Transcutaneous Auricular Vagal Nerve Stimulation Is Effective for the Treatment of Functional Dyspepsia: A Multicenter, Randomized Controlled Study.

INTRODUCTION: Vagal nerve stimulation (VNS) can be used to modulate gastrointestinal motility, inflammation, and nociception. However, it remains unclear whether VNS is effective in adult patients with functional dyspepsia (FD). We investigated the effectiveness of transcutaneous auricular VNS (taVNS) in patients with FD. METHODS: Consecutive patients with FD meeting Rome IV criteria with modified FD Symptom Diary score ≥10 were enrolled. Patients were randomly allocated to 10-Hz taVNS (V10 group), 25-Hz taVNS (V25 group), or sham group, with 30 minutes of treatment twice a day for 4 weeks. The primary outcome was the response rate at week 4, defined as the proportion of patients whose modified FD Symptom Diary score was reduced ≥5 when compared with the baseline. Secondary outcomes included adequate relief rate and adverse events. RESULTS: A total of 300 patients were randomized to V10 (n = 101), V25 (n = 99), and sham groups (n = 100). After 4 weeks of treatment, V10 and V25 groups had a higher response rate (81.2% vs 75.9% vs 47%, both P < 0.001) and adequate relief rate (85.1% vs 80.8% vs 67%, both P < 0.05) compared with the sham group. There was no significant difference between V10 and V25 in response rate and adequate relief rate (both P > 0.05). The efficacy of taVNS (both 10 and 25 Hz) lasted at week 8 and week 12 during follow-up period. Adverse events were all mild and comparable among the 3 groups (1%-3%). DISCUSSION: Our study firstly showed that 4-week taVNS (both 10 and 25 Hz) was effective and safe for the treatment of adult FD ( clinicaltrials.gov number: NCT04668534).

Effect of urban form on PM2.5 concentrations in urban agglomerations of China: Insights from different urbanization levels and seasons.

Planned urban form has become an important strategy to improve air quality in urban agglomerations (UAs), especially pollution due to PM2.5, but the influencing mechanisms are not yet clear. This study explores the relationship between four metrics of urban form (size, fragmentation, shape, and dispersion) as determined by analysis of remotely sensed images at 30-m resolution and PM2.5 concentrations in 19 Chinese UAs. The influence of level of urban development and season is examined. Five control variables, including population density, temperature, precipitation, wind speed, and the normalized difference vegetation index (NDVI) are selected for use in multiple linear regression models. Size, fragmentation, and shape of urban form, but not dispersion, were found to have significant effects on PM2.5 concentrations of different urbanization-level UAs. Urban size and fragmentation have stronger impacts on PM2.5 concentrations in UAs with lower urbanization levels while urban shape has a greater impact in higher-level UAs. In terms of seasonal variation in all UAs, urban form is more pronouncedly associated with PM2.5 concentrations during spring and autumn than summer and winter. Urban size and fragmentation are positively associated with PM2.5 concentrations whereas urban shape and dispersion are on the contrary. The relationships between urban form and PM2.5 uncovered here underscore the importance of urban planning as a tool to minimize PM2.5 pollution. Specifically, local government should encourage polycentric urban form with lower fragmentation in urban agglomerations. UAs with lower urbanization levels should control the disordered expansion of construction land and higher-level UAs should promote the mix of green land and construction land. Moreover, measures to control air pollution from anthropogenic activities in spring, autumn and winter are likely to be more effective in decreasing PM2.5 concentrations in UAs.

Genome Duplication Increases Meiotic Recombination Frequency: A Saccharomyces cerevisiae Model.

Genetic recombination characterized by reciprocal exchange of genes on paired homologous chromosomes is the most prominent event in meiosis of almost all sexually reproductive organisms. It contributes to genome stability by ensuring the balanced segregation of paired homologs in meiosis, and it is also the major driving factor in generating genetic variation for natural and artificial selection. Meiotic recombination is subjected to the control of a highly stringent and complex regulating process and meiotic recombination frequency (MRF) may be affected by biological and abiotic factors such as sex, gene density, nucleotide content, and chemical/temperature treatments, having motivated tremendous researches for artificially manipulating MRF. Whether genome polyploidization would lead to a significant change in MRF has attracted both historical and recent research interests; however, tackling this fundamental question is methodologically challenging due to the lack of appropriate methods for tetrasomic genetic analysis, thus has led to controversial conclusions in the literature. This article presents a comprehensive and rigorous survey of genome duplication-mediated change in MRF using Saccharomyces cerevisiae as a eukaryotic model. It demonstrates that genome duplication can lead to consistently significant increase in MRF and rate of crossovers across all 16 chromosomes of S. cerevisiae, including both cold and hot spots of MRF. This ploidy-driven change in MRF is associated with weakened recombination interference, enhanced double-strand break density, and loosened chromatin histone occupation. The study illuminates a significant evolutionary feature of genome duplication and opens an opportunity to accelerate response to artificial and natural selection through polyploidization.

