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Voriconazole remains the mainstay for the treatment of invasive fungal infections in heart transplant patients and can significantly increase tacrolimus exposure because of drug-drug interaction (DDI). However, the magnitude of this DDI is highly variable and difficult to predict. The purpose of this study was to present the characteristics of the DDI between tacrolimus and voriconazole, and further identify the various predictors of tacrolimus dose modification.We retrospectively enrolled 69 heart transplant recipients who did not use voriconazole as the control and 68 patients received voriconazole treatment in voriconazole group. CYP3A4*1G, CYP3A5*3 and CYP2C19*2 or *3 were thereafter genotyped by Sanger sequencing. The dose of tacrolimus required to achieve the therapeutic concentrations and tacrolimus dose-corrected trough concentration (CThe DDI between tacrolimus and voriconazole displayed a large interindividual variability with more than 10-fold changes in tacrolimus dose (range 1.28-13.00) and CThe findings of this study have identified the various important factors to adjust tacrolimus dosage when co-administrated with voriconazole in individual patients. CYP2C19 genotype and haematocrit should be considered when tailoring tacrolimus dose.

Background This study retrospectively analyzed and evaluated the potential correlations of serum calcium, serum phosphorus, and calcium-phosphorus product (Ca–P product) with the incidence of osteoporotic vertebral compression fractures (OVCFs), with the aim of exploring whether the Ca–P product can be used as a serological indicator to predict the risk of OVCFs. Methods This study randomly enrolled 400 elderly patients in our hospital with OVCFs and 400 patients with hip and knee arthroplasty due to femoral head necrosis or osteoarthritis from August 2013 to April 2021. Age, sex, past medical history, and admission biochemical indicators, including albumin, blood urea nitrogen, serum creatinine, serum calcium and serum phosphorus, were collected for statistical analysis. Results Albumin, serum calcium, serum phosphorus, Ca–P product, corrected serum calcium and corrected Ca–P product were lower in the OVCF group than in the non-OVCF group (P Conclusion The Ca–P product and corrected Ca–P product can be used as serological indicators to predict the risk of OVCFs in elderly individuals. Early clinical interventions targeting this risk factor can further reduce the risk of OVCFs. Also, timely and regular testing of the serum calcium and phosphorus level is recommended and encouraged for this group of people.

To observe the effect of navel acupuncture on bladder emptying function in patients with urinary retention after stroke based on the conventional treatment.A total of 106 patients with urinary retention after stroke were randomly divided into an observation group (53 cases, 3 cases dropped off) and a control group (53 cases, 3 cases dropped off). Patients in the control group were treated with drugs, catheterization and bladder function rehabilitation training. On the basis of the treatment in the control group, the observation group was treated with navel acupuncture, 30 min each time, once every other day, for 4 weeks. The bladder residual urine volume, spontaneous urination volume and catheterization times before and after treatment were compared between the two groups, and the clinical efficacy was evaluated.After treatment, in the two groups, the bladder residual urine volume and catheterization times were lower than those before treatment (On the basis of conventional treatment, navel acupuncture can effectively improve the bladder emptying function of patients with urinary retention after stroke.

Ovarian cancer is one of the deadliest gynecological cancer, with a low overall 5-year survival rate. RDM1, RAD52 motif-containing protein 1, is sensitive to cisplatin, a common chemotherapy drug and it has an important role inDNA damage repair pathway. Until now, the effect of RDM1 in ovarian cancer is undiscovered. Here, clinical data shows that the tumour tissues of ovarian carcinoma patients with higher mRNA and protein expression of RDM1. Knockdown of

Lung cancer is one of the cancers with highest morbidity and mortality rates and the metastasis of lung cancer is a leading cause of death. Mechanisms of lung cancer metastasis are yet to be fully understood. Herein, we demonstrate that mice deficient for REGγ, a proteasome activator, exhibited a significant reduction in tumor size, numbers, and metastatic rate with prolonged survival in a conditional Kras/p53 mutant lung cancer model. REGγ enhanced the TGFβ-Smad signaling pathway by ubiquitin-ATP-independent degradation of Smad7, an inhibitor of the TGFβ pathway. Activated TGFβ signaling in REGγ-positive lung cancer cells led to diminished expression of E-cadherin, a biomarker of epithelial-mesenchymal transitions (EMT), and elevated mesenchymal markers compared with REGγ-deficient lung cancer cells. REGγ overexpression was found in lung cancer patients with metastasis, correlating with the reduction of E-Cadherin/Smad7 and a poor prognosis. Overall, our study indicates that REGγ promotes lung cancer metastasis by activating TGF-β signaling via degradation of Smad7. Thus, REGγ may serve as a novel therapeutic target for lung cancers with poor prognosis.

Coronary artery aneurysm (CAA) is an aortic catastrophe with low prevalence. Giant CAA is even more uncommon, requiring surgical intervention. Giant CAA usually originates from the proximal segments of the right coronary and the anterior descending arteries. Here we report a rare case of giant left CAA with fistula formation treated with successful surgery.

Asthma has been a global problem, especially in children. We aim to evaluate the contemporary prevalence and influencing factors of asthma among children aged 3-7 years in Shanghai, China.A random sample of preschool children was included in this study. The International Study of Asthma and Allergies in Childhood questionnaire was adopted to assess the childhood asthma. Multivariable logistic regression models were used to evaluate the associations between independent variables and childhood asthma.Of 6389 preschool children who were invited to take part in this study, 6163 (response rate: 96.5%) completed the questionnaire and were included in the analysis. The overall prevalence of asthma was 14.6% which increased more than six folds from 2.1% in 1990. Being male, younger age, preterm delivery, being born in spring or autumn, being delivered by elective cesarean section without indication, miscarriage, high socioeconomic status, having allergy history, and exposure to passive smoking, latex paint, and dust were potential risk factors for childhood asthma. Spending more time outdoors ( 30 min/day), having indoor plants, and cleaning rooms more frequently were potential protective factors.The prevalence of childhood asthma in Shanghai has increased dramatically during the past three decades. The findings about risk and protective factors of childhood asthma could be used to develop appropriate strategies to prevent and control childhood asthma in Shanghai and in other similar metropolitan cities.

Covering: 2000 to 2020 Triptolide is a bioactive diterpene triepoxide isolated from Tripterygium wilfordii Hook F, a traditional Chinese medicinal plant whose extracts have been used as anti-inflammatory and immunosuppressive remedies for centuries. Although triptolide and its analogs exhibit potent bioactivities against various cancers, and inflammatory and autoimmune diseases, none of them has been approved to be used in the clinic. This review highlights advances in material sourcing, molecular mechanisms, clinical progress and new drug design strategies for triptolide over the past two decades, along with some prospects for the future course of development of triptolide.

