Protocol for enhancing visualization clarity for categorical spatial datasets using Spaco.

In categorical data visualization, appropriate color arrangements can avoid perceptual ambiguity and help perceive underlying data patterns. We introduce a protocol to assign contrastive colors to neighboring categories using both Python and R packages. We describe steps for calculating the interlacement between clusters and generating a proper color palette and calculating color contrast. We then detail procedures for aligning cluster interlacement and color contrast to get an optimized cluster-color assignment, achieving clear categorical visualization. For complete details on the use and execution of this protocol, please refer to Jing et al.1.

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 (ß value = 0.166, 95%CI: 0.02 to 0.31) and decreasing IBDQ score (ß value = -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.

NCAPD3 exerts tumor-promoting effects in prostatic cancer via dual impact on miR-30a-5p by STAT3-MALAT1 and MYC.

Non-SMC condensin II complex subunit D3 (NCAPD3) is a subunit of the non-structural maintenance of chromosomes condensin II complex, which involves chromosome condensation and segregation during mitosis. NCAPD3 has recently been demonstrated as a crucial oncogenic factor. However, the underlying mechanism of NCAPD3 in prostate cancer (PCa) remains not completely clear. In this study, we confirmed that lncRNA MALAT1 was induced by NCAPD3-STAT3, and the expression of miR-30a-5p was controlled by NCAPD3 in PCa cells by miRNA-seq. Through quantitative real-time PCR, fluorescence in situ hybridization, western blotting, and immunohistochemistry assay, we demonstrated that miR-30a-5p was lowly expressed in PCa cells and tissues compared to the controls, which was contrary to NCAPD3 expression and markedly downregulated by NCAPD3. Then, MALAT1 was analyzed for the complementary sequence in the potential interaction with miR-30a-5p by using the predicted target module of public databases. Dual-luciferase reporter assay and RNA immunoprecipitation were carried out to verify that MALAT1 functioned as a sponge for miR-30a-5p to reduce miR-30a-5p expression. Meanwhile, MYC acted as a transcriptional repressor to directly bind the promoter of the miR-30a-5p located gene and repress the miR-30a-5p expression. Furthermore, the upregulation of NCAPD3 on cell viability and migration was significantly attenuated in PC-3 cells when miR-30a-5p was overexpressed. NCAPD3 overexpression also accelerated tumor growth in the xenograft mouse model and repressed miR-30-5p. In summary, this work elucidates NCAPD3 inhibits miR-30a-5p through two pathways: increasing STAT3-MALAT1 to sponge miR-30a-5p and increasing MYC to directly inhibit miR-30a-5p transcription, which could serve as potential therapeutic targets for prostate cancer.

Spaco: A comprehensive tool for coloring spatial data at single-cell resolution.

Understanding tissue architecture and niche-specific microenvironments in spatially resolved transcriptomics (SRT) requires in situ annotation and labeling of cells. Effective spatial visualization of these data demands appropriate colorization of numerous cell types. However, current colorization frameworks often inadequately account for the spatial relationships between cell types. This results in perceptual ambiguity in neighboring cells of biological distinct types, particularly in complex environments such as brain or tumor. To address this, we introduce Spaco, a potent tool for spatially aware colorization. Spaco utilizes the Degree of Interlacement metric to construct a weighted graph that evaluates the spatial relationships among different cell types, refining color assignments. Furthermore, Spaco incorporates an adaptive palette selection approach to amplify chromatic distinctions. When benchmarked on four diverse datasets, Spaco outperforms existing solutions, capturing complex spatial relationships and boosting visual clarity. Spaco ensures broad accessibility by accommodating color vision deficiency and offering open-accessible code in both Python and R.

Monitoring-Based Model for Personalizing Fecal Incontinence in Patients With Crohn's Disease: A Multicenter Inception Cohort Study.

