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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 | Pancreatic regenerating protein (regⅠ) and regⅠreceptor mRNA are upregulated in rat pancreas after induction of acute pancreatitis显示文摘AIM: Pancreatic regenerating protein (regⅠ) stimulates pancreatic regeneration after pancreatectomy and is mitogenic to ductal andβ-cells. This suggests that regⅠand its receptor may play a role in recovery after pancreatic injury. We hypothesized that regⅠand its receptor are induced in acute pancreatitis. METHODS: Acute pancreatitis was induced in male Wistar rats by retrograde injection of 3% sodium taurocholate into the pancreatic duct. Pancreata and serum were collected 12, 24, and 36 hours after injection and from normal controls (4 rats/group). RegⅠreceptor mRNA, serum regⅠprotein, and tissue regⅠprotein levels were determined by Northern analysis, enzyme-linked immunosorbent assay (ELISA), and Western analysis, respectively. Immunohistochemistry was used to localize changes in regⅠand its receptor. RESULTS: Serum amylase levels and histology confirmed necrotizing pancreatitis in taurocholate treated rats. There was no statistically significant change in serum regⅠconcentrations from controls. However, Western blot demonstrated increased tissue levels of regⅠat 24 and 36 h. This increase was localized primarily to the acinar cells and the ductal cells by immunohistochemistry. Northern blot demonstrated a significant increase in regⅠreceptor mRNA expression with pancreatitis. Immunohistochemistry localized this increase to the ductal cells, islets, and acinar cells. CONCLUSION: Acute pancreatitis results in increased tissue regⅠprotein levels localized to the acinar and ductal cells, and a parallel threefold induction of regⅠreceptor in the ductal cells, islets, and acinar cells. These changes suggest that induction of reg I and its receptor may be important for recovery from acute pancreatitis. | Martin H Bluth Sameer A Patel Brian K Dieckgraefe Hiroshi Okamoto Michael E Zenilman | 2006 | World Journal of Gastroenterology2006，12，28： | 19 |
| 3 | Gut microbiome in acute pancreatitis:A review based on current literature显示文摘The gut microbiome is a complex microbial community,recognized for its potential role in physiology,health,and disease.The available evidence supports the role of gut dysbiosis in pancreatic disorders,including acute pancreatitis(AP).In AP,the presence of gut barrier damage resulting in increased mucosal permeability may lead to translocation of intestinal bacteria,necrosis of pancreatic and peripancreatic tissue,and infection,often accompanied by multiple organ dysfunction syndrome.Preserving gut microbial homeostasis may reduce the systemic effects of AP.A growing body of evidence suggests the possible involvement of the gut microbiome in various pancreatic diseases,including AP.This review discusses the possible role of the gut microbiome in AP.It highlights AP treatment and supplementation with prebiotics,synbiotics,and probiotics to maintain gastrointestinal microbial balance and effectively reduce hospitalization,morbidity and mortality in an early phase.It also addresses novel therapeutic areas in the gut microbiome,personalized treatment,and provides a roadmap of human microbial contributions to AP that have potential clinical benefit. | Bharati Kadamb Patel Kadamb H Patel Madhav Bhatia Shridhar Ganpati Iyer Krishnakumar Madhavan Shabbir M Moochhala | 2021 | World Journal of Gastroenterology2021，27，30： | 10 |
