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| 1 | 帕博利珠单抗单用或与放疗联用治疗转移性非小细胞肺癌:两个随机试验的汇总分析显示文摘背景放疗可以提高整个机体对免疫治疗的应答。在Ⅱ期PEMBRO-RT研究和Ⅰ/Ⅱ期MDACC研究中,患有转移性非小细胞肺癌(NSCLC)的患者被随机分配入组,接受免疫治疗(帕博利珠单抗)+放疗联合疗法,或免疫治疗单一疗法。当上述2个研究单独分析时,联合疗法组显示出潜在获益。由于每个研究的样本量较小,缓解率和结局并未显示出统计学意义,然而却有显著的临床获益。因此,本研究进行汇总分析,来判断放疗是否会改善转移性NSCLC患者的免疫治疗应答。方法PEMBRO-RT和MDACC研究纳入标准:患者年龄≥18岁,患有转移性NSCLC,且有≥1处未经放疗照射的病灶,以便进行射野外应答监测。PEMBRO-RT研究纳入曾接受过化疗患者,MDACC研究纳入曾接受过治疗或新诊断患者。2个研究中的患者均未接受过免疫治疗。在PEMBRO-RT研究中患者被等比例随机分配入组,并根据吸烟状态进行分层(分为<10年组和≥10年组)。MDACC研究的患者根据放疗计划可行性被等比例随机分配入2个受试组。由于联合治疗组的干预本质,每个研究中的放疗均不适用盲法。在2个研究中,不论是否进行放疗,均静脉滴入帕博利珠单抗(每3周200 mg)。在PEMBRO-RT研究中,在放疗(24 Gy 3次分割照射)结束后1周给予第1剂帕博利珠单抗。在MDACC研究中,在第1次放疗(50 Gy 4次分割照射或45 Gy 15次分割照射)同时给予帕博利珠单抗。仅检测未经照射病灶的应答。本研究的终点为最佳射野外(远隔)应答率(ARR)、最佳射野外疾病控制率(ACR)、12周时ARR、12周时ACR、无进展生存期(PFS)和总生存期(OS)。2个研究的意向治疗(ITT)人群均纳入分析。PEMBRO-RT研究(NCT02492568)和MDACC研究(NCT02444741)均在ClinicalTrials.gov上注册。发现纳入148例患者,76例接受帕博利珠单抗治疗,72例接受帕博利珠单抗+放疗治疗。所有患者随访时间中位数为33个月[四分位距(IQR):32.4~33.6]。148例患者中124例(84%)组织学特征为非鳞癌,111例(75%)患者曾经接受过化疗。组间没有基线特征差异,包括PD-L1表达状态和转移灶体积。最常见的照射部位为肺转移灶(39%,28/72)、胸腔内淋巴结(21%,15/72)和非原发灶(17%,12/72)。帕博利珠单抗组和联合治疗组的最佳ARR分别为19.7%(15/76)和41.7%(30/72),OR=2.96,95%CI:1.42~6.20,P=0.0039;最佳ACR分别为43.4%(33/76)和65.3%(47/72),OR=2.51,95%CI:1.28~4.91,P=0.0071;PFS中位数分别为4.4(IQR:2.9~5.9)和9.0个月(IQR:6.8~11.2),HR=0.67,95%CI:0.45~0.99,P=0.045;OS中位数分别为8.7(IQR:6.4~11.0)和19.2个月(IQR:14.6~23.8),OR=0.67,95%CI:0.54~0.84,P=0.0004。在汇总分析中没有发现新的安全问题。解读帕博利珠单抗免疫疗法+放疗显著提高转移性NSCLC患者的应答和改善治疗结局。这些结果需要在三期临床试验中进行验证。 | 陈大卫(翻译) 于金明(校对) Willemijn S M E Theelen Vivek Verma Brian P Hobbs Heike M U Peulen Joachim G J V Aerts Idris Bahce Anna Larissa N Niemeijer Joe Y Chang Patricia M de Groot Quynh-Nhu Nguyen Nathan I Comeaux George R Simon Ferdinandos Skoulidis Steven H Lin Kewen He Roshal Patel John Heymach Paul Baas James W Welsh | 2021 | 中华肿瘤防治杂志2021，28，24： | 49 |
| 2 | Ellagic acid induces apoptosis through inhibition of nuclear factor κB in pancreatic cancer cells显示文摘AIM:To determine the effect of ellagic acid on apop-tosis and proliferation in pancreatic cancer cells and to determine the mechanism of the pro-survival effects of ellagic acid. METHODS:The effect of ellagic acid on apoptosis was assessed by measuring Phosphatidylserine externalization,caspase activity,mitochondrial membrane potential and DNA fragmentation;and proliferation by measuring DNA thymidine incorporation. Mitochondrial membrane potential was measured in permeabilized cells,and in isolated mitochondria. Nuclear factor kB(NF-kB) activity was measured by electromobility shift assay(EMSA) . RESULTS:We show that ellagic acid,a polyphenolic compound in fruits and berries,at concentrations 10 to 50 mmol/L stimulates apoptosis in human pancreatic adenocarcinoma cells. Further,ellagic acid decreases proliferation by up to 20-fold at 50 mmol/L. Ellagic acid stimulates the mitochondrial pathway of apoptosis associated with mitochondrial depolarization,cytochrome C release,and the downstream caspaseactivation. Ellagic acid does not directly affect mitochondria. Ellagic acid dose-dependently decreased NF-kB binding activity. Furthermore,inhibition of NF-kB activity using IkB wild type plasmid prevented the effect of ellagic acid on apoptosis. CONCLUSION:Our data indicate that ellagic acid stimulates apoptosis through inhibition of the prosu-rvival transcription factor NF-kB. | Mouad Edderkaoui Irina Odinokova Izumi Ohno Ilya Gukovsky Vay Liang W Go Stephen J Pandol Anna S Gukovskaya | 2008 | World Journal of Gastroenterology2008，14，23： | 30 |
