中国非小细胞肺癌免疫检查点抑制剂治疗专家共识（2020年版）

非小细胞肺癌（non-small cell lung cancer, NSCLC）是肺癌最常见的病理类型。晚期NSCLC的系统性抗肿瘤治疗经历了化疗、靶向治疗及免疫治疗的变革，患者总体生存时间不断延长。免疫检查点抑制剂（immune checkpoint inhibitors, ICIs），尤其是程序性死亡分子-1（programmed cell death protein 1, PD-1）/程序性死亡分子配体-1（programmed death-ligand 1, PD-L1）抗体已成为表皮生长因子受体（epidermal growth factor receptor, EGFR）/间变性淋巴瘤激酶（anaplastic lymphoma kinase, ALK）阴性晚期NSCLC一线及二线的标准治疗和局部晚期NSCLC同步放化疗后标准治疗，并在辅助/新辅助治疗中显示出可喜的结果，改变了NSCLC整体治疗格局。随着越来越多的ICIs在国内获批肺癌适应证，中国临床肿瘤学会（Chinese Society of Clinical Oncology, CSCO）NSCLC专家委员会牵头，组织该领域的专家，结合2019年版专家共识，参考最新国内外文献、临床研究数据及系统评价，在专家共同讨论的基础上，达成统一意见并制定、更新本共识，为国内同行更好地应用ICIs治疗NSCLC提供参考意见。     

Technological Advances in Penile Implant Surgery

BackgroundDuring the last century, surgical management of erectile dysfunction has evolved from an experimental concept to a core treatment modality with widespread use among the men's health community. Over time, innovations in materials, mechanical design elements, device coatings, and surgical technique have provided patients with low-risk, reliable, and reproducible erectile function with high satisfaction rates.AimTo provide a foundation for future innovation by improving understanding of historical penile prosthetics and the rationale behind incremental technological improvements for the contemporary Men's Health physician.MethodsLiterature review was conducted to generate a comprehensive review of historical technological innovations in penile implant surgery. Companies with FDA approved penile prosthetics in use in the United States were contacted for information regarding technological innovations in the past and future devices in development. A separate literature review was performed to identify any significant future device design elements being tested, even in the ex vivo setting, which may have future clinical applications.OutcomesTechnological innovations in penile implant surgery were described.ResultsCurrent options for the prosthetic surgeon include malleable penile prostheses (MPP), self-contained (2-piece) inflatable penile prostheses, and multicomponent (3-piece) inflatable penile prostheses. Current MPPs consist of a synthetic coated solid core which allow for manipulation of the penis for concealability while maintaining sufficient axial rigidity to achieve penetration when desired. Multi-component (3-Piece) IPPs currently include the Coloplast Titan and Boston Scientific/AMS 700 which consist of a fluid reservoir, intrascrotal pump, and intracavernosal cylinders. The devices have undergone numerous design updates to the cylinders, pump, reservoir, tubing, and external coatings to increase reliability and decrease short- and long-term complications.Clinical ImplicationsFuture innovations in penile prosthetic surgery seek to broaden the indications and applicability to the transgender community and improve both safety and functionality for patient and partner.Strengths & LimitationsThe review is limited primarily to penile prosthetics approved for current or historical clinical use in the United States and may not be representative of the global prosthetic environment. Additionally, the research and development of future innovations, particularly those provided by device manufacturers, is likely limited by non-disclosure to maintain a competitive advantage.ConclusionsPenile prosthetic surgery will undoubtedly remain integral to the treatment of erectile dysfunction, and education regarding the current state of technological innovation will empower the prosthetic surgeon and biomedical engineering community to improve contemporary patient care and drive the development of the next generation of implantable penile prosthetics.Barnard JT, Cakir OO, Ralph D, et al. Technological Advances in Penile Implant Surgery. J Sex Med 2021;18:1158–1166.     

Incidence rate of prostate cancer in men treated for erectile dysfunction with phosphodiesterase type 5 inhibitors: retrospective analysis

The purpose of this study was to determine the incidence rate of prostate cancer among men with erectile dysfunction (ED) treated with phosphodiesterase type 5 inhibitors (PDE-5i) over a 7-year period vs. men with ED of the same age and with similar risk factors who were not treated with PDE-5i. In a retrospective review of electronic medical records and billing databases between the years 2000 and 2006, men with ED between the ages of 50 and 69 years and no history of prostate cancer prior to 2000 were identified. These individuals were divided into two groups: 2362 men who had treatment with PDE-5i, and 2612 men who did not have treatment. Demographic data in each group were compared. During the study period, 97 (4.1%) men with ED treated with PDE-5i were diagnosed with prostate cancer compared with 258 (9.9%) men with ED in the non-treated group (P<00001). A higher percentage of African Americans were treated with PDE-5i vs. those who were not (10.5% vs. 7.1% P<0.0001). The PDE-5i group had lower documented diagnosis of elevated prostate-specific antigen (10.0% vs. 13.1% P=0.0008) and higher percentage of benign prostatic hyperplasia (38.4% vs. 35.1% P=0.0149). Men with ED treated with PDE-5i tended to have less chance (adjusted odds ratio: 0.4; 95% confidence intervals: 0.3–0.5; P<0.0001) of having prostate cancer. Our data suggest that men with ED treated with PDE-5i tended to have less of a chance of being diagnosed with prostate cancer. Further research is warranted.     

