Prevalence and risk factors of depression among patients with perianal fistulizing Crohn’s disease

BACKGROUND Psychological distress,especially depression,associated with perianal fistulizing Crohn’s disease(PFCD)is widespread and refractory.However,there is a surprising paucity of studies to date that have sought to identify the prevalence and risk factors of depression associated with PFCD.AIM To estimate the prevalence of depressive symptoms and investigate the depression-related risk factors in patients with PFCD.METHODS The study was conducted in the form of survey and clinical data collection via questionnaire and specialized medical staff.Depressive symptoms,life quality,and fatigue severity of patients with PFCD were assessed by Patient Health Questionnaire-9,Inflammatory Bowel Disease Patient Quality of Life Questionnaire(IBDQ),and Inflammatory Bowel Disease(IBD)Fatigue Patient Self-assessment Scale.The basic demographic information,overall disease features,perianal clinical information,and laboratory inflammation indicators were also gathered.Multivariate regression analysis was ultimately used to ascertain the risk factors of depression associated with PFCD.RESULTS A total of 123 patients with PFCD were involved,and 56.91%were suffering from depression.According to multivariate logistic regression analysis,Perianal Disease Activity Index(PDAI)score[odds ratio(OR)=0.69,95%confidence interval(CI):0.50 to 0.95],IBDQ score(OR=0.93,95%CI:0.88 to 0.97),modified Van Assche index(OR=1.24,95%CI:1.01 to 1.53),and IBD Fatigue score(OR=1.72,95%CI:1.23 to 2.42)were independent risk factors of depression-related prevalence among patients with PFCD(P<0.05).Multiple linear regression analysis revealed that the increasing perianal modified Van Assche index(βvalue=0.166,95%CI:0.02 to 0.31)and decreasing IBDQ score(βvalue=-0.116,95%CI:-0.14 to-0.09)were independently associated with the severity of depression(P<0.05).CONCLUSION Depressive symptoms in PFCD patients have significantly high prevalence.PDAI score,modified Van Assche index,quality of life,and fatigue severity were the main independent risk factors.

Total flavone of Abelmoschus manihot suppresses epithelial-mesenchymal transition via interfering transforming growth factor-β1 signaling in Crohn's disease intestinal fibrosis

AIM To explore the role and mechanism of total flavone of Abelmoschus manihot(TFA) on epithelial-mesenchymal transition(EMT) progress of Crohn's disease(CD) intestinal fibrosis.METHODS First,CCK-8 assay was performed to assess TFA on the viability of intestinal epithelial(IEC-6) cells and select the optimal concentrations of TFA for our further studies.Then cell morphology,wound healing and transwell assays were performed to examine the effect of TFA on morphology,migration and invasion of IEC-6 cells treated with TGF-β1.In addition,immunofluorescence,real-time PCR analysis(q RT-PCR) and western blotting assays were carried out to detect the impact of TFA on EMT progress.Moreover,western blotting assay was performed to evaluate the function of TFA on the Smad and MAPK signaling pathways.Further,the role of co-treatment of TFA and si-Smad or MAPK inhibitors has been examined by q RTPCR,western blotting,morphology,wound healing andtranswell assays.RESULTS In this study,TFA promoted transforming growth factor-β1(TGF-β1)-induced(IEC-6) morphological change,migration and invasion,and increased the expression of epithelial markers and reduced the levels of mesenchymal markers,along with the inactivation of Smad and MAPK signaling pathways.Moreover,we revealed that si-Smad and MAPK inhibitors effectively attenuated TGF-β1-induced EMT in IEC-6 cells.Importantly,co-treatment of TFA and si-Smad or MAPK inhibitors had better inhibitory effects on TGF-β1-induced EMT in IEC-6 cells than either one of them.CONCLUSION These findings could provide new insight into the molecular mechanisms of TFA on TGF-β1-induced EMT in IEC-6 cells and TFA is expected to advance as a new therapy to treat CD intestinal fibrosis.

