Endoscopic ultrasound-guided lauromacrogol injection for treatment of colorectal cavernous hemangioma: Two case reports.

BACKGROUND: Colorectal cavernous hemangioma is a rare vascular malformation resulting in recurrent lower gastrointestinal hemorrhage, and can be misinterpreted as colitis. Surgical resection is currently the mainstay of treatment, with an emphasis on sphincter preservation. CASE SUMMARY: We present details of two young patients with a history of persistent hematochezia diagnosed with colorectal cavernous hemangioma by endoscopic ultrasound (EUS). Cavernous hemangioma was relieved by several EUS-guided lauromacrogol injections and the patients achieved favorable clinical prognosis. CONCLUSION: Multiple sequential EUS-guided injections of lauromacrogol is a safe, effective, cost-efficient, and minimally invasive alternative for colorectal cavernous hemangioma.

Lower ultra-short-term heart rate variability can predict worse mucosal healing in ulcerative colitis.

BACKGROUND: Psychological stress has been proved to be a risk factor for exacerbation for ulcerative colitis (UC). However, traditional approaches of quantifying psychological stress using psychological scales are time-consuming and the results may not be comparable among patients with different educational levels and cultural backgrounds. Alternatively, heart rate variability (HRV) is an indicator for psychological stress and not biased by educational and cultural backgrounds. AIMS: In this study, we try to explore the relationship between psychological stress and UC by analyzing the effect of ultra-short-term HRV on mucosal and histological remission status of UC. METHODS: This is a retrospective case-control study on UC inpatients from 2018 through 2020. Ultra-short-term HRV were calculated using baseline electrocardiography. Patients were divided intocase and control groups according to their Mayo endoscopic scores or histological Geboes scores. Three variables of ultra-short-term HRV (the standard deviation of normal to normal R-R intervals (SDNN), the standard deviation of successive differences between adjacent normal to normal R-R intervals (SDSD), the root mean square of successive differences of normal to normal R-R intervals (RMSSD)) were compared between different groups. And for those variables with significant differences, we built univariate and multivariate logistic regressions to depict the relationship between HRV variables and remission status of UC. RESULTS: All three HRV variables showed significant differences between the mucosal groups. However, none of them showed significant difference between the histological groups. In further logistic regression analyses, smaller RMSSD can predict severe mucosal healing status (OR = 5.21). CONCLUSIONS: Lower ultra-short-term HRV (i.e. smaller RMSSD) is shown to positively correlate with worse mucosal healing status. However, ultra-short-term HRV cannot predict histological healing status according to our data.

Gastric metastasis presenting as submucosa tumors from renal cell carcinoma: A case report.

BACKGROUND: Gastric metastasis from renal cell carcinoma (RCC) is an extremely rare clinical entity. Due to an easily neglected RCC history, nonspecific symptoms and under-recognized endoscopic presentation may lead to a potential diagnostic pitfall in daily clinical practice. CASE SUMMARY: We present a case of metastatic gastric tumors arising from RCC 5 years after radical nephrectomy. Simultaneous, multifocal metastases to the gallbladder, pancreas and soft tissue were observed. One year previously, a solitary submucosal discoid tumor with a central depression was detected in the gastric fundus in a 65-year-old man. Endoscopic ultrasonography (EUS) showed a 1.12 x 0.38 cm lesion originating from the deeper mucosal layers with partially discontinuous submucosa. One year later, the endoscopic findings of the lesion showed various changes. A large lesion of the protruding type (2.5 cm × 2 cm) was found in the fundus at the same location. EUS showed a heterogeneous mass that involved the mucosa and submucosal layer. In addition, two small similar submucosal lesions 0.4-0.6 cm in size were detected. These lesions had a central depression, surface mucosal congestion and thickened vessels. The two adjacent lesions in the fundus were resected by endoscopic submucosal dissection. Based on the postoperative pathological analysis, the patient was diagnosed with gastric metastasis from RCC. CONCLUSION: Gastric metastasis from RCC should be considered in patients with a history of RCC irrespective of the time interval involved.

