Hypertrophic cardiomyopathy (HCM) is a serious monogenic disease characterized by cardiac hypertrophy, fibrosis, sudden cardiac death, and heart failure. Previously, we identified that miR-139-5p was down-regulated in HCM patients. However, the regulatory effects of miR-139-5p remain unclear. Thus, we investigated the role of miR-139-5p in the regulation of cardiac hypertrophy. The expression of miR-139-5p in left ventricular tissues in HCM patients and mice subjected to transverse aortic constriction (TAC) was significantly down-regulated. Knockdown of miR-139-5p expression in neonatal rat cardiomyocytes (NRCMs) induced cardiomyocyte enlargement and increased atrial natriuretic polypeptide (ANP) expression. Overexpression of miR-139-5p antagonized isoproterenol (ISO)-induced cardiomyocyte enlargement and ANP/brain natriuretic peptide (BNP) up-regulation. More importantly, we found that c-Jun expression was inhibited by miR-139-5p in NRCMs. Knockdown of c-Jun expression significantly attenuated cardiac hypertrophy induced by miR-139-5p deprivation. Our data indicated that miR-139-5p was down-regulated in the hearts of HCM patients and that it inhibited cardiac hypertrophy by targetting c-Jun expression.

We describe a study leading to the discovery of compound 11, a pangenotypic hepatitis C virus (HCV) nonstructural protein 5A (NS5A) inhibitor with excellent potency, metabolic stability, and pharmacokinetics (PK). Compound 11 incorporating a 4-silapiperidine group was discovered by further optimizing our previous lead with a triethylsilyl moiety. It displayed great potency against genotype 1 subtype a (GT1a), -1b, -2a, -3a, -4a, -5a, and -6a with an EC 50 range of 0.33−17 pM and improved potency against the resistance-associated variant GT1a_M28T. Pharmacokinetics (PK) study indicated that compound 11 has reasonable PK exposures with a high liver distribution in preclinical animal species (mouse, rat, and dog). The results of a 14 day repeat-dose toxicity study identified the safety of compound 11.

BackgroundEfficient and precise circulating tumor cells’ (CTCs) capture and release with minimal effect on cell viability for CTCs’ analysis are general requirements of CTCs’ detection device in clinical application. However, these two essential factors are difficult to be achieved simultaneously.MethodsIn order to reach the aforementioned goal, we integrated multiple strategies and technologies of staggered herringbone structure, nanowires’ substrate, peptides, enzymatic release, specific cell staining, and gene sequencing into microfluidic device and the sandwich structure peptide-silicon nanowires’ substrate was termed as Pe-SiNWS.ResultsThe Pe-SiNWS demonstrated excellent capture efficiency (95.6%) and high release efficiency (92.6%). The good purity (28.5%) and cell viability (93.5%) of CTCs could be obtained through specific capture and biological release by using Pe-SiNWS. The good purity of CTCs facilitated precise and quick biological analysis, and five types of KRAS mutation were detected in 16 pancreatic cancer patients but not in healthy donors.ConclusionThe results proved that the effective capture, minor damage release, and precise analysis of CTCs could be realized simultaneously by our novel strategy. The successful clinical application indicated that our work was anticipated to open up new opportunities for the design of CTC microfluidic device.

The co-reactivation of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) in patients undergoing hematopoietic stem cell transplantation (HSCT) has been found. Research has shown that the reactivation of CMV or EBV is closely related to poor HSCT outcomes. In this study, we describe the clinical characteristics of HSCT patients with co-reactivation of CMV and EBV. We retrospectively reviewed the medical records of 327 patients who underwent HSCT at the Peking University People’s Hospital Institute of Hematology. Co-reactivation of CMV and EBV was observed in a total of 75 patients (22.9%) who also had a higher incidence of hemorrhagic cystitis (P=0.000). HSCT patients with CMV and co-reactivation of CMV and EBV had a significantly lower 1-year overall survival (OS; P=0.050). Further, COX regression analysis showed that viral infection was a risk factor for 1-year OS (HR, 12.625 for co-reactivation vs. no reactivation, p=0.021, and HR 13.580 for CMV reactivation vs. no reactivation, P=0.013). In conclusion, the patients with CMV reactivation had poorer outcome after HSCT regardless of EBV reactivation.

Background: The purpose of this study was to evaluate the necessity of a nasogastric decompression in radical gastrectomy for gastric cancer patients by a prospective randomized controlled trial. Methods: From 2007 to 2009, 161 gastric cancer patients who underwent radical gastrectomy were randomly selected and entered into three groups: tube group (TG), intra-operative tube group (ITG), and no-tube group (NTG). The variables studied among the groups were demographic characteristics, surgical characteristics, postoperative recovery and complications. Results: With respect to demographic and surgical characteristics, there were no significant differences among the 3 groups. The time of the first passage of flatus, tolerance of water intake, liquid diet and semiliquid diet were similar among TG, ITG and NTG. Postoperative hospital stay was increased in patients from TG compared to NTG (11.3 vs. 10.2 days, p = 0.031). The incidence of nausea was significantly higher in TG than in ITG or NTG (64 vs. 36.8 and 29.6%). The overall postoperative complication rate was not significantly different among these groups (20, 15.8 and 20.4% in TG, ITG and NTG, respectively, p = 0.612). Conclusions: Radical gastrectomy can be performed safely without nasogastric decompression for gastric cancer patients. The routine prophylactic nasogastric decompression is unnecessary.