急性冠脉综合征患者NLR、MPV与Gensini评分的相关性分析

目的:探讨急性冠脉综合征(Acute Coronary Syndrome,ACS)患者的中性粒细胞/淋巴细胞(Neutrophils/lymphocyte,NLR)、平均血小板体积(Mean platelet volume,MPV)与Gensini评分的相关性。方法:将156例ACS患者依据冠状动脉造影结果分为单支病变组、双支病变组及三支病变组,比较各组间NLR、MPV、Gensini评分及一般临床资料,并分析不同指标之间的相关性。结果:与双支病变组、单支病变组相比较,三支病变组吸烟、糖尿病、低密度脂蛋白胆固醇(low density lipoprotein cholesterol,LDL-C)、高密度脂蛋白胆固醇(high density lipoprotein cholesterol,HDL-C)、尿酸(uric acid,UA)、NLR、MPV、Gensini评分均显著升高(P0.05);与单支病变组相比较,双支病变组吸烟、糖尿病、LDL-C、HDL-C、UA、NLR、MPV、Gensini评分均显著升高(P0.05);三组间年龄、性别、高血压、总胆固醇(total cholesterol,TC)、甘油三酯(triglyceride,TG)、肌酐(creatinine,Cr)比较差异均无统计学意义(P0.05)。Pearson相关性分析表明:NLR、MPV与Gensini评分均呈正相关(r=0.482、0.702, P0.05)。结论:ACS患者MPV和NLR与冠状动脉病变程度呈显著正相关,可有效评估冠状动脉狭窄程度。     

Ultrasound mediated efficient synthesis of new 4-oxoquinazolin-3(4H)-yl)furan-2-carboxamides as potent tyrosinase inhibitors: Mechanistic approach through chemoinformatics and molecular docking studies

We have carried out the synthesis of new 4-oxoquinazolin-3(4H)-yl)furan-2-carboxamide derivatives by the reaction between isatoic anhydride, 2-furoic hydrazide and substituted salicylaldehydes in ethanol: water (5:5 v/v) solvent system using p-TSA as a catalyst under ultrasound irradiation at room temperature. The structures of newly synthesized compounds were confirmed through spectral techniques such as IR, ¹H NMR, ¹³C NMR, and LCMS. The important features of this protocol include simple and easy workup procedure, reaction carried out at ambient temperature, use of ultrasound and high yield of oxoquinazolin-3(4H)-yl)furan-2-carboxamides in short reaction time. The synthesized compounds 4a–4j were screened against tyrosinase enzyme and all these compounds found to be potent inhibitors with much lower IC₅₀ value of 0.028 ± 0.016 to 1.775 ± 0.947 µM than the standard kojic acid (16.832 ± 1.162 µM). The kinetics mechanism for compound 4e was analyzed by Lineweaver-Burk plots which revealed that compound inhibited tyrosinase non-competitively by forming an enzyme-inhibitor complex. Along with this all the synthesized compounds (4a–4j) were scanned for their DPPH free radical scavenging ability. The outputs received through in vitro and in silico analysis are coherent to the each other with good binding energy values (kcal/mol) posed by synthesized ligands.     

Assessing the skill of yes/no predictions

Summary Should healthy, middle‐aged women receive precautionary mammograms? Should trauma surgeons use the popular TRISS score to predict the likelihood of patient survival? These are examples of questions confronting us when we decide whether to use a yes/no prediction. In order to trust a prediction we must show that it is more valuable than would be our best guess of the future in the absence of the prediction. Calculating value means identifying our loss should the prediction err and examining the past performance of the prediction with respect to that loss. A statistical test to do this is developed. Predictions that pass this test are said to have skill. Only skillful predictions should be used. Graphical and numerical methods to identify skill will be demonstrated. The usefulness of mammograms is explored.     

