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培美曲塞加铂类联合或不联合帕博利珠单抗对初治转移性非鳞状NScLc患者的疗效与安全性分析：KEYNOTE-189研究方案指定的最终分析

中国肺癌杂志 2022年第6期25卷 443-456页

作者：周彩存 Delvys RODRíGUEZ-ABREU S.F.POWELL m.J.HOcHmAIR S.GAD GEEL E.ESTEBAN E.FELIP G.SPERANZA F.De ANGELIS m.DómINE S.Y.cHENG H.G.BIScHOFF N.PELED m.REcK R.HUI E.B.GARON m.BOYER T.KURATA J.YANG m.c.PIETANZA F.souza m.c.GARASSINO 同济大学附属上海市肺科医院肿瘤科 medical Oncology Complejo Hospitalario Universitario Insular Materno-Infantil de Gran CanariaUniversidad de Las Palmas de Gran Canaria Oncology Sanford Health 4. Department of Respiratory and Critical Care MedicineKarl Landsteiner Institute of Lung Research and Pulmonary Oncology Thoracic Oncology Karmanos Cancer InstituteWayne State University Department of medical Oncology Hospital Universitario Central de Asturias medical Oncology Department Vall d'Hebron UniversityVall d'Hebron Institute of Oncology (VHIO) 8. Centre Integre de Cancerologie de la MontérégieH?pital Charles-Le Moyne 9. Medical Oncology DepartmentHospital Universitario Fundacidn Jiménez DiazIIS-FJD Sunnybrook Health Sciences centre Thoraxklinik Heidelberg Department of Oncology Shaare Zedek Medical Center Lungenclinic Airway Research Center NorthGerman Center for Lung Research Department of medical Oncology Westmead Hospital and University of Sydney Department of medicine David Geffen School of Medicine at UCLA Department of medical Oncology Chris O'Brien Lifehouse Department of Thoracic Oncology Kansai Medical University Hospital merck & co. Inc. Fondazione IRccS Istituto Nazionale dei Tumori University of chicago medicine & Biological Sciences Knapp Center for Biomedical Discovery

背景在KEYNOTE-189此项Ⅲ期研究(NcT02578680)中,与安慰剂联合培美曲塞加铂类相比,帕博利珠单抗联合培美曲塞加铂类化疗(培美曲塞-铂类)显著改善了初治转移性非鳞状非小细胞肺癌(non-small cell lung cancer,NScLc)患者的总生存期(over... 详细信息

背景在KEYNOTE-189此项Ⅲ期研究(NcT02578680)中,与安慰剂联合培美曲塞加铂类相比,帕博利珠单抗联合培美曲塞加铂类化疗(培美曲塞-铂类)显著改善了初治转移性非鳞状非小细胞肺癌(non-small cell lung cancer,NScLc)患者的总生存期(overall survival,OS)和无进展生存期(progression-free survival,PFS)。本研究报告了研究方案指定的最终分析的疗效结局,包括从培美曲塞-铂类交叉至帕博利珠单抗治疗的患者,以及完成35个周期(约2年)帕博利珠单抗治疗组的疗效。方法符合条件的患者以2:1随机分配至帕博利珠单抗,每3周一次,200 mg (n=410)或安慰剂(n=206)(共35周期,约2年),加上4个周期的培美曲塞(500 mg/m~2)和由研究者选择的每3周顺铂(75 mg/m~2)或卡铂(曲线下面积5 mg/min/mL)治疗,随后使用培美曲塞直至疾病进展。若符合纳入标准,分配至安慰剂联合培美曲塞加铂类治疗的患者可在疾病进展时转向帕博利珠单抗治疗。主要研究终点为OS和PFS。结果中位随访31.0个月,无论PD-L1的表达水平如何,与安慰剂联合培美曲塞-铂类治疗相比,帕博利珠单抗联合培美曲塞-铂类治疗可使患者的OS[风险比(hazard ratio,HR)为0.56;95%可信区间(confidence interval,cI) 0.46-0.69]和PFS (HR=0.49;95%cI:0.41-0.59)显著获益。接受帕博利珠单抗联合培美曲塞-铂类治疗的患者客观缓解率(objective response rate,ORR)(48.3%vs 19.9%)和第二次/后续无进展生存期(PFS2;HR=0.50;95%cI:0.41-0.61)均得到改善。安慰剂联合培美曲塞-铂类组的84例患者(40.8%)交叉至帕博利珠单抗治疗组。72.1%的接受帕博利珠单抗联合培美曲塞-铂类的患者和66.8%的接受安慰剂联合培美曲塞-铂类的患者发生了3级-5级不良事件。56例患者完成了35个周期(约2年)的帕博利珠单抗治疗;ORR为85.7%,53例(94.6%)患者存活至数据截止时间。结论与安慰剂联合培美曲塞-铂类治疗相比,帕博利珠单抗联合培美曲塞-铂类可持续提高疗效,且安全性可控。该研究结果支持将帕博利珠单抗联合培美曲塞-铂类作为初治转移性非鳞状NScLc患者的一线治疗方案。