Inhibition of Histone Deacetylation by MS-275 Alleviates Colitis by Activating the Vitamin D Receptor.

BACKGROUND: Ulcerative colitis [UC] is a common chronic inflammatory bowel disease without curative treatment. METHODS: We conducted gene set enrichment analysis to explore potential therapeutic agents for UC. Human colon tissue samples were collected to test H3 acetylation in UC. Both in vivo and in vitro colitis models were constructed to verify the role and mechanism of H3 acetylation modification in UC. Intestine-specific vitamin D receptor [VDR]-/- mice and VD [vitamin D]-deficient diet-fed mice were used to explore downstream molecular mechanisms accordingly. RESULTS: According to the Connectivity Map database, MS-275 [class I histone deacetylase inhibitor] was the top-ranked agent, indicating the potential importance of histone acetylation in the pathogenesis of UC. We then found that histone H3 acetylation was significantly lower in the colon epithelium of UC patients and negatively associated with disease severity. MS-275 treatment inhibited histone H3 deacetylation, subsequently attenuating nuclear factor kappa B [NF-κB]-induced inflammation, reducing cellular apoptosis, maintaining epithelial barrier function, and thereby reducing colitis activity in a mouse model of colitis. We also identified VDR as be a downstream effector of MS-275. The curative effect of MS-275 on colitis was abolished in VDR-/- mice and in VD-deficient diet-fed mice and VDR directly targeted p65. In UC patients, histone H3 acetylation, VDR and zonulin-1 expression showed similar downregulation patterns and were negatively associated with disease severity. CONCLUSIONS: We demonstrate that MS-275 inhibits histone deacetylation and alleviates colitis by ameliorating inflammation, reducing apoptosis, and maintaining intestinal epithelial barrier via VDR, providing new strategies for UC treatment.

Effectiveness of mesalazine to treat irritable bowel syndrome: A meta-analysis.

AIM: Accumulating evidence has explored the effect of mesalazine on irritable bowel syndrome (IBS). However, these studies remain inconsistent. Thus, a meta-analysis was conducted to estimate the role of mesalazine on IBS. METHODS: PubMed, Medline, Embase, Web of Science, and the Cochrane Library Database were searched for all relevant randomized, controlled, blinded trials on mesalazine in patients with IBS between January 1980 and October 2018. All statistical analyses were performed using Revman 5.3 software. A fixed-effects model was adopted, 95% confidence intervals for SMD was calculated. Heterogeneity was evaluated by χ test and I statistic. RESULTS: Five studies involving 387 participants were finally included in this meta-analysis. The results showed that the SMD for clinical efficacy on abdominal pain in IBS patients treated with mesalazine in comparison to placebo was 0.19 (95% CI = -0.01 to 0.39, P = .06), which was statistically non-significant but clinically important. For beneficial effect of abdominal bloating, the SMD was 0.05 (95% CI = -0.20 to 0.30, P = .70), which was statistically non-significant. In regard to clinical efficacy on defecation frequency per day, the results revealed that the SMD was 0.29 (95% CI = -0.14 to 0.73, P = .18), which was statistically non-significant but clinically important. As for beneficial effect of general well-being, we found that the SMD was 0.41 (95% CI = -0.75 to 1.58, P = .49), which was statistically non-significant. With respect to stool consistency, the SMD was 0.01 (95% CI = -0.31 to 0.33, P = .96), which was statistically non-significant. For the effect of defecation urgency severity in IBS patients treated with mesalazine in comparison to placebo, we detected a surprising result with an SMD of 0.54 (95% CI = 0.05-1.04, P = .03), which was statistically significant. There was no significant difference between mesalazine group and placebo group on total mucosal immune cell counts of the patients with IBS with an SMD of -1.64 (95% CI = -6.17 to 2.89, P = .48) and there was also no significant difference in adverse reactions between two groups with an SMD of 1.05 (95% CI = 0.76-1.46 P = .77). CONCLUSION: Mesalazine is not superior to placebo in relieving clinical symptoms of abdominal pain, abdominal bloating, and general well-being of IBS and has no advantage of reducing defecation frequency per day and immune cell infiltration and improving stool consistency though without adverse reactions of mesalazine compared with placebo. For defecation urgency severity, placebo is even superior to mesalazine for IBS patients. Thus, mesalazine might be a cost burden to patients without providing good effectiveness. In view of the small sample size of the current study and the differences in every experimental designs, this study has high heterogeneity and requires subsequent verification.

