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BACKGROUND Co-morbidity of SRY gene turner syndrome (TS) with positive SRY gene and non-classical congenital adrenal hyperplasia (NCAH) is extremely rare and has never been reported to date. CASE SUMMARY In this article, we present a 14-year-old girl who was referred to our hospital with short stature (weight of 43 kg and height of 143 cm, < -2 SD) with no secondary sexual characteristics (labia minora dysplasia). Laboratory tests indicated hypergonadotropic hypogonadism with significantly increased androstenedione and 17-hydroxyprogesterone (17-OHP) levels. This was accompanied by the thickening of the extremity of the left adrenal medial limb. The patient’s karyotype was 45,X/46,X, +mar, and cytogenetic analysis using multiplex ligation-dependent probe amplification and high-throughput sequencing indicated that the SRY gene was positive with compound heterozygous mutations in CYP21A2 as the causative gene for congenital adrenal hyperplasia. The sites of the suspected candidate mutations were amplified and verified using Sanger sequencing. The patient was finally diagnosed as having SRY positive TS with NCAH. The patient and her family initially refused medical treatment. At her most recent follow-up visit (age = 15 years old), the patient presented facial hair, height increase to 148 cm, and weight of 52 kg, while androstenedione and 17-OHP levels remained high. The patient was finally willing to take small doses of hydrocortisone (10 mg/d). CONCLUSION In conclusion, upon evaluation of the patient mentioned in the report, we feel that 17-OHP measurement and cytogenetic analysis are necessary for TS patients even in the absence of significant virilization signs. This will play a significant role in guiding diagnosis and treatment.

Alpha-sheet is believed to be a significant structural compo-nent, formed in the fibrillation process of the amyloid pep-tide. However, the knowledge about the role of a-sheet played in the amyloidosis and toxicity is lack. In this work, we modi-fied a short peptide derived from the core region of human islet amyloid polypetide(hIAPP, hIAPP18–27) with an alternating D-amino acid replacement and investigated the effects of the L/D alternating peptide on the fibrillar aggregation and the membrane damage of hIAPP using NMR, ThT fluorescence assay, circular dichroism(CD), transmission electron microscopy(TEM) and leakage assay, and com-pared the results with those of hIAPP18–27 without D-amino acid re-placement. We show that the short peptide with alternating L- and D-amino acids forms an a-sheet structure and is more potent in pro-moting the fibrillation of hIAPP and reducing the ability of hIAPP to disrupt the membrane composed of POPG and POPC[1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-(1′-rac-glycerol) and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine] 1:4 lipids than the short pep-tide with all L-amino acids in a random coil structure. The higher po-tency of the D/L alternating peptide in these activities is attributed to its ability to induce the a-sheet-like structure in the core region of hIAPP and block the interaction of hIAPP with the membrane more effectively.

Background: Osteoporosis is the most common bone metabolic disease. Abnormal osteoclast formation and resorption play a fundamental role in osteoporosis pathogenesis. Recent researches have greatly broadened our understanding of molecular mechanisms of osteoporosis. However, the molecular mechanisms leading to osteoporosis are still not entirely clear. Objective: The purpose of this work is to study the critical regulatory genes, functional modules, and signaling pathways. Methods: Differential expression analysis, network topology-based analysis, and overrepresentation enrichment analysis (ORA) were used to identify differentially expressed genes (DEGs), gene subnetworks, and signaling pathways related to osteoporosis, respectively. Results: Differential expression analysis identified DEGs, such as POGLUT1, DAPK3 and NFKBIA, associated with osteoclastogenesis, which highlighted Notch, apoptosis and NF-kB signaling pathways. Network topology-based analysis identified the upregulated subnetwork characterized by EXOSC8 and DIS3L from the RNA exosome complex, and the downregulated subnetwork composed of histone deacetylases and the cofactors, MORF4L1 and JDP2. Furthermore, the overrepresentation enrichment analysis highlighted that corticotrophin-releasing hormone signaling pathway might affect osteoclastogenesis through its component NR4A1, and suppressing osteoclast differentiation and osteoclast bone resorption with urocortin (UCN). Conclusion: Our systematic analysis not only discovered novel molecular mechanisms but also proposed potential drug targets for osteoporosis.