Non-SMC condensin Ⅰ complex subunit D2 and non-SMC condensin Ⅱ complex subunit D3 induces inflammation via the IKK/NF-κB pathway in ulcerative colitis

BACKGROUND Ulcerative colitis(UC)is a chronic,nonspecific intestinal inflammatory disease with undefined pathogenesis.Non-SMC condensin I complex subunit D2(NCAPD2)and non-SMC condensin II complex subunit D3(NCAPD3)play pivotal roles in chromosome assembly and segregation during both mitosis and meiosis.To date,there has been no relevant report about the functional role of NCAPD2 and NCAPD3 in UC.AIM To determine the level of NCAPD2/3 in intestinal mucosa and explore the mechanisms of NCAPD2/3 in UC.METHODS Levels of NCAPD2/3 in intestinal tissue were detected in 30 UC patients and 30 healthy individuals with in situ hybridization(ISH).In vitro,NCM60 cells were divided into the NC group,model group,si-NCAPD2 group,si-NCAPD3 group and si-NCAPD2+si-NCAPD3 group.Inflammatory cytokines were measured by ELISA,IKK and NF-κB were evaluated by western blot,and IKK nucleation and NF-κB volume were analyzed by immunofluorescence assay.RESULTS Compared with expression in healthy individuals,NCAPD2 and NCAPD3 expression in intestinal tissue was significantly upregulated(P<0.001)in UC patients.Compared with levels in the model group,IL-1β,IL-6 and TNF-αin the si-NCAPD2,si-NCAPD3 and si-NCAPD2+si-NCAPD3 groups were significantly downregulated(P<0.01).IKK and NF-κB protein expression in the si-NCAPD2,si-NCAPD3 and si-NCAPD2+si-NCAPD3 groups was significantly decreased(P<0.01).Moreover,IKK nucleation and NF-κB volume were suppressed upon si-NCAPD2,si-NCAPD3 and si-NCAPD2+si-NCAPD3 transfection.CONCLUSION NCAPD2/3 is highly expressed in the intestinal mucosa of patients with active UC.Overexpression of NCAPD2/3 promotes the release of pro-inflammatory cytokines by modulating the IKK/NF-κB signaling pathway.

Long-term outcome of infliximab combined with surgery for perianal fistulizing Crohn's disease

AIM:To evaluate the efficacy and long-term outcome of infliximab combined with surgery to treat perianal fistulizing Crohn’s disease(CD).METHODS:The work was performed as a prospective study.All patients received infliximab combined withsurgery to treat perianal fistulizing CD,which was followed by an immunosuppressive agent as maintenance therapy.RESULTS:A total of 28 patients with perianal fistulizing CD were included.At week 30,89.3%(25/28)of the patients were clinically cured with an average healing time of 31.4 d.The CD activity index decreased to70.07±77.54 from 205.47±111.13(P<0.01)after infliximab treatment.The perianal CD activity index was decreased to 0.93±2.08 from 8.54±4.89(P<0.01).C-reactive protein,erythrocyte sedimentation rate,platelets,and neutrophils all decreased significantly compared with the pretreatment levels(P<0.01).Magnetic resonance imaging results for 16 patients after therapy showed that one patient had a persistent presacral-rectal fistula and another still had a cavity without clinical symptoms at follow-up.After a median follow-up of 26.4 mo(range:14-41 mo),96.4%(27/28)of the patients had a clinical cure.CONCLUSION:Infliximab combined with surgery is effective and safe in the treatment of perianal fistulizing CD,and this treatment was associated with better longterm outcomes.

Optimized timing of using infliximab in perianal fistulizing Crohn's disease

Infliximab(IFX),as a drug of first-line therapy,can alter the natural progression of Crohn’s disease(CD),promote mucosal healing and reduce complications,hospitalizations,and the incidence of surgery.Perianal fistulas are responsible for the refractoriness of CD and represent a more aggressive disease.IFX has been demonstrated as the most effective drug for the treatment of perianal fistulizing CD.Unfortunately,a significant proportion of patients only partially respond to IFX,and optimization of the therapeutic strategy may increase clinical remission.There is a significant association between serum drug concentrations and the rates of fistula healing.Higher IFX levels during induction are associated with a complete fistula response in these patients.Given the apparent relapse of perianal fistulizing CD,maintenance therapy with IFX over a longer period seems to be more beneficial.It appears that patients without deep remission are at an increased risk of relapse after stopping anti-tumor necrosis factor agents.Thus,only patients in prolonged clinical remission should be considered for withdrawal of IFX treatment when biomarker and endoscopic remission is demonstrated,especially when the hyperintense signals of fistulas on T2-weighed images have disappeared on magnetic resonance imaging.Fundamentally,the optimal timing of IFX use is highly individualized and should be determined by a multidisciplinary team.

