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| 1 | 帕博利珠单抗治疗伴脑转移NSCLC患者的一项非随机、开放Ⅱ期试验的长期随访结果和生物标志物分析显示文摘背景与目的我们开展了一项帕博利珠单抗用于伴未治疗脑转移的非小细胞肺癌(non-small cell lung cancer,NSCLC)或黑色素瘤患者的疗效和安全性的II期试验,旨在评估程序性死亡受体1(programmed cell death 1,PD-1)抑制剂在中枢神经系统(central nervous system,CNS)中的疗效。中期结果已发表,现报道对NSCLC队列的更新分析结果。方法这是一项开放性、单中心、II期试验。纳入标准:年龄≥18岁,诊断为晚期NSCLC并伴有≥1个5 mm-20 mm脑转移病灶,既往从未治疗或之前放疗后进展,无神经系统症状,不需要激素治疗且美国东部肿瘤协作组(Eastern Cooperative Oncology Group,ECOG)<2分。患者每2周接受一次帕博利珠单抗(10 mg/kg)治疗。队列1为程序性死亡配体1(programmed cell death ligand 1,PD-L1)≥1%的患者,队列2为PD-L1<1%或未评估的患者。主要终点是脑转移患者缓解比例。所有经治患者均纳入疗效与安全性终点的分析。该研究已结束入组,并于Clinicaltrials.gov登记注册,注册号为NCT02085070。结果2014年3月31日-2018年5月21日,共42例患者接受治疗。中位随访时间为8.3个月(IQR:4.5个月-26.2个月)。队列1的37例患者中11例有脑转移缓解[29.7%(95%CI:15.9%-47.0%)]。队列2未观察到缓解。治疗相关的3级-4级不良事件(adverse events,AEs)包括2例肺炎、1例全身症状、1例结肠炎、1例肾上腺皮质功能不全、1例高血糖症和1例低钾血症。6例(14%)患者发生了治疗相关的严重不良事件,包括肺炎、急性肾损伤、低钾血症和肾上腺皮质功能不全。没有观察到治疗相关死亡病例。结论帕博利珠单抗治疗PD-L1≥1%的NSCLC伴脑转移患者有效,且对所有纳入的未经治疗的脑转移患者安全。需要进一步探索免疫治疗用于NSCLC合并CNS转移。 | Sarah B GOLDBERG Kurt A SCHALPER Scott N GETTINGER Amit MAHAJAN Roy S HERBST Anne C CHANG Rogerio LILENBAUM Frederick H WILSON Sacit Bulent OMAY James B YU Lucia JILAVEANU Thuy TRAN Kira PAVLIK Elin ROWEN Heather GERRSH Annette KOMLO Richa GUPTA Hailey WYATT Matthew RIBEIRO Yuval KLUGER Geyu ZHOU Wei WEI Veronica L CHANG Harriet M KLUGER 董晓荣(翻译/校对) | 2021 | 中国肺癌杂志2021，24，9： | 34 |
| 2 | 1990—2017年中国伤害负担:2017年全球疾病负担研究结果(摘译)显示文摘伤害是全球性的公共卫生挑战,涉及各年龄组和不同性别的人群。过去三十年来,中国经济快速发展,人口老龄化趋势加重,社会呈现出城镇化、机动化和老龄化等特征。随着人们生活环境和生活方式的改变,伤害已跃居人群致死原因第五位,仅排在恶性肿瘤、心脑血管疾病、呼吸系统疾病和心肌梗死之后。据估计,中国每年在伤害方面消耗的直接医疗费用约为650亿元人民币. | 林泽婷(译) 吕来文(译) 黄晓晴(译) 李丽萍(审校) Duan Leilei Ye Pengpeng Juanita A Haagsma Jin Ye Wang Yuan Er Yuliang Deng Xiao Gao Xin Ji Cuirong Wang Linhong Marlena S Bannick W Cli Mountjoy-Venning Caitlin N Hawley Zichen Liu Mari Smith Spencer L James Theo Vos Christopher J L Murray | 2020 | 伤害医学(电子版)2020，9，2： | 15 |
| 3 | Relationship between the exocrine and endocrine pancreas after acute pancreatitis显示文摘AIM:To determine the prevalence and time course of pancreatic exocrine insufficiency in individuals with newly diagnosed prediabetes or diabetes mellitus after acute pancreatitis.METHODS:Relevant literature cited in three major biomedical journal databases(EMBASE,MEDLINE,and Scopus)was reviewed independently by two authors.There were no language constraints but the search was limited to human studies.Studies included were cohort studies of adult patients who were discharged after an attack of acute pancreatitis.Patients were excluded if they were under 18 years of age or had a previous diagnosis of prediabetes or diabetes mellitus,pancreatic exocrine insufficiency,or chronic pancreatitis.The main outcome measure was the prevalence of concomitant pancreatic exocrine insufficiency in patients who were diagnosed with prediabetes and diabetes mellitus after an attack of acute pancreatitis.Subgroup analysis was conducted for patients who were diagnosed with prediabetes only and those who were diagnosed withdiabetes mellitus only.Subgroup analysis looking at the time course of concomitant pancreatic exocrine and endocrine insufficiency was also conducted.Pooled prevalence and corresponding 95%confidence intervals were calculated for all outcome measures and P-values<0.05 were deemed statistically significant.RESULTS:Eight clinical studies comprising of 234patients met all eligibility criteria.The pooled prevalence of newly diagnosed prediabetes or diabetes in individuals after acute pancreatitis was 43%(95%CI:30%-56%).The pooled prevalence of pancreatic exocrine insufficiency in individuals after acute pancreatitis was 29%(95%CI:19%-39%).The prevalence of concomitant pancreatic exocrine insufficiency in individuals with newly diagnosed prediabetes or diabetes was 40%(95%CI:25%-55%).The prevalence of concomitant pancreatic exocrine insufficiency among individuals with prediabetes alone and diabetes mellitus alone was 41%(95%CI:12%-75%)and 