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| 1 | 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 |
| 2 | Daclatasvir plus asunaprevir in treatment-na?ve patients with hepatitis C virus genotype 1b infection显示文摘AIM To assess daclatasvir plus asunaprevir(d UAL) in treatment-na?ve patients from China's Mainland, Russia and South Korea with hepatitis C virus(HCV) genotype 1 b infection. METHODS Patients were randomly assigned(3:1) to receive 24 wk of treatment with d UAL(daclatasvir 60 mg once daily and asunaprevir 100 mg twice daily) beginning on day 1 of the treatment period(immediate treatment arm) or following 12 wk of matching placebo(placebodeferred treatment arm). The primary endpoint was a comparison of sustained virologic response at posttreatment week 12(SVR12) compared with the historical SVR rate for peg-interferon plus ribavirin(70%) among patients in the immediate treatment arm. The first 12 wk of the study were blinded. Safety was assessed in d UAL-treated patients compared with placebo patients during the first 12 wk(doubleblind phase), and during 24 wk of d UAL in both arms combined.RESULTS In total, 207 patients were randomly assigned to immediate(n = 155) or placebo-deferred(n = 52) treatment. Most patients were Asian(86%), female(59%) and aged < 65 years(90%). Among them, 13% had cirrhosis, 32% had IL28 B non-CC genotypes and 53% had baseline HCV RNA levels of ≥ 6 million IU/m L. Among patients in the immediate treatment arm, SVR12 was achieved by 92%(95% confidence interval: 87.2-96.0), which was significantly higher than the historical comparator rate(70%). SVR12 was largely unaffected by cirrhosis(89%), age ≥ 65 years(92%), male sex(90%), baseline HCV RNA ≥ 6 million(89%) or IL28 B non-CC genotypes(96%), although SVR12 was higher among patients without(96%) than among those with(53%) baseline NS5 A resistanceassociated polymorphisms(at L31 or Y93 H). during the double-blind phase, aminotransferase elevations were more common among placebo recipients than among patients receiving d UAL. during 24 wk of d UAL therapy(combined arms), the most common adverse events(≥ 10%) were elevated alanine aminotransferase and upper respiratory tract infection; emergent grade 3-4 laboratory abnormalities were infrequently observed, and all grade 3-4 aminotransferase abnormalities(alanine aminotransferase, n = 9; aspartate transaminase, n = 6) reversed within 8-11 d. Two patients discontinued d UAL treatment; one due to aminotransferase elevations, nausea, and jaundice and the other due to a fatal adverse event unrelated to treatment. There were no treatment-related deaths.CONCLUSION d UAL was well-tolerated during this phase 3 study, and SVR12 with d UAL treatment(92%) exceeded thehistorical SVR rate for peg-interferon plus ribavirin of 70%. | Lai Wei Fu-Sheng Wang Ming-Xiang Zhang Ji-Dong Jia Alexey A Yakovlev Wen Xie Eduard Burnevich Jun-Qi Niu Yong Jin Jung Xiang-Jun Jiang Min Xu Xin-Yue Chen Qing Xie Jun Li Jin-Lin Hou Hong Tang Xiao-guang Dou Yash Gandhi Wen-Hua Hu Fiona McPhee Stephanie Noviello Michelle Treitel Ling Mo Jun Deng | 2018 | World Journal of Gastroenterology2018，24，12： | 17 |
| 3 | 肽酰基精氨酸脱亚氨酶4和中性粒细胞胞外诱捕网形成在实验性动脉粥样硬化和动脉损伤中的作用:浅表糜烂的影响显示文摘中性粒细胞可能促进人类动脉粥样硬化的血栓并发症的发生。特别是中性粒细胞胞外诱捕网(neutrophil extracellular traps,NETs)可加剧局部炎症,并放大和加剧动脉内膜损伤和血栓形成。肽酰基精氨酸脱亚氨酶4(peptidyl arginine deiminase 4,PAD4)参与NET的形成,但对该酶在动脉粥样硬化血栓形成中的作用的认识仍然不足。 | 刘青 叶鹏 Franck G Mawson TL Folco EJ Molinaro R Ruvkun V Engelbertsen D Liu X Tesmenitsky Y Shvartz F Sukhova GK Michel JB Nicoletti A Lichtman AH Wagner DD Croce KJ Libby P | 2018 | 中华高血压杂志2018，26，5： | 13 |
