乌司他丁干预对急性脑梗死患者血清D－二聚体、脑钠肽水平及认知功能的影响

目的：探讨乌司他丁干预对急性脑梗死患者血清D－二聚体、脑钠肽（brain natriuretic peptide,BNP）水平及认知功能的影响。方法：选取2012年1月—2013年1月急性脑梗死患者98例作为观察组,另选取30例健康自愿者作为对照组。观察组患者在基础治疗的基础上给予乌司他丁10万U静脉滴注,每8h给药1次,连续治疗7d。检测对照组人群和观察组患者治疗前和治疗1、3、5、7d时血清D－二聚体、BNP水平,并采用蒙特利尔认知评估量表对2组人群进行认知功能评价。结果：治疗前,观察组患者血清D－二聚体、BNP水平均明显高于对照组（P＜0．01）。观察组患者治疗3、5、7 d时血清D－二聚体、BNP水平均明显低于治疗前（P＜0．05）,并于治疗1 d时达到最高值[分别为（3．27±0．46）mg／L、（161．78±45．98）ng／ml],治疗7 d时达到最低值[分别为（1．67±0．76）mg／L、（109．67±31．78）ng／ml];观察组患者认知功能障碍发生率为28％（28．57％,28／98）。结论：乌司他丁干预可有效降低急性脑梗死患者血清D－二聚体、BNP水平,并可预防认知功能障碍的发生,是急性脑梗死的有效辅助治疗方法,值得临床推广。     

尼可地尔治疗冠心病不稳定型心绞痛的临床效果及安全性研究

目的 探究冠心病不稳定型心绞痛患者应用尼可地尔治疗的临床疗效及安全性。方法 选取2019年10月至2020年9月福建医科大学附属南平第一医院的82例冠心病不稳定型心绞痛患者作为研究对象,采用随机数字表法将其分为对照组和研究组（各41例）。对照组患者采用常规治疗,研究组患者采用对照组基础上联合尼可地尔治疗。比较两组患者的临床疗效、心绞痛发作次数及持续时间、不良反应发生率、不良心血管事件发生率。结果研究组治疗总有效率高于对照组,差异有统计学意义（P<0.05）;两组患者治疗前心绞痛发作次数、持续时间比较,差异无统计学意义（P>0.05）,两组患者治疗后心绞痛发作次数、持续时间低于治疗前,且研究组治疗后心绞痛发作次数、持续时间低于对照组,差异有统计学意义（P<0.05）;两组患者腹泻、恶心呕吐、头痛等不良反应发生率比较,差异无统计学意义（P>0.05）,且经对症处理后所有不良反应均缓解;两组不良心血管事件发生率比较,差异无统计学意义（P>0.05）。结论 针对冠心病不稳定型心绞痛患者应用尼可地尔治疗,能显著改善患者胸闷、胸痛、乏力等症状,缓解心绞痛的发作,改善心...     

Safety and efficacy of anti-EGFR monoclonal antibody (SCT200) as second-line therapy in advanced esophageal squamous cell carcinoma

Objective: The mainstay treatment of esophageal squamous cell carcinoma(ESCC) involves chemotherapy and immunotherapy. However, alternative therapies are required for patients who are refractory or intolerant to existing therapies.Methods: In this single-arm, multicenter, open-label phase Ib study, 30 patients received an intravenous infusion of SCT200, an antiepidermal growth factor receptor(EGFR) monoclonal antibody, 6.0 mg/kg once a week for 6 weeks, followed by 8.0 mg/kg once every 2 weeks u...     