Bortezomib is a boronate proteasome inhibitor widely used as an efficient anticancer drug; however, the clinical use of bortezomib is hampered by its adverse effects such as hematotoxicity and peripheral neuropathy, and low efficacy on solid tumors due to unfavorable pharmacokinetics and poor penetration in the solid tumors. In this study, we developed a tripeptide Arg-Gly-Asp (RGD)-targeted dendrimer conjugated with catechol and poly(ethylene glycol) groups for the targeted delivery of bortezomib to metastatic bone tumors. Bortezomib was loaded on the dendrimer via a boronate-catechol linkage with pH-responsive property, which plays an essential role in the control of bortezomib loading and release. The nontargeted bortezomib nanomedicine showed minimal cytotoxicity at pH 7.4, but significantly increased anticancer activity when cyclic RGD (cRGD) moieties were anchored on the dendrimer surface. The ligand cRGD enabled efficient internalization of the bortezomib complex by breast cancer cells such as MDA-MB-231 cells. The targeted nanomedicine efficiently depressed the progression of metastatic bone tumors and significantly inhibited the tumor-associated osteolysis in a model of bone tumors. This study provided an insight into the development of nanomedicine for metastatic bone tumors.

Background Increasing evidence has demonstrated that circular RNAs (circRNAs) may play an important role in oncogenesis and tumor development; however, their role in lung adenocarcinoma (LUAD) remains unclear. We identified the differentially expressed circRNAs in LUAD and investigated the potential mechanisms for cancer progression. Methods We examined differentially expressed circRNAs in LUAD and paired normal tissues using downloaded circRNA microarrays from the Gene Expression Omnibus. We constructed gene co‐expression networks based on the degree of Pearson correlation to predict the critical circRNA in LUAD. Gene Ontology analysis was performed on the genes in the network. We observed one novel circRNA upregulated in LUAD, hsa_circ_0000792, as well as its potential sponged microRNA, miR‐375. Subsequent real‐time quantitative PCR was used to verify the bioinformatics analysis. Results Several circRNAs showed significantly different expression levels in LUAD tissues. Real‐time quantitative PCR and further co‐expression network analysis of 42 matched tissue samples showed a significant difference in expression between LUAD and normal tissues in hsa_circ_0000792 (P < 0.001). We built a network of hsa_circ_0000792‐targeted miRNA gene interactions, including miR‐375 and the corresponding messenger RNAs. Gene Ontology analysis revealed that hsa_circ_0000792 could participate in signal transduction and cell communication during LUAD development. Larger area under the curve by receiver operating characteristic curve analysis of hsa_circ_0000792 and miR‐375 (0.815 and 0.772, respectively) in LUAD indicated greater potential as biomarkers. Conclusions We identified hsa_circ_0000792 as a potential LUAD biomarker; however, further studies are required to determine the mechanism of this circRNA in LUAD development.

Pictilisib, a weakly basic compound, is an orally administered, potent, and selective pan‐inhibitor of phosphatidylinositol 3‐kinases for oncology indications. To investigate the significance of high‐fat food and gastric pH on pictilisib pharmacokinetics (PK) and enable label recommendations, a dedicated clinical study was conducted in healthy volunteers, whereby both top‐down (population PK, PopPK) and bottom‐up (physiologically based PK, PBPK) approaches were applied to enhance confidence of recommendation and facilitate the clinical development through scenario simulations. The PopPK model identified food (for absorption rate constant (Ka)) and proton pump inhibitors (PPI, for relative bioavailability (Frel) and Ka) as significant covariates. Food and PPI also impacted the variability of Frel. The PBPK model accounted for the supersaturation tendency of pictilisib, and gastric emptying physiology successfully predicted the food and PPI effect on pictilisib absorption. Our research highlights the importance of applying both quantitative approaches to address critical drug development questions.

This study aimed to investigate the biomechanical properties of anterior cruciate ligament (ACL); tibial, femoral articular cartilage; and meniscus in knee joints receiving computer-aided or conventional ACL reconstruction. Three-dimensional (3D) knee joint finite element models were established for healthy volunteers (normal group) and patients receiving computer-aided surgery (CAS) or conventional (traditional surgery [TS]) ACL reconstruction. The stress and stress distribution on the ACL, tibial, femoral articular cartilage, and meniscus were examined after force was applied on the 3D knee joint finite element models. No significant differences were observed in the stress on ACL among normal group, CAS group, and TS group when a femoral backward force was loaded. However, when a vertical force of 350 N was loaded on the knee joints, TS group had significant higher stress on the articular cartilage and meniscus than the other two groups at any flexion angle of 0, 30, 60, and 90 degrees. However, no significant differences were observed between CAS group and normal group. In conclusion, computer-aided ACL reconstruction has advantages over conventional surgery approach in restoring the biomechanical properties of knee joints, thus reducing the risk of damage to the knee joint cartilage and meniscus after ACL reconstruction.

SMAD4 is mutated in human lung cancer, but the underlying mechanism by which Smad4 loss-of-function (LOF) accelerates lung cancer metastasis is yet to be elucidated. Here, we generate a highly aggressive lung cancer mouse model bearing conditional KrasG12D, p53fl/fl LOF and Smad4fl/fl LOF mutations (SPK), showing a much higher incidence of tumor metastases than the KrasG12D, p53fl/fl (PK) mice. Molecularly, PAK3 is identified as a downstream effector of Smad4, mediating metastatic signal transduction via the PAK3-JNK-Jun pathway. Upregulation of PAK3 by Smad4 LOF in SPK mice is achieved by attenuating Smad4-dependent transcription of miR-495 and miR-543. These microRNAs (miRNAs) directly bind to the PAK3 3′UTR for blockade of PAK3 production, ultimately regulating lung cancer metastasis. An inverse correlation between Smad4 and PAK3 pathway components is observed in human lung cancer. Our study highlights the Smad4-PAK3 regulation as a point of potential therapy in metastatic lung cancer., The underlying mechanisms by which Smad4 loss-of-function accelerates lung cancer metastasis is unclear. Here, the authors show PAK3 as a downstream effector of Smad4 promoting metastatic signalling and suggest Smad4-PAK3 regulation as a point of potential therapy in metastatic lung cancer.

