Association Between Clinical Tumor Burden and Efficacy of Immune Checkpoint Inhibitor Monotherapy for Advanced Non–Small-Cell Lung Cancer

BackgroundProgrammed cell death 1 (PD-1) inhibitors have become a standard treatment, albeit not completely effective, for patients with advanced non–small-cell lung cancer (NSCLC). Previous studies of advanced melanoma have revealed that the tumor burden predicted the response to PD-1 inhibitors, although this relationship has remained unclear for NSCLC.Patients and MethodsThe present single-center retrospective study evaluated 163 patients with advanced NSCLC who had received PD-1/programmed cell death ligand 1 (PD-L1) inhibitor monotherapy from December 2015 to December 2018. The clinical tumor burden was estimated using the baseline sum of the target lesions’ longest diameters (BSLDs), measured according to the Response Evaluation Criteria for Solid Tumors, and the baseline number of metastatic lesions (BNMLs).ResultsThe optimal cutoff values for predicting progression-free survival (PFS) were 5 for the BNMLs and 76 mm for the BSLDs, using the minimum P value method. The low-BNML group included 73 patients (44.8%). The median PFS was 12.2 months in the low-BNML group and 2.8 months in the high-BNML group (hazard ratio, 0.51; P = .0005). The low-BSLD group included 92 patients (56.4%). The median PFS was 9.6 months in the low-BSLD group and 3.4 months in the high-BSLD group (hazard ratio, 0.52; P = .0006). Multivariable analysis revealed that low-BSLD, low-BNML, nonsquamous histologic type and a PD-L1 tumor proportion score of ≥ 50% were independently associated with prolonged PFS.ConclusionsPD-L1 expression and the clinical tumor burden can predict the efficacy of PD-1/PD-L1 inhibitor monotherapy for NSCLC.     

142例胎儿唇腭裂的超声诊断与遗传因素分析

目的探讨胎儿唇腭裂的影像学特征与遗传基础。方法142例病例均接受产前超声系统检查,经过两级医生检查及会诊做出最终诊断。同时收集活产胎儿的胎儿脐带或引产胎儿的大腿肌肉组织,进行全基因组测序(whole genome sequening,WGS),以发现染色体数目异常和拷贝数异常(copy number variations,CNVs)。结果142例孕妇年龄分布为21~41岁,孕周为12~35周。142例胎儿中,男性94例,女性48例,男女比例为1∶0.51。根据唇腭裂的类型,单纯唇裂有84/142例(59.15%),唇裂合并其他系统畸形情况有31/142例(21.83%)。单纯唇腭裂有14/142例(9.86%),唇腭裂合并其他系统畸形情况有13/142例(9.15%)。9.2%(13/142)的胎儿有染色体数目异常,8.4%(12/142)的胎儿检出了致病性CNV。结论对CNVs的检测可以增加胎儿腭裂的遗传检测诊断率,在临床中应重视检测致病性CNVs。     

Geometric architecture of viruses

In the current SARS-CoV-2 disease (COVID-19) pandemic, the structural understanding of new emerging viruses in relation to developing effective treatment and interventions are very necessary. Viruses present remarkable differences in geometric shapes, sizes, molecular compositions and organizations. A detailed structural knowledge of a virion is essential for understanding the mechanisms of capsid assembly/disassembly, antigenicity, cell-receptor interaction, and designing therapeutic strategies. X-ray crystallography, cryo-electron microscopy and molecular simulations have elucidated atomic-level structure of several viruses. In view of this, a recently determined crystal structure of SARS-CoV-2 nucleocapsid has revealed its architecture and self-assembly very similar to that of the SARS-CoV-1 and the Middle-East respiratory syndrome virus (MERS-CoV). In structure determination, capsid symmetry is an important factor greatly contributing to its stability and balance between the packaged genome and envelope. Since the capsid protein subunits are asymmetrical, the maximum number of inter-subunit interactions can be established only when they are arranged symmetrically. Therefore, a stable capsid must be in a perfect symmetry and lowest possible free-energy. Isometric virions are spherical but geometrically icosahedrons as compared to complex virions that are both isometric and helical. Enveloped icosahedral or helical viruses are very common in animals but rare in plants and bacteria. Icosahedral capsids are defined by triangulation number (T = 1, 3, 4, 13, etc.), i.e., the identical equilateral-triangles formed of subunits. Biologically significant defective capsids with or without nucleic acids are common in enveloped alpha-, flavi- and hepadnaviruses. The self-assembling, stable and non-infectious virus-like particles have been widely exploited as vaccine candidates and therapeutic molecules delivery vehicles.     