关键词：帕博利珠单抗化疗非鳞状非小细胞肺癌

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Synthetic biology identifies the minimal gene set required for paclitaxel biosynthesis in a plant chassis

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molecular Plant 2023年第12期16卷 1951-1961页

作者： Youjun Zhang Lorenz Wiese Hao Fang Saleh Alseekh Leonardo Perez de souza Federico Scossa John molloy mathias christmann Alisdair R.Fernie max-Planck-Institut fur molekulare Pflanzenphysiologie Am Muhlenberg 114476 Potsdam-GolmGermany center of Plant Systems Biology and Biotechnology 4000 PlovdivBulgaria Institute of chemistry and Biochemistry Freie Universitat BerlinTakustraBe 314195 BerlinGermany Department of Biomolecular Systems Max Planck Institute of Colloids and Interfaces14476 PotsdamGermany Research center for Genomics and Bioinformatics(cREA-GB) Via Ardeatina 54600178 RomeItaly

The diterpenoid paclitaxel(Taxol)is a chemotherapy medication widely used as a first-line treatment against several types of solid *** supply of paclitaxel from natural sources is ***,missing knowledge about the genes involved in several specific metabolic steps of paclitaxel biosynthesis has rendered it difficult to engineer the full *** this study,we used a combination of transcriptomics,cell biology,metabolomics,and pathway reconstitution to identify the complete gene set required for the heterologous production of *** identified the missing steps from the current model of paclitaxel biosynthesis and confirmed the activity of most of the missing enzymes via heterologous expression in Nicotiana ***,we identified a new c4β-c20 epoxidase that could overcome the first bottleneck of metabolic *** used both previously characterized and newly identified oxomutases/epoxidases,taxane 1β-hydroxylase,taxane 9aα-hydroxylase,taxane 9α-dioxygenase,and phenylalanine-coA ligase,to successfully biosynthesize the key intermediate baccatin Ill and to convert baccatin Ill into paclitaxel in *** combination,these approaches establisha metabolic route to taxoidbiosynthesis and provide insights into the unique chemistry that plants use to generate complex bioactive metabolites.

关键词： paclitaxel biosynthesis synthetic biology baccatin Ill biosynthesis Taxus

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Kinetic Rates of the Fischer Tropsch Synthesis on a co/Nb_2O_5 catalyst

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Journal of Natural Gas chemistry 2006年第4期15卷 307-312页

作者： Víctor R.Ahón Paulo L.c.Lage carlos D.D.de souza Fabiana m.mendes martin Schmal Federal University of Rio de Janeiro Programa de Engenharia Química COPPE/UFRJ C.P.6850221941-972Rio de JaneiroRJBrazil

