The MUC1-HIF-1α signaling axis regulates pancreatic cancer pathogenesis through polyamine metabolism remodeling.

Dysregulation of polyamine metabolism has been implicated in cancer initiation and progression; however, the mechanism of polyamine dysregulation in cancer is not fully understood. In this study, we investigated the role of MUC1, a mucin protein overexpressed in pancreatic cancer, in regulating polyamine metabolism. Utilizing pancreatic cancer patient data, we noted a positive correlation between MUC1 expression and the expression of key polyamine metabolism pathway genes. Functional studies revealed that knockdown of spermidine/spermine N1-acetyltransferase 1 (SAT1), a key enzyme involved in polyamine catabolism, attenuated the oncogenic functions of MUC1, including cell survival and proliferation. We further identified a regulatory axis whereby MUC1 stabilized hypoxia-inducible factor (HIF-1α), leading to increased SAT1 expression, which in turn induced carbon flux into the tricarboxylic acid cycle. MUC1-mediated stabilization of HIF-1α enhanced the promoter occupancy of the latter on SAT1 promoter and corresponding transcriptional activation of SAT1, which could be abrogated by pharmacological inhibition of HIF-1α or CRISPR/Cas9-mediated knockout of HIF1A. MUC1 knockdown caused a significant reduction in the levels of SAT1-generated metabolites, N1-acetylspermidine and N8-acetylspermidine. Given the known role of MUC1 in therapy resistance, we also investigated whether inhibiting SAT1 would enhance the efficacy of FOLFIRINOX chemotherapy. By utilizing organoid and orthotopic pancreatic cancer mouse models, we observed that targeting SAT1 with pentamidine improved the efficacy of FOLFIRINOX, suggesting that the combination may represent a promising therapeutic strategy against pancreatic cancer. This study provides insights into the interplay between MUC1 and polyamine metabolism, offering potential avenues for the development of treatments against pancreatic cancer.

Identification and validation of an immunotherapeutic signature for colon cancer based on the regulatory patterns of ferroptosis and their association with the tumor microenvironment.

The integrated landscape of ferroptosis regulatory patterns and their association with colon microenvironment have been demonstrated in recent studies. However, the ferroptosis-related immunotherapeutic signature for colon cancer (CC) remains unclear. We comprehensively evaluated 1623 CC samples, identified patterns of ferroptosis modification based on ferroptosis-associated genes, and systematically correlated these patterns with tumor microenvironment (TME) cell infiltration characteristics. In addition, the ferroptosis-regulated gene score (FRG-score) was constructed to quantify the pattern of ferroptosis alterations in individual tumors. Three distinct patterns of ferroptosis modification were identified, including antioxidant defense, iron toxicity, and lipid peroxidation. The characteristics of TME cell infiltration under these three patterns were highly consistent with the three immune phenotypes of tumors, including immune-inflamed, immune-excluded and immune-desert phenotypes. We also demonstrated that evaluation of ferroptosis regulatory patterns within individual tumors can predict tumor inflammatory status, tumor subtype, TME stromal activity, genetic variation, and clinical outcome. Immunotherapy cohorts confirmed that patients with low FRG-scores showed remarkable therapeutic and clinical benefits. Furthermore, the hub gene apolipoprotein L6 (APOL6), a drug-sensitive target associated with cancer cell ferroptosis, was identified through our proposed novel key gene screening process and validated in CC cell lines and scRNA-seq.

Extra intravenous Ustekinumab reinduction is an effective optimization strategy for patients with refractory Crohn's disease.