39%(95%CI:28%-51%),respectively.Further analysis showed that the prevalence of concomitant pancreatic exocrine insufficiency in individuals with prediabetes or diabetes decreases over time after an attack of acute pancreatitis.CONCLUSION:Pancreatic exocrine insufficiency occurs in 40%of individuals with newly diagnosed prediabetes or diabetes mellitus after acute pancreatitis.Further studies are needed to investigate the pathogenesis of diabetes in this setting. | Stephanie L M Das James I C Kennedy Rinki Murphy Anthony R J Phillips John A Windsor Maxim S Petrov | 2014 | World Journal of Gastroenterology2014，20，45： | 9 |
| 4 | Predictors of disease severity in ulcerative colitis patients from Southwestern Ontario显示文摘AIM:To understand the demographic characteristics of patients in Southwestern Ontario,Canada with ulcerative colitis(UC)in order to predict disease severity. METHODS:Records from 1996 to 2001 were exam- ined to create a database of UC patients seen in the London Health Sciences Centre South Street Hospital Inflammatory Bowel Disease Clinic.To be included, patients'charts were required to have information of their disease presentation and a minimum of 5 years of follow-up.Charts were reviewed using standardized data collection forms.Disease severity was generated during the chart review process,and non-endoscopic Mayo Score criteria were collected into a composite. RESULTS:One hundred and two consecutive patients'data were entered into the database.Demographic analyses revealed that 51%of the patients were male, the mean age at diagnosis was 39 years,13.7%had a first degree relative with inflammatory bowel disease (IBD),61.8%were nonsmokers and 24.5%were ex-smokers.In 22.5%of patients the disease was limited to the rectum,in 21.6%disease was limited to the sigmoid colon,in 22.5%disease was limited to the left colon,and 32.4%of patients had pancolitis. Standard multiple regression analysis which regressed a composite of physician global assessment of disease severity,average number of bowel movements,and average amount of blood in bowel movements on year of diagnosis and age at time of diagnosis was significant,R 2=0.306,F(7,74)=4.66,P<0.01. Delay from symptoms to diagnosis of UC,gender, family history of IBD,smoking status and disease severity at the time of diagnosis didnot significantly predict the composite measure. CONCLUSION:UC severity is associated with younger age at diagnosis and year of diagnosis in a longitudinal cohort of UC patients,and may identify prognostic UC indicators. | Lee S Roth Nilesh Chande Terry Ponich Maya L Roth James Gregor | 2010 | World Journal of Gastroenterology2010，16，2： | 4 |
| 5 | Risk for emerging bipolar disorder, variants, and symptoms in children with attention deficit hyperactivity disorder, now grown up显示文摘AIM: To determine the prevalence of bipolar disorder(BD) and sub-threshold symptoms in children with attention deficit hyperactivity disorder(ADHD) through 14 years' follow-up, when participants were between 21-24 years old.METHODS: First, we examined rates of BD type Ⅰ?and Ⅱ diagnoses in youth participating in the NIMH-funded Multimodal Treatment Study of ADHD(MTA). We used the diagnostic interview schedule for children(DISC), administered to both parents(DISC-P) and youth(DISCY). We compared the MTA study subjects with ADHD(n = 579) to a local normative comparison group(LNCG, n = 289) at 4 different assessment points: 6, 8, 12, and 14 years of follow-ups. To evaluate the bipolar variants, we compared total symptom counts(TSC) of DSM manic and hypomanic symptoms that were generated by DISC in ADHD and LNCG subjects. Then we sub-divided the TSC into pathognomonic manic(PM) and non-specific manic(NSM) symptoms. We compared the PM and NSM in ADHD and LNCG at each assessment point and over time. We also evaluated the irritability as category A2 manic symptom in both groups and over time. Finally, we studied the irritability