BACKGROUND AND AIMS: Fecal incontinence (FI) is a common complaint that greatly affects the quality of life of patients with Crohn's disease (CD) and is associated with the clinical characteristics of CD. We aimed to identify risk factors related to FI and construct a risk prediction model for FI in patients with CD. METHODS: This retrospective study included 600 Chinese patients with CD from 4 IBD centers between June 2016 and October 2021. The patients were assigned to the training (n = 480) and testing cohorts (n = 120). Two nomograms were developed based on the logistic regression and Cox regression models to predict the risk factors for FI in patients with CD. The discriminatory ability and accuracy of the nomograms were evaluated using the receiver operating characteristic (ROC) curves and the area under the ROC curves (AUCs). Additionally, the Kaplan-Meier survival curve was also used further to validate the clinical efficacy of the Cox regression model. RESULTS: The overall prevalence of FI was 22.3% (n = 134 of 600). In the logistic regression model, age at diagnosis (odds ratio [OR], 1.032; P = .033), penetrating behavior of disease (OR, 3.529; P = .008) and Perianal Disease Activity Index score >4 (OR, 3.068; P < .001) were independent risk factors for FI. In the Cox regression model, age at diagnosis (hazard ratio [HR], 1.027; P = .018), Montreal P classification (HR, 2.608; P = .011), and Perianal Disease Activity Index score >4 (HR, 2.190; P = .001) were independent predictors of the prevalence of FI over time. Two nomograms were developed to facilitate risk score calculation, and they showed good discrimination ability according to AUCs. CONCLUSIONS: In this study, we identified 4 risk factors related to the prevalence of FI and developed 2 models to effectively predict the risk scores of FI in CD patients, helping to delay the course of FI and improve the prognosis with timely intervention.

In this retrospective multicenter study, we identified 4 risk factors related to the prevalence of fecal incontinence and developed 2 models to effectively predict the risk scores of fecal incontinence in Crohn's disease patients, helping to improve prognosis with timely intervention.

Licochalcone A Inhibits Proliferation and Metastasis of Colon Cancer by Regulating miR-1270/ADAM9/Akt/NF-κB axis.

Background: We aimed to explor the therapeutic effect and molecular mechanism of licochalcone A (LCA) on colon cancer. Methods: This study was carried out in 2020-2021 in Nanjing Tongren Hospital, China. Colon cancer HCT116 cells were treated with different concentrations of LCA. Cell counting kit-8, colony formation and flow cytometry assays were used to analyze cell viability, proliferation and apoptosis. Wound healing and transwell experiments were used to measure cell migration and invasion ability. The expression of ADAM9 and apoptosis-related proteins in different LCA treatment groups was detected by western blot. HCT116 cells were transfected with ADAM9 small interfering RNAs (siRNAs) or overexpression vectors. The database screened the upstream miRNA targeting ADAM9 and predicted the targeted binding site between miR-1270 and ADAM9, which was verified by a dual-luciferase reporter assay. Rescue experiments were performed to confirm the effects of the miR-1270/ADAM9 axis on cell proliferation and metastasis. Results: LCA decreased cell growth (P<0.05), migration (P<0.05), and invasion (P<0.05) of colon cancer cells and inhibited ADAM9 expression in a dose-dependent manner. LCA affected the functions of colon cancer cells by negatively regulating the expression of ADAM9. MiR-1270, increased by LCA, targeted and suppressed ADAM9 expression significantly (P<0.001). ADAM9 overexpression restrained miR-1270 mimic and LCA-induced changes in cell proliferation, migration, and invasion, and promoted apoptosis in HCT116 cells significantly (P<0.01). LCA and miR-1270 mimic inactivated the Akt/NF-κB pathway, while ADAM9 over-expression rescued it. Conclusion: LCA exhibited antitumor efficacy in HCT116 cells by inhibiting the Akt/NF-κB signaling pathway by regulating the miR-1270/ADAM9 axis.

Is histological healing more clinically valuable than endoscopic healing in Crohn's disease?