The kinetics of the Fischer-Tropsch reaction over a co/Nb2O5 catalyst in a fixed bed reactor was investigated experimentally. Experiments were carried out under isothermal and isobaric conditions （T=543 K, P=2.1 mPa） and under different conditions of several H2/cO feed molar ratio （0.49-4.79）, space velocities （0.2-3.8 h^-1）, mass of catalyst （0.3-1.5 g）, and cO conversion （10%-29%）. Synthesis gas conversion was measured and data were reduced to estimate the kinetic parameters for different Langmuir-Hinshelwood rate expressions. Differential and integral reactor models were used for the nonlinear regression of kinetics parameters. One of the rate equations could well explain the data. The hydrocarbon product distributions that were experimentally determined exhibited an unusual behavior, and a possible explanation was discussed.

关键词： Fischer-Tropsch natural gas kinetics selectivity

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Pediatric functional constipation treatment with Bifi dobacterium-containing yogurt:A crossover,double-blind,controlled trial

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World Journal of Gastroenterology 2011年第34期17卷 3916-3921页

作者： Paula VP Guerra Luiza N Lima Tassia c souza Vanessa mazochi Francisco J Penna Andreia m Silva Jacques R Nicoli Elizabet V Guimares Departamento de Pediatria Faculdade de Medicina Universidade Federal de Minas Gerais30130-100 Belo Horizonte MG Brazil Departamento de micro-biologia Instituto de Ciências Biológicas Universidade Federalde Minas Gerais32270-901 Belo Horizonte MG Brazil Andreia m Silva Universidade Federal deSo Joo del Rei Campus de Sete Lagoas35701-970 So Joodel Rey MG Brazil

AIm: To evaluate the treatment of pediatric functional chronic intestinal constipation (FcIc) with a probiotic goat yogurt. mETHODS: A crossover double-blind formula-controlled trial was carried out on 59 students (age range: 5-15 years) of a public school in Belo Horizonte, mG, Brazil, presenting a FcIc diagnostic, according to Roma Ⅲ criteria. The students were randomized in two groups to receive a goat yogurt supplemented with 109 colony forming unit/mL Bifidobacterium longum (***) (probiotic) daily or only the yogurt for a period of 5 wk (formula). Afterwards, the groups were intercrossed for another 5 wk. Defecation frequency, stool consistency and abdominal and defecation pain were ***: Both treatment groups demonstrated improvement in defecation frequency compared to baseline. However, the group treated with probiotic showed most signif icant improvement in the f irst phase of the study. An inversion was observed after crossing over, resulting in a reduction in stool frequency when this group was treated by formula. Probiotic and formula improved stool consistency in the f irst phase of treatment, but the improvement obtained with probiotic was significantly higher (P = 0.03). In the second phase of treatment, the group initially treated with probiotic showed worseningstool consistency when using formula. However, the difference was not signif icant. A signif icant improvement in abdominal pain and defecation pain was observed with both probiotic and formula in the first phase of treatment, but again the improvement was more signif icant for the group treated with B. longum during phase I (P crossover study were analyzed, significant differences were observed between probiotic yogurt and yogurt only for defecation frequency (P = 0.012), defecation pain (P = 0.046) and abdominal pain (P = 0.015).

关键词：配方治疗对照试验酸奶小儿便秘益生菌 IRST 一致性

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In the lack of extreme pioneers:trait relationships and ecological strategies of 66 subtropical tree species

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Journal of Plant Ecology 2015年第4期8卷 359-367页

作者： cristiane Forgiarini Alexandre F.souza Solon J.Longhi Juliano m.Oliveira Programa de Pós-Graduação em Biologia Diversidade e Manejo da Vida SilvestreUniversidade do Vale do Rio dos SinosAv.UNISINOS 950C.P.275São Leopoldo 93022-000RSBrazil Departamento de Ecologia CBUniversidade Federal do Rio Grande do NorteCampus UniversitárioLagoa NovaNatal 59072-970RNBrazil PPG-Engenharia Florestal Dep.de Ciências FlorestaisUniversidade Federal de Santa MariaAv.Roraimas/nBairro CamobiSanta Maria 97105-900RSBrazil Present address:Departamento de Botânica Instituto BiociênciasUniversidade Federal do Rio Grande do SulAv.Bento Gonçalves9500Prédio 43433Campus AgronomiaPorto Alegre 91501-970RSBrazil.