EZH2 Regulates Intestinal Inflammation and Necroptosis Through the JNK Signaling Pathway in Intestinal Epithelial Cells.

BACKGROUND: Inflammatory bowel disease (IBD) is a common disorder of chronic intestinal inflammation that can be caused by the disruption of intestinal immune homeostasis. AIM: We aimed to evaluate the role of enhancer of zeste homolog 2 (EZH2) in the inflammatory response and explore the association between EZH2 and necroptosis in human epithelial colorectal adenocarcinoma cell lines. METHODS: In both in vitro and in vivo models, expression of EZH2 in intestinal tissues was verified by histology. The expression of inflammatory cytokines in cell lines treated with EZH2 siRNA with or without stimulus was analyzed by quantitative real-time polymerase chain reaction. An intestinal necroptosis cell model was established to elucidate whether EZH2 is involved in necroptosis. RESULTS: Our present data indicated that EZH2 expression was decreased in in vitro and in vivo models and in patients with inflammatory bowel disease. EZH2 downregulation increased the expression of inflammatory factors, including TNF-α, IL-8, IL-17, CCL5, and CCL20 in a Caco-2 cell model. The JNK pathway was activated with the reduction of EZH2. In the necroptosis model, downregulation of EZH2 was detected with the upregulation of necroptotic markers RIP1 and RIP3. In addition, EZH2 knockdown with siRNA increased p-JNK and p-c-Jun. CONCLUSION: Our data suggest that EZH2 plays an important role in the development of intestinal inflammation and necroptosis. Hence, EZH2 could be a potential therapeutic target for IBD.

Phlebosclerotic colitis: Our clinical experience of 25 patients in China.

The aim of the current study was to enhance the awareness of phlebosclerotic colitis (PC) through our clinical experience.A retrospective review of 25 patients who were diagnosed as PC in our 2 affiliated hospitals from January 2013 to October 2017 was conducted.The patients were found at a mean age of 63.5 years, range 47 to 87years. The majority of patients were male (23 cases). Only 4 patients (16%, 4/25) had the history about long-term use of Chinese herbs and medical liquor. The most common symptoms were abdominal pain (40%) and intestinal obstruction (16%), followed by diarrhea (12%), and gastrointestinal bleeding (12%), etc. Three cases (12%) had no symptoms. The varying degrees of calcifications along the colon and mesenteric venous were found in all of their computed tomography (CT) images. The lesions mainly located in transverse and ascending colon (60%, 15/25). The terminal ileum, the whole colon and rectum involvement were also been found. Fourteen patients had the examination of colonoscopy which all presented characteristic dark purple-colored endoscopic findings. Conservative treatment with close follow-up was preferred in our group. Three cases had the surgery of colectomy due to the repeatedly intestinal obstruction, perforation.The PC was a very rare but characteristic entity with unclear etiopathogenesis. Examination of abdomen CT and colonoscopy could help you to make clinical diagnosis.

Large heterotopic gastric mucosa and a concomitant diverticulum in the rectum: Clinical experience and endoscopic management.

Heterotopic gastric mucosa (HGM) in the rectum is an extremely rare clinical entity which may be missed or misdiagnosed due to a lack of knowledge. In the present study, a 14-year-old girl visited our hospital due to a 5-year history of repeated hematochezia. Colonoscopy showed a solitary superficial depressed lesion approximately 5 cm in size and a concomitant 1.5 cm deep diverticulum in the rectum. Histological examination of the endoscopic biopsy showed typical ectopic gastric mucosa in the depressed lesion and inside the diverticulum. Narrow band imaging further confirmed the histological results. Endoscopic ultrasound indicated that the lesion originated from the mucosal layer, and partially involved the submucosal layer. Endoscopic submucosal dissection was performed in this patient due to the large size and shape of the lesion. No bleeding, perforation or other adverse events were observed. The presence of HGM in the diverticular cavity greatly increased the surgical difficulty. A literature review was also carried out in our study.