Purpose. To determine whether the radiomic features of 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) contribute to prognosis prediction in primary gastric diffuse large B-cell lymphoma (PG-DLBCL) patients. Methods. This retrospective study included 35 PG-DLBCL patients who underwent PET/CT scans at West China Hospital before curative treatment. The volume of interest (VOI) was drawn around the tumor, and radiomic analysis of the PET and CT images, within the same VOI, was conducted. The metabolic and textural features of PET and CT images were evaluated. Correlations of the extracted features with the overall survival (OS) and progression-free survival (PFS) were evaluated. Univariate and multivariate analyses were conducted to assess the prognostic value of the radiomic parameters. Results. In the univariate model, many of the textural features, including kurtosis and volume, extracted from the PET and CT datasets were significantly associated with survival (5 for OS and 7 for PFS (PET); 7 for OS and 14 for PFS (CT)). Multivariate analysis identified kurtosis (hazard ratio (HR): 28.685, 95% confidence interval (CI): 2.067–398.152, p=0.012), metabolic tumor volume (MTV) (HR: 26.152, 95% CI: 2.089–327.392, p=0.011), and gray-level nonuniformity (GLNU) (HR: 14.642, 95% CI: 2.661–80.549, p=0.002) in PET and sphericity (HR: 11.390, 95% CI: 1.360–95.371, p=0.025) and kurtosis (HR: 11.791, 95% CI: 1.583–87.808, p=0.016), gray-level nonuniformity (GLNU) (HR: 6.934, 95% CI: 1.069–44.981, p=0.042), and high gray-level zone emphasis (HGZE) (HR: 9.805, 95% CI: 1.359–70.747, p=0.024) in CT as independent prognostic factors. Conclusion. 18F-FDG PET/CT radiomic features are potentially useful for survival prediction in PG-DLBCL patients. However, studies with larger cohorts are needed to confirm the clinical prognostication of these parameters.

Background: The clinical use of tirofiban remains controversial for patients with acute ischemic stroke (AIS), we aimed to conduct a meta- analysis of cohort studies to assess the efficacy and safety of tirofiban for AIS patients. Methods: All apparently unconfounded randomized controlled trials (RCTs) and case-controlled studies, with or without blinding, of tirofiban in individuals with AIS will be included in this review. We will conduct a literature search in 2 databases Pubmed and Embase, using indexing terms related to cerebral infarctions and tirofiban to include articles indexed as of Jan 31, 2019 in the English language only. Two reviewers will independently select trials for inclusion and assess trial quality. Two pairs of review authors will independently extract information for each included trials. Primary outcomes are any intracerebral hemorrhage (aICH), symptomatic intracranial hemorrhage (sICH), fatal ICH, recanalization rate and long-term outcome. The risk of bias of the included studies will be evaluated based on Cochrane assessment tool. Revman 5.3 will be used for heterogeneity assessment, generating funnel-plots, data synthesis, subgroup analysis, and sensitivity analysis. Result: We will provide practical and targeted results assessing the efficacy and safety of tirofiban for AIS patients, to provide reference for clinical use of tirofiban. Conclusion: The stronger evidence about the efficacy and safety of tirofiban for AIS patients will be provided for clinicians.

Infection rates of rodents have a significant influence on the transmission of hemorrhagic fever with renal syndrome (HFRS). In this study, four cities and two counties with high HFRS incidence in eastern Hunan Province in China were studied, and surveillance data of rodents, as well as HFRS cases and related environmental variables from 2007 to 2010, were collected. Results indicate that the distribution and infection rates of rodents are closely associated with environmental conditions. Hantavirus infections in rodents were positively correlated with temperature vegetation dryness index and negatively correlated with elevation. The predictive risk maps based on multivariate regression model revealed that the annual variation of infection risks is small, whereas monthly variation is large and corresponded well to the seasonal variation of human HFRS incidence. The identification of risk factors and risk prediction provides decision support for rodent surveillance and the prevention and control of HFRS.

RAD52 motif containing 1 (RDM1) is involved in DNA damage repair pathway and RDM1−/− cells increase sensitivity to cisplatin, a common chemotherapy drug. Lung cancer is the leading cause of cancer death worldwide. However, the role of RDM1 in lung cancer is unknown. Here, we find that the mRNA and protein expression levels of RDM1 are significantly increased in human lung tumors, especially in lung adenocarcinoma. The lung adenocarcinoma patients with higher mRNA expression of RDM1 show the worse clinical outcomes. Knockdown of RDM1 in lung adenocarcinoma cells reduces cell proliferation and promotes apoptosis, consistent with the role RDM1 in the overexpression experiments. Xenograft mouse model shows stable knockdown of RDM1 significantly inhibits lung adenocarcinoma tumor growth. These in vitro and in vivo results conclude that RDM1 plays an oncogenic role in human lung adenocarcinoma. Interestingly, P53/RAD51/RAD52 can be regulated by RDM1, and the negative regulation of P53 by RDM1 may be one of major mechanisms for RDM1 to accomplish its oncogenic functions in lung adenocarcinoma. Therefore, RDM1 may be a new target for the treatment of lung adenocarcinoma.

It has been reported that the proteasome activator REGγ is associated with multiple oncogenic pathways in human cancers. However, the role of REGγ in the development of melanoma and the underlying mechanisms remain unclear. In this study, we attempted to investigate the effects of REGγ on human melanoma cell proliferation in vitro and in vivo. We demonstrated that knockdown of REGγ inhibited melanoma cell growth and arrested melanoma cell at G1 phase. Furthermore, depletion of REGγ also inhibited the xenograft growth of human melanoma. Mechanistically, REGγ activates Wnt/β-catenin signal pathway by degrading GSK-3β in melanoma cell lines and mouse models. Transient knockdown of β-catenin effectively blocked cell proliferation in REGγ wild-type melanoma cells. In human melanoma samples, REGγ was overexpressed and positively correlated with β-catenin levels. This study demonstrates that REGγ is a central molecule in the development of melanoma by regulating Wnt/β-catenin pathway. This suggests that targeting REGγ could be an alternative therapeutic approach for melanoma.

Background Extracorporeal membrane oxygenation (ECMO) has developed rapidly and becomes a significant treatment for emergency. Current blood pumps for ECMO have different disadvantages. Objective To design a pulsatile DC electromagnetic blood pump for ECMO. Methods The design is presented with a driving principle which the rectilinear reciprocation of a magnet inside energized solenoids is implemented, and with a structure of solenoids with compensation coils. Furthermore, a prototype was constructed and the performance indexes of it were measured with the experimental evaluations, where the acceleration experiment was performed without any loads, and the flows were measured in the ranges of preload and afterload are 5 to 30 mmHg and 50 to 80 mmHg respectively when the frequency of the motion is 80 beats per minute. Results The electromagnetic force is greater than 1.4 N when the DC reaches 2.7 A and the flow of the prototype is greater than 3.0 L/min except the differences between the preload and the afterload are greater than or equal to 70 mmHg. Conclusions The design of the blood pump for ECMO meets the theoretical and clinical requirements.

