Intelligent anti-impact elastomers by precisely tailoring the topology of modular polymer networks.

High-performance elastomers are essential in daily life and various industrial sectors such as personal protection, soft electronics, and vibration control. Nevertheless, despite massive efforts, concurrently achieving ultrahigh flexibility and remarkable impact resistance continues to be elusive. Herein, we report an innovative modular construction strategy that employs a topology-tailoring polymer network consisting of stereoscopic (epoxy-oligosiloxane nanoclusters) and linear (amino-terminated polyurea) building blocks as independent modules to develop intelligent anti-impact elastomers via an epoxy-amine mechanism. By precisely tailoring the topology of building blocks, the elastomers demonstrate high flexibility and toughness, remarkable impact responsiveness and ultrahigh energy dissipation. Their anti-impact ability surpasses those of most common soft and rigid materials such as steel, plastic, rubber, foam, or even polyborosiloxane. Moreover, the elastomers are well-qualified for use in flexible display technologies, owing to their high transparency (>92% transmittance), exceptional fold-resistance (no creasing after 10 000 bends), and good thermal stability (no discoloration at 100 °C). Furthermore, the elastomers exhibit excellent versatility, enabling them to be combined with either soft or rigid materials to generate composites with ultrahigh puncture and ballistic resistance. This study offers a promising framework for the design and fabrication of intelligent anti-impact elastomers and provides valuable insights into the development of next-generation protective materials.

Creation of an Inflammatory Bowel Disease Referral Pathway for Identifying Patients Who Would Benefit From Inflammatory Bowel Disease Specialist Consultation.

BACKGROUND: Recommendations regarding signs and symptoms that should prompt referral of patients with inflammatory bowel disease (IBD) to an IBD specialist for a consultation could serve to improve the quality of care for these patients. Our aim was to develop a consult care pathway consisting of clinical features related to IBD that should prompt appropriate consultation. METHODS: A scoping literature review was performed to identify clinical features that should prompt consultation with an IBD specialist. A panel of 11 experts was convened over 4 meetings to develop a consult care pathway using the RAND/UCLA Appropriateness Method. Items identified via scoping review were ranked and were divided into major and minor criteria. Additionally, a literature and panel review was conducted assessing potential barriers and facilitators to implementing the consult care pathway. RESULTS: Of 43 features assessed, 13 were included in the care pathway as major criteria and 15 were included as minor criteria. Experts agreed that stratification into major criteria and minor criteria was appropriate and that 1 major or 2 or more minor criteria should be required to consider consultation. The greatest barrier to implementation was considered to be organizational resource allocation, while endorsements by national gastroenterology and general medicine societies were considered to be the strongest facilitator. CONCLUSIONS: This novel referral care pathway identifies key criteria that could be used to triage patients with IBD who would benefit from IBD specialist consultation. Future research will be required to validate these findings and assess the impact of implementing this pathway in routine IBD-related care.

This study aimed to develop a care pathway consisting of clinical features that should prompt inflammatory bowel disease expert consultation. A scoping literature review was performed to identify attributes, and an expert panel finalized the structure and components of the pathway.

Study on the uranium (U(⠥)) adsorption stability of high-dose γ-ray-irradiated clay.

The Alxa region (Inner Mongolia, China) is one of the areas preselected for use as a geological repository of high-level radioactive waste in China. Radioactive waste produces radioactive rays during long-term storage, and the cumulative absorbed dose in 1000 years can significantly exceed the maximum of 0.7 MGy, thereby challenging the long-term adsorption stability of clay. This study employed 60Co gamma (γ)-rays to irradiate clay in air under a dose rate of 10 kGy/h. The changes in the internal structure and mechanisms of clay under different gamma radiation doses (1, 2, and 3 MGy) were investigated. Additionally, the adsorption properties of irradiated clay for U(Ⅵ) were tested under different conditions. The clay samples underwent minimal structural changes following high-dose irradiation, and the interlayer spacing was altered due to the fractured framework, dehydroxylation, and radiolysis of water. After irradiation, the Fe (Ⅱ) content in clay was significantly increased, unlike Fe (Ⅲ) content. The adsorption mechanisms of clay before and after the experiments were verified, revealing that the adsorption capacity of irradiated clay to U(Ⅵ) is reduced.