| 4 | Value of screening endoscopy in evaluation of esophageal,gastric and colon cancers显示文摘Esophageal,gastric,and colorectal cancers are deadly diseases that continue to plague our world today.The value of screening endoscopy in evaluating these types of cancers is a critical area of discussion due to a potential reduction in morbidity and mortality.This article describes how to identify a good screening test and explains what are important criteria in the field of screening endoscopy.Furthermore,the current status and progress of screening endoscopy for esophageal,gastric,and colorectal cancer will be evaluated and discussed.Mass screening programs have not been implemented for esophageal and gastric carcinomas in those with average or low risk populations.However,studies of high-risk populations have found value and a cost-benefit in conducting screening endoscopy.Colorectal cancer,on the other hand,has had mass screening programs in place for many years due to the clear evidence of improved outcomes.As the role of endoscopy as a screening tool has continued to develop,newer technology and techniques have emerged to improve its utility.Many new image enhancement techniques and computer processing programs have shown promise and may have a significant role in the future of endoscopic screening.These developments are paving the way for improving the diagnostic and therapeutic capability of endoscopy in the field of gastroenterology. | Tae H Ro Michelle A Mathew Subhasis Misra | 2015 | World Journal of Gastroenterology2015，21，33： | 9 |
| 5 | Photodynamic therapy:Palliation and endoscopic technique in cholangiocarcinoma显示文摘Cholangiocarcinoma is the primary malignancy arising from the biliary epithelium.The disease is marked by jaundice,cholestasis,and cholangitis.Over 50 percent of patients present with advanced stage disease,precluding curative surgical resection as an option of treatment.Prognosis is poor,and survival has been limited even after biliary decompression.Palliative management has become the standard of care for unresectable disease and has evolved to include an endoscopic approach. Photodynamic therapy(PDT)consists of administration of a photosensitizer followed by local irradiation with laser therapy.Several studies conducted in Europe and the United States have shown a marked improvement in the symptoms of cholestasis,survival,and quality of life.This article summarizes the published experience regarding PDT for cholangiocarcinoma and the steps required to administer this therapy safely. | James A Richter Michel Kahaleh | 2010 | World Journal of Gastrointestinal Endoscopy2010，2，11： | 7 |
| 6 | Association between calcium sensing receptor gene polymorphisms and chronic pancreatitis in a US population:Role of serine protease inhibitor Kazal 1type and alcohol显示文摘AIM: To test the hypothesis that calcium sensing receptor (CASR) polymorphisms are associated with chronic pancreatitis (CP), and to determine whether serine protease inhibitor Kazal 1type (SPINK1) N34S oralcohol are necessary co-factors in its etiology. METHODS: Initially, 115 subjects with pancreatitis and 66 controls were evaluated, of whom 57 patients and 21 controls were predetermined to carry the high-risk SPINK1 N34S polymorphism. We sequenced CASR gene exons 2, 3, 4, 5 and 7, areas containing the majority of reported polymorphisms and novel mutations. Based on the initial results, we added 223 patients and 239 controls to analyze three common nonsynonymous single nucleotide polymorphisms (SNPs) in exon 7 (A986S, R990G, and Q1011E). RESULTS: The CASR exon 7 R990G polymorphism was signifi cantly associated with CP (OR, 2.01; 95% CI, 1.12-3.59; P = 0.015). The association between CASR R990G and CP was stronger in subjects who reported moderate or heavy alcohol consumption (OR, 3.12; 95% CI, 1.14-9.13; P = 0.018). There was no association between the various CASR genotypes and SPINK1 N34S in pancreatitis. None of the novel CASR polymorphisms reported from Germany and India was detected. CONCLUSION: Our United States-based study confirmed an association of CASR and CP and for the first time demonstrated that CASR R990G is a signifi cant risk factor for CP. We also conclude that the risk of CP with CASR R990G is increased in subjects with moderate to heavy alcohol consumption. | Venkata Muddana Janette Lamb Julia B Greer Beth Elinoff Robert H Hawes Peter B Cotton Michelle A Anderson Randall E Brand Adam Slivka David C Whitcomb | 2008 | World Journal of Gastroenterology2008，14，28： | 7 |
