Exosomes are nanoscale (30-150 nm) biological vesicles that are actively released from living cells and circulating into all body fluids. Recently, exosomes in cerebrospinal fluid (CSF) have been recognized as promising biomarkers for central nervous system (CNS) neoplasms. In this study, we report a label-free method that can be used to rapidly isolate exosomes from CSF for proteomic analysis. Compared to ultracentrifugation and polyethylene glycol-based precipitation, our method isolates exosomes from 2 mL of CSF within 10 min, which is 18 times and 72 times shorter, respectively; the yield was increased by 4.47 times and 2.09 times and the purity was increased by 4.54 times and 9.76 times, respectively. The proteomic analysis further revealed that the exosomes isolated by our method identified more exosome-related proteins, which may reflect the physiological status of diseases for exosome-based diagnosis. Therefore, the effective isolation of pure exosomes from CSF samples for protein analysis will benefit the downstream analysis and clinical translation of exosomes, thus promoting the early diagnosis of CNS neoplasms.

Esophageal squamous cell carcinoma (ESCC) is a worldwide malignancy with high mortality rates and poor prognosis due to the lack of effective biomarkers for early detection. Exosomes have been extensively explored as attractive biomarkers for cancer diagnosis and treatment. However, little is known about exosome metabolomics and their roles in ESCC. Here, we performed a targeted metabolomic analysis of plasma exosomes and identified 196 metabolites, mainly including lipid fatty acids, benzene, amino acids, organic acids, carbohydrates and fatty acyls. We systematically compared metabolome patterns of exosomes via machine learning from patients with recrudescence and patients without recrudescence and demonstrated a marker set consisting of 3'-UMP, palmitoleic acid, palmitaldehyde, and isobutyl decanoate for predicting ESCC recurrence with an AUC of 98%. These metabolome signatures of exosomes retained a high absolute fold change value at all ESCC stages and were very likely associated with cancer metabolism, which could be potentially applied as novel biomarkers for diagnosis and prognosis of ESCC.

Background: Formulae of estimated glomerular filtration rate (eGFR) based on serum creatinine (Scr) are routinely used in oncology patients, however, they are inaccurate in some populations. Our aim was to assess the agreement of eGFR formulae and thereby build a nomogram to predict the reliability of estimates. Methods: Measured GFR (mGFR) using isotope from 445 oncology patients were compared with eGFR from six formulae (Cockcroft-Gault, Modification of Diet in Renal Disease (MDRD), modified MDRD formulae for Chinese (C-MDRD), Chronic Kidney Disease Epidemiology (CKD-EPI) Collaboration, Wright and full age spectrum (FAS)). Bias, precision and accuracy of eGFR formulae were examined. We also evaluated statistics of agreement: the total deviation index (TDI), the concordance correlation coefficient (CCC) and the coverage probability (CP). Multivariate logistic regression was applied to identify characteristics associated with inaccurate eGFR and construct a predictive nomogram. Results: All eGFR formulae tended to overestimate the eGFR. The percentage of patients with eGFR within 30% the mGFR ranged from 38.0% to 62.8%. Cockcroft-Gault and MDRD showed low bias and high precision. The MDRD formula exhibited lowest TDI, meaning that 90% of estimations ranged from -36 to 36% of mGFR. Multivariate logistic regression showed that inaccuracy of MDRD was found in elderly patients or in patients with eGFR greater than 120 ml/min. A nomogram was constructed to help oncologists to predict the risk of inaccuracy of eGFR. The calibration curve showed good agreement. Conclusions: Our results suggest that the error of eGFR by any formulae was common and wide in Chinese oncology patients. Our nomogram may assist oncologists in decision-making when mGFR is needed.

