DNA damage levels are raised in Barrett's oesophageal mucosa relative to the squamous epithelium of the oesophagus

Barrett's oesophagus (BE) is a pre-malignant metaplastic tissue predisposing to oesophageal adenocarcinoma (EC), and gastro-oesophageal reflux is a risk factor for both conditions. Reflux of acid and bile can cause mucosal injury and initiate chronic inflammation. These processes can induce DNA damage, possibly via an oxidative stress mechanism, thus increasing the likelihood of progression from Barrett's metaplasia to dysplasia and finally carcinoma. The comet assay was optimized for the detection of DNA damage (strand breaks and alkali-labile sites) in oesophageal biopsies, including incorporation of the DNA repair enzyme Fapy-DNA glycosylase (Fpg). Fpg allows the detection of 8-hydroxy-2-deoxyguanosine (8-OHdG) sites, a known pro-mutagenic DNA lesion. BE patients were recruited from BE surveillance clinics and oesophageal biopsies collected at endoscopy. Comet analysis revealed significantly increased (p<0.001) DNA damage in Barrett's epithelium compared with matched squamous epithelium, with median % tail DNA values of 25.1% (first to third quartile 21.7–29.6%) and 18.6% (first to third quartile 16.9–21.4%), respectively. The median % tail DNA was up to 70% higher in the matched BE tissue compared with squamous epithelium from the same patient. Fpg sensitive sites were demonstrated in both tissue types at similar levels. The raised level of DNA damage in the premalignant BE may contribute to the accumulation of genetic alterations occurring during progression to EC. Understanding these underlying mechanisms provides a basis for cancer prevention strategies in BE patients.     

Computational model of rib movement and its application in studying the effects of age-related thoracic cage calcification on respiratory system

A 3D finite element model of rib cage movement is developed and used to study the role of age-related costal cartilage and sternocostal joint calcification, as well as respiratory muscle weakness on the ‘bucket-handle’ movement of human rib. The volume displacement of the rib cage is related to changes in its circumference using an empirical equation presented by Agostoni et al. (1965, J Appl Physiol, 20:1179–1186). A systematic study is carried out to quantify the role of costal cartilage, sternocostal joint calcification and muscle weakness on the volume displacement of the rib cage. The results provide insight into some of the mechanisms underlying age-related changes in the respiratory system.     

Superoxide Anion,the Main Species of ROS in the Development of ARDS Induced by Oleic Acid

It is believed that reactive oxygen species (ROS) play a very important role in the pathogenesis of acute respiratory distress syndrome (ARDS), but the mechanism has not been so clear, owing to the absence of direct measurable (experimental) data. In majority of the medical studies on free radicals, the analysis of ROS has generally been done by the way of measuring their secondary and breakdown products. In our study, we used electron spin resonance (ESR), a sensitive and accurate technique to detect ROS directly and also used some other sensitive techniques including ultra-weak luminescence and chemical luminescence to identify the species and relative amount of ROS. Furthermore, superoxide dismutase (SOD) was pre-administrated in ARDS rats to verify the results from the above studies and explore the possibility of the clinical application of SOD in ARDS. The spectra of ESR showed that the concentration of ROS increased at 10?min and reached a summit at 30?min after injection of oleic acid (OA), then dropped gradually. The scavenging effects of different scavenging agents on ROS by the analysis of ultra-weak luminescence proved that superoxide anion was the main species of ROS in the development of OA-induced ARDS. Moreover, the results of quantified measure of superoxide anion by chemical luminescence also showed the accordant tendency exhibited in ESR measurement. The pre-treatment of SOD might distinctly inhibit the production of superoxide anion, obviously improve the blood gas status, lung wet/dry ratio and lung/body ratio in ARDS rats. It is suggested that ROS may play a key role in the initiation phase of ARDS, while superoxide anion may be a leading actor in this process and SOD could effectively protect rats from ARDS. These results may provide helpful information for the treatment and prevention of ARDS.     

Astragaloside IV ameliorates fat metabolism in the liver of ageing mice through targeting mitochondrial activity

Astragaloside IV (AST) is a major bioactive compound of Radix Astragali with medical and health benefits. Previous studies have found that AST can reduce the body weights of high-fat diet fed mice. However, the effect of AST on fat metabolism of ageing mice is unclear. In this study, naturally ageing mice were administered intragastrically with AST at 30 mg/kg/day (ageing + AST-L group) and 90 mg/kg/day (ageing + AST-H group) for 16–20 months. Adult (4 months old) and ageing mice were given 1% sodium carboxyl methylcellulose as vehicle. Energy metabolism-related biological parameters of living mice were examined. Moreover, mRNA and protein levels of key enzymes/proteins involved in triglyceride (TG) lipolysis, fatty acid β-oxidation (FAO), ketone body (KB) production and mitochondrial respiratory chain were also examined after sacrifice. Results demonstrated that treatment with AST significantly reduced body weight, white fat and liver/body weight ratio of ageing mice, significantly reduced serum/hepatic TG levels, respiratory quotient, promoted fatty acid mobilization in white adipose tissue, mitochondrial FAO and KB production and mitochondrial biosynthesis/functions in the liver of ageing mice. AST also up-regulated the expression of phosphorylated AMP-activated protein kinase, acetyl-CoA carboxylase, acetyl-coenzyme A synthetase, carnitine palmitoyltransferase 1a/1b, enoyl coenzyme A hydratase-short chain, acyl-CoA dehydrogenase medium chain and mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase-2 involved in fat metabolism. These results indicated that mitochondrial activity could be the target of AST to treat abnormal fat metabolism during ageing.     