疏风解毒胶囊辅以综合管理干预对慢性阻塞性肺疾病患者呼吸及运动功能的影响

摘要 目的：探讨疏风解毒胶囊辅以综合管理干预对慢性阻塞性肺疾病（COPD）患者呼吸及运动功能改善的影响。方法：选取2018年10月-2019年10月到我院进行治疗的COPD患者84例作为研究对象,随机数字表法分为两组,患者均使用疏风解毒胶囊进行治疗,对照组（n=42）予以常规干预,试验组（n=42）进行综合管理干预。对比两组患者的临床治疗有效率、肺功能改善情况、肺功能指标、呼吸困难指数（MRC）评分以及6分钟步行实验（6MWT）结果。结果：试验组的临床治疗有效率高于对照组（P<0.05）。干预后,两组动脉血二氧化碳分压（PaCO₂）和MRC评分较干预前降低（P<0.05）,动脉血氧分压（PaO₂）、动脉血氧饱和度（SaO₂）、第1秒用力呼气容器（FEV₁）、用力肺活量（FVC）、FEV₁/FVC均较干预前升高（P<0.05）,6MWT距离较干预前增加（P<0.05）,且试验组上述指标改善情况更优（P<0.05）。结论：疏风解毒胶囊辅以综合管理干预可提高COPD患者的临床治疗效果,改善其肺功能,可有效缓解呼吸困难,提升运动强度,值得在临床上应用与推广。     

房颤射频消融术后复发风险预测评分系统的建立及评价

目的:探讨心房颤动(房颤)患者射频消融术后复发的风险因素,并依此构建个性化的风险评分系统。方法:选取2017年1~8月行射频消融术的房颤患者154例作为研究对象,依据术后3个月的随访结果将患者分为复发组及未复发组,采用单因素分析和Logistic回归分析对各风险因素进行分析,构建其评分系统,采用Hosmer-Lemeshow拟合优度检验和ROC曲线下面积评价评分系统的准确度及区分度。结果:术后随访3个月的结果显示共37例(24.03%)房颤患者出现复发,房颤类型、病程、体质量指数(BMI)、左房前后径(LAD)、左房容积(LAV)及超敏C反应蛋白(hs-CRP)水平均是房颤复发的独立风险因素(P<0.05)。构建的风险评分系统得分为0~26分,Hosmer-Lemeshow拟合优度检验:x^2=7.520,P=0.482;ROC曲线下面积为0.864(95%CI:0.837~0.891),预测评分值为15分时,约登指数最大(0.605),此时的敏感度和特异度分别为77.3%和83.2%。结论:房颤患者射频消融术后的复发率较高,依据风险因素构建的风险评分系统具有较高的预测效率和区分能力,可作为房颤患者射频消融术后复发风险评估的参考工具。     

Comparison of growth performance and agonistic interaction in weaned piglets of different weight classes from farrowing systems with group or single housing

The present study was designed to analyze the growth performance, behavioral patterns and intensity of injuries of weaned pigs (26 days) during a rearing period of 6 weeks. The farrowing system (group housing (GH) v. single housing (SH)) and the post-weaning regrouping weight class (light, medium, heavy) were considered as the main factors. A number of 120 GH-pigs and 120 SH-pigs were kept in three batches (20 pens, 12 pigs each). The GH- and SH-pigs were divided by weight into three groups: light (5 to ⩽7 kg), medium (>7 to ⩽9 kg) and heavy (>9 to ⩽12 kg), with two pigs of six different litters in each pen. The pigs were weighed individually at weaning (week 1) and during rearing (weeks 2, 3 and 7). The feed conversion ratio (FCR) was calculated between weeks 1 and 7. The duration and number of fights (NF) per pen and hour were determined by continuous sampling (40 h after weaning). Lesions of the integument were scored into four classes (none, minor, medium, severe) and recorded at weaning and 48 h afterwards. The farrowing system had no effect on the weights in week 1 (GH: 7.8 kg v. SH: 7.7 kg; week as linear, quadratic regression nested within housing systems) or in week 7 (GH: 29.4 kg v. SH: 28.6 kg). The body weights were influenced significantly by the weaning weight class (light: 11.7 kg (s.e.m.: 0.30), medium: 14.8 kg (s.e.m.: 0.22), heavy: 17.3 kg (s.e.m.: 0.26)). The FCR of the GH-pigs was 1.64 (s.e.m.: 0.03) and 1.58 (s.e.m.: 0.03) for SH-pigs. A reduced agonistic behavior of the GH-pigs was observed with 2.1 fights per pen and hour (s.e.m.: 0.07) v. the SH-pigs with 4.6 fights per pen and hour (s.e.m.: 0.05). The fight duration of the GH-pigs with 10.3 s per pen and hour (s.e.m.: 1.07) was significantly lower in comparison to the SH-pigs with 18.8 s per pen and hour (s.e.m.: 1.06). The SH-pigs had more new skin lesions at the shoulders than the GH-pigs 48 h after weaning (P < 0.05). In conclusion, early mixing of unacquainted litters during lactation had no influence on their growth performance during rearing but reduced agonistic behavior and lesion score difference during the first 2 days after weaning. No significant interaction between the farrowing system and weaning weight class was detected with regard to growth performance and NF.     