Objectives: Ustekinumab (UST) optimization strategies, including shortening intervals and intravenous reinduction, should be administered to patients with partial or loss of respond. Evidence comparing these types of optimization treatments is limited. We evaluated the efficacy and safety of weight-based UST intravenous reinduction in patients with refractory Crohn's disease (CD). Methods: This was a single-center retrospective observational study. Optimization strategies were designed for patients showing partial or loss of response to standardized UST therapy. Clinical, biochemical, and endoscopic response and remission rate were determined by Crohn's disease activity index (CDAI), C-reactive protein (CRP) levels, and SES-CD evaluation. UST trough concentrations were detected and adverse events were recorded. Results: A total of 128 patients receiving UST optimization therapies were included, with 105 patients administered shortening intervals of q8w or q4w, and 23 receiving intravenous reinduction followed by subcutaneous q8w or q4w. The follow-up duration for the shortening interval and reinduction cohorts were 15.0 (10.0, 31.0) and 23.0 (13.0, 70.0) weeks, respectively. A significant CDAI delta variation pre-and post-treatment could be found between groups [17.0 (-4.4, 65.9) vs. 69.0(10.7, 151.0), p = 0.013]. the trough concentration of UST increased [2.5 (1.3, 5.3) vs. 1.1 (0.5, 2.3), p = 0.001] after intravenous reinduction. Clinical and endoscopic remission were achieved in 69.6 and 31.8% of patients in the intravenous reinduction cohort, and 62.9 and 22.2% of patients in the shortening interval cohort, respectively. No significant difference was found between groups regarding safety. Conclusion: Intravenous reinduction brought about favorable recapture of clinical and endoscopic remission, and should have significant priority over the strategy of merely shortening drug intervals, which should be launched before switching to other biologics targeting different inflammatory pathways.Clinical Trial Registration: identifier NCT04923100. https://classic.clinicaltrials.gov/ct2/show/NCT04923100?id=04923100&draw=2&rank=1.

Health Information Processing and Symptom Management in a Cross-Cultural Setting: Insights from IBD Patients.

The affordances of social media, have significantly transformed how patients seek and process health information online, including those with chronic diseases like irritable bowel disease (IBD). Few studies have explored how information processing may impact symptom management. Guided by social cognitive theory, this study investigates how Chinese and U.S. patients (N = 838) process health information in a cross-cultural setting and the impact on symptom management. It finds that efficient information processing improves treatment understanding and symptom management for IBD patients, regardless of their cultural backgrounds. It also reveals a U-shaped quadratic relationship between IBD severity and emotional and peer support, indicating varying support needs at different IBD stages. These findings provide valuable insights for healthcare professionals, patients, and caregivers in designing interventions for chronic diseases. The study underscores the importance of recognizing the dynamics of health information processing and the need for a more nuanced approach to patient support and care.

Immunogenic cell death-associated biomarkers classification predicts prognosis and immunotherapy efficacy in pancreatic ductal adenocarcinoma.

Introduction: Immunogenic cell death (ICD) is a sort of regulated cell death (RCD) sufficient to trigger an adaptive immunological response. According to the current findings, ICD has the capacity to alter the tumor immune microenvironment by generating danger signals or damage-associated molecular patterns (DAMPs), which may contribute in immunotherapy. It would be beneficial to develop ICD-related biomarkers that classify individuals depending on how well they respond to ICD immunotherapy. Methods and results: We used consensus clustering to identify two ICD-related groupings. The ICD-high subtype was associated with favorable clinical outcomes, significant immune cell infiltration, and powerful immune response signaling activity. In addition, we developed and validated an ICD-related prognostic model for PDAC survival based on the tumor immune microenvironment. We also collected clinical and pathological data from 48 patients with PDAC, and patients with high EIF2A expression had a poor prognosis. Finally, based on ICD signatures, we developed a novel PDAC categorization method. This categorization had significant clinical implications for determining prognosis and immunotherapy. Conclusion: Our work emphasizes the connections between ICD subtype variations and alterations in the immune tumor microenvironment in PDAC. These findings may help the immune therapy-based therapies for patients with PDAC. We also created and validated an ICD-related prognostic signature, which had a substantial impact on estimating patients' overall survival times (OS).

Computed tomography-based radiomics nomogram using machine learning for predicting 1-year surgical risk after diagnosis of Crohn's disease.

