Design, synthesis, and in vitro biological evaluation of 1H-1,2,3-triazole-4-carboxamide derivatives as new anti-influenza A agents targeting virus nucleoprotein

The influenza virus nucleoprotein (NP) is an emerging target for anti-influenza drug development. Nucleozin (1) and its closely related derivatives had been identified as NP inhibitors displaying anti-influenza activity. Utilizing 1 as a lead molecule, we successfully designed and synthesized a series of 1H-1,2,3-triazole-4-carboxamide derivatives as new anti-influenza A agents. One of the most potent compounds, 3b, inhibited the replication of various H3N2 and H1N1 influenza A virus strains with IC(50) values ranging from 0.5 to 4.6 μM. Compound 3b also strongly inhibited the replication of H5N1 (RG14), amantidine-resistant A/WSN/33 (H1N1), and oseltamivir-resistant A/WSN/1933 (H1N1, 274Y) virus strains with IC(50) values in sub-μM ranges. Further computational studies and mechanism investigation suggested that 3b might directly target influenza virus A nucleoprotein to inhibit its nuclear accumulation.     

气泡式鼻塞持续气道正压通气预防及治疗新生儿呼吸窘迫综合征的临床分析

目的探讨气泡式鼻塞持续气道正压通气（BNCPAP）早期应用于预防和治疗新生儿呼吸窘迫综合征（NRDS）的l临床疗效。方法选取2010年1月～2011年4月于本院分娩后30rain内转入我科的58例早产儿为研究对象,分为预防组30例（治疗前未出现呼吸窘迫症状）和治疗组28例（治疗前出现呼吸窘迫症状）,两组均于出生后30min内应用BNCPAP来预防和治疗NRDS,观察两组患儿的治疗效果,对其相关数据进行统计分析及比较。结果预防组预防成功率92_3％,预防后2h、12h、24hPa02／Fi02、PaC02值与预防前相比较有显著性差异（P〈0．05）,预防后2h、12hpH值与预防前相比较无显著性差异（P〉0．05）,预防后24hpH值与预防前相比较有显著性差异（P〈0．05）;治疗组治疗成功率89．3％,治疗后2h、12h、24hPa02／Fi02、PaC02值与治疗前相比较有显著性差异（P〈0．05）,治疗后2hpH值与治疗前相比较无显著性差异（P〉0．05）,治疗后12h、24hpH值与治疗前相比较有显著性差异（P〈0．05）。结论早期应用气泡式鼻塞持续气道正压通气（BNCPAP）预防和治疗早产儿呼吸窘迫综合征（NRDS）疗效显著,值得临床上合理推广应用。     

热量限制联合心理引导及高压氧治疗协同改善胶质母细胞瘤患者预后的前瞻性研究

目的 探讨热量限制联合心理引导及高压氧治疗对胶质母细胞瘤(GBM)全切术后患者预后的影响.方法 将45例行GBM全切术患者分为试验组(15例)和对照组(30例),手术时间为2007年11月至2011年5月,术后均经普通放疗+化疗(替莫唑胺150 mg/m2,5/28 d方案,即第1～5天用化疗药,第6 ～ 28天休息).试验组行热量限制联合心理引导及高压氧治疗,其中2例血管内皮生长因子(VEGF)++患者加行贝伐珠单抗治疗(5 mg/kg,2周1次,连续4次),1例第2次手术术中应用卡莫司汀贴片.对照组患者自行设计饮食,不进行心理引导,行放疗+化疗(方案同试验组),其中3例VEGF++患者加行贝伐珠单抗治疗(方案同试验组),2例第2次手术术中应用卡莫司汀贴片.比较2组患者生存时间,分析患者年龄、性别、肿瘤体积、肿瘤累及脑叶数量、肿瘤位于优势半球与否、手术次数、67蛋白标记指数(Ki-67)、6-氧-甲基鸟嘌呤DNA甲基转移酶(MGMT)、VEGF阳性率、卡莫司汀贴片、贝伐珠单抗与GBM患者预后的相关性.结果 与对照组比较,试验组生存期延长,差异有统计学意义[(35±13)个月比(19±11)个月,P =0.000].热量限制联合心理引导及高压氧治疗和手术次数与患者生存期呈正相关(r=0.559,P=0.000;r =0.313,P=0.036);肿瘤体积与生存期呈负相关(r=-0.436,P=0.003);Ki67、MGMT、VEGF的阳性率与患者生存期呈负相关(r=-0.497,P=0.001;r=-0.377,P=0.011;r=-0.540,P=0.000);患者年龄、性别、肿瘤累及脑叶数量及肿瘤是否位于优势半球与生存期无相关性(r=0.166,P=0.276,r=0.134,P=0.380;r =0.005,P=0.972;r =0.018,P=0.908);术中应用卡莫司汀贴片和术后应用贝伐珠单抗并不能延长患者生存期(r =0.144,P=0.345;r =0.098,P=0.522).结论 热量限制联合心理引导及高压氧治疗可以明显延长GBM患者的生存期;肿瘤体积越大、患者生存期越短;手术次数越多,患者生存期越长;MGMT、Ki-67、VEGF阳性率越低,患者生存期越长;累及脑叶数量、年龄、性别对生存期无明显影响;术中应用卡莫司汀贴片和术后应用贝伐珠单抗不能延长GBM患者生存期.     