OBJECTIVES: Small bowel (SB) endoscopic healing has not been well explored in patients with Crohn's disease (CD). This study aimed to assess the clinical utility of SB endoscopic mucosal and histological healing in patients with CD. METHODS: In total, 99 patients with CD in clinical-serological remission were retrospectively followed after they underwent colonoscopy and double-balloon enteroscopy. Time until clinical relapse (CD activity index of >150 with an increase of >70 points) and serological relapse (abnormal elevation of C-reactive protein levels) constituted the primary endpoints. RESULTS: Of the 99 patients, 75 (74.7%) exhibited colonoscopic healing and 43 (43.4%) exhibited SB endoscopic healing. Clinical relapse, serological relapse, hospitalization, and surgery occurred in 8 (18.6%), 11 (25.6%), 11 (25.6%), and 2 (4.6%) patients, respectively. Of the 43 patients who exhibited SB endoscopic healing, 21 (48.8%) achieved histological healing. Clinical relapse, serological relapse, hospitalization, and surgery occurred in 4 (19.0%), 7 (33.3%), 7 (33.3%), and 1 (4.8%) patient, respectively. There was no statistically significant difference in the number of patients who relapsed, were hospitalized, or underwent surgery between those who exhibited histological healing and those who did not. CONCLUSION: A substantial number of patients who were in clinical-serological remission did not undergo SB endoscopic healing, and the lesions increased their risk of clinical relapse. Thus, endoscopic healing may be of greater clinical value than histological healing when evaluating the remission of patients with CD.

Comparision of Ligasure hemorrhoidectomy and conservative treatment for thrombosed external hemorrhoids (TEH) in pregnancy.

BACKGROUND: Ligasure hemorrhoidectomy for thrombosed external hemorrhoids in pregnancy has been rarely studied. OBJECTIVE: The purpose of this article is to study the efficacy and safety of Ligasure hemorrhoidectomy comparing with conservative treatment for thrombosed external hemorrhoids in pregnancy. DESIGN: This was a retrospective cohort study. SETTING: The patients were treated at a tertiary referral center in China. PATIENTS: 94 pregnant patients hospitalized for thrombosed external hemorrhoids from September 2020 to December 2021. INTERVENTIONS: Ligasure hemorrhoidectomy treatment or conservative treatment according to the patient's wishes. MAIN OUTCOME MEASURES: Symptom relief, recurrence and satisfaction of thrombosed external hemorrhoids in pregnancy with different interventions. RESULTS: There were no differences between groups in maternal age, gestational age, body mass index, parity, constipation and a prior history of thrombosed external hemorrhoids. The pain scores were less in surgical group than in conservative group in post-treatment days 1 and 7. Time to return to normal activities was shorter in surgical group than in conservative group (6.51 vs. 13.52 days, P < 0.001). Post-treatment complications were mild in surgical group and there were no significant differences concerning the rate of abortion, preterm birth, cesarean delivery and weight of fetus. Recurrence rate was significantly lower in surgical group (8.57% vs. 30.43%, P = 0.017). The patient satisfaction scores were significantly higher in surgical group than in conservative group (Z = - 2.979, P = 0.003). LIMITATIONS: This was a retrospective study with a limited number of patients, the data was obtained from only one center. CONCLUSIONS: Comparing with conservative treatment, Ligasure hemorrhoidectomy for TEH in pregnancy results in more rapid pain relief, shorter time to return to normal activities, lower incidence of recurrence, and better patient satisfaction. This type of surgery has low and mild postoperative complications, is not attended by any risk to the mother or her fetus.

Adjuvant chemoradiotherapy does not improve outcomes in patients with fistula-associated anal adenocarcinoma undergoing abdominoperineal resection.

Objective: Abdominoperineal resection (APR) is currently established as a standard treatment regimen for fistula-associated anal adenocarcinoma (FAAA), however, the efficacy of chemoradiotherapy (CRT) remains unclear. The aim of this study is to evaluate the role of CRT in patients with FAAA treated with APR through single-center experience and literature review. Methods: A retrospective review was performed on patients with FAAA consecutive treated in our institution from 2005 to 2022. In addition, a systematic literature search was performed using PubMed and MEDLINE. All patients with FAAA who received APR in our institution and reported in the literature were included and divided into three categories for statistical analysis: APR alone (APR group), neoadjuvant therapy combined APR (CRT+APR group), and APR combined postoperative therapy (APR+CRT group). Results: Fifteen patients with FAAA were identified from our retrospective charts review. At a median follow-up time of 18 months, the recurrence-free survival rate was 53.3% and the survival rate was 73.3%. Eight patients underwent APR and 6 received postoperative chemotherapy. Among them, one died, one developed recurrence and the remaining six patients were alive with disease free. We found 37 publications describing 62 patients with FAAA treated with APR. Clinical data from these articles were analyzed together with the 8 cases in our institution. The overall survival rates were 94.1%, 70.8%, and 38.5% at 1-, 3-, 5-years respectively. Combining (neo)adjuvant therapy did not appear to improve outcomes in FAAA treated with APR (CRT+APR vs. APR, p=0.977; APR+CRT vs. APR, p=0.351). Lymph node involvement was shown to be significantly associated with poor outcomes by multivariate analysis (p=0.020). Conclusions: For patients with FAAA without lymph node involvement, APR is adequate to control disease and the addition of CRT does not appear to prolong survival.