目的:探讨NTRK基因突变肺癌患者的临床特征、治疗情况以及与预后的关系.方法:回顾性分析2016年10月至2019年11月就诊于华中科技大学同济医学院附属同济医院胸部肿瘤科且NGS检测伴有NTRK突变的原发性肺癌患者的临床资料,应用Kaplan-Meier法和Log-rank检验进行单因素生存分析.结果:研究共纳入28例患者,27例为Ⅳ期,基因检测结果均为NTRK点突变或拷贝数扩增;1例为ⅢC期,基因检测结果为AEN-NTRK3(A1:N18)融合.单因素分析结果显示,接受一线治疗的NTRK突变患者无进展生存期(progression-free survival,PFS)与肿瘤组织病理类型相关(腺癌vs.鳞癌:9.4个月vs.2.5个月,P<0.05),而与年龄、性别、吸烟史、NTRK突变位点、突变类型、是否合并经典突变无关(均P>0.05).一线接受表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKIs)治疗的NTRK1突变合并EGFR突变患者PFS明显长于NTRK3突变合并EGFR突变患者,中位PFS分别为12.4个月和3.0个月,差异具有统计学意义(P<0.05).结论:接受一线治疗的NTRK突变肺腺癌患者PFS较鳞癌患者长.EGFR突变合并NTRK3突变肺癌患者接受EGFR-TKIs治疗的预后较差,合并NTRK3突变可能是EGFR突变肺癌预后不良的因素之一.

OBJECTIVES:To illustrate the clinical course and difficulties in early diagnosis of coronavirus disease 2019 (COVID-19) in patients after thoracic surgery.METHODS:We retrospectively analyzed the clinical course of the first 11 patients diagnosed with COVID-19 after thoracic surgery in early January 2020. Postoperative clinical, laboratory, and radiologic records and the time line of clinical course were summarized. Potential prognostic factors were evaluated.RESULTS:In the 11 confirmed cases (3 female, 8 male), median days from symptom onset to case detection was 8. Insidious symptom onset and misinterpreted postoperative changes on chest computed tomography (CT) resulted in delay in diagnosis. There were 3 fatalities due to respiratory failure, whereas 4 severe and 4 mild cases recovered and were discharged. All patients had once experienced leukocytosis and eosinopenia. Remittent fever and resected lung segments ≥5 were associated with fatality.CONCLUSIONS:The case fatality rate of postsurgical patients subsequently diagnosed with COVID-19 was 27.3%. Insidious symptom onset, postoperative leukocytosis with lymphopenia, and postsurgical CT changes overshadowed the early signs of viral pneumonia. Dynamic symptom monitoring, serial chest CTs, and tests for viral RNA and serum antibody improve the chance for prompt detection of COVID-19. Consideration should be given to preadmission and preoperative screening and strict contact isolation during the postoperative period.

Non-small cell lung cancer (NSCLC) has the highest morbidity and mortality worldwide. OTU deubiquitinase 5 (OTUD5), a deubiquitinating enzyme, can enhance the stability of p53 and programmed cell death 5 (PDCD5), a protein related to the apoptosis, by deubiquitination. This study aimed to explore the biological function and underlying mechanism of OTUD5 in NSCLC. Western blot and qRT-PCR were used to detect the expression of OTUD5 protein and mRNA in NSCLC tissues and cells, respectively. RNAi was adopted to construct an OTUD5 low-expression model while the plasmids overexpressing p53 and PDCD5 were used to establish the overexpression models, respectively. CCK-8 assay, transwell assay, and apoptosis assay were carried out to analyze the changes in the proliferation, migration, and chemoresistance of A549 and HCC827 cells. The mechanism of OTUD5 in NSCLC was studied by Western blot. Down-regulated OTUD5 in NSCLC tissues was significantly correlated to a poor prognosis. The knockdown of OTUD5 inactivated p53 and PDCD5, promoting the proliferation and metastasis of NSCLC cells while inhibiting their apoptosis. OTUD5 knockdown also enhanced the resistance of NSCLC cells to doxorubicin and cisplatin. OTUD5 acted as a tumor suppressor in NSCLC by regulating the p53 and PDCD5 pathways.

