Search

BackgroundRecurrent acute pancreatitis (RAP) poses significant clinical challenges, with 32.3% developing to chronic pancreatitis within 5 years. The underlying microbial factors contributing to RAP remain poorly understood. This study aims to identify blood microbial signatures associated with RAP and explore the potential microbial predictors for RAP.MethodsIn this prospective cohort, 90 acute pancreatitis patients are classified into non-recurrent acute pancreatitis (NRAP, n=68) and RAP (n=22) groups based on the number of pancreatitis episodes. Microbial composition of blood samples is analyzed using 5-region (5R) 16S rRNA gene sequencing. Key microbial taxa and functional predictions are made. A random forest model is used to assess the predictive value of microbial features for RAP. The impact of Staphylococcus hominis (S. hominis) on RAP is further evaluated in an experimental mouse model.ResultsLinear discriminant analysis effect size (LEfSe) analysis highlights significant microbial differences, with Paracoccus aminovorans, Corynebacterium glucuronolyticum and S. hominis being prominent in RAP. Functional predictions indicate enrichment of metabolic pathways in the RAP group. Random forest analysis identifies key microbial taxa with an AUC value of 0.759 for predicting RAP. Experimental validation shows that S. hominis exacerbates pancreatic inflammation in mice.ConclusionsThis study identifies distinct clinical and microbial features associated with RAP, emphasizing the role of specific bacterial taxa in pancreatitis recurrence. The findings suggest that microbial profiling could enhance the diagnosis and management of RAP, paving the way for personalized therapeutic approaches.

Background: Esophageal squamous cell carcinoma (ESCC) is one of the most lethal malignancies worldwide, with a 5-year survival rate of less than 30%. Early diagnosis of ESCC is clinically challenging due to the lack of non-invasive screening and diagnostic methods. Salivary exosomal RNA has been reported to have promising applications in cancer liquid biopsy and in vitro diagnosis. The aim of this study was to investigate the significantly differentially expressed mRNAs in salivary exosomes in ESCC patients and healthy population (HC), so as to provide potential molecular targets for non-invasive diagnosis of ESCC. Methods: A total of 90 cases of ESCC patients and healthy volunteers were recruited, saliva and blood samples were collected, exosomes were isolated and total RNA was extracted using the exoRNeasy Midi Kit exosome extraction kit, and salivary exosomes were identified in four samples (ESCC = 2, HC = 2) by three methods, namely, transmission electron microscope, particle size analysis and protein blotting. Salivary exosomes, salivary cfRNA, and blood cfRNA (ESCC = 6, HC = 6 in each group) were sequenced by mRNA transcriptomics using 12 samples, respectively, and compared with differentially expressed genes (DEGs) identified by transcriptomics sequencing of 24 pairs of ESCC cancers and paracancer tissues under the condition that |log2FC| > 1, P < 0.05. Twenty potential candidate biomarkers were screened by taking intersection, expression differential fold analysis and combining with literature reports. Finally, qRT-PCR was used to detect the expression status of the above 20 markers in 40 saliva samples (ESCC = 19, HC = 21) for preliminary clinical validation. Findings: Firstly, we successfully extracted and identified salivary exosomes, and completed transcriptomics sequencing of salivary exosomes, salivary supernatants, and serum. The results of transcriptome expression comparison with tissues showed that based on this dataset, the salivary exosomes show the most co-upregrated mRNAs (86 upregulated DEGs). Among these 86 DEGs, 20 mRNAs with diagnostic potential were further screened out. qRT-PCR results showed that mRNA KPNA2 was stably expressed in salivary exosomes of ESCC patients and was significantly up-regulated in ESCC patients compared to HC (P < 0.0001) and the area under the curve of the subjects with diagnosed ESCC was 81.70% [95% CI, 66.53% -96.88%] with a sensitivity of 100%, a specificity of 76.91%, and a Youden index of 0.762. Interpretation: Salivary exosomal mRNA KPNA2 in ESCC patients showed significantly higher expression compared with the healthy ones, which shows promises in the non-invasive diagnosis of esophageal squamous cell carcinoma.