| 4 | Redox therapeutics in hepatic ischemia reperfusion injury显示文摘Ischemia-reperfusion plays a major role in the injury experienced by the liver during transplantation. Much work has been done recently investigating the role of redox species in hepatic ischemia-reperfusion. As animal models are better characterized and developed, and more insights are gained into the pathophysiology of hepatic ischemia reperfusion injury in humans the questions into exactly how oxidants participate in this injury are becoming more refined. These questions include effects of cellular location, timing of injury, and ability of therapeutics to access this site are increasing our appreciation of the complexity of ischemia reperfusion and improving attempts to ameliorate its effects. In this review, we aim to discuss the various methods to alter redox chemistry during ischemia reperfusion injury and future prospects for preventing organ injury during hepatic ischemia reperfusion. | Rakesh P Patel John D Lang Alvin B Smith Jack H Crawford | 2014 | World Journal of Hepatology2014，6，1： | 9 |
| 5 | Ever-increasing diversity of drug-induced pancreatitis显示文摘With over 100000 hospital admissions per annum,acute pancreatitis remains the leading gastrointestinal cause of hospitalization in the United States and has farreaching impact well beyond.It has become increasingly recognized that druginduced pancreatitis(DIP),despite accounting for less than 3%of all cases,represents an important and growing though often inconspicuous cause of acute pancreatitis.Nevertheless,knowledge of DIP is often curtailed by the limited availability of evidence needed to implicate given agents,especially for nonprescription medications.Indeed,the majority of available data is derived from case reports,case series,or case control studies.Furthermore,the mechanism of injury and causality for many of these drugs remain elusive as a definitive correlation is generally not established(<10%of cases).Several classification systems have been proposed,but no single system has been widely adopted,and periodic updates are required in light of ongoing pharmacologic expansion.Moreover,infrequently prescribed medications or those available over-thecounter(including herbal and other alternative remedies)are often overlooked as a potential culprit of acute pancreatitis.Herein,we review the ever-increasing diversity of DIP and the potential mechanisms of injury with the goal of raising awareness regarding the nature and magnitude of this entity.We believe this manuscript will aid in increasing both primary and secondary prevention of DIP,thus ultimately facilitating more expedient diagnosis and a decrease in DIPrelated morbidity. | Simcha Weissman Muhammad Aziz Ryan B Perumpail Tej I Mehta Rutwik Patel James H Tabibian | 2020 | World Journal of Gastroenterology2020，26，22： | 8 |
| 6 | 中心和外周动脉脉搏波传导速度测量的重复性:社区动脉粥样硬化风险研究显示文摘通过脉搏波传导速度(pulsewavevelocity,PwV)检测动脉硬化程度是当前对高血压和心血管病风险评估和分层所日渐常用的方式。颈股动脉脉搏波传导速度(catroidfemoralarteryPWV,cfPWV)是一项公认的测定中心动脉硬化程度的方式。 | Meyer ML Tanaka H Palta P Patel MD Camplain R Couper D Cheng S Al Qunaibet A Poon AK Heiss G 陈云 叶鹏 | 2016 | 中华高血压杂志2016，24，5： | 6 |
| 7 | Counter-regulatory phosphatases TNAP and NPP1 temporally regulate tooth root cementogenesis显示文摘Cementum is critical for anchoring the insertion of periodontal ligament fibers to the tooth root. Several aspects of cementogenesis remain unclear, including differences between acellular cementum and cellular cementum, and between cementum and bone.Biomineralization is regulated by the ratio of inorganic phosphate(Pi) to mineral inhibitor pyrophosphate(PPi), where local Piand PPi concentrations are controlled by phosphatases including tissue-nonspecific alkaline phosphatase(TNAP) and ectonucleotide pyrophosphatase/phosphodiesterase 1(NPP1). The focus of this study was to define the roles of these phosphatases in cementogenesis. TNAP was associated with earliest cementoblasts near forming acellular and cellular cementum. With loss of TNAP in the Alpl null mouse, acellular cementum was inhibited, while cellular cementum production increased, albeit as hypomineralized cementoid. In contrast, NPP1 was detected in cementoblasts after acellular cementum formation, and at low levels around cellular cementum. Loss of NPP1 in the Enpp1 null mouse increased