Dysregulated Up-Frameshift Protein 1 Promotes Ulcerative Colitis Pathogenesis Through the TNFR1-NF-κB/MAPKs Pathway.

BACKGROUND: Ulcerative colitis (UC) is an idiopathic colonic mucosal disease, and its pathogenesis has not been fully understood. Up-frameshift protein 1 (UPF1) is a potential molecule for UC predicted by a computational approach. AIM: The present study aimed to validate the underlying mechanism of UPF1 in UC. METHODS: UPF1 expression was detected by qRT-PCR, western blotting, and immunohistochemistry in dextran sulfate sodium-induced colitis in mice. To simulate the intestinal inflammation microenvironment, NCM460 human colonic epithelial cells were exposed to a mixture of inflammatory mediators. The potential mechanism involving TNFR1-NF-κB/MAPKs pathway activation was addressed by western blotting, reporter gene assays, and siRNA (siUPF1) or UPF1-expressing plasmid pENTER-transfected cells. RESULTS: UPF1 was downregulated in colonic epithelial cells of colitic mice, and in vitro, contrary to the mRNA levels of the associated cytokines enhanced in the UPF1 dysregulation group within stimulatory factors, most relevant cytokines were significantly decreased in UPF1 overexpression group. Mechanistically, the increased expression of tumor necrosis factor receptor 1 (TNFR1) was found in NCM460 cells pre-treated with siUPF1, with the activation of IKK/NF-κB and MAPKs pathways, including JNK/AP-1 and P38, but not the ERK1/2 pathway. Moreover, the repression of TNFR1 required the interaction of UPF1 with the promoter. CONCLUSION: UPF1, which negatively regulated the transcription of TNFR1, is a novel factor regulating intestinal inflammation. The downregulation of UPF1 activated the TNFR1-dependent NF-κB/MAPKs pathway, and promoting inflammatory responses in colon might act as a causal role in UC.

A spontaneous hematoma arising within an intrapancreatic accessory spleen: A case report and literature review.

RATIONAL: Hematoma arising within an intrapancreatic accessory spleen (IPAS) is an extremely rare pathological entity. PATIENT CONCERN: We present the case of a 39-year-old man with acute abdominal pain. DIAGNOSES: The patient was initially diagnosed as pancreatic cystic neoplasm according to CT and MRI imaging. INTERVENTIONS: Distal pancreatectomy was conducted because of the possibility of malignancy. OUTCOMES: Surgical resection showed that the lesion was a hematoma in an IPAS. LESSONS: Our case indicated that the differential diagnosis of hematoma in IPAS should be born in mind for cases with cystic neoplasm in tail of pancreas and an epidermoid cyst arising within an intrapancreatic accessory spleen (ECIAS).

Double-balloon enteroscopy in small bowel diseases: Eight years single-center experience in China.