Primary malignant tumours and malignant transformation of cysts in the retrorectal space: MRI diagnosis and treatment outcomes.

Background: There are no clear guidelines for the diagnosis and treatment of malignant retrorectal tumours. The purpose of this study was to increase preoperative diagnostic knowledge and to describe the outcomes of treatment for these patients. Methods: This retrospective study was conducted on patients who underwent complete retrorectal tumour resection between May 2006 and July 2018, and had confirmed post-operative pathology reports. Demographic and clinical data (including imaging, perioperative, pathological, and prognostic data) were collected and analysed. Results: Malignant lesions were identified in 15 (9 [60%], female) patients. The median age of the patients was 59 years (range, 34-72 years). Primary malignant tumours were identified in seven patients with solid tumours, in which gastrointestinal stromal tumours accounted for 71.4% (five of seven) and the remainder were chordoma or mucinous adenocarcinoma. Malignant transformation of cysts occurred in another eight patients with heterogeneous tumours, while histopathological features were present in 75% (six of eight) of patients with mucinous adenocarcinoma, and the remainder were squamous-cell carcinoma or neuroendocrine tumour (Grade 2). The malignant characteristics of the solid portions observed using magnetic resonance imaging (MRI) were as follows: the cyst wall of the tumour was irregularly thickened; the surface was convex or lobed; the solid tumour had no capsule, or the capsule was destroyed; and the surface had a gyrus-like morphology. At a median follow-up time of 52 months (range, 13-100 months), the overall recurrence-free survival rate was 40.0% and the survival rate was 46.7%. Conclusion: Some MRI features can be used to distinguish malignant retrorectal tumours from benign retrorectal tumours. The survival rate of patients with malignant retrorectal tumours is poor.

Temperature-dependent mechanical properties and the microscopic deformation mechanism of bilayerγ-graphdiyne under tension.

γ-graphdiyne (γ-GDY) is a new two-dimensional carbon allotrope that has received increasing attention in scientific and engineering fields. The mechanical properties ofγ-GDY should be thoroughly understood for realizing their practical applications. Althoughγ-GDY is synthesized and employed mainly in their bilayer or multilayer forms, previous theoretical studies mainly focused on the single-layer form. To evaluate the characteristics of the multilayer form, the mechanical properties of the bilayerγ-GDY (γ-BGDY) were tested under uniaxial tension using the molecular dynamics simulations. The stress-strain relation ofγ-BGDY is highly temperature-dependent and exhibits a brittle-to-ductile transition with increasing temperature. When the temperature is below the critical brittle-to-ductile transition temperature,γ-BGDY cracks in a brittle manner and the fracture strain decreases with increasing temperature. Otherwise, it exhibits ductile characteristics and the fracture strain increases with temperature. Such a temperature-dependent brittle-to-ductile transition is attributed to the interlayer cooperative deformation mechanism, in which the co-rearrangement of neighboring layers is dominated by thermal vibrations of carbon atoms in diacetylenic chains. Furthermore, the brittle-to-ductile transition behavior ofγ-BGDY is independent of loading direction and loading rate. The ultimate stress and Young's modulus decrease at higher temperatures. These results are beneficial for the design of advancedγ-GDY-based devices.