BACKGROUND: Identifying patients with aggressive Crohn's disease (CD) threatened by a high risk of early onset surgery is challenging. PURPOSE: We aimed to establish and validate a radiomics nomogram to predict 1-year surgical risk after the diagnosis of CD, thereby facilitating therapeutic strategies making. METHODS: Patients with CD who had undergone baseline computed tomography enterography (CTE) examination at diagnosis were recruited and randomly divided into training and test cohorts at a ratio of 7:3. Enteric phase CTE images were obtained. Inflamed segments and mesenteric fat were semiautomatically segmented, followed by feature selection and signature building. A nomogram of radiomics was constructed and validated using a multivariate logistic regression algorithm. RESULTS: A total of 268 eligible patients were retrospectively included, 69 of whom underwent surgery 1-year after diagnosis. A total of 1218 features from inflamed segments and 1218 features from peripheral mesenteric fat were extracted, and reduced to 10 and 15 potential predictors, respectively, to construct two radiomic signatures. By incorporating the radiomics signatures and clinical factors, the radiomics-clinical nomogram showed favorable calibration and discrimination in the training cohort, with an area under the curve (AUC) of 0.957, which was confirmed in the test set (AUC, 0.898). Decision curve analysis and net reclassification improvement index demonstrated the clinical usefulness of the nomogram. CONCLUSIONS: We successfully established and validated a CTE-based radiomic nomogram with both inflamed segment and mesenteric fat simultaneously evaluated to predict 1-year surgical risk in CD patients, which assisted in clinical decision-making and individualized management.

Ustekinumab Promotes Radiological Fistula Healing in Perianal Fistulizing Crohn's Disease: A Retrospective Real-World Analysis.

There is insufficient evidence to confirm the efficacy of ustekinumab (UST) in promoting fistula closure in perianal fistulizing Crohn's disease (CD) patients. We aimed to evaluate the efficacy of UST in a real-world setting. The data were retrospectively analyzed. Intestinal clinical and endoscopic changes were evaluated. Fistula radiological outcomes were determined using the Van Assche score. A total of 108 patients were included, 43.5% of whom had complex perianal fistulas. Intestinal clinical and endoscopic remission was achieved in 65.7% and 31.5% of patients, respectively. The fistula clinical remission and response rates were 40.7% and 63.0%, respectively, with a significant reduction in Perianal Crohn's disease Activity Index [5.0(3.0, 8.0) vs. 7.5(5.0, 10.0), p < 0.001] and Crohn's Anal Fistula Quality of Life [23.5(9.3, 38.8) vs. 49.0(32.3, 60.0), p < 0.001]. Radiological healing, partial response, no change, and deterioration were observed in 44.8%, 31.4%, 13.4%, and 10.4% of patients, respectively. The cut-off UST trough concentration for predicting fistula clinical remission was 2.11 µg/mL with an area under the curve of 0.795, a sensitivity of 93.3%, and a specificity of 67.6%. UST is efficacious in promoting radiological fistula closure in patients with perianal fistulizing CD. A UST trough concentration over 2.11 µg/mL was correlated with a higher likelihood of perianal fistula clinical remission.

MYBL2 regulates de novo purine synthesis by transcriptionally activating IMPDH1 in hepatocellular carcinoma cells.

