Transcatheter occlusion of ruptured sinus of valsalva aneurysm: innovative use of available technology.

A 9-year-old boy was found to have ruptured sinus of Valsalva aneurysm (RSVA) and aortic coarctation. Following relief of aortic coarctation by balloon angioplasty, transcatheter coil occlusion of the RSVA was performed successfully under transesophageal echocardiographic and fluoroscopic monitoring; bioptome-assisted delivery of 0.052" Gianturco coil was undertaken via a 7 Fr sheath stabilized by an 0.035" guidewire passing through the RSVA and the sheath. This report details the technique of occlusion.     

慢性充血性心力衰竭心脏干细胞移植后心肌电生理学特性的变化

研究慢性充血性心力衰竭(简称心衰)时,干细胞移植对心肌电生理学特性的影响。日本大耳白兔分为健康对照(8只)和心衰两大组,后者包括骨髓间充质细胞移植组(8只)、骨骼肌成肌细胞移植组(6只)和假手术组(8只)。慢性心衰模型由阿霉素制成。干细胞移植采用经双球囊封堵主动脉窦上部灌注自体骨髓间充质细胞或骨骼肌成肌细胞。比较干细胞移植前后心功能有无变化。测定多部位的有效不应期(ERP)及离散度(ERPd);右室流出道、左室心尖部或室间隔连续刺激(S1S1)或早搏刺激时,其它各部位的兴奋传导时间(AT)和兴奋传导时间离散度(ATd),比较各组间有无差异。结果:骨髓间充质细胞移植4周后,左室射血分数有改善的趋势。各组间ERP及ERPd无差异。与健康对照组和假手术组相比,骨骼肌成肌细胞移植组和骨髓间充质细胞移植组的AT和ATd有增加,在骨骼肌成肌细胞移植组更加明显。AT和ATd的变化在左室心尖部刺激时最为显著。在骨髓间充质细胞移植组,出现1例自发性室性心动过速,并猝死。结论:慢性充血性心衰时,干细胞自体心脏移植后,心肌组织的电传导能力下降,离散度增大。     

IL28B genetic variants and gender are associated with spontaneous clearance of hepatitis C virus infection

Summary. Single nucleotide polymorphisms (SNPs) near the IL28B gene have been shown to be associated with response to treatment for chronic hepatitis C and also with spontaneous clearance of hepatitis C virus (HCV) infection. We analysed the association between IL28B genetic variants and spontaneous clearance of HCV infection in 376 HCV‐infected Chinese paid plasma donors. Genotyping of eight SNPs near the IL28B region was performed by the iPLEX system (MassARRAY^® SNP Genotyping; Sequenom) in all donors, and sequencing was performed on all 80 donors who cleared HCV and on 160 of 296 donors who did not clear HCV to validate the genotypes. Eighty (21.3%) donors spontaneously cleared HCV. Four SNPs were significantly associated with spontaneous HCV clearance: rs8099917 TT (vs GT), rs8105790 TT (vs CT), rs12980275 AA (vs AG) and rs10853728 CC (vs CG or GG) with OR (95% CI) 15.27 (2.07–112.50), 14.88 (2.02–109.72), 7.92 (1.88–33.32) and 2.32 (1.22–4.42) respectively. No association between the other four IL28B SNPs including rs12979860 and spontaneous HCV clearance was found. Women had a higher rate of spontaneous HCV clearance than men [56/213 (26.3%) vs 24/163 (14.6%), P = 0.007], and this was true even after stratification for IL28B genotypes with OR of 1.9–2.2 among those with favourable genotypes. Our results confirmed that IL28B polymorphism is associated with spontaneous clearance of HCV in Chinese subjects, but the SNPs that predict HCV clearance in Chinese subjects were different from those reported in Caucasians. Women were more likely to clear HCV infection regardless of IL28B genotypes.     

瘦素抵抗与男性非酒精性脂肪肝的关系

研究瘦素抵抗和男性非酒精性脂肪肝(nonalcoholic fatty liver,NAFL)的关系。我们用放射免疫法检测52例NAFL患者和45例正常对照者血清中的瘦素水平,分析血清瘦素与男性NAFL患者以及与HOMA-IR(以HOMA模型计算胰岛素抵抗指数)、总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)和低密度脂蛋白胆固醇(LDL-C)等指标的关系。NAFL患者血清中的瘦素水平(6.75±1.32μg/ml)显著高于正常对照组(3.21±0.95μg/ml),P<0.01,且肥胖的NAFL患者血清中的瘦素水平(7.95±0.85ng/ml)显著高于非肥胖NAFL患者的瘦素水平(6.11±1.21μg/ml),P<0.01。NAFL患者血清中的FINS、HOMA-IR和TG水平均高于正常对照组,且NAFL患者血清瘦素水平与HOMA-IR呈负相关(r=0.521,P<0.05),与BMI呈正相关(r=0.718,P<0.00),与TG呈正相关(r=0.425,P<0.01)。男性NAFL患者存在着明显的瘦素抵抗,提示瘦素抵抗在NAFL的发病机制中具有十分重要的作用。     

Delta Variant with P681R Critical Mutation Revealed by Ultra-Large Atomic-Scale Ab Initio Simulation: Implications for the Fundamentals of Biomolecular Interactions

The SARS-CoV-2 Delta variant is emerging as a globally dominant strain. Its rapid spread and high infection rate are attributed to a mutation in the spike protein of SARS-CoV-2 allowing for the virus to invade human cells much faster and with an increased efficiency. In particular, an especially dangerous mutation P681R close to the furin cleavage site has been identified as responsible for increasing the infection rate. Together with the earlier reported mutation D614G in the same domain, it offers an excellent instance to investigate the nature of mutations and how they affect the interatomic interactions in the spike protein. Here, using ultra large-scale ab initio computational modeling, we study the P681R and D614G mutations in the SD2-FP domain, including the effect of double mutation, and compare the results with the wild type. We have recently developed a method of calculating the amino-acid–amino-acid bond pairs (AABP) to quantitatively characterize the details of the interatomic interactions, enabling us to explain the nature of mutation at the atomic resolution. Our most significant finding is that the mutations reduce the AABP value, implying a reduced bonding cohesion between interacting residues and increasing the flexibility of these amino acids to cause the damage. The possibility of using this unique mutation quantifiers in a machine learning protocol could lead to the prediction of emerging mutations.     