The aim of the study was to evaluate the diagnostic and therapeutic value of double-balloon entoroscopy (DBE) in small bowel diseases (SBDs) in China.A retrospective review of 674 consecutive patients who underwent DBE between January 2007 and November 2015 was conducted. Patients were divided into 3 groups by age, young group (<45 years), middle-aged group (45-65 years), and elderly group (>65 years). Data were collected with regard to demographics, clinical, endoscopic findings, complications, diagnostic yield, and management.A total of 729 DBE procedures were performed successfully in our series. More than 20 types of SBDs were found with the detection rate of 70.9%(517/729). The majority of patients were Crohn's disease (33.4%,225/674), followed by tumor (18.8%,127/674) and angioectasia (7.9%, 53/674). Endoscopic treatment was performed in 60 patients in which hemostasis (17,28.3%) and polypectomy (15,25%) were the predominant form of intervention used. Adverse events occurred in 6 patients (0.96%,6/729) including perforation, hemorrhage, aspiration pneumonia. No acute pancreatitis or other major complications occurred. Adenocarcinoma, GIST, and lymphoma were the most common tumor detected, the majority of tumors located in the jejunum (56.7%), The detection rate of angioectasia was also higher in the jejunum (54.7%),77.8% of Crohn's disease was located in the ileum. The positive rate of DBE in small bowel tumor and Crohn's disease were significantly higher than that of angioectasia (P<0.05). In young cohort, Crohn's disease (48.1%) was the most commonly diseases followed by tumor (10.4%) and nonspecific enteritis (7.1%). Yet in the elderly group, the majority of patients were tumor (27.6%); angioectasia (21.3%) was also detected frequently. The positive rate of capsule endoscopy was 75.44 %(202/268) which was a little high than DBE (67.9%, 182/268) (P > 0.05). The obscure gastrointestinal bleeding (OGIB) was the most common indication, and the diagnostic yield was 71.8%.DBE is a useful diagnostic and therapeutic tool with high clinical practice value for the investigation of SBDs. With growing experience of endoscopist, we believe that DBE must be kept in mind as the first-line modality for suspected SBDs.

[Not Available]. / Aumento del nivel de betatrofina en suero en sujetos con síndrome metabólico: estudio de casos y controles.

Introducción: la betatrofina es una novedosa adipoquina que provoca la proliferación de células ß pancreáticas e interviene en el metabolismo de los lípidos. Objetivos: el propósito de este estudio es evaluar el papel de la betatrofina en el síndrome metabólico. Método: se llevó a cabo un estudio hospitalario de casos y controles según sexo y edad. El nivel de betatrofina en suero fue evaluado mediante ensayo por inmunoabsorción ligado a enzimas. Se midieron las concentraciones en suero de 12 adipoquinas para evaluar las asociaciones con la betatrofina usando los kits comerciales Adipokine Magnetic Bead Panel. Los análisis estadísticos incluyeron correlación bivariada, análisis de curva ROC y análisis de regresión lineal multivariable. Resultados: el nivel de betatrofina en suero fue más elevado en pacientes con síndrome metabólico (997,36 ± 475,92 pg/ml, p = 0,001) que en los controles (735,35 ± 526,51 pg/ml). Frente al tercil más bajo, el tercil más alto del nivel de betatrofina mostró una asociación con mayor riesgo de síndrome metabólico (odds ratio ajustado = 3,521, intervalo de confianza [IC] 95% [1,191-10,413], p = 0,023). Se desarrolló la curva ROC de betatrofina para pronosticar la presencia de síndrome metabólico (área bajo la curva ROC = 0,682 [95% IC, 0,597-0,767], p < 0,001). Además, la betatrofina mostró correlación con distintos parámetros, como edad (r = 0,286, p < 0,001), índice de masa corporal (r = 0,160, p = 0,046), índice cintura-cadera (r = 0,241, p = 0,002), lipoproteína de alta densidad (r = -0,167, p = 0,037), lipoproteína de baja densidad (r = -0,195, p = 0,015), glucosa plasmática en ayunas (r = 0,266, p = 0,001), hemoglobina A1C (r = 0,314, p < 0,001), índice de resistencia a la insulina mediante HOMA (r = 0,272, p = 0,001) y diversas adipoquinas, entre ellas resistina (r = 0,571, p < 0,001), interleucina-8 (r = 0,435, p < 0,001), factor de necrosis tumoral alfa (r = 0,295, p = 0,011) y lipocalina-2 (r = 0,346, p = 0,003). Conclusiones: este estudio demuestra que la betatrofina en suero desempeña una importante labor en el síndrome metabólico, implicando la regulación del metabolismo de la glucosa y los lípidos y la inflamación.

Serum periostin is a potential biomarker for non-alcoholic fatty liver disease: a case-control study.