Aims Despite the growing interest in the topic of functional ecology,there are still forest regions that have not been examined,as most work has been done in the *** issues include the strength of a growth-mortality trade-off in trees(originally identified for seedlings)and the nature of the association between plant traits and vital rates,if *** objectives were to examine whether(i)ecological strategies in south american mixed forests are organ-ized along the fast competitor×slow stress-tolerator and height gradients as the main strategy axes depicted in the overall trait and vital rate correlation structure,and(ii)a tentative path model we proposed can explain the patterns of covariation among traits and vital *** We studied a different habitat(subtropical mixed conifer-hardwood forests)and region(brazilian atlantic Forest)from the majority of related studies in forests,carried out in the Neotropical *** on total height,stem slenderness,crown depth,wood density,specific leaf area,leaf and seed length,seed dispersal mode,annual mortality,diameter relative growth rate and relative growth rate under favorable conditions were measured in southern brazil for 66 tree *** were subjected to principal components analysis and path *** data on saplings and treelets were analyzed through *** Findingsstudied traits were reduced to four principal *** components analysis produced axes that fit the resource acquisition versus resource-conservation and the height-mortality trade-offs,although the former was split into two distinct *** size and seed dispersal mode appeared independently of these axes.a path model showed that leaf length and specific leaf area caused direct changes in trunk slenderness and,indirectly through growth,affected *** trade-offs between growth and survivorship and between wood density and stem slenderness trade-offs were not *** may

关键词： Araucaria angustifolia atlantic forest ecological strategies life-history trade-offs mixed forests

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SARS-coV-2 productively infects primary human immune system cells in vitro and in coviD-19 patients

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Journal of molecular cell Biology 2022年第4期14卷 51-64页

作者： marjorie c.Pontelli italo A.castro Ronaldo B.martins Leonardo La Serra Flavio P.Veras Daniele c.Nascimento camila m.Silva Ricardo S.cardoso Roberta Rosales Rogério Gomes Thais m.Lima Juliano P.souza Brenda c.Vitti Diego B.caetite mikhael H.F.de Lima Spencer D.Stumpf cassandra E.Thompson Louis-marie Bloyet Juliana E Toller-Kawahisa marcela c.Giannini Leticia P.Bonjorno marial.F.Lopes Sabrina S.Batah Li Siyuan Rodrigo Luppino-Assad Sergio c.L.Almeida Fabiola R.Oliveira maira N.Benatti Lorena L.F.Pontes Rodrigo c.Santana Fernando c.Vilar maria Auxiliadora-martins Pei-Yong Shi Thiago m.cunha Rodrigo T.calado Joséc.Alves-Filho Dario S.Zamboni Alexandre T.Fabro Paulo Louzada-Junior Rene D.R.Oliveira Sean P.J.Whelan Fernando Q.cunha Eurico Arruda Virology Research center Ribeirao Preto Medical SchoolUniversity of Sao Pauloibeirao PretoSao Paulo 14049-900.Brazil center of Research in Inflammatory Diseases Ribeirao Preto Medical SchoolUniversity of Sao PauloRibeirao PretoSao Paulo 14049-900Brazil Department of celland molecular Biology Ribeirao Preto Medical SchoolUniversityof Sao PauloRibeirao PretoSao Paulo 14049-900 Brazil Regional Blood centerof Ribeirao Preto Ribeirao Preto Medical ScholUniversity of Sao PauloRibeirao PretoSao Paulo 14049-900Brazil Department of Biochemistry&molecular Biology the University of Texas Medical BranchGalvestonTX7755USA Divisions of clinical lmmunology Infectious Diseases and Intensive Care UnitRibeirao Preto Medical Schooniversity of Sao PauloRibeirao PretoSao Paulo 14049-900Brazil Department of Pathology Ribeirao Preto Medical Scholniversity of Sao PauloRibeirao PretoSao Paulo 14049-900Brazil Department of molecular microbiology.Washington University in St.Louis Saint LouisMO 63110USA