acellular cementum, with little effect on cellular cementum.Developmental patterns were recapitulated in a mouse model for acellular cementum regeneration, with early TNAP expression and later NPP1 expression. In vitro, cementoblasts expressed Alpl gene/protein early, whereas Enpp1 gene/protein expression was significantly induced only under mineralization conditions. These patterns were confirmed in human teeth, including widespread TNAP, and NPP1 restricted to cementoblasts lining acellular cementum. These studies suggest that early TNAP expression creates a low PPienvironment promoting acellular cementum initiation, while later NPP1 expression increases PPi, restricting acellular cementum apposition. Alterations in PPihave little effect on cellular cementum formation, though matrix mineralization is affected. | Laura E Zweifler Mudita K Patel Francisco H Nociti Jr Helen F Wimer Jose L Milln Martha J Somerman Brian L Foster | 2015 | International Journal of Oral Science2015，7，1： | 5 |
| 8 | Coagonist of glucagon-like peptide-1 and glucagon receptors ameliorates kidney injury in murine models of obesity and diabetes mellitus显示文摘AIM To investigate the role of glucagon-like peptide-1(GLP-1)/glucagon receptors coagonist on renal dysfunction associated with diabetes and obesity. METHODS Chronic high-fat diet fed C57 BL/6 J mice, streptozotocintreated high-fat diet fed C57 BL/6 J mice and diabeticC57 BLKS/J db/db mice were used as models of diabetes-induced renal dysfunction. The streptozotocintreated high-fat diet fed mice and db/db mice were treated with the GLP-1 and glucagon receptors coagonist(Aib2 C24 Chimera2, 150 μg/kg, sc) for twelve weeks, while in chronic high-fat diet fed mice, coagonist(Aib2 C24 Chimera2, 150 μg/kg, sc) treatment was continued for forty weeks. Kidney function, histology, fibrosis, inflammation, and plasma biochemistry were assessed at the end of the treatment. RESULTS Coagonist treatment decreased body weight, plasma lipids, insulin resistance, creatinine, blood urea nitrogen, urinary albumin excretion rate and renal lipids. In kidney, expression of lipogenic genes(SREBP-1 C, FAS, and SCD-1) was decreased, and expression of genes involved in β-oxidation(CPT-1 and PPAR-α) was increased due to coagonist treatment. In plasma, coagonist treatment increased adiponectin and FGF21 and decreased IL-6 and TNF-?. Coagonist treatment reduced expression of inflammatory(TNF-α, MCP-1, and MMP-9) and pro-fibrotic(TGF-β, COL1 A1, and α-SMA) genes and also improved histological derangement in renal tissue.CONCLUSION Coagonist of GLP-1 and glucagon receptors alleviated diabetes and obesity-induced renal dysfunction by reducing glucose intolerance, obesity, and hyperlipidemia. | Vishal J Patel Amit A Joharapurkar Samadhan G Kshirsagar Brijesh K Sutariya Maulik S Patel Hiren M Patel Dheerendra K Pandey Rajesh H Bahekar Mukul R Jain | 2018 | World Journal of Diabetes2018，9，6： | 5 |
| 9 | Neutrophil-lymphocyte ratio:A prognostic tool in patients with inhospital cardiac arrest显示文摘BACKGROUND In-hospital cardiac arrest(IHCA) portends a poor prognosis and survival to discharge rate. Prognostic markers such as interleukin-6, S-100 protein and high sensitivity C reactive protein have been studied as predictors of adverse outcomes after return of spontaneous circulation(ROSC); however; these variables are not routine laboratory tests and incur additional cost making them difficult to incorporate and less attractive in assessing patient's prognosis. The neutrophil-lymphocyte ratio(NLR) is a marker of adverse prognosis for many cardiovascular conditions and certain types of cancers and sepsis. We hypothesize that an elevated NLR is associated with poor outcomes including mortality at discharge in patients with IHCA.AIM To determine the prognostic significance of NLR in patients suffering IHCA who achieve ROSC.METHODS A retrospective study was performed on all patients who