Endoscopic Papillary Large Balloon Dilation Reduces Further Recurrence in Patients With Recurrent Common Bile Duct Stones: A Randomized Controlled Trial.

INTRODUCTION: Up to 60% of patients with common bile duct stone (CBDS) recurrence suffer from further recurrence after endoscopic retrograde cholangiopancreatography (ERCP). There are no effective methods to prevent recurrence in most patients. In this study, we aimed to assess the short-term and long-term efficacies of endoscopic papillary large balloon dilation (EPLBD) for the management of recurrent CBDS in a randomized controlled trial. METHODS: Consecutive patients with recurrent CBDS were eligible and randomly assigned in a 1:1 ratio to the EPLBD group or the control group. The primary outcome was the CBDS recurrence rate within 2 years after ERCP. The analysis followed the intention-to-treat principle. RESULTS: From 2014 to 2021, 180 patients with recurrent CBDS were included, with 90 in each group. All patients underwent complete CBDS clearance by 1 or several sessions of ERCP. The rate of complete clearance in 1 session was significantly higher with EPLBD treatment (95.6% vs 85.6%, P = 0.017). During the follow-up, the CBDS recurrence rate within 2 years was significantly lower in the EPLBD group than in the control group (21.1% [19/90] vs 36.7% [33/90], relative risk 0.58, 95% confidence interval 0.36-0.93, P = 0.021). At a median follow-up of approximately 56 months, CBDS recurrence was found in 34.4% of the patients (31/90) in the EPLBD group and 51.1% (46/90) in the control group (hazard ratio 0.57, 95% confidence interval 0.36-0.89, P = 0.012). Multiple recurrences (≥2) were also decreased in the EPLBD group (4.4% vs 18.9%, P = 0.020). DISCUSSION: During the long-term follow-up, nearly half of the patients with recurrent CBDS experienced stone recurrence after traditional ERCP. Our study was the first to show that EPLBD effectively reduced the recurrence of CBDS.

Difficult biliary cannulation in ERCP procedures with or without trainee involvement: a comparative study.

BACKGROUND: The 5-5-1 criteria (> 5 minutes - 5 cannulation attempts - 1 unintended pancreas duct cannulation) were proposed by the European Society of Gastrointestinal Endoscopy to define difficult biliary cannulation. However, the criteria may be inappropriate for trainee-involved procedures. We developed criteria for difficult cannulation in trainee-involved procedures. METHODS: Patients undergoing biliary cannulation with or without trainee involvement were eligible. Procedures that might be too easy (e. g. fistula) or too difficult (e. g. altered anatomy) were excluded. The primary outcome was difficult cannulation, defined as cannulation time, attempts, or inadvertent pancreatic duct (PD) cannulation exceeding the 75 % percentile of each variable. Propensity score matching (PSM) analysis was used. RESULTS: After PSM, there were 1596 patients in each group. Trainee-involved procedures had longer median (interquartile range [IQR]) cannulation time (7.5 [2.2-15.3] vs. 2.0 [0.6-5.2] minutes), and more attempts (5 [2-10] vs. 2 [1-4]) and inadvertent PD cannulation (0 [0-2] vs. 0 [0-1]) vs. procedures without trainee involvement (all P < 0.001). The 15-10-2 criteria for difficult cannulation were proposed for trainee-involved cannulation and the 5-5-1 criteria were nearly confirmed for cannulation without trainee involvement. The proportions of difficult cannulation using these respective criteria were 35.5 % (95 % confidence interval [CI] 33.2 %-37.9 %) and 31.8 % (95 %CI 29.5 %-34.2 %), respectively (odds ratio 1.18 [95 %CI 1.02-1.37]). Incidences of post-ERCP pancreatitis following difficult cannulation were comparable (7.8 % [95 %CI 5.7 %-10.3 %] vs. 9.8 % [95 %CI 7.4 %-12.8 %], respectively). CONCLUSION: By using the 75 % percentiles as cutoffs, the proposed 15-10-2 criteria for difficult cannulation could be appropriate in trainee-involved procedures.

