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简介：Interleukin-18(IL-18)wasdiscoveredasaninterferon-γ-inducingfactorandhadacriticalroleininflammatoryandimmuneresponse.Itstimulatesnaturalkiller(NK)andTcellsandenhancesTh1immuneresponse.Theseactivatedimmunecellseliminatecancercellsandvirus-infectedcellseffectively.However,IL-18hasalsobeenfoundtopromotetumorprogression.HigherexpressionorsecretionlevelofIL-18isdetectedinvariouscancercellsincomparisonwithnormalcontrol,andIL-18isabletoinduceangiogenesis,migration/metastasis,proliferationandimmuneescape.ThesedualeffectsandthemechanismofIL-18needtobeinvestigatedfurtherasitrelatestocancer.

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简介：BackgroundStatinsreduceadversecardiovascularoutcomesandslowtheprogressionofcoronaryatherosclerosisinproportiontotheirabilitytoreducelow-densitylipoprotein(LDL)cholesterol.However,fewstudieshaveeitherassessedtheabilityofintensivestatintreatmentstoachievediseaseregressionorcomparedalternativeapproachestomaximalstatinadministration.MethodsWeperformedserialintravascularultrasonographyin1039patientswithcoronarydisease,atbaselineandafter104weeksoftreatmentwitheitheratorvastatin,80mgdaily,orrosuvastatin,40mgdaily,tocomparetheeffectofthesetwointensivestatinregimensontheprogressionofcoronaryatherosclerosis,aswellastoassesstheirsafetyandside-effectprofiles.ResultsAfter104weeksoftherapy,therosuvastatingrouphadlowerlevelsofLDLcholesterolthantheatorvastatingroup(62.6vs.70.2mgperdeciliter[1.62vs.1.82mmolperliter],P<0.001),andhigherlevelsofhigh-densitylipoprotein(HDL)cholesterol(50.4vs.48.6mgperdeciliter[1.30vs.1.26mmolperliter],P=0.01).Theprimaryefficacyendpoint,percentatheromavolume(PAV),decreasedby0.99%(95%confidenceinterval[CI],1.19to-0.63)withatorvastatinandby1.22%(95%CI,-1.52to-0.90)withrosuvastatin(P=0.17).Theeffectonthesecondaryefficacyendpoint,normalizedtotalatheromavolume(TAV),wasmorefavorablewithrosuvastatinthanwithatorvastatin:-6.39mm3(95%CI,-7.52to-5.12),ascomparedwith?4.42mm3(95%CI,-5.98to-3.26)(P=0.01).Bothagentsinducedregressioninthemajorityofpatients:63.2%withatorvastatinand68.5%withrosuvastatinforPAV(P=0.07)and64.7%and71.3%,respectively,forTAV(P=0.02).Bothagentshadacceptableside-effectprofiles,withalowincidenceoflaboratoryabnor-malitiesandcardiovascularevents.ConclusionsMaximaldosesofrosuvastatinandatorvastatinresultedinsignificantregressionofcoronaryatherosclerosis.DespitethelowerlevelofLDLcholesterolandthehi

简介：AbstractGastric intestinal metaplasia (GIM) is a precancerous lesion of gastric cancer (GC) and is considered an irreversible point of progression for GC. Helicobacter pylori infection can cause GIM, but its eradication still does not reverse the process. Bile reflux is also a pathogenic factor in GIM and can continuously irritate the gastric mucosa, and bile acids in refluxed fluid have been widely reported to be associated with GIM. This paper reviews in detail the relationship between bile reflux and GIM and the mechanisms by which bile acids induce GIM.