Phylogenetic Analysis of Spread of Hepatitis C Virus Identified during HIV Outbreak Investigation,Unnao, India

An HIV outbreak investigation during 2017–2018 in Unnao District, Uttar Pradesh, India, unearthed high prevalence of hepatitis C virus (HCV) antibodies among the study participants. We investigated these HCV infections by analyzing NS5B and core regions. We observed no correlation between HIV–HCV viral loads and clustering of HCV sequences, regardless of HIV serostatus. All HCV isolates belonged to genotype 3a. Monophyletic clustering of isolates in NS5B phylogeny indicates emergence of the outbreak from a single isolate or its closely related descendants. The nucleotide substitution rate for NS5B was 6 × 10⁻³ and for core was 2 × 10⁻³ substitutions/site/year. Estimated time to most recent common ancestor of these isolates was 2012, aligning with the timeline of this outbreak, which might be attributable to unsafe injection practices while seeking healthcare. HIV–HCV co-infection underlines the need for integrated testing, surveillance, strengthening of healthcare systems, community empowerment, and molecular analyses as pragmatic public health tools.     

Apoptogenic activity of ethyl acetate extract of leaves of Memecylon edule on human gastric carcinoma cells via mitochondrial dependent pathway

ObjectiveTo evaluate the anti-proliferative and apoptogenic activity of ethyl acetate extract from the leaves of Memecylon edule (EtAc-LME) in MKN-74, NUGC gastric cancer cells and non cancerous gastric mucous cells (GES-1), and to explore the mechanism of EtAc-LME induced apoptosis.MethodsThe mechanism of EtAc-LME induced apoptosis was explored by analysing the activation of pro-caspases, PARP cleavage, expression of cytochrome-c (Cyt-c) was determined by western blotting, mRNA expression of Bcl-2, Bax by RT-PCR, loss of mitochondrial potential using DiOC6 dye, annexin binding assay and its influence on cell cycle arrest by flow cytometry.ResultsThe results indicated that EtAc-LME inhibited the gastric cancer cell growth in dose-dependent manner and cytotoxicity was more towards the gastric cancer cells (NUGC and MKN-74) compared to normal gastric cells (GES-1), suggesting more specific cytotoxicity to the malignant cells. Over expression of Cyt-c and subsequent activation of caspases-3 and down regulation of Bcl-2 and loss in mitochondrial potential in EtAc-LME treated MKN-74 and NUGC cells suggested that EtAc-LME induced apoptosis by mitochondrial dependent pathway.ConclusionsThe present findings suggest that ethyl acetate extract of Memecylon edule induces apoptosis selectively in gastric cancer cells emphasizing the importance of this traditional medicine for its potential in the treatment of gastric cancer.     

Assessing racial/ethnic disparities in chemotherapy treatment among breast cancer patients in context of changing treatment guidelines

Conflicting study results with regards to racial/ethnic disparities in chemotherapy use among breast cancer patients may be due to the different sample populations, treatment data sources, and treatment eligibility definitions used. This study examined chemotherapy disparity in the context of changing treatment guidelines and explored factors that may help explain treatment differences observed. The data come from a population-based study that included interview and medical record data (including state cancer registry) from non-Hispanic (nH) White, nH Black, and Hispanic breast cancer patients diagnosed in 2005–2008. Logistic regression using model-based standardization was used to estimate age-adjusted risk differences and multivariate analysis was conducted to identify explanatory factors of the differences. Per the 2005/2006 National Comprehensive Cancer Network (NCCN) guidelines, minority patients appeared more likely than nH White patients to receive a chemotherapy recommendation (0.87 vs 0.75, p = 0.003). When eligibility was determined per the 2007 guidelines, there was no disparity because under these guidelines, nH White patients were more likely than minority patients to have tumors that no longer required chemotherapy. There was evidence that chemotherapy advances for breast cancer patients are implemented in the clinical setting well ahead of NCCN guidelines. Finally, among eligible patients, chemotherapy recommendation was very high and virtually always accepted and received, with no disparities found at these points of clinical care. The findings suggest that an evaluation of guideline-adherent chemotherapy treatment patterns must carefully consider the definition of treatment eligibility, given ongoing changes in treatment guidelines and early uptake of new diagnostic tools and treatments.     

晚期NSCLC吉非替尼治疗失败后的再次治疗(病例报告及文献复习)

目的:对吉非替尼治疗失败后的晚期NSCLC患者再次使用吉非替尼治疗,分析其疗效及安全性。方法:复习1例吉非替尼治疗失败后的晚期NSCLC患者再次使用吉非替尼治疗及临床资料,结合相关文献探讨其临床特征、治疗及预后。结果:该患者首次使用吉非替尼约8月后耐药,停药5月后再次使用吉非替尼,1月后复查肺部CT提示肺部病灶明显缩小,2个月后再次失效,最终总生存期达21月,使用吉非替尼期间不良反应轻微。结论:曾使用吉非替尼有效的晚期NSCLC患者,再次使用吉非替尼仍有可能延长其生存时间且不良反应轻微。