从国际非专利名称纵观全球生物药发展

生物药(bio-therapeutics)是指采用生物技术制备的、临床上用于疾病治疗的大分子生物制品,具有结构复杂、异质性高等特点,科学严谨的生物药通用名命名,是区分生物药物质基础的主要依据,也是药品生命周期管理的重要基础。世界卫生组织(World Health Organization,WHO)协调建立的国际非专利名称(International Nonproprietary Names,INN)是全球药物命名的标准化体系。从INN的起源,以及生物药INN的类别、发生与发展为主线,以较为详实的数据统计和分析,呈现了全球生物药的衍化进程,从不同的角度纵览生物药技术发展历程,对生物药的研发设计、技术标准及监管策略的考量均具有一定的参考意义。     

IL‐17A‐producing T cells exacerbate fine particulate matter‐induced lung inflammation and fibrosis by inhibiting PI3K/Akt/mTOR‐mediated autophagy

Fine particulate matter (PM2.5) is the primary air pollutant that is able to induce airway injury. Compelling evidence has shown the involvement of IL‐17A in lung injury, while its contribution to PM2.5‐induced lung injury remains largely unknown. Here, we probed into the possible role of IL‐17A in mouse models of PM2.5‐induced lung injury. Mice were instilled with PM2.5 to construct a lung injury model. Flow cytometry was carried out to isolate γδT and Th17 cells. ELISA was adopted to detect the expression of inflammatory factors in the supernatant of lavage fluid. Primary bronchial epithelial cells (mBECs) were extracted, and the expression of TGF signalling pathway‐, autophagy‐ and PI3K/Akt/mTOR signalling pathway‐related proteins in mBECs was detected by immunofluorescence assay and Western blot analysis. The mitochondrial function was also evaluated. PM2.5 aggravated the inflammatory response through enhancing the secretion of IL‐17A by γδT/Th17 cells. Meanwhile, PM2.5 activated the TGF signalling pathway and induced EMT progression in bronchial epithelial cells, thereby contributing to pulmonary fibrosis. Besides, PM2.5 suppressed autophagy of bronchial epithelial cells by up‐regulating IL‐17A, which in turn activated the PI3K/Akt/mTOR signalling pathway. Furthermore, IL‐17A impaired the energy metabolism of airway epithelial cells in the PM2.5‐induced models. This study suggested that PM2.5 could inhibit autophagy of bronchial epithelial cells and promote pulmonary inflammation and fibrosis by inducing the secretion of IL‐17A in γδT and Th17 cells and regulating the PI3K/Akt/mTOR signalling pathway.     

Monophosphoryl lipid A alleviated radiation-induced testicular injury through TLR4-dependent exosomes

Radiation protection on male testis is an important task for ionizing radiation-related workers or people who receive radiotherapy for tumours near the testicle. In recent years, Toll-like receptors (TLRs), especially TLR4, have been widely studied as a radiation protection target. In this study, we detected that a low-toxicity TLR4 agonist monophosphoryl lipid A (MPLA) produced obvious radiation protection effects on mice testis. We found that MPLA effectively alleviated testis structure damage and cell apoptosis induced by ionizing radiation (IR). However, as the expression abundance differs a lot in distinct cells and tissues, MPLA seemed not to directly activate TLR4 singling pathway in mice testis. Here, we demonstrated a brand new mechanism for MPLA producing radiation protection effects on testis. We observed a significant activation of TLR4 pathway in macrophages after MPLA stimulation and identified significant changes in macrophage-derived exosomes protein expression. We proved that after MPLA treatment, macrophage-derived exosomes played an important role in testis radiation protection, and specially, G-CSF and MIP-2 in exosomes are the core molecules in this protection effect.     

Challenges and Emerging Opportunities in High‐Mobility and Low‐Energy‐Consumption Organic Field‐Effect Transistors

Organic field‐effect transistors (OFETs) are the basic elements of organic circuits towards flexible, printable, and wearable electronics. Low‐energy‐consumption OFETs with high mobility are the prerequisite for practical applications. After 30 years of development, OFETs have progressed rapidly, from field‐effect materials to devices, and from individual device to small‐ and medium‐scale integration. Here, a brief retrospective of OFETs' development over the past decades, and the emerging opportunities and challenges from device physics, multifunctional materials to integrated application are presented.     

Double the Capacity of Manganese Spinel for Lithium‐Ion Storage by Suppression of Cooperative Jahn–Teller Distortion

The relatively low capacity and capacity fade of spinel LiMn₂O₄ (LMO) limit its application as a cathode material for lithium‐ion batteries. Extending the potential window of LMO below 3 V to access double capacity would be fantastic but hard to be realized, as it will lead to fast capacity loss due to the serious Jahn–Teller distortion. Here using experiments combined with extensive ab initio calculations, it is proved that there is a cooperative effect among individual Jahn–Teller distortions of Mn³⁺O₆ octahedrons in LMO, named as cooperative Jahn–Teller distortion (CJTD) in the text, which is the difficulty to access the capacity beyond one lithium intercalation. It is further proposed that the cationic disordering (excess Li at Mn sites and Li/Mn exchange) can intrinsically suppress the CJTD of Mn³⁺O₆ octahedrons. The cationic disordering can break the symmetry of Mn³⁺ arrangements to disrupt the correlation of distortions arising from individual JT centers and prevent the Mn³⁺? O bonds distorting along one direction. Interestingly, with the suppressed CJTD, the original octahedral vacancies in spinel LMO are activated and can serve as extra Li‐ion storage sites to access the double capacity with good reversible cycling stability in microsized LMO.     