Crosstalk of Oxidative Phosphorylation-Related Subtypes, Establishment of a Prognostic Signature and Immune Infiltration Characteristics in Colorectal Adenocarcinoma.

Oxidative phosphorylation (OXPHOS) is an emerging target in cancer therapy. However, the prognostic signature of OXPHOS in colorectal adenocarcinoma (COAD) remains non-existent. We comprehensively investigated the expression pattern of OXPHOS-related genes (ORGs) in COAD from public databases. Based on four ORGs, an OXPHOS-related prognostic signature was established in which COAD patients were assigned different risk scores and classified into two different risk groups. It was observed that the low-risk group had a better prognosis but lower immune activities including immune cells and immune-related function in the tumor microenvironment. Combining with relevant clinical features, a nomogram for clinical application was also established. Receiver operating characteristic (ROC) and calibration curves were constructed to demonstrate the predictive ability of this risk signature. Moreover, a higher risk score was significantly positively correlated with higher tumor mutation burden (TMB) and generally higher gene expression of immune checkpoint, N6-methyladenosine (m6A) RNA methylation regulators and mismatch repair (MMR) related proteins. The results also indicated that the high-risk group was more sensitive to immunotherapy and certain chemotherapy drugs. In conclusion, OXPHOS-related prognostic signature can be utilized to better understand the roles of ORGs and offer new perspectives for clinical prognosis and personalized treatment.

NCAPD3 enhances Warburg effect through c-myc and E2F1 and promotes the occurrence and progression of colorectal cancer.

BACKGROUND: NCAPD3 is one of the three non-SMC subunits of condensin II complex, which plays an important role in the chromosome condensation and segregation during mitosis. Notably, elevated levels of NCAPD3 are found in many somatic cancers. However, the clinical role, biological functions of NCAPD3 in cancers especially in colorectal cancer (CRC) and the underlying molecular mechanisms remain poorly elucidated. METHODS: Clinical CRC and adjacent normal tissues were used to confirm the expression of NCAPD3. The association of NCAPD3 expression with clinicopathological characteristics and patient outcomes were analyzed by using online database. In vivo subcutaneous tumor xenograft model, NCAPD3 gene knockout following azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced tumor mouse model, Co-IP, western blot, qRT-PCR, IHC, ChIP assays and cell functional assays were used to investigate the biological functions of NCAPD3 in CRC and the underlying molecular mechanisms. RESULTS: NCAPD3 was overexpressed in CRC tissues and positively correlated with poor prognosis of CRC patients. NCAPD3 knockout suppressed CRC development in AOM/DSS induced and xenograft mice models. Moreover, we found that NCAPD3 promoted aerobic glycolysis in CRC. Mechanistically, NCAPD3 up-regulated the level of c-Myc and interacted with c-Myc to recruit more c-Myc to the gene promoter of its downstream glycolytic regulators GLUT1, HK2, ENO1, PKM2 and LDHA, and finally enhanced cellular aerobic glycolysis. Also, NCAPD3 increased the level of E2F1 and interacted with E2F1 to recruit more E2F1 to the promoter regions of PDK1 and PDK3 genes, which resulted in the inhibition of PDH activity and TCA cycle. CONCLUSIONS: Our data demonstrated that NCAPD3 promoted glucose metabolism reprogramming and enhanced Warburg effect in colorectal tumorigenesis and CRC progression. These findings reveal a novel mechanism underlying NCAPD3 mediated CRC cell growth and provide new targets for CRC treatment.

Combined therapy with early initiation of infliximab following drainage of perianal fistulising Crohn's disease: a retrospective cohort study.