Aim Metastasis of tumor cells occurs through lymphatic vessels, blood vessels and transcoelomic spreading. Growing evidence from in vivo and in vitro studies has indicated that tumor lymphangiogenesis facilitates metastasis. However, the regulation of lymphangiogenesis in colon cancer remains unclear. The aims of this study were to identify key miRNAs in colon cancer lymphangiogenesis and to investigate its target and mechanism. Methods miRNA microarray analysis was conducted to identify miRNAs in human lymphatic endothelial cells (HLECs) that were regulated by co-cultured human colon cancer cells. Gain- and loss-of-function studies were performed to determine the function of miR-27a, a top hint, on lymphangiogenesis and migration in HLECs. Furthermore, bioinformatics prediction and experimental validation were performed to identify miR-27a target genes in lymphangiogenesis. Results We found that expression of miR-27a in HLECs was induced by co-culturing with colon cancer cells. Over-expression of miR-27a in HLECs enhanced lymphatic tube formation and migration, whereas inhibition of miR-27a reduced lymphatic tube formation and migration. Luciferase reporter assays showed that miR-27a directly targeted SMAD4, a pivotal component of the TGF-β pathway. In addition, gain-of-function and loss-of-function experiments showed that SMAD4 negatively regulated the length of lymphatic vessels formed by HLECs and migration. Conclusions Our data indicated that colon cancer cell induced the expression of miR-27a in HLECs, which promoted lymphangiogenesis by targeting SMAD4. Our finding implicated miR-27a as a potential target for new anticancer therapies in colon cancer.

To assess the prevalence and potential risk factors of latent tuberculosis infection (LTBI) in Chinese patients with inflammatory bowel disease (IBD) and to evaluate the role of chest computed tomography (CT) in the screening of LTBI.A single-center retrospective study was conducted and all IBD patients who had been screened for LTBI by T-SPOT.TB between December 2011 and January 2016 were enrolled in the study. Both inpatient and outpatient records were collected and comprehensively reviewed.Altogether 534 IBD patients were included. The positivity rate of T-SPOT.TB was 18.0% overall, 31.9% in IBD unclassified, 22.5% in ulcerative colitis and 13.0% in Crohn's disease patients, respectively. Age, history of TB and the administration of immunosuppressants were significantly associated with T-SPOT.TB positivity. Among 123 patients who underwent serial testing, the conversion and reversion rate of T-SPOT.TB was 10.2% and 42.9%, respectively. Furthermore, 102 of 447 (22.8%) patients who underwent chest computed tomography (CT) were found with abnormal CT findings suggestive of LTBI. The concordance rate was 75% between the T-SPOT.TB and chest CT with a kappa value of 0.25 (95% CI 0.15-0.35).The prevalence of LTBI in IBD patients is high in China. Chest CT is recommended as an alternative to IGRA for screening LTBI of IBD patients before commencing immunosuppressive therapy in high-prevalence regions.

Lgr5 marks stem cells in digestive epithelial tissues by lineage tracing, and in vitro ever-expansion of Lgr5 stem cells form organoids, which can be directed to differentiate into functional somatic cells. Organoids derived from gastrointestinal epithelium even recapitulate the morphologic features of their in vivo counterpart. Culture conditions are also modified to establish cancer organoids from individual patients. With great genetic stability during derivation and expansion, organoids retain either single mutation in patients with inherited disease or multiple mutations of cancer tissues. Together with efficient gene-editing protocol, organoids are emerging as powerful in vitro disease models.

Here we report that mice deficient for the proteasome activator, REGγ, exhibit a marked resistance to TPA (12-O-tetradecanoyl-phorbol-13-acetate)-induced keratinocyte proliferation, epidermal hyperplasia and onset of papillomas compared with wild-type counterparts. Interestingly, a massive increase of REGγ in skin tissues or cells resulting from TPA induces activation of p38 mitogen-activated protein kinase (MAPK/p38). Blocking p38 MAPK activation prevents REGγ elevation in HaCaT cells with TPA treatment. AP-1, the downstream effector of MAPK/p38, directly binds to the REGγ promoter and activates its transcription in response to TPA stimulation. Furthermore, we find that REGγ activates Wnt/β-catenin signalling by degrading GSK-3β in vitro and in cells, increasing levels of CyclinD1 and c-Myc, the downstream targets of β-catenin. Conversely, MAPK/p38 inactivation or REGγ deletion prevents the increase of cyclinD1 and c-Myc by TPA. This study demonstrates that REGγ acts in skin tumorigenesis mediating MAPK/p38 activation of the Wnt/β-catenin pathway.

This study aimed to evaluate the predictive and prognostic roles of BRAF mutation in patients with metastatic colorectal cancer (mCRC) treated with anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (MoAbs).Computer searches of the literature on BRAF mutation in mCRC patients were performed. Studies with objective response rate (ORR) to anti-EGFR MoAbs and/or overall survival (OS) and progression-free survival (PFS) with different BRAF gene expression in mCRC patients were eligible.A total of 19 studies including 2875 patients was enrolled in the meta-analysis. BRAF mutation was detected in 246 patients. The ORR was 18.4% (40/217) in mutant BRAF group and 41.7% (831/1993) in the wild-type BRAF group. The overall risk ratio (RR) for the ORR of BRAF mutation patients compared with wild-type BRAF patients was 0.58 (95% confidence intervals [CI] 0.35-0.94, P = 0.027). The median PFS of patients with BRAF mutation was significantly shorter than that of patients with wild-type BRAF (hazard ratio [HR] 2.98, 95% CI 2.07-4.27, P 0.001) and the median OS of patients with BRAF mutation was also significantly shorter than that of those with wild-type BRAF (HR 2.85, 95% CI 2.31-3.52, P 0.001).BRAF mutation is associated with poor response to anti-EGFR MoAbs and it is an adverse prognostic biomarker of the survival of patients with mCRC.

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).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.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.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.

To review the research progress of the location marker of rotational alignment of the distal.The recent literature concerning the location marker of rotational alignment of the distal femur at home.Femoral prosthesis malrotational alignment could lead to some and abroad was extensively reviewed and analyzed. patellofemoral complications, such as dislocation of the patella, snapping, wear, and patellar pain. There are many methods to determining femoral component rotational alignment in the artificial total knee arthroplasty, including transepicondylar axis line, anterior posterior axis, the posterior condyles line, flexion gap balance technology, and computer navigation technology. Correct choice of the rotational alignment of the distal femur is crucial in reducing postoperative complications and the revision rate. Suitable reference axis is chosen during total knee arthroplasty to ensure the accuracy of the rotation axis of the femoral prosthesis, but it is currently still controversial.The rotational alignment of the distal femur is an extremely important part to affect the prognosis of total knee arthroplasty. The methods to determine the rotational alignment of the distal

To review recent advance in the application and research of three-dimensional digital knee model.The recent original articles about three-dimensional digital knee model were extensively reviewed and analyzed.The digital three-dimensional knee model can simulate the knee complex anatomical structure very well. Based on this, there are some developments of new software and techniques, and good clinical results are achieved.With the development of computer techniques and software, the knee repair and reconstruction procedure has been improved, the operation will be more simple and its accuracy will be further improved.

