NUDT15 genotyping during azathioprine treatment in patients with inflammatory bowel disease: implications for a dose-optimization strategy.

BACKGROUND: NUDT15 R139C is an Asian-prevalent genetic variant related to azathioprine (AZA) intolerance in patients with inflammatory bowel disease (IBD). However, it remains unclear how to utilize the genotyping results to improve the step-up dosing strategy with an already low starting dose in Asian practice. METHODS: Clinical data of eligible IBD patients who received AZA therapy and NUDT15 R139C testing were retrospectively collected. The relationship between NUDT15 genotype, AZA doses, and AZA-induced toxicity and efficacy were comprehensively analysed. RESULTS: A total of 159 patients were included for toxicity analysis. Compared with the wild genotype, patients heterozygous for R139C are more prone to developing myelotoxicity and alopecia (P = 0.007; P = 0.042). In particular, they had a 5.4-fold risk of developing myelotoxicity when AZA dosage was increased from 25 mg/d to 50 mg/d (P < 0.001). Regarding efficacy, 115 patients who had received AZA for >4 months and maintained clinical remission on AZA monotherapy were included for further analysis. R139C heterozygotes were finally titrated to a significantly lower dose than the wild genotype [median (interquartile range): 0.83 (0.75-0.96) vs 1.04 (0.89-1.33) mg/kg/d, P = 0.001], whereas the clinical remission rates did not differ between groups (P = 0.88). CONCLUSIONS: IBD patients with R139C heterozygote are highly susceptible to AZA-induced myelotoxicity at an escalated dose of 50 mg/d. Thus, they may require a smaller dose increase after a starting dose of 25 mg/d. The final target dose of these patients could be set lower than that of the wild genotypes without compromising efficacy.

[Advances in three important signaling pathways related to aging in Drosophila melanogaster and screening of anti-aging traditional Chinese medicine].

Aging is the most basic life feature of organisms. It is a phenomenon of dysfunction of cells,tissues and organs under the influence of external environment and internal factors during the growth of organisms. During the process,many cellular signaling pathways and biologically active substances,such as insulin/insulin-like growth factor( IGF)-1 signaling( IIS) pathway,apoptotic signaling pathway,mTOR signaling pathway,AMPK pathway,sirtuin pathway,deacetylases have been found to be closely related to the molecular mechanism of aging. Modern studies have indicated that anti-aging natural compounds can cause great side effects,while delaying aging and even inducing another disease,which is against with the purpose of delaying aging and achieving healthy aging. Therefore,the researches of anti-aging traditional Chinese medicines with fewer side effects are extremely important. Based on the different mechanisms and theories of aging,many traditional Chinese medicines have been discovered to be related to anti-aging. As one of the most important model organisms,Drosophila melanogaster has been widely used in studies of aging process in recent years. In this paper,we reviewed three important signaling pathways related to aging,such as insulin/insulin-like growth factor( IGF)-1 signaling( IIS) pathway,m TOR pathway,AMPK pathway,and screened out anti-aging traditional Chinese medicines based on D. melanogaster in recent years.

Transcribed ultraconserved region (T-UCR) uc.261 expression is closely correlated with disease activity and intestinal permeability in Crohn's disease.

OBJECTIVES: Transcribed ultraconserved region (T-UCR) uc.261 is reported to participate in intestinal mucosa barrier damage in Crohn's disease (CD). The aim of this study was to determine the association with disease activity and intestinal permeability. METHODS: Uc.261 level in colon mucosa and Harvey-Bradshaw Index (HBI) were evaluated in 20 active CD patients. Uc.261 expression and transepithelial electrical resistance (TEER) were determined in Caco2 and T84 cells treated with tumor necrosis factor alpha (TNF-α), respectively. Body weight, disease activity index (DAI), colon length, histological index (HI), intestinal permeability to FITC-dextran, uc.261, and tight junction proteins (TJPs) levels were evaluated in BALB/C mice treated with saline enema, trinitrobenzene sulfonic acid (TNBS)/ethanol enema, and anti-TNF-α monoclonal antibody injection, respectively. RESULTS: Uc.261 expression was overexpressed in CD patients, TNF-α treated cells, and colitis mice. Uc.261 expression was positively correlated with HBI (r = 0.582, p = 0.007) in CD patients, and positively correlated with TNF-α concentration and negatively correlated TEER in Caco2 and T84 cells (all p < 0.05). Furthermore, uc.261 was positively correlated with DAI (r = 0.824, p = 0.008), HI (r = 0.672, p = 0.021), and intestinal permeability (r = 0.636, p = 0.012), while negatively correlated with body weight (r = -0.574, p = 0.035), colon length (r = -0.866, p = 0.017), and TJP expression (all p < 0.05) in colitis mice. CONCLUSIONS: Uc.261 expression was closely correlated with disease activity and intestinal permeability in CD. Anti-TNF-α treatment may play its role through suppressing uc.261 expression in colitis mice.