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

The minimum resolution is one of the most important characteristics of human vision, during the flight of the aircraft, the pilot uses the head-up display(HUD) to observe and distinguish the information of the external scenery. Analyzing the impact of different transmittance HUD combiner under different environment brightness on the external resolution has important instruction and application value for aviation safety. The experiment uses the UASF1951 target plate and the transmittance of HUD combiners under two different environmental brightness. Record the minimum resolution angle and the difference between the two conditions. The result shows that, under the same brightness, the lower the contrast, the weaker the human eye can recognize; the minimum resolvability of the human eye is affected by contrast: when the brightness is lower, the lower the brightness, the higher the minimum contrast requirement for human eye to recognize objects. When the brightness is higher, the minimum contrast requirement for human eye to recognize objects does not change much with brightness, and after the brightness is increased to a certain range, the minimum contrast required by the human eye to recognize the object is almost unchanged. It can be seen that the resolution of the human eye is simultaneously affected by environmental brightness and contrast, and the experimental results basically conform to the Adrian’s Visual Acuity Model.

BackgroundOvarian cancer is a common gynecological disease and seriously endangers women's health. Currently, there is still a lack of effective molecular markers for the diagnosis and treatment of ovarian cancer. The present study aimed to investigate the molecular markers associated with ovarian cancer.MethodsThe molecular and gene related to ovarian cancer were extracted from GEO database and TCGA database by bioinformatics, and the related genes and functions were further analyzed. The results were verified by qPCR, WB, CCK-8 and Transwell experiments.ResultsData analysis showed that PTH2R gene was highly expressed in tumors, and 51 HUB genes were obtained. Finally, experimental verification showed that PTH2R gene was highly expressed in ovarian cancer, and PTH2R gene was involved in the proliferation, invasion and metastasis of ovarian cancer cells.ConclusionsAfter experimental verification, we found that knocking down the expression of PTH2R can inhibit the proliferation, invasion and migration of tumor cells.PTH2R is expected to become a new molecular marker for ovarian cancer.

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.

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.

A tricationic cage was synthesized via click chemistry. The cage has a preorganized cavity, which is surrounded by six relatively acidic C-H bonds. In organic solvent, the cage can recognize a variety of anions, among which the Cl

Abstract Dendritic cells (DCs) are the most powerful antigen-presenting cells known to date and play an important role in initiating and amplifying both innate and adaptive immune responses. Extracellular acidosis is an important hallmark of a variety of inflammatory processes and solid tumors. However, few studies have focused on the effect of extracellular acidosis on DCs and their functions. Cellular mechanical properties reflect the relationship between cell structure and function, including cytoskeleton (especially F-actin organization), membrane negative charges, membrane fluidity, and osmotic fragility. The study investigated the effects of extracellular acidosis on the DCs functions from the perspective of cellular migration and mechanical properties. The results showed that migration ability, F-actin contents, and membrane negative charges of DCs were reduced by extracellular acidosis no matter whether LPS stimulated its maturation or not. And these functions could not return to normal after removing acidic microenvironment, which revealed that the function impairment induced by extracellular acidosis might be irreversible. In addition, the proliferation capacity of stimulated allogeneic T cells was impaired by extracellular acidosis. Our results suggest extracellular acidosis may play an immunosuppressive role in DCs-mediated immune process.

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.