The transcription factor AtGLK1 acts upstream of MYBL2 to genetically regulate sucrose-induced anthocyanin biosynthesis in Arabidopsis.

BACKGROUND: The regulation of anthocyanin biosynthesis by various factors including sugars, light and abiotic stresses is mediated by numerous regulatory factors acting at the transcriptional level. Here experimental evidence was provided in order to demonstrate that the nuclear GARP transcription factor AtGLK1 plays an important role in regulating sucrose-induced anthocyanin biosynthesis in Arabidopsis. RESULTS: The results obtained using real-time quantitative PCR and GUS staining assays revealed that AtGLK1 was mainly expressed in the green tissues of Arabidopsis seedlings and could be induced by sucrose. The loss-of-function glk1 glk2 double mutant has lower anthocyanin levels than the glk2 single mutant, although it has been determined that loss of AtGLK1 alone does not affect anthocyanin accumulation. Overexpression of AtGLK1 enhances the accumulation of anthocyanin in transgenic Arabidopsis seedlings accompanied by increased expression of anthocyanin biosynthetic and regulatory genes. Moreover, we found that AtGLK1 also participates in plastid-signaling mediated anthocyanin accumulations. Genetic, physiological, and molecular biological approaches demonstrated that AtGLK1 acts upstream of MYBL2, which is a key negative regulator of anthocyanin biosynthesis, to genetically regulate sucrose-induced anthocyanin biosynthesis. CONCLUSION: Our results indicated that AtGLK1 positively regulates sucrose-induced anthocyanin biosynthesis in Arabidopsis via MYBL2.

Fe-TCPP@CS nanoparticles as photodynamic and photothermal agents for efficient antimicrobial therapy.

Traditional antimicrobial therapies always rely on antibiotics, which have led to the overuse of antibiotics and caused the emergence of multidrug-resistant (MDR) bacteria in recent years. In this study, an efficient and broad-spectrum antimicrobial system based on chitosan (CS)-encapsulated multifunctional metal-organic nanoparticles (Fe-TCPP@CS NPs) was constructed to integrate the electrostatic targeting property and photodynamic and photothermal antimicrobial therapies. Tetrakis (4-carboxyphenyl) porphyrin (TCPP) coordinated with Fe3O clusters to form nanoparticles, Fe3O clusters enabled low-temperature photothermal therapy as well as avoiding the porphyrins self-aggregation to ensure the singlet oxygen yield under irradiation, and CS as the outer layer covered on Fe-TCPP nanoparticles could improve the dispersibility in aqueous solution and enhance the electrostatic binding with bacterial cell membranes to improve the antibacterial activities. After simple synthesis, we successfully obtained ideal and biocompatible multifunctional nanoparticles and verified their antimicrobial properties. Under light irradiation, Fe-TCPP@CS NPs could produce enough ROS and heat to kill S. aureus, E. coli and methicillin-resistant S. aureus with a synergistic effect. Therefore, Fe-TCPP@CS NPs would be an efficient and broad-spectrum antimicrobial agent, providing a novel approach to bacterial infection therapy.

Sucrose transportation control mediates the fresh-keeping effects of burdock fructooligosaccharide in 'Crimson Seedless' grapes.

In 'Crimson Seedless' grapes, the appearance of senescence caused by abnormal dark red color, the loss of crisp taste caused by the decrease in firmness, and the fading of sweetness caused by the decrease in total soluble sugar (TSS) are the main problems affecting its edible qualities after storage. In the mesocarp, burdock fructooligosaccharide (BFO) restricted sucrose export; therefore, more carbohydrates were retained directly leading to higher TSS and sweetness, and cell osmotic pressure and firmness were retained indirectly. In the exocarp, BFO restricted sucrose import; therefore, the signal molecule sucrose was reduced and the senescence-related processes were inhibited. The downregulation of SUC12 and SUC27 by BFO may play an important role in restricting sucrose transportation. The opposing effects exhibited by exogenous sucrose treatments compared to those of BFO further verified these mechanisms. Based on the above mechanisms, sucrose transportation mediates the fresh-keeping effects of BFO in 'Crimson Seedless' grapes.