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简介：AbstractBackground:Keloids are benign fibrous growths that are caused by excessive tissue build-up. Severe keloids exert more significant effects on patients’ quality of life than do mild keloids. We aimed to identify factors associated with the progression from mild keloids to severe keloids, as distinct from those associated with the formation of keloids.Methods:In this retrospective case-control study, 251 patients diagnosed with keloids at West China Hospital between November 2018 and April 2021 were grouped according to the severity of lesions (mild [n = 162] or severe [n = 89]). We collected their basic characteristics, living habits, incomes, comorbidities, and keloid characteristics from Electronic Medical Records in the hospital and the patients’ interviews. Conditional multivariable regression was performed to identify the independent risk factors for the progression of keloids.Results:Eighty-nine patients (35.5%) were classified as having severe keloids. We found the distribution of severe keloids varied with sex, age, excessive scrubbing of keloids, family income, the comorbidity of rheumatism, disease duration, characteristics of the location, location in sites of high-stretch tension, the severity and frequency of pain, the severity of pruritus, and infection. Multivariable analysis revealed significant associations between severe keloids and infection (odds ratio [OR], 3.55; P = 0.005), excessive scrubbing of keloids (OR, 8.65; P = 0.001), low or middle family income (OR, 13.44; P = 0.021), comorbidity of rheumatism (OR, 18.97; P = 0.021), multiple keloids located at multiple sites (OR, 3.18; P = 0.033), and disease duration >15 years (OR, 2.98; P = 0.046).Conclusion:Doctors should implement more active and thorough measures to minimize the progression of mild keloids in patients who have any of the following risk factors: infection, excessive scrubbing of keloids, low or middle family income, comorbidity of rheumatism, multiple keloids located at multiple sites, and disease duration >15 years.

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简介：Objective:IL-22-producingCD4+Thelpercells(Th22cells)havebeenidentifiedasmajorinducersoftissueinflammationandimmuneresponses.Currently,nopreviousstudyexploredtheroleofTh22cellsinthepathogenesisofhepatocellularcarcinoma(HCC).ThestudyaimedtodeterminethebiologicalfunctionofTh22cellsanditseffectorIL-22inHCCpatients.Methods:Forty-fiveHCCpatientsand19healthycontrolswererecruitedandtheirperipheralbloodwascollected.ThefreshHCCtissues,adjacentHCCtissuesandtennormallivertissueswerealsocollected.FlowcytometryanalysiswasusedtodeterminethefrequenciesofcirculatingTh22cellsandTh17cells.SerumIL-22levelsweretestedbyenzyme-linkedimmunosorbentassay(ELISA).Immunohistochemicalstainingandreal-timepolymerasechainreaction(PCR)wereusedtodetectIL-22proteinandmRNAintissuesspecimens,respectively.Results:CirculatingTh22cells,Th17cellsandserumIL-22levelsweresignificantlyelevatedinHCCpatientscomparedwiththoseofhealthycontrols(P<0.001).Th22cellswereshowedtobepositivelycorrelatedwithIL-22inHCCpatients(P<0.05),butnotinhealthycontrols.NosignificantdifferenceswerefoundinHCCpatientswithHBeAgpositivityornegativityintermofTh22cellsandserumIL-22levels.TheexpressionofIL-22proteinandmRNAwashighestinHCCtissues,followedbyadjacentHCCtissuesandnormallivertissues.Furthermore,Th22cells,serumIL-22levelsandIL-22mRNAwereelevatedatstageIII-IVcomparedwithstageI-IIofHCC(P<0.05).Conclusions:ElevationofcirculatingTh22cellsandIL-22maybeimplicatedinthepathogenesisofHCC,andpotentiallybecellulartargetsfortherapeuticintervention.

