外伤性青光眼引流阀植入术与小梁切除术的疗效对比

目的:比较Ahmed引流阀植入术与小梁切除术治疗外伤性青光眼的效果。方法:前瞻性研究。选取2014年3月至2019年3月杭州市余杭第一人民医院外伤性青光眼120例(124眼),随机分为两组,A组60例(62眼),进行小梁切除术;B组60例(62眼),进行Ahmed引流阀植入术。术后随访12个月,比较两组手术疗效。结果:...     

结核分枝杆菌HSP 65亚单位疫苗和基因疫苗的构建及免疫学特性

目的:构建HSP 65蛋白的亚单位疫苗和基因疫苗,并与BCG相比较,评价这两种疫苗在小鼠体内的免疫学特性.方法:从结核分枝杆菌H37Rv基因组中扩增出hsp 65基因,连接进入pMD18-T载体中,测序后,利用不同酶切位点将完整的hsp 65基因分别克隆到pProEX HTb原核表达载体和pcDNA3.1(-)真核表达载体,前者在大肠杆菌中诱导表达,经SDS-PAGE和Western Blot分析后,用Ni-NTA亲和层析柱进行纯化;后者通过阳离子聚合物瞬转P815细胞,用间接免疫荧光检测细胞内HSP 65蛋白的表达.用上述原核表达蛋白和真核质粒(分别为亚单位疫苗和基因疫苗)免疫BALB/c小鼠,ELISA测定特异性抗体的滴度,MTT测定脾淋巴细胞特异性增殖指数.结果:获得的结核分枝杆菌hsp 65基因序列与GenBank公布的完全一致;Western Blot结果显示,在M<,r>约65000处有与鼠抗HSP 65 mAb和临床结核患者血清的特异性结合带;免疫荧光结果显示转染重组质粒的P815细胞的表达蛋白与HSP 65 mAb有特异性结合.两种疫苗免疫小鼠体内产生特异性抗体,经蛋白刺激后可引起脾淋巴细胞特异性增殖.结论:所构建的两种疫苗能引起免疫动物的特异性体液和细胞免疫反应,应进一步研究其抵抗结核分支杆菌感染的保护力机制,以用于结核病的防治研究.     

肠间质细胞和神经生长因子受体及一氧化氮合酶在先天性巨结肠的分布及意义

目的:探讨肠间质细胞(ICC)、神经生长因子受体(NGFR)及一氧化氮合酶(NOS)与先天性巨结肠(HD)发病的关系.方法:应用c-kit及NGFR免疫组化法和NADPH黄递酶组化法观察10例HD患者病变结肠及8例对照组结肠ICC,NGFR及NOS的分布.结果:ICC密布于对照组结肠环肌浅表层及肌间神经丛周围并相互交织成网状结构,肠壁内含丰富的NGFR及NOS阳性神经节细胞和神经纤维.HD病变肠壁内ICC数量减少、网状结构破坏,缺乏NGFR及NOS阳性神经节细胞和神经纤维.结论:ICC,NGFR及NOS的异常分布可能与HD无神经节细胞结肠的舒张功能障碍有关.     

皮肤老化的几种常见细胞和富血小板血浆治疗进展

皮肤抗老化领域的细胞治疗技术自问世以来,经历多次更新和优化,目前临床上公认安全性和效果较好的细胞治疗制剂包括脂肪干细胞及其培养基提取物、成纤维细胞、皮肤间充质干细胞以及富血小板浓缩物、富血小板血浆制剂等.然而,针对这些制剂的作用机制及优缺点还缺乏系统的总结,本文将对此进行详细阐述.     

