[Effect of recombinant human thrombin for hemostasis in liver resection: a randomized controlled phase â ¢ clinical trial].

Objective: To evaluate the hemostatic efficacy, safety and immunogenicity of recombinant human thrombin in the treatment of liver wounds that still ooze after conventional surgical hemostasis. Methods: A multicenter, stratified randomized, double-blind, placebo-controlled phase Ⅲ trial with a planned enrollment of 510 subjects at 33 centers, with a 2∶1 randomization to the thrombin group versus the placebo group. An interim analysis will be conducted after approximately 70% of the subjects have completed the observation period. The primary efficacy endpoint was the rate of hemostasis within 6 minutes at the point of bleeding that could be evaluated. Safety analysis was performed one month after surgery, and the positive rates of anti-drug antibody (ADA) and neutralizing antibody were evaluated. Results: At the interim analysis, a total of 348 subjects had been randomized and received the study drug (215 were male and 133 were female). They were aged 19-69 (52.9±10.9)years. Among them, 232 were in the thrombin group and 116 were in the placebo group, with balanced and comparable demographics and baseline characteristics between the two groups. The hemostasis rate at 6 minutes was 71.6% (95%CI:65.75%-77.36%) in the thrombin group and 44.0% (95%CI: 34.93%-53.00%) in the placebo group, respectively (P<0.001). No grade≥3 drug-related adverse events and no drug-related deaths were reported from the study.No recombinant human thrombin-induced immunologically-enhanced ADA or immunologically-induced ADA was detected after topical use in subjects. Conclusion: Recombinant human thrombin has shown significant hemostatic efficacy and good safety in controlling bleeding during liver resection surgery, while also demonstrating low immunogenicity characteristics.

Consensus recommendations for the screening, diagnosis, and management of Helicobacter pylori infection in Hong Kong.

Helicobacter pylori infection causes chronic gastric inflammation that contributes to various gastroduodenal diseases, including peptic ulcer and gastric cancer. Despite broad regional variations, the prevalence of resistance to antibiotics used to manage H pylori infection is increasing worldwide; this trend could hinder the success of eradication therapy. To increase awareness of H pylori and improve the diagnosis and treatment of its infection in Hong Kong, our consensus panel proposed a set of guidance statements for disease management. We conducted a comprehensive review of literature published during 2011 and 2021, with a focus on articles from Hong Kong or other regions of China. We evaluated the evidence using the Oxford Centre for Evidence-Based Medicine's 2011 Levels of Evidence and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system and sought consensus through online voting and a subsequent face-to-face meeting, which enabled us to develop and refine the guidance statements. This report consists of 24 statements regarding the epidemiology and burden, screening and diagnosis, and treatment of H pylori. Key guidance statements include a recommendation to use the test-and-treat approach for high-risk individuals, as well as the confirmation that triple therapy with a proton pump inhibitor, amoxicillin, and clarithromycin remains a valid first-line option for adults and children in Hong Kong.

Circular RNA circCRIM1 suppresses lung adenocarcinoma cell migration, invasion, EMT, and glycolysis through regulating miR-125b-5p/BTG2 axis.

The article "Circular RNA circCRIM1 suppresses lung adenocarcinoma cell migration, invasion, EMT, and glycolysis through regulating miR-125b-5p/BTG2 axis, by S.-J. Zhang, J. Ma, J.-C. Wu, Z.-Z. Hao, Y.-A. Zhang, Y.-J. Zhang, published in Eur Rev Med Pharmacol Sci 2020; 24 (7): 3761-3774-DOI: 10.26355/eurrev_202004_20841-PMID: 32329853" has been withdrawn from the authors due to some technical reasons. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/20841.

CircRNA EPB41L2 inhibits tumorigenicity of lung adenocarcinoma through regulating CDH4 by miR-211-5p.

The article "CircRNA EPB41L2 inhibits tumorigenicity of lung adenocarcinoma through regulating CDH4 by miR-211-5p, by S.-J. Zhang, J. Ma, J.-C. Wu, Z.-Z. Hao, Y.-N. Zhang, Y.-J. Zhang, published in Eur Rev Med Pharmacol Sci 2020; 24 (7): 3749-3760-DOI: 10.26355/eurrev_202004_20839-PMID: 32329852" has been withdrawn from the authors due to inaccuracies and mistakes. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/20839.