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).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.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).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.

To study the feasibility of virtual intercondylar notchplasty by applying MRI two-dimensional (2D) images to reconstruct three-dimensional (3D) images and measure the size of intercondylar notch.Thirty healthy volunteers who had no knee joint disease and surgery history were selected. There were 15 females and 15 males with an age range of 20-30 years, weight range of 45-74 kg, and height range of 150-185 cm. They were divided into male group and female group, and the knees of each group were divided into 2 subgroups (the left group and right group). MRI scan of the left and right knees was performed, and the 2D images of MRI were imported into Mimics 10.01 medical image control system for 3D reconstruction. The related anatomical data as follows were measured from the 3D digital model and analyzed by statistical software: notch width (NW), condylar width (CW), and notch width index (NWI). Then the 3D knee images of patients with anterior cruciate ligament (ACL) injury were collected between January and March 2010, and 4 patients with narrow intercondylar notch (NWIor = 0.2) were selected for reconstructing the 3D model of the knee and simulating the intercondylar notch plasty. Then, the volume of osteotomy in 3D model was calculated and applied in the ACL reconstruction surgery, and whether the graft had impingement with intercondylar notch or not was evaluated.There were significant differences in NW and CW between male group and female group (P0.05), but no significant difference was found in the NWI (P0.05). And there was no significant difference in NW, CW, and NWI between the left and right knees both in male group and female group (P0.05). After ACL reconstruction and intercondylar notchplasty, the shape of intercondylar notch became normal (NWI0.22), no impingement occurred between the graft and intercondylar notch under arthroscopy within 3-month follow-up.The shape of intercondylar notch of 3D model based on MRI 2D images is similar to the real intercondylar notch. NWI is one of important indexes which can reflect the narrow level of intercondylar notch. The virtual intercondylar notchplasty may provide preoperative plan and guidence for ACL reconstruction operation to avoid the impingement between graft and intercondylar notch after surgery.

To systematically review the efficacy and safety of once-daily (OD) mesalamine for the treatment of ulcerative colitis (UC) compared with multiple-daily (MD) mesalamine.Electronic databases up to July 2011 were searched for related studies evaluating the efficacy of OD vs MD for treatment of UC. Only randomized controlled trials (RCTs) were considered eligible. Remission rates or relapse rates were analyzed using intention-to-treat (ITT) and per-protocol (PP) analysis. Pooled relative risk (RR) and 95% confidence interval (CI) were calculated. Publication bias was assessed with a funnel plot.Overall 10 RCTs including 9 full-text manuscripts and one abstract met the inclusion criteria. OD dosing of mesalamine was shown to be as effective as MD dosing for the maintenance of clinical remission in patients with quiescent UC (RR = 1.00, 95% CI 0.89-1.12) by ITT analysis. For active UC, a mild but significant benefit was achieved by OD dosing compared with MD dosing (RR = 0.80, 95% CI 0.64-0.99). Total adverse events were similar using OD and MD mesalamine in quiescent UC (RR = 1.06, 95% CI 0.93-1.20). Compliance with OD was slightly better than with MD (RR = 0.92, 95% CI 0.82-1.03).OD mesalamine is as effective and has a comparable safety profile as MD regimens for the maintenance treatment of UC, and is even more effective for inducing remission in active UC.

To provide a systematic review with a meta-analysis for addressing the association between circulating adiponectin levels and the risk of colorectal cancer and adenoma.Multiple electronic sources including MEDLINE, EMBASE and the Science Citation Index Expanded databases were searched to identify relevant studies for this systematic review. All existing observational studies that examined the relationship between circulating adiponectin and colorectal cancer or adenoma were included. Weighted mean difference and 95% confidence intervals (CI) were estimated and pooled using meta-analysis methods.Overall 13 case control or nested case control studies met the inclusion criteria. A total of 6175 participants and 3015 cases of colorectal cancer and adenoma were included in this meta-analysis. The weighted mean difference (95% CI) were -1.084 µg/mL (-1.836, -0.331), P = 0.005 in colorectal cancer and -1.43 µg/mL (-2.231, -0.628), P = 0.000 in adenoma. In men, a 2% decreased risk of colorectal neoplasm for a 1 µg/mL increment in adiponectin levels was observed (OR = 0.98, 95% CI 0.96-0.99) whereas among women there is no evidence of such a trend (OR = 0.99, 95% CI 0.97-1.01).Patients with colorectal cancer and adenoma demonstrated markedly lower adiponectin values than controls, yet there was significant heterogeneity among studies. A negative dose response relationship between levels of adiponectin and the risk of colorectal neoplasm was observed in men.

Chemotherapeutic drug resistance remains a major obstacle to the successful treatment of colon cancer. Here, we show that 77 differentially expressed miRNAs were identified in SW1116/HCPT versus SW1116, and over-expressed miR-506 in SW1116/HCPT cells was validated. Then it was indicated that PPARα is a common target of miR-506 by using a luciferase reporter assay. Our results also demonstrated that cytotoxic ability of HCPT requires the concomitant presence of PPARα, and that loss of PPARα expression imparts resistance to HCPTs anti-tumor effects. All together, our studies indicate that miR-506 over-expression in established HCPT-resistant colon cancer cell line confers resistance to HCPT by inhibiting PPARα expression, then providing a rationale for the development of miRNA-based strategies for reversing resistance in HCPT-resistant colon cancer cells.