Recent animal studies support close associations of Periostin with hepatosteatosis and steatohepatitis. This study is to evaluate the role of serum periostin in non-alcoholic fatty liver disease (NAFLD). A hospital-based age-/sex-matched case-control study was conducted. Binary logistic regression and receiver operating characteristic (ROC) curve were performed. Serum adipokines were measured by Adipokine Magnetic Bead Panel kits. The serum concentration of Periostin in NAFLD (1914.16 [1323.59-2654.88] ng/ml, P < 0.001) was higher than it in control (1244.94 [837.87-2028.55] ng/ml). The frequency of NAFLD grew (29.8, 52.6, and 67.2%, P < 0.001), as Periostin concentration increased among its tertiles. Compared with the 1st tertile, the 2nd and the 3rd tertiles of Periostin indicated significant associations with higher odds of NAFLD [adjusted odds ratio = 2.602 (95% confidence interval (CI) 1.030-6.575), P = 0.043 and 2.819 (95% CI 1.629-4.878), P < 0.001]. ROC curve of Periostin was developed to predict the presence of NAFLD (area under ROC = 0.693 [95% CI 0.614-0.771], P < 0.001). Lastly, Periostin correlated with several adipokines, including Resistin (r = 0.269, P = 0.018), Adiponectin (r = -0.352, P = 0.002), Interleukin (IL)-6 (r = 0.359, P = 0.001), IL-8 (r = 0.364, P = 0.001), Lipocalin-2 (r = 0.623, P < 0.001), Hepatocyte growth factor (r = 0.522, P < 0.001), and Nerve growth factor (r = 0.239, P = 0.036). It suggests Periostin as a potential biomarker in the management of NAFLD.

A case-control study: Association between serum neuregulin 4 level and non-alcoholic fatty liver disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a great health burden. Neuregulin 4 (Nrg4) is a recently identified secret factor that may be associated with NAFLD. AIM: To investigate the association between serum Nrg4 level and NAFLD by conducting a case-control study. METHOD: A total of 174 subjects were included. 87 NAFLD subjects and 87 age- and sex-matched non-NAFLD controls were identified by hepatic ultrasound examination. Anthropometric and biochemical data were measured and recorded. Serum Nrg4 level was evaluated by using enzyme-linked immunosorbent assay. SPSS software was used for statistical analyses. RESULTS: Compared to the controls, subjects with NAFLD presented with reduced level of serum Nrg4 (0.40 (0.27, 0.55) vs. 0.50 (0.30, 0.81)ng/mL (median (interquartile range)), P=0.029). By multivariate logistic regression analysis, reduced serum levels of Nrg4 were associated with higher NAFLD odds (OR=0.251, 95% confidence interval=0.081-0.779, P=0.017). By dividing the distribution of serum Nrg4 level into quartiles, there was borderline statistical difference of NAFLD prevalence among the four groups (P=0.058). There was no significant difference of serum Nrg4 levels in subjects according to the grades of fatty liver by ultrasound (P=0.080). No statistical difference of serum Nrg4 level was observed between obese and non-obese subjects (P=0.932). CONCLUSION: Decreased serum Nrg4 level is prevalent in NAFLD subjects compared to non-NAFLD controls, and is an independent risk factor associated with NAFLD, indicating that Nrg4 might have a protective role in the development of NAFLD.

Screening for pancreatic cancer in familial high-risk individuals: A systematic review.