| 3 | Meta-analyses on prevalence of selected Parkinson’s nonmotor symptoms before and after diagnosis显示文摘Background:Nonmotor symptoms are common among patients with Parkinson’s disease(PD)and some may precede disease diagnosis.Methods:We conducted a meta-analysis on the prevalence of selected nonmotor symptoms before and after PD diagnosis,using random-effect models.We searched PubMed(1965 through October/November 2012)for the following symptoms:hyposmia,constipation,rapid eye movement sleep behavior disorder,excessive daytime sleepiness,depression,and anxiety.Eligible studies were publications in English with original data on one or more of these symptoms.Results:The search generated 2,373 non-duplicated publications and 332 met the inclusion criteria,mostly(n=320)on symptoms after PD diagnosis.For all symptoms,the prevalence was substantially higher in PD cases than in controls,each affecting over a third of the patients.Hyposmia was the most prevalent(75.5%in cases vs.19.1%in controls),followed by constipation(50%vs.17.7%),anxiety(39.9%vs.19.1%),rapid eye movement sleep behavior disorder(37.0%vs.7.0%),depression(36.6%vs.14.9%),and excessive daytime sleepiness(33.9%vs.10.5%).We observed substantial heterogeneities across studies and meta-regression analyses suggested that several factors might have contributed to this.However,the prevalence estimates were fairly robust in several sensitivity analyses.Only 20 studies had data on any symptoms prior to PD diagnosis,but still the analyses revealed higher prevalence in future PD cases than in controls.Conclusion:These symptoms are common among PD patients both before and after diagnosis.Further studies are needed to understand the natural history of nonmotor symptoms in PD and their etiological and clinical implications. | Honglei Chen Edward J Zhao Wen Zhang Yi Lu Rui Liu Xuemei Huang Anna J Ciesielski-Jones Michele A Justice Deborah S Cousins Shyamal Peddada | 2015 | Translational Neurodegeneration2015，4，1： | 18 |
| 4 | The circulating non-coding RNA landscape for biomarker research: lessons and prospectsfrom cardiovascular diseases显示文摘人的染色体的弥漫的抄写为无数非编码的 RNA 分子(ncRNAs ) 的生产负责有规章的功能的他们的一些。在心血管的生物学的 ncRNAs 的枢轴的角色在最后十年被揭开了,从在心血管的开发和功能的 micro-RNAs 的参与的描述开始,并且作为心血管的疾病的 biomarkers 由传播 ncRNAs 的使用列在后面。人的非编码的 secretome 被几 RNA 种填写在身体液体传播并且能为诊断和结果预言被用作 biomarkers。在心血管的疾病,分泌了 ncRNAs 包括心肌的梗塞,心脏的失败,和 atrial 纤维性颤动被描述了为几个条件的 biomarkers。在传播之中, ncRNAs, micro-RNAs (miRNAs ) ,长 noncoding RNA (lncRNAs ) 和圆形的 RNA (circRNAs ) 在不同心血管的疾病作为 biomarkers 被建议了。与标准 biomarkers 比较, ncRNAs 的生物化学的性质为更好的稳定性和灵活存储提供样品,和增加的敏感和特性的条件。在这评论,我们把当前的趋势和 ncRNA secretome 部件的使用的未来前景描述为心血管的疾病的 biomarkers,包括与他们的分泌物机制和规章的行动联系的开的问题。 | Ewa STFPIEN Marina C COSTA Szczepan KURC Anna DROZDZ Nuno CORTEZ-DIAS Francisco J ENGUITA | 2018 | Acta Pharmacologica Sinica2018，39，7： | 14 |
| 5 | Association of symptoms with gastrointestinal microbiota in irritable bowel syndrome显示文摘AIM:To investigate the correlations between selfreported symptoms of irritable bowel syndrome(IBS) and the gastrointestinal(GI) microbiota composition.METHODS:Fecal samples were collected from a total of 44 subjects diagnosed with IBS.Their symptoms were monitored with a validated inflammatory bowel disease questionnaire adjusted for IBS patients.Thirteen quantitative real-time polymerase chain reaction assays were applied to evaluate the GI microbiota composition.Eubacteria and GI bacterial genera(Bifidobacterium,Lactobacillus and Veillonella),groups(Clostridium