First-line nivolumab plus chemotherapy vs chemotherapy in patients with advanced gastric,gastroesophageal junction and esophageal adenocarcinoma: CheckMate 649 Chinese subgroup analysis

First-line chemotherapy for advanced/metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric/gastroesophageal junction cancer (GC/GEJC) has poor median overall survival (OS; <1 year). We report efficacy and safety results from Chinese patients in the phase III global CheckMate 649 study of nivolumab plus chemotherapy vs chemotherapy for the first-line treatment of GC/GEJC/esophageal adenocarcinoma (EAC). Chinese patients with previously untreated advanced or metastatic GC/GEJC/EAC were randomized to receive nivolumab (360 mg Q3W or 240 mg Q2W) plus chemotherapy (XELOX [capecitabine and oxaliplatin] Q3W or FOLFOX [oxaliplatin, leucovorin and 5-fluorouracil] Q2W), nivolumab plus ipilimumab (not reported) or chemotherapy alone. OS, blinded independent central review-assessed progression-free survival (PFS), objective response rate (ORR), duration of response (DOR) and safety are reported. Of 1581 patients enrolled and randomized, 208 were Chinese. In these patients, nivolumab plus chemotherapy resulted in clinically meaningful improvement in median OS (14.3 vs 10.2 months; HR 0.61 [95% CI: 0.44-0.85]), median PFS (8.3 vs 5.6 months; HR 0.57 [95% CI: 0.40-0.80]), ORR (66% vs 45%) and median DOR (12.2 vs 5.6 months) vs chemotherapy, respectively. The safety profile was acceptable, with no new safety signals observed. Consistent with results from the global primary analysis of CheckMate 649, nivolumab plus chemotherapy demonstrated a clinically meaningful improvement in OS and PFS and higher response rate vs chemotherapy and an acceptable safety profile in Chinese patients. Nivolumab plus chemotherapy represents a new standard first-line treatment for Chinese patients with non-HER2-positive advanced GC/GEJC/EAC.     

The Combination of Glycolytic Inhibitor 2-Deoxyglucose and Microbubbles Increases the Effect of 5-Aminolevulinic Acid-Sonodynamic Therapy in Liver Cancer Cells

Sonodynamic therapy (SDT) overcomes the shortcoming of photodynamic therapy in the treatment of cancer. Previous studies indicated that the glycolysis inhibitor 2-deoxyglucose (2-DG) potentiated photodynamic therapy induced tumor cell death and microbubbles (MBs) improved the SDT performance. We hypothesized that the combination of 2-DG and MBs will increase the effect of 5-aminolevulinic acid (ALA)-SDT in HepG2 liver cancer cells. When cells were treated with 5-min ALA-SDT and 2-mmol/L 2-DG, the cell survival rate decreased to 73.0 ± 7.1% and 75.2 ± 7.9%, respectively. Furthermore, 2 mmol/L 2-DG increased 5-min ALA-SDT induced growth inhibition and augmented ALA-SDT induced cell apoptotic rate from 9.8 ± 0.7% to 17.4 ± 2.2%. In the combination group (2-DG and ALA-SDT group), HepG2 cells possessed typical apoptotic characters. 2-DG also increased ALA-SDT associated intracellular reactive oxygen species generation and loss of mitochondrial membrane potential. Moreover, SonoVue MBs had stimulatory function on cell viability inhibition, apoptosis, reactive oxygen species production and mitochondrial membrane potential loss for combination treatment. This study suggests a promising therapeutic strategy using a combination of 2-DG, MBs and ALA-SDT for treating liver cancer.     

DNA Duplexes with Hydrophobic Modifications Inhibit Fusion between HIV-1 and Cell Membranes

Discovery of new drugs for the treatment of AIDS typically possessing unique structures associated with novel mechanisms of action has been of great importance due to the quick drug-resistant mutations of HIV-1 strains. The work presented in this report describes a novel class of DNA duplex-based HIV-1 fusion inhibitors. Hydrophobic groups were introduced into a DNA duplex skeleton either at one end, at both ends, or in the middle. These modified DNA duplexes inhibited fusion between HIV-1 and human cell membranes at micro- or submicromolar concentrations. Respective inhibitors adopted an aptamer pattern instead of a base-pairing interaction pattern. Structure-activity relationship studies of the respective DNA duplexes showed that the rigid and negatively charged DNA skeletons, in addition to the presence of hydrophobic groups, were crucial to the anti-HIV-1 activity of these compounds. A fluorescent resonance energy transfer (FRET)-based inhibitory assay showed that these duplex inhibitors interacted with the primary pocket in the gp41 N-terminal heptad repeat (NHR) instead of interacting with the lipid bilayers.     