Circular RNA expression alterations in colon tissues of Crohn's disease patients.

Genetic factors are crucial in the development of Crohn's disease (CD). Circular RNAs (circRNAs) are known to function as microRNA (miRNA) sponges and regulate a number of signalling pathways via circRNA­miRNA interactions. As competing endogenous RNAs, the functions of circRNAs in CD should be investigated. In the present study, colon biopsy tissues were collected from ileocolon (L3)­active CD patients and healthy controls. circRNA microarrays were performed with colon tissues from 3 CD patients and 3 controls. Subsequently, the candidate circRNAs were verified via reverse transcription­quantitative polymerase chain reaction using colon tissues from a further 10 CD patients and 10 controls. Targeted miRNAs, genes and pathways of candidate circRNAs were predicted and analysed. Arraystar circRNA microarrays demonstrated that there were 163 upregulated circRNAs targeting 435 miRNAs and 55 downregulated circRNAs targeting 207 miRNAs (fold­change >2 and P<0.01) in CD patients. As a candidate circRNA, hsa­circRNA­102685 was observed to putatively target hsa­miR­146b­5p, hsa­miR­182­5p and hsa­miR­146a­5p. Furthermore, Kyoto Encyclopaedia of Genes and Genomes pathway analysis predicted that hsa­circRNA­102685 potentially participated in apoptosis, and in the Toll­like receptor and p53 signalling pathways. Overall, the current study suggested that circRNA alterations serve an important role in the pathogenesis of CD. circRNAs, such as hsa­circRNA­102685, are involved in certain important signalling pathways of CD, and may be novel targets for diagnosis or treatment in this disease.

A single-center experience with methotrexate in the treatment of Chinese Crohn's disease patients.

OBJECTIVE: Methotrexate (MTX) can be used as an alternative for patients with Crohn's disease (CD) who are intolerant of thiopurine. This retrospective study aimed to provide some clues about MTX treatment in Chinese patients with CD. METHODS: Medical records of 27 adult patients with CD who were treated with MTX between 2012 and 2017 at Renji Hospital were reviewed. MTX was administered at 15 mg or 20 mg intramuscularly once per week. The remission and response rates and adverse reactions of MTX were recorded and analyzed. RESULTS: Thirteen (48.1%) of the patients achieved remission for more than 12 months, whereas four (14.8%) responded clinically. Eight (29.6%) patients discontinued MTX due to adverse events. The mean age of those who maintained remission was significantly younger than that of those who did not ([35.62 ± 10.99] years vs. [45.43 ± 11.93] years, P < 0.05). The pretreatment C-reactive protein (CRP) level was higher in the group who maintained remission than that in those who did not ([17.20 ± 17.26] mg/L vs. [6.98 ± 5.66] mg/L, P < 0.05). CONCLUSIONS: MTX is effective and relatively safe for patients at doses of 15 mg/week or 20 mg/week and may be an alternative therapy for patients who are intolerant of thiopurine. Elderly patients with CD and patients with normal pretreatment CRP level may have a reduced response to MTX.

Noncoding Transcribed Ultraconserved Region (T-UCR) uc.261 Participates in Intestinal Mucosa Barrier Damage in Crohn's Disease.