肺结核合并下呼吸道感染患者CT影像特点及IL-23R水平表达的临床意义

摘要 目的：探讨肺结核合并下呼吸道感染患者CT影像特点及IL-23R水平表达的临床意义。方法：选取2015年1月-2018年8月于我院就诊的123例肺结核患者,将所选取的患者按是否合并下呼吸道感染分为单纯肺结核组73例和肺结核合并下呼吸道感染组50例。分析两组组患者临床表现、CT影像学图片、CT影像学表现、血清IL-23R的表达水平的差异。结果：单纯肺结核组患者出现14例低热、11例胸闷、17例消瘦、14例气短、18例痰中带血、14例颈部淋巴结肿大、23例咳嗽、21例胸痛。肺结核合并下呼吸道感染组患者出现16例低热、13例胸闷、21例消瘦、19例气短、20例痰中带血、15例颈部淋巴结肿大、26例咳嗽、23例胸痛,两组患者临床表现差异均无统计学意义（P＞0.05）。单纯肺结核组CT影像学图片显示可见结节影或包块影,呈明显分叶征、短毛刺征、空泡征并发肺不张、棘状突起,边缘较清晰,增强扫描后明显强化。肺结核合并下呼吸道感染组CT影像学图片显示有分叶、毛刺,同时肺内肿物周边存在晕征、血管聚集征、卫星灶征、胸膜凹陷等表现,此外伴纵膈及肺门淋巴结明显肿大,胸壁侵犯。肺结核合并下呼吸道感染组CT影像中毛刺状结节、胸膜凹陷、空洞、分叶征、肿块、条索影比例均高于单纯肺结核组,差异有统计学意义（P＜0.05）。肺结核合并下呼吸道感染组患者IL-23R水平明显高于单纯肺结核组,差异有统计学意义（P＜0.05）。结论：与单纯肺结核患者相比较,肺结核合并下呼吸道感染患者临床表现更为严重,CT影像学特点更为明显,患者血清中IL-23R表达水平明显升高,临床可通过CT影像学结合血清IL-23R检测,以提高肺结核合并下呼吸道感染患者的临床诊断。     

Seroprevalence of Neutralizing Antibodies against Six Human Adenovirus Types Indicates the Low Level of Herd Immunity in Young Children from Guangzhou,China

Human adenoviruses(HAdVs) commonly cause many diseases such as respiratory diseases, gastroenteritis, cystitis worldwide. HAdV-3,-7,-4 and emergent HAdV-55 and HAdV-14 are the most important types causing severe respiratory diseases. There is no effective drug available for clinical treatment, and no vaccine available for the general population.Therefore, it is important to investigate the seroprevalence against HAdV for developing novel vaccines and vectors. In this study, we investigated the seroprevalence and titer levels of neutralizing antibodies(NAb) against HAdV-3,-4,-7,-14,-55,and-11 in total 278 healthy populations between 0 months and 49 years of age(228 children and 50 adults) from Guangzhou. In children under the age of 18 years, the seropositive rates were significantly increased against HAdV-3 at12.07%, 33.96%, and 64.29% and against HAdV-7 at 0%, 18.87%, and 19.05% in age groups of 1–2, 3–5, and 6–17 years,respectively. The seroprevalence was very low(0% * 8.1%) for all other four types. In adults aged between 18 and49 years, HAdV-3,-4, and-7([ 50.00%) were the most common types, followed by HAdV-14(38.00%),-55(34.00%),and-11(24.00%). Adults tended to have high NAb titers against HAdV-4 and-55. HAdV-55-seropositive donors tended to be HAdV-11-and HAdV-14-seropositive. These results indicated the low level of herd immunity against all six HAdV types in young children, and HAdV-14,-55,-11 in adults from Guangzhou City. Our findings demonstrate the importance of monitoring HAdV types and developing vaccines against HAdV for children and adults.     

A multi-center study on Molecular Epidemiology of Human Respiratory Syncytial Virus from Children with Acute Lower Respiratory Tract Infections in the Mainland of China between 2015 and 2019

Virologica Sinica - Human respiratory syncytial virus (RSV) is a major pathogen of acute lower respiratory tract infection among young children. To investigate the prevalence and genetic...     

Protective Efficacy of Inactivated Vaccine against SARS-CoV-2 Infection in Mice and Non-Human Primates

Virologica Sinica - The ongoing coronavirus disease 2019 (COVID-19) pandemic caused more than 96 million infections and over 2 million deaths worldwide so far. However, there is no approved vaccine...