Risk factors and milk yield losses associated with lameness in Holstein-Friesian dairy cattle

Weekly locomotion scores on a scale of 1 to 5 were used to investigate the relationship between cattle lameness, management systems and the impact of lameness on milk production. The data were 14026 locomotion scores from 248 Holstein-Friesian cows. Cows were managed in two groups, XE (high-concentrate feed and housed indoors all year) and XM (low-concentrate feed and outdoors in summer). Analysis was performed using residual maximum likelihood. Results indicated that the most significant variables affecting locomotion were time of year when the animal was locomotion scored and management group. Cows scored during February and August had increased locomotion problems. Cows in the more intensively managed group had significantly poorer locomotion compared with those in the more extensive group. Older animals were more susceptible to lameness than heifers. Body weight, body condition score and days in milk (DIM) also accounted for significant variation in locomotion score. Poor locomotion was associated with a significant reduction in the milk yield of later lactation cows. There was a significant difference in the shape of the lactation curve depending on whether or not the cow was lame during lactation. Average persistency was greater for the group of cows never lame throughout lactation compared with those lame before 60 DIM.     

Quality control and integration of genotypes from two calling pipelines for whole genome sequence data in the Alzheimer's disease sequencing project

The Alzheimer's Disease Sequencing Project (ADSP) performed whole genome sequencing (WGS) of 584 subjects from 111 multiplex families at three sequencing centers. Genotype calling of single nucleotide variants (SNVs) and insertion-deletion variants (indels) was performed centrally using GATK-HaplotypeCaller and Atlas V2. The ADSP Quality Control (QC) Working Group applied QC protocols to project-level variant call format files (VCFs) from each pipeline, and developed and implemented a novel protocol, termed “consensus calling,” to combine genotype calls from both pipelines into a single high-quality set. QC was applied to autosomal bi-allelic SNVs and indels, and included pipeline-recommended QC filters, variant-level QC, and sample-level QC. Low-quality variants or genotypes were excluded, and sample outliers were noted. Quality was assessed by examining Mendelian inconsistencies (MIs) among 67 parent-offspring pairs, and MIs were used to establish additional genotype-specific filters for GATK calls. After QC, 578 subjects remained. Pipeline-specific QC excluded ~12.0% of GATK and 14.5% of Atlas SNVs. Between pipelines, ~91% of SNV genotypes across all QCed variants were concordant; 4.23% and 4.56% of genotypes were exclusive to Atlas or GATK, respectively; the remaining ~0.01% of discordant genotypes were excluded. For indels, variant-level QC excluded ~36.8% of GATK and 35.3% of Atlas indels. Between pipelines, ~55.6% of indel genotypes were concordant; while 10.3% and 28.3% were exclusive to Atlas or GATK, respectively; and ~0.29% of discordant genotypes were. The final WGS consensus dataset contains 27,896,774 SNVs and 3,133,926 indels and is publicly available.     

Recent advancement in the discovery and development of COX-2 inhibitors: Insight into biological activities and SAR studies (2008–2019)

Cyclooxygenase-2 is a very important physiological enzyme playing key roles in various biological functions especially in the mechanism of pain and inflammation, among other roles, making it a molecule of high interest to the pharmaceutical community as a target. COX 2 enzyme is induced only during inflammatory processes or cancer and reflects no role in the guarding stomach lining. Thus, selective COX-2 inhibition can significantly reduce the adverse effects including GI tract damage and hepatotoxic effects of traditional NSAIDs like aspirin, ibuprofen, etc. Recent developments on COX-2 inhibitors is primarily focused on improving the selectivity index of the drug towards COX-2 along with enhancing the potency of the drug by modifying the scaffolds of Coxibs currently in the market like Celecoxib, Indomethacin, Oxaprozin, etc. We have reported the progress on new COX-2 inhibitors in the last decade (2008–2019) focussing on five heterocyclic rings- Pyrazole, Indole, Oxazole, Pyridine and Pyrrole. The addition of various moieties to these core rings and their structure-activity relationship along with their molecular modelling data have been explored in the article. This review aims to aid medicinal chemists in the design and discovery of better COX-2 inhibitors constructed on these five heterocyclic pharmacophores.