BACKGROUND: To date, 481 ultraconserved regions (UCRs) have been discovered in human genome. We aimed to investigate the transcribed UCR (T-UCR) characteristics in Crohn's disease (CD ) and determine whether T-UCR uc.261 participated in intestinal mucosa barrier damage. METHODS: T-UCRs were screened in active CD mucosa using the Arraystar Human T-UCR Microarray and validated with quantitative real-time reverse transcription PCR, together with tight junction proteins (TJPs) including junctional adhesion molecule-A, occludin, claudin-1, and zonula occluden-1. T-UCR uc.261 in active CD mucosa was validated by RNA fluorescence in situ hybridization. Caco2 and T84 cells were employed to determine transepithelial electrical resistance. Cdc42, protein kinase C ζ, PAR3, and PAR6 were assessed with quantitative real-time reverse transcription PCR and Western blotting. The assembly of TJPs was detected using cell immunofluorescence assay. RESULTS: Four T-UCRs were significantly upregulated (uc.290-, uc.144-, uc.261-, and uc.477+) and 4 T-UCRs were downregulated (uc.166-, uc.141-, uc.478+, and uc.479+). Uc.261 was inversely correlated with transepithelial electrical resistance during tight junction formation. The levels of TJPs were diminished in active CD mucosa. Most uc.261s were located in the cytoplasm of colonic epithelial cells. Overexpression of uc.261 reduced transepithelial electrical resistance, inhibited the expression and assembly of TJPs, activated Cdc42, and suppressed protein kinase C ζ. Silencing of uc.261 in TNF-α-treated cells reversed the tight junction damage. CONCLUSIONS: Overexpression of uc.261 participates in intestinal mucosa barrier damage. Suppression of uc.261 reverses the damage to tight junction in inflammation. Attenuation of uc.261 overexpression might be a rational strategy to manage patients with CD.

Usefulness of spectral computed tomography for evaluation of intestinal activity and severity in ileocolonic Crohn's disease.

BACKGROUND: Assessment of intestinal activity and severity of Crohn's disease (CD) is crucial to guide treatment. In this study, we aimed to investigate the accuracy of spectral computed tomography (CT) in this assessment and make a comparison with conventional CT. METHODS: A total of 50 patients with ileocolonic CD underwent spectral CT scanning. Conventional CT and spectral CT images were reconstructed. Endoscopic lesions were classified as absent, mild lesions and severe lesions. Qualitative and quantitative findings in CT images were compared in these segments. Logistic regressions were established, based on conventional and spectral CT parameters, to predict intestinal activity and severity. Comparisons were made by receiver operating characteristic (ROC) curve. RESULTS: The results showed that bowel wall hyperenhancement, ulcers on CT images, comb sign, bowel wall thickness, normalized iodine concentration (NIC) and slope of HU curve (λHU) increased significantly (p < 0.01) with endoscopic severity. In predicting intestinal activity, spectral CT demonstrated higher accuracy (99.6% versus 94.7%), sensitivity (99.1% versus 93.4%) and specificity (99.9% versus 94.4%) than conventional CT. In predicting intestinal severity, spectral CT also had higher accuracy (96.5% versus 91.9%), sensitivity (96.5% versus 92.1%) and specificity (95.8% versus 89.8%) than conventional CT. Besides, both NIC and λHU correlated significantly with Simple Endoscopic Score for CD (r = 0.833 and r = 0.771; both p < 0.001), but their correlations with C-reactive protein (r = 0.578 and r = 0.513; both p < 0.01) and Harvey-Bradshaw Index (r = 0.545 and r = 0.522; both p < 0.01) were moderate. CONCLUSIONS: Compared with conventional CT, spectral CT had higher accuracy in detecting intestinal activity and severity of CD, which could be an alternative choice in evaluation of CD.

Therapeutic modulation of gut microbiota in inflammatory bowel disease: More questions to be answered.

Patients with inflammatory bowel disease (IBD) exhibit impaired control of the microbiome in the gut, and 'dysbiosis' is commonly observed. Western diet is a risk factor for the development of IBD, but it may have different effects on gut microbiota between IBD and non-IBD individuals. Exclusive enteral nutrition (EEN) can induce remission in pediatric Crohn's disease with a decrease in gut microbial diversity. Although there are some theoretical benefits, actual treatment effects of prebiotics and probiotics in IBD vary. High-quality studies have shown that VSL#3 (a high-potency probiotic medical food containing eight different strains) exhibits benefits in treating ulcerative colitis, and gut microbial diversity is reduced after treated with VSL#3 in animal models. The effect of fecal microbiome transplantation on IBD is controversial. Increasing microbial diversity compared with impaired handling of bacteria presents a dilemma. Antibiotics are the strongest factors in the reduction of microbiome ecological diversity. Some antibiotics may help to induce remission of the disease. Microbiome alteration has been suggested to be an intrinsic property of IBD and a potential predictor in diagnosis and prognosis. However, the effects of therapeutic modulations are variable; thus, more questions remain to be answered.