To investigate whether RNA interference (RNAi) of the ubiquitin fusion-degradation 1-like protein (Ufd1) could sensitize hydroxycamptothecin (HCPT)-resistant colon cancer cell line SW1116/HCPT to the cytotoxic effect of HCPT.SW1116/HCPT cells were transfected with plasmids containing Ufd1-specific small interfering RNA (siRNA) (Ufd1 knockdown cells) and non-specific siRNA (control cells). A drug sensitivity analysis, 3-(4,5)-dimethylthiahiazol (-z-y1)-3,5-di- phenytetrazoliumromide (MTT) assay was performed on Ufd1 knockdown cells and control cells. After treating the cells with HCPT, a caspase-3 and caspase-4 activity assay, flow cytometric analysis and Western blot for detecting phosphorylated c-Jun N-terminal kinase (p-JNK), phosphorylated protein kinases B (p-Akt), P53, ubiquitin, GADD 153 and Grp78/Bip were performed.According to the MTT assay, the survival rate of knockdown cells was significantly lower than that of the control cells (P0.01). Both caspase-3 and caspase-4 activity assay showed higher activation level in Ufd1 knockdown cells than that in the control cells (P0.01). A flow cytometric analysis revealed more severe S-phase arrest in the Ufd1 knockdown cells than that in the control cells (P0.05). The Western blot showed that increasing the concentration of HCPT resulted in a higher expression level of p-JNK, P53, ubiquitin, GADD 153 and Grp78/Bip in the Ufd1 knockdown cells than that in the control cells.Ufd1 plays a key role in HCPT resistance of SW1116/HCPT and RNAi of Ufd1 can sensitize SW1116/HCPT to the cytotoxic effect of HCPT via strengthening the activation of caspase-3 pathway and disturbing endoplasmic reticulum functions.

Background Testing for genetic risks of Factor V Leiden ( FVL ) in inflammatory bowel disease (IBD) patients with thromboembolism (TE) is common, but the safety and utility of such testing need review. Aim The aim of the present study was to investigate whether the FVL polymorphisms would be one inherited prothrombotic risk factor that could significantly increase the risk of thrombosis in patients with IBD. Methods We performed an electronic databases search to identify published studies correlating the FVL mutations with four populations including one IBD group with TE complications, one control IBD group without TE complications, one control non-IBD group with TE complications and another healthy control (HC) group. Statistical analysis was performed with Review Manager (RevMan) 5.0. Sub-analysis/sensitivity analysis was also performed. Results We identified 112 titles and included 22 studies in this meta-analysis. The odds ratio (OR) of TE in IBD patients with FVL was higher as compared with IBD patients (OR: 4.00; 95%CI: 2.04, 7.87) and HC (OR: 3.19; 95%CI: 1.38, 7.36). There was a 1.25-fold (95%CI: 0.90-1.74) increase in incidence of FVL gene mutation in IBD patients compared with HC. The FVL mutations were not significantly different between IBD patients with thrombosis and non-IBD patients with thrombosis (OR: 0.79; 95%CI: 0.43, 1.47). Conclusion FVL plays a role in IBD-TE, but to no greater extent than it does in the general population with TE.

To systematically evaluate whether immunochemical fecal occult blood tests (iFOBT) could improve clinical performance and test accuracy in screening and surveillance for advanced colorectal neoplasms.Eligible articles were identified by searches of electronic databases. All randomized trials and diagnostic cohort trials directly comparing iFOBT with guaiac-based FOBT (gFOBT) were included. A statistical analysis was performed using RevMan 4.2.8. A sensitivity, specificity and summary receiver operating characteristic curve was performed using Meta Disc.We identified five randomized trials and 11 diagnostic cohort trials. In the randomized trials, the detection rates of advanced colorectal neoplasms with iFOBT or gFOBT were 2.23 percent and 1.24 percent, respectively. The pooled odds ratio (OR) was 1.50 (95% CI 0.94-2.39). In cohort trials, the advanced neoplasm detection rates of iFOBT or gFOBT were 1.44 percent and 0.50 percent (OR 1.99, 95% CI 1.24-3.19) in the average-risk screened population, and were 8.8 percent and 7.1 percent (OR 1.27, 95% CI 1.01-1.60) in diagnosed patients scheduled for colonoscopy. The sensitivity of iFOBT (0.67, 95% CI 0.61-0.73) was superior to that of gFOBT (0.54, 95% CI 0.48-0.60), as well as the specificities (0.85, 95% CI 0.83-0.87 vs 0.80, 95% CI 0.78-0.82) and positive predictive values (0.41 vs 0.29) in cohort trials of diagnosed patients.Our review suggests that iFOBT could perform better in increasing the detection rate of advanced colorectal neoplasm than gFOBT and possesses higher sensitivity and specificity in the surveillance of advanced colorectal neoplasm for patients.

To investigate the cytotoxic effect of epigallocatechin gallate (EGCG) on human hepatocellular carcinoma cell line HepG2 cells and corresponding changes of TGF-beta1-Smad pathway.The cytotoxic effect of EGCG on HepG2 cells was determined by MTT assay. Cell cycle and apoptosis rate were detected by flow cytometry. RT-PCR and luciferase assay were used to verify whether TGF-beta1-Smad signaling pathway is intact in HepG2. The mRNA expression of Smad 2, Smad3, Smad4 and Smad7 was detected by real-time PCR.EGCG induced apoptosis in the HepG2 cells in a time- and concentration-dependent manner. The proportion of G(1) phase cells was increased gradually as the concentration increased. However, the percentage of cells in S phase was decreased gradually. Annexin V/PI assay demonstrated that early apoptosis increased as the concentration increased, and late apoptosis also increased, when treated with high-concentration EGCG. The intact TGF-beta1-Smad pathway was verified by luciferase assay and RT-PCR. There was no significant effect of EGCG on mRNA level of Smad 2, Smad 3, and Smad 4 in HepG2 cells, but downregulated mRNA level of Smad 7.EGCG can reduce apoptosis in human hepatocellular carcinoma cell line HepG2 cells. The activation of TGF-beta1-Smad signaling pathway may be involved in its cytotoxicity mechanisms.

OBJECTIVE: To evaluate systematically the efficacy and safety of anti-epidermal growth factor receptor (EGFR) monoclonal antibody added to a chemotherapeutic regimen in the treatment of patients with metastatic colorectal cancer (mCRC). METHODS: Eligible articles were identified by searching electronic databases. All randomized trials comparing the arm with an anti-EGFR monoclonal antibody to the arm without an anti-EGFR monoclonal antibody during the treatment of mCRC were included. A statistical analysis was performed with Review Manager 4.2.8. RESULTS: Seven randomized trials (n= 4186) were identified. The pooled response rates were 25.4% and 17.6% by intention-to-treat analyses for patients with or without an anti-EGFR monoclonal antibody, respectively, the OR was 3.36 (95% CI 1.42–7.95); the incidence of grades 3–4 adverse events were 71.2% and 54.3% for two groups, respectively, the OR was 2.23 (95% CI 1.74–2.86). The incidence of diarrhea, skin toxicity, hypomagnesemia was 62.3% versus 55.7%; 79.3% versus 19.7%; 27.2% versus 5.6%; and the summary OR was 1.36 (95% CI 1.03–1.80); 33.47 (95% CI 14.81–75.61); 6.73 (95% CI 3.84–11.82), respectively. CONCLUSION: Our results confirmed that monoclonal antibody targeted to EGFR could be effective in increasing response rates and could be a key therapeutic agent in the optimal treatment of mCRC, despite a moderate increase in grades 3–4 adverse events.