针对亚热带地区伏旱频发条件下,丝茅入侵细叶结缕草草坪引起功能退化的问题,通过设置4个干旱梯度(水分充足、轻度、中度和重度干旱),采用取代试验设计了5个不同比例的丝茅入侵细叶结缕草草坪试验,进行60 d干旱处理后,测定丝茅和结缕草地下和地上相对产量、相对产量总和、攻击力、竞争平衡指数等竞争指标,分析两种植物的株高、分蘖数、叶片数、生物量和根冠比等生长指标,比较超氧化物歧化酶(SOD)、过氧化物酶(POD)、过氧化氢酶(CAT)、可溶性糖(SS)、可溶性蛋白(SP)、脯氨酸(Pro)、丙二醛(MDA)等生理指标,研究干旱对两种植物之间的竞争、生长及抗性系统的影响.结果表明:1)干旱程度和丝茅入侵比例对两种植物的地上和地下竞争指标产生显著影响(P<0.05),轻度干旱且丝茅入侵比例≤30％时,结缕草地下攻击力指数和地下竞争平衡指数为正值,中度和重度干旱使结缕草种间竞争力丧失,当丝茅入侵比例≥20％时,拮抗作用使结缕草易被排挤出群落.2)干旱主要影响结缕草地下竞争力,丝茅入侵主要影响结缕草地上竞争力,干旱和丝茅入侵协同作用对结缕草地下攻击力和地下平衡指数影响大于地上部分,随干旱程度和丝茅入侵比例增加结缕草地上和地下竞争力降为负值.3)轻度干旱利于两种植物生长,中度和重度干旱降低了结缕草的株高、分蘖数、叶片数和单株生物量,对丝茅影响较少;>10％丝茅入侵比例限制了结缕草分蘖数和叶片数,>20％则降低了结缕草单株生物量和根冠比,干旱和丝茅入侵协同作用抑制了结缕草生长与再生能力.4)结缕草SOD、POD和CAT含量随干旱程度增加而显著增加(P<0.05),轻度干旱对丝茅SOD无影响而降低了CAT活性(P<0.05);>10％丝茅入侵比例增加了结缕草SOD活性,>20％增加了CAT活性,>30％增加了POD活性(P<0.05).干旱对结缕草影响为CAT>SOD>POD,对丝茅为SOD>POD>CAT,丝茅入侵比例对两种植物影响均为SOD>CAT>POD,干旱对结缕草抗氧化酶系统影响大于丝茅入侵.5)轻度干旱增加了结缕草SS和SP的含量(P<0.05),增加了丝茅SP的含量,中、重度干旱使两种植物的SS、SP、Pro和MDA含量增加(P<0.05);>10％丝茅入侵比例增加了结缕草SS、SP和MDA的含量(P<0.05),>20％时增加了Pro的含量(P<0.05),干旱程度和丝茅入侵比例协同作用加剧了两种植物的受伤程度,对生境胁迫时结缕草反映为SS>Pro>SP>MDA,丝茅反映为MDA>Pro>SS>SP.故夏季避免重度干旱和控制丝茅侵入比例≤10％是维持结缕草草坪健康的基本养护要求.

Background To find out the optimal number of examined lymph nodes (ELNs) in stage IA non-small cell lung cancer (NSCLC). To figure out whether there was a turning point beyond which ELNs might have adverse effects on survival. Methods Using the Surveillance, Epidemiology, and End Results registry (SEER) database, we selected all NSCLC patients diagnosed with stage IA (T1N0M0) from 1995 to 2015. Cases from 1995 to 2005 were as analytical data set (group 1) and from 2006 to 2015 were as Validation data set (group 2). The overall survival (OS) of patients with different ELNs was compared statistically by SPSS. The optimal cut point of ELNs was calculated by X-Tile and verified by univariable and multivariable analyses. Propensity score matching (PSM) was did by R software 3.5.2. Results In total, we extracted 57481 stage IA NSCLC patients (group 1, n = 20814; group 2, n = 36667). The PSM of Group 1 and Group 2 were balanced based on sex, age and race. In both group 1 and group 2, when divided patients into 3 subgroups, recording as ELN = 0, 1 ≤ ELNs Conclusion For stage IA NSCLC, we suggested that to resect 6 to 9 LNs were enough, and no more than 16 LNs were accepted. More than 16 ELNs did not improve survival and more than 30 ELNs may have bad effect on survival.