Proteomics identifies a novel role of fibrinogen-like protein 1 in Crohn’s disease

BACKGROUND Crohn’s disease(CD)is an incurable intestinal disorder with unclear etiology and pathogenesis.Currently,there is a lack of specific biomarkers and drug targets for CD in clinical practice.It is essential to identify the precise pathophysiological mechanism of CD and investigate new therapeutic targets.AIM To explore a new biomarker and therapeutic target for CD and verify its role in the CD pathological mechanism.METHODS Proteomics was performed to quantify the protein profile in the plasma of 20 CD patients and 20 matched healthy controls.Hub genes among the selected differentially expressed proteins(DEPs)were detected via the MCODE plugin in Cytoscape software.The expression level of one hub gene with an immunoregulatory role that interested us was verified in the inflamed intestinal tissues of 20 CD patients by immunohistochemical analysis.After that,the effects of the selected hub gene on the intestinal inflammation of CD were identified in a CD cell model by examining the levels of proinflammatory cytokines by enzymelinked immunosorbent assays and the expression of the NF-κB signalling pathway by quantitative real-time PCR analysis and Western blot assays.RESULTS Thirty-five DEPs were selected from 393 credible proteins identified by proteomic analysis.Among the DEPs,fibrinogen-like protein 1(FGL1),which attracted our attention due to its function in the regulation of the immune response,had 1.722-fold higher expression in the plasma of CD patients and was identified as a hub gene by MCODE.Furthermore,the expression of FGL1 in the intestinal mucosal and epithelial tissues of CD patients was also upregulated(P<0.05).In vitro,the mRNA levels of FGL1 and NF-κB;the protein expression levels of FGL1,IKKα,IKKβ,p-IKKα/β,p-IκBα,and p-p65;and the concentrations of the proinflammatory cytokines IL-1β,IL-6,IL-17,and TNF-αwere increased(P<0.05)after stimulation with lipopolysaccharide,which were reversed by knockdown of FGL1 with siRNA transfection(P<0.05).Conversely,FGL1 overexpression enhanced the abovementioned results(P<0.05).CONCLUSION FGL1 can induce intestinal inflammation by activating the canonical NF-κB signalling pathway,and it may be considered a potential biomarker and therapeutic target for CD.

Association of hidradenitis suppurativa with Crohn’s disease

Hidradenitis suppurativa(HS)is a chronic inflammatory skin disorder characterized by recurrent nodules,abscesses,and sinus tracts.Crohn’s disease(CD)is characterized by inflammation of the entire digestive tract and belongs to the group of inflammatory bowel diseases,and there are many extraintestinal manifestations,among which hidradenitis suppurativa is one of the rare extraintestinal manifestations.There appears to be a strong association between CD and HS based on clinical and histological similarities(sinus tract development,granulomatous inflammation,and scarring),intersections in pathogenesis(genetic loci,immune dysregulation mechanisms,and microbiome changes),and commonality in treatment.In this review,we summarize recent studies on the association between HS and CD.

Effect of nano-graphite on mechanical properties and oxidation resistance of ZrB_(2)-SiC-graphite electrode ceramics

ZrB_(2)-based ceramic composites were prepared by spark plasma sintering using ZrB_(2) powder prepared by molten salt method as raw material and SiC and nano-graphite as additives.The effects of nano-graphite addition on the physical properties and oxidation resistance of ZrB_(2)-based ceramic samples were investigated.The results show that the addition of an appropriate amount of nano-graphite can effectively improve the density of ZrB_(2)-based ceramic composites and improve the physical properties of the materials.The flexural strength of the ceramic sample with 8 vol.%nano-graphite reached 418.54 MPa,which was 53.14% higher than that of ZrB_(2)-SiC ceramic material(273.31 MPa),and its oxidation resistance was also significantly improved.It demonstrats that the addition of an appropriate amount of nano-graphite can effectively improve the physical properties and oxidation resistance of ZrB_(2)-SiC ceramic composites.Via prolonging its service life in application and promoting the development of ZrB_(2)-based ceramic composites,it is of great significance for clean steel smelting.

Survey of design and security evaluation of authenticated encryption algorithms in the CAESAR competition

The Competition for Authenticated Encryption: Security, Applicability, and Robustness(CAESAR)supported by the National Institute of Standards and Technology(NIST) is an ongoing project calling for submissions of authenticated encryption(AE) schemes. The competition itself aims at enhancing both the design of AE schemes and related analysis. The design goal is to pursue new AE schemes that are more secure than advanced encryption standard with Galois/counter mode(AES-GCM) and can simultaneously achieve three design aspects: security,applicability, and robustness. The competition has a total of three rounds and the last round is approaching the end in 2018. In this survey paper, we first introduce the requirements of the proposed design and the progress of candidate screening in the CAESAR competition. Second, the candidate AE schemes in the final round are classified according to their design structures and encryption modes. Third, comprehensive performance and security evaluations are conducted on these candidates. Finally, the research trends of design and analysis of AE for the future are discussed.