Dynamic mislocalizations of nuclear pore complex proteins after focal cerebral ischemia in rat

Nuclear pore complexes (NPCs) play an important role in coordinating the transport of proteins and nucleic acids between the nucleus and cytoplasm, and are therefore essential for maintaining normal cellular function and liability. In the present study, we investigated the temporal immunohistochemical distribution of five representative components of NPCs—Ran GTPase‐activating protein 1 (RanGap1), glycoprotein‐210 (Gp210), nucleoporin 205 (Nup205), nucleoporin 107 (Nup107), and nucleoporin 50 (Nup50)—after 90 min of transient middle cerebral artery occlusion (tMCAO) up to 28 days after the reperfusion in rat brains. Single immunohistochemical analyses showed ring‐like stainings along the periphery of the nucleus in sham control brains. After tMCAO, Gp210 and Nup107 immunoreactivity continuously increased from 1 day, and RanGap1, Nup205, and Nup50 increased from 2 days until 28 days, which also displayed progressive precipitations within the nucleus in the peri‐ischemic area, while the ischemic core showed scarce expression with collapsed structure. Double immunofluorescent analyses revealed nuclear retention and apparent colocalization of RanGap1 with Nup205, Gp210 with Nup205, and partial colocalization of Nup205 with Nup107; most of the ischemic changes above were similar to those observed in patients with C9orf72‐genetic amyotrophic lateral sclerosis. Taken together, these observations suggest that the mislocalization of these nucleoporins may be a common pathogenesis of both ischemic and neurodegenerative disease. © 2016 Wiley Periodicals, Inc.     

Discussion of: Statistical and Regulatory Issues with the Application of Propensity Score Analysis to Nonrandomized Medical Device Clinical Studies

In this paper, the original up-and-down method, modified up-and-down method, the Robbins-Monro method, and a fixed-sample Spearman-Kärber method are compared for the point estimator as well as the confidence interval of LD₅₀. In particular, three different designs of the modified up-and-down approach based on the combination of experiments on one test space and reduced test space are investigated. The standard normal distribution and chi-square distribution are used as tolerance distributions. Simulation results indicate that the modified up-and-down method tends to be some-what better than the original up-and-down method in terms of the mean squared error under normal tolerance distribution. In case of chi-square distribution, the modified method is shown to be substantially better when the test space is wide and the initial dose is further away from the LD₅₀.     

Impact of the association between elevated oestradiol and low testosterone levels on erectile dysfunction severity

Our aim was to assess the impact of the association between elevated oestradiol (E₂) and low testosterone (T) levels on erectile dysfunction (ED) severity. A total of 614 male patients with ED and a normal or low T level in association with normal or elevated E₂ levels were enrolled. Patients underwent routine laboratory investigations in addition to measurements of total T, total E₂, follicle-stimulating hormone (FSH), luteinizing hormone (LH) and prolactin. We compared the responses to the erectile function domain, Q3 (achieving erection) and Q4 (maintaining erection) of the International Index for Erectile Function (IIEF) score in patients with the following: normal T and E₂ levels; low T level; low T level and elevated E₂ level; and elevated E₂ level. Of the patients included, 449 (73.1%) had normal T and E₂ levels, 110 (17.9%) had a low T level, 36 (5.9%) had a low T level and an elevated E₂ level, and 19 (3.1%) had an elevated E₂ level. Increased ED severity was significantly associated with low T levels, elevated E₂ levels, and both a low T level and an elevated E₂ level. Additionally, the mean values of the EF-domain, Q3 and Q4 were significantly lower in patients with both a low T level and an elevated E₂ level compared to patients with any condition alone. In conclusion, a low T level had the primary effect on erectile function; however, a concomitantly elevated E₂ level had an additive impairment effect.     

非编码 RNA 调控骨关节炎的分子生物学研究进展

目的总结非编码 RNA 调控骨关节炎（osteoarthritis，OA）的分子生物学研究进展，为生物学研究及临床治疗 OA 提供参考。方法广泛查阅近年国内外有关非编码 RNA 调控 OA 病理过程的相关研究报道，并进行总结。结果根据 RNA 长度可将非编码 RNA 分为 3 类。相关研究采用高通量测序技术以及基因芯片技术筛选出大量与 OA 发病过程相关的非编码 RNA，并经 RT-PCR 验证此类非编码 RNA 多参与了 OA 的调控；通过对 OA 中表达最显著的非编码 RNA 进行基因敲减及过表达，明确了其调控 OA 的作用靶点；以及了解了非编码 RNA 间以及非编码 RNA 与编码 RNA 间存在复杂的基因共表达网络拓扑结构，为明确基因间结构及功能的相互作用、寻求 OA 治疗靶点提供线索。结论目前对于非编码 RNA 调控 OA 病理过程的分子生物学机制已有初步研究，但每个非编码 RNA 发挥调控作用的关键结构或序列，以及其效应复合结构的组建及相互作用机制仍未明确，有待进一步研究。