CircRNA EPB41L2 inhibits tumorigenicity of lung adenocarcinoma through regulating CDH4 by miR-211-5p.

OBJECTIVE: Circular RNAs (circRNAs) can make contributions to cell proliferation, migration and invasion in lung adenocarcinoma (LUAD). Circ_Band 4.1-like protein 2 (circ_EPB41L2) was found to have anti-tumor roles in lung cancer. Herein, we investigated the roles of circ_EPB41L2 in LUAD tumorigenicity. PATIENTS AND METHODS: The expression of circ_EPB41L2, microRNA (miR)-211-5p, and Cadherin-4 (CDH4) was measured using quantitative real-time polymerase chain reaction. Western blot was used to detect the levels of CDH4, Ki67, and E-cadherin. Cell proliferation, migration and invasion were examined using 3-(4,5)-dimethylthiazol(-z-y1)-3,5-di-phenyltetrazoliumbromide (MTT) assay and transwell assay, respectively. The interaction between miR-211-5p and circ_EPB41L2 or CDH4 was confirmed by Dual-Luciferase reporter assay. In vivo experiments were conducted using the murine xenograft model. RESULTS: Circ_EPB41L2 and CDH4 were down-regulated in LUAD tissues and cell lines. Overexpressed circ_EPB41L2 or CDH4 acted as a suppressor in the LUAD cell proliferation, invasion and migration in vitro. MiR-211-5p directly bound to circRNA_EPB41L2 and CDH4 3'-UTR, and circ_EPB41L2 indirectly regulated CDH4 expression by binding to miR-211-5p in LUAD cells. Furthermore, rescue assay showed circ_EPB41L2 played a protective role by repressing proliferation, migration and invasion through regulating CDH4 and miR-211-5p in LUAD cells. Besides, in vivo experiments indicated circ_EPB41L2 overexpression also inhibited tumor growth through regulating miR-211-5p and CDH4. CONCLUSIONS: Circ_EPB41L2 functioned as a tumor suppressor to inhibit the proliferation, migration and invasion through regulating CDH4 by miR-211-5p in LUAD cells, suggesting a new understanding on the tumorigenesis of LUAD and novel molecular therapeutic targets.

Circular RNA circCRIM1 suppresses lung adenocarcinoma cell migration, invasion, EMT, and glycolysis through regulating miR-125b-5p/BTG2 axis.

OBJECTIVE: The present studies indicate that circRNAs play pivotal roles in human cancers. Lung adenocarcinoma (LUAC), one of lung cancer types, has high metastasis rate. Herein, we focused our study on the function and mechanism of circular RNA circCRIM1 in LUAC development. PATIENTS AND METHODS: Quantitative Real-time polymerase chain reaction (qRT-PCR) was performed to detect the levels of circCRIM1, miR-125b-5p, and BTG anti-proliferation factor 2 (BTG2). Transwell assay was carried out to assess cell migration and invasion. The protein levels of BTG2, EMT markers, and HK2 were measured by Western blot. Glycolysis was analyzed through determining glucose consumption and lactate production. Furthermore, the targets of circCRIM1 and miR-125b-5p were predicted and verified by starBase and the dual-luciferase reporter assay, respectively. Also, whether circCRIM1 affecting tumor growth in vivo was explored using mouse xenograft assay. RESULTS: CircCRIM1 and BTG2 were downregulated, and miR-125b-5p was upregulated in LUAC tissues/cells. CircCRIM1 upregulation inhibited LUAC cell migration, invasion, epithelial-mesenchymal transition (EMT), glycolysis, and tumor growth. Moreover, circCRIM1 regulated LUAC cell development through targeting miR-125b-5p. MiR-125b-5p affected LUAC cell growth via binding to BTG2. Also, circCRIM1 promoted BTG2 expression by inhibiting miR-125b-5p expression in LUAC cells. CONCLUSIONS: CircCRIM1 was lowly expressed in LUAC. Moreover, circCRIM1 functioned as a sponge of miR-125b-5p to improve BTG2 expression, thereby suppressing LUAC development. Our finding indicated that circCRIM1 could be considered as a biomarker and target for the diagnosis and therapy of LUAC patients.

Faecal microbiota transplantation for treatment of recurrent or refractory Clostridioides difficile infection in Hong Kong.