The severe acute respiratory syndrome coronavirus 2(SARS-covV-2)infection is associated with a hyperinflammatory state and lymphocytopenia,a hallmark that appears as both signature and prognosis of disease severity *** cytokine storm and a sustained inflammatory state are commonly associated with immune cell depletion,it is still unclear whether direct SARS-cov-2 infection of immune cells could also play a role in this scenario by harboring viral *** found that monocytes,as well as both B and T lymphocytes,were susceptible to SARS-cov-2 infection in vitro,accumulating double-stranded RNA consistent with viral RNA replication and ultimately leading to expressive T cell *** addition,flow cytometry and immunofluorescence analysis revealed that SARS-cov-2 was frequently detected in monocytes and B lymphocytes from coronavirus disease 2019(coVID-19)*** rates of SARS-cov-2-infected monocytes in peripheral blood mononuclear cells from coVID-19 patients increased over time from symptom onset,with SARS-coV-2-positive monocytes,B cells,and cD4+T lymphocytes also detected in postmortem lung *** results indicated that SARS-coV-2 infection of blood-circulating leukocytes in covID-19 patients might have important implications for disease pathogenesis and progression,immune dysfunction,and virus spread within the host.

关键词： SARS-coV-2 coVID-19 lymphocytopenia peripheral blood mononuclear cell(PBmc) lymphocytes monocytes apoptosis

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Apparent soil electrical conductivity in the delineation of management zones for cocoa cultivation

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Information Processing in Agriculture 2022年第3期9卷 443-455页

作者： Samuel de Assis Silva Railton Oliveira dos Santos Daniel marcal de Queiroz Juliao Soares de souza Lima Levi Fraga Pajehua caique carvalho medauar center for Agricultural Sciences and Engineering Federal University of Espirito SantoAlegre CampusEspirito Santo 29500-000Brazil Department of Agricultural Sciences Santa Cruz State UniversityIlheusBahia 45662-900Brazil Department of Agricultural Engineering Federal University of Vic¸osaVic¸osaMinas Gerais 36570-900Brazil

Apparent electrical conductivity is an important parameter for describing the spatial vari-ability of physical and chemical attributes of the soil and for the delineation of manage-ment *** objective of this work is to outline management zones for the cocoa cultivation based on the spatial variability of the productivity and the apparent electrical conductivity(Eca)of the *** collection was performed in a regular sample grid con-taining 120 points in an area cultivated with cocoa trees,located in the municipality of Ilhe´us,state of Bahia,*** each sampling point(cocoa tree),soil samples were col-lected to determine chemical *** was measured for one year,counting,monthly,the number of fruits,which were classified into off-season cocoa,harvest and annual *** of the apparent electrical conductivity of the soil were performed at different times of the year using a portable conductivity *** data were analyzed using classical statistics and *** management zones were delin-eated using the fuzzy k-means *** ideal number of class was defined using the fuzziness performance index(FPI)and the entropy of the modified partition(mPE)*** Kappa coefficient was used to validate the management zones,assessing their agreement with the chemical attributes of the *** Eca of the soil values pre-sented moderate temporal variation,with maximum amplitude of 19.37 mS m1 and min-imum of 0.82 mS m1 between measurement periods;higher averages of the Eca coincided with the highest levels of water in the *** measurements of the Eca of the soil carried out in April and October showed greater correlation with the chemical attributes of the soil,with significant values for 11 and 8 of the 17 attributes evaluated,*** man-agement zones from the Eca measured in April showed:a)reduced number of classes;b)spatial continuity between classes,and;c)agreement from reasonable(kappa between