白蛋白静脉滴注联合茵栀黄颗粒治疗新生儿黄疸血清 AKP、TBA、 FFA、γ-GT、HS-CRP的影响

目的:研究白蛋白静脉滴注联合茵栀黄颗粒对新生儿黄疸血清碱性磷酸酶(alkaline phosphatase,AKP)、总胆汁酸(totalbileacids,TBA)、游离脂肪酸(free fatty acid,FFA)、γ-谷氨酰基转移酶(γ-glutamyltransferase,γ-GT)、超敏C-反应蛋白(hypersensitive C-reactive protein, HS-CRP)的影响。方法:选择2016年1月～2019年1月我院收治的95例新生儿病理性黄疸患儿,随机分为两组。对照组服用茵栀黄颗粒治疗,观察组在服用茵栀黄的基础上静脉滴注白蛋白治疗。检测两组的血清间接胆红素(indirectreacting bilirubin,,IBIL)、总胆红素(total bilirubin,TBIL)和AKP、TBA、FFA、y-GT、HS-CRP水平。结果:观察组的有效率明显高于对照组(P0.05);两组治疗后的血清IBIL、TBIL水平明显降低(P0.05),观察组的IBIL、TBIL水平明显低于对照组(P0.05);两组治疗后的血清AKP、TBA、FFA、γ-GT、HS-CRP水平明显降低(P0.05),观察组的血清AKP、TBA、FFA、γ-GT、HS-CRP水平明显低于对照组(P0.05)。结论:白蛋白静脉滴注联合茵栀黄颗粒对新生儿黄疸的治疗效果良好,有助于促进血清胆红素和其他血清学相关指标恢复正常,且安全性好。     

持续颅内压监测对大面积脑梗死外科治疗预后的应用价值

目的:探讨持续颅内压(ICP)监测对大面积脑梗死外科治疗预后的应用价值。方法:选取2013年3月至2018年3月期间在我院接受治疗的大面积脑梗死患者100例作为研究对象,所有患者经去骨瓣减压术后行ICP监测和生命体征监测,通过结果分为:低压组62例(2.70kPa≤ICP5.30kPa),高压组38例(ICP≥5.30 kPa)。记录患者ICP监测数值,接收者操作特征(ROC)曲线分析患者预后情况,对患者进行术后3个月内随访,了解患者平常活动能力进行判断预后的状况。观察ICP与预后的相关性。结果:两组患者性别、年龄、室速、室性早搏、糖尿病、高血压病、脑卒中、高脂血症、风心病、冠心病、扩张性心肌病、既往心肌梗死、肥厚性心肌病、甲亢性心脏病等资料比较差异无统计学意义(P0.05)。低压组患者中预后良好的ICP监测值显著低于预后不良者(P0.05),高压组中预后良好的ICP监测值显著低于预后不良者(P0.05)。ICP预测大面积脑梗死外科治疗预后的ROC曲线面积0.704,采用最大约等指数计算得出ICP预测大面积脑梗死外科治疗预后的最大AUC面积相应参数截止值为4.89,其中敏感度为0.435,特异性为0.896。结论:持续ICP监测结果显示ICP值越小,患者的预后就越好,ICP值越高,患者的预后越差。ICP监测对大面积脑梗死外科治疗的预后具有预测价值,对判断和改善预后能起到有效帮助,值得在临床推广应用。     

开窗减压术与传统刮治术治疗颌骨囊肿的手术效果、生活质量和预后的对比研究

目的:对比颌骨囊肿经传统刮治术与开窗减压术治疗后的手术效果、生活质量和预后。方法:回顾性选取2016年1月～2018年7月期间我院收治的90例颌骨囊肿患者的临床资料,上述患者根据手术方式的不同分为A组(n=45,传统刮治术)和B组(n=45,开窗减压术),比较两组患者疗效、临床指标、生活质量和预后。结果:B组患者临床总有效率为97.78%(44/45),高于A组的84.44%(38/45)(P0.05)。B组患者伤口愈合时间、手术时间、均短于A组,术中出血量少于A组(P0.05)。两组患者末次随访时情绪、外貌、味觉、疼痛、唾液、咀嚼等项目评分均升高,且B组高于A组(P0.05)。B组并发症发生率、复发率均低于A组(P0.05)。结论:与传统刮治术治疗相比,开窗减压术治疗颌骨囊肿,在手术效果、生活质量和预后方面效果显著,具有较高的临床应用价值。