A phase I randomized,double‐blind,single subcutaneous dose escalation study to determine the safety,tolerability, and pharmacokinetics of rezafungin in healthy adult subjects

Rezafungin is a novel echinocandin being developed for the treatment and prevention of invasive fungal infections. The objectives of this randomized, double‐blind study in healthy adults were to determine the safety, tolerability, and pharmacokinetics of rezafungin after subcutaneous (s.c.) administration. The study design consisted of six sequential cohorts of eight subjects, except for the first cohort with four subjects. The subjects were randomized in a 3:1 ratio of rezafungin to placebo and were to receive a single dose of 1, 10, 30, 60, 100, or 200 mg. The most common adverse events (AEs) were increased alanine aminotransferase and sinus bradycardia (unsolicited) and erythema at the injection site (solicited). Unsolicited AEs were generally mild to moderate and not rezafungin‐related. Although the study was terminated after the 10 mg dose cohort due to concerns of potential increased severity of injection site reactions, no predetermined dose escalation halting criteria were met. Following the 10 mg single s.c. dose of rezafungin (n = 6), the geometric mean (GM) maximum concentration (C _max) was 105.0 ng/ml and the median time to C _max was 144 h. The GM area under the concentration‐time curve was 32,770 ng*h/ml. The median estimated terminal half‐life was 193 h. The GM apparent oral clearance was 0.255 L/h and the GM apparent volume of distribution was 68.5 L. This study demonstrates that a single s.c. dose of rezafungin in healthy adult subjects: (1) did not result in serious AEs, death, or withdrawal from the study due to an AE; and (2) produced a pharmacokinetic profile with long exposure period postadministration. In an effort to reduce the occurrence of injection site reactions, a re‐evaluation of the rezafungin s.c. formulation could be considered in the future.

Study Highlights

• WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?

Currently marketed antifungal agents of the echinocandin class are dosed by i.v. once daily and are therefore not practical for prolonged or outpatient prophylaxis. Rezafungin is an investigational echinocandin (currently in phase III trials studying once‐weekly i.v. administration) that has excellent activity against clinically relevant Candida and Aspergillus spp. and Pneumocystis jirovecii, a prolonged half‐life allowing for longer dosing intervals, and a stability/solubility profile that allows for the possibility of subcutaneous (s.c.) dosing.

• WHAT QUESTION DID THE STUDY ADDRESS?

The objectives of this randomized, double‐blind study in healthy adults were to determine the safety, tolerability, and pharmacokinetics (PKs) of rezafungin after s.c. administration.

• WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?

This study provided safety data regarding s.c. administration of rezafungin. Despite common solicited injection site reactions, s.c. administration of 10 mg of rezafungin did not result in serious adverse event (AEs), death, or withdrawals due to an AE in healthy adult subjects. The study also showed that rezafungin had a PK profile with a long exposure period.

• HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?

In an effort to reduce the occurrence of injection site reactions, these findings may lead to a future re‐evaluation of the s.c. formulation of rezafungin.     

胰高血糖素样肽-1受体激动剂治疗多囊卵巢综合征患者有效性与安全性的Meta分析

目的 评价胰高血糖素样肽-1(glucagon like peptide-1,GLP-1)受体激动剂与二甲双胍治疗多囊卵巢综合征(polycystic ovarian syndrome,PCOS)的有效性与安全性.方法 计算机检索英文数据库PubMed、CENTRAL(2020年第3期)、EMbase;中文数据库Wan...     

An integrated strategy for the comprehensive profiling of the chemical constituents of Aspongopus chinensis using UPLC-QTOF-MS combined with molecular networking