had IHCA with the advanced cardiac life support protocol administered in a large urban community United States hospital over a one-year period. Patients were divided into two groups based on their NLR value(NLR < 4.5 or NLR ≥ 4.5). This cutpoint was derived from receiving operator characteristic curve analysis(area under the curve = 0.66) and provided 73% positive predictive value, 82% sensitivity and42% specificity for predicting in-hospital death after IHCA. The primary outcome was death or discharge at 30 d, whichever came first.RESULTS We reviewed 153 patients with a mean age of 66.1 ± 16.3 years; 48% were female.In-hospital mortality occurred in 65%. The median NLR in survivors was 4.9(range 0.6-46.5) compared with 8.9(0.28-96) in non-survivors(P = 0.001). A multivariable logistic regression model demonstrated that an NLR above 4.55[odds ratio(OR) = 5.20, confidence interval(CI): 1.5-18.3, P = 0.01], older age(OR= 1.03, CI: 1.00-1.07, P = 0.05), and elevated serum lactate level(OR = 1.20, CI:1.03-1.40, P = 0.02) were independent predictors of death.CONCLUSION An NLR ≥ 4.5 may be a useful marker of increased risk of death in patients with IHCA. | Vishal H Patel Philip Vendittelli Rajat Garg Susan Szpunar Thomas LaLonde John Lee Howard Rosman Rajendra H Mehta Hussein Othman | 2019 | World Journal of Critical Care Medicine2019，8，2： | 5 |
| 10 | FibroSURE^(TM) and FibroScan~ in relation to treatment response in chronic hepatitis C virus显示文摘AIM:To compare histological endpoint assessment using noninvasive alternatives to biopsy during treatment in a chronic hepatitis C virus(HCV)cohort.METHODS:Patients with chronic HCV were randomized to receive interferon-based therapy for 24(genotypes 2/3)or 48(genotype 1)wk.FibroSURE~TM(FS)was assessed at baseline and at week-12 post-treatment follow-up.Baseline biopsy for METAVIR was assessed by a single pathologist.FibroScan~ transient elastogra-phy(TE)was performed during treatment in a patient subset.RESULTS:Two thousand and sixty patients(n = 253 in Asia)were classif ied as METAVIR F0-1(n = 1682)or F2-4(n = 378).For F2-4,FS(n = 2055)had sensitiv-ity and specif icity of 0.87 and 0.61,respectively,with area under the receiver-operating curve of 0.82;corre-sponding values for TE(n = 214)and combined FS/TE(n = 209)were 0.77,0.88 and 0.88,and 0.93,0.68 and 0.88.Overall FS/TE agreement for F2-4 was 71%(κ = 0.41)and higher in Asians vs non-Asians(κ = 0.86 vs 0.35;P < 0.001).Combined FS/TE had 97% accuracy in Asians(n = 33).Baseline FS(0.38 vs 0.51,P < 0.001)and TE(8.0 kPa vs 11.9 kPa,P = 0.006)scores were lower in patients with sustained virological response than in nonresponders,and were maintained through follow-up.CONCLUSION:FS and TE may reliably differentiate mild from moderate-advanced disease,with a potential for high diagnostic accuracy in Asians with chronic HCV. | Keyur Patel Mireen Friedrich-Rust Yoav Lurie Mircea Grigorescu Carol Stanciu Chuan-Mo Lee Eugene R Schiff Dieter Hussinger Michael P Manns Guido Gerken Isabelle Colle Michael Torbenson Erik Pulkstenis G Mani Subramanian John G McHutchison Stefan Zeuzem | 2011 | World Journal of Gastroenterology2011，17，41： | 4 |
| 11 | 高血压对肾小球滤过率降低与脑卒中预后相关性的影响显示文摘该研究旨在比较高血压和非高血压患者估算的肾小球滤过率(estimatedglomerularfiltrationrate,eGFR)较低与脑卒中预后的相关性。方法:获取2012和2013年中国脑卒中登记处确定出院脑卒中患者的资料。低eGFR定义为eGFR%60mL/(min·1.73m2)。应用多因素分析评估低eGFR与1年全因死亡率、复发性脑卒中、功能预后不良(改良的Rankin量表评分3~6分)的关系,分析高血压对相关性的影响。 | 刘莉 叶鹏 Wang X Wang Y Patel UD Xie Barnhart H Li Z Li H Wang C Zhao X Liu L Laskowitz DT | 2017 | 中华高血压杂志2017，25，5： | 4 |
| 12 | Guidelines for the Management of Aneurysmal Subarachnoid Hemorrhage: A Statement for Healthcare Professionals From a Special Writing Group of the Stroke Council, American Heart Association显示文摘 | Joshua B. Bederson E Sander Connolly H Hunt Batjer Ralph G. Dacey Jacques E. Dion Michael N. Diringer John E. Duldner Robert E. Harbaugh Aman B. Patel Robert H. Rosenwasser | 2009 | Stroke2009，，3： | 4 |