Thyroid antibody status exerts insignificant effect on lymph node metastasis of thyroid cancer.

BACKGROUND: To investigate whether high thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb) levels are associated with increased risk of lymph node metastasis (LNM) of thyroid cancer. METHODS: Data of 2,352 patients who committed thyroidectomy from January 2018 to December 2018 at our institution were retrospectively reviewed. Of which, 806 patients diagnosed with thyroid cancer with available data of both TPOAb and TgAb were finally included, and were divided into four groups: (I) TPOAb-/TgAb- (control, n=493), (II) TPOAb+/TgAb- (n=96), (III) TPOAb-/TgAb+ (n=104), and (IV) TPOAb+/TgAb+ (n=113). The demographic and clinicopathological data were analyzed. RESULTS: Compared to control, significantly less extrathyroidal invasions were identified in TPOAb+ and/or TgAb+ patients (P<0.05), while no significant differences for tumor size, multifocality, or central/lateral neck LNM rate were found for TPOAb+ and/or TgAb+ groups (all P>0.05). Compared to control, significantly more lymph nodes were removed during neck dissection (P<0.05), but there were no significant differences for the number or size of lymph nodes involved (all P>0.05) for TPOAb+ and/or TgAb+ patients. TPOAb+ and/or TgAb+ were not identified as risk factors or protect factors of LNM of thyroid cancer in Logistic regression analyses. CONCLUSIONS: In the present study, we demonstrated that anti-thyroid peroxidase and thyroglobulin antibodies are not associated with increased risk of lymph node metastasis of thyroid cancer.

AtDPG1 is involved in the salt stress response of Arabidopsis seedling through ABI4.

Although the genes controlling chloroplast development play important roles in plant responses to environmental stresses, the molecular mechanisms remain largely unclear. In this study, an Arabidopsis mutant dpg1 (delayed pale-greening1) with a chloroplast development defect was studied. By using quantitative RT-PCR and histochemical GUS assays, we demonstrated that AtDPG1 was mainly expressed in the green tissues of Arabidopsis seedlings and could be induced by salt stress. Phenotypic analysis showed that mutation in AtDPG1 lead to an enhanced sensitivity to salt stress in Arabidopsis seedlings. Further studies demonstrated that disruption of the AtDPG1 in Arabidopsis increases its sensitivity to salt stress in an ABA-dependent manner. Moreover, expression levels of various stress-responsive and ABA signal-related genes were remarkably altered in the dpg1 plants under NaCl treatment. Notably, the transcript levels of ABI4 in dpg1 mutant increased more significantly than that in wild type plants under salt conditions. The seedlings of dpg1/abi4 double mutant exhibited stronger resistance to salt stress after salt treatment compared with the dpg1 single mutant, suggesting that the salt-hypersensitive phenotype of dpg1 seedlings could be rescued via loss of ABI4 function. These results reveal that AtDPG1 is involved in the salt stress response of Arabidopsis seedling through ABI4.

Comparison Of The Effects Of Focus Harmonic Scalpel And Conventional Haemostasis On Parathyroid Function In Thyroid Surgery.