Functional dyspepsia symptom diary is correlated with other questionnaires and associated with severity in patients with functional dyspepsia: a multicenter, prospective observational study.

BACKGROUND AND AIM: Functional dyspepsia symptom diary (FDSD) is a newly designed questionnaire of functional dyspepsia (FD). The relationships between FDSD and other FD-related questionnaires and patient-reported severity remain unclear. This study aims to investigate the correlations between FDSD and other questionnaires and to determine the relationships between FDSD and FD severity. METHODS: Consecutive outpatients with FD were prospectively enrolled in four tertiary hospitals. All patients were evaluated by six FD-related questionnaires, including FDSD, Dyspepsia Symptom Severity Index (DSSI), Gastrointestinal Symptom Rating Scale, Short-Form Nepean Dyspepsia Index, and Hamilton Depression and Anxiety Scale (HAMD and HAMA). The severity of FD was also graded as mild, moderate, and severe by patients themselves. Correlations between different scores were assessed by Spearman correlation coefficient (ρ), and risk factors for patient-reported severity were identified. RESULTS: For 512 enrolled FD patients, the overall median FDSD score was 19 (2-42). FDSD was well correlated with DSSI (ρ = 0.64) and fairly correlated with the other four scores (ρ = 0.32-0.55) (all P < 0.001). Mild, moderate, and severe FD were reported by 18.5%, 55.9%, and 25.6% of patients, respectively. There were seven factors associated with the severe FD, including education level, duration, and subtypes of FD, prior treatment, FDSD, HAMD, and HAMA scores (all P < 0.10). FDSD ≥ 20 (odds ratio [OR] 3.3, 95% confidence interval [CI]: 2.0-5.2, P < 0.001) and HAMD ≥ 13 (OR 2.9, 95% CI: 1.8-4.6, P < 0.001) were independently associated with patient-reported severe FD. CONCLUSIONS: This study firstly revealed that the newly developed FDSD correlated with other FD-related questionnaires. FDSD ≥ 20 and HAMD ≥ 13 were independently associated with severe FD reported by patients (clinicaltrials.gov number: NCT04953975).

A tetrasomic inheritance model and likelihood-based method for mapping quantitative trait loci in autotetraploid species.

Dissecting the genetic architecture of quantitative traits in autotetraploid species is a methodologically challenging task, but a pivotally important goal for breeding globally important food crops, including potato and blueberry, and ornamental species such as rose. Mapping quantitative trait loci (QTLs) is now a routine practice in diploid species but is far less advanced in autotetraploids, largely due to a lack of analytical methods that account for the complexities of tetrasomic inheritance. We present a novel likelihood-based method for QTL mapping in outbred segregating populations of autotetraploid species. The method accounts properly for sophisticated features of gene segregation and recombination in an autotetraploid meiosis. It may model and analyse molecular marker data with or without allele dosage information, such as that from microarray or sequencing experiments. The method developed outperforms existing bivalent-based methods, which may fail to model and analyse the full spectrum of experimental data, in the statistical power of QTL detection, and accuracy of QTL location, as demonstrated by an intensive simulation study and analysis of data sets collected from a segregating population of potato (Solanum tuberosum). The study enables QTL mapping analysis to be conducted in autotetraploid species under a rigorous tetrasomic inheritance model.

Discrimination of Tourette Syndrome Based on the Spatial Patterns of the Resting-State EEG Network.