INTRODUCTION: Clostridioides difficile infection (CDI) is a leading cause of healthcare-associated infection globally, causing significant morbidity and mortality. Faecal microbiota transplantation (FMT) has emerged as a promising option for recurrent and refractory CDI. This study aimed to assess the safety, efficacy, and feasibility of FMT for CDI in Hong Kong. METHODS: We conducted a single-centre, retrospective study for all consecutive cases of recurrent or refractory CDI who underwent FMT from 2013 to 2018. Clinical demographics, outcome, and safety parameters were collected. RESULTS: A total of 24 patients with recurrent or refractory CDI (median age 70 years, interquartile range=45.0-78.3 years; 67% male) were included. Over 80% had been recently hospitalised or were long-term care facility residents. Faecal microbiota transplantation was delivered by feeding tube in 11 (45.8%), oesophagogastroduodenoscopy in eight (33.3%), and colonoscopy in six (25%) of the patients. Resolution of diarrhoea without relapse within 8 weeks was achieved in 21 out of 24 patients (87.5%) after FMT. No deaths occurred within 30 days. The FMT was well tolerated and no serious adverse events attributable to FMT were reported. CONCLUSION: Our results confirm that FMT is a safe, efficacious, and feasible intervention for patients with refractory or recurrent CDI in Hong Kong. Given the increasing disease burden and the lack of effective alternatives in Hong Kong for difficult-to-treat cases of CDI, we recommend that a territory-wide FMT service be established to address increasing demand for this treatment.

Universal intracellular biomolecule delivery with precise dosage control.

Intracellular delivery of mRNA, DNA, and other large macromolecules into cells plays an essential role in an array of biological research and clinical therapies. However, current methods yield a wide variation in the amount of material delivered, as well as limitations on the cell types and cargoes possible. Here, we demonstrate quantitatively controlled delivery into a range of primary cells and cell lines with a tight dosage distribution using a nanostraw-electroporation system (NES). In NES, cells are cultured onto track-etched membranes with protruding nanostraws that connect to the fluidic environment beneath the membrane. The tight cell-nanostraw interface focuses applied electric fields to the cell membrane, enabling low-voltage and nondamaging local poration of the cell membrane. Concurrently, the field electrophoretically injects biomolecular cargoes through the nanostraws and into the cell at the same location. We show that the amount of material delivered is precisely controlled by the applied voltage, delivery duration, and reagent concentration. NES is highly effective even for primary cell types or different cell densities, is largely cargo agnostic, and can simultaneously deliver specific ratios of different molecules. Using a simple cell culture well format, the NES delivers into >100,000 cells within 20 s with >95% cell viability, enabling facile, dosage-controlled intracellular delivery for a wide variety of biological applications.

Protein kinase C -activating isophthalate derivatives mitigate Alzheimer's disease-related cellular alterations.

Abnormal protein kinase C (PKC) function contributes to many pathophysiological processes relevant for Alzheimer's disease (AD), such as amyloid precursor protein (APP) processing. Phorbol esters and other PKC activators have been demonstrated to enhance the secretion of soluble APPα (sAPPα), reduce the levels of ß-amyloid (Aß), induce synaptogenesis, and promote neuroprotection. We have previously described isophthalate derivatives as a structurally simple family of PKC activators. Here, we characterised the effects of isophthalate derivatives HMI-1a3 and HMI-1b11 on neuronal viability, neuroinflammatory response, processing of APP and dendritic spine density and morphology in in vitro. HMI-1a3 increased the viability of embryonic primary cortical neurons and decreased the production of the pro-inflammatory mediator TNFα, but not that of nitric oxide, in mouse neuron-BV2 microglia co-cultures upon LPS- and IFN-γ-induced neuroinflammation. Furthermore, both HMI-1a3 and HMI-1b11 increased the levels of sAPPα relative to total sAPP and the ratio of Aß42/Aß40 in human SH-SY5Y neuroblastoma cells. Finally, bryostatin-1, but not HMI-1a3, increased the number of mushroom spines in proportion to total spine density in mature mouse hippocampal neuron cultures. These results suggest that the PKC activator HMI-1a3 exerts neuroprotective functions in the in vitro models relevant for AD by reducing the production of TNFα and increasing the secretion of neuroprotective sAPPα.

Long noncoding RNA RUSC1-AS-N indicates poor prognosis and increases cell viability in hepatocellular carcinoma.