To determine the validity and safety of selective cyclooxygenase (COX)-2 inhibitors for the prevention of colorectal adenomas.The relevant data were retrieved from Medline (1966 to 2006), OVID (1996 to January 2007), EMBASE (1980 to January 2007), Chinese Cochrane Centre databases (up to January 2007) and Chinese Biological Medicine Disk (CBM disk, 1997 to 2007). Methodological quality assessment was based on the Cochrane Reviewers' Handbook and Jadad's Score Scale. Statistical software RevMan4.2 was used for meta-analysis.Six randomized clinical trials (5708 patients) were included in the study. Compared with placebo, selective COX-2 inhibitors lowered the detection rates of both adenomas and advanced adenomas (RR: 0.70, 95% CI: 0.55 - 0.88, P = 0.0003 and RR: 0.69, 95% CI: 0.53 - 0.89, P = 0.005). No significant difference was observed in the number of adverse events between patients taking selective COX-2 inhibitors and those taking placebo (RR: 1.07, 95% CI: 0.98 - 1.17, P = 0.11). Compared with placebo, selective COX-2 inhibitors increased the risk of cardiovascular events (RR: 1.21, 95% CI: 1.09 - 1.33, P = 0.0002).Selective COX-2 inhibitors can induce sufficient regression of colorectal adenomatous polyps and thus be used for chemoprevention of colorectal neoplasms. However, because of the potential cardiovascular events, it is not routinely recommended for this indication.

In order to demonstrate the validity of using scalp hair rare earth elements (REEs) content as a biomarker of human REEs exposure, data were collected on REEs exposure levels from children aged 11-15 years old and living in an ion-adsorptive type light REEs (LREEs) mining and surrounding areas in southern China. Sixty scalp hair samples were analyzed by ICP-MS for 16 REEs (La Lu, Y and Sc). Sixteen REEs contents in the samples from the mining area (e.g., range: La: 0.14-6.93 microg/g; Nd: 0.09-5.27 microg/g; Gd: 12.2-645.6ng/g; Lu: 0.2-13.3 ng/g; Y: 0.03-1.27 microg/g; Sc: 0.05-0.30 microg/g) were significantly higher than those from the reference area (range: La: 0.04-0.40 microg/g; Nd: 0.04-0.32 microg/g; Gd: 8.3-64.6 ng/g; Lu: 0.4-3.3ng/g; Y: 0.03-0.29 microg/g; Sc: 0.11-0.36 microg/g) and even much higher than those published in the literature. The distribution pattern of REEs in scalp hair from the mining area was very similar to that of REEs in the mine and the atmosphere shrouding that area. In conclusion, the scalp hair REEs contents may indicate not only quantitatively but also qualitatively (distribution pattern) the absorption of REEs from environmental exposure into human body. The children living in this mining area should be regarded as a high-risk group with REEs (especially LREEs) exposure, and their health status should be examined from a REEs health risk assessment perspective.

This study examined the status of health-related behaviors among rural residents and the factors influencing the practice of such behaviors.One thousand and ninety subjects aged 15 years or over in a rural community, Anhui Province, China were surveyed. A questionnaire was used to collect information on the health knowledge, attitude and behavior of the subjects. Information on health behavior included smoking, drinking, dietary habits, regular exercises, sleeping pattern and oral health behavior.The prevalence of smoking and drinking in the male subjects was 46.5% and 46.9%, respectively. There was a positive significant association between smoking and drinking. Only 8.3% of all subjects ate three regular meals a day regularly. Among subjects who ate two meals a day, 89.7% did not have breakfast. Only 1.7% of subjects took part in regular exercise. About 85% of subjects slept 6 to 8 h per day. Only 38.4% of the respondents had the habit of hand washing before eating and after using the lavatory. 79.3% of the subjects brushed their teeth every day, and among them, only 10.6 percent brushed their teeth twice a day. Further analyses showed that 64.8% of subjects had 3-5 items of positive health behaviors out of 8 items and only 16.9% had six or more items. Logistical regression analyses suggested that better health behavior was affected by sex, age, years of education, income and health knowledge.The status of health behaviors among rural residents was generally poor. It is thus urgent to reinforce health education in rural communities in China.

AIM: To determine the optimal b value of diffusion-weighted imaging for detecting active inflammation in Crohn’s disease. METHODS: Thirty-one patients clinically diagnosed with active Crohn’s disease were referred for magnetic resonance examination. All patients were scanned on a 3.0T magnetic resonance scanner using the same protocol involving four different b values (800, 1500, 2000 and 2500 s/mm2). The diagnostic effect of diffusion-weighted imaging was evaluated and compared with endoscopic findings. The diffusion-weighted image quality of four b value groups was evaluated and apparent diffusion coefficient was measured for both normal and inflammatory intestinal segments. RESULTS: The contrast-to-noise ratio and signal-to-noise ratio were not satisfied when b value 2000 or 2500 s/mm2 was adopted (36.52 ± 14.95 vs 34.78 ± 24.83, P > 0.05; 53.58 ± 23.45 vs 47.58 ± 29.67, P > 0.05). The qualitative image quality was not enough to meet diagnostic requirement. No matter which b value was chosen, the apparent diffusion coefficient of inflammatory intestinal segments was significantly lower than that of normal intestinal segments (1.38 ± 0.28 vs 2.00 ± 0.38, P < 0.01; 1.09 ± 0.20 vs 1.50 ± 0.28, P < 0.01; 0.95 ± 0.19 vs 1.34 ± 0.28, P < 0.01; 0.88 ± 0.14 vs 1.20 ± 0.21, P < 0.01). The lesion detection rate (90.32%), diagnostic sensitivity (81.18%) and specificity (95.10%) would be appropriate when b value 1500 s/mm2 was adopted. CONCLUSION: High b value is suitable for intestinal DW examination on a high field MR scanner.