Tourette syndrome (TS) is a neuropsychiatric disorder with childhood onset characterized by chronic motor and vocal tics; however, the current diagnosis of TS patients is subjective, as it is mainly assessed based on the parents' description alongside specific evaluations. The early and accurate diagnosis of TS based on its potential symptoms in children would be of benefit in their future therapy, but reliable diagnoses are difficult due to the lack of objective knowledge of the etiology and pathogenesis of TS. In this study, resting-state electroencephalograms were first collected from 36 patients and 21 healthy controls (HCs); the corresponding resting-state functional networks were then constructed, and the potential differences in network topology between the two groups were extracted by using the topology of the spatial pattern of the network (SPN). Compared to the HCs, the TS patients exhibited decreased frontotemporal/occipital/parietal connectivity. When classifying the two groups, compared to the network properties, the derived SPN features achieved a much higher accuracy of 92.31%. The intrinsic long-range connectivity between the frontal and the temporal/occipital/parietal lobes was damaged in the patient group, and this dysfunctional network pattern might serve as a reliable biomarker to differentiate TS patients from HCs as well as to assess the severity of tic symptoms.

Combination prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis in patients undergoing double-guidewire assisted biliary cannulation: A case-control study with propensity score matching.

BACKGROUND AND AIM: Rectal indomethacin and pancreatic duct stenting (PDS) are recommended for the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP). However, the effects of the combination of the two methods on preventing PEP are controversial. We hypothesized that some group of difficult patients might benefit from the combination of indomethacin plus PDS (IP) compared with indomethacin alone (IN). METHODS: Patients with native papilla who underwent endoscopic retrograde cholangiopancreatography in eight tertiary hospitals were screened. They were enrolled if the cannulation proved difficult and post-procedure indomethacin was administered. Propensity score matching (PSM) was used to balance the baseline characteristics between IP and IN groups. The primary outcome was PEP. RESULTS: Among 4456 patients with available cannulation-related data, 1889 (42.4%) patients had difficult cannulation and received indomethacin. After PSM, both IP and IN groups included 332 patients. PEP was comparable between the two groups (12.7% vs 10.2%, P = 0.329). By subgroup analysis, the PEP rate was found to be lower in the IP group than in the IN group (7.3% vs 18.2%, P = 0.026) in patients undergoing double-guidewire technique (DGT). The results of an additional analysis using PSM in DGT patients were consistent with the subgroup analysis results (7.8% vs 19.4%, P = 0.036). CONCLUSIONS: The current study indicated that the combined prevention of PEP with indomethacin plus PDS was useful in PEP prevention in patients undergoing DGT. Other groups of patients with difficult cannulation may not benefit from the combination strategy.

Inter-subject P300 variability relates to the efficiency of brain networks reconfigured from resting- to task-state: Evidence from a simultaneous event-related EEG-fMRI study.

The P300 event-related potential (ERP) varies across individuals, and exploring this variability deepens our knowledge of the event, and scope for its potential applications. Previous studies exploring the P300 have relied on either electroencephalography (EEG) or functional magnetic resonance imaging (fMRI). We applied simultaneous event-related EEG-fMRI to investigate how the network structure is updated from rest to the P300 task so as to guarantee information processing in the oddball task. We first identified 14 widely distributed regions of interest (ROIs) that were task-associated, including the inferior frontal gyrus and the middle frontal gyrus, etc. The task-activated network was found to closely relate to the concurrent P300 amplitude, and moreover, the individuals with optimized resting-state brain architectures experienced the pruning of network architecture, i.e. decreasing connectivity, when the brain switched from rest to P300 task. Our present simultaneous EEG-fMRI study explored the brain reconfigurations governing the variability in P300 across individuals, which provided the possibility to uncover new biomarkers to predict the potential for personalized control of brain-computer interfaces.

Predicting individual decision-making responses based on single-trial EEG.

Decision-making plays an essential role in the interpersonal interactions and cognitive processing of individuals. There has been increasing interest in being able to predict an individual's decision-making response (i.e., acceptance or rejection). We proposed an electroencephalogram (EEG)-based computational intelligence framework to predict individual responses. Specifically, the discriminative spatial network pattern (DSNP), a supervised learning approach, was applied to single-trial EEG data to extract the DSNP feature from the single-trial brain network. A linear discriminate analysis (LDA) trained on the DSNP features was then used to predict the individual response trial-by-trial. To verify the performance of the proposed DSNP, we recruited two independent subject groups, and recorded the EEGs using two types of EEG systems. The performances of the trial-by-trial predictors achieved an accuracy of 0.88 ±â€¯0.09 for the first dataset, and 0.90 ±â€¯0.10 for the second dataset. These trial-by-trial prediction performances suggested that individual responses could be predicted trial-by-trial by using the specific pattern of single-trial EEG networks, and our proposed method has the potential to establish the biologically inspired artificial intelligence decision system.