OBJECTIVE: This study aimed at exploring the expression and prognostic values of a novel long noncoding RNA RUSC1-AS-N in hepatocellular carcinoma (HCC), and to investigate the biological roles of RUSC1-AS-N in HCC cells. PATIENTS AND METHODS: RUSC1-AS-N expression in public available microarray data was analyzed. The expression of RUSC1-AS-N in our cohort containing 66 HCC tissues and paired adjacent non-cancerous hepatic tissues was measured by qRT-PCR. The correlation between RUSC1-AS-N expression and clinicopathological characteristics was evaluated by Pearson χ2-test. The prognostic value of RUSC1-AS-N was analyzed by Kaplan-Meier survival analysis. The biological roles of RUSC1-AS-N on HCC cell viability were evaluated by Glo cell viability assays and Ethynyl deoxyuridine incorporation assays. The effects of RUSC1-AS-N on HCC cell cycle were evaluated by fluorescence-activated cell sorting (FACS) analyses of propidium-iodide (PI) stained cells. The effects of RUSC1-AS-N on HCC cell apoptosis were evaluated by TdT-mediated dUTP nick end-labeling (TUNEL) assays. RESULTS: RUSC1-AS-N is upregulated in HCC tissues and associated with poor prognosis of HCC patients from GSE54238 and GSE40144. In our cohort, we further confirmed the upregulation of RUSC1-AS-N in HCC tissues. High expression of RUSC1-AS-N associates with large tumor size, vein invasion, encapsulation incompletion, advanced BCLC stage, and poor recurrence-free survival and overall survival. Functional assays revealed that RUSC1-AS-N knockdown markedly decreases cell viability, induces cell-cycle arrest and apoptosis of HCC cells. CONCLUSIONS: RUSC1-AS-N is upregulated and acts as an oncogene in HCC. RUSC1-AS-N may be a promising prognostic biomarker and therapeutic target for HCC.

Association between TXNRD1 polymorphisms and anti-tuberculosis drug-induced hepatotoxicity in a prospective study.

Anti-tuberculosis drug-induced hepatotoxicity (ATDH) is a serious adverse reaction to anti-tuberculosis (TB) treatment. Thioredoxin reductase 1 (TXNRD1), encoded by the TXNRD1 gene, is an important enzyme involved in oxidant challenge. TXNRD1 plays a key role in regulating cell growth and transformation, and protects cells against oxidative damage. We investigated the association between TXNRD1 polymorphisms and ATDH susceptibility. In this prospective study, 280 newly diagnosed TB patients were followed-up for 3 months after beginning anti-TB therapy. Tag single-nucleotide polymorphisms (tag-SNPs) of TXNRD1 were selected using Haploview 4.2 based on the HapMap database of the Chinese Han in Beijing (CHB) panel. Genotyping was performed using the MassARRAY platform. Of the 280 patients enrolled in this study, 33 were lost to follow-up, 24 had ATDH, and 223 were free from ATDH. After adjusting for sex, age, smoking status, and body mass index, there were no significant differences in the allele and genotype frequency distributions of TXNRD1 SNPs between the ATDH and non-ATDH groups (all P > 0.05). The haplotype analysis showed that haplotype TCAGCC was associated with an increased risk of ATDH susceptibility [P = 0.024, OR (95%CI) = 6.273 (1.023-38.485)]. Further stratified analyses showed that the haplotype TCAGCC was associated with ATDH susceptibility in female subjects [P = 0.036, OR (95%CI) = 5.711 (0.917-35.560)] and non-smokers [P = 0.029, OR (95%CI) = 6.008 (0.971-37.158)]. Our results suggest that TXNRD1 variants may favor ATDH susceptibility in females and non-smokers. Further studies are required to verify this association.

Systematic review with meta-analysis: faecal occult blood tests show lower colorectal cancer detection rates in the proximal colon in colonoscopy-verified diagnostic studies.

