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Protective effects of cyclosporine and its analog NIM-811 in a murine model of hepatic ischemia-reperfusion injury

Liver Research 2024年第1期8卷 46-53页

作者： Joshua Hefler Rena Pawlick Braulio A.Marfil-Garza Aducio Thiesen Nerea Cuesta-Gomez Sanaz Hatami Darren H.Freed Constantine Karvellas David L.Bigam A.M.James Shapiro Department of Surgery Faculty of Medicine&DentistryUniversity of AlbertaEdmontonABCanada Department of medicine Faculty of Medicine&DentistryUniversity of AlbertaEdmontonABCanada CHRISTUS-LatAm Hub Excellence&Innovation Center MonterreyMexico Alberta Diabetes Institute University of AlbertaEdmontonABCanada Clinical Islet Transplant Program University of AlbertaEdmontonABCanada Department of Laboratory medicine&pathology Faculty of Medicine&DentistryUniversity of AlbertaEdmontonABCanada

Background and aim:The liver is susceptible to ischemia-reperfusion injury(IRI)during hepatic surgery,when the vessels are compressed to control bleeding,or liver transplantation,when there is an obligate period of *** hallmark of IRI comprises mitochondrial dysfunction,which generates reactive oxygen species,and cell death through necrosis or ***(CsA),which is a well-known immunosuppressive agent that inhibits calcineurin,has the additional effect of inhibiting the mito-chondrial permeability transition pore(mPTP),thereby,preventing mitochondrial swelling and ***-811,which is the nonimmunosuppressive analog of CsA,has a similar effect on the *** this study,we tested the effect of both agents on mitigating warm hepatic IRI in a murine *** and methods:Before ischemic insult,the mice were administered with intraperitoneal normal saline(control);CsA at 2.5,10,or 25 mg/kg;or NIM-811 at 10 mg/***,the mice were subjected to partial warm hepatic ischemia by selective pedicle clamping for 60 min,followed by 6 h of recovery after *** alanine transaminase(ALT)was measured,and the liver tissue was examined histologically for the presence of apoptosis and the levels of inflammatory ***:Compared with the control mice,the mice treated with 10 and 25 mg/kg of CsA and NIM-811 had significantly lower ALT levels(P<0.001,0.007,and 0.031,respectively).Moreover,the liver tissue showed reduced histological injury scores after treatment with CsA at 2.5,10,and 25 mg/kg and NIM-811(P=0.041,<0.001,0.003,and 0.043,respectively)and significant decrease in apoptosis after treatment with CsA at all doses(P=0.012,0.007,and<0.001,respectively).Levels of the pro-inflammatory cyto-kines,particularly interleukin(IL)-1β,IL-2,IL-4,IL-10,and keratinocyte chemoattractant/human growth-regulated oncogene significantly decreased in the mice treated with the highest dose of CsA(25 mg/kg)than those in the control ***

关键词： Cyclosporine(CsA) Cyclosporine analogue Liver surgery Ischemia-reperfusion injury(IRI) Animal model NIM-811

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Hypoxia-inducible factor 1alpha and vascular endothelial growth factor in Glioblastoma Multiforme:a systematic review going beyond pathologic implications

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Oncology Research 2024年第8期32卷 1239-1256页

作者： DIMITRA P.VAGELI PANAGIOTIS G.DOUKAS KERASIA GOUPOU ANTONIOS D.BENOS KYRIAKI ASTARA KONSTANTINA ZACHAROULI SOTIRIS SOTIRIOU MARIA IOANNOU Department of Surgery Yale UniversityNew HavenCT 06510USA Department of pathology Faculty of MedicineSchool of Health SciencesUniversity of ThessalyLarissa41500Greece Department of medicine Rutgers/Saint Peter’s University HospitalNew BrunswickNJ 08901USA Department of Neurology Army Share Fund Hospital(NIMTS)Athens11521Greece Laboratory of Embryology Faculty of MedicineSchool of Health SciencesUniversity of ThessalyLarissa41500Greece