coccoides/Eubacterium rectale,Desulfovibrio desulfuricans) and distinct bacterial phylotypes [closest 16S rDNA sequence resemblance to species Bifidobacterium catenulatum,Clostridium cocleatum,Collinsella aerofaciens(C.aerofaciens),Coprococcus eutactus(C.eutactus),Ruminococcus torques and Streptococcus bovis ] with a suspected association with IBS were quantified.Correlations between quantities or presence/absence data of selected bacterial groups or phylotypes and various IBSrelated symptoms were investigated.RESULTS:Associations were observed between subjects' self-reported symptoms and the presence or quantities of certain GI bacteria.A Ruminococcus torques(R.torques)-like(94% similarity in 16S rRNA gene sequence) phylotype was associated with severity of bowel symptoms.Furthermore,among IBS subjects with R.torques 94% detected,the amounts of C.cocleatum 88%,C.aerofaciens-like and C.eutactus 97% phylotypes were significantly reduced.Interesting observations were also made concerning the effect of a subject's weight on GI microbiota with regard to C.aerofaciens like phylotype,Bifidobacterium spp.and Lactobacillus spp.CONCLUSION:Bacteria seemingly affecting the symptom scores are unlikely to be the underlying cause or cure of IBS,but they may serve as biomarkers of the condition. | Erja Malinen Lotta Krogius-Kurikka Janne Nikkil Airi Palva Anna Lyra Anne Jskelinen Teemu Rinttil Terttu Vilpponen-Salmela Atte Johannes von Wright | 2010 | World Journal of Gastroenterology2010，16，36： | 13 |
| 6 | 西那卡塞降低血液透析患者钙性尿毒症小动脉病变的发生显示文摘终末期肾病(ESRD)患者未控制的继发性甲状旁腺功能亢进(secondary hyperparathyroidism,SHPT),是钙性尿毒症小动脉病变(calcific uremic arteriolopathy,CUA,即钙化防御)的危险因素。CUA是相对罕见的综合症,1年生存率仅为45%;其主要病变是皮肤和脂肪组织小动脉和中动脉壁的中层钙化,导致进行性和极其痛苦的皮肤溃疡、感染,是CUA高死亡率的主要原因。CUA很少见于肾功能正常的患者,大多数CUA都局限于晚期CKD尤其是ESRD患者。在所有ESRD患者中CUA的患病率估计为1%到4%。 | Jürgen Floege Yumi Kubo Anna Floege 王建中 | 2015 | 中华肾病研究电子杂志2015，4，3： | 13 |
| 7 | Review of nonalcoholic fatty liver disease in women with polycystic ovary syndrome显示文摘Polycystic ovary syndrome(PCOS) is the most common endocrine disorder in reproductive-aged women. Women with PCOS frequently have metabolic complications including insulin resistance(IR), early diabetes, hypertension and dyslipidemia. Recent studies have demonstrated an association between PCOS and another metabolic complication: nonalcoholic fatty liver disease(NAFLD). NAFLD occurs as a result of abnormal lipid handling by the liver, which sensitizes the liver to injury and inflammation. It can progress to nonalcoholic steatohepatitis(NASH), which is characterized by hepatocyte injury and apoptosis. With time and further inflammation, NASH can progress to cirrhosis. Thus, given the young age at which NAFLD may occur in PCOS, these women may be at significant risk for progressive hepatic injury over the course of their lives. Many potential links between PCOS and NAFLD have been proposed, most notably IR and hyperandrogenemia. Further studies are needed to clarify the association between PCOS and NAFLD. In the interim, clinicians should be aware of this connection and consider screening for NAFLD in PCOS patients who have other metabolic risk factors. The optimal method of screening is unknown. However, measuring alanine aminotransferase and/or obtaining ultrasound on high-risk patients can be considered. First line treatment consists of lifestyle interventions and weight loss, with possible pharmacologic interventions in some cases. | Carly E Kelley Ann J Brown Anna Mae Diehl Tracy L Setji | 2014 | World Journal of Gastroenterology2014，20，39： | 11 |