Updates in Version 2.2018 of the NCCN guidelines for small cell lung cancer from version 1.2018 The Discussion section has been updated to reflect the changes in the algorithm.（MS-1）Updates in version 1.2018 of the NCCN

Updates in version 2.2018 of the NCCN guidelines for head and neck cancers from version 1.2018ST-15 Staging table added.MS-1The Discussion section has been updated to reflect the changes in the algorithm.Table 7American Joint Committee on Cancer（AJCC）TNM Staging System for Cervical Lymph Nodes and Unknown Primary Tumors of the Head and Neck（8th ed.,2017）

Objectvies To explore an effectvie education mode to improve the document retrieval and clinical research designing ability among eight-year medical students.Methods Eight-year medical students who had complete clinical practice and enter secondary discipline training stage were recruited.The student learned document retrieval practice skills,discussed the clinical research literatures published by our hospital in"Journal Club"and learned writing skills of clinical research project plan on the internet.The effect of this education mode was assessed by questionnaire investigation and face to face interview.Results The scores of problem finding ability,document retrieval ability,clinical research designing ability and clinical research practice ability among eight-year medical students in experimental group(7.40 ± 0.26,11.30 ± 0.51,11.45 ± 0.51,10.20 ± 0.61,11.35 ± 0.49)were significantly higher in those in control groups(6.15 ± 0.27,9.20 ± 0.43,9.30 ± 0.52,8.75 ± 0.23,9.85 ± 0.42).The number of clinical research literatures published by student taking this education course was significant higher than that from control group.Conclusions This education mode using"Journal club"and internet could significantly improve clinical research practice ability among eight-year medical students.

Objectives To investigate the participation status and demands for scientific research of clinical medi-cine undergraduates and put forward the corresponding countermeasures.Methods One hundred students majored in 5-year clinical medicine were randomly enrolled in the research. They had completed basic medicine learning and were from a medical college of Wuhan.Questionnaire was used to collect relative information.Results 82 (82.00％ ) students wanted to participate in scientific research at the undergraduate stage.33(33.00％ )once participated in the research activities arranged by the school ,of which 28 students (84.45％ )were not satisfied with the arrange-ments.Their ability of project design ,researching of documents ,statistical analysis and writing papers were poor.Conclusions The enthusiasms for scientific research are high in undergraduates of clinical medicine. They need platform to participate in scientific research.We may try out"undergraduates'tutorial system"to increase their inter-ests and improve abilities in scientific research.

Problem based learning is a student centered learning strategy in which learners confront ill-structured problems similar to real world situations. PBL guides learners to discover the knowledge themselves. PBL is also well known for shaping learners in collaborating team work and allows the development of critical thinking,content knowledge and problem-solving skills. However,PBL requires teachers to experience high quality professional development to learn how to design high quality experiential learning activities that maximize student potential and teachers and students to meet face to face. Wechat platform combined with PBL teaching model could help students master the progress of medical oncology and improve their learning efficiency and interests. Application of the Wechat plus PBL model in oncology teaching should be explored further.