Relationship between papilla-related variables and post endoscopic retrograde cholangiopancreatography pancreatitis: A multicenter, prospective study.

BACKGROUND AND AIM: Papilla with hooknose or long protruding shape may increase the difficulty of cannulation during endoscopic retrograde cholangiopancreatography (ERCP). However, the relationship between papilla anatomy and complications of ERCP has not been fully understood. We aimed to investigate the effect of major duodenal papilla morphology on post-ERCP pancreatitis (PEP) and the procedure of cannulation. METHODS: Patients with native papilla who underwent ERCP were recruited to this multicenter study. Papilla-related variables were collected, including the length of long axis (L), short axis (S) and opening width (OW), transverse fold, periampullary diverticulum (PAD), papilla location, orientation, swelling, and presence of duodenal stenosis. Demographic data and the procedure of cannulation were also prospectively evaluated. The primary outcome was PEP incidence. Multivariate analysis was used to identify high risk factors for PEP. RESULTS: Six hundred and fifty-eight patients were enrolled. Overall PEP incidence was 4.7% (31/658). The papilla of patients complicated with PEP had higher long to short axis (L/S) ratio (odds ratio [OR] 3.84, 95% confidence interval [CI]: 1.37-10.74, P = 0.010), higher long axis to opening width (L/OW) ratio (OR 1.35, 95%CI: 1.06-1.71, P = 0.014), more transverse folds (OR 2.53, 95%CI: 1.02-6.26, P = 0.044), and less periampullary diverticulum (OR 0.21, 95%CI: 0.06-0.70, P = 0.011). Multivariate analysis revealed that the indication of common bile duct stones, normal bilirubin, inadvertent pancreatic duct cannulation > 1, L/S ratio ≥ 1.5, and absence of PAD were independent risk factors for PEP. CONCLUSION: Besides patient-related and procedure-related factors, papilla-related variables, such as L/S ratio and PAD, can be considered as a third type of factors associated with PEP (Clinicaltrials.gov number: NCT03550768).

Learning curve of double-guidewire technique by trainees during hands-on endoscopic retrograde cholangiopancreatography training.

BACKGROUND AND AIMS: Double-guidewire technique (DWT) has been successfully performed by experts in difficult biliary cannulation as an advanced technique. This study aimed to define the learning curve and safety of DWT by trainees during hands-on endoscopic retrograde cholangiopancreatography (ERCP) training. METHODS: Patients were eligible for inclusion in the study if the biliary cannulation was difficult and the pancreatic duct was inadvertently cannulated. DWT was performed by two trainees randomly under trainers' guidance. The primary outcome was the success rate of DWT biliary cannulation of trainees. Cumulative sum analysis was used to generate visual learning curves. RESULTS: A total of 60 patients with difficult cannulation were enrolled. The main indications for ERCP were common bile duct stones (65%) and biliary stricture (31.7%). The learning curve analysis showed that to achieve a 70% rate of successful DWT, 12 procedures were needed for trainee A and 15 for trainee B. Higher targeted success rate of DWT could be achieved if the number of DWT procedures increased. Compared with the early stage of learning DWT (case 1 to 15 for each trainee), trainees had significantly higher DWT success rate in the late stage (36.7% [11/30] vs 80% [24/30], P = 0.001). The final success rate of cannulation was 98.3% (59/60). The overall rate of post-ERCP pancreatitis and adverse events was 6.7% (4/60) and 8.3% (5/60), respectively. CONCLUSIONS: Double-guidewire technique was safely performed by two novel trainees during hands-on ERCP training. Fifteen procedures may be enough for trainees to achieve the competency of performing DWT. (Clinicaltrials.gov number: NCT03707613).

Risk Factors Associated with Inadequate Bowel Preparation in Patients with Functional Constipation.