BACKGROUND: Metabolic reprogramming is a hallmark of cancer, alteration of nucleotide metabolism of hepatocellular carcinoma (HCC) is not well-understood. MYBL2 regulates cell cycle progression and hepatocarcinogenesis, its role in metabolic regulation remains elusive. PATIENTS AND METHODS: Copy number, mRNA and protein level of MYBL2 and IMPDH1 were analyzed in HCC, and correlated with patient survival. Chromatin Immunoprecipitation sequencing (Chip-seq) and Chromatin Immunoprecipitation quantitative polymerase chain reaction (ChIP-qPCR) were used to explore the relationship between MYBL2 and IMPDH1. Metabolomics were used to analyze how MYBL2 affected purine metabolism. The regulating effect of MYBL2 in HCC was further validated in vivo using xenograft models. RESULTS: The Results showed that copy-number alterations of MYBL2 occur in about 10% of human HCC. Expression of MYBL2, IMPDH1, or combination of both were significantly upregulated and associated with poor prognosis in HCC. Correlation, ChIP-seq and ChIP-qPCR analysis revealed that MYBL2 activates transcription of IMPDH1, while knock-out of MYBL2 retarded IMPDH1 expression and inhibited proliferation of HCC cells. Metabolomic analysis post knocking-out of MYBL2 demonstrated that it was essential in de novo purine synthesis, especially guanine nucleotides. In vivo analysis using xenograft tumors also revealed MYBL2 regulated purine synthesis by regulating IMPDH1, and thus, influencing tumor progression. CONCLUSION: MYBL2 is a key regulator of purine synthesis and promotes HCC progression by transcriptionally activating IMPDH1, it could be a potential candidate for targeted therapy for HCC.

The efficacy and safety of thalidomide in the treatment of refractory Crohn's disease in adults: a double-center, double-blind, randomized-controlled trial.

Background: Thalidomide is applied in therapy for refractory Crohn's disease (CD) in adults, but systematic and rigorous clinical evidence is scant. The aim was to provide theoretical references for the efficacy of thalidomide in the therapy for refractory CD in adults. Methods: A double-center, double-blind, placebo-controlled, randomized clinical trial of refractory CD in adults in two inflammatory bowel disease centers in China. In the double-blind trial, patients were randomly assigned to 100 mg of thalidomide or placebo daily for 8 weeks. The primary outcome was considered as the clinical remission rate calculated based on the Crohn's disease activity index at the eighth week following thalidomide or placebo treatment. In open label, non-response to placebo was additionally treated with 8 weeks of thalidomide; all responders were continuously treated with thalidomide until the 48th week. Results: Twenty-five patients were randomly assigned to each group. At the eighth week, the clinical remission rate in the thalidomide group was significantly higher than that in the placebo group (68.0% [17/25] vs 16.0% [4/25]; relative risk, 4.2; 95% confidence interval, 1.8-10.9, P < 0.001). After a 48-week follow-up, the continuous treatment rate of thalidomide was 46.3% (19/41). Adverse events during the whole process were reported in 58.5% of patients, mainly involving drowsiness, rash, and peripheral neuropathy that were mild and tolerable. Conclusion: Thalidomide can be used in the induction and maintenance therapy of refractory CD in adults. And it could be one of the treatment options for refractory CD.

An integrated analysis of prognostic mRNA signature in early- and progressive-stage gastric adenocarcinoma.

The pathogenesis and vital factors of early and progressive stages of stomach adenocarcinoma (STAD) have not been fully elucidated. In order to discover novel and potential targets to guide effective treatment strategies, a comprehensive bioinformatics study was performed, and the representative results were then validated by quantitative polymerase chain reaction (qPCR) and immunohistochemical (IMC) staining in clinical samples. A total of 4,627, 4,715, and 3,465 differentially expressed genes (DEGs) from overall-, early-, and progressive-stage STAD were identified, respectively. Prognostic models of 5-year OS were established for overall-, early-, and progressive-stage STAD, and ROC curves demonstrated AUC values for each model were 0.73, 0.87, and 0.92, respectively. Function analysis revealed that mRNAs of early-stage STAD were enriched in chemical stimulus-related pathways, whereas remarkable enrichment of mRNAs in progressive-stage STAD mainly lay in immune-related pathways. Both qPCR and IHC data confirmed the up-regulation of IGFBP1 in the early-stage and CHAF1A in progressive-stage STAD compared with their matched normal tissues, indicating that these two representative targets could be used to predict the prognostic status of the patients in these two distinct STAD stages, respectively. In addition, seven mRNAs (F2, GRID2, TF, APOB, KIF18B, INCENP, and GCG) could be potential novel biomarkers for STAD at different stages from this study. These results contributed to identifying STAD patients at high-risk, thus guiding targeted treatment with efficacy in these patients.