Glioblastoma multiforme(GBM)is an aggressive primary brain tumor characterized by extensive heterogeneity and vascular *** conditions in the tissue microenvironment are considered a pivotal player leading tumor ***,hypoxia is known to activate inducible factors,such as hypoxia-inducible factor 1alpha(HIF-1α),which in turn can stimulate tumor neo-angiogenesis through activation of various downward mediators,such as the vascular endothelial growth factor(VEGF).Here,we aimed to explore the role of HIF-1α/VEGF immunophenotypes alone and in combination with other prognostic markers or clinical and image analysis data,as potential biomarkers of GBM prognosis and treatment *** performed a systematic review(Medline/Embase,and Pubmed database search was completed by 16th of April 2024 by two independent teams;PRISMA 2020).We evaluated methods of immunoassays,cell viability,or animal or patient survival methods of the retrieved studies to assess unbiased *** used inclusion criteria,such as the evaluation of GBM prognosis based on HIF-1α/VEGF expression,other biomarkers or clinical and imaging manifestations in GBM related to HIF-1α/VEGF expression,application of immunoassays for protein expression,and evaluation of the effectiveness of GBM therapeutic strategies based on HIF-1α/VEGF *** used exclusion criteria,such as data not reporting both HIF-1αand VEGF or *** included 50 studies investigating in total 1319 GBM human specimens,18 different cell lines or GBM-derived stem cells,and 6 different animal models,to identify the association of HIF-1α/VEGF immunophenotypes,and with other prognostic factors,clinical and macroscopic data in GBM prognosis and therapeutic *** found that increased HIF-1α/VEGF expression in GBM correlates with oncogenic factors,such as miR-210-3p,Oct4,AKT,COX-2,PDGF-C,PLDO3,M2 polarization,or ALK,leading to unfavorable *** HIF-1α/VEGF expression correlates with F

关键词： Glioblastoma multiforme(GBM) Astrocytoma Grade III Astrocytoma Grade IV Hypoxia-inducible factor 1alpha(HIF-1α) Vascular endothelial growth factor(VEGF)

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The role of polymorphic cytochrome P450 gene(CYP2B6)in B-chronic lymphocytic leukemia(B-CLL)incidence and outcome among Egyptian patients

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Oncology Research 2024年第4期32卷 785-797页

作者： MENNA AL-ADL MAGDY MYOUSSEF AHMED EL-SEBAIE SHERIF REFAAT AFAF EL-SAID Division of Biochemistry Department of ChemistryFaculty of ScienceMansoura UniversityMansoura35511Egypt Hematology Unit Department of Clinical PathologyFaculty of MedicineMansoura UniversityMansoura35511Egypt Medical Oncology Unit Oncology Center Mansoura UniversityMansoura35511Egypt Department of Genetics Mansoura University Children’s HospitalMansoura35511Egypt

Cytochromes P450(CYPs)play a prominent role in catalyzing phase I xenobiotic biotransformation and account for about 75%of the total metabolism of commercially available drugs,including *** gene expression and enzyme activity of CYPs are variable between individuals,which subsequently leads to different patterns of susceptibility to carcinogenesis by genotoxic xenobiotics,as well as differences in the efficacy and toxicity of clinically used *** research aimed to examine the presence of the CYP2B6*9 polymorphism and its possible association with the incidence of B-CLL in Egyptian patients,as well as the clinical outcome after receiving cyclophosphamide *** was isolated from whole blood samples of 100 de novo B-CLL cases and also from 100 sex-and age-matched healthy *** presence of the CYP2B6*9(G516T)polymorphism was examined by PCR-based allele specific amplification(ASA).Patients were further indicated for receiving chemotherapy,and then they were followed *** CYP2B6*9 variant indicated a statistically significant higher risk of B-CLL under different genetic models,comprising allelic(T-allele vs.G-allele,OR=4.8,p<0.001)and dominant(GT+TT ***,OR=5.4,p<0.001)*** cyclophosphamide chemotherapy,we found that the patients with variant genotypes(GT+TT)were less likely to achieve remission compared to those with the wild-type genotype(GG),with a response percentage of(37.5%vs.83%,respectively).In conclusion,our findings showed that the CYP2B6*9(G516T)polymorphism is associated with B-CLL susceptibility among Egyptian *** variant greatly affected the clinical outcome and can serve as a good therapeutic marker in predicting response to cyclophosphamide treatment.