symptom in correlation with PM and NSM in ADHD and LNCG subjects.RESULTS: DISC-generated BD diagnosis did not differ significantly in rates between ADHD(1.89%) and LNCG 1.38%). Interestingly, no participant met BD diagnosis more than once in the 4 assessment points in 14 years. However, on the symptom level, ADHD subjects reported significantly higher mean TSC scores: ADHD 3.0; LNCG 1.7; P < 0.001. ADHD status was associated with higher mean NSM: ADHD 2.0 vs LNCG 1.1; P < 0.0001. Also, ADHD subjects had higher PM symptoms than LNCG, with PM means over all time points of 1.3 ADHD; 0.9 LNCG; P = 0.0001. Examining both NSM and PM, ADHD status associated with greater NSM than PM. However, Over 14 years, the NSM symptoms declined and changed to PM over time(df 3, 2523; F = 20.1; P < 0.0001). Finally, Irritability(BD DSM criterion-A2) rates were significantly higher in ADHD than LNCG(χ2 = 122.2, P < 0.0001), but irritability was associated more strongly with NSM than PM(df 3, 2538; F = 43.2; P < 0.0001).CONCLUSION: Individuals with ADHD do not appear to be at significantly greater risk for developing BD, but do show higher rates of BD symptoms, especially NSM. The greater linkage of irritability to NSM than to PM suggests caution when making BD diagnoses based on irritability alone as one of 2(A-level) symptoms for BD diagnosis, particularly in view of its frequent presentation with other psychopathologies. | Ahmed Z Elmaadawi Peter S Jensen L Eugene Arnold Brooke SG Molina Lily Hechtman Howard B Abikoff Stephen P Hinshaw Jeffrey H Newcorn Laurence Lee Greenhill James M Swanson Cathryn A Galanter | 2015 | World Journal of Psychiatry2015，5，4： | 3 |
| 6 | Wilson’s disease显示文摘 | Aftab Ala Ann P Walker Keyoumars Ashkan James S Dooley Michael L Schilsky | 2007 | The Lancet . 2007 (9559)2007，，9559： | 3 |
| 7 | 选择性雄激素受体调节剂治疗迟发性男性性腺功能低下症显示文摘几种睾酮制剂用于治疗老年男性性腺功能减退。这些疗法在其便利性、灵活性、区域供应和费用等方面有区别,但有共同的药代动力学基础,同时缺乏长期安全性数据。简洁和成本较低的基于药代动力学的注册临床试验使得开发改善性的治疗迟发性性腺功能减退的新疗法的商业动机减少了。在前列腺、头发、皮肤受雄激素缺乏影响的患者中,选择性雄激素受体调节剂已被证明可以提供合成代谢的好处。(目前,选择性雄激素受体调节剂的临床进展集中在有限定身体功能的临床终点的急性肌肉萎缩和低体重)。在具有有益的药理、理想的药代动力学的选择性雄激素受体调节剂应用于治疗迟发性男性性腺功能低下症前,其在男性性腺功能低下治疗中关于临床缺陷的更清晰的监管是必须的。 | Christopher C Coss Amanda Jones Michael L Hancock Mitchell S Steiner James T Dalton | 2014 | Asian Journal of Andrology2014，16，2： | 3 |
| 8 | Towards a standard diet-induced and biopsy-confirmed mouse model of non-alcoholic steatohepatitis: Impact of dietary fat source显示文摘BACKGROUND The trans-fat containing AMLN(amylin liver non-alcoholic steatohepatitis,NASH)diet has been extensively validated in C57BL/6J mice with or without the Lep^ob/Lep^ob(ob/ob)mutation in the leptin gene for reliably inducing metabolic and liver histopathological changes recapitulating hallmarks of NASH.Due to a recent ban on trans-fats as food additive,there is a marked need for developing a new diet capable of promoting a compatible level of disease in ob/ob and C57BL/6J mice.AIM To develop a biopsy-confirmed mouse model of NASH based on an obesogenic diet with trans-fat substituted by saturated fat.METHODS Male ob/ob mice were fed AMLN diet or a modified AMLN diet with trans-fat(Primex shortening)substituted by equivalent amounts of palm oil[Gubra amylin NASH,(GAN)diet]for 8,12 and 16 wk.C57BL/6J mice were fed the same diets for 28 wk.AMLN and GAN diets had similar caloric content(40%fat kcal),fructose(22%)and cholesterol(2%)level.RESULTS The GAN diet was more obesogenic compared to the AMLN diet and impaired glucose tolerance.Biopsy-confirmed steatosis,lobular inflammation,hepatocyte ballooning,fibrotic liver lesions and hepatic transcriptome changes were similar in ob/ob mice fed the GAN or AMLN diet.C57BL/6J mice developed a mild to moderate fibrotic NASH phenotype when fed the same diets.CONCLUSION Substitution of Primex with palm oil promotes a similar phenotype of biopsyconfirmed NASH in ob/ob and C57BL/6J mice,making GAN diet-induced obese mouse models suitable for characterizing novel NASH treatments. | Michelle L Boland Denise Oro Kirstine S T■lb■l Sebastian T Thrane Jens Christian Nielsen Taylor S Cohen David E Tabor Fiona Fernandes Andrey Tovchigrechko Sanne S Veidal Paul Warrener Bret R Sellman Jacob Jelsing Michael Feigh Niels Vrang James L Trevaskis Henrik H Hansen | 2019 | World Journal of Gastroenterology2019，25，33： | 3 |