| 7 | Irritable bowel syndrome: A concise review of current treatment concepts显示文摘Irritable bowel syndrome(IBS) is one of the most common gastrointestinal disorders causing patients to seek medical treatment. It is relatively resource intensive and the source of significant morbidity. Recent insights into the pathophysiology and treatment of IBS has given clinicians more options than ever to contend with this disorder. The purpose of our paper is to review older, 'classic' treatments for IBS as well as newer agents and 'alternative' therapies. We discuss the evidence base of these drugs and provide context to help develop appropriate treatment plans for IBS patients. | Geoffrey C Wall Ginelle A Bryant Michelle M Bottenberg Erik D Maki rew R Miesner | 2014 | World Journal of Gastroenterology2014，20，27： | 5 |
| 8 | Pancreatic trauma: The role of computed tomography for guiding therapeutic approach显示文摘AIM: To evaluate the role of computed tomography(CT) for diagnosing traumatic injuries of the pancreas and guiding the therapeutic approach.METHODS: CT exams of 6740 patients admitted to our Emergency Department between May 2005 and January 2013 for abdominal trauma were retrospectively evaluated. Patients were identified through a search of our electronic archive system by using such terms as 'pancreatic injury', 'pancreatic contusion', 'pancreatic laceration', 'peri-pancreatic fluid', 'pancreatic active bleeding'. All CT examinations were performed before and after the intravenous injection of contrast material using a 16-slice multidetector row computed tomography scanner. The data sets were retrospectively analyzed by two radiologists in consensus searching for specific signs of pancreatic injury(parenchymal fracture and laceration, focal or diffuse pancreatic enlargement/edema, pancreatic hematoma, active bleeding, fluid between splenic vein and pancreas) and non-specific signs(inflammatory changes in peri-pancreatic fat and mesentery, fluid surrounding the superior mesentericartery, thickening of the left anterior renal fascia, pancreatic ductal dilatation, acute pseudocyst formation/peri-pancreatic fluid collection, fluid in the anterior and posterior pararenal spaces, fluid in transverse mesocolon and lesser sac, hemorrhage into peri-pancreatic fat, mesocolon and mesentery, extraperitoneal fluid, intraperitoneal fluid).RESULTS: One hundred and thirty-six/Six thousand seven hundred and forty(2%) patients showed CT signs of pancreatic trauma. Eight/one hundred and thirty-six(6%) patients underwent surgical treatment and the pancreatic injures were confirmed in all cases. Only in 6/8 patients treated with surgical approach, pancreatic duct damage was suggested in the radiological reports and surgically confirmed in all cases. In 128/136(94%) patients who underwent non-operative treatment CT images showed pancreatic edema in 97 patients, hematoma in 31 patients, fluid between splenic vein and pancreas in 113 patients. Non-specific CT signs of pancreatic injuries were represented by peri-pancreatic fat stranding and mesentery fluid in 89% of cases, thickening of the left anterior renal fascia in 65%, pancreatic ductal dilatation in 18%, acute pseudocyst/peri-pancreatic fluid collection in 57%, fluid in the pararenal spaces in 45%, fluid in transverse mesocolon and lesser sac in 29%, hemorrhage into peri-pancreatic fat, mesocolon and mesentery in 66%, extraperitoneal fluid in 66%, intra-peritoneal fluid in 41% cases.CONCLUSION: CT represents an accurate tool for diagnosing pancreatic trauma, provides useful information to plan therapeutic approach with a detection rate of 75% for recognizing ductal lesions. | Marco Moschetta Michele Telegrafo Valeria Malagnino Laura Mappa Amato A Stabile Ianora Dario Dabbicco Antonio Margari Giuseppe Angelelli | 2015 | World Journal of Radiology2015，7，11： | 4 |