中性粒细胞与淋巴细胞比值在肺部常见疾病中的研究进展

中性粒细胞与淋巴细胞比值(NLR)是指外周血中中性粒细胞与淋巴细胞的比值,是近年来不断受到重视的一种新型炎症指标,它反映了外周血中中性粒细胞与淋巴细胞的动态平衡,被应用于许多疾病的诊断、严重程度及预后评估。本文综述了NLR在肺部常见疾病中的研究进展,旨在提高临床医师对NLR的认识。     

Clinical Guideline for Microwave Ablation of Bone Tumors in Extremities

Microwave ablation has been used to treat bone tumors in extremities for more than 30 years. With improved recognition, updated microwave equipment, and expanded clinical application, microwave ablation has recently been widely used to treat bone tumors. To standardize the application of microwave ablation in the clinical treatment of bone tumors in the limbs, research results and clinical experience involving the use of microwave ablation to treat bone tumors in the limbs have been summarized, and a clinical guideline has been designed. This guideline is aimed at providing a reliable clinical basis for indications, preoperative evaluation and decision‐making, perioperative treatment, complications, and other issues via evidence‐based medicine. Two aspects are considered—percutaneous microwave ablation and intraoperative microwave ablation of bone tumors in extremities. Ultimately, the guideline is intended to standardize treatment and improve the clinical efficacy of microwave ablation of bone tumors in extremities.     

早产儿、低出生体重儿喂养方式与体重增长关系的探讨

目的探讨早产儿、低出生体重儿喂养方式与体重增长关系。方法选择 98例早产儿 ,分成三组 ,一组采用静脉内营养 ,其余两组在消化道喂养同等条件下 ,对其中一组采取头高脚低 (成 2 0°角 )斜坡位。结果观察组与对照组比较体重增长有明显差异 (P <0 .0 5) ;消化道喂养组与静脉内营养组比较体重增长无明显差异 (P >0 .0 5)。结论通过对早产儿及低出生体重儿喂养方式的改进 ,配合全面的综合护理 ,可防止生理性体重下降和维持正常体重的增长。     

A novel 1,2-benzenediamine derivative FC-99 suppresses TLR3 expression and ameliorates disease symptoms in a mouse model of sepsis

Background and Purpose

Sepsis is a clinical condition characterized by overwhelming systemic inflammation with high mortality rate and high prevalence, but effective treatment is still lacking. Toll-like receptor 3 (TLR3) is an endogenous sensor, thought to regulate the amplification of immune response during sepsis. Modulators of TLR3 have an advantage in the treatment of sepsis. Here, we aimed to explore the mechanism of a monosubstituted 1,2-benzenediamine derivative FC-99 {N¹-[(4-methoxy)methyl]-4-methyl-1,2-benzenediamine}on modulating TLR3 expression and its therapeutic potential on mouse model of sepsis.

Experimental Approach

Cells were pretreated with FC-99 followed by poly(I:C) or IFN-α stimulation; TLR3 and other indicators were assayed. Female C57BL/6 mice were subjected to sham or caecal ligation puncture (CLP) surgery after i.p. injection of vehicle or FC-99; serum and tissues were collected for further experiments.

Key Results

FC-99 suppressed inflammatory response induced by poly(I:C) with no effect on cell viability or uptake of poly(I:C). FC-99 also inhibited TLR3 expression induced by not only poly(I:C) but also by exogenous IFN-α. This inhibition of FC-99 was related to the poly(I:C)-evoked IRF3/IFN-α/JAK/STAT1 signalling pathway. In CLP-induced model of sepsis, FC-99 administration decreased mice mortality and serum levels of inflammatory factors, attenuated multiple organ dysfunction and enhanced bacterial clearance. Accordingly, systemic and local expression of TLR3 was reduced by FC-99 in vivo.

Conclusion and Implications

FC-99 reversed TLR3 expression and ameliorate CLP-induced sepsis in mice. Thus, FC-99 will be a potential therapeutic candidate for sepsis.Table of Links