关键词： Theobroma cacao Precision agriculture Spatial variability Fuzzy k-means

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Anodic oxidation of formic acid on PdAuIr /c-Sb2O5·SnO2 electrocatalysts prepared by borohydride reduction

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燃料化学学报 2014年第7期42卷 851-857页

作者： A. O. Neto J. Nandenha R. F. B. De souza G. S Buzzo J. c. m . Silva E. V. Spinacé m . H. m . T. Assumpo Instituto de Pesquisas Energeticas e Nucleares-IPEN-cNEN/SP Cidade UniversitCtria Sao Paulo 05508-900 Brazil

PdAuIr/c-Sb2O5·SnO2electrocatalysts with Pd∶Au∶Ir molar ratios of 90∶5∶5,70∶20∶10 and 50∶45∶5 were prepared by borohydride reduction *** electrocatalysts were characterized by EDX,X-ray diffraction,transmission electron microscopy and the catalytic activity toward formic acid electro-oxidation in acid medium investigated by cyclic voltammetry(cV),chroamperometry(cA)and tests on direct formic acid fuel cell(DFAFc)at 100℃.X-ray diffractograms of PdAuIr/c-Sb2O5·SnO2electrocatalysts showed the presence of Pd fcc phase,Pd-Au fcc alloys,carbon and ATO phases,while Ir phases were not *** micrographs and histograms indicated that the nanoparticles were not well dispersed on the support and some *** cyclic voltammetry and chroamperometry studies showed that PdAuIr/c-Sb2O5·SnO2(50∶45∶5)had superior performance toward formic acid electro-oxidation at 25℃compared to PdAuIr/c-Sb2O5·SnO2(70∶20∶10),PdAuIr/c-Sb2O5·SnO2(90∶5∶5)and Pd/c-Sb2O5·*** experiments in a single DFAFc also showed that all PdAuIr/c-Sb2O5·SnO2electrocatalysts exhibited higher performance for formic acid oxidation in comparison with Pd/c-Sb2O5·SnO2electrocatalysts,however PdAuIr/c-Sb2O5·SnO2(90∶5∶5)had superior *** results indicated that the addition of Au and Ir to Pd favor the electro-oxidation of formic acid,which could be attributed to the bifunctional mechanism(the presence of ATO,Au and Ir oxides species)associated to the electronic effect(Pd-Au fcc alloys).

关键词： PdAuIr/c—Sb2O5·SnO2 甲酸氧化燃料电池电力

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Portomesenteric Venous Thrombosis in Patients after Laparoscopic Bariatric Surgery

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Surgical Science 2022年第9期13卷 419-428页

作者： Augusto Tinoco Renam c. Tinoco Luciana El-Kadre matheus P. S. Netto Júlia m. Rocha Diogo R. de souza Douglas G. Tavares Department of Surgery S&#227o Jos&#233 do Ava&#237 Hospital Itaperuna RJ Brazil São José do Avaí Hospital Itaperuna RJ Brazil

Objective: Obesity has become a worldwide epidemic that is directly related to chronic tissue inflammation and impaired fibrinolysis, both of which lead to an increased risk of thrombosis. The management of complications after bariatric surgery is still a challenge. The study aims to report the incidence of portomesenteric venous thrombosis (PmVT) in patients undergoing bariatric surgery. Introduction: Bariatric surgery is the procedure of choice for the treatment of obesity type III. Despite the safe technique, the surgeon must be aware of the risks linked to laparoscopy such as the PmVT. computed tomography (cT) with intravenous contrast was the imaging method of choice for diagnosis. materials and methods: We performed a retrospective analysis of 4790 patients from August 1999 to June 2020 was observed the incidence of PmVT in this group. Of all patients, 72.8% were female and 27.2% male. The mean age was 46.3 years (34 - 72) and the mean BmI before bariatric surgery was 41.4 kg/m2. Results: The study showed an incidence of PmVT of 0.12% (N = 6), portal vein thrombosis was of 0.10% (n = 5) and 0.03% of mVT (n = 1). Of these, 72.5% (n = 3473 patients) underwent laparoscopic gastric bypass, 23.6% (n = 1131 patients) were submitted to the laparoscopic sleeve gastrectomy and 3.8% (n = 186 patients) to other procedures. The mean postoperative hospital stay for bariatric surgery was 3.3 days. The average time of hospital stay of patients complicated with PmVT range from 5 to 14 days. No patient died of complications related to PmVT. conclusion: Portomesenteric vein thrombosis is a rare presentation after laparoscopic bariatric surgery. However, it is a serious complication that has a high index of suspicion for making its diagnosis. conservative treatment using anticoagulants and thrombolytics is effective, it should always be considered the main treatment option. However, these patients must be followed up in the long term, as late complications can occur i