| 9 | Reproducibility of thrombus volume quantification in multicenter computed tomography pulmonary angiography studies显示文摘AIM To evaluate reproducibility of pulmonary embolism(PE) clot volume quantification using computed tomography pulmonary angiogram(CTPA) in a multicenter setting.METHODS This study was performed using anonymized data in conformance with HIPAA and IRB Regulations(March 2015-November 2016). Anonymized CTPA data was acquired from 23 scanners from 18 imaging centers using each site's standard PE protocol. Two independent analysts measured PE volumes using a semi-automated region-growing algorithm on an FDA-approved image analysis platform. Total thrombus volume(TTV) was calculated per patient as the primary endpoint. Secondary endpoints were individual thrombus volume(ITV), Qanadli score and modified Qanadli score per patient. Inter-and intra-observer reproducibility were assessed using intra-class correlation coefficient(ICC) and BlandAltman analysis. RESULTS Analyst 1 found 72 emboli in the 23 patients with a mean number of emboli of 3.13 per patient with a range of 0-11 emboli per patient. The clot volumes ranged from 0.0041-47.34 cm3(mean +/-SD, 5.93 +/-10.15 cm3). On the second read, analyst 1 found the same number and distribution of emboli with a range of volumes for read 2 from 0.0041 – 45.52 cm3(mean +/-SD, 5.42 +/-9.53 cm3). Analyst 2 found 73 emboli in the 23 patients with a mean number of emboli of 3.17 per patient with a range of 0-11 emboli per patient. The clot volumes ranged from 0.00459-46.29 cm3(mean +/-SD, 5.91 +/-10.06 cm3). Inter-and intraobserver variability measurements indicated excellent reproducibility of the semi-automated method for quantifying PE volume burden. ICC for all endpoints was greater than 0.95 for inter-and intra-observer analysis. Bland-Altman analysis indicated no significant biases.CONCLUSION Semi-automated region growing algorithm for quantifying PE is reproducible using data from multiple scanners and is a suitable method for image analysis in multicenter clinical trials. | Audrey E Kaufman Alison N Pruzan Ching Hsu Sarayu Ramachandran Adam Jacobi Indravadan Patel Lee Schwocho Michele F Mercuri Zahi A Fayad Venkatesh Mani | 2018 | World Journal of Radiology2018，10，10： | 3 |
| 10 | 121例腹腔镜Roux-en-Y胃空肠吻合术后随访结果显示文摘目的探讨腹腔镜Roux-en-Y胃空肠吻合术(laparoscopic Roux-en-Y gastric bypass,LRYGBP)治疗病态肥胖的术后营养和代谢方面的变化。方法121例LRYGBP,男40例,女81例。分别测定术前1个月及术后6个月的体重指数(body mass index,BMI)。对比分析6个月、12个月,24个月血清铁(Fe)、钙(Ca)、锌(Zn)、硒(Se)及维生素A(VitA)、维生素D(VitD)、维生素B12(VitB12)和甲状旁腺素(parathyroid hormone,PTH)的水平变化。结果术前1个月BMI(47.00±7.15)kg/m^2,术后6个月BMI(33.79±6.06)kg/m^2,BMI下降(13.21±5.47)kg/m^2(t=26.103,P=0.000)。术后血清Fe、Ca、Zn、Se及ViLA、VitD、VitB12均在正常范围,其中术后6个月血清Zn、Se和VitA水平虽然在正常范围内,但分别有19.5%(17/87)、22.7%(20/88)和33.7%(28/83)的患者低于正常水平,但术后2年仅有6.7%(2/30)、11.5%(3/26)和17.2%(5/29)的患者低于正常水平。血清PTH术后6个月11~161pg/ml,(66±34)pg/ml、1年24~154pg/ml,(72±34)pg/ml、2年21~194pg/ml,(75±40)pg/ml(正常值9~44pg/ml)。结论LRYGBP治疗病态肥胖是有效、安全的。术后2年血清Fe、Ca及VitD、VitB12均正常;血清锌、硒及维生素A经术后6个月给予补充剂大多接近正常;血清PTH水平明显高于正常。建议患者术后长期服用复合维生素、矿物质补充剂,定期到医院随访。 | 宫轲 Michel Gagner Alfons Pomp Taghreed A | 2007 | 中国微创外科杂志2007，7，1： | 3 |
| 11 | Pharmacology of adapalene 显示文摘 | Michel S Jomard A Demarchez M | 1998 | Br J Dermatol1998，139，52： | 2 |