// Shaojun Chen 1 , Longsheng Wang 1 , Xudong Yao 1 , Hui Chen 2 , Chen Xu 1 , Lu Tong 2 , Abdussaboor Shah 2 , Tingmei Huang 2 , Geng Chen 2 , Jiwei Chen 2 , Tie-Long Liu 3 , Xiao-Tao Li 2, 4 , Jun-Hua Zheng 1 and Lei Li 2 1 Department of Urology, Shanghai Tenth People’s Hospital, Tongji University, Shanghai 200072, China 2 Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences, School of Life Sciences, East China Normal University, Shanghai 200241, China 3 Department of Orthopedic Oncology, Changzheng Hospital, The Second Military Medical University, Shanghai 200003, China 4 Department of Molecular and Cellular Biology, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas 77030, USA Correspondence to: Tie-Long Liu, email: czyyltl@163.com Xiao-Tao Li, email: xiaotaol@bcm.edu Jun-Hua Zheng, email: renalzjh@163.com Lei Li, email: lllkzj@163.com Keywords: miR-195-5p, REGγ, wnt/β-catenin, renal cell carcinoma Received: March 21, 2017 Accepted: June 12, 2017 Published: July 15, 2017 ABSTRACT Renal cell carcinoma (RCC) is the most prevalent malignancy of kidney and accounts for approximately 4% of all cancer diagnoses in adults. Previous studies demonstrated microRNA-195-5p (miR-195-5p) as a tumor suppressor which is deregulated in many human cancers. However, the role of miR-195-5p in RCC is largely unknown. In the present study, we demonstrated that miR-195-5p was downregulated and negatively correlated with advanced clinical stage in RCC. Overexpression of miR-195-5p significantly suppressed RCC cells growth in vitro and in vivo , induced apoptosis and enhanced chemosensitivity to sorafenib. Conversely, suppression of miR-195-5p exhibited a reverse effect. REGγ, a proteasome activator, was identified as a novel downstream target of miR-195-5p in RCC. Knockdown of REGγ inhibited proliferation, induced apoptosis, increased sorafenib chemosensitivity and suppressed the wnt/β-catenin pathway in RCC cells. Moreover, restoration of REGγ markedly abolished the effects of miR-195-5p in RCC, and the wnt/β-catenin pathway was suppressed by miR-195-5p overexpression while activated by miR-195-5p inhibition in RCC cells. Our findings suggest that miR-195-5p is critical in REGγ-mediated regulation of wnt/β-catenin pathway in RCC development and may serve as a novel target for RCC treatment.

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.

Objectives 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. Methods 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. Results 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). Conclusions 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.

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.

Supermolecular hydrogels were prepared by α-cyclodeatrin (α-CD) and Tyloxapol, which can be considered as an oligomer of the nonionic surfactant polyoxyethylene tert-octylphenyl ether (TX-100) with a polymerization degree below 7. Two carbon materials, graphene oxide (GO) and graphene, were mixed into the α-CD/Tyloxapol hydrogel to adjust the physicochemical properties of hydrogel. In order to get stable graphene dispersion and then mix it with α-CD/Tyloxapol hydrogel, both TX-100 and Tyloxapol were used to disperse graphene for comparison. Interestingly, it can be found that TX-100 could disperse graphene better than Tyloxapol owing to smaller molecular size of TX-100 compared with Tyloxapol. Then, both the α-CD/Tyloxapol/GO and α-CD/Tyloxapol/graphene hydrogels were characterized by transmission electron microscopy (TEM), field emission scanning electron microscopy (FE-SEM), Fourier transform infrared (FT-IR) spectroscopy, small angle X-ray scattering (SAXS), X-ray diffraction (XRD) and rheological measurements. The results revealed that the addition of carbon materials into α-CD/Tyloxapol hydrogel can change their microstructures and the rheological properties. Furthermore, it can be confirmed that a little amount of carbon materials could induce fluorescence quenching sharply which could be a promising candidate for optical sensor.