Ustekinumab trough concentration affects clinical and endoscopic outcomes in patients with refractory Crohn's disease: a Chinese real-world study.

BACKGROUND: Ustekinumab (UST), a newly-used biologic targeting p40 subunit of IL12 and IL23 in China, exerts a confirmed therapeutic effect on the induction and maintenance therapies for refractory Crohn's disease (CD). Therapeutic drug monitoring based on trough and antibody concentration is of core importance when treating patients who lose response to UST. We aimed to analyze the UST exposure-response relationship in CD treatment in the real-world setting. METHODS: We retrospectively enrolled patients with CD who received UST between March 1, 2020 and May 31, 2021, at the inflammatory bowel disease (IBD) center of the Sun Yat-Sun Affiliated Sixth Hospital. Baseline characteristic information, biomarker examination, clinical outcomes determined by the Crohn's disease activity index (CDAI), and endoscopic outcomes evaluated using a simple endoscopic score for Crohn's disease (SES-CD) at week 16/20 were collected. The optimal UST cut-off trough concentration was identified using receiver operating characteristic curve (ROC) analysis. RESULTS: Nineteen eligible patients were included in the study, the mean age was 29.1 ± 9.1 years and the mean disease duration was 5.5 ± 4.7 years. At the initiation of the study, 89.5% of the patients had been exposed to prior biologics, 42.1% had previous CD-related surgeries, and 52.6% had perianal diseases. At week 16/20 after the UST initiation, clinical response, clinical remission, endoscopic response, and endoscopic remission were 89.5%, 84.2%, 42.2%, and 73.7%, respectively. The cut-off optimal trough concentration for UST was 1.12 µg/mL, as determined by the ROC with an area under the curve (AUC) of 0.78, sensitivity of 87.5%, and specificity of 72.7%. Patients with a UST trough concentration > 1.12 µg/mL had a significantly higher rate of endoscopic remission than those without (70.0% vs. 11.1%, P = 0.02). CONCLUSIONS: UST is an effective therapeutic option for refractory CD treatment. A UST trough concentration above 1.12 µg/mL was associated with endoscopic remission at week 16/20 after UST initiation. Trial registration This study was approved and retrospectively registered by the Ethics Committee of Sun Yat-Sen University (2021ZSLYEC-066, March 29, 2021) and the Clinical Trial Registry (NCT04923100, June 10, 2021).

Selenite inhibits glutamine metabolism and induces apoptosis by regulating GLS1 protein degradation via APC/C-CDH1 pathway in colorectal cancer cells.

Glutaminolysis is important for metabolism and biosynthesis of cancer cells, and GLS is essential in the process. Selenite is widely regarded as a chemopreventive agent against cancer risk. Emerging evidence suggests that it also has chemotherapeutic potential in various cancer types, but the mechanism remains elusive. We demonstrate for the first time that supranutritional dose of selenite suppresses glutaminolysis by promoting GLS1 protein degradation and apoptosis. Mechanistically, selenite promotes association of APC/C-CDH1 with GLS1 and leads to GLS1 degradation by ubiquitination, this process is related to induction of PTEN expression. In addition, GLS1 expression is increased in human colorectal cancer tissues compared with normal mucosae. Our data provide a novel mechanistic explanation for the anti-cancer effect of selenite from a perspective of cell metabolism. Moreover, our results indicate that glutaminolysis especially GLS1 could be an attractive therapeutic target in colorectal cancer.

Upregulated SLC1A5 promotes cell growth and survival in colorectal cancer.