简介：AbstractBackground:Previously, dihydroceramide (d18:0/24:0) (dhCer (d18:0/24:0)) was reported to be a potential biomarker for acute-onchronic liver failure (ACLF) prognosis. In this study, we further explored the role of dhCer (d18:0/24:0) in the progression of ACLF to validate the biomarker using ACLF rat model.Methods:ACLF rats were sacrificed at 4 and 8 h post-D-galactosamine (D-gal)/lipopolysaccharide (LPS) administration to investigate the liver biochemical markers, prothrombin time and liver histopathology. Change in dhCer and other sphingolipids levels were investigated by high-performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS). Rats were treated with N-(4-hydroxyphenyl) retinamide (4-HPR) to examine the mortality rate and its role in improving ACLF.Results:LPS/D-gal administration resulted in significant elevation in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. Prothrombin time was prolonged and histopathological examination showed abnormality. HPLC-MS/MS results showed total dhCer levels in ACLF group (64.10 ± 8.90 pmol/100 μL, 64.22 ± 6.78 pmol/100 μL for 4 and 8 h, respectively) were decreased significantly compared with control group (121.61 ± 23.09 pmol/100 μL) (P < 0.05). In particular, dhCer (d18:0/24:0), dhCer (d18:0/20:0), and dhCer (d18:0/22:0) levels were decreased. Treatment with 4-HPR significantly increased the levels of dhCers, including dhCer (d18:0/24:0) compared with ACLF group, for the level of dhCer (d18:0/24:0) in 4-HPR group was 20.10 ± 8.60 pmol/100 μL and the level of dhCer (d18:0/24:0) in ACLF group was 9.74 ± 2.99 pmol/100 μL (P < 0.05). This was associated with reduced mortality rate and prolonged survival time. The ALT and AST in 4-HPR group were significantly decreased compared with ACLF group. The prothrombin time of 4-HPR group (41.49 s) was significantly lower than the prothrombin time of ACLF group (57.96 s) (P < 0.05). 4-HPR also decreased plasma ammonia levels slightly, as the plasma ammonia levels in 4-HPR group and ACLF group were 207.37 ± 60.43, 209.15 ± 60.43 μmol/L, respectively. Further, 4-HPR treatment improved histopathological parameters.Conclusions:DhCer, especially dhCer (d18:0/24:0), is involved in the progression of ACLF. Increasing the levels of dhCer can reduce the mortality rate of ACLF rats and alleviate liver injury.

简介：Objective:Stromalinteractionmolecule1(STIM1)overexpressionhasbeenreportedtoplayanimportantroleinprogressionofseveralcancers.However,themechanismofSTIM1overexpressionanditsrelationshipwithhypoxiainpancreaticductaladenocarcinoma(PDAC)remainsunclear.Methods:STIM1andHIF-1αexpressionwastestedusingimmunohistochemistryintissuemicroarray(TMA)includingpancreaticcancerandmatchednormalpancreatictissues,andtheirrelationshipswithclinicopathologicalparameterswerestatisticallyanalyzed.q-PCR,Westernblot,ChIP,andluciferaseassaywereemployedto030analyzetranscriptionalregulationbetweenHIF-1αandSTIM1inpancreaticcancerPANC-1cells.Results:BothSTIM1andHIF-1αshowedhigherpositiveratesandup-regulatedexpressionincancertissuescomparedtothatofnormaltissues(P<0.05).TheKaplan–MeiermethodrevealedthathigherHIF-1αandSTIM1expressionlevelsweresignificantlycorrelatedwithdecreaseddisease-freesurvival(P=0.025andP=0.029,respectively).TheexpressionofHIF-1αshowedasignificantpositivecorrelationwiththatofSTIM1incancertissues(rs=0.3343,P=0.0011)andpancreaticcancercelllines.Furthermore,ChIPandluciferaseassaysconfirmedthatHIF-1αboundtotheSTIM1promoterandregulateditsexpressioninPANC-1cells.Conclusions:Inhypoxiamicroenvironment,up-regulatedexpressionofSTIM1mediatedbyHIF-1αpromotesPDACprogression.HIF-1αandSTIM1arepotentialprognosticmarkersand/ortherapeutictargetsforPDACtreatment.

