Discovery of small molecule agonists targeting neuropeptide Y4 receptor using homology modeling and virtual screening

Neuropeptide Y4 receptor has the most significant effect on body weight and fat mass in its physiological functions, and the activation of Y4 receptor has explicit role on losing weight. The Y4 receptor has been successfully applied in the development of anti‐obesity agent, thus representing a potential therapeutic target for obesity treatment. Here, we reported the first discovery of small molecule agonists targeting Y4 receptor: three Y4 receptor models with active and inactive conformations were built, each model was submitted following structure‐based virtual screening, and finally six hits were identified as Y4 receptor agonists. These results confirm the reliability of the constructed Y4 receptor models and the proposed computational strategy for investigating novel Y4 receptor agonists. These new small molecule Y4 receptor agonists will contribute to the further development of Y4 agonists as potential therapeutics and functional probes.     

结直肠侧向发育型肿瘤黏膜下层侵犯的危险因素分析

目的 探索结直肠侧向发育型肿瘤黏膜下层浸润的危险因素。 方法 2015年11月—2019年2月,在大连医科大学附属第一医院消化内镜中心行内镜黏膜下剥离术治疗,直径≥2.0 cm的侧向发育型肿瘤病例211例（221处病变）纳入回顾性分析,根据术后病理分成黏膜下层侵犯组（13例患者,14处病变）和非黏膜下层侵犯组（198例患者,207处病变）,临床特征、内镜特征、手术特征、病理特征组间比较行χ2检验或连续矫正χ2检验或Fisher精确检验,多因素分析使用Logistic回归分析。 结果 单因素分析发现结直肠癌病史（P=0.037）、病变直径（P=0.036）、部位（P=0.024）、非抬举征（P=0.040）是黏膜下层浸润的影响因素。进一步多因素Logistic回归分析提示：有结直肠癌病史者较无结直肠癌病史者更易发生黏膜下层浸润（OR=3.76,95%CI：1.338～23.768,P=0.018）,直肠病变较右半结肠病变更易发生黏膜下层浸润（OR=7.091,95%CI：1.437～34.274,P=0.016）,直径≥2.5 cm病变较直径＜2.5 cm病变更易发生黏膜下层浸润（OR=6.297,95%CI：1.375～28.836,P=0.018）,非抬举征阳性病变较非抬举征阴性病变更易发生黏膜下层浸润（P=0.021,OR=5.373,95%CI：1.291～22.360）。 结论 对于结直肠侧向发育型肿瘤,患者有结直肠癌病史,以及病变直径≥2.5 cm、位于直肠、术中非抬举征阳性均是发生黏膜下层浸润的独立危险因素。     

Cryptotanshinone ameliorates renal ischaemia–reperfusion injury by inhibiting apoptosis and inflammatory response

Cryptotanshinone (CTS) is a natural compound from the Chinese herb Salvia miltiorrhiza. Previous studies demonstrated that CTS possesses anti‐apoptotic and anti‐inflammatory properties. However, its effects and underlying mechanism on renal ischaemia reperfusion (IR) injury remain unknown. In the present study, we investigated the effects of CTS on renal IR injury and its potential underlying mechanisms. Mice were randomized into four groups as follows: (a) sham operation + vehicle, (b) sham operation + CTS, (c) IR + vehicle, (d) IR + CTS. The CTS‐treated group were injected intraperitoneally with CTS (10 mg/kg/d) for 7 days prior to IR operation. Renal IR injury was induced by clamping the bilateral renal artery for 30 minutes followed by 24 hours of reperfusion. The mice were then killed to collect the serum and the kidneys for analysis. The results of the present study showed that CTS pretreatment significantly attenuates IR‐induced renal functional and morphological injuries, which was accompanied with inhibition of cell apoptosis and inflammatory response. Moreover, the phosphorylation of p38 mitogen‐activated protein kinase (MAPK) and the activation of nuclear factor‐κB (NF‐κB) signalling were inhibited by CTS. Therefore, CTS could be a useful therapeutic agent in the fight against renal IR injury.     