BACKGROUND: The performance of faecal occult blood tests (FOBTs) to screen proximally located colorectal cancer (CRC) has produced inconsistent results. AIM: To assess in a meta-analysis, the diagnostic accuracy of FOBTs for relative detection of CRC according to anatomical location of CRC. METHODS: Diagnostic studies including both symptomatic and asymptomatic cohorts assessing performance of FOBTs for CRC were searched from MEDINE and EMBASE. Primary outcome was accuracy of FOBTs according to the anatomical location of CRC. Bivariate random-effects model was used. Subgroup analyses were performed to evaluate test performance of guaiac-based FOBT (gFOBT) and immunochemical-based FOBT (iFOBT). RESULTS: Thirteen studies, with 17 cohorts, reporting performance of FOBT were included; a total of 26 342 patients (mean age 58.9 years; 58.1% male) underwent both colonoscopy and FOBT. Pooled sensitivity, specificity, positive likelihood ratio and negative likelihood ratio of FOBTs for CRC detection in the proximal colon were 71.2% (95% CI 61.3-79.4%), 93.6% (95% CI 90.7-95.7%), 11.1 (95% CI 7.8-15.8) and 0.3 (95% CI 0.2-0.4) respectively. Corresponding findings for CRC detection in distal colon were 80.1% (95% CI 70.9-87.0%), 93.6% (95% CI 90.7-95.7%), 12.6 (95% CI 8.8-18.1) and 0.2 (95% CI 0.1-0.3). The area-under-curve for FOBT detection for proximal and distal CRC were 90% vs. 94% (P = 0.0143). Both gFOBT and iFOBT showed significantly lower sensitivity but comparable specificity for the detection of proximally located CRC compared with distal CRC. CONCLUSION: Faecal occult blood tests, both guaiac- and immunochemical-based, show better diagnostic performance for the relative detection of colorectal cancer in the distal colon than in the proximal bowel.

Phytoremediation of soils contaminated with phenanthrene and cadmium by growing willow (Salix × aureo-pendula CL 'j1011').

To assess the phytoremediation potential of an autochthonous willow (Salix × aureo-pendula CL 'J1011') for phenanthrene (PHE)-contaminated soils and PHE-cadmium (PHE-Cd) co-contaminated soils, we conducted field experiments in the lower reaches of the Yangtze River, China. Ethylenediaminetetraacetic acid (EDTA) and ethyl lactate were tested for individual and combined effects on the phytoremediation efficiency. For PHE-contaminated soils, willow plus ethyl lactate resulted in significant removal of PHE from soils after 45 days, and the PHE concentration in the shoots was significantly higher with than without ethyl lactate. For PHE-Cd co-contaminated soils, both willow plus EDTA and willow plus EDTA and ethyl lactate led to a significant decrease in the concentrations of PHE and Cd in the soils after 45 days, whereas willow alone did not. The PHE and Cd concentrations in the willow shoots were significantly enhanced in the presence of EDTA alone and with ethyl lactate, except for the PHE concentration in stems with EDTA alone. Under the same treatment, the presence of Cd had no significant influence on the PHE removal from soils. The results indicate the feasibility of using this willow together with both EDTA and ethyl lactate for the simultaneous removal of PHE and Cd from soils.

Control of Immune Response to Allogeneic Embryonic Stem Cells by CD3 Antibody-Mediated Operational Tolerance Induction.

Implantation of embryonic stem cells (ESCs) and their differentiated derivatives into allogeneic hosts triggers an immune response that represents a hurdle to clinical application. We established in autoimmunity and in transplantation that CD3 antibody therapy induces a state of immune tolerance. Promising results have been obtained with CD3 antibodies in the clinic. In this study, we tested whether this strategy can prolong the survival of undifferentiated ESCs and their differentiated derivatives in histoincompatible hosts. Recipients of either mouse ESC-derived embryoid bodies (EBs) or cardiac progenitors received a single short tolerogenic regimen of CD3 antibody. In immunocompetent mice, allogeneic EBs and cardiac progenitors were rejected within 20-25 days. Recipients treated with CD3 antibody showed long-term survival of implanted cardiac progenitors or EBs. In due course, EBs became teratomas, the growth of which was self-limited. Regulatory CD4(+)FoxP3(+) T cells and signaling through the PD1/PDL1 pathway played key roles in the CD3 antibody therapeutic effect. Gene profiling emphasized the importance of TGF-ß and the inhibitory T cell coreceptor Tim3 to the observed effect. These results demonstrate that CD3 antibody administered alone promotes prolonged survival of allogeneic ESC derivatives and thus could prove useful for enhancing cell engraftment in the absence of chronic immunosuppression.

Characteristics of Small Intestinal Diseases on Single-Balloon Enteroscopy: A Single-Center Study Conducted Over 6 Years in China.

