Establishment of Murine Infection Models with Biological Clones of Dengue Viruses Derived from a Single Clinical Viral Isolate

Virologica Sinica - Dengue virus (DENV) is a single-stranded RNA virus transmitted by mosquitoes in tropical and subtropical regions. It causes dengue fever, dengue hemorrhagic fever and dengue...     

Intra-strain biological and epidemiological characterization of plum pox virus

Plum pox virus (PPV) is one of the most important plant viruses causing serious economic losses. Thus far, strain typing based on the definition of 10 monophyletic strains with partially differentiable biological properties has been the sole approach used for epidemiological characterization of PPV. However, elucidating the genetic determinants underlying intra-strain biological variation among populations or isolates remains a relevant but unexamined aspect of the epidemiology of the virus. In this study, based on complete nucleotide sequence information of 210 Japanese and 47 non-Japanese isolates of the PPV-Dideron (D) strain, we identified five positively selected sites in the PPV-D genome. Among them, molecular studies showed that amino acid substitutions at position 2,635 in viral replicase correlate with viral titre and competitiveness at the systemic level, suggesting that amino acid position 2,635 is involved in aphid transmission efficiency and symptom severity. Estimation of ancestral genome sequences indicated that substitutions at amino acid position 2,635 were reversible and peculiar to one of two genetically distinct PPV-D populations in Japan. The reversible amino acid evolution probably contributes to the dissemination of the virus population. This study provides the first genomic insight into the evolutionary epidemiology of PPV based on intra-strain biological variation ascribed to positive selection.     

Review: Prevention and management of gastric cancer

Gastric cancer (GC) is still the fifth most frequently diagnosed cancer and the third leading cause of cancer deaths in both sexes worldwide. Although the incidence of GC is predicted to continue declining in a growing number of countries in the future, on a global scale the number of newly diagnosed GC cases will remain high, or increase even further, due to changes in population size and increasing risks observed in younger generations. In a retrospective cohort study, collecting data from the Veterans Health Administration, treatment of Helicobacter pylori infection decreased GC risk only if eradication was successful. In a German case‐control study, among GC patients with autoimmune gastritis, pernicious anemia was associated with earlier detection of GC, which translated into a significantly better 5‐year survival. In an updated meta‐analysis, H. pylori eradication therapy in healthy individuals significantly reduced both GC incidence and mortality from GC with a number needed to treat of 72 and 135, respectively. In Korea, successful H. pylori eradication substantially reduced GC incidence in first‐degree relatives of GC patients as well. A meta‐analysis of four trials including 1,556 patients with resectable GC reported that the patient subgroup tumors with high microsatellite instability undergoing surgery did not benefit from perioperative or adjuvant chemotherapy.     

Review: Helicobacter pylori infection in children

Helicobacter pylori infection in children and adolescents differs in comparison to adults with respect to epidemiology, host responses, and disease manifestations. Furthermore, treatment options are limited in this population and antibiotic resistance rates continue to increase. Therefore, ongoing research is vital to understand disease pathogenesis and provide optimal management of children with infection. This review summarizes relevant publications from April 2019 to March 2020. Similar to adults, recent studies show a decreasing prevalence of infection in the pediatric population. Studies of pathogenesis investigated serum immune responses and the potential inverse association of infection and allergy. Several studies investigated the effect of H pylori and related inflammation on the gut microbiome. The recommendation of endoscopy‐based testing to identify the cause of symptoms and not just H pylori, reserving noninvasive UBT or stool antigen tests for post‐eradication follow‐up, was supported by the current literature.     

肺炎支原体感染对川崎病的影响及机制探讨

目的分析肺炎支原体感染对川崎病的影响及其机制,以期指导临床诊疗。方法回顾性分析2013年8月至2018年8月我科住院的496例川崎病患儿临床资料,其中合并肺炎支原体感染组193例,未合并肺炎支原体感染组303例。应用倾向评分匹配法1∶1校正2组的年龄、性别、是否为不完全型川崎病、是否使用糖皮质激素、丙种球蛋白使用时间、丙种球蛋白使用方法和阿司匹林初始剂量,比较2组患儿的总发热天数、冠状动脉直径、冠状动脉扩张发生率、冠状动脉瘤发生率和丙种球蛋白无反应发生率。结果川崎病合并肺炎支原体感染组男性患儿多,更易发生颈部淋巴结肿大,年龄、中性粒细胞百分比、血沉和低密度脂蛋白高于川崎病未合并肺炎支原体感染组,血钾、血钙、高密度脂蛋白和白蛋白低于川崎病未合并肺炎支原体感染组,差异有统计学意义(均P<0.05)。应用倾向评分匹配法1∶1配对后发现,川崎病合并肺炎支原体感染组患儿总发热时间更长[8(6~10)d vs 7(6~9)d,Z=-2.089,P<0.05),冠状动脉直径值更大[(2.81±0.81)mm vs(2.63±0.45)mm,t=2.532,P<0.05],冠状动脉瘤发生率更高(5.5% vs 1.1%,χ²=5.516,P<0.05)。结论肺炎支原体感染可能引起川崎病患儿脂质代谢及电解质的紊乱,其炎症反应更强,持续时间更长,对冠状动脉损伤更大。     

Brain tumors: Cancer stem-like cells interact with tumor microenvironment

Cancer stem-like cells (CSCs) with potential of self-renewal drive tumorigenesis. Brain tumor microenvironment (TME) has been identified as a critical regulator of malignancy progression. Many researchers are searching new ways to characterize tumors with the goal of predicting how they respond to treatment. Here, we describe the striking parallels between normal stem cells and CSCs. We review the microenvironmental aspects of brain tumors, in particular composition and vital roles of immune cells infiltrating glioma and medulloblastoma. By highlighting that CSCs cooperate with TME via various cellular communication approaches, we discuss the recent advances in therapeutic strategies targeting the components of TME. Identification of the complex and interconnected factors can facilitate the development of promising treatments for these deadly malignancies.     

