitro and in vivo, as well as the mechanism of differentiation induction. Methods: The current study over-expressed Shh in BMSCs by lentivirus transduction. Reversetranscription quantitative polymerase chain reaction (RT-qPCR) analysis was performed to determine the angiogenic factors in both control BMSCs and Shh over-expressed BMSCs. Immunocytochemistry was also conducted to examine the EC markers. Angiogenesis was determined by in vitro tube-forming assay on Matrigel and in vivo Matrigel plug in severe combined immunodeficient (SCID) mice. Last, mRNA sequencing analysis was used to elaborate the underlying mechanisms. Loss of function study was performed by vascular endothelial growth factor D (VEGF-D) siRNA. Results: Shh expression was increased by about 3,000-fold and 5,000-fold at 3 days-transfection and 7 daystransfection, respectively. Patched 1 (Ptch1), the receptor for Shh, had a twofold increase after transduction. The angiogenic factors such as hepatocyte growth factor (HGF), angiopoietin-1 (Ang-1), insulin-like growth factor 1 (IGF1) and vascular endothelial growth factor A (VEGF-A) had at least a 1.5-fold increase after transduction. Expression of EC-lineage markers, CD31 and VE-cadherin, on Shh-overexpressed BMSCs were increasingly detected by immunocytostaining. Angiogenesis of BMSCs could be efficiently induced by Shh overexpression in the in vitro tube-formation assay and in vivo Matrigel plug. Additionally, mRNA sequencing analysis revealed that Shh activation upregulated the expression of several pro-angiogenic factors, like Angptl4, Egfl6, VEGF-D. Loss of function study by VEGF-D siRNA confirmed that Shh enhanced the angiogenic ability of BMSCs via VEGF-D. Conclusions: This study demonstrated that Shh could promote endothelial differentiation of BMSCs via VEGF-D.

S tent implantation is a common percutaneous coronary intervention (PCI) procedure. Although the rate of adverse events after a procedure has been minimized with modern techniques, stent thrombosis (ST) remains a significant concern. The incidence of ST varies with the patient population, treatment assignment, and duration of follow-up; estimates report that the 1-year incidence of definite ST ranges from 0.1% to 3%, 1-9 with the majority of events occurring within 30Background-Stent thrombosis (ST) is an important end point in cardiovascular clinical trials. Adjudication is traditionally based on clinical event committee (CEC) review of case report forms and source documentation rather than angiograms. However, the degree to which this method of adjudication is concordant with the review of independent angiographic core laboratories (ACLs) has not been studied. This report represents the first assessment of variability between local investigators (LIs), a CEC, and an ACL.

Background Neuropathic pain severely impacts patients’ life quality. Dezocine can be used for the treatment of pain. The present study intended to explore the effects of dezocine in chronic constriction injury (CCI) induced neuropathic pain as well as the possible responsible molecules in rats. Methods There were 3 subgroups, ie, control group, CCI group and dezocine+CCI group. The values of paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) in rats were determined by a dynamic plantar esthesiometer. The ipsilateral lumbar spinal cords in rats were extracted for the detection of protein levels of phosphorylated-mammalian target of rapamycin (p-mTOR) and p-extracellular signal-regulated kinase 1/2 (p-ERK1/2) by western blot analysis; and the mRNA and protein expression levels of interleukin (IL)-6, tumor necrosis factor (TNF)-α, and cyclooxygenase-2 (COX-2) by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Results In comparison with control group, there were lower values of PWT and PWL in CCI group, which were partially reversed by dezocine. In addition, compared to control group, the expression levels of p-mTOR, p-ERK1/2, IL-6, TNF-α and COX-2 were upregulated by CCI, which were attenuated by dezocine. Conclusions In conclusion, the analgesic effect of dezocine on CCI induced neuropathic pain might be correlated with inhibiting of the p-mTOR and p-ERK1/2 signaling pathway.

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