股骨转子间骨折的稳定性重建概念演化与研究进展

目的总结近年来股骨转子间骨折在稳定性重建方面的概念演化与研究进展。方法查阅国内外相关文献并结合自身经验，从股骨转子间骨折的解剖特点、稳定型骨折与不稳定型骨折分类、稳定性复位与不稳定性复位、术中加压初始稳定与术后滑动二次稳定、内固定术后稳定性评估、早期下地站立负重等方面进行总结分析。结果股骨转子间骨折发生于股骨颈干骺端转换区，具有天然的内翻不稳定倾向。骨折复位质量是影响后续内固定物安放的最重要前提因素。判断骨折复位质量有对线和对位两方面，对线采用 Garden 指数；在对位方面，随着皮质对位理念（正性、中性、负性）的提出，特别强调前内侧皮质的相互砥住支撑（解剖、正性），是获得骨折稳定性复位的关键，而不再强调后内侧小转子骨块的作用。术后影像学的稳定性评分为早期下地站立负重提供了量化指标。但术中的前内侧皮质支撑复位，在术后头颈骨块滑动获得二次稳定的过程中，仍有皮质对位丢失现象，需研究其危险因素和防范措施。结论股骨转子间骨折在取得良好对线的基础上，只要获得了前内侧皮质的相互砥住和支撑，并用内固定器械维持住，就获得了术后稳定性。术后稳定性评分优良者，可以安全地早期下地负重、站立行走活动。     

Similarities between interstitial cystitis/bladder pain syndrome and vulvodynia: implications for patient management

Interstitial cystitis/bladder pain syndrome (IC/BPS) and vulvodynia are chronic pain syndromes that appear to be intertwined from the perspectives of embryology, pathology and epidemiology. These associations may account for similar responses to various therapies.     

Dissecting the biological heterogeneity of HER2-positive breast cancer

HER2-positive (HER2+) breast cancer (BC) is a heterogenous and multifaceted disease, with interesting therapeutic implications. First, all intrinsic molecular subtypes can be identified in HER2+ tumors, with the HER2-enriched being the most frequent. Such subtypes do not differ much from their counterparts in HER2-negative disease, apart for the high expression of genes in/near the HER2 amplicon on chromosome 17. Intrinsic subtyping, along with the quantification of ERBB2 mRNA levels, is associated with higher rates of pathologic complete response across neoadjuvant trials of dual HER2 blockade and might help select patients for de-escalation and escalation treatment strategies. Secondly, HER2+ tumors have a broad range of DNA alterations. ERBB2 mutations and alterations in the PI3K/Akt/mTOR pathway are among the most frequent and might predict benefit from potent pan-HER, PI3K and mTOR inhibitors. Moreover, HER2+ tumors are usually infiltrated by lymphocytes. These tumor infiltrating-lymphocytes (TILs) predict response to neoadjuvant anti-HER2-based treatment and exert a prognostic role. PD-L1, detected in ∼42 % of HER2+ BC, might also be useful to define patients responding to novel anti-PD1/PD-L1 immunotherapies. New multiparametric clinicopathologic and genomic tools accounting for this complexity, such as HER2DX, are under development to define more tailored treatment approaches. Finally, HER2-targeted antibody-drug conjugates (ADC) such as trastuzumab deruxtecan might be active in tumors with low expression of HER2. Overall, there is a need to molecularly characterize and develop novel targeted therapies for HER2+ disease.     

Development of an IgG-Fc fusion COVID-19 subunit vaccine,AKS-452

AKS-452 is a biologically-engineered vaccine comprising an Fc fusion protein of the SARS-CoV-2 viral spike protein receptor binding domain antigen (Ag) and human IgG1 Fc (SP/RBD-Fc) in clinical development for the induction and augmentation of neutralizing IgG titers against SARS-CoV-2 viral infection to address the COVID-19 pandemic. The Fc moiety is designed to enhance immunogenicity by increasing uptake via Fc-receptors (FcγR) on Ag-presenting cells (APCs) and prolonging exposure due to neonatal Fc receptor (FcRn) recycling. AKS-452 induced approximately 20-fold greater neutralizing IgG titers in mice relative to those induced by SP/RBD without the Fc moiety and induced comparable long-term neutralizing titers with a single dose vs. two doses. To further enhance immunogenicity, AKS-452 was evaluated in formulations containing a panel of adjuvants in which the water-in-oil adjuvant, Montanide™ ISA 720, enhanced neutralizing IgG titers by approximately 7-fold after one and two doses in mice, including the neutralization of live SARS-CoV-2 virus infection of VERO-E6 cells. Furthermore, ISA 720-adjuvanted AKS-452 was immunogenic in rabbits and non-human primates (NHPs) and protected from infection and clinical symptoms with live SARS-CoV-2 virus in NHPs (USA-WA1/2020 viral strain) and the K18 human ACE2-trangenic (K18-huACE2-Tg) mouse (South African B.1.351 viral variant). These preclinical studies support the initiation of Phase I clinical studies with adjuvanted AKS-452 with the expectation that this room-temperature stable, Fc-fusion subunit vaccine can be rapidly and inexpensively manufactured to provide billions of doses per year especially in regions where the cold-chain is difficult to maintain.     