Temporal changes in MRI appearance of the prostate after focal ablation

Purpose

The purpose of our study was to retrospectively evaluate and categorize temporal changes in MRI appearances of the prostate in patients who underwent focal therapy with MRI follow-up.

Methods

The Institutional Review Board approved this retrospective study and waived the requirement for informed consent. Thirty-seven patients (median age 61; 48–70 years) with low-to-intermediate-risk, clinically organ-confined prostate cancer underwent focal ablation therapy from 2009 to 2014. Two radiologists reviewed post-treatment MRIs (n = 76) and categorized imaging features blinded to the time interval between the focal therapy and the follow-up MRI. Inter-reader agreement was assessed (kappa) and generalized linear regression was used to examine associations between an imaging feature being present/absent and days between ablation and MRI.

Results

Inter-reader agreement on MRI features ranged from fair to substantial. Edema was found present at earlier times after ablation (median 16–25 days compared to MRIs without edema, median 252–514 days), as was rim enhancement of the ablation zone (18–22.5 days vs. 409–593 days), a hypointense rim around the ablation zone on T2-weighted images (53-57.5 days vs. 279–409 days) and the presence of an appreciable ablation cavity (48.5–60 days vs. 613–798 days, all p < 0.05). Enhancement of the ablation zone/scar (553–731 days vs. 61.5–162 days) and the formation of a T2-hypointense scar were found to be present on later MRI scans (514–553 days vs. 29–32 days, one reader).

Conclusions

The MRI appearance of the prostate after focal ablation changes substantially over time. Identification of temporal patterns in the appearance of imaging features should help reduce image interpretation variability and errors when assessing post-therapeutic scans.

     

Evaluation of diffusion kurtosis and diffusivity from baseline staging MRI as predictive biomarkers for response to neoadjuvant chemoradiation in locally advanced rectal cancer

Abdominal Radiology - To evaluate the role of diffusion kurtosis and diffusivity as potential imaging biomarkers to predict response to neoadjuvant chemoradiation therapy (CRT) from baseline...     

血浆置换在脓毒症相关性弥漫性血管内凝血患者治疗中的应用

目的:观察血浆置换在脓毒症相关性DIC患者治疗中的临床疗效。方法:36例脓毒症相关性DIC患者,用随机数字表法随机分为血浆置换组(TPE)16例和对照组20例。两组患者均予抗休克、抗感染、CRRT清除炎症因子、补充凝血因子、升血小板等常规治疗。常规治疗为对照组,在常规治疗基础上行血浆置换治疗为TPE组。结果:TPE后48h、72h、后7d,TPE组血小板计数高于对照组,两组差异有统计学意义(P0.05);TPE后24h、48h、72h,TPE组PT低于对照组,两组差异有统计学意义(P0.05);TPE后6h、72h、7d,TPE组APTT低于对照组,两组差异有统计学意义(P0.05);TPE后6h、24h、48h、72h、7d,TPE组FIB高于对照组,两组差异有统计学意义(P0.05);TPE后6h、24h、48h、72h、7d,TPE组D二聚体低于对照组,两组差异有统计学意义(P0.05);TPE后24h、48h、72h、7d,TPE组APACHEⅡ评分低于对照组,两组差异有统计学意义(P0.05);TPE组ICU住院时间低于对照组,两组差异有统计学意义(P0.05);TPE组28d病死率低于对照组,两组差异有统计学意义(P0.05)。结论:常规治疗基础上联合TPE能改善脓毒症相关性DIC患者的凝血功能、升高血小板计数、降低APACHEⅡ评分,并减少ICU住院时间及28d病死率。