The small intestine has been considered inaccessible for a long term. The development of single-balloon endoscopy has greatly improved the diagnosis and treatment possibilities for small intestinal diseases.In this study, we aimed to explore the demographic characteristics and small intestinal diseases of patients who underwent single-balloon enteroscopy between 2009 and 2014 at our endoscopy center. We determined the enteroscopic findings for each small intestinal disease and the most susceptible age groups.In total, 186 patients were included in the study. Their mean age was 45.87 ± 15.77 years. Patients who underwent single-balloon enteroscopy were found to have neoplasms (most common age group: 14-45 years, most common lesion location: jejunum), lymphoma (46-59 and 60-74 years, ileum), protuberant lesions (45-59 years, jejunum), inflammation (14-45 and 46-59 years, ileum), benign ulcers (14-45 years, jejunum), diverticulum (14-45 years, ileum), vascular malformations (60-74 years, jejunum), polyps (14-45 years, jejunum), Crohn's disease (14-45 years, jejunum), hookworm infection (14-45 years, jejunum), lipid pigmentation (14-45 and 46-59 years, jejunum), undetermined bleeding (46-59 years, ileum), or undetermined stenosis (31 years, duodenum). Each small intestinal disease had distinct enteroscopic findings.

DRAM1 regulates apoptosis through increasing protein levels and lysosomal localization of BAX.

DRAM1 (DNA damage-regulated autophagy modulator 1) is a TP53 target gene that modulates autophagy and apoptosis. We previously found that DRAM1 increased autophagy flux by promoting lysosomal acidification and protease activation. However, the molecular mechanisms by which DRAM1 regulates apoptosis are not clearly defined. Here we report a novel pathway by which DRAM1 regulates apoptosis involving BAX and lysosomes. A549 or HeLa cells were treated with the mitochondrial complex II inhibitor, 3-nitropropionic acid (3NP), or an anticancer drug, doxorubicin. Changes in the protein and mRNA levels of BAX and DRAM1 and the role of DRAM1 in BAX induction were determined. The interaction between DRAM1 and BAX and its effect on BAX degradation, BAX lysosomal localization, the release of cathepsin B and cytochrome c by BAX and the role of BAX in 3NP- or doxorubicin-induced cell death were studied. The results showed that BAX, a proapoptotic protein, was induced by DRAM1 in a transcription-independent manner. BAX was degraded by autophagy under basal conditions; however, its degradation was inhibited when DRAM1 expression was induced. There was a protein interaction between DRAM1 and BAX and this interaction prolonged the half-life of BAX. Furthermore, upregulated DRAM1 recruited BAX to lysosomes, leading to the release of lysosomal cathepsin B and cleavage of BID (BH3-interacting domain death agonist). BAX mediated the release of mitochondrial cytochrome c, activation of caspase-3 and cell death partially through the lysosome-cathepsin B-tBid pathway. These results indicate that DRAM1 regulates apoptosis by inhibiting BAX degradation. In addition to mitochondria, lysosomes may also be involved in BAX-initiated apoptosis.

Association between serrated polyps and the risk of synchronous advanced colorectal neoplasia in average-risk individuals.

BACKGROUND: Serrated polyps of the colorectum have distinct histological features and malignant potential. AIM: To assess the association between the presence of serrated polyps and synchronous advanced colorectal neoplasia. METHODS: Among 4989 asymptomatic Chinese individuals aged 50-70 years who underwent screening colonoscopy, 281 cases with advanced neoplasia (adenoma ≥1 cm, with tubulovillous/villous histology, with high-grade dysplasia, or invasive adenocarcinoma) were compared with 4708 controls without advanced neoplasia for age, sex, smoking history, body mass index, family history of colorectal cancer and the presence of serrated polyps. Independent predictors of advanced neoplasia were determined by multivariate logistic regression analysis. RESULTS: The prevalence of advanced neoplasia and serrated polyps (excluding small distal hyperplastic polyps) was 5.7% and 5.6%, respectively. 3.7% and 0.4% subjects had proximal and large (≥10 mm) serrated polyps, respectively. Independent predictors of synchronous advanced colorectal neoplasia were the presence of sessile serrated adenomas (OR: 4.52; 95% CI: 2.40-8.49), proximal serrated polyps (OR: 2.23, 95% CI: 1.38-3.60), large serrated polyps (OR: 59.25; 95% CI: 18.85-186.21), hyperplastic polyps (OR: 1.66; 95% CI: 1.03-2.67), three or more serrated polyps (OR: 4.86; 95% CI: 1.24-19.15) and one or more non-advanced tubular adenomas (OR: 3.58, 95% CI: 2.59-4.96). CONCLUSION: Detection of proximal, sessile and/or large serrated polyps at screening colonoscopy is independently associated with an increased risk for synchronous advanced neoplasia.

