Molecular Epidemiological Analysis of Echovirus 19 Isolated From an Outbreak Associated With Hand, Foot, and Mouth Disease (HFMD) in Shandong Province of China

To elucidate the genetic characterization and molecular epidemiological features of Echovirus 19 （El9） isolates collected from an outbreak associated with hand, foot and mouth disease （HFMD） in Tai＇an city of Shandong Province of China from July to September, 2003. Methods Thirty seven Echovirus 19 isolates were isolated from stool specimens and throat swabs collected during the outbreak, then major capsid （VP1） genomic sequence was determined, and phylogenetic tree was done based on the VP1 sequences among these 37 and other El9 viruses deposited in the Genbank. Also a representative strain named CHN-SD03-TN12 was selected for sequencing of 5′-untranslated regions （5′-UTR）. Results The identity rate was about 98.9%-100% among all these 37 El9 viruses. The genetic relationships between these 37 El9 isolates and other strains reported were also depicted. The identity rate was about 78.4%-78.9% compared with El9 reference strain Burke. The substitutions in the sequence of 5′-UTR resulted in changes in the conjectural properties of 5′-UTR of El9 viruses. Condusion The genetic features of El9 viruses isolated during the outbreak in Shandong Province in 2003 may be associated with a genetic and antigenic drift that changes the virulence of the Shandong isolates, but the molecular changes in Shandong El9 viruses contributing to their phenotype remain to be further illuminated. However, the sequences described in this paper substantiate the changes taken place in capsid VPI and 5′UTR regions. These substitutions may contribute to their tropism and virulence, and play a significant role in pathogenesis and clinical manifestations of the disease.

Systematic screening reveals synergistic interactions that overcome MAPK inhibitor resistance in cancer cells

Objective:Effective adjuvant therapeutic strategies are urgently needed to overcome MAPK inhibitor(MAPKi)resistance,which is one of the most common forms of resistance that has emerged in many types of cancers.Here,we aimed to systematically identify the genetic interactions underlying MAPKi resistance,and to further investigate the mechanisms that produce the genetic interactions that generate synergistic MAPKi resistance.Methods:We conducted a comprehensive pair-wise sgRNA-based high-throughput screening assay to identify synergistic interactions that sensitized cancer cells to MAPKi,and validated 3 genetic combinations through competitive growth,cell viability,and spheroid formation assays.We next conducted Kaplan-Meier survival analysis based on The Cancer Genome Atlas database and conducted immunohistochemistry to determine the clinical relevance of these synergistic combinations.We also investigated the MAPKi resistance mechanisms of these validated synergistic combinations by using co-immunoprecipitation,Western blot,qRTPCR,and immunofluorescence assays.Results:We constructed a systematic interaction network of MAPKi resistance and identified 3 novel synergistic combinations that effectively targeted MAPKi resistance(ITGB3+IGF1R,ITGB3+JNK,and HDGF+LGR5).We next analyzed their clinical relevance and the mechanisms by which they sensitized cancer cells to MAPKi exposure.Specifically,we discovered a novel protein complex,HDGF-LGR5,that adaptively responded to MAPKi to enhance cancer cell stemness,which was up-or downregulated by the inhibitors of ITGB3+JNK or ITGB3+IGF1R.Conclusions:Pair-wise sgRNA library screening provided systematic insights into elucidating MAPKi resistance in cancer cells.ITGB3-+IGF1R-targeting drugs(cilengitide+linsitinib)could be used as an effective therapy for suppressing the adaptive formation of the HDGF-LGR5 protein complex,which enhanced cancer stemness during MAPKi stress.

Hemodynamic improvement by right ventricular septal pacing in elderly patients with chronic atrial fibrillation and slow ventricular response

Background and objectives Right ventricular apical (RVA) pacing has been reported impairing left ventricular (LV)performance. Alternative pacing sites in right ventricle (RV) has been explored to obtain better cardiac function. Our study was designed to compare the hemodynamic effects of right ventricular septal (RVS) pacing with RVA pacing. Methods Ten elderly patients with chronic atrial fibrillation (AF) and long RR interval or slow ventricular response (VR) received VVI pacing. The hemodynamic difference between RVS and RVA pacing were examined by transthoracic echocardiography (TTE). Results Pacing leads were implanted successfully at the RVA and then RVS in all patients without complication. The left ventricular (LV) parameters,measured during RVA pacing including left ventricular ejection fraction (LVEF), FS, stroke volume (SV) and peak E wave velocity (EV) were decreased significantly compared to baseline data, while during RVS pacing, they were significantly better than those during RVA pacing. However, after 3-6 weeks there was no statistical significant difference between pre- and post- RVS pacing.Conclusions The LV hemodynamic parameters during RVA pacing were significantly worse than baseline data. The short term LV hemodynamic parameters of RVS pacing were significantly better than those of RVA pacing; RVS pacing could improve the hemodynamic effect through maintaining normal ventricular activation sequence and biventricular contraction synchrony in patients with chronic AF and slow ventricular response.

Single-cell transcriptional profile of ACE2 in healthy and failing human hearts

Dear Editor,The coronavirus disease 2019(COVID-19)pandemic,which is caused by SARS-Co V-2,has gained serious attention from medical practitioners around the world in the past few months.Approximately 20%of critically ill COVID-19 patients were reported to have suffered myocardial injury.The specific mechanism of this pathology requires further investigation(Yang et al.,2020).

Eccrine Spiradenoma of the Forehead: A Case Report

Introduction Condyloma acuminatum(CA),also known as genital warts,is an anogenital warty growth caused by some types of the human papilloma virus(HPV).CA is usually found within the anal or genital area,but it occasionally presents in the oral,respiratory,conjunctival,nasal,or nipple region.We herein report a rare case of a 29-year-old Chinese woman with a tiny CA on her nipple,which was diagnosed through dermoscopy.With noninvasion and convenience,dermoscopy is valuable for the early diagnosis of tiny CA that is unable to be discerned by the naked eye.