Glutamine metabolism is essential for tumorigenesis of colorectal cancer, cancer cells remodel their glutamine metabolic pathways to fuel rapid proliferation. SLC1A5 is an important transporter of glutamine various cancer cells. In this study, we investigated SLC1A5 protein expression in colorectal cancer and evaluated its clinical significance and functional importance. Immunohistochemical analysis was performed on tissue microarrays containing 90 pairs of cancer and adjacent normal tissues from colorectal cancer patients, we found that SLC1A5 expression increased significantly in colorectal cancer compared with normal mucosa tissues (P < 0.001). We further validated SLC1A5 overexpression in 12 pairs of fresh cancer and adjacent normal mucosa tissues from colorectal cancer patients by Western blot (P < 0.05). SLC1A5 expression levels were strongly associated with T stage of tumor (P < 0.05), and the tubular adenocarcinoma subtype (P < 0.001). Moreover, downregulation of SLC1A5 by synthetic siRNA could suppress proliferation and induce apoptosis in colorectal cancer cell lines HT29 and HCT116. In conclusion, our results provide for the first time the differential expression in human colorectal cancer and normal tissues, and a functional link between SLC1A5 expression and growth and survival of colorectal cancer, making it an attractive target in colorectal cancer treatment.

Herpes zoster in Crohn's disease during treatment with infliximab.

Infliximab is widely used in both inducing and maintaining remission of patients with Crohn's disease (CD). The efficacy of infliximab has been undoubtedly proven; however, various opportunistic infections have emerged. Herpes virus infections (being a type of opportunistic infection) in CD patients treated with infliximab alone with no other concomitant medications are, however, rare and have not aroused enough attention. Gastroenterologists have limited knowledge of the immunization status of patients with CD, and rarely do they take an adequate immunization history before immunosuppressive therapy. Here we report two herpes zoster (HZ) events in CD patients while using infliximab alone: in the first case, HZ occurred during the patient's 12th infusion for maintance therapy, and in the second case, HZ occurred during the patient's first course of infliximab after surgery for therapy of inducing remission. We hope to increase the gastroenterologists' awareness of this potential infection in CD patients during treatment with infliximab.

The utility of platelet, mean platelet volume, and red cell distribution width in the diagnosis of active Crohn's disease and intestinal tuberculosis.

OBJECTIVE: To evaluate the diagnostic utility of platelet count (PLT), mean platelet volume (MPV), and red cell distribution width (RDW) in patients with active Crohn's disease (CD) and intestinal tuberculosis (ITB). METHODS: This study was conducted in the Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, China. Sixty-eight patients with active CD, 35 with ITB, and 22 as control group were recruited. Blood routine test including white blood cell, red blood cell, PLT, MPV, RDW, and so forth was investigated. RESULTS: Patients with active CD and ITB have increased PLT and RDW (both p<0.001), and decreased MPV (p=0.002). The RDW performed preferably in predicting both active CD (odds ratio [OR]=2.390, p=0.007), and ITB (OR=2.338, p=0.017), and had better diagnostic value (area under the receiver operating characteristics curve [AUC] - 0.812; p<0.001) than CRP (AUC - 0.716; p=0.007) and ESR (AUC - 0.804; p<0.001) in ITB diagnosis. CONCLUSION: Among the laboratory markers, RDW not only possessed the favorable capability to predict active CD, but also showed outstanding predicting capability, and good diagnostic value in ITB.

Elevated risk of opportunistic viral infection in patients with Crohn's disease during biological therapies: a meta analysis of randomized controlled trials.

BACKGROUND: Biological agents have been widely used in the treatment of Crohn's disease (CD). These drugs carry the risk of excessive immunosuppression, indicating possible opportunistic infections including opportunistic viral infections, but no meta analysis has ever focused on this issue. PURPOSE: To evaluate whether there is an association between biological agents therapy and the risk of opportunistic viral infections and serious infections in patients with CD. METHODS: A search of online databases was performed and literature selection was carried out according to the inclusion and exclusion criteria by reading titles, abstracts and full texts. Study heterogeneity and publication bias were assessed. Whether to choose a fixed effects model or a random effects model depended on the result of heterogeneity test. RESULTS: There was a statistical significance in opportunistic viral infection events between the biological agents group and the placebo group. However, our analysis didn't observe statistically significant differences between the two groups when combined analyses were carried out for herpes zoster and herpes simplex separately. A risk trend in the biological agents group was observed in the analysis for herpes zoster. More analyses aimed at the outcome measures and including influenza and serious infection were carried out separately, but no statistical significance was found in them. CONCLUSION: Biological agents use might increase the risk of opportunistic viral infections in patients with CD, but not the risk of herpes simplex and serious infections. More randomized controlled trials (RCTs) are needed to draw the conclusion of whether they could elevate the risk of herpes zoster.