| 12 | Stratification of outcomes for mucinous appendiceal adenocarcinoma with peritoneal metastasis by histological grade显示文摘AIM To investigate the importance of a three-tiered histologic grade on outcomes for patients with mucinous appendiceal adenocarcinoma(MAA).METHODS Two hundred and sixty-five patients with MAA undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy were identified from a prospective database from 2004 through 2014. All pathology was reviewed by our gastrointestinal subspecialty pathologists and histological grade was classified as well-differentiated, moderately differentiated, and poorly differentiated. Survival analysis was performed using Cox proportional hazards regression.RESULTS There were 201(75.8%) well-, 45(16.9%) moderatelyand 19(7.2%) poorly-differentiated tumors. Histological grade significantly stratified the 5-year overall survival(OS), 94%, 71% and 30% respectively(P < 0.001) as well as the 5-year disease-free survival(DFS) 66%, 21% and 0%, respectively(P < 0.001). Independent predictors of DFS included tumor grade(HR = 1.78, 95%CI: 1.21-2.63, P = 0.008), lymph node involvement(HR = 0.33, 95%CI: 0.11-0.98, P < 0.02), previous surgical score(HR = 1.31, 95%CI: 1.1-1.65, P = 0.03) and peritoneal carcinomatosis index(PCI)(HR = 1.05, 95%CI: 1.02-1.08, P = 0.002). Independent predictors of OS include tumor grade(HR = 2.79, 95%CI: 1.26-6.21, P = 0.01), PCI(HR = 1.10, 95%CI: 1.03-1.16, P = 0.002), and complete cytoreduction(HR = 0.32, 95%CI: 0.11-0.92, P = 0.03). Tumor grade and PCI were the only independent predictors of both DFS and OS. Furthermore, histological grade and lymphovascular invasion stratified the risk of lymph node metastasis into a low(6%) and high(40%) risk groups. CONCLUSION Our data demonstrates that moderately differentiated MAA have a clinical behavior and outcome that is distinct from well-and poorly-differentiated MAA. The threetier grade classification provides improved prognostic stratification and should be incorporated into patient selection and treatment algorithms. | Travis Edward Grotz Richard E Royal Paul F Mansfield Michael James Overman Gary N Mann Kristen Ashlee Robinson Karen A Beaty Safiea Rafeeq Auerlio Matamoros Michelle W Taggart Keith Francis Fournier | 2017 | World Journal of Gastrointestinal Oncology2017，9，9： | 2 |
| 13 | Role of retinoids in the prevention and treatment of colorectal cancer显示文摘Vitamin A and its derivatives, retinoids, have been widely studied for their use as cancer chemotherapeutic agents. With respect to colorectal cancer(CRC), several critical mutations dysregulate pathways implicated in progression and metastasis, resulting in aberrant Wnt/β-catenin signaling, gain-of-function mutations in K-ras and phosphatidylinositol-3-kinase/Akt, cyclooxygenase-2 over-expression, reduction of peroxisome proliferatoractivated receptor γ activation, and loss of p53 function. Dysregulation leads to increased cellular proliferation and invasion and decreased cell-cell interaction and differentiation. Retinoids affect these pathways by various mechanisms, many involving retinoic acid receptors(RAR). RAR bind to all-trans-retinoic acid(ATRA) to induce the transcription of genes responsible for cellular differentiation. Although most research concerning the chemotherapeutic efficacy of retinoids focuses on the ability of ATRA to decrease cancer cell proliferation, increase differentiation, or promote apoptosis; as CRC progresses, RAR expression is often lost, rendering treatment of CRCs with ATRA ineffective. Our laboratory focuses on the ability of dietary vitamin A to decrease CRC cell proliferation and invasion via RAR-independent pathways. This review discusses our research and others concerning the ability of retinoids to ameliorate the defective signaling pathways listed above and decrease tumor cell proliferation and invasion through both RAR-dependent and RAR-independent mechanisms. | Catherine C Applegate Michelle A Lane | 2015 | World Journal of Gastrointestinal Oncology2015，7，10： | 2 |