BACKGROUND: Protection of parathyroid is very important in thyroid surgery. Our aim was to compare the effect of Focus Harmonic Scalpel and Conventional Haemostasis on parathyroid function in thyroid surgery. METHODS: To analyse the clinical data of patients in our hospital from November 2011-December 2015 retrospectively. Operations have been performed with Focus Harmonic Scalpel in thyroid surgery since May 2013. Seventy-four patients with nodular goitre constituted Harmonic Scalpel group and Conventional Haemostasis group, and so did 139 patients with thyroid papillary carcinoma. Clinical data were compared such as age, gender, thyroid volume, operation procedure, preoperative parathyroid hormone and serum calcium concentration between the two groups. The differences between the two groups were observed in serum calcium concentration, parathyroid hormone concentration, incidence of transient hypocalcaemia and hypoparathyroidism after operation. RESULTS: The preoperative data showed no significant difference between Harmonic Scalpel group and Conventional Haemostasis group. No significant difference existed in postoperative clinic data at six a.m. the first day after operation between the two groups for patients with nodular goitre. The incidence of transient hypoparathyroidism and hypocalcaemia in Harmonic Scalpel group were less than that in Conventional Haemostasis group in thyroid surgery. Significant differences existed in the mean of serum calcium concentration and incidence of transient hypocalcaemia between the two groups for thyroid papillary carcinoma statistically. CONCLUSION: Focus Harmonic Scalpel has certain advantages than conventional Haemostasis in protecting parathyroid glands, reducing the incidence of transient hypoparathyroidism and hypocalcaemia in thyroid surgery, especially for patients with thyroid cancer.

A Novel Auto-Sorting System for Chinese Cabbage Seeds.

This paper presents a novel machine vision-based auto-sorting system for Chinese cabbage seeds. The system comprises an inlet-outlet mechanism, machine vision hardware and software, and control system for sorting seed quality. The proposed method can estimate the shape, color, and textural features of seeds that are provided as input neurons of neural networks in order to classify seeds as "good" and "not good" (NG). The results show the accuracies of classification to be 91.53% and 88.95% for good and NG seeds, respectively. The experimental results indicate that Chinese cabbage seeds can be sorted efficiently using the developed system.

Prognostic significance of X-ray cross-complementing gene 1 expression in gastric cancer.

OBJECTIVE: The aim of this study is to identify the prognostic significance of X-ray cross-complementing gene 1 (XRCC1) in patients with gastric cancer undergoing surgery and platinum-based adjuvant chemotherapy. METHODS: Immunohistochemistry (IHC) was used to evaluate XRCC1 protein expression profiles on surgical specimens of 612 gastric cancer patients. The relationship between XRCC1 expression and existing prognostic factors, platinum-based adjuvant chemotherapy, disease-free survival (DFS) and overall survival (OS) were analyzed. RESULTS: Among 612 patients staged Ⅱ/Ⅲ in our study, 182 (29.74%) were evaluated as XRCC1 IHC positive. XRCC1 expression was not significantly related to OS (P = 0.347) or DFS (P = 0.297). Compared with surgery only, platinum-based adjuvant chemotherapy significantly improved the OS (P = 0.031). And the patients with negative XRCC1 expression benefited more from platinum-based adjuvant chemotherapy (P = 0.049). Multivariate analysis demonstrated that tumor size, T category, N category, vascular or nerve invasion and platinum-based chemotherapy were good prognostic factors for OS (P < 0.05). Though XRCC1 plays an important role in DNA repair pathways, no significant relationship is found in XRCC1 expression and OS among gastric cancer in our study. CONCLUSIONS: XRCC1 might be an alternative prognostic marker for the patients of gastric cancer after radical resection. The patients with negative XRCC1 expression can benefit more from platinum-based adjuvant chemotherapy.

The novel protein DELAYED PALE-GREENING1 is required for early chloroplast biogenesis in Arabidopsis thaliana.