| 9 | Stereotactic body radiation therapy for management of spinal metastases in patients without spinal cord compression: a phase 1–2 trial显示文摘 | Xin Shelley Wang Laurence D Rhines Almon S Shiu James N Yang Ugur Selek Ibrahima Gning Ping Liu Pamela K Allen Syed S Azeem Paul D Brown Hadley J Sharp David C Weksberg Charles S Cleeland Eric L Chang | 2012 | Lancet Oncology2012，，4： | 2 |
| 10 | Outcomes after arthroscopic repair of rotator cuff tears in the setting of mild to moderate glenohumeral osteoarthritis显示文摘BACKGROUND Rotator cuff pathology is a very common source of shoulder pain.Similarly,osteoarthritis of the glenohumeral joint can cause shoulder pain and produce similar symptoms.Surgical management can be indicated for both pathologies,however,outcomes data is limited when examining rotator cuff repair(RCR) in the setting of glenohumeral arthritis(GHOA).Thus,this study sought to determine outcomes for patients who undergo RCR in the setting of GHOA.AIM To evaluate if a relationship exists between outcomes of RCR in the setting of GHOA.METHODS This was a retrospective analysis of patients who underwent arthroscopic rotator cuff repair with concurrent glenohumeral osteoarthritis between 2010-2017.Patients were stratified based on rotator cuff tear size and glenohumeral osteoarthritis severity.Cohorts were paired 1:1 with patients without glenohumeral osteoarthritis.Patients included had a minimum two year follow-up.Rate of conversion to total shoulder arthroplasty,complication rates following initial surgery,and patient-reported outcome measures were collected.RESULTS A total of 142 patients were included.The number of patients that required total shoulder arthroplasty within two years after index surgery was low.2/71(2.8%) patients with GHOA,and 1/71(1.4%) without GHOA.Following rotator cuff repair,both groups showed favorable patientreported outcomes.CONCLUSION Patients with glenohumeral osteoarthritis who underwent arthroscopic rotator cuff repair showed comparable outcomes to patients without glenohumeral osteoarthritis. | Ian S Hong Allison J Rao Tyler L CarlLee Joshua D Meade Daniel J Hurwit Gregory Scarola David P Trofa Shadley C Schiffern Nady Hamid Patrick M Connor James E Fleischli Bryan Michael Saltzman | 2022 | World Journal of Orthopedics2022，13，7： | 2 |
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| 13 | Heart mito-chondria contain functional ATP-dependent K^+ channels 显示文摘 | Zsombor L James A S AllisonW M | 2003 | J M Cell Cardiol2003，35，13： | 1 |
| 14 | Complete genomes of two clinical Staphylococcus aureus strains:evidence for the rapid evolution of virulence and drug resistance显示文摘 | Holden MT Feil EJ Lindsay JA Peacock SJ Day NP Enright MC Foster TJ Moore CE Hurst L Atkin R Barron A Bason N Bentley SD Chillingworth C Chillingworth T Churcher C Clark L Corton C Cronin A Doggett J Dowd L Feltwell T Hance Z Harris B Hauser H Holroyd S Jagels K James KD Lennard N Line A Mayes R Moule S Mungall K Ormond D Quail MA Rabbinowitsch E Rutherford K Sanders M Sharp S Simmonds M Stevens K Whitehead S Barrell BG Spratt BG Parkhill J | 2004 | Proc Natl Acad Sci USA2004，101，26： | 1 |
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| 16 | Effect of CYP2C19 and ABCB1 single nucleotide polymorphisms on outcomes of treatment with ticagrelor versus clopidogrel for acute coronary syndromes : a genetic substudy of the Plato trial 显示文摘 | Ticagrelor versus clopidogrel in paN Engl J Med 2009 361(11): Wallentin L James S Storey RF | 2010 | Lancet2010，376，9749： | 1 |
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