关键词： morbid Obesity Laparoscopy Portomesenteric Venous Thrombosis Bariatric Surgery

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Study of the roles of caspase-3 and nuclear factor kappa B in myenteric neurons in a P2X7 receptor knockout mouse model of ulcerative colitis

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World Journal of Gastroenterology 2023年第22期29卷 3440-3468页

作者： Henrique Inhauser Riceti magalhães Felipe Alexandre machado Roberta Figueiroa souza marcos Antônio Ferreira caetano Vanessa Ribeiro Figliuolo Robson coutinho-Silva Patricia castelucci Department of Surgery School of Veterinary Medicine and Animal SciencesUniversity of São PauloSão Paulo 05508-270Brazil Department of Anatomy University of São PauloSão Paulo 05508-000Brazil Biophysics Institute carlos chagas Filho Federal University of Rio de JaneiroRio de Janeiro 21941-902Brazil

BAcKGROUND The literature indicates that the enteric nervous system is affected in inflammatory bowel diseases(IBDs)and that the P2X7 receptor triggers neuronal ***,the mechanism by which enteric neurons are lost in IBDs is *** To study the role of the caspase-3 and nuclear factor kappa B(NF-κB)pathways in myenteric neurons in a P2X7 receptor knockout(KO)mouse model of *** Forty male wild-type(WT)c57BL/6 and P2X7 receptor KO mice were euthanized 24 h or 4 d after colitis induction by 2,4,6-trinitrobenzene sulfonic acid(colitis group).mice in the sham groups were injected with *** mice were divided into eight groups(n=5):The WT sham 24 h and 4 d groups,the WT colitis 24 h and 4 d groups,the KO sham 24 h and 4 d groups,and the KO colitis 24 h and 4 d *** disease activity index(DAI)was analyzed,the distal colon was collected for immunohistochemistry analyses,and immunofluorescence was performed to identify neurons immunoreactive(ir)for calretinin,P2X7 receptor,cleaved caspase-3,total caspase-3,phospho-NF-κB,and total NF-κ*** analyzed the number of calretinin-ir and P2X7 receptor-ir neurons per ganglion,the neuronal profile area(μm^(2)),and corrected total cell fluorescence(cTcF).RESULTS cells double labeled for calretinin and P2X7 receptor,cleaved caspase-3,total caspase-3,phospho-NF-κB,or total NF-κB were observed in the WT colitis 24 h and 4 d *** number of calretinin-ir neurons per ganglion was decreased in the WT colitis 24 h and 4 d groups compared to the WT sham 24 h and 4 d groups,respectively(2.10±0.13 vs 3.33±0.17,Pcantly different between the KO *** calretinin-ir neuronal profile area was increased in the WT colitis 24 h group compared to the WT sham 24 h group(312.60±7.85 vs 278.41±6.65,Pclear profile area was decreased in the WT colitis 4 d group compared to the WT sham 4 d group(104.63±2.49 vs 117.41±1.14,Pmber of

关键词： cell death Enteric nervous system Gastroenterology Inflammatory bowel diseases P2X7 receptor Purinergic signaling

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