Handgrip Strength Index Predicts Nutritional Status as a Complement to Body Mass Index in Crohn's Disease.

BACKGROUND: Body mass index [BMI] is widely used to measure nutritional status in Crohn's disease [CD] patients, but limitations remain. Measuring handgrip strength index, in addition to BMI, may aid in overcoming limitations. METHODS: A total of 150 patients with CD and 254 controls were included in this study. All patients and controls underwent BMI, handgrip strength and bioelectrical impedance analysis. Bioelectrical impedance analysis included body cell mass, bone mineral content, skeletal muscle mass and body fat mass. A total of 88 CD patients were age-, sex- and BMI-matched with healthy controls for further analysis. RESULTS: BMI, body cell mass, body cell mass index, handgrip strength and handgrip strength index were all significantly decreased in the group of CD patients compared with controls [p < 0.0001]. When paired by BMI, healthy controls had significantly increased body cell mass index[p = 0.0344] and handgrip strength index [p = 0.0010] compared to patients. In addition, handgrip strength was well correlated with body cell mass [r = 0.8365, p < 0.0001]. CONCLUSIONS: BMI is widely used for detecting malnutrition, but it is less sensitive in predicting loss of body cell mass and skeletal muscle mass. Our study shows that handgrip strength index is an effective and convenient parameter to predict the functional nutritional status and muscular health in CD patients.

CNTNAP3 associated ATG16L1 expression and Crohn's disease.

Autophagy is a common physiological process in cell homeostasis and regulation. Autophagy-related gene mutations and autophagy disorders are important in Crohn's disease (CD). The nucleotide oligomerization domain 2-autophagy genes autophagy 16-like 1 (NOD2-ATG16L1) signaling axis disorder contributes to the dysfunction of autophagy. This paper is focused on the relationship between contactin associated protein-like 3 (CNTNAP3) and ATG16L1 expression in Crohn's disease. The results indicated that the expression of ATG16L1 is higher in some CD patients compared to normal controls. ATG16L1 was well correlated with the C-reactive protein (CRP) in some CD patients. In vitro study revealed that CNTNAP3 could upregulate the expression of ATG16L1 and increase autophagy vacuoles.

High suppressor of cytokine signaling-3 expression impairs STAT3-dependent protective effects of interleukin-22 in ulcerative colitis in remission.

BACKGROUND: High SOCS3 expression in intestinal epithelial cells (IECs) of patients with ulcerative colitis (UC) in remission reflects the shorter time to relapse. We investigated whether high SOCS3 increased risk for relapse through violating STAT3-dependent protective effects of interleukin (IL)-22 during UC remission. METHODS: Expression of IL-22 and c-Myc in UC remission mucosa was analyzed by immunohistochemistry. Effects of IL-22 on migration and proliferation of IEC cell lines with enforced SOCS3 expression were assessed with wounding assay and CCK-8 assay, respectively. Influence of STAT3 interference and SOCS3 overexpression on IL-22-regulated expression of antimicrobial peptide and proliferation-related molecules, including DMBT1, c-Myc, Survivin, Bcl-2, and Bcl-xL, were performed with quantitative real-time polymerase chain reaction or Western blot. RESULTS: Patients with UC in remission showed significantly more IL-22-positive immune cells, but no difference of epithelial c-Myc levels, in mucosa compared with healthy controls. Overexpression of SOCS3 nearly abolished IL-22-induced activation of STAT3. By inhibiting STAT3 signaling, SOCS3 influenced IL-22-induced expression of DMBT1, c-Myc, Survivin, and Bcl-2 as well as proliferation and migration processes in cultured IEC cell line. CONCLUSIONS: SOCS3 overexpression impairs IL-22-mediated epithelial homeostasis and mucosal wound healing, which could be the mechanism for high SOCS3 IEC expression contributed early relapse of mucosal inflammation. Prevention of SOCS3 expression or enhancement of IL-22/STAT3 signaling in IEC seems to be rational therapeutic strategies for UC remission maintenance.

Helicobacter pylori regulates TLR4 and TLR9 during gastric carcinogenesis.