| 8 | The enhanced X-ray Timing and Polarimetry mission—eXTP显示文摘In this paper we present the enhanced X-ray Timing and Polarimetry mission—eXTP. eXTP is a space science mission designed to study fundamental physics under extreme conditions of density, gravity and magnetism. The mission aims at determining the equation of state of matter at supra-nuclear density, measuring effects of QED, and understanding the dynamics of matter in strong-field gravity. In addition to investigating fundamental physics, eXTP will be a very powerful observatory for astrophysics that will provide observations of unprecedented quality on a variety of galactic and extragalactic objects. In particular, its wide field monitoring capabilities will be highly instrumental to detect the electro-magnetic counterparts of gravitational wave sources.The paper provides a detailed description of:(1) the technological and technical aspects, and the expected performance of the instruments of the scientific payload;(2) the elements and functions of the mission, from the spacecraft to the ground segment. | ShuangNan Zhang Andrea Santangelo Marco Feroci YuPeng Xu FangJun Lu Yong Chen Hua Feng Shu Zhang Sφren Brandt Margarita Hernanz Luca Baldini Enrico Bozzo Riccardo Campana Alessandra De Rosa YongWei Dong Yuri Evangelista Vladimir Karas Norbert Meidinger Aline Meuris Kirpal Nandra Teng Pan Giovanni Pareschi Piotr Orleanski QiuShi Huang Stephane Schanne Giorgia Sironi Daniele Spiga Jiri Svoboda Gianpiero Tagliaferri Christoph Tenzer Andrea Vacchi Silvia Zane Dave Walton ZhanShan Wang Berend Winter Xin Wu Jean J.M.in't Zand Mahdi Ahangarianabhari Giovanni Ambrosi Filippo Ambrosino Marco Barbera Stefano Basso Jörg Bayer Ronaldo Bellazzini Pierluigi Bellutti Bruna Bertucci Giuseppe Bertuccio Giacomo Borghi XueLei Cao Franck Cadoux Francesco Ceraudo TianXiang Chen Yu Peng Chen Jerome Chevenez Marta Civitani Wei Cui WeiWei Cui Thomas Dauser Ettore Del Monte Sergio Di Cosimo Sebastian Diebold Victor Doroshenko Michal Dovciak YuanYuan Du Lorenzo Ducci QingMei Fan Yannick Favre Fabio Fuschino JoséLuis Ga'lvez Min Gao MingYu Ge Olivier Gevin Marco Grassi QuanYing Gu YuDong Gu DaWei Han Bin Hong Wei Hu Long Ji ShuMei Jia WeiChun Jiang Thomas Kennedy Ingo Kreykenbohm Irfan Kuvvetli Claudio Labanti Luca Latronico Gang Li MaoShun Li Xian Li Wei Li ZhengWei Li Olivier Limousin HongWei Liu XiaoJing Liu Bo Lu Tao Luo Daniele Macera Piero Malcovati Adrian Martindale Malgorzata Michalska Bin Meng Massimo Minuti Alfredo Morbidini Fabio Muleri Stephane Paltani Emanuele Perinati Antonino Picciotto Claudio Piemonte JinLu Qu Alexandre Rachevski Irina Rashevskaya Jerome Rodriguez Thomas Schanz ZhengXiang Shen LiZhi Sheng JiangBo Song LiMing Song Carmelo Sgro Liang Sun Ying Tan Phil Uttley Bo Wang DianLong Wang GuoFeng Wang Juan Wang LangPing Wang YuSa Wang Anna L.Watts XiangYang Wen Jörn Wilms ShaoLin Xiong JiaWei Yang Sheng Yang YanJi Yang Nian Yu WenDa Zhang Gianluigi Zampa Nicola Zampa Andrzej A.Zdziarski AiMei Zhang ChengMo Zhang Fan Zhang Long Zhang Tong Zhang Yi Zhang XiaoLi Zhang ZiLiang Zhang BaoSheng Zhao ShiJie Zheng Yu Peng Zhou Nicola Zorzi J.Frans Zwart | 2019 | Science China(Physics,Mechanics & Astronomy)2019，62，2： | 11 |