The ubiquitin-proteasome system plays a pivotal role in breast tumorigenesis by controlling transcription factors, thus promoting cell cycle growth, and degradation of tumor suppressor proteins. However, breast cancer patients have failed to benefit from proteasome inhibitor treatment partially due to proteasome heterogeneity, which is poorly understood in malignant breast neoplasm. Chemical crosslinking is an increasingly important tool for mapping protein three-dimensional structures and proteinprotein interactions. In the present study, two cross-linkers, bis (sulfosuccinimidyl) suberate (BS(3)) and its water-insoluble analog disuccinimidyl suberate (DSS), were used to map the subunit-subunit interactions in 20S proteasome core particle (CP) from MDA-MB-231 cells. Different types of gel electrophoresis technologies were used. In combination with chemical cross-linking and mass spectrometry, we applied these gel electrophoresis technologies to the study of the noncovalent interactions among 20S proteasome subunits. Firstly, the CP subunit isoforms were profiled. Subsequently, using native/SDSPAGE, it was observed that 0.5 mmol/L BS(3) was a relatively optimal cross-linking concentration for CP subunit-subunit interaction study. 2-DE analysis of the cross-linked CP revealed that α1 might preinteract with α2, and α3 might pre-interact with α4. Moreover, there were different subtypes of α1α2 and α3α4 due to proteasome heterogeneity. There was no significant difference in cross-linking pattern for CP subunits between BS(3) and DSS. Taken together, the gel-based characterization in combination with chemical cross-linking could serve as a tool for the study of subunit interactions within a multi-subunit protein complex. The heterogeneity of 20S proteasome subunit observed in breast cancer cells may provide some key information for proteasome inhibition strategy.

OBJECTIVE:Recent epidemiological evidence indicates an association between chronic kidney disease (CKD) and the risk of new-onset atrial fibrillation (AF), but the results are inconclusive. This meta-analysis examined the association between CKD and new-onset AF.METHODS:PubMed, EMBASE, the Cochrane Collaboration and the reference lists of relevant articles were searched to identify eligible studies. The random effect model was used to calculate the overall multivariable-adjusted hazard ratio (HR) with its corresponding 95% confidence interval (CI). Associations were tested in subgroups of study characteristics and study quality criteria. We also performed sensitivity analyses and assessments of publishing bias.RESULTS:Seven prospective cohort studies (n = 400,189 participants) were included in this meta-analysis. Pooled results suggested that CKD was associated with an increased adjusted risk estimate for new-onset AF (HR, 1.47; 95% CI, 1.21-1.78), with significant heterogeneity between these studies (I2 = 79.7%, P<0.001). Results were not different in any subgroup except sample size. Stratified analyses found that the diagnostic method of CKD and eGFR (estimated glomerular filtration rate), the number of confounders adjusted for, and study quality explained little of the variation between studies. Sensitivity analysis further demonstrated the results to be robust.CONCLUSIONS:CKD is associated with an increased risk of incident AF. Further research is needed to investigate the biological association between CKD and AF and identify a preventive strategy to decrease the incidence of AF in CKD patients.

Objective To investigate the effects of a novel scientific research practice model on medical undergraduates'!cognition and behavior. Method Totally, 60 medical undergraduates took part in the research. All of them accepted scientific research training by using improved tutorial system + team-based learning (TBL) combat training models. Before and after training, students completed the same ques-tionnaires respectively. The content included the purpose of participating in scientific research activities, the interest of scientific research, and the confidence and satisfaction of publishing scientific research papers, etc.. SPSS 16.0 was used to conduct non parametric Mann-Whitney test or Wilcoxon non parametric test to the pre and post survey data. Results Fifty-seven students (95.0%) were satisfied with the novel teaching model. Before and after training, the liking scores for scientific research practice rose from 1.12 (95%CI=0.65 to 1.59) to 5.87 (95%CI=5.34 to 6.39), P=0.001. Fifty-three students (88.3%) proactively participated in research work after training compared with 21 students (35.0%) before training, P=0.000. More students had confidence in publishing academic papers on Chinese core journals or Science Citation Index journals after training (P=0.000, P=0.003 respectively). 57 students (95%) said they were very satisfied or satisfied with the training of scientific research and practice. Conclusion Improved tutorial system+TBL research combat training model can stimulate students'!interest in scientific research and make them have more pos-itive cognition and behavior on scientific research work.