Abstract Chronic pancreatitis (CP) is a complex disease with genetic and environmental factors at play. Through trio exome sequencing, a de novo SEC16A frameshift variant in a Chinese teenage CP patient is identified. Subsequent targeted next‐generation sequencing of the SEC16A gene in 1,061 Chinese CP patients and 1,196 controls reveals a higher allele frequency of rare nonsynonymous SEC16A variants in patients (4.90% vs 2.93%; odds ratio [OR], 1.71; 95% confidence interval [CI], 1.26–2.33). Similar enrichments are noted in a French cohort (OR, 2.74; 95% CI, 1.67–4.50) and in a biobank meta‐analysis (OR, 1.16; 95% CI, 1.04–1.31). Notably, Chinese CP patients with SEC16A variants exhibit a median onset age 5 years earlier than those without (40.0 vs 45.0; p = 0.012). Functional studies using three CRISPR/Cas9‐edited HEK293T cell lines show that loss‐of‐function SEC16A variants disrupt coat protein complex II (COPII) formation, impede secretory protein vesicles trafficking, and induce endoplasmic reticulum (ER) stress due to protein overload. Sec16a+/− mice, which demonstrate impaired zymogen secretion and exacerbated ER stress compared to Sec16a+/+, are further generated. In cerulein‐stimulated pancreatitis models, Sec16a+/− mice display heightened pancreatic inflammation and fibrosis compared to wild‐type mice. These findings implicate a novel pathogenic mechanism predisposing to CP.

Chronic pancreatitis (CP) is a multifaceted disorder influenced by environmental and genetic factors, with smoking and alcohol consumption being major contributors. Recent developments encompass the advent of innovative transgenic models and the identification of susceptibility genes, shedding light on the genetic aspect of CP. The pathogenesis of this disease involves a complex interplay of pancreatic acinar cell dysfunction, inflammatory reactions, and fibrosis. Current research delves into understanding these molecular mechanisms. Pain, a pivotal symptom of CP, has been increasingly studied to develop effective therapeutic interventions. Diagnostic advancements, including endoscopic ultrasound, radiomics, and blood-based markers, have shown potential in enhancing early CP detection. Moreover, recent clinical trials have optimized treatment approaches, such as pancreatic stone fragmentation, stent placement, and decision-making between endoscopic and surgical procedures. Emerging therapies, including chemical pancreatectomy and gene therapy, present promising opportunities for improved CP management.

Abstract Pancreatic stones are the result of pathophysiologic changes in chronic pancreatitis with an incidence of more than 90%. At present, pancreatic extracorporeal shock wave lithotripsy (P-ESWL) can be used as the first-line treatment for large or complex stones. Although a large number of studies have proven the safety and effectiveness of P-ESWL, we should also pay attention to postoperative adverse events, mainly due to the scattering of shock waves in the conduction pathway. Adverse events can be classified as either complications or transient adverse events according to the severity. Because the anatomic location of organs along the shock wave conducting pathway differs greatly, adverse events after P-ESWL are varied and difficult to predict. This paper outlines the mechanism, definition, classification, management and risk factors for adverse events related to P-ESWL. It also discusses the technique of P-ESWL, indications and contraindications of P-ESWL, and adverse events in special populations.

Abstract Pancreatic enzyme replacement therapy (PERT) has been recommended as the preferred method for pancreatic exocrine insufficiency caused by chronic pancreatitis (CP). However, at present, the patient-related factors for the poor PERT management are not clear, and there are no studies on the adherence to PERT in patients with CP in East China. This was a mixed-method study following the principle of sequential explanatory design and included two parts: a quantitative and qualitative study. A cross-sectional survey of medication adherence (MA) was first carried out, followed by a semi-structured interview to further explore and explain the influencing factors of adherence to PERT. Of the 148 patients included in this study, 48.0% had poor MA and only 12.8% had good MA. Multivariate logistic regression showed that lower levels of education and income were contributing factors for non-adherence to PERT. Semi-structured interviews with 24 patients revealed that the reasons for non-adherence also included lack of knowledge, self-adjustment of PERT, lifetime of medication, side effects of PERT, forgetfulness, financial burdens, and accessibility issues. The adherence to PERT was poor among patients with CP in East China. Healthcare providers should personalize medication strategies to improve patients’ MA.