| 9 | Management of hypertension in primary aldosteronism显示文摘Hypertension causes significant morbidity and mortal-ity worldwide, owing to its deleterious effects on the cardiovascular and renal systems. Primary hyperaldo-steronism(PA) is the most common cause of revers-ible hypertension, affecting 5%-18% of adults with hypertension. PA is estimated to result from bilateral adrenal hyperplasia in two-thirds of patients, and from unilateral aldosterone-secreting adenoma in approxi-mately one-third. Suspected cases are initially screened by measurement of the plasma aldosterone-renin-ratio, and may be confirmed by additional noninvasive tests. Localization of aldostosterone hypersecretion is then determined by computed tomography imaging, and in selective cases with adrenal vein sampling. Solitary adenomas are managed by laparoscopic or robotic re-section, while bilateral hyperplasia is treated with min-eralocorticoid antagonists. Biochemical cure following adrenalectomy occurs in 99% of patients, and hemo-dynamic improvement is seen in over 90%, prompting a reduction in quantity of anti-hypertensive medica-tions in most patients. End-organ damage secondary to hypertension and excess aldosterone is significantly improved by both surgical and medical treatment, asmanifested by decreased left ventricular hypertrophy, arterial stiffness, and proteinuria, highlighting the im-portance of proper diagnosis and treatment of primary hyperaldosteronism. Although numerous independent predictors of resolution of hypertension after adrenalec-tomy for unilateral adenomas have been described, the Aldosteronoma Resolution Score is a validated multifac-torial model convenient for use in daily clinical practice. | Anna Aronova Thomas J Fahey Ⅲ Rasa Zarnegar | 2014 | World Journal of Cardiology2014，6，5： | 11 |
| 10 | Intravenous vitamin C as adjunctive therapy for enterovirus/rhinovirus induced acute respiratory distress syndrome显示文摘We report a case of virus-induced acute respiratory distress syndrome(ARDS) treated with parenteral vitamin C in a patient testing positive for enterovirus/rhinovirus on viral screening. This report outlines the first use of high dose intravenous vitamin C as an interventional therapy for ARDS, resulting from enterovirus/rhinovirus respiratory infection. From very significant preclinical research performed at Virginia Commonwealth Universitywith vitamin C and with the very positive results of a previously performed phase Ⅰ safety trial infusing high dose vitamin C intravenously into patients with severe sepsis, we reasoned that infusing identical dosing to a patient with ARDS from viral infection would be therapeutic. We report here the case of a 20-year-old, previously healthy, female who contracted respiratory enterovirus/rhinovirus infection that led to acute lung injury and rapidly to ARDS. She contracted the infection in central Italy while on an 8-d spring break from college. During a return flight to the United States, she developed increasing dyspnea and hypoxemia that rapidly developed into acute lung injury that led to ARDS. When support with mechanical ventilation failed, extracorporeal membrane oxygenation(ECMO) was initiated. Twelve hours following ECMO initiation, high dose intravenous vitamin C was begun. The patient's recovery was rapid. ECMO and mechanical ventilation were discontinued by day-7 and the patient recovered with no long-term ARDS sequelae. Infusing high dose intravenous vitamin C into this patient with virus-induced ARDS was associated with rapid resolution of lung injury with no evidence of post-ARDS fibroproliferative sequelae. Intravenous vitamin C as a treatment for ARDS may open a new era of therapy for ARDS from many causes. | Alpha A Fowler Ⅲ Christin Kim Lawrence Lepler Rajiv Malhotra Orlando Debesa Ramesh Natarajan Bernard J Fisher Aamer Syed Christine DeWilde Anna Priday Vigneshwar Kasirajan | 2017 | World Journal of Critical Care Medicine2017，6，1： | 9 |