关键词： B-CLL Xenobiotics Cytochromes P450 CYP2B6

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In vivo and in vitro study of resorbable magnesium wires for medical implants:Mg purity,surface quality,Zn alloying and polymer coating

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Journal of Magnesium and Alloys 2024年第6期12卷 2472-2488页

作者： K.Tesar J.Luňácková M.Jex M.Žaloudková R.Vrbová M.Bartoš P.Klein L.Vištejnová J.Dušková E.Filová Z.Sucharda M.Steinerová S.Habr K.Balík A.Singh Department of Materials Faculty of Nuclear Sciences and Physical EngineeringCzech Technical University in PragueTrojanova 13Prague 12000Czech Republic Institute of Physics Czech Academy of SciencesNa Slovance 2Prague 18221Czech Republic Institute of Dental medicine First Faculty of MedicineCharles University and General University Hospital in PragueKaterinská32Prague 12801Czech Republic Department of Physics Faculty of Nuclear Sciences and Physical EngineeringCzech Technical University in PragueBrehová7Prague 11519Czech Republic Department of Composites and Carbon Materials Institute of Rock Structure and MechanicsCzech Academy of SciencesV Holešovickách 41Prague 18209Czech Republic Institute of Anatomy First Faculty of MedicineCharles UniversityU Nemocnice 3Prague 12800Czech Republic Biomedical Center Faculty of Medicine in PilsenCharles UniversityAlej Svobody 76Pilsen 32300Czech Republic Department of Pathological Physiology Faculty of Medicine in PilsenCharles UniversityAlej Svobody 7632300 PilsenCzech Republic Department of Histology and Embryology Faculty of Medicine in PilsenCharles UniversityAlej Svobody 7632300 PilsenCzech Republic Institute of pathology First Faculty of MedicineCharles University and General University Hospital in PragueStudnickova 2Prague 12800Czech Republic Department of Biomaterials and Tissue Engineering Institute of PhysiologyCzech Academy of SciencesVidenska 1083Prague 14200Czech Republic Research Center for Structural Materials National Institute for Materials Science1-2-1 SengenTsukuba 305-0047Japan

Magnesium is an excellent material in terms of biocompatibility and its corrosion products can serve as an active source for new bone ***,localized corrosion and H_(2)generation limit the potential of Mg-based *** low-alloyed Mg-Zn wires can strongly reduce problems with large H_(2)bubbles and improve the mechanical properties considerably while maintaining excellent long-term *** pickling and a polymer coating can be effectively used to lower the rate of in vivo *** this work,microstructural,mechanical,and in vitro characterization of 250μm and 300μm extruded wires made from ultra-pure Mg,commercially pure Mg,Mg-0.15Zn,Mg-0.4Zn and Mg-1Zn was ***,Mg-0.4Zn wires together with a variant coated with a copolymer of L-lactide andε-caprolactone were tested in vivo on artificially damaged Wistar rat *** on the observed Mg-induced osteogenesis,polymer-coated Mg wires with a small addition of Zn are a perspective material for bone-support applications,such as cerclage and fixation wires.

关键词： Magnesium Resorbable Mg wire Mg-Zn implant degradation Biocompatibility study Zn grain boundary segregation

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Experimental models of high-risk bowel anastomosis in rats:A systematic review

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World Journal of Experimental medicine 2024年第2期14卷 114-131页