| 14 | Appropriateness of systemic treatments in unresectable metastatic well-differentiated pancreatic neuroendocrine tumors显示文摘AIM:To evaluate systemic treatment choices in unresectable metastatic well-differentiated pancreatic neuroendocrine tumors(PNETs)and provide consensus treatment recommendations.METHODS:Systemic treatment options for pancreatic neuroendocrine tumors have expanded in recent years to include somatostatin analogs,angiogenesis inhibitors,inhibitors of mammalian target of rapamycinand cytotoxic agents.At this time,there is little data to guide treatment selection and sequence.We therefore assembled a panel of expert physicians to evaluate systemic treatment choices and provide consensus treatment recommendations.Treatment appropriateness ratings were collected using the RAND/UCLA modified Delphi process.After studying the literature,a multidisciplinary panel of 10 physicians assessed the appropriateness of various medical treatment scenarios on a 1-9 scale.Ratings were done both before and after an extended discussion of the evidence.Quantitative measurements of agreement were made and consensus statements developed from the second round ratings.RESULTS:Specialties represented were medical and surgical oncology,interventional radiology,and gastroenterology.Panelists had practiced for a mean of15.5 years(range:6-33).Among 202 rated scenarios,disagreement decreased from 13.2%(26 scenarios)before the face-to-face discussion of evidence to 1%(2)after.In the final ratings,46.5%(94 scenarios)were rated inappropriate,21.8%(44)were uncertain,and30.7%(62)were appropriate.Consensus statements from the scenarios included:(1)it is appropriate to use somatostatin analogs as first line therapy in patients with hormonally functional tumors and may be appropriate in patients who are asymptomatic;(2)it is appropriate to use everolimus,sunitinib,or cytotoxic chemotherapy therapy as first line therapy in patients with symptomatic or progressive tumors;and(3)beyond first line,these same agents can be used.In patients with uncontrolled secretory symptoms,octreotide LAR doses can be titrated up to 60 mg every4 wk or up to 40 mg every 3 or 4 wk.CONCLUSION:Using the Delphi process allowed physician experts to systematically obtain a consensus on the appropriateness of a variety of medical therapies in patients with PNETs. | Jonathan R Strosberg George A Fisher Al B Benson Lowell B Anthony Bulent Arslan John F Gibbs Edward Greeno Renuka V Iyer Michelle K Kim William J Maples Philip A Philip Edward M Wolin Dasha Cherepanov Michael S Broder | 2015 | World Journal of Gastroenterology2015，21，8： | 2 |
| 15 | Interferon-β induced in female genital epithelium by HIV-1 glycoprotein 120 via Toll-like-receptor 2 pathway acts to protect the mucosal barrier显示文摘More than 40%of HIV infections occur via female reproductive tract(FRT)through heterosexual transmission.Epithelial cells that line the female genital mucosa are the first line of defense against HIV-1 and other sexually transmitted pathogens.These sentient cells recognize and respond to external stimuli by induction of a range of carefully balanced innate immune responses.Previously,we have shown that in response to HIV-1 gp120,the genital epithelial cells(GECs)from upper reproductive tract induce an inflammatory response that may facilitate HIV-1 translocation and infection.In this study,we report that the endometrial and endocervical GECs simultaneously induce biologically active interferon-β(IFNβ)antiviral responses following exposure to HIV-1 that act to protect the epithelial tight junction barrier.The innate antiviral response was directly induced by HIV-1 envelope glycoprotein gp120 and addition of gp120 neutralizing antibody inhibited IFNβproduction.Interferon-βwas induced by gp120 in upper GECs through Toll-like receptor 2 signaling and required presence of heparan sulfate on epithelial cell surface.The induction of IFNβwas dependent upon activation of transcription factor IRF3(interferon regulatory factor 3).The IFNβwas biologically active,had a protective effect on epithelial tight junction barrier and was able to inhibit HIV-1 infection in TZM-bl indicator cells and HIV-1 replication in T cells.This is the first report that recognition of HIV-1 by upper GECs leads to induction of innate antiviral pathways.This could explain the overall low infectivity of HIV-1 in the FRT and could be exploited for HIV-1 prophylaxis. | Aisha Nazli Sara Dizzell Muhammad Atif Zahoor Victor H Ferreira Jessica Kafka Matthew William Woods Michel Ouellet Ali A Ashkar Michel J Tremblay Dawn ME Bowdish Charu Kaushic | 2019 | Cellular & Molecular Immunology2019，16，2： | 2 |