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简介：AbstractBackground:According to the amyloid, tau, neurodegeneration research framework classification, amyloid and tau positive (A+T+) mild cognitive impairment (MCI) individuals are defined as prodromal Alzheimer disease. This study was designed to compare the clinical and biomarker features between A+T+MCI individuals who progressed to progressive MCI (pMCI) and those who remained stable MCI (sMCI), and to identify relevant baseline clinical biomarker and features that could be used to predict progression to dementia within 2 years.Methods:We stratified 197 A+T+MCI individuals into pMCI (n = 64) and sMCI (n = 133) over 2 years. Demographics and cognitive assessment scores, cerebrospinal fluid (CSF), and neuroimaging biomarkers (18F-florbetapir positron emission tomography mean standardized uptake value ratios [SUVR] and structural magnetic resonance imaging [MRI]) were compared between pMCI and sMCI at baseline, 12- and 24-month follow-up. Logistic regression models then were used to evaluate clinical baseline and biomarker features that predicted dementia progression in A+T+MCI.Results:pMCI individuals had higher mean 18F-florbetapir SUVR, CSF total-tau (t-tau), and p-tau181P than those in sMCI individuals. pMCI individuals performed poorer in cognitive assessments, both global and domain specific (memory, executive, language, attention, and visuospatial skills) than sMCI. At baseline, there were significant differences in regions of interest of structural MRI between the two groups, including bilateral amygdala, hippocampus and entorhinal, bilateral inferior lateral ventricle, left superior and middle temporal, left posterior and caudal anterior cingulate (P < 0.05). Baseline CSF t-tau levels and cognitive scores of Montreal cognitive assessment, functional assessment questionnaire, and everyday cognition by the patient’s study partner language domain could predict progression to dementia in A+T+MCI within 2 years.Conclusions:In future clinical trials, specific CSF and cognitive measures that predict dementia progression in A+T+MCI might be useful risk factors for assessing the risk of dementia progression.

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简介：各种各样的研究证明了那变换血管收缩素的酶(王牌)基因插入/删除(标志)多型性可以在前进起一个作用结束舞台在有IgA肾炎(IgAN)的病人的肾的失败(ESRF)。在这使随机化的控制试用，病人们被跟随在上面5年决定他们的长期的肾的结果到ACEI/ATRA治疗并且如果他们的王牌基因侧面能在决定他们的反应到治疗起一个作用，查明。有IgAN的七十五个病人被获得。37在为62的ACEI/ATRA治疗上??H

简介：AbstractBackground:Circular RNA ciRS-7 has been reported to be involved in the progression of various cancers. However, ciRS-7 expression and its role in clear cell renal cell carcinoma (ccRCC) progression remains unclear. This study aimed to investigate the effect of ciRS-7 expression on ccRCC and the related signaling pathway.Methods:ciRS-7 expression was analyzed using quantitative reverse transcription polymerase chain reaction in 87 pairs of ccRCC and matched adjacent normal tissues. The role of ciRS-7 in ccRCC cell proliferation and invasion was determined using the cell counting kit-8 and invasion assays, respectively. Potential mechanisms underlying the role of ciRS-7 in promoting ccRCC progression were explored by Western blotting. The relationship between the expression of ciRS-7 and features of ccRCC was analyzed by the Chi-square test and progression-free survival was determined using a Kaplan-Meier plot.Results:ciRS-7 was overexpressed in ccRCC tissues compared with that in matched adjacent normal tissues. In addition, ciRS-7 up-regulation was closely associated with tumor diameter (P = 0.050), clinical stage (P = 0.009), and distant metastasis (P = 0.007). ciRS-7 knockdown in 786O and 769P cells markedly inhibited their proliferative and invasive abilities. In addition, ciRS-7 inhibition reduced phosphorylated epidermal growth factor receptor (p-EGFR) and phosphorylated serine/threonine kinase (p-Akt) levels.Conclusions:ciRS-7 up-regulation could promote ccRCC cell proliferation and invasion, which may be related with the EGFR/Akt signaling pathway. ciRS-7 might be a potential ccRCC therapeutic target.

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