AIM: To analyze the benefits and harms of pancreatic cancer screening in familial high-risk individuals (HRIs). METHODS: Studies were identified by searching PubMed, EBSCO, ClinicalTrials.gov and the Cochrane database from database inception to June 2014. We also obtained papers from the reference lists of pertinent studies and systematic reviews. English-language trials and observational studies were searched. The key words used as search terms were "screening" and "surveillance". Cost-effectiveness, diagnostic rate, survival rate, mortality and adverse events were the outcomes of interest. Age, sex, lifestyle and other confounding factors were also considered. However, anticipating only a few of these studies, we also included observational studies with or without control groups. We also included studies concerning the anxiety associated with pancreatic cancer risk and other psychological changes in familial HRIs. We extracted details on study design, objectives, population characteristics, inclusion criteria, year of enrollment, method of screening, adjusted and unadjusted mortality, cost-effectiveness and adverse events from the included studies. Studies were assessed using the Reporting of Observational studies in Epidemiology (STROBE) checklist. RESULTS: Sixteen studies on pancreatic cancer screening were included. Five studies included control groups, nine were observational studies without control groups, and the other two studies investigated the worry associated with pancreatic cancer risk. We found that pancreatic cancer screening resulted in a high curative resection rate (60% vs 25%, P = 0.011), longer median survival time (14.5 mo vs 4 mo, P < 0.001), and higher 3-year survival rate (20% vs 15.0%, P = 0.624). We also found that familial HRIs had a higher diagnostic rate of pancreatic tumors than controls (34% vs 7.2%, P < 0.001). In patients who underwent regular physical examinations, more stage I pancreatic cancers were observed (19% vs 2.6%, P = 0.001). In addition, endoscopic ultrasonography, which was the main means of detection, diagnosed 64.3% of pancreatic cancers. In comparison, endoscopic retrograde cannulation of the pancreas, magnetic resonance imaging, and computed tomography diagnosed 28.6%, 42.9%, and 21.4%, respectively. For mass lesions, instant surgery was recommended because of the beneficial effects of post-operative chemotherapy. However, in patients with intraductal papillary mucinous neoplasms, we did not find a significant difference in outcome between surgery and follow-up without treatment. Moreover, pancreatic cancer screening in familial HRIs had a greater perceived risk of pancreatic cancer (P < 0.0001), higher levels of anxiety regarding pancreatic cancer (P < 0.0001), and increased economic burden. CONCLUSION: Pancreatic cancer screening in familial HRIs is associated with a higher detection rate and longer survival, although screening may influence psychological function and increase the economic burden.

Computational Prediction and Validation of BAHD1 as a Novel Molecule for Ulcerative Colitis.

Ulcerative colitis (UC) is a common inflammatory bowel disease (IBD) producing intestinal inflammation and tissue damage. The precise aetiology of UC remains unknown. In this study, we applied a rank-based expression profile comparative algorithm, gene set enrichment analysis (GSEA), to evaluate the expression profiles of UC patients and small interfering RNA (siRNA)-perturbed cells to predict proteins that might be essential in UC from publicly available expression profiles. We used quantitative PCR (qPCR) to characterize the expression levels of those genes predicted to be the most important for UC in dextran sodium sulphate (DSS)-induced colitic mice. We found that bromo-adjacent homology domain (BAHD1), a novel heterochromatinization factor in vertebrates, was the most downregulated gene. We further validated a potential role of BAHD1 as a regulatory factor for inflammation through the TNF signalling pathway in vitro. Our findings indicate that computational approaches leveraging public gene expression data can be used to infer potential genes or proteins for diseases, and BAHD1 might act as an indispensable factor in regulating the cellular inflammatory response in UC.

Is Helicobacter pylori infection associated with glycemic control in diabetics?