Chloroplast biogenesis is one of the most important subjects in plant biology. In this study, an Arabidopsis early chloroplast biogenesis mutant with a delayed pale-greening phenotype (dpg1) was isolated from a T-DNA insertion mutant collection. Both cotyledons and true leaves of dpg1 mutants were initially albino but gradually became pale green as the plant matured. Transmission electron microscopic observations revealed that the mutant displayed a delayed proplastid-to-chloroplast transition. Sequence and transcription analyses showed that AtDPG1 encodes a putatively chloroplast-localized protein containing three predicted transmembrane helices and that its expression depends on both light and developmental status. GUS staining for AtDPG1::GUS transgenic lines showed that this gene was widely expressed throughout the plant and that higher expression levels were predominantly found in green tissues during the early stages of Arabidopsis seedling development. Furthermore, quantitative real-time RT-PCR analyses revealed that a number of chloroplast- and nuclear-encoded genes involved in chlorophyll biosynthesis, photosynthesis and chloroplast development were substantially down-regulated in the dpg1 mutant. These data indicate that AtDPG1 plays an essential role in early chloroplast biogenesis, and its absence triggers chloroplast-to-nucleus retrograde signalling, which ultimately down-regulates the expression of nuclear genes encoding chloroplast-localized proteins.

Vedolizumab for induction and maintenance of remission in ulcerative colitis: a Cochrane systematic review and meta-analysis.

BACKGROUND: We performed a systematic review to evaluate the efficacy and safety of vedolizumab for induction and maintenance of remission in ulcerative colitis. METHODS: A literature search to June 2014 identified all applicable randomized trials. Outcome measures were clinical and endoscopic remission, clinical and endoscopic response, quality of life, and adverse events. The risk ratio (RR) and 95% confidence intervals (CI) were estimated for each outcome. Study quality was evaluated using the Cochrane risk of bias tool. The GRADE criteria were used to assess the quality of the evidence. MAIN RESULTS: Four studies (606 patients) were included. The risk of bias was low. Pooled analyses indicated that vedolizumab was significantly superior to placebo for induction of remission (RR = 0.86, 95% CI, 0.80-0.91), clinical response (RR = 0.82, 95% CI, 0.75-0.91), endoscopic remission (RR = 0.82, 95% CI, 0.75-0.91), and for achieving remission at 52 weeks in week 6 responders (RR = 2.73, 95% CI, 1.78-4.18). GRADE analyses suggested that the overall quality of the evidence was high for induction of remission and moderate for maintenance therapy (due to sparse data consisting of 246 events). No statistically significant difference was observed in the incidence of adverse events between vedolizumab and placebo. CONCLUSIONS: Vedolizumab is superior to placebo as induction and maintenance therapy for ulcerative colitis. Future studies are needed to define long-term efficacy and safety of this agent.

Vedolizumab for induction and maintenance of remission in ulcerative colitis.