Multidrug resistance remains a major obstacle to effective chemotherapy of colon cancer. ABCG2, as a half-transporter of the G subfamily of ATP-binding cassette transporter genes (ABC transporters), is known to play a crucial role in multidrug resistance. However, the molecular mechanism of controlling ABCG2 expression in drug resistance of colon cancer is unclear and scarcely reported. In the present study, we systematically investigate the potential role of the c-Jun NH2-terminal kinase (JNK) signal pathway in ABCG2-induced multidrug resistance in colon cancer. In the hydroxycamptothecin (HCPT) resistant cell line SW1116/HCPT from human colon cancer cell line SW1116, ABCG2 is the major factor for multidrug resistance, other than well-studied ABCB1 or ABCC1. Our findings indicate that blocking the JNK pathway by pathway inhibitor SP600125 reduces the expression level and transport function of ABCG2 in drug-resistant cells SW116/HCPT. Notably, the experiments of small interfering RNA directed against JNK1 and JNK2 show that only silence of JNK1 gene has the equal effect as SP600125 on dephosphorylation of transcription factor c-Jun and the expression of ABCG2 protein, while the corresponding phenomena were not observed after silence of JNK2 gene. Meanwhile, SP600125 induces the apoptosis of SW116/HCPT cells by promoting the cleavage of PARP and suppressing the anti-apoptotic protein survivin and bcl-2, and increases the sensitivity of SW1116/HCPT to HCPT. Taken together, our work demonstrated that JNK1/c-jun signaling pathway was involved in ABCG2-mediated multidrug resistance in colon cancer cells. Definitely, inhibition of the JNK1/c-jun pathway is useful for reversing ABCG2-mediated drug resistance in HCPT-resistant colon cancer cells.

AIM: To evaluate the relationship between thiopurine S-methyltransferase (TPMT) polymorphisms and thiopurine-induced adverse drug reactions (ADRs) in inflammatory bowel disease (IBD). METHODS: Eligible articles that compared the frequency of TPMT polymorphisms among thiopurine-tolerant and -intolerant adult IBD patients were included. Statistical analysis was performed with Review Manager 5.0. Sub-analysis/sensitivity analysis was also performed. RESULTS: Nine studies that investigated a total of 1309 participants met our inclusion criteria. The incidence of TPMT gene mutation was increased 2.93-fold (95% CI: 1.68-5.09, P = 0.0001) and 5.93-fold (95% CI: 2.96-11.88, P < 0.00001), respectively, in IBD patients with thiopurine-induced overall ADRs and bone marrow toxicity (BMT), compared with controls. The OR for TPMT gene mutation in IBD patients with thiopurine-induced hepatotoxicity and pancreatitis was 1.51 (95% CI: 0.54-4.19, P = 0.43) and 1.02 (95% CI: 0.26-3.99, P = 0.98) vs controls, respectively. CONCLUSION: This meta-analysis suggests that the TPMT polymorphisms are associated with thiopurine-induced overall ADRs and BMT, but not with hepatotoxicity and pancreatitis.

Purpose To provide a systematic review with meta-analysis for addressing the relationship between fecal bile acids (FBAs) and colorectal cancer. Materials and Methods Electronic databases were searched for all observational studies that examined the relationship between FBAs and colorectal cancer or adenoma, and calculated weighted mean difference (WMD) and 95% confidence interval (CI). Publication bias was assessed with funnel plot. Results Twenty case-control or cohort studies were identified. All studies were pooled to assess the relationship between total FBAs and cancer/adenoma of the large bowel, however, no association was seen (WMD 0.61 mg/g freeze-dried feces; 95% CI: - 0.35 - 1.57). Significantly increased concentration of chenodeoxycholic acid (CDCA) was seen while pooling to assess the relationship between CDCA and cancer/adenoma of the large bowel (WMD 0.13 mg/g freeze-dried feces; 95% CI: 0.01 - 0.25), especially for colorectal cancer (WMD 0.28 mg/g freeze-dried feces; 95% CI: 0.10 - 0.46). However, no significant differences in deoxycholic acid (DCA), lithocholic acid (LCA), and primary and secondary bile acids, were seen between patients with cancer and patients with matched controls regardless of fixed and random effects models. Conclusion CDCA might play a role in the etiology of colorectal cancer.

To compare the diagnostic yield of capsule endoscopy (CE) with that of double-balloon enteroscopy (DBE).Pubmed, Embase, Elsevier ScienceDirect, the China Academic Journals Full-text Database, and Cochrane Controlled Trials Register were searched for the trials comparing the yield of CE with that of DBE. Outcome measure was odds ratio (OR) of the yield. Fixed or random model method was used for data analysis.Eight studies (n = 277) which prospectively compared the yield of CE and DBE were collected. The results of meta-analysis indicated that there was no difference between the yield of CE and DBE [170/277 vs 156/277, OR 1.21 (95% CI: 0.64-2.29)]. Based on sub analysis, the yield of CE was significantly higher than that of double-balloon enteroscopy without combination of oral and anal insertion approaches [137/219 vs 110/219, OR 1.67 (95% CI: 1.14-2.44), P0.01), but not superior to the yield of DBE with combination of the two insertion approaches [26/48 vs 37/48, OR 0.33 (95% CI: 0.05-2.21), P0.05)]. A focused meta-analysis of the fully published articles concerning obscure GI bleeding was also performed and showed similar results wherein the yield of CE was significantly higher than that of DBE without combination of oral and anal insertion approaches [118/191 vs 96/191, fixed model: OR 1.61 (95% CI: 1.07-2.43), P0.05)] and the yield of CE was significantly lower than that of DBE by oral and anal combinatory approaches [11/24 vs 21/24, fixed model: OR 0.12 (95% CI: 0.03-0.52), P0.01)].With combination of oral and anal approaches, the yield of DBE might be at least as high as that of CE. Decisions made regarding the initial approach should depend on patient's physical status, technology availability, patient's preferences, and potential for therapeutic endoscopy.

To investigate whether Epigallocatechin-3-gallate (EGCG) can induce apoptosis of the gastric cancer cell line MKN45 and its apoptotic pathway.To determine this, apoptotic rates of MKN45 cells after EGCG treatment with or without caspase-3 inhibitor were evaluated by Annexin V-FITC + PI staining The influence of EGCG on the activity of caspase-3 in the MKN45 cells was determined by ELISA. By Rhodamine123 staining, the membrane potential change of the mitochondrion was also investigated, and mRNAs and protein expression of the bcl-2 family were analyzed by RT-PCR and Western blot.EGCG can induce apoptosis of MKN45 cells in time- and dose-dependent manner. Eight hours after EGCG treatment, the activity of caspase-3 in the MKN45 increased, especially 12 h after treatment. The mitochondrial membrane potential was significantly weakened 4 h after EGCG insult. The mRNA and protein expression levels of pro-apoptotic members, such as Bax, Bid and Bad, were upregulated gradually as treated time increased. Moreover, the mRNA and protein expression levels of anti-apoptotic members, such as Bcl-xL and Bcl-2, were inhibited.These data support that EGCG can induce apoptosis of the human gastric cancer cell line MKN45, and the effect is in a time- and dose-dependent manner. The apoptotic pathway triggered by EGCG in MKN45 is mitochondrial-dependent.