| 11 | 如何设计高质量针刺临床研究:基于证据的专家共识显示文摘本针刺随机对照试验(Randomised controlled trials, RCT)专家共识是基于目前针刺试验面临的最普遍、最关键问题,由临床医生、研究人员、从事针灸和外科的临床试验专家、统计专家、临床流行病学和方法学专家以及患者组成的国际临床研究小组联合制订。该共识将有助于临床试验资助者、注册者以及期刊编辑等评估针刺RCT方案及研究结果的相关性、重要性和质量。 | 张誉清 焦睿珉 Claudia M Witt 劳力行 刘建平 Lehana Thabane Karen J Sherman Mike Cummings Dawn P Richards Eun-Kyung Anna Kim Tae-Hun Kim Myeong Soo Lee Michael E Wechsler Benno Brinkhaus Jun J Mao Caroline A Smith 岗卫娟 刘保延 刘志顺 刘岩 郑晖 吴佳霓 AloBSO Carrasco-Labra Mohit Bhandari Philip J Devereaux 景向红 Gordon Guyatt | 2022 | 英国医学杂志中文版2022，25，6： | 7 |
| 12 | Ghrelin and gastrin in advanced gastric cancer before and after gastrectomy显示文摘AIM: To investigate plasma ghrelin, gastrin and growth hormone secretagogue receptor (GHS-R) expression in advanced gastric cancer (GC) before and after resection. METHODS: Seventy subjects in whom endoscopy of the upper gastrointestinal tract was performed in the Department of General Surgery at Cracow University during the past decade: (1) 25 patients with GC associated with Helicobacter pylori (H. pylori) infection; (2) 10 patients with GC 4-5 years after (total or subtotal) gastrectomy; (3) 25 healthy H. pylori-negative controls, matched by age and BMI to the above two groups; and (4) 10 GC patients 4-5 years after total gastrectomy. Ghrelin and gastrin plasma concentrations were measured by specific radioimmunoassay under fasting conditions and postprandially at 60 and 90 min after ingestion of a mixed meal. GHS-R expression was examined in biopsy samples from intact healthy mucosa and GC tissue using semi-quantitative reverse transcription-polymerase chain reaction. RESULTS: In healthy controls, fasting plasma ghrelin levels were significantly elevated and declined markedly at 60 and 90 min after a mixed meal. The concomitant enhanced ghrelin, GHS-R and gastrin expression in GC tissue over that recorded in intact mucosa, and the marked rise in plasma gastrin in these subjects under fasting conditions indicate the role of these hormonal factors in GC formation. Fasting plasma levels and postprandial response of ghrelin and gastrin appear to be inversely correlated in healthy subjects. Feeding in the controls resulted in a significant fall in plasma ghrelin with a subsequent rise in plasma gastrin, but in H. pylori-positive GC patients submitted to total or distal gastrectomy, feeding failed to affect significantly the fall in plasma ghrelin that was recorded in these patients before surgery. Fasting ghrelin concentrations were significantly lower in patients 4-5 years after total gastrectomy compared to those in healthy controls and to these in GC patients before surgery. CONCLUSION: Elevated plasma gastrin and suppression of fasting ghrelin in patients with GC suggest the existence of a close relationship between these two hormones in gastric carcinogenesis. | Anna Zub-Pokrowiecka Kazimierz Rembiasz Peter C Konturek Andrzej Budzyński Stanisaw J Konturek Marek Winiarski Wadysaw Bielański | 2011 | World Journal of Gastroenterology2011，17，4： | 7 |