BACKGROUND: Cellular adhesion molecules play an important role in the pathogenesis of ulcerative colitis, making selective blockade of these molecules a promising therapeutic strategy. Vedolizumab, a recombinant humanized IgG1 monoclonal antibody, inhibits adhesion and migration of leukocytes into the gastrointestinal tract by binding the alpha4beta7 integrin. Animal studies have suggested that vedolizumab may be a useful therapy for ulcerative colitis. This updated systematic review summarizes the current evidence on the use of vedolizumab for induction and maintenance of remission in ulcerative colitis. OBJECTIVES: The primary objectives were to determine the efficacy and safety of vedolizumab used for induction and maintenance of remission in ulcerative colitis. SEARCH METHODS: A computer-assisted search for relevant studies (inception to 15 June 2014) was performed using PubMed, MEDLINE, EMBASE and CENTRAL. References from published articles and conference proceedings were searched to identify additional citations. SELECTION CRITERIA: Randomized controlled trials comparing vedolizumab to placebo or a control therapy for induction or maintenance of remission in ulcerative colitis were included. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data and assessed the risk of bias for each trial. The primary outcomes were failure to induce clinical remission and relapse. Secondary outcomes included failure to induce a clinical response, failure to induce endoscopic remission, failure to induce an endoscopic response, quality of life, adverse events, serious adverse events and withdrawal due to adverse events. We calculated the relative risk (RR) and 95% confidence intervals (CI) for each outcome. Data were analyzed on an intention-to-treat basis. The overall quality of the evidence supporting the outcomes was evaluated using the GRADE criteria. MAIN RESULTS: Four studies (606 patients) were included. All of the studies were rated as having a low risk of bias. Pooled analyses revealed that vedolizumab was significantly superior to placebo for induction of remission, clinical response, and endoscopic remission and prevention of relapse. After 4 to 6 weeks of therapy 77% (293/382) of vedolizumab patients failed to enter clinical remission compared to 92% (205/224) of placebo patients (RR 0.86, 95% CI 0.80 to 0.91; 4 studies 606 patients). After 6 weeks of therapy 48% of vedolizumab patients failed to have a clinical response compared to 72% of placebo patients (RR 0.68, 95% CI 0.59 to 0.78; 3 studies 601 patients). After 4 to 6 weeks of therapy 68% of vedolizumab patients failed to enter endoscopic remission compared to 81% of placebo patients (RR 0.82, 95% CI 0.75 to 0.91; 3 studies, b583 patients). After 52 weeks of therapy, 54% of vedolizumab patients had a clinical relapse compared to 84% of placebo patients (RR 0.67, 95% CI 0.59 to 0.77; 1 study, 373 patients). One small study (28 patients) found no statistically significant difference in endoscopic response (RR 1.00, 95% CI 0.62 to 1.61). GRADE analyses indicated that the overall quality of the evidence for the primary outcomes was high for induction of remission and moderate for relapse (due to sparse data 246 events). There was no statistically significant difference between vedolizumab and placebo in terms of the risk of any adverse event (RR 0.99, 95% CI 0.93 to 1.07), or serious adverse events (RR 1.01, 95% CI 0.72 to 1.42). There was a statistically significant difference in withdrawals due to adverse events. Six per cent of vedolizumab patients withdrew due to an adverse event compared to 11% of placebo patients (RR 0.55, 95% CI 0.35 to 0.87; 2 studies, 941 patients). Adverse events commonly reported across the studies included: worsening ulcerative colitis, headache, nasopharyngitis, upper respiratory tract infection, nausea, and abdominal pain. AUTHORS' CONCLUSIONS: Moderate to high quality data from four studies shows that vedolizumab is superior to placebo for induction of clinical remission and response and endoscopic remission in patients with moderate to severely active ulcerative colitis and prevention of relapse in patients with quiescent ulcerative colitis. Moderate quality data from one study suggests that vedolizumab is superior to placebo for prevention of relapse in patients with quiescent ulcerative colitis. Adverse events appear to be similar to placebo. Future trials are needed to define the optimal dose, frequency of administration and long-term efficacy and safety of vedolizumab used for induction and maintenance therapy of ulcerative colitis. Vedolizumab should be compared to other currently approved therapies for ulcerative colitis in these trials.

Prognostic significance of ERCC1 expression in postoperative patients with gastric cancer.

AIM: This study explored the correlation between the expression of excision repair cross-complementation group 1 (ERCC1) and the prognosis of gastric cancer patients. METHODS: From January 2005 to December 2008, 605 patients who underwent radical surgery in The First Affiliated Hospital of Nanjing Medical University were enrolled. We conducted the follow-up every 6 months and its contents included a comprehensive medical history, tumor markers and abdominal ultrasound or CT and other imaging findings. Deadline was April 30, 2013 and follow-up time between 51 to 91 months. Survival time is calculated from the date of diagnosis to death or last follow-up date. Immunohistochemistry (IHC) was used to assess the expression of ERCC1 in resected samples. The relationship between ERCC1 expression and survival of patients was investigated. The comparison of count data were analyzed by Chi-square test. Median survival time (MST) and the 5-year survival rate were calculated by life table analysis. The Kaplan-Meier curves were used for survival analysis. RESULTS: ERCC1 expression was positive in 412 patients (68.1%). There is no significant difference between ERCC1-positive group and ERCC1-negative group in terms of the MST and 5-year survival rate (P=0.455). The MST and 5-year survival rate have no significant difference (P=0.162) between group with chemotherapy and group with no chemotherapy in patients with ERCC1-positive expression. However, the MST and 5-year survival rate in patients with ERCC1-negative expression benefited more from with chemotherapy (P=0.019). The ERCC1-positive patients survived longer than those ERCC1-negative patients (P=0.183) in subgroup with no adjuvant chemotherapy. In the subgroup analysis, ERCC1 expression had no significant relationship with overall survival in patients with stage II or III gastric cancer (P>0.05). CONCLUSIONS: ERCC1 might be a good prognostic factor for the patients of gastric cancer after radical resection. Patients with ERCC1-negative expression could benefit more from adjuvant chemotherapy.