小分子抗血管生成药物在非小细胞肺癌中的研究进展

肺癌是世界上发病率最高的癌症之一，且尚无二线进展后的标准治疗方案，而肿瘤血管生成目前已被确定为恶性肿瘤的重要治疗靶点，小分子多靶点血管激酶抑制剂可通过抑制血管生成相关信号通路，抑制肿瘤血管的生成。目前已开展多项小分子抗血管生成药物治疗非小细胞肺癌的临床试验，且已有部分血管内皮生长因子受体酪氨酸激酶抑制剂（vascular endothelial growth factor receptor-tyrosine kinase inhibitors, VEGFR-TKIs）获批治疗晚期非小细胞肺癌，本文基于国内外多项小分子抗血管生成药物治疗非小细胞肺癌的发展现状，归纳了多个VEGFR-TKIs及成纤维细胞生长因子受体（fibroblast growth factor receptor, FGFR）-TKI单药或联合[包括分别与化疗、表皮生长因子受体（epidermal growth factor receptor, EGFR）-TKIs、免疫治疗、放疗等联合）]治疗非小细胞肺癌的疗效与安全性研究，同时探讨了VEGFR-TKIs可能存在的耐药机制及疗效预测指标等，并对未来抗血管治疗非小细胞肺癌的发展趋势以及存在的潜在问题进行展望，同时为肺癌后续的精准治疗及个体化治疗提供新的思路。     

Safety profile of the adjuvanted recombinant zoster vaccine: Pooled analysis of two large randomised phase 3 trials

Background

The ZOE-50 (NCT01165177) and ZOE-70 (NCT01165229) phase 3 clinical trials showed that the adjuvanted recombinant zoster vaccine (RZV) was ≥90% efficacious in preventing herpes zoster in adults. Here we present a comprehensive overview of the safety data from these studies.

臀部筋膜脂肪瓣修复坐骨结节和大转子复发性窦道型压疮

目的总结臀部筋膜脂肪瓣修复坐骨结节、大转子复发性窦道型压疮的效果。方法2018 年 2 月—2019 年 6 月，收治 12 例 13 处长期截瘫伴坐骨结节、大转子复发性窦道型压疮患者。其中男 10 例 11 处，女 2 例 2 处；年龄 46～56 岁，平均 51 岁。截瘫 10～20 年，平均 13 年；所有患者均有压疮手术史，术后 3 个月～12 年复发。其中坐骨结节处压疮 11 例，坐骨结节合并大转子处压疮 1 例。创面清创、切除窦道假性滑液囊，采用单侧或双侧臀部筋膜脂肪瓣填塞窦道，术区一期缝合闭合切口。结果术后 13 处压疮切口均Ⅰ期愈合，局部无红肿、渗液，术后 14 d 拆线出院。术后局部平坦，外观理想。术后患者均获随访，随访时间 8～24 个月，平均 14 个月。随访期间压疮均无复发。结论臀部脂肪组织丰富，利用筋膜脂肪瓣修复坐骨结节、大转子复发性窦道型压疮设计、操作简便，临床效果良好。     

分瓶法测定果蝇吸入麻醉药半数麻醉有效浓度

目的　建立测定果蝇吸入麻醉药半数麻醉有效浓度 (ED50 )的方法学。方法　在 11个 32 5ml的三角烧瓶中各放入 30只雄性果蝇 ,分别加入不同容量的异氟醚标准气 ,使 11个烧瓶中异氟醚浓度分布在零效应浓度与百分之百效应浓度之间。以果蝇失去附壁及运动能力为标准计算各瓶中被麻醉果蝇数 ,用正规法计算出ED50 。结果　 11次实验在 2 5及 5 0min时的量 -效关系曲线均呈S形 ,用各自的对数浓度与概率单位作图都呈直线相关 ,相关系数分别为 0 .972± 0 .0 14和 0 .971± 0 .0 2 5 ,ED50 值分别为 (0 .5 1± 0 .0 6 8) %和 (0 .4 7± 0 .0 85 ) % ,变异系数分别为 13.3%和 18.0 %。结论　本法稳定性较好 ,实用可行     

酸枣仁提取物急性毒性实验研究

目的 观察酸枣仁醇提取物的急性毒性反应.方法 ①小鼠尾静脉注射不同剂量的酸枣仁醇提取物,连续观察14 d,记录小鼠的急性毒性反应,并计算LD50及LD50 95%可信限;②小鼠灌胃给药,测定一次给予酸枣仁醇提取物的安全剂量.结果 ①静脉注射酸枣仁醇提取物后,部分小鼠出现中毒反应并死亡,测得LD50为27.5 g·kg-1,LD50 95%可信限为25.1～30.1 g·kg-1,死亡动物尸检,其主要脏器未见病理改变.14 d后存活小鼠体重平均增加20.4%,略高于生理盐水组(18.2%).②小鼠灌胃给药(340 g·kg-1,相当于成人一次用量的326倍)后,连续观察14 d,小鼠全部存活,无明显毒性反应,小鼠体重平均增长17.2%.结论 酸枣仁醇提取物毒性很低,临床给药安全可靠.     

中国经络研究的现状分析

近年来，经络研究文章大量涌现，说明经络研究逐渐得到国内外同行的重视，已经成为具有竞争性和挑战意义的科学命题。从论文发表的期刊来看，中国仍然是开展经络研究的主要国家，但是没有形成具有广泛影响的科研成果，所以中国经络研究的总体科研环境和研究氛围没有得到根本性改善。笔者认为经络研究应包括中医学领域的经络研究、中西医结合领域的经络研究以及生物学领域的经络研究。当务之急是根据学科的不同，理清研究内容的归属。