Trends and risk factors of elderly-onset Crohn's disease: A nationwide cohort study

BACKGROUND The incidence of inflammatory bowel disease(IBD)is increasing in Asia.Numerous risk factors associated with IBD development have been investigated.AIM To investigate trends and environmental risk factors of Crohn’s disease(CD)diagnosed in persons aged≥40 years in South Korea.METHODS Using the National Health Insurance Service database,a total of 14060821 persons aged>40 years who underwent national health screening in 2009 were followed up until December 2017.Patients with newly diagnosed CD were enrolled and compared with non-CD cohort.CD was identified according to the International Classification of Diseases 10th revision and the rare/intractable disease registration program codes from the National Health Insurance Service database.The mean follow-up periods was 7.39 years.Age,sex,diabetes,hypertension,smoking,alcohol consumption,regular exercise,body mass index,anemia,chronic kidney disease(CKD)and dyslipidemia were adjusted for in the multivariate analysis model.RESULTS During the follow-up,1337(1.33/100000)patients developed CD.Men in the middle-aged group(40-64 years)had a higher risk than women[adjusted hazard ratio(aHR)1.46,95%confidence interval(CI):1.29-1.66];however,this difference tended to disappear as the age of onset increases.In the middle-aged group,patients with a history of smoking[(aHR 1.46,95%CI:1.19-1.79)and anemia(aHR 1.85,95%CI:1.55-2.20)]had a significantly higher CD risk.In the elderly group(age,≥65 years),ex-smoking and anemia also increased the CD risk(aHR 1.68,95%CI:1.22-2.30)and 1.84(95%CI:1.47-2.30,respectively).Especially in the middle-aged group,those with CKD had a statistically elevated CD risk(aHR 1.37,95%CI:1.05-1.79).Alcohol consumption and higher body mass index showed negative association trend with CD incidence in both of the age groups.[Middle-aged:aHR 0.77(95%CI:0.66-0.89)and aHR 0.73(95% CI:0.63-0.84),respectively][Elderly-group:aHR 0.57(95% CI:0.42-0.78)and aHR 0.84(95%CI 0.67-1.04),respectively].For regular physical activity and dyslipidemia,negative correlation between CD incidences was proved only in the middle-aged group[aHR 0.88(95%CI:0.77-0.89)and aHR 0.81(95%CI:0.68-0.96),respectively].CONCLUSION History of cigarette smoking,anemia,underweight and CKD are possible risk factors for CD in Asians aged>40 years.     

紧密型医联体内社区卫生服务中心全科医生医疗能力培训教学需求分析

背景　目前医联体内社区卫生服务中心全科医生医疗能力培训教学安排缺乏需求证据支持。目的　为紧密型医联体模式下社区卫生服务中心全科医生培训制定以需求为导向的培训计划。方法　2019年11-12月,采用整群抽样法,对四川大学华西医院紧密型医联体模式中9家社区卫生服务中心的65名全科医生进行全科培训需求内容的问卷调查,问卷内容包括全科医学基本理论知识、全科医学基本技能、全科医学其他技能、全科医学临床操作4部分37个条目,每个条目均采用Likert 10级评分法,并根据条目需求评分设置优先等级。结果　按条目评分≥9分的全科医生人数占比从高到低排序,在全科医学基本理论知识部分,需求最高的是全科医生的临床诊疗策略〔47.7%（31/65）〕;在全科医学基本技能部分,需求最高的是呼吸系统常见疾病的全科处理〔55.4%（36/65）〕;在全科医学其他技能部分,培训需求最高的是社区营养指导〔36.9%（24/65）〕;在全科医学临床操作部分,需求最高的是氧气疗法、呼吸疾病常用吸入器和喷雾器使用方法〔46.2%（30/65）〕。根据评分优先等级标准,筛选出全科医生的临床诊疗策略、心脑血管常见疾病的全科处理、呼吸系统常见疾病的全科处理、社区常见症状和急症的全科医学处理、急救技术、常见实验室检查结果解读、常见影像识别解读（放射、B超）、十二导联及动态心电图判读8项作为首选培训内容,以及消化系统常见疾病的全科处理等13项主要备选培训内容。结论　本研究提出了紧密型医联体社区卫生服务中心系统性培训方案中的8项首选培训内容和13项主要备选培训内容,可为医疗机构根据其自身资源定制培训方案提供参考。     

Gemcitabine-Induced Hemolytic Uremic Syndrome in Pancreatic Cancer: A Case Report and Review of the Literature

Hemolytic uremic syndrome (HUS) is a rare thrombotic complication characterized by a triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure. HUS may be caused by several different conditions, including infection, malignancy, and chemotherapeutic agents, such as mitomycin, cisplatin, and most recently, gemcitabine. The outcome of gemcitabine-induced HUS is poor, and the disease has a high mortality rate. This study reports a case of gemcitabine-induced HUS in a patient with pancreatic cancer in Korea.