BACKGROUND: Constipation is a common reason of poor bowel preparation, which negatively influences the quality of colonoscopy. Risk factors for inadequate bowel preparation in constipated patients remain unclear. AIMS: This study aimed to investigate the high-risk factors that might influence the quality of bowel preparation in patients with functional constipation. METHODS: Consecutive patients with functional constipation who underwent colonoscopy between June 2016 and April 2017 were enrolled. A standard split dose of 4 l polyethylene glycol was used for bowel preparation. Patient- and procedure-related parameters were recorded. The primary outcome was an adequate rate of bowel preparation. Risk factors for inadequate bowel preparation were screened by multivariate logistic regression analysis. RESULTS: A total of 199 patients were included. Adequate bowel preparation was found in 62.8% (125/199) of patients. At multivariate analysis, Bristol stool form scale (BSFS) 1 [odds ratio (OR) 2.73, 95% confidence interval (CI) 1.26-5.90; P = 0.011], rectal pain score during defecation < 2 (OR 4.14, 95% CI 1.22-13.97; P = 0.022), and starting-to-defecation interval ≥ 4 h (OR 3.83, 95% CI 1.34-10.91; P = 0.012) were risk factors for inadequate bowel preparation in patients with constipation. For patients with no, 1, 2, or 3 risk factors, the rates of inadequate bowel preparation were 11%, 23%, 49%, and 65%, respectively. CONCLUSIONS: With the standard preparation regime, > 1/3 of patients with functional constipation had inadequate bowel cleansing. BSFS 1, rectal pain score during defecation < 2, and starting-to-defecation interval ≥ 4 h were identified as independent risk factors for inadequate bowel preparation in constipated patients. TRIAL REGISTRATION: ClinicalTrials.gov number NCT02842411.

Effect of cap-assisted esophagogastroduodenoscopy on examination of the major duodenal papilla: a noninferior, randomized controlled trial.

BACKGROUND: Cap-assisted esophagogastroduodenoscopy (CA-EGD) using a transparent cap fitted to the tip of the scope has emerged as an alternative method for examination of the major duodenal papilla (MDP). However, it remains unclear whether CA-EGD is noninferior to standard duodenoscopy for MDP examination. The aim of this study was to compare the efficacies of the two methods for complete examination of the MDP. METHODS: This prospective, noninferior, randomized controlled study was conducted at two endoscopy centers. Consecutive patients who underwent endoscopic retrograde cholangiopancreatography were randomized (1:1) to undergo CA-EGD or standard duodenoscopy for MDP examination. The primary outcome was complete examination of the MDP, defined as visualization of the upper end, opening, and lower end of the papilla. Secondary outcomes included endoscopic findings and the time taken for the MDP examination. RESULTS: The study was terminated for futility after the interim analysis. A total of 171 patients were randomly allocated to CA-EGD (n = 85) or standard duodenoscopy (n = 86). The baseline characteristics were comparable between the two groups. Complete examination of the MDP was achieved in 58/85 patients (68.2 %) in the CA-EGD group and in 74/86 (86.0 %) in standard duodenoscopy group. The difference in proportions was - 17.81 percentage points (95 % confidence interval [CI] -28.14 to -7.48) by intention-to-treat analysis and - 18.22 percentage points (95 %CI -28.34 to -8.10) by per-protocol analysis, both of which were significantly lower than the noninferiority margin of -5 %, and therefore the noninferiority of CA-EGD could not be confirmed. Examination time was significantly longer with CA-EGD (69.5 [SD 46.4] vs. 33.0 [SD 28.9] seconds; P < 0.001). CONCLUSIONS: Although complete examination of the MDP can be achieved by CA-EGD in most patients, it could not replace duodenoscopy as the standard method for examination of the MDP.

Phenotypic and Genetic Characterization of Botrytis cinerea Population from Kiwifruit in Sichuan Province, China.

Botrytis cinerea (anamorph of Botryotinia fuckeliana) causes gray mold on numerous plants, including kiwifruit. The primary aim of this study was to investigate the phenotypic and genetic characteristics of the Botrytis cinerea population from kiwifruit in Sichuan Province, China. In all, 176 isolates were collected from kiwifruit orchards from eight geographic regions in Sichuan. All isolates were identified as B. cinerea sensu stricto based on the combined datasets, including morphological criteria, determination of the Bc-hch allele, and phylogenetic analysis of the genes RPB2, G3PDH, and HSP60. Three colony types (i.e., sclerotial, mycelial, and conidial) were observed on potato dextrose agar after 2 weeks, with sclerotial isolates, the predominant category, accounting for 40.91%. No obvious differences in microscopic characteristics were observed among the three types. Three genotypes of transposable elements were identified in the B. cinerea population: boty, flipper, and transposa types. The most prevalent genotype from different geographic populations of B. cinerea was transposa; in contrast, the flipper genotype accounted for only 3.98% of the total population, whereas the vacuma genotype was absent. According to MAT locus amplification, 87 and 89 isolates are MAT1-1 and MAT1-2 type, respectively, and the two mating types were found to be balanced overall in the population. Forty-eight representative isolates were all able to cause gray mold to some extent, and disease severities were significantly different between the cultivars Hongyang and Hort16A (P < 0.01). Disease severity was significantly greater on young leaves than on mature leaves (P < 0.01). No significant relationship was found between pathogenicity and geographical region, colony type, or transposon distribution. The results obtained in the present study suggest a relatively uniform species diversity of Botrytis but rich phenotypic and genetic differentiation within the B. cinerea population on kiwifruit in China. Utilizing resistant cultivars and rain-shelter cultivation instead of fungicides may be an effective approach to delaying pathogen variability.