OBJECTIVE: To investigated the influence of H. pylori on TLR4 and TLR9 in gastric mucosa during gastric carcinogenesis. METHODS: Gastric biopsy specimens were taken from 148 patients and divided into five groups, including normal group (n = 10), chronic superficial gastritis group (n = 35), atrophy/intestinal metaplasia group (n = 35), dysplasia group (n = 34) and gastric carcinoma group (n = 34). Immunohistochemistry was used to detect the expression of TLR4 and TLR9. Geimsa staining and rapid urea test were used for determine H. pylori infection. RESULTS: TLR4 was detected in gastric epithelium and monocytes/macrophages in superficial gastritis, atrophy/intestinal metaplasia, dysplasia or carcinoma. TLR9 was mainly accentuated in monocytes/macrophages. TLR4 positive cells in epithelium and in monocytes/macrophages with H. pylori infection were much more than those without H. pylori infection. Similar results were also found in TLR9. When gastric epithelium was accompanied with H. pylori infection, TLR4 was significant higher in superficial gastritis and atrophy/intestinal metaplasia groups compared with dysplasia and carcinoma groups. When gastric epithelium was infected by H. pylori, TLR9 was significant higher in carcinoma group compared with superficial gastritis, atrophy/intestinal metaplasia and dysplasia. TLR4 and TLR9 show significant correlation with the severity of inflammation. CONCLUSIONS: H. pylori infection was associated with increased expression of TLR4 and TLR9 in gastric mucosa. In superficial gastritis and atrophy/intestinal metaplasia the inflammation was predominately mediated by TLR4, while in gastric cancer the inflammation was mainly mediated by TLR9.

Therapeutic potential of microRNA: a new target to treat intrahepatic portal hypertension?

Intrahepatic portal hypertension accounts for most of the morbidity and mortality encountered in patients with liver cirrhosis, due to increased portal inflow and intrahepatic vascular resistance. Most treatments have focused only on portal inflow or vascular resistance. However, miRNA multitarget regulation therapy may potentially intervene in these two processes for therapeutic benefit in cirrhosis and portal hypertension. This review presents an overview of the most recent knowledge of and future possibilities for the use of miRNA therapy. The benefits of this therapeutic modality--which is poorly applied in the clinical setting--are still uncertain. Increasing the knowledge and current understanding of the roles of miRNAs in the development of intrahepatic portal hypertension and hepatic stellate cells (HSCs) functions, as well as their potential as novel drug targets, is critical.

Using cognitive theory to facilitate medical education.

BACKGROUND: Educators continue to search for better strategies for medical education. Although the unifying theme of reforms was "increasing interest in, attention to, and understanding of the knowledge base structures", it is difficult to achieve all these aspects via a single type of instruction. METHODS: We used related key words to search in Google Scholar and Pubmed. Related search results on this topic were selected for discussion. RESULTS: Despite the range of different methods used in medical education, students are still required to memorize much of what they are taught, especially for the basic sciences. Subjects like anatomy and pathology carry a high intrinsic cognitive load mainly because of the large volume of information that must be retained. For these subjects, decreasing cognitive load is not feasible and memorizing appears to be the only strategy, yet the cognitive load makes learning a challenge for many students. Cognitive load is further increased when inappropriate use of educational methods occurs, e.g., in problem based learning which demands clinical reasoning, a high level and complex cognitive skill. It is widely known that experts are more skilled at clinical reasoning than novices because of their accumulated experiences. These experiences are based on the formation of cognitive schemata. In this paper we describe the use of cognitive schemata, developed by experts as worked examples to facilitate medical students' learning and to promote their clinical reasoning. CONCLUSION: We suggest that cognitive load theory can provide a useful framework for understanding the challenges and successes associated with education of medical professionals.

Prevalence and factors related to hepatitis B and C infection in inflammatory bowel disease patients in China: a retrospective study.