| 13 | Osteoclast activity modulates B-cell development in the bone marrow显示文摘B 房间开发开是依赖的在 B 房间先锋和骨头髓 stromal 房间之间的相互作用,而是在这的骨破折(OCL ) 的角色处理未知的遗体。B lymphocytopenia 是 osteopetrosis 的一个特征,建议由 OCL 活动的 B 淋巴细胞增殖的调整。探讨这个问题,我们首先由树枝状的房间转移在 osteopetrotic oc/oc 鼠标救了 OCL 功能,导致骨头显型和 B 房间开发的恢复。为了推进,探索在 OCL 活动和 B 淋巴细胞增殖之间的连接,我们由 zoledronic 酸(ZA ) 的注射在正常老鼠导致了 osteopetrosis,骨头再吞的一个禁止者。B 房间数字在对待 ZA 的老鼠的骨头髓明确地减少了。ZA 直接没影响 B 房间区别,增长和 apoptosis,但是由 stromal 房间在 CXCL12 和 IL-7 的表示导致减少,与减少的 osteoblastic 约会联系了。在 oc/oc 老鼠的相等的低 osteoblastic 约会证实它在造骨细胞上源于减少的 OCL 活动而非从 ZA 的直接效果。骨头微型环境的这些戏剧的改变为 B 淋巴细胞增殖是不利的,导致在他们在导致 ZA 的 osteopetrotic 模型的骨头髓壁龛外面的 B 房间祖先的保留。总的来说,我们的数据表明 OCL 由控制骨头微型环境和造骨细胞的命运在骨头髓调制 B 房间开发。他们由 OCL 活动在他们的壁龛为 B 房间的保留的规定提供新奇基础。 | Anna Mansour | 2011 | Cell Research2011，21，7： | 6 |
| 14 | Relationship between Th17 immune response and cancer显示文摘Cancer is the second leading cause of death worldwide and epidemiological projections predict growing cancer mortality rates in the next decades.Cancer has a close relationship with the immune system and,although Th17 cells are known to play roles in the immune response against microorganisms and in autoimmunity,studies have emphasized their roles in cancer pathogenesis.The Th17 immune response profile is involved in several types of cancer including urogenital,respiratory,gastrointestinal,and skin cancers.This type of immune response exerts pro and antitumor functions through several mechanisms,depending on the context of each tumor,including the protumor angiogenesis and exhaustion of T cells and the antitumor recruitment of T cells and neutrophils to the tumor microenvironment.Among other factors,the paradoxical behavior of Th17 cells in this setting has been attributed to its plasticity potential,which makes possible their conversion into other types of T cells such as Th17/Treg and Th17/Th1 cells.Interleukin(IL)-17 stands out among Th17-related cytokines since it modulates pathways and interacts with other cell profiles in the tumor microenvironment,which allow Th17 cells to prevail in tumors.Moreover,the IL-17 is able to mediate pro and antitumor processes that influence the development and progression of various cancers,being associated with variable clinical outcomes.The understanding of the relationship between the Th17 immune response and cancer as well as the singularities of carcinogenic processes in each type of tumor is crucial for the identification of new therapeutic targets. | Hanna Santos Marques Breno Bittencourt de Brito Filipe Antônio França da Silva Maria Luísa Cordeiro Santos Júlio César Braga de Souza Thiago Macêdo Lopes Correia Luana Weber Lopes Nayara Silva de Macêdo Neres Rafael Santos Dantas Miranda Dórea Anna Carolina Saúde Dantas Lorena Lôbo Brito Morbeck Iasmin Souza Lima Amanda Alves de Almeida Maiara Raulina de Jesus Dias Fabrício Freire de Melo | 2021 | World Journal of Clinical Oncology2021，12，10： | 5 |
| 15 | Deletion or underexpression of the Y-chromosome genes CDY2 and HSFY is associated with maturation arrest in American men with nonobstructive azoospermia显示文摘成熟拘捕(麻省) 指导致临床的 nonobstructive 精子缺乏的细菌房间开发的失败。尽管人的 Y 染色体的 azoospermic 因素(AZF ) 区域清楚地在一些情况中被含有,因此,远,很,很少对哪个个人, Y 染色体基因为完全的男细菌房间开发是重要的被知道。我们寻求了在可以在在美国人口与麻省联系的 nonobstructive 精子缺乏的致病被含有的 Y 染色体上识别单个基因。有 Y 染色体 microdeletions 的 132 个人的遗传型显型分析被执行。与麻省联系的编码蛋白质的基因被一张遗传型显型地图的视觉分析识别。与麻省联系的基因在 Y 染色体的一个片断以内作为那些基因被选择完全或部分删除了,总是与可恢复的阴囊的精子的麻省和缺席被联系。每个识别基因抄本的表示然后与自发的麻省和妨碍的精子缺乏从病人的分开的队在阴囊的织物与量的 RT-PCR 被测量。为有麻省的协会的十候选人基因在重叠的 Y 染色体的一个 8.4-Mb 片断以内被识别 AZFb 区域。CDY2 和 HSFY 是唯一的识别了在表示的差别在麻省和妨碍的精子缺乏队之间为被观察的基因。有妨碍的精子缺乏的人有 12 褶层 CDY2 抄本的更高相对的表示(1.33 ± 0.40 对 0.11 ± 0.04;P=0.0003 ) 并且 16 褶层 HSFY 抄本的更高的表示(0.78 ± 0.32 对 0.05 ± 0.02;P=0.0005 ) 与有麻省的人相比。CDY2 和 HSFY 也仅仅是在有 Sertoli 房间的病人的 underexpressed 症候群。这些数据显示 CDY2 和 HSFY 位于为精子成熟是重要的,并且是在与麻省从人导出的阴囊的织物的 underexpressed 的 Y 染色体的一个片断以内。这些观察建议在 CDY2 或 HSFY 表示的缺陷能在麻省的致病被含有。 | Peter J Stahl Anna N Mielnik Christopher E Barbieri Peter N Schlegel Darius A Paduch | 2012 | Asian Journal of Andrology2012，14，5： | 3 |