Diagnostic accuracy of faecal immunochemical test for screening individuals with a family history of colorectal cancer.

BACKGROUND: The role of a faecal immunochemical test (FIT) in screening individuals with a positive family history of colorectal cancer (CRC) is not clear. AIM: To assess the diagnostic accuracy of FIT using colonoscopy findings as the gold standard in identifying colorectal neoplasms. METHODS: We analysed data from 4539 asymptomatic subjects aged 50-70 years who had both colonoscopy and FIT (Hemosure; W.H.P.M., Inc, El Monte, CA, USA) at our bowel cancer screening centre between 2008 and 2012. A total of 572 subjects (12.6%) had a family history of CRC. Our primary outcome was the sensitivity of FIT in detecting advanced neoplasms and cancers in subjects with a family history of CRC. A family history of CRC was defined as any first-degree relative with a history of CRC. RESULTS: Among 572 subjects with a family history of CRC, adenoma, advanced neoplasm and cancer were found at screening colonoscopy in 29.4%, 6.5% and 0.7% individuals, respectively. The sensitivity of FIT in detecting adenoma, advanced neoplasm and cancer was 9.5% [95% confidence interval (CI), 5.7-15.3], 35.1% (95% CI, 20.7-52.6) and 25.0% (95% CI, 1.3-78.1), respectively. Among FIT-negative subjects who have a family history of CRC, adenoma was found in 152 (29.6%), advanced neoplasm in 24 (4.7%) and cancer in 3 (0.6%) individuals. CONCLUSION: Compared with colonoscopy, FIT is more likely to miss advanced neoplasms or cancers in individuals with a family history of CRC.

Systematic review: the efficacy of herbal therapy in inflammatory bowel disease.

BACKGROUND: Complementary and alternative medicine (CAM), particularly herbal therapy, is widely used by patients with inflammatory bowel disease (IBD) but controlled data are limited. AIM: To systematically review the literature on the efficacy of herbal therapy in the treatment of ulcerative colitis (UC) and Crohn's disease (CD). METHODS: Publications in English and non-English literatures (MEDLINE, EMBASE, EBM Reviews, AMED, Global Health) were searched from 1947 to 2013 for controlled clinical studies of herbal therapy in IBD. Outcome measures included response and remission rates. RESULTS: Twenty-one randomised controlled trials (14 UC; 7 CD) including a total of 1484 subjects (mean age 41, 50% female) were analysed. In UC, aloe vera gel, Triticum aestivum (wheat grass juice), Andrographis paniculata extract (HMPL-004) and topical Xilei-san were superior to placebo in inducing remission or response, and curcumin was superior to placebo in maintaining remission; Boswellia serrata gum resin and Plantago ovata seeds were as effective as mesalazine, whereas Oenothera biennis (evening primrose oil) had similar relapse rates as omega-3 fatty acids in the treatment of UC. In CD, Artemisia absinthium (wormwood) and Tripterygium wilfordii were superior to placebo in inducing remission, and preventing clinical recurrence of post-operative CD respectively. CONCLUSIONS: Randomised controlled trials of herbal therapy for the treatment of IBD show encouraging results but studies remain limited and heterogenous. Larger controlled studies with stricter endpoints and better-defined patient groups are required to obtain more conclusive results on the use of CAM therapies in IBD.

CD34+ stem cell therapy in nonischemic dilated cardiomyopathy patients.

Recent trends indicate that patients with nonischemic dilated cardiomyopathy represent the largest subpopulation of heart failure patients with a significant need for alternative treatment modalities. Similar to patients with ischemic cardiomyopathy, patients with nonischemic dilated cardiomyopathy have been found to have myocardial regions with flow abnormalities, which may represent targets for neoangiogenic therapies. CD34(+) stem cells might contribute to the formation of new blood vessels from existing vascular structures in ischemic tissues by the direct incorporation of injected cells into the newly developing vasculature or by the production and secretion of angiogenic cytokines. This review summarizes the long-term clinical effects and potential underlying mechanisms of CD34(+) cell therapy in patients with nonischemic dilated cardiomyopathy.