OBJECTIVES: The objectives of this retrospective study were to assess the prevalence of HBV and HCV infection in Chinese IBD patients, identify potential risk factors of the infection in this population, and discuss the prevalence of HBV and HCV in the general Chinese population. METHODS: A total of 714 IBD patients who had been investigated for HBV and/or HCV infection were consecutively enrolled in the study. Clinical and laboratory data on IBD and hepatitis infection were collected. A control group of 22,373 healthy individuals was also included in the study. RESULTS: Present and past HBV infection was found in 40.62% of IBD patients (ulcerative colitis: HBsAg+, 5.68%; anti-HBc+, 41.64%; Crohn's disease: HBsAg+, 5.29%; anti-HBc+, 39.80%;), and 27.58% of the non-IBD group (HBsAg+, 5.52%; anti-HBc+, 27.58% [P = 0.00]). HCV infection was found in 0.42% of IBD patients and 0.36% of the non-IBD group (P=0.80). One hundred and fifty-four of the IBD patients (21.57%) had been effectively vaccinated for HBV. In a multivariate analysis, age, family history of hepatitis B, and IBD-related admission were significantly related to HBV infection in IBD patients. Potential risk factors for HCV were not analyzed due to the limited number of HCV-positive patients in the study. CONCLUSIONS: Prevalence of HBV infection in IBD patients was higher than that in the non-IBD patients, whereas prevalence of HCV infection was similar to that of the non-IBD group. Effective vaccination for HBV was present in only a small proportion of IBD patients.

LncRNA DQ786243 affects Treg related CREB and Foxp3 expression in Crohn's disease.

BACKGROUND: Long non-coding RNAs (lncRNAs) have different functions in cells. They work as signals, decoys, guides, and scaffolds. Altered lncRNA levels can affect the expression of gene products. There are seldom studies on the role of lncRNAs in inflammatory bowel disease (IBD). RESULTS: Quantitative RT-PCR showed that DQ786243 was significantly overexpressed in clinical active CD patients compared with clinical inactive CD patients (P = 0.0118) or healthy controls (P = 0.002). CREB was also more highly expressed in active CD than in inactive CD (P = 0.0034) or controls (P = 0.0241). Foxp3 was interestingly lower in inactive CD than in active CD (P = 0.0317) or controls (P = 0.0103), but there were no apparent differences between active CD and controls. CRP was well correlated with DQ786243 (r = 0.489, P = 0.034), CREB (r = 0.500, P = 0.029) and Foxp3 (r = 0.546, P = 0.016). At 48 hours after DQ786243 transfection, qRT-PCR showed both CREB (P = 0.017) and Foxp3 (P = 0.046) had an increased mRNA expression in Jurkat cells. Western blot showed the same pattern. After DQ786243 transfection, CREB phosphorylation ratio (p-CREB/t-CREB) was increased (P = 0.0043). CONCLUSION: DQ786243 can be related with severity of CD. It can affect the expression of CREB and Foxp3 through which regulates the function of Treg. CREB itself seems not the mediator of DQ786243 to up-regulate Foxp3. The phosphorylation of CREB might play a more important role in the process.

Dynamic expression of miR-126* and its effects on proliferation and contraction of hepatic stellate cells.

In our previous study, miR-126 was identified as one of the leading miRNAs that is downregulated during activation of hepatic stellate cells (HSCs). However, the roles and related mechanisms of miR-126 in HSCs are not understood. In this study, we compared expression of miR-126 during HSC activation both in vitro and in vivo. We also applied RNA interference to analyze the role and mechanism of miR-126(*) in the activation of HSCs. Restoring HSCs with Lv-miR-126(*) resulted in decreased proliferation, accumulation of extracellular matrix components, and cell contraction, while also negatively regulating the vascular endothelial growth factor (VEGF) signal transduction pathways by partially targeted VEGF-A. Thus, we postulate that miR-126 may be a biological marker for the activation of HSCs, and useful for reducing intrahepatic vascular resistance and improving the sinusoidal microcirculation in chronic liver diseases.

Computed tomography enterography versus balloon-assisted enteroscopy for evaluation of small bowel lesions in Crohn's disease.