作者： Georgios Ntampakis Manousos-Georgios Pramateftakis Elissavet Anestiadou Stefanos Bitsianis Orestis Ioannidis Chryssa Bekiari George Koliakos Maria Karakota Anastasia Tsakona Angeliki Cheva Stamatios Angelopoulos Fourth Department of Surgery Medical SchoolAristotle University of ThessalonikiThessaloniki 57010Greece Laboratory of Anatomy and Histology School of Veterinary MedicineFaculty of Health SciencesAristotle University of ThessalonikiThessaloniki 54124Greece Experimental and Research Center Papageorgiou General Hospital of ThessalonikiThessaloniki 56403Greece Laboratory of Biochemistry Faculty of MedicineAristotle University of ThessalonikiThessaloniki 54124Greece Department of pathology Faculty of MedicineAristotle University of ThessalonikiThessaloniki 54124Greece

BACKGROUND Anastomotic leaks remain one of the most dreaded complications in gastrointestinal surgery causing significant morbidity,that negatively affect the patients’quality of *** studies play an important role in understanding the pathophysiological background of anastomotic healing and there are still many fields that require further *** drawn from these studies can lead to interventions or techniques that can reduce the risk of anastomotic leak in patients with high-risk *** the advances in experimental protocols and techniques,designing a high-quality study is still challenging for the investigators as there is a plethora of different models *** To review current state of the art for experimental protocols in high-risk anastomosis in *** This systematic review was performed according to The Preferred Reporting Items for Systematic Reviews and Meta-Analyses *** identify eligible studies,a comprehensive literature search was performed in the electronic databases PubMed(MEDLINE)and Scopus,covering the period from conception until 18 October *** From our search strategy 102 studies were included and were categorized based on the mechanism used to create a high-risk *** of assessing anastomotic healing were extracted and were individually *** Anastomotic healing studies have evolved over the last decades,but the findings are yet to be translated into human *** is a need for high-quality,well-designed studies that will help to the better understanding of the pathophysiology of anastomotic healing and the effects of various interventions.

关键词： High-risk anastomosis Rats Experimental models Bowel Colon Anastomotic leak Colon resection Inflammatory bowel disease Intra-abdominal sepsis Bursting pressure

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Transformed gastric mucosa-associated lymphoid tissue lymphoma originating in the colon and developing metachronously after Helicobacter pylori eradication:A case report

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World Journal of Gastrointestinal Oncology 2024年第10期16卷 4281-4288页

作者： Makoto Saito Zen-Ichi Tanei Masumi Tsuda Toma Suzuki Emi Yokoyama Minoru Kanaya Koh Izumiyama Akio Mori Masanobu Morioka Takeshi Kondo Blood Disorders Center Aiiku HospitalSapporo 064-0804HokkaidoJapan Department of Cancer pathology Faculty of MedicineHokkaido UniversitySapporo 060-8638HokkaidoJapan

BACKGROUND Helicobacter pylori(***)eradication treatment for primary gastric mucosaassociated lymphoid tissue(MALT)lymphoma has already been ***,t(11;18)(q21;q21)/API2-MALT1 translocation-positive lesions are a type of primary gastric MALT lymphoma in which a response to eradication treatment is difficult to *** addition,trisomy 18 may be associated with diffuse large B-cell lymphoma(DLBCL)transformation of gastric MALT *** SUMMARY A 66-year-old man was diagnosed with MALT lymphoma in the ascending colon by colonoscopy and *** years later,esophagogastroduodenoscopy revealed chronic atrophic gastritis that was positive for ***,and eradication treatment was *** years and nine months later(at the age of 70),a new ulcerative lesion suggestive of MALT lymphoma appeared in the gastric body,and six months later,a similar lesion was also found in the *** year later(4 years and 3 months after *** eradication),at the age of 72,the lesion in the gastric body had become deeper and had propagated.A biopsy revealed a pathological diagnosis of *** MALT lymphoma lesions in the ascending colon and DLBCL lesions in the stomach were positive for the t(11;18)(q21;q21)/API2-MALT1 translocation,and trisomy 18q21 was also *** 6 courses of R-CHOP(rituximab,cyclophosphamide,doxorubicin,vincristine and prednisone)chemotherapy,all of the above lesions disappeared[complete remission(CR)],and CR has been maintained for more than 3 *** addition,both the colonic and gastric lesions were proven to have the same *** Because the patient had a MALT1 translocation with trisomy 18q21,it was thought that this gastric MALT lymphoma developed independently of *** infection and progressed.