Why genetic selection to reduce the prevalence of infectious diseases is way more promising than currently believed

Genetic selection for improved disease resistance is an important part of strategies to combat infectious diseases in agriculture. Quantitative genetic analyses of binary disease status, however, indicate low heritability for most diseases, which restricts the rate of genetic reduction in disease prevalence. Moreover, the common liability threshold model suggests that eradication of an infectious disease via genetic selection is impossible because the observed-scale heritability goes to zero when the prevalence approaches zero. From infectious disease epidemiology, however, we know that eradication of infectious diseases is possible, both in theory and practice, because of positive feedback mechanisms leading to the phenomenon known as herd immunity. The common quantitative genetic models, however, ignore these feedback mechanisms. Here, we integrate quantitative genetic analysis of binary disease status with epidemiological models of transmission, aiming to identify the potential response to selection for reducing the prevalence of endemic infectious diseases. The results show that typical heritability values of binary disease status correspond to a very substantial genetic variation in disease susceptibility among individuals. Moreover, our results show that eradication of infectious diseases by genetic selection is possible in principle. These findings strongly disagree with predictions based on common quantitative genetic models, which ignore the positive feedback effects that occur when reducing the transmission of infectious diseases. Those feedback effects are a specific kind of Indirect Genetic Effects; they contribute substantially to the response to selection and the development of herd immunity (i.e., an effective reproduction ratio less than one).     

不同体质量指数对腹腔镜结直肠癌切除术患者临床疗效和远期预后的影响

摘要 目的：研究不同体质量指数（BMI）对腹腔镜结直肠癌切除术患者临床疗效和远期预后的影响。方法：将从2014年1月～2016年1月于我院接受腹腔镜结直肠癌切除术治疗的110例患者纳入研究。将所有受试者根据BMI的差异分作正常组（18.6 kg/m²≦BMI<23.0 kg/m²）35例、超重组（23.0 kg/m²≦BMI<25.0 kg/m²）53例、肥胖组（BMI≧25.0 kg/m²）22例。分析三组患者各项基线资料,临床疗效,术后并发症发生情况,远期预后等方面的差异。结果：三组患者各项基线资料比较差异均不明显（均P＞0.05）。肥胖组手术时长为（268.01±36.14）min,均明显高于正常组、超重组的（211.73±30.56）min、（224.12±34.87）min（均P＜0.05）;三组术中失血量、肛门排气时间以及住院康复时间对比均不明显（均P＞0.05）。三组患者术后肺部感染、下肢静脉血栓、切口感染以及吻合口出血发生率对比均不明显（均P＞0.05）。正常组5年生存率为45.71%（16/35）,超重组5年生存率为47.17%（25/53）,肥胖组5年生存率为45.45%（10/22）,三组比较差异无统计学意义（均P＞0.05）。结论：不同BMI对腹腔镜结直肠癌切除术患者的手术时长具有一定影响,但和远期预后无关,值得临床重点关注。     

熊去氧胆酸联合非诺贝特对原发性胆汁性胆管炎的临床疗效及安全性

摘要 目的：分析熊去氧胆酸联合非诺贝特对原发性胆汁性胆管炎无熊去氧胆酸生化反应的临床疗效及安全性。方法：151例原发性胆汁性胆管炎无熊去氧胆酸患者按随机数表法分为73例对照组和78例研究组。对照组在常规治疗基础上给予安慰剂联合熊去氧胆酸治疗,研究组在常规基础上给予非诺贝特联合熊去氧胆酸治疗,两组均持续治疗12个月。比较两组临床疗效,肝功能,血脂指标,肝纤维化指标,免疫球蛋白G（IgG）、免疫球蛋白M（IgM）,瘙痒及乏力评分,不良反应发生情况。结果：治疗后,研究组总有效率高于对照组,比较差异有统计学意义（P<0.05）。治疗后,两组肝功能指标均降低,研究组低于对照组,比较有统计学意义（P<0.05）。治疗后,两组总胆固醇（TC）、甘油三酯（TG）均降低,研究组低于对照组,比较有统计学意义（P<0.05）,两组治疗前后低密度脂蛋白胆固醇（LDL-C）、高密度脂蛋白胆固醇（HDL-C）比较无统计学意义（P>0.05）。治疗后,两组肝纤维化指标均降低,研究组低于对照组,比较有统计学意义（P<0.05）。治疗后,两组IgG、IgM均降低,研究组低于对照组,比较有统计学意义（P<0.05）。治疗后,两组瘙痒、乏力评分均降低,研究组低于对照组,比较有统计学意义（P<0.05）。两组不良反应发生率比较差异无统计学意义（P>0.05）。结论：熊去氧胆酸联合非诺贝特对原发性胆汁性胆管炎无熊去氧胆酸生化反应的疗效较好,能够改善肝功能,且未明显增加药物不良反应。