ContextThe extracts of Aspongopus chinensis Dallas (Pentatomidae), an insect used in traditional Chinese medicine, have a complex chemical composition and possess multiple pharmacological activities.ObjectiveThis study comprehensively characterizes the chemical constituents of A. chinensis by an integrated targeted and untargeted strategy using UPLC-QTOF-MS combined with molecular networking.Materials and methodsThe ultra-performance liquid chromatography-tandem quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) combined with molecular networking-based dereplication was proposed to facilitate the identification of the chemical constituents of aqueous and ethanol extracts of A. chinensis. The overall strategy was designed to avoid the inefficiency and costliness of traditional techniques. The targeted compounds discovered in the A. chinensis extracts were identified by searching a self-built database, including fragment ions, precursor ion mass, and other structural information. The untargeted compounds were identified by analyzing the relationship between different categories, fragmentation pathways, mass spectrometry data, and the structure of the same cluster of nodes within the molecular network. The untargeted strategy was verified using commercial standard samples under the same mass spectrometry conditions.ResultsThe proposed integrated targeted and untargeted strategy was successfully applied to the comprehensive profiling of the chemical constituents of aqueous and ethanol extracts of A. chinensis. A total of 124 compounds such as fatty acids, nucleosides, amino acids, and peptides, including 74 compounds that were reported for the first time, were identified in this study.ConclusionsThe integrated strategy using LC tandem HRMS combined with molecular networking could be popularised for the comprehensive profiling of chemical constituents of other traditional insect medicines.     

反射式共聚焦显微镜在海姆泊芬光动力疗法治疗紫红型鲜红斑痣疗效评估中的应用

目的:探讨反射式共聚焦显微镜（RCM）在评估海姆泊芬光动力疗法治疗鲜红斑痣临床疗效中的应用价值。方法:2018年4月至2020年1月在武汉市第一医院皮肤科收集面中部紫红型鲜红斑痣患者39例,采用海姆泊芬光动力疗法治疗3次。首次治疗前及海姆泊芬光动力疗法治疗3次后3~6个月皮损拍照后,使用RCM检测皮损内100 μm深度...     

免疫标记和BRAF V600E突变联合检测在细胞学诊断不确定甲状腺结节中的应用

目的评估免疫标记半乳糖凝集素-3 (Gal-3)、细胞角蛋白-19 (CK-19)、间皮细胞角蛋白-1 (HBME-1)和BRAF V600E突变联合检测对术前甲状腺细胞学诊断不确定结节的良恶甄别作用。方法选取四川大学华西医院2014年12月至2019年3月术前细胞学诊断不确定的甲状腺结节患者992例为研究对象,其中行3项免疫标记和/或BRAF V600E突变辅助检测的314例患者为观察组,未行上述辅助检测的678例为对照组,以术后病理学诊断评估上述检测单独或联合应用辅助技术的诊断价值。结果观察组术后恶性率高于对照组(P<0.001)。观察组中,195例患者行Gal-3、CK-19和HBME-1的免疫标记检测,301例患者行BRAF V600E突变检测,其中仅182例患者行3项免疫标记和BRAF V600E突变联合分析。对于单个检测,BRAF V600E突变和CK-19的特异性和敏感性最高,分别为100.0%和90.6%,当联合使用时诊断效能明显提高。BRAF V600E突变检测、Gal-3和CK-19组合的诊断效果最好,准确率最高达92.9%,该组合术前正确分类了168个恶性结...     

灵芪胶囊对H22荷瘤小鼠p53和bcl-2蛋白表达的影响

目的：探讨灵芪胶囊对H22荷瘤小鼠的抑瘤作用及其抑瘤作用机制。方法：采用体内实验法,于无菌条件下抽取传代7d、生长良好的H22荷瘤小鼠腹水,无菌0．9％氯化钠溶液1：3稀释（约含瘤细胞2×10^6／ml）,按0．2ml／7,接种于消毒后的小鼠右前肢腋部皮下,制成肿瘤模型,灌胃给药灵芪胶囊11d后,称取小鼠体重,脱椎处死小鼠,取脾脏及胸腺称重并计算胸腺指数和脾脏指数。用免疫组化法检测各组凋亡相关基因突变型p53和bcl-2基因的表达。结果：灵芪胶囊在明显抑制肿瘤生长的同时不降低体重,在一定剂量对荷瘤动物的免疫器官指数无明显影响;灵芪胶囊三个剂量组突变型p53基因和bcl-2基N的表达均低于模型组。结论：灵芪胶囊对H22荷瘤小鼠有明显抑瘤作用,其机制可能与抑制突变型p53基N和bcl-2基因表达有关。