| 16 | 3D additive manufactured composite scaffolds with antibiotic-loaded lamellar fillers for bone infection prevention and tissue regeneration显示文摘Bone infections following open bone fracture or implant surgery remain a challenge in the orthopedics field.In order to avoid high doses of systemic drug administration,optimized local antibiotic release from scaffolds is required.3D additive manufactured(AM)scaffolds made with biodegradable polymers are ideal to support bone healing in non-union scenarios and can be given antimicrobial properties by the incorporation of antibiotics.In this study,ciprofloxacin and gentamicin intercalated in the interlamellar spaces of magnesium aluminum layered double hydroxides(MgAl)andα-zirconium phosphates(ZrP),respectively,are dispersed within a thermoplastic polymer by melt compounding and subsequently processed via high temperature melt extrusion AM(~190◦C)into 3D scaffolds.The inorganic fillers enable a sustained antibiotics release through the polymer matrix,controlled by antibiotics counterions exchange or pH conditions.Importantly,both antibiotics retain their functionality after the manufacturing process at high temperatures,as verified by their activity against both Gram+and Gram-bacterial strains.Moreover,scaffolds loaded with filler-antibiotic do not impair human mesenchymal stromal cells osteogenic differentiation,allowing matrix mineralization and the expression of relevant osteogenic markers.Overall,these results suggest the possibility of fabricating dual functionality 3D scaffolds via high temperature melt extrusion for bone regeneration and infection prevention. | María C´amara-Torres Stacy Duarte Ravi Sinha Ainhoa Egizabal Noelia´Alvarez Maria Bastianini Michele Sisani Paolo Scopece Marco Scatto Alessandro Bonetto Antonio Marcomini Alberto Sanchez Alessandro Patelli Carlos Mota Lorenzo Moroni | 2021 | Bioactive Materials2021，6，4： | 2 |
| 17 | Dendritic cell deficiencies persist seven months after SARS-CoV-2 infection显示文摘Severe Acute Respiratory Syndrome Coronavirus(SARS-CoV)-2 infection induces an exacerbated inflammation driven by innate immunity components.Dendritic cells(DCs)play a key role in the defense against viral infections,for instance plasmacytoid DCs(pDCs),have the capacity to produce vast amounts of interferon-alpha(IFN-α).In COVID-19 there is a deficit in DC numbers and IFN-αproduction,which has been associated with disease severity.In this work,we described that in addition to the DC deficiency,several DC activation and homing markers were altered in acute COVID-19 patients,which were associated with multiple inflammatory markers.Remarkably,previously hospitalized and nonhospitalized patients remained with decreased numbers of CD1c+myeloid DCs and pDCs seven months after SARS-CoV-2 infection.Moreover,the expression of DC markers such as CD86 and CD4 were only restored in previously nonhospitalized patients,while no restoration of integrinβ7 and indoleamine 2,3-dyoxigenase(IDO)levels were observed.These findings contribute to a better understanding of the immunological sequelae of COVID-19. | Alberto Pérez-Gómez Joana Vitallé Carmen Gasca-Capote Alicia Gutierrez-Valencia María Trujillo-Rodriguez Ana Serna-Gallego Esperanza Muñoz-Muela María de los Reyes Jiménez-Leon Mohamed Rafii-El-Idrissi Benhnia Inmaculada Rivas-Jeremias Cesar Sotomayor Cristina Roca-Oporto Nuria Espinosa Carmen Infante-Domínguez Juan Carlos Crespo-Rivas Alberto Fernández-Villar Alexandre Pérez-González Luis Fernando López-Cortés Eva Poveda Ezequiel Ruiz-Mateos JoséMiguel Cisneros Sonsoles Salto-Alejandre Judith Berastegui-Cabrera Pedro Camacho-Martínez Carmen Infante-Domínguez Marta Carretero-Ledesma Juan Carlos