Endoscopic papillary large balloon dilation vs endoscopic sphincterotomy for retrieval of common bile duct stones: a meta-analysis.

AIM: To compare the efficacy and safety of endoscopic papillary large balloon dilation (EPLBD) with endoscopic sphincterotomy (EST) in retrieval of common bile duct stones (≥ 10 mm). METHODS: PubMed, Web of Knowledge, EBSCO, the Cochrane Library, and EMBASE were searched for eligible studies. Randomized controlled trials (RCTs) that compared EPLBD with EST were identified. Data extraction and quality assessment were performed by two independent reviewers using the same criteria. Any disagreement was discussed with a third reviewer until a final consensus was reached. Pooled outcomes of complete bile duct stone clearance, stone clearance in one session, requirement for mechanical lithotripsy, and overall complication rate were determined using relative risk and 95%CI. The separate post-endoscopic retrograde cholangiopancreatography complications were pooled and determined with the Peto odds ratio and 95%CI because of the small number of events. Heterogeneity was evaluated with the chi-squared test with P ≤ 0.1 and I(2) with a cutoff of ≥ 50%. A fixed effects model was used primarily. A random effects model was applied when significant heterogeneity was detected. Sensitivity analysis was applied to explore the potential bias. RESULTS: Five randomized controlled trials with 621 participants were included. EPLBD compared with EST had similar outcomes with regard to complete stone removal rate (93.7% vs 92.5%, P = 0.54) and complete duct clearance in one session (82.2% vs 77.7%, P = 0.17). Mechanical lithotripsy was performed less in EPLBD in the retrieval of whole stones (15.5% vs 25.2%, P = 0.003), as well as in the stratified subgroup of stones larger than 15 mm (24.2% vs 40%, P = 0.001). There was no statistically significant difference in the incidence of overall adverse events (7.9% vs 10.7%, P = 0.25), post-ERCP pancreatitis (4.0% vs 5.0%, P = 0.54), hemorrhage (1.7% vs 2.8%, P = 0.32), perforation (0.3% vs 0.9%, P = 0.35) or acute cholangitis (1.3% vs 1.3%, P = 0.92). CONCLUSION: EPLBD could be advocated as an alternative to EST in the retrieval of large common bile duct stones.

Metabolic profiling reveals that PNPLA3 induces widespread effects on metabolism beyond triacylglycerol remodeling in Huh-7 hepatoma cells.

PNPLA3 was recently associated with the susceptibility to nonalcoholic fatty liver disease, a common cause of chronic liver disease characterized by abnormal triglyceride accumulation. Although it is established that PNPLA3 has both triacylglycerol lipase and acylglycerol O-acyltransferase activities, is still unknown whether the gene has any additional role in the modulation of the human liver metabolome. To uncover the functional role of PNPLA3 on liver metabolism, we performed high-throughput metabolic profiling of PNPLA3 siRNA-silencing and overexpression of wild-type and mutant Ile148Met variants (isoleucine/methionine substitution at codon 148) in Huh-7 cells. Metabolomic analysis was performed by using GC/MS and LC/MS platforms. Silencing of PNPLA3 was associated with a global perturbation of Huh-7 hepatoma cells that resembled a catabolic response associated with protein breakdown. A significant decrease in amino- and γ-glutamyl-amino acids and dipeptides and a significant increase in cysteine sulfinic acid, myo-inositol, lysolipids, sphingolipids, and polyunsaturated fatty acids were observed. Overexpression of the PNPLA3 Met148 variant mirrored many of the metabolic changes observed during gene silencing, but in the opposite direction. These findings were replicated by the exploration of canonical pathways associated with PNPLA3 silencing and Met148 overexpression. Overexpression of the PNPLA3 Met148 variant was associated with a 1.75-fold increase in lactic acid, suggesting a shift to anaerobic metabolism and mitochondrial dysfunction. Together, these results suggest a critical role of PNPLA3 in the modulation of liver metabolism beyond its classical participation in triacylglycerol remodeling.