BACKGROUND: Recent studies have confirmed that combined surgery and anti-TNF therapy could improve outcomes in patients with perianal fistulising Crohn's disease (PFCD). However, the optimal timing for infliximab infusion after surgical intervention is uncertain. We aimed to determine the long-term efficacy of early initiation of infliximab following surgery among PFCD patients. METHODS: We performed a retrospective cohort study of PFCD patients who received combined infliximab and surgical treatment between 2010 and 2018 at a tertiary referral hospital. Patients were grouped according to the time interval between surgery and infliximab infusion, with < 6 weeks into early infliximab induction group and > 6 weeks into delayed infliximab induction group. The primary outcome was to compare surgical re-intervention between early and delayed infliximab induction groups. The secondary outcomes were fistula healing and predictors associated with these outcomes of early infliximab induction approach. RESULTS: One hundred and seventeen patients were included (73 in early infliximab induction, 44 in delayed infliximab induction). The median interval between surgery and infliximab initiation was 9.0 (IQR 5.5-17.0) days in early infliximab induction group and 188.0 (IQR 102.25-455.75) days in delayed infliximab induction group. After followed-up for a median of 36 months, 61.6% of patients in early infliximab induction group and 65.9% in delayed infliximab induction group attained fistula healing (p = 0.643). The cumulative re-intervention rate was 23%, 32%, 34% in early infliximab induction group and 16%, 25%, 25% in delayed infliximab induction group, at 1, 2, and 3 years respectively (p = 0.235). Presence of abscess at baseline (HR = 5.283; 95% CI, 1.61-17.335; p = 0.006) and infliximab maintenance therapy > 3 infusions (HR = 3.691; 95% CI, 1.233-11.051; p = 0.02) were associated with re-intervention in early infliximab induction group. Presence of abscess at baseline also negatively influenced fistula healing (HR = 3.429, 95% CI, 1.216-9.668; p = 0.02). CONCLUSION: Although no clear benefit was shown compared with delayed infliximab induction group, early initiation of infliximab after surgery could achieve promising results for PFCD patients. Before infliximab infusion, durable drainage is required for patients with concomitant abscess or prolonged infliximab maintenance therapy.

Depression and anxiety in patients with active ulcerative colitis: crosstalk of gut microbiota, metabolomics and proteomics.

Patients with ulcerative colitis (UC) have a high prevalence of mental disorders, such as depression and anxiety. Gut microbiota imbalance and disturbed metabolism have been suggested to play an important role in either UC or mental disorders. However, little is known about their detailed multi-omics characteristics in patients with UC and depression/anxiety. In this prospective observational study, 240 Chinese patients were enrolled, including 129 patients with active UC (69 in Phase 1 and 60 in Phase 2; divided into depression/non-depression or anxiety/non-anxiety groups), 49 patients with depression and anxiety (non-UC), and 62 healthy people. The gut microbiota of all subjects was analyzed using 16S rRNA sequencing. The serum metabolome and proteome of patients with UC in Phase 2 were analyzed using liquid chromatography/mass spectrometry. Associations between multi-omics were evaluated by correlation analysis. The prophylactic effect of candidate metabolites on the depressive-like behavior of mice with colitis was investigated. In total, 58% of patients with active UC had depression, while 50% had anxiety. Compared to patients with UC without depression/anxiety, patients with UC and depression/anxiety had lower fecal microbial community richness and diversity, with more Lactobacillales, Sellimonas, Streptococcus, and Enterococcus but less Prevotella_9 and Lachnospira. Most metabolites (e.g., glycochenodeoxycholate) were increased in the serum, while few metabolites, including 2'-deoxy-D-ribose and L-pipecolic acid, were decreased, accompanied by a general reduction in immunoglobulin proteins. These related bacteria, metabolites, and proteins were highly connected. A prophylactic administration of 2'-deoxy-D-ribose and L-pipecolic acid significantly reduced the depressive-like behaviors in mice with colitis and alleviated the inflammatory cytokine levels in their colon, blood and brain. This study has identified a comprehensive multi-omics network related to depression and anxiety in active UC. It is composed of a certain set of gut microbiota, metabolites, and proteins, which are potential targets for clinical intervention for patients with UC and depression/anxiety.

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 enzyme-linked 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, IKKß, p-IKKα/ß, p-IκBα, and p-p65; and the concentrations of the proinflammatory cytokines IL-1ß, IL-6, IL-17, and TNF-α were 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.

NCAPD2 inhibits autophagy by regulating Ca2+/CAMKK2/AMPK/mTORC1 pathway and PARP-1/SIRT1 axis to promote colorectal cancer.