Crespo-Rivas Eduardo Márquez JoséManuel Lomas Claudio Bueno Rosario Amaya JoséAntonio Lepe Jerónimo Pachón Elisa Cordero Javier Sánchez-Céspedes Manuela Aguilar-Guisado Almudena Aguilera Clara Aguilera Teresa Aldabo-Pallas Verónica Alfaro-Lara Cristina Amodeo Javier Ampuero María Dolores Avilés Maribel Asensio Bosco Barón-Franco Lydia Barrera-Pulido Rafael Bellido-Alba Máximo Bernabeu-Wittel Candela Caballero-Eraso Macarena Cabrera Enrique Calderón Jesús Carbajal-Guerrero Manuela Cid-Cumplido Yael Corcia-Palomo Juan Delgado Antonio Domínguez-Petit Alejandro Deniz Reginal Dusseck-Brutus Ana Escoresca-Ortega Fátima Espinosa Nuria Espinosa Michelle Espinoza Carmen Ferrándiz-Millón Marta Ferrer Teresa Ferrer Ignacio Gallego-Texeira Rosa Gámez-Mancera Emilio García Horacio García-Delgado Manuel García-Gutiérrez María Luisa Gascón-Castillo Aurora González-Estrada Demetrio González Carmen Gómez-González Rocío González-León Carmen Grande-Cabrerizo Sonia Gutiérrez Carlos Hernández-Quiles Inmaculada Concepción Herrera-Melero Marta Herrero-Romero Luis Jara Carlos Jiménez-Juan Silvia Jiménez-Jorge Mercedes Jiménez-Sánchez Julia Lanseros-Tenllado Carmina López Isabel López Álvaro López-Barrios Luis F.López-Cortés Rafael Luque-Márquez Daniel Macías-García Guillermo Martín-Gutiérrez Luis Martín-Villén JoséMolina Aurora Morillo María Dolores Navarro-Amuedo Dolores Nieto-Martín Francisco Ortega María Paniagua-García Amelia Peña-Rodríguez Esther Pérez Manuel Poyato Julia Praena-Segovia Rafaela Ríos Cristina Roca-Oporto Jesús F.Rodríguez María Jesús Rodríguez-Hernández Santiago Rodríguez-Suárez Ángel Rodríguez-Villodres Nieves Romero-Rodríguez Ricardo Ruiz Zida Ruiz de Azua Celia Salamanca Sonia Sánchez Víctor Manuel Sánchez-Montagut César Sotomayor Alejandro Suárez Benjumea Javier Toral | 2021 | Cellular & Molecular Immunology2021，18，9： | 2 |
| 18 | Label-retaining liver cancer cells are relatively resistant to sorafenib显示文摘 | Hong-Wu Xin Chenwi M Ambe Danielle M Hari Gordon W Wiegand Tyler C Miller Jin-Qiu Chen Andrew J Anderson Satyajit Ray John E Mullinax Tomotake Koizumi Russell C Langan Douglas Burka Michelle A Herrmann Paul K Goldsmith Alexander Stojadinovic Udo Rudloff S | 2013 | Gut2013，，12： | 2 |
| 19 | Vulvar granular cell tumor显示文摘Granular cell tumors are rare,usually benign,soft tissue neoplasms of neural origin.They occur more often in females than males,the peak age incidence is in the fourth through fifth decades.They can occur anywhere in the body with up to 15% situated in the vulva.The commonest presentation is as an asymptomatic mass.Microscopic findings are usually sufficient,but immunohistochemistry can also be helpful in confirming the diagnosis.The vulvar tumors are benign in 98% of cases with 2% reported as malignant.In this case report we describe a woman with a granular cell tumor confirmed by biopsy who underwent excision of the mass but with focal extension to the resection margin on microscopy.Our recommendation of re-excision was declined.Since it is not uncommon with these tumors to find groups of tumor cells extending beyond the macroscopic limits of growth,we conclude that it is advisable to have margins assessed intraoperatively by frozen section such that further excision can be performed for positive margins.Our patient has been followed for 18 mo without recurrence,should the tumor recur,re-excision,with frozen section control,is indicated.Recurrence rates are reported as 2%-8% with clear margins and 20% with positive margins. | Michel E Rivlin G Rodney Meeks Mohamed A Ghafar Jack R Lewin | 2013 | World Journal of Clinical Cases2013，1，4： | 2 |
| 20 | 14 Years of Eosinophilic Esophagitis: Clinical Features and Prognosis显示文摘 | Jonathan M Spergel Terri F Brown-Whitehorn Janet L Beausoleil James Franciosi Michele Shuker Ritu Verma Chris A Liacouras | 2009 | Journal of Pediatric Gastroenterology and Nutrition2009，，1： | 2 |
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