Post-paracentesis circulatory derangements are related to monocyte activation.

BACKGROUND & AIMS: Post-paracentesis circulatory dysfunction is associated with development of hepatorenal syndrome and increased mortality. The impact of large volume paracentesis (LVP) on the 24-h blood pressure (BP) profile is unknown, and the relationship to Na+-retentive and pro-inflammatory cytokines also remains unknown. The aims of this study were to (i) define the effects of LVP with albumin administration on 24-h BP profiles, and (ii) relate changes in BP over time to changes in Na+-retentive hormones, clinical factors and inflammatory cytokines. METHODS: Ten patients undergoing LVP had 24-h ambulatory BP monitoring performed pre- and post-paracentesis. Markers of the innate immune system, bacterial translocation and Na+-retentive hormones were drawn pre- and post-LVP. RESULTS: Mean arterial pressure (MAP) dropped in nine of the 10 patients in the 24 h following a paracentesis compared to 24 h preceding the procedure (mean drop of 5.5 mmHg, P<0.005). A mixed effects model was used to define time-covariate interactions in predicting changes in BP profile. Monocyte chemotactic protein-1 (MCP1) was associated with Δsystolic BP (ß=-0.011, P<0.05), Δdiastolic BP (ß=-0.012, P<0.05) and ΔMAP (ß=-0.012, P<0.05). Plasma renin activity was also significantly associated with Δsystolic BP (ß=-0.21, P<0.05). Renal function was also significantly reduced following LVP. CONCLUSIONS: Systolic, diastolic and MAP decreased over 24 h after LVP compared to the 24 h pre-LVP. This drop is related to increases in MCP-1 after LVP. Increased MCP-1, a marker of monocyte activation, was strongly related to changes in BP.

Review of inflammatory bowel disease in China.

Inflammatory bowel disease mainly consisting of ulcerative colitis and Crohn's disease has been rising gradually during the last two decades in China. In this review article, we provide the latest epidemiological trends in incidence, prevalence, and mortality of IBD patients in China and summarize the risk factors and genetic susceptibility of Chinese IBD patients. We also compare these characteristics to those of IBD patients in Western countries.

Adalimumab treatment in Crohn's disease: an overview of long-term efficacy and safety in light of the EXTEND trial.

The advent of anti-tumor necrosis factor (TNF) therapies revolutionized the treatment of inflammatory bowel disease. Adalimumab is a subcutaneous anti-TNF agent indicated for use in patients with moderate-to-severe Crohn's disease and those with moderate-to-severe ulcerative colitis. In both diseases, it can be used for both induction of remission and for maintenance of remission. This review focuses on its use in Crohn's disease as described in the EXTEND (Extend the Safety and Efficacy of Adalimumab through Endoscopic Healing) trial. Several clinical trials using traditional instruments to measure clinical response have had endoscopic substudies looking for endoscopic healing. The EXTEND trial is the first to use mucosal healing on endoscopy as a primary endpoint for patients with moderate-to-severe Crohn's disease and baseline ulcerative disease treated with continuous adalimumab. In this well designed trial, the primary endpoint was narrowly missed, but the secondary endpoints further the notion that mucosal healing should be a more mainstream measure of drug efficacy. How this will translate from clinical trials to the clinic is not yet clear, but identifying noninvasive markers for mucosal healing, and understanding the implications of mucosal healing for safety, resource utilization, and quality of life are all worthy targets for further study. The aim of this review is to understand the role of mucosal healing, safety profile, and efficacy in patients treated with anti-TNF therapy, with particular attention to adalimumab and the EXTEND trial.