Objective To observe the efficacy and safety of lobaplatin(LBP) combined with etoposide or irinotecan for patients with advanced small cell lung cancer(SCLC).Methods Forty-five patients with histologically diagnosed SCLC were divided into two groups.The LE regimen group(lobaplatin 30mg/m2 iv d1,VP-16 100mg iv d1-d3,21 days were a cycle) had 25 patients and the LI regimen group(lobaplatin 30mg/m2 iv d1,irinotecan 60 mg/m2 iv d1,d8,d15,28 days were a cycle) had 20 patients.The efficacy and toxicity were evaluated after at least two cycles of chemotherapy.Results Forty-five patients were evaluable for response,in which 2 achieved complete response(CR),24 partial responses(PR),and the response rate(RR) was 57.8%.The RR in LE regimen group was 48.0%(12/25),while in LI regimen group was 70.0%(14/20).The median overall survival(OS) of LE regimen and LI regimen were 8.0 months and 7.0 months,respectively(P=0.255).The main toxicities were reversible bone marrow suppression and gastrointestinal reaction.Grade 3-4 thrombocytopenia rate was 17.8%(8/45),the occurence rate was higher in LI regimen than LE regimen(30.0% vs.8.0%,P=0.002).All grade 3-4 diarrhea was all occurred in patients with LI regimen(8.9%,4/45),who were retreated patints too.There was no treatment-related death.Conclusion Lobaplatin combined with etoposide or irinotecan is effective and tolerated for patients with advanced small cell lung cancer,and worth further study.

0 引言 肺癌合并下呼吸道感染,是临床常见且处理起来非常棘手的问题,常导致病情急剧恶化甚至危及患者生命.目前呼吸道感染诊治指南,对肿瘤患者针对性不强;而NCCN肿瘤相关性感染诊治指南,则主要针对中性粒细胞减少症并发热的患者.

Primary skeletal muscle ALCL is very rare. Here the authors report a case of skeletal muscle ALCL that was proven pathologically. A 14-year-old boy presented with a persistent fever, chills, night sweats, headache, and significant weight loss. A CT scan of the abdomen showed a hazy mass about 3.2 x 1.2 cm in his left sacrospinalis. Ultrasonography revealed a low-echo and irregular mass in the left lumbar muscle measuring 8 x 1.4 x 3.6 cm in size and a similar mass 8 x 3.5 x 3.7 cm in size in the femoral muscle of the left thigh. MRI demonstrated an abnormal mass signal 4 x 3 x 9 cm in size infiltrating the left sacrospinalis muscle. The biopsy specimen was taken from the femoral muscle of the left thigh at surgery. Histopathological examination revealed a diffuse infiltration of large and atypical cells with pleomorphic nuclei and abundant cytoplasm. Immunohistological staining showed these atypical cells were positive for CD30 (Ki-l), anaplastic lymphoma kinase (ALK), epithelial membrane antigen (EMA), CD3, CD45RO, and CD68. The morphology and immunophenotype were consistent with CD30-positive, ALK-positive, and ALCL of T-cell lineage. The patient's condition was diagnosed as CD30-positive primary skeletal muscle ALCL.

目前乙型肝炎的抗病毒治疗效果并不令人满意,表现为干扰素长期有效率不高、核苷类似物易出现变异病毒株、需长期服用等.基因治疗作为一种全新的治疗手段,主要方法有RNAi技术、反义RNA技术、核酶技术等.RNAi是指由21～23个核苷酸组成的双链RNA(dsRNA)ph引发的生物细胞内同源基因转录后沉默的现象.其作为以HBV基因转录为靶点的基因治疗手段越来越受到关注[1].本文主要对RNAi技术在HBV基因治疗中的作用作一综述.