Non-SMC condensin I complex subunit D2 (NCAPD2) is one of the three non-SMC subunits in condensin I. Previous studies have shown that NCAPD2 plays an important role in the chromosome condensation and segregation. However, its role in the development of colorectal cancer (CRC) and specific molecular mechanisms still need to be further studied. Here we show that NCAPD2 inhibits autophagy and blocks autophagic flux via Ca2+/CAMKK/AMPK/mTORC1 pathway and PARP-1/SIRT1 axis. NCAPD2 acts as a tumor promoter both in vitro and in vivo. NCAPD2 knockout suppresses colorectal cancer development in AOM/DSS induced mice model. Therefore, our findings support a role for NCAPD2 in autophagy to promote CRC development and highlight NCAPD2 as a potential target for CRC therapy.

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.

Total Flavone of Abelmoschus manihot Ameliorates TNBS-Induced Colonic Fibrosis by Regulating Th17/Treg Balance and Reducing Extracellular Matrix.

Background and Aims: Surgery remains the major available strategy in inflammatory bowel disease (IBD) fibrotic strictures because no available drugs have sufficient prevention and treatment in this complication. This study aimed to evaluate the efficacy of the total flavone of Abelmoschus manihot L. Medic (TFA) on the development of colonic fibrosis in mice and its possible mechanism. Methods: The 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced chronic colonic inflammation-associated fibrosis mice were used to evaluate anti-fibrosis of TFA using macroscopic, histological, immunohistochemical analyses, ELISA, Masson staining, Verhoeff's von Gieson staining, transcription-quantitative polymerase chain reaction, and immunoblot analysis. Results: Oral administration of TFA attenuated body weight loss, reduced colon length shortening, lowered the morphological damage index score, and notably ameliorated the inflammatory response. TFA downregulated proinflammatory cytokines IL-6, IL-17, TNF-α, IFN-γ productions, and increased the levels of anti-inflammatory cytokine IL-10 and TGF-ß. The histological severity of the colonic fibrosis was also notably improved by the TFA treatment and associated with a significant reduction in the colonic expression of col1a2, col3a2, and hydroxyproline. TFA inhibits α-SMA, TGF-ß, vimentin, TIMP-1 expression, increasing MMPs, thereby inhibiting activated intestinal mesenchymal cells and extracellular matrix (ECM) deposition. Conclusion: Together, we herein provide the evidence to support that TFA may restore the imbalance of Th17/Treg and decrease the generation of ECM. This may be a potential mechanism by which TFA protects the intestine under inflammatory conditions and acts as a therapeutic agent for the treatment of intestinal fibrosis in Crohn's disease.

Molecular screening and clinicopathologic characteristics of Lynch-like syndrome in a Chinese colorectal cancer cohort.

Colorectal cancers (CRC) with microsatellite instability (MSI) or mismatch repair-deficiency (dMMR), but without detectable MMR germline mutations are termed Lynch-like syndrome (LLS). We assess the clinicopathologic and molecular characteristics of LLS tumors and the proportion in LLS, which remain poorly investigated in China. We enrolled 404 CRC patients with surgery in our institution from 2014 to 2018. LLS tumors were detected by a molecular stratification based on MMR protein expression, MLH1 methylation and MMR gene mutation. LLS tumors were profiled for germline mutations in 425 cancer-relevant genes. Among 42 MMR-deficient tumors, 7 (16.7%) were attributable to MLH1 methylation and 7 (16.7%) to germline mutations, leaving 28 LLS cases (66.6%). LLS tumors were diagnosed at a mean age of 60.7 years, had an almost equivalent ratio among rectum, left colon and right colon, and had high rates of lymph node metastases (50%, 4/28 N2). Most MMR gene mutations (88.2%, 15/17) in LLS tumors were variants of unknown significance (VUS). Two novel frameshift mutations were detected in ATM and ARID1A, which are emerging as candidate responsible genes for LLS. In this study, 28 (66.6%) MMRd tumors were classified as LLS, which were significantly higher than reports of western countries. LLS tumors were more likely to carry lymph node metastases. However, it's hard to differentiated LLS tumors from LS through family history, tumor location, histological type of tumors, immunohistochemistry (IHC) for MMR proteins and MSI analysis.