| 13 | Cytoplasmic expression of p27^(kip1) is associated with a favourable prognosis in colorectal cancer patients显示文摘AIM: To evaluate the prognostic significance of p27kip1 in colorectal cancer patients. METHODS: Cytoplasmic and nuclear p27kip1 expression was evaluated in 418 colorectal cancers using tissue microarrays. Data were associated with known patient and tumor variables and long-term patient outcomes, providing further insight into the mechanisms by which p27kip1 may influence tumor development. RESULTS: Nuclear and cytoplasmic p27Kip1 expressions were detected in 59% and 19% of tumors respectively. Cytoplasmic p27Kip1 was almost invariably associated with positive nuclear p27Kip1 expression. Neither case correlat- ed with known clinical or pathological variables, includ- ing tumor stage, grade or extramural vascular invasion. Furthermore, nuclear p27kip1 expression had no impact on survival. However, we identified a significant correla- tion between expression of cytoplasmic p27kip1 and longer disease-specific survival times. On multivariate analysis, TNM stage and extramural vascular invasion were highly significant independent prognostic factors, with positive cytoplasmic p27 expression showing a trend towards im- proved patient survival (P = 0.059).CONCLUSION: These findings support the recent evi- dence that cytoplasmic p27kip1 has a distinct and impor- tant biological role that can influence tumor outcome. | Nicholas FS Watson Lindy G Durrant John H Scholefield Zahra Madjd Duncan Scrimgeour Ian Spendlove Ian O Ellis Poulam M Patel | 2006 | World Journal of Gastroenterology2006，12，39： | 3 |
| 14 | Efficient photon coupling from a diamond nitrogen vacancy center by integration with silica fiber显示文摘A central goal in quantum information science is to efficiently interface photons with single optical modes for quantum networking and distributed quantum computing.Here,we introduce and experimentally demonstrate a compact and efficient method for the low-loss coupling of a solid-state qubit,the nitrogen vacancy(NV)center in diamond,with a single-mode optical fiber.In this approach,single-mode tapered diamond waveguides containing exactly one high quality NV memory are selected and integrated on tapered silica fibers.Numerical optimization of an adiabatic coupler indicates that near-unity-efficiency photon transfer is possible between the two modes.Experimentally,we find an overall collection efficiency between 16%and 37%and estimate a single photon count rate at saturation above 700 kHz.This integrated system enables robust,alignment-free,and efficient interfacing of single-mode optical fibers with single photon emitters and quantum memories in solids. | Rishi N Patel Tim Schröder Noel Wan Luozhou Li Sara L Mouradian Edward H Chen Dirk R Englund | 2016 | Light(Science & Applications)2016，5，1： | 2 |
| 15 | A randomized,controlled trial of the effectiveness of nebulized therapy with epinephrine compared with albuterol and saline in infants hospitalized for acute viral bronchiolitis显示文摘 | Patel H Platt RW Pekeles GS | 2002 | J Pediatr2002，141，6： | 1 |
| 16 | In vitro and in vivo release of vas~:ular endothelial growth factor from gelatin microparticles and biodegradable composite scaffolds 显示文摘 | Patel ZS Ueda H Yamamoto M | 2008 | Pharm Res2008，25，10： | 1 |
| 17 | Primary idiopathic chylopericardium显示文摘 | OSSIANI M MCCAULEY R PATEL H | 2003 | Pediatr Radiol2003，33，： | 1 |
| 18 | T ( p-e)/QT ratio as an index of arrhythmogenesis 显示文摘 | Gupta P Pate1 C Patel H | 2008 | J Electrocardiol2008，41，6： | 1 |
| 19 | A novel medium devoid of ruminant peptone for high yield growth of Mycoplasma ovipneumoniae显示文摘 | Patel H Mackintosh D Ayling R D | 2008 | Vet Microbiol2008，127，34： | 1 |
| 20 | International Journal of Powder Metallurgy显示文摘 | Joshi P B Krishnan P S Patel R H | 1998 | 34(4):63-741998，34，4： | 1 |
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