Molecular pathogenesis of spontaneous abortions – Whole genome copy number analysis and expression of angiogenic factors

ObjectiveTo study two major molecular alterations in spontaneous abortions (SA) with unexplained etiology – fetal genomic anomalies and the endometrial expression of main angiogenic factors VEGFA/VEGFR2 and chemokines SDF-1/CXCR4.Materials and methodsWhole genome copy number analysis by arrayCGH or Next Generation Sequencing (NGS) was applied for detection of fetal genomic imbalances. The abortive decidua of SA without fetal aneuploidies was further investigated for expression levels of the abovementioned factors using real time PCR analysis. A total of 30 abortive materials were collected from spontaneous abortions after exclusion of known predisposing factors.ResultsIn 21 of 30 spontaneous abortions (70%), genomic anomalies were discovered by whole genome copy number analysis. Numerical anomalies were detected in 90% of aberrant cases, and in 10% - structural aberrations were revealed. An increased expression for essential factors of angiogenesis was identified in spontaneous abortions’ tissues - 3.44 times for VEGFA and 10.29 times for VEGFR2. We found an average of 14 times increase in the expression levels of SDF-1 and 3.21 times for its receptor CXCR4.ConclusionWe could suggest the occurrence of increased angiogenesis in SA without fetal aneuploidies, compared to the control tissues, which could lead to increased oxidative stress and fetal loss.     

新冠疫情下留学生医学基础课网上教学探索与实践

目的探讨新冠疫情下留学生医学基础课程网上授课的手段、方法和效果,以期在"停课不停学"下保障教学质量。方法利用雨课堂、企业微信和慕课等技术手段完成理论课的教学任务,同时通过随堂测试和问卷对教学效果进行评估。结果前期开展线上教学的问题主要集中在教学时差、缺少课堂互动、实践性课程的取消三个方面。因此,我们相应采取了录播课程、增加互动形式以及推迟实践性课程的方式,帮助学生渡过难关。结论现代化的网络教学方法比较受留学生的欢迎,同时多样化的教学方式满足了学生的不同需求。     

Effectiveness of simplified 15-min refresher BLS training program: A randomized controlled trial

ObjectivesTo evaluate the long-term effectiveness of 15-min refresher basic life support (BLS) training following 45-min chest compression-only BLS training.MethodsAfter the 45-min chest compression-only BLS training, the participants were randomly assigned to either the refresher BLS training group, which received a 15-min refresher training 6 months after the initial training (refresher training group), or to the control group, which did not receive refresher training. Participants’ resuscitation skills were evaluated by a 2-min case-based scenario test 1 year after the initial training. The primary outcome measure was the number of appropriate chest compressions during a 2-min test period.Results140 participants were enrolled and 112 of them completed this study. The number of appropriate chest compressions performed during the 2-min test period was significantly greater in the refresher training group (68.9 ± 72.3) than in the control group (36.3 ± 50.8, p = 0.009). Time without chest compressions was significantly shorter in the refresher training group (16.1 ± 2.1 s versus 26.9 ± 3.7 s, p < 0.001). There were no significant differences in time to chest compression (29.6 ± 16.7 s versus 34.4 ± 17.8 s, p = 0.172) and AED use between the groups.ConclusionsA short-time refresher BLS training program 6 months after the initial training can help trainees retain chest compression skills for up to 1 year. Repeated BLS training, even if very short, would be adopted to keep acquired CPR quality optimal (UMIN-CTR UMIN 000004101).     

Prophylactic clips to reduce delayed polypectomy bleeding after resection of large colorectal polyps: a systematic review and meta-analysis of randomized trials

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Motor unit number index (MUNIX) in the quantitative assessment of severity and surgical outcome in cervical spondylotic amyotrophy

ObjectiveTo assess the feasibility of motor unit number index (MUNIX) in the quantitative assessment of the cervical spondylotic amyotrophy (CSA).MethodsMUNIX was recorded bilaterally on the abductor pollicis brevis, abductor digiti minimi, biceps brachii and middle deltoid in 41 normal controls and 47 patients with CSA (distal-type to proximal-type ratio: 25 to 22). Additionally, patients were assessed on handgrip strength (HGS), the disabilities of arm, shoulder and hand (DASH) and Medical Research Council (MRC) scales. These examinations were re-evaluated approximately 18 months after surgery in 37 of these CSA patients.ResultsMUNIX values were noticeably lower in the mainly affected muscles of CSA patients than those in controls (P < 0.05), and 49.0% (51/104) of the tested muscles with abnormal MUNIX measurements showed normal muscle strength. Significant correlations between MUNIX measurements and both DASH and MRC scores were observed in both CSA patient groups (P < 0.05). Postoperative longitudinal follow-up analysis identified significant increase in motor unit number in both CSA patient groups within approximately 18 months (P < 0.05), with or without improved measures of motor function.ConclusionsA significant reduction in MUNIX values related to motor impairment was observed in CSA patients, even in the subclinical stage. Compared to measures of motor function, the MUNIX measurements in the patients with CSA improved more noticeably after surgical intervention.SignificanceMUNIX may serve as an available supplementary test to quantitatively evaluate the motor dysfunction in CSA and to track its progression, that is complementary to conventional electromyography.