Along with epidemiological changes in tuberculosis (TB) and an increased incidence of Crohn's disease (CD), the differential diagnosis of intestinal TB (ITB) and CD is of vital importance and has become a clinical challenge because treatment based on misdiagnosis may lead to fatal outcomes. In this study, we reviewed the similarities and differences in clinical, endoscopic, radiological and histological features of these two diseases. Concomitant pulmonary TB, ascites, night sweats, involvement of fewer than four segments of the bowel, patulous ileocecal valve, transverse ulcers, scars or pseudopolyps strongly indicate ITB. Bloody stools, perianal signs, chronic diarrhea, extraintestinal manifestations, anorectal lesions, longitudinal ulcers and a cobblestone appearance are all suggestive of CD. Significant differences in the size, number, location and patterns of granulomas in ITB and CD with regard to their histopathologic features have been noted. Immune stain of cell surface markers is also helpful. Interferon-γ release assay and polymerase chain reaction analysis have achieved satisfactory sensitivity and specificity in the diagnosis of ITB. Computed tomography enterographic findings of segmental small bowel or left colon involvement, mural stratification, the comb sign and fibrofatty proliferation are significantly more common in CD, whereas mesenteric lymph node changes (calcification or central necrosis) and focal ileocecal lesions are more frequently seen in ITB. A diagnosis should be carefully established before the initiation of the therapy. In suspicious cases, short-term empirical anti-TB therapy is quite efficient to further confirm the diagnosis.

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.

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.

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.

Sleep quality has great effect on physical and mental health. Severe insomnia will cause autonomic neurological dysfunction. For making good clinical decisions, it is crucial to extract features of sleep quality and accurately predict the mental illness. Prior studies have a number of deficiencies to be overcome. On the one hand, the selected features for sleep quality are not good enough, as they do not account for multisource and heterogeneous features. On the other hand, the mental illness prediction model does not work well and thus needs to be enhanced and improved. This paper presents a multi-dimensional feature extraction method and an ensemble prediction model for mental illness. First, we do correlation analysis for every indicators and sleep quality, and further select the optimal heterogeneous features. Next, we propose a combinational model, which is integrated by basic modules according to their weights. Finally, we perform abundant experiments to test our method. Experimental results demonstrate that our approach outperforms many state-of-the-art approaches.

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.

The presence of nicotine and nicotinic acid (NA) in the marine environment has caused great harm to human health and the natural environment. Therefore, there is an urgent need to use efficient and economical methods to remove such pollutants from the environment. In this study, a nicotine and NA-degrading bacterium—strain JQ581—was isolated from sediment from the East China Sea and identified as a member of Pseudomonas putida based on morphology, physio-biochemical characteristics, and 16S rDNA gene analysis. The relationship between growth and nicotine/NA degradation suggested that strain JQ581 was a good candidate for applications in the bioaugmentation treatment of nicotine/NA contamination. The degradation intermediates of nicotine are pseudooxynicotine (PN) and 3-succinoyl-pyridine (SP) based on UV, high performance liquid chromatography, and liquid chromatography-mass spectrometry analyses. However, 6-hydroxy-3-succinoyl-pyridine (HSP) was not detected. NA degradation intermediates were identified as 6-hydroxynicotinic acid (6HNA). The whole genome of strain JQ581 was sequenced and analyzed. Genome sequence analysis revealed that strain JQ581 contained the gene clusters for nicotine and NA degradation. This is the first report where a marine-derived Pseudomonas strain had the ability to degrade nicotine and NA simultaneously.

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.

We isolated a bacterial strain JQ135 from municipal wastewater, which was capable of efficiently degrading picolinic acid (PA). Based on the physico-biochemical characteristics and 16S rDNA analysis, strain JQ135 was identified as Alcaligenes faecalis. In addition, strain JQ135 produced an orange pigment when cultured in the Luria-Bertani medium, which is different from the previously reported strains of A. faecalis. During the degradation of PA by the resting strain JQ135 cells, only one intermediate, 6-hydroxypicolinic acid (6HPA), was detected by ultraviolet spectrophotometry, high-pressure liquid chromatography, and liquid chromatography-mass spectrometry. A random transposon mutagenesis library of strain JQ135 was constructed. One mutant, Mut-G31, could convert PA into 6HPA without further degradation. The disrupted gene (orf2) was amplified from Mut-G31, and its product showed 32% identity to the 3-deoxy-D-manno-octulosonic acid kinase (KdkA) from Haemophilus influenzae. Results from complementation analysis confirmed that GTG was the initiation codon of the kdkA-like orf2, and that it was essential for PA biodegradation by strain JQ135. This study provides the first genetic evidence for the bacterial degradation of PA.