AIM: To investigate whether Helicobacter pylori (H. pylori) infection is associated with glycemic control and whether hyperglycemia is modified by eradication therapy. METHODS: The databases of PubMed, Cochrane Library, Chinese BioMedicine Web Base and Chinese Science and Technology Journals were searched from inception to June 2014. Studies examining the association between H. pylori infection and glycemic control and/or the effect of eradication treatment on glycemic control in diabetic humans were eligible for inclusion. Meta-analyses were conducted using the Review Manager software version 5.2. The outcome measures are presented as weighed mean differences (WMDs) with 95% confidence intervals (CIs). Statistical heterogeneity was assessed by the Cochran Q test and the I(2) statistic. RESULTS: A total of 21 relevant publications were identified. A meta-analysis of 11 studies with 513 patients with diabetes mellitus (DM) showed significantly lower glycosylated hemoglobin (HbA1c) levels in the H. pylori-negative than H. pylori-positive DM participants (WMD = 0.43, 95%CI: 0.07-0.79; P = 0.02). In children and adolescents with type 1 DM (T1DM), there was a positive association between H. pylori infection and HbA1c level (WMD = 0.35, 95%CI: 0.05-0.64; P = 0.02), but there was no difference in those with type 2 DM (T2DM, WMD = 0.51, 95%CI: -0.63-1.65; P = 0.38). A meta-analysis of six studies with 325 T2DM participants showed a significant difference in the fasting plasma glucose levels between H. pylori-positive and H. pylori-negative participants (WMD = 1.20, 95%CI: 0.17-2.23; P = 0.02). Eradication of H. pylori did not improve glycemic control in the T2DM participants in a three-month follow-up period (HbA1c decrease: WMD = -0.03, 95%CI = -0.14-0.08; P = 0.57; fasting plasma glucose decrease: WMD = -0.06, 95%CI: -0.36-0.23; P = 0.68). Glycemic control was significantly better in T1DM participants who were not reinfected than in those who were reinfected (HbA1c: WMD = 0.72, 95%CI: 0.32-1.13: P = 0.00). CONCLUSION: H. pylori infection is associated with poorer glycemic control in T1DM patients, but eradication may not improve glycemic control in DM in a short-term follow-up period.

Lipotoxic effect of p21 on free fatty acid-induced steatosis in L02 cells.

Nonalcoholic fatty liver disease (NAFLD) is increasingly regarded as a hepatic manifestation of metabolic syndrome. Though with high prevalence, the mechanism is poorly understood. This study aimed to investigate the effects of p21 on free fatty acid (FFA)-induced steatosis in L02 cells. We therefore analyzed the L02 cells with MG132 and siRNA treatment for different expression of p21 related to lipid accumulation and lipotoxicity. Cellular total lipid was stained by Oil Red O, while triglyceride content, cytotoxicity assays, lipid peroxidation markers and anti-oxidation levels were measured by enzymatic kits. Treatment with 1 mM FFA for 48 hr induced magnificent intracellular lipid accumulation and increased oxidative stress in p21 overload L02 cells compared to that in p21 knockdown L02 cells. By increasing oxidative stress and peroxidation, p21 accelerates FFA-induced lipotoxic effect in L02 cells and might provide information about potentially new targets for drug development and treatments of NAFLD.

Helicobacter pylori induces increased expression of the vitamin d receptor in immune responses.

BACKGROUND: Vitamin D receptor (VDR) is a member of the nuclear receptor family of transcription factors that play a critical role in innate immunity. This study examined the role of VDR in gastric innate immune defence against the gastric pathogen Helicobacter pylori. MATERIALS AND METHODS: Seventeen H. pylori-infected patients and sixteen controls participated in the study. The GES-1 cells were transfected with siRNA or incubated with or without 1α,25(OH)2 D3 (100 nmol/L) then infected with H. pylori. VDR, cathelicidin antimicrobial protein (CAMP), and cytokine mRNA expression levels in normal and H. pylori-infected gastric mucosa and GES-1 cells was determined by qRT-PCR and correlated with the histopathologic degree of gastritis. Bactericidal activity was measured by using a colony-forming unit assay. RESULTS: Vitamin D receptor mRNA expression levels were significantly upregulated in H. pylori-infected patients and positively correlated with chronic inflammation scores. There was a significant positive correlation between VDR and CAMP mRNA expression in H. pylori-positive gastric mucosa. VDR siRNA reduced H. pylori-induced CAMP production and conversely increased IL-6 and IL8/CXCL8 expression levels. The vitamin D agonist 1α,25(OH)2 D3 increased CAMP expression and reduced cytokine activation in GES-1 cells infected with H. pylori. 1α,25(OH)2 D3 could enhance the intracellular killing of the replicating bacteria, but the presence of siVDR and siCAMP led to a decline in its bactericidal ability. CONCLUSIONS: The expression of VDR and CAMP in the gastric epithelium is up-regulated in the case of H. pylori infection; thus, VDR plays an important role in gastric mucosa homeostasis and host protection from H. pylori infection.