关键词： Gastric mucosa-associated lymphoid tissue lymphoma Transform Diffuse large B-cell lymphoma Colonic mucosa-associated lymphoid tissue lymphoma Helicobacter pylori eradication MALT1 translocation Case report

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First report of the histopathological effect of electrocautery using on the urethral taste rosea during glans penis injury by incision in rabbits

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Asian Journal of Urology 2024年第1期11卷 115-120页

作者： Ozgur Caglar Ayhan Kanat Mehmet Dumlu Aydin Nezih Akca Sevilay Ozmen Ataturk university Medical FacultyDepartment of Pediatric SurgeryErzurumTurkey Recep Tayyip Erdogan university Medical FacultyDepartment of NeurosurgeryRizeTurkey Ataturk university Medical FacultyDepartment of NeurosurgeryErzurumTurkey Recep Tayyip Erdogan university Medical FacultyDepartment of UrologyRizeTurkey Ataturk university Medical FacultyDepartment of PathologyErzurumTurkey

Objective:Currently,electrocautery devices have frequently been used in penile surgical *** hypothesized that electrocautery using during penile surgical procedures may harm the taste rosea and the dorsal nerve of the penis or ***:Eighteen young age male New Zealand rabbits were studied:five in the control(Group I,n=5),five in the penile surgery without using electrocautery(sham group,Group II,n=5),eight in the monopolar cautery(study group,Group III,n=8)groups under general *** animals were followed for 3 weeks and *** tissue—pudendal nerve root complexes and dorsal root ganglion of sacral 3 level were examined using stereological *** results were compared ***:The live and degenerated taste bud-like structures and degenerated neuron densities of pudendal ganglia(mean±standard deviation,n/mm^(3))were estimated as 198±24/mm^(3),4±1/mm^(3),and 5±1/mm^(3) in Group I;8±3/mm^(3),174±21/mm^(3),and 24±7/mm^(3) in Group II;and 21±5/mm^(3),137±14/mm^(3),and 95±12/mm^(3) in Group III,*** of taste buds and pudendal ganglia was significantly different between ***:Intact spinal cord and normal parasympathetic and thoracolumbar sympathetic networks are crucial for human sexual *** present study indicates that the glans penis injury by using electrocautery may lead to pudendal ganglia *** damage to taste rosea and retrograde degeneration of the pudendal nerve may be the cause of sexual dysfunction responsible mechanism.

关键词： Urethral taste rosea Tastebuds Pudendalnerve Degeneration Penile surgery

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Surgical Management of a Collision Tumor: The Association of Intracranial Meningioma and Macroadenoma

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Open Journal of Modern Neurosurgery 2024年第1期14卷 48-56页

作者： Salma Abbas Yao Christian Hugues Dokponou Thameen Jaradat Mahjouba Boutarbouch Nadia Cherradi Hafsa El Ouazzani Abdessamad El Ouahabi Department of Neurosurgery Faculty of Medicine and Pharmacy Mohammed V University Rabat Morocco Department of pathology Faculty of Medicine and Pharmacy Mohammed V University Rabat Morocco

Background: The simultaneous presence of a pituitary adenoma and a meningioma is a rare and underreported condition. The randomly encountered cases need to be reported to further allow our understanding of this collision tumors that are still not understood nor fully described. Patients and Method: We report a case of coexisting nonfunctioning pituitary adenoma and a left temporal lobe meningioma revealed by a 1-year history of progressive vision loss and occasional headaches in a 56-year-old woman. Her clinical condition worsened in the last 5 months with ptosis, cavernous sinus syndrome, and ophthalmoplegia of the right eye without papilledema. There was an improvement in the visual symptoms after subtotal resection of both lesions through a right frontotemporal craniotomy. Histology confirmed a collision tumor. The patient was referred for adjuvant treatment with gamma knife radiosurgery. He was doing well and back to his usual duties 6 months later. Conclusion: A gross total or subtotal resection with adjuvant therapy is the gold standard for the surgical management of collision tumors for a favorable patient outcome.