| 16 | Epithelial-Mesenchymal Transition: A Hallmark in Metastasis Formation Linking Circulating Tumor Cells and Cancer Stem Cells显示文摘 | Ksiazkiewicz Magdalena Markiewicz Aleksandra Zaczek Anna J | 2012 | Pathobiology2012，，4： | 3 |
| 17 | Zulu medicinal plants with antibacterial activity显示文摘 | Jonathan E. Kelmanson Anna K. J?ger Johannes van Staden | 2000 | Journal of Ethnopharmacology2000，，3： | 2 |
| 18 | Liver stiffness reversibly increases during pregnancy and independently predicts preeclampsia显示文摘AIM To study liver stiffness(LS) during pregnancy and its association with complications during pregnancy.METHODS In this observational, diagnostic study, 537 pregnant women were prospectively enrolled at the Department of Obstetrics and Gynecology, University hospital Heidelberg and Salem Medical Center. LS was measured using the Fibroscan device(Echosens, Paris) in all women and in 41 cases 24 h after delivery. Clinical and morphological data were recorded and abdominal ultrasound and standard laboratory tests were performed. No complications were observed in 475 women(controls) while preeclampsia and intrahepatic cholestasis of pregnancy(ICP) developed in 22 and 40 women, respectively.RESULTS In controls, LS increased significantly from initially 4.5 ± 1.2 kPa in the second trimester to 6.0 ± 2.3 kPa(P < 0.001) in the third trimester. In the third trimester, 41% of women had a LS higher than 6 kPa. Elevated LS in controls was significantly correlated with alkaline phosphatase, leukocytes, gestational age and an increase in body weight and body mass index(BMI). In women with pregnancy complications, LS was significantly higher as compared to controls(P < 0.0001). Moreover, in multivariate analysis, LS was an independent predictor for preeclampsia with an odds ratio of 2.05(1.27-3.31) and a cut-off value of 7.6 kPa. In contrast, ICP could not be predicted by LS. Finally, LS rapidly decreased in all women within 24 h after delivery from 7.2 ± 3.3 kPa down to 4.9 ± 2.2 kPa(P < 0.001).CONCLUSION During pregnancy, LS significantly and reversibly increases in the final trimester of pregnant women without complications. In women with preeclampsia, LS is significantly elevated and an independent noninvasive predictor. | Franziska J Ammon Anna Kohlhaas Omar Elshaarawy Johannes Mueller Thomas Bruckner Christof Sohn Gabriele Fluhr Herbert Fluhr Sebastian Mueller | 2018 | World Journal of Gastroenterology2018，24，38： | 2 |
| 19 | Embryonic stem cell-derived chondrogenic differentiation in vitro: activation by BMP-2 and BMP-4显示文摘 | Jan Kramer Claudia Hegert Kaomei Guan Anna M Wobus Peter K Müller Jürgen Rohwedel | 2000 | Mechanisms of Development2000，，2： | 2 |
| 20 | Global review and synthesis of trends in observed terrestrial near-surface wind speeds: Implications for evaporation显示文摘 | Tim R. McVicar Michael L. Roderick Randall J. Donohue Ling Tao Li Thomas G. Van Niel Axel Thomas Jürgen Grieser Deepak Jhajharia Youcef Himri Natalie M. Mahowald Anna V. Mescherskaya Andries C. Kruger Shafiqur Rehman Yagob Dinpashoh | 2011 | Journal of Hydrology2011，，： | 2 |
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