Different pattern of risk factors for post-ERCP pancreatitis in patients with biliary stricture.

OBJECTIVE: To identify possible risk factors associated with post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) in biliary stricture (BS), common bile duct stone (CBDS) and unselected patients. MATERIALS AND METHODS: Consecutive ERCP patients with native papilla from January 2010 to December 2014 in Xijing Hospital were eligible. Patient-related and procedure-related parameters were collected retrospectively. The primary outcome was PEP. Univariate and multivariate logistic regression were used for data analysis. RESULTS: Totally 3133 unselected patients were included. 695 (22.2%) had BS alone and 1893 (60.4%) had CBDS alone. PEP incidence was higher in BS group compared with CBDS group (6.8% vs. 3.8%, p = .001). Among patient-related factors, duodenal stenosis (OR, 2.74; 95%CI, 1.14-6.59) and hilar stricture (OR, 2.59; 95%CI, 1.41-4.77) were found to be independently associated with PEP in BS group. While female gender (OR, 2.11; 95%CI, 1.20-3.73) and normal total bilirubin (OR, 1.93; 95%CI, 1.13-3.32) were related to PEP in CBDS group. Among procedure-related factors, cannulation time ≥ 5 min (OR, 2.38; 95%CI, 1.06-5.33) and precut (OR, 3.20; 95%CI, 1.35-7.59) was respectively the only independent risk factor for PEP in BS and CBDS group. CONCLUSIONS: Patients with BS and CBDS had different patterns of patient-related and procedure-related risk factors for PEP. The prophylaxis of PEP may need to be individualized based on different indications.

Routine pre-procedural rectal indometacin versus selective post-procedural rectal indometacin to prevent pancreatitis in patients undergoing endoscopic retrograde cholangiopancreatography: a multicentre, single-blinded, randomised controlled trial.

BACKGROUND: Rectal indometacin decreases the occurrence of pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP). However, the population most at risk and the optimal timing of administration require further investigation. We aimed to assess whether pre-procedural administration of rectal indometacin in all patients is more effective than post-procedural use in only high-risk patients to prevent post-ERCP pancreatitis. METHODS: We did a multicentre, single-blinded, randomised controlled trial at six centres in China. Eligible patients with native papilla undergoing ERCP were randomly assigned in a 1:1 ratio (with a computer-generated list) to universal pre-procedural indometacin or post-procedural indometacin in only high-risk patients, with stratification by trial centres and block size of ten. In the universal indometacin group, all patients received a single dose (100 mg) of rectal indometacin within 30 min before ERCP. In the risk-stratified, post-procedural indometacin group, only patients at predicted high risk received rectal indometacin, immediately after ERCP. Investigators, but not patients, were masked to group allocation. The primary outcome was overall ocurrence of post-ERCP pancreatitis. The analysis followed the intention-to-treat principle. This study was registered with ClinicalTrials.gov, number NCT02002650. FINDINGS: Between Dec 15, 2013, and Sept 21, 2015, 2600 patients were randomly assigned to universal, pre-procedural indometacin (n=1297) or risk-stratified, post-procedural indometacin (n=1303). Overall, post-ERCP pancreatitis occurred in 47 (4%) of 1297 patients assigned to universal indometacin and 100 (8%) of 1303 patients assigned to risk-stratified indometacin (relative risk 0·47; 95% CI 0·34-0·66; p<0·0001). Post-ERCP pancreatitis occurred in 18 (6%) of 305 high-risk patients in the universal group and 35 (12%) of 281 high-risk patients in the risk-stratified group (p=0·0057). Post-ERCP pancreatitis was also less frequent in average-risk patients in the universal group (3% [29/992]), in which they received indometacin, than in the risk-stratified group (6% [65/1022]), in which they did not receive the drug (p=0·0003). Other than pancreatitis, adverse events occurred in 41 (3%; two severe) patients in the universal indometacin group and 48 (4%; one severe) patients in the risk-stratified group. The most common adverse events were biliary infection (22 [2%] patients vs 33 [3%] patients) and gastrointestinal bleeding (13 [1%] vs ten [1%]). INTERPRETATION: Compared with a risk-stratified, post-procedural strategy, pre-procedural administration of rectal indometacin in unselected patients reduced the overall occurrence of post-ERCP pancreatitis without increasing risk of bleeding. Our results favour the routine use of rectal indometacin in patients without contraindications before ERCP. FUNDING: National Key Technology R&D Program, National Natural Science Foundation of China.