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

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.

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

OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

OBJECTIVE: To investigate the chemopreventive effect and mechanisms of epigallocatechin-3-gallate (EGCG) and folic acid on N-methyl-N′-nitro-N-nitrosoguanidine (MNNG)-induced gastrointestinal cancer in rats, and to investigate and compare the combinatorial effects of EGCG and folic acid on the chemoprevention of gastrointestinal carcinogenesis. METHODS: A total of 159 healthy male Wistar rats were randomly divided into seven groups to have the MNNG in drink (group M), MNNG in drink and EGCG in the feed (group ME), MNNG in drink and folic acid in the feed (group MF), MNNG in drink and EGCG + folic acid in the feed (group MEF), EGCG in the feed (group E), folic acid in the feed (group F) or normal feed (group C), respectively. At 44 weeks, all the rats were killed and assessed for the presence of gastrointestinal tumor. The occurrence of cancer was evaluated by histology. Ki-67 in cancerous tissues and in situ apoptosis were determined by immunohistochemical staining or terminal deoxyribonucleotide transferase-mediated nick-end labeling (TUNEL) assay, respectively. RESULTS: The experiment was completed in 157 rats (98.74%). As compared with group M, the tumor incidence of group MEF decreased significantly (P = 0.011). Ki-67 expression in cancerous tissues of group ME and MEF also decreased significantly (P = 0.038, P = 0.009), while apoptosis of group ME, MF and MEF increased significantly (P = 0.000, P = 0.003, P = 0.000). CONCLUSION: EGCG combined with folic acid has an obvious chemopreventive effect on gastrointestinal carcinogenesis induced by MNNG in rats.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

The effects of supplemental UV-B radiation on Taxus chinensis var. mairei were studied. Leaf traits, gas exchange parameters and the concentrations of photosynthetic pigments, cellular defense system products, secondary metabolites and ultrastructure were determined. UV-B radiation significantly decreased leaf area (p0.05). Leaf number, secondary branch number, leaf weight per plant and leaf moisture all increased dramatically (p0.05). Neither the leaf weight nor the specific leaf weight (SLW) exhibited significant differences between ambient and enhanced UV-B radiation. Gas exchange parameters were all dramatically reduced by enhanced UV-B radiation (p0.05). The contents of chlorophyll and the chlorophyll a/b ratio were not distinctly affected by UV-B radiation, while carotenoids content significantly decreased (p0.05). Supplemental UV-B treatment induced significant flavonoid accumulation (p0.05), which was able to protect plant from radiation damage. Meanwhile, the appendage content, abaxial stomatal density, papilla density and particulate matter content in substomatic chambers increased noticeably by supplemental UV-B radiation, whereas the aperture size of single stomata was diminished. The number and area of plastoglobuli were apparently reduced by UV-B radiation, but stroma and grana lamellae were not destroyed. Our results demonstrated that T. chinensis var. mairei can activate several defense mechanisms against oxidative stress injury caused by supplemental UV-B radiation.

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.

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.

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.

A needle-holding robot for microwave ablation therapy is developed to free two hands of the surgeon, so that more effort can be concentrated on monitoring the ablation procedure, which in turn guarantees good tumor ablation effect. The overall architecture of the robot is introduced first with the explanation of the mechanism of 3D motion tracking and how to minimize damping force for the robotic hand. Two experiments were conducted, one to quantify the force required for motion tracking, the other to assess the performance of motion tracking. The results of force-measuring experiment show that the force required for rotation and radial translation motion tracking are less than 15 grams, which indicates the high sensitivity of the holding robot. The results of in-vivo animal test performed on a swine show that the holding robot is accurate enough in tracking the 3D motion of the ablation needle, which allows for stable and precise holding of the needle compared to that of freehand holding.

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.

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.