关键词： Collision Tumors Meningioma Pituitary Adenoma

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Novel insights into autophagy in gastrointestinal pathologies,mechanisms in metabolic dysfunction-associated fatty liver disease and acute liver failure

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World Journal of Gastroenterology 2024年第27期30卷 3273-3277页

作者： Tsvetelina Velikova Milena Gulinac Medical faculty Sofia University St Kliment OhridskiSofia 1407Bulgaria Department of General and Clinical pathology Medical University of PlovdivPlovdiv 4002Bulgaria

In this editorial,we comment on three articles published in a recent issue of World Journal of *** is a pressing need for new research on autophagy's role in gastrointestinal(GI)disorders,and also novel insights into some liver conditions,such as metabolic dysfunction-associated fatty liver disease(MAFLD)and acute liver failure(ALF).Despite advancements,understanding autophagy's intricate mechanisms and implications in these diseases remains ***,MAFLD's pathogenesis,encompassing hepatic steatosis and metabolic dysregulation,require further ***,the mechanisms underlying ALF,a severe hepatic dysfunction,are poorly *** studies exploring the interplay between autophagy and GI disorders,as well as defined mechanisms of MAFLD and ALF,are crucial for identifying therapeutic targets and enhancing diagnostic and treatment strategies to mitigate the global burden of these diseases.

关键词： Gastrointestinal diseases Autophagy Metabolic dysfunction-associated fatty liver disease High-normal alanine aminotransferase level Silent information regulator sirtuin 1 Acute liver failure

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Transient receptor potential channels as predictive marker and potential indicator of chemoresistance in colon cancer

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Oncology Research 2024年第1期32卷 227-239页

作者： WEI HU THOMAS WARTMANN MARCO STRECKER ARISTOTELIS PERRAKIS ROLAND CRONER ARPAD SZALLASI WENJIE SHI ULF D.KAHLERT The Fourth Clinical Medical College of Yangzhou university Nantong Rich HospitalNantongChina Molecular and Experimental Surgery Clinic for General-Visceral-Vascular and Transplant SurgeryFaculty of Medicine and University Hospital MagdeburgOtto-von-Guericke UniversityMagdeburgGermany Department of pathology and Experimental Cancer Research Semmelweis UniversityBudapestHungary

Transient receptor potential(TRP)channels are strongly associated with colon cancer development and *** study leveraged a multivariate Cox regression model on publicly available datasets to construct a TRP channels-associated gene signature,with further validation of signature in real world samples from our hospital treated patient ***-Meier(K-M)survival analysis and receiver operating characteristic(ROC)curves were employed to evaluate this gene signature’s predictive accuracy and robustness in both training and testing cohorts,***,the study utilized the CIBERSORT algorithm and single-sample gene set enrichment analysis to explore the signature’s immune infiltration landscape and underlying functional *** support vector machine algorithm was applied to evaluate the signature’s potential in predicting chemotherapy *** findings unveiled a novel three TRP channels-related gene signature(MCOLN1,TRPM5,and TRPV4)in colon adenocarcinoma(COAD).The ROC and K-M survival curves in the training dataset(AUC=0.761;p=1.58e-05)and testing dataset(AUC=0.699;p=0.004)showed the signature’s robust predictive capability for the overall survival of COAD *** of the immune infiltration landscape associated with the signature revealed higher immune infiltration,especially an increased presence of M2 macrophages,in high-risk group patients compared to their low-risk ***-risk score patients also exhibited potential responsiveness to immune checkpoint inhibitor therapy,evident through increased CD86 and PD-1 expression ***,the TRPM5 gene within the signature was highly expressed in the chemoresistance group(p=0.00095)and associated with poor prognosis(p=0.036)in COAD patients,highlighting its role as a hub gene of ***,this signature emerged as an independent prognosis factor for COAD patients(p=6.48e-06)and expression of model gene are validated by public data a

关键词： Colon cancer Transient receptor potential channels Prognostic signature Chemotherapy efficiency TRPM5

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