Enhanced instructions improve the quality of bowel preparation for colonoscopy: a meta-analysis of randomized controlled trials.

BACKGROUND AND AIMS: The success of a colonoscopy is highly dependent on the quality of bowel preparation (BP). Many patients have poor BP due to non-compliance with regular instructions. Reports concerning the effects of enhanced instructions on BP quality are inconsistent. The aim of this meta-analysis was to compare BP quality between patients receiving enhanced instructions in addition to regular instructions and those who received regular instructions only. METHODS: MEDLINE, EMBASE, Web of Science, and the Cochrane Library were searched to identify relevant studies published for August 2015. The quality of BP (adequate/inadequate), adenoma detection rate, polyp detection rate, willingness to repeat preparation, and adverse events were estimated by using odds ratios (OR) and 95% confidence intervals (CI) with random effects models. RESULTS: Eight randomized controlled trials (n = 3795) were included. Patients who received enhanced instructions showed significantly better BP quality than those receiving only regular instructions (OR, 2.35; 95% CI, 1.65-3.35; P < .001). Subgroup analysis showed that the beneficial effects of enhanced instructions on BP quality were consistent among patients receiving different purgative types, administration methods, or diet restriction (all P < .05). Patients in the enhanced instructions group showed more willingness to repeat the preparation (OR, 1.91; 95% CI, 1.20-3.04; P = .006). CONCLUSIONS: Enhanced instructions significantly improved the quality of BP and willingness to repeat the preparation in patients undergoing colonoscopy. Factors related to patient instructions appear to be as important as the preparation method itself in improving BP quality.

Delivery of Instructions via Mobile Social Media App Increases Quality of Bowel Preparation.

BACKGROUND & AIMS: Bowel preparation is closely linked to the quality of colonoscopy. We investigated whether delivery of instructions via a social media app increases the quality of colonoscopy by improving adequacy of bowel preparation. METHODS: We performed a prospective study at 3 endoscopic centers in China of 770 colonoscopy outpatients (18-80 years old) with convenient access to Wechat (a widely used mobile social media app) from May through November 2014. Patients were randomly assigned to groups that received standard education along with delivery of interactive information via Wechat (n = 387) or standard education (controls, n = 383). The primary outcome was proportion of patients with adequate bowel preparation (Ottawa score <6). Secondary outcomes included rates of adenoma detection and cecal intubation, cecal intubation time, rates of incomplete compliance with instructions, and patient willingness to repeat bowel preparation. RESULTS: Demographic features were comparable between the groups. A higher proportion of patients in the group that received social media instruction had adequate bowel preparation than the control group (82.2% vs 69.5%, P < .001). Among patients with successful colonoscopies, the group that received social media instruction had lower mean total and segmental Ottawa scores (P < .05). A higher proportion of patients receiving social media instruction also had cecal intubation (97.2% vs 93.2% in controls, P = .014) and were found to have adenomas (18.6% vs 12.0% in controls, P = .012). CONCLUSIONS: Instruction via a mobile social media app, in conjunction with regular instruction, increases subjective measures of adequacy of bowel preparation. Use of the app significantly increased the proportion of patients with successful cecal intubation and in whom adenomas were detected, indicating increased quality of colonoscopy. ClinicalTrials.gov number: NCT02140827.