BACKGROUND AND AIM: We aimed to assess the correlation between computed tomography enterography (CTE) and balloon-assisted enteroscopy on severity of small bowel lesions, and evaluated the accuracy of CTE parameters in assessing small intestine lesions in patients with Crohn's disease (CD). METHODS: We performed an observational study of a single-center cohort. Data were retrieved from our inpatient databases starting from October 2007. Correlations between computed tomography parameters (bowel wall thickness, mural enhancement, comb sign, extramural findings, and stricture), endoscopic and histological severity scores, CD Activity Index [CDAI], and C-reactive protein were assessed using Spearman's rank correlation. RESULTS: Seventy patients were included in this study. One hundred fifty-seven segments were examined. Bowel wall thickness (r = 0.6334, P < 0.0001), mural enhancement (r = 0.5477, P < 0.0001), comb sign (r = 0.5898, P < 0.0001), and extramural findings (r = 0.4754, P < 0.0001) were moderately correlated with the segmental Capsule Endoscopy CDAI. The segmental CTE score also moderately correlated with the segmental Capsule Endoscopy CDAI (r = 0.6714, P < 0.0001), while the total CTE score strongly correlated with the total Capsule Endoscopy CDAI (r = 0.7252, P < 0.0001). Both total CTE score (r = 0.5937, P < 0.0001) and total Capsule Endoscopy CDAI (r = 0.6364, P < 0.0001) correlated significantly with the Harvey-Bradshaw Index. Of five computed tomography parameters, bowel wall thickness have the best accuracy to detect small intestine lesions with an area under the receiver operating characteristic curve of 0.811 (P < 0.0001), with a sensitivity and specificity of 81.82% and 74.14%, respectively. CONCLUSION: CTE is a reliable technique for detecting small intestine lesions in patients with CD, also provides accurate information on small bowel CD severity and activity, with close agreement to inflammatory markers, CDAI, and histopathology.

Gene expression of tumor necrosis factor receptor associated-factor (TRAF)-1 and TRAF-2 in inflammatory bowel disease.

OBJECTIVE: This study aimed to investigate the expression of tumor necrosis factor receptor-associated factor (TRAF)-1 and TRAF-2 in patients with inflammatory bowel disease (IBD). METHODS: Immunostaining, western blot and real-time polymerase chain reaction (PCR) were used to detect the expression of TRAF-1 and TRAF-2 in colonic mucosa of IBD patients and control. Furthermore, serum protein levels of TRAF-1 and TRAF-2 were measured by ELISA and the receiver operating characteristic (ROC) curve was used to determine their diagnostic value. RESULTS: The expression of TRAF-1 and TRAF-2 was significantly higher in inflamed and non-inflamed tissues of IBD patients than those in control (P < 0.05). Moreover, inflamed tissues had higher TRAF-1 and TRAF-2 expression than non-inflamed tissues (P < 0.05). Both TRAF-1 and TRAF-2 were shown to have a fair to excellent value in the differentiation of control and IBD patients with the area under the ROC curve (AUROC) of 0.680-1.000 (P < 0.001). CONCLUSION: The activation of TRAF-1 and TRAF-2 may be early events in the pathogenesis of IBD and their functions are not quite the same.

Safety and efficacy of calcium and magnesium infusions in the chemoprevention of oxaliplatin-induced sensory neuropathy in gastrointestinal cancers.

OBJECTIVE: To derive a more precise estimation on the safety and efficacy of calcium and magnesium (Ca and Mg) infusions in the prevention of oxaliplatin-induced sensory neuropathy. METHODS: A total of 16 studies including 1765 individuals were involved in this meta-analysis. Odds ratio (OR) and its 95% confidence interval (CI) were calculated. RESULTS: The difference in the incidence of oxaliplatin-induced neuropathy grade ≥ 1 was statistically significant between the Ca and Mg infusions treatment group and the untreated group (National Cancer Institute common toxicity criteria [NCI CTC]: OR 0.44, 95% CI 0.31-0.62, P = 0.000; oxaliplatin-specific scale [OSS]: OR 0.30, 95% CI 0.20-0.45, P = 0.000). Similar results were found in the incidences of oxaliplatin-induced neuropathy grade ≥ 2 (NCI CTC: OR 0.60, 95% CI 0.46-0.77, P = 0.000; OSS: OR 0.45, 95% CI 0.30-0.67, P = 0.000). However, we did not detect a trend of fewer oxaliplatin-induced neuropathy grade ≥ 3 incidences in the Ca and Mg infusions treatment group than the untreated group (NCI CTC: OR 0.67, 95% CI 0.44-1.01, P = 0.054; OSS: OR 0.66, 95% CI 0.34-1.29, P = 0.224). There was no difference in the response rate between the Ca and Mg treated group and the untreated group (OR 0.89, 95% CI 0.67-1.17, P = 0.391). CONCLUSION: Ca and Mg infusions do not alter the efficacy of oxaliplatin-based chemotherapy in gastrointestinal cancers, which may be reasonable to add them to lessen the incidence of neuropathy.