The Association Study between Twenty One Polymorphisms in Seven Candidate Genes and Coronary Heart Diseases in Chinese Han Population.

Previous genome-wide association studies (GWAS) in multiple populations identified several genetic loci for coronary heart diseases (CHD). Here we utilized a 2-stage candidate gene association strategy in Chinese Han population to shed light on the putative association between several metabolic-related candidate genes and CHD. At the 1(st) stage, 190 patients with CHD and 190 controls were genotyped through the MassARRAY platform. At the 2(nd) stage, a larger sample including 400 patients and 392 controls was genotyped by the High Resolution Melt (HRM) method to confirm or rule out the associations with CHD. MLXIP expression level was quantified by the real time PCR in 65 peripheral blood samples. From the 21 studied single nucleotide polymorphisms (SNPs) of seven candidate genes: MLXIPL, MLXIP, MLX, ADIPOR1, VDR, SREBF1 and NR1H3, only one tag SNP rs4758685 (T→C) was found to be statistically associated with CHD (P-value = 0.02, Odds ratio (OR) of 0.83). After adjustment for the age, sex, lipid levels and diabetes, the association remained significant (P-value = 0.03). After adjustment for the hypertension, P-value became 0.20 although there was a significant difference in the allele distribution between the CHD patients with hypertension and the controls (P-value = 0.04, 406 vs 582). In conclusion, among the 21 tested SNPs, we identified a novel association between rs4758685 of MLXIP gene and CHD. The C allele of common variant rs4758685 interacted with hypertension, and was found to be protective against CHD in both allelic and genotypic models in Chinese Han population.

The trend in newly diagnosed Crohn's disease and extraintestinal manifestations of Crohn's disease in central China: a retrospective study of a single center.

BACKGROUND AND AIMS: The incidence of Crohn's disease (CD) is increasing and has already become a refractory disorder in China. Data on extraintestinal manifestations (EIMs) in CD are rare, especially in Asians. We aimed to evaluate the trend of newly diagnosed CD and the prevalence and risk factors of EIMs in a clinical center in central China. MATERIALS AND METHODS: A total of 153 patients with CD were selected from the center from 1986 to 2011. Demographic and clinical data were collected from the center. The prevalence and risk factors of EIMs were retrospectively analyzed. RESULTS: The cases of CD increased from one in 1986 to 24 in 2011. It seemed to have two peaks for age at diagnosis: 21-25 and 36-40 years. Among these patients, 20 (13.07%) had one to three EIMs. The following EIMs were diagnosed: arthritis (4.58%), pyoderma gangrenosum (0.65%), erythema nodosum (1.31%), aphthous stomatitis (7.84%), ankylosing spondylitis (0.65%), and psoriasis (0.65%). In univariate analysis, patients with EIMs seemed to have shorter disease duration at diagnosis (P<0.001); those treated with intravenous injection of corticosteroids, immunosuppressants, and infliximab before or recently were the most susceptible to EIMs (P=0.012, 0.005, and 0.026, respectively). Multivariate analysis was performed by logistic regression to identify the risk factors of EIMs subsequently; however, no risk factors were identified (P>0.005). CONCLUSION: The incidence of CD was increasing remarkably at our center, and the age distributions were concentrated in the 21-25- and 36-40-year age groups. EIMs seemed to be rare in our Chinese patients with CD, and no risk factors correlated with EIMs, which was quite different from Western countries.