Introduction Both cigarette smoking and gut microbiota play important roles in colorectal carcinogenesis. We explored whether the association between smoking and colorectal cancer (CRC) risk varies by gut microbial enterotypes and how smoking-related enterotypes promote colorectal carcinogenesis. Methods A case-control study was conducted. Fecal microbiota was determined by 16S rDNA sequencing. The cases with CRC or adenoma were subclassified by gut microbiota enterotypes. Multivariate analyses were used to test associations between smoking and the odds of colorectal neoplasm subtypes. Mann-Whitney U tests were used to find differential genera, genes, and pathways between the subtypes. Results Included in the study were 130 CRC patients (type I: n=77; type II: n=53), 120 adenoma patients (type I: n=66; type II: n=54), and 130 healthy participants. Smoking increased the odds for type II tumors significantly (all p for trend

Background/Aims: We aimed to investigate the comfort, safety, and endoscopic visibility during esophagogastroduodenoscopy (EGD) afforded by a modified 4-hour semifluid and 2-hour water (“4+2”) fasting protocol.Methods: In this parallel group, endoscopist-blinded, randomized controlled trial, outpatients undergoing unsedated diagnostic EGD from 10:30 AM to 12:00 PM were randomly assigned to either a “4+2” protocol group or a conventional fasting group. The participants’ comfort during the fasting period and procedure was measured using the visual analog scale, and mucosal visibility was measured by endoscopists using the total visibility score. Satisfaction was defined as a visual analog scale score of ≤3. The primary outcome was the participants’ comfort during fasting.Results: One hundred and six and 108 participants were randomized to the “4+2” protocol and control groups, respectively. Participants’ comfort before EGD was significantly higher in the “4+2” protocol group measured by both the proportion of satisfaction (86.8% vs 63.9%, p=0.002) and the visual analog scale score (median [interquartile range]: 1.0 [1.0–2.0] vs 3.0 [1.0–4.0], p

Abstract Backgrounds and Aims Complete and consecutive observation of the gastrointestinal (GI) tract continues to present challenges for current endoscopy systems. We developed a novel upper and mid gastrointestinal (UMGI) capsule endoscopy using the modified detachable string magnetically controlled capsule endoscopy (DS-MCE) and inspection method and aimed to assess the clinical application. Methods Patients were recruited to undergo UMGI capsule endoscopy followed by esophagogastroduodenoscopy. All capsule procedures in the upper gastrointestinal (UGI) tract were conducted under the control of magnet and string. The main outcome was technical success, and the secondary outcomes included visualization of the UMGI tract, examination time, diagnostic yield, compliance, and safety evaluation. Results Thirty patients were enrolled and all UMGI capsule procedures realized repeated observation of the esophagus and duodenum with detection rates of 100.0%, 80.0%, and 86.7% of Z-line, duodenal papilla, and reverse side of pylorus, respectively. String detachment was succeeded in 29 patients (96.7%) and the complete examination rate of UMGI tract was 95.45% (21/22). All UMGI capsule procedures were well tolerated with low discomfort score, and had a good diagnostic yield with per-lesion sensitivity of 96.2% in UGI diseases. No adverse events occurred. Conclusions This new capsule endoscopy system provides an alternative screening modality for the UMGI tract, and might be indicated in cases of suspected upper and small bowel GI bleeding. Trial registration DS-MCE-UGI and SB, NCT04329468. Registered 27 March 2020, https://clinicaltrials.gov/ct2/results?cond=&term=NCT04329468 .

Abstract Background Anxiety and depression are common psychological comorbidities in patients with chronic pancreatitis (CP). There is still a lack of epidemiological studies on anxiety and depression in Chinese CP patients. This study aimed to identify the incidence and related factor of anxiety and depression among East Chinese CP patients and explore the relationship between anxiety, depression, and coping styles. Methods This prospective observational study was conducted from June 1, 2019 to March 31, 2021 in Shanghai, China. Patient diagnosed with CP were interviewed using the sociodemographic and clinical characteristics questionnaire, Self-rating Anxiety Scale (SAS), Self-rating Depression Scale (SDS), and Coping Style Questionnaire (CSQ). Multivariate logistic regression analysis was conducted to identify the related factors of anxiety and depression. Correlation test was preformed to analyze the correlation between anxiety, depression, and coping styles. Results The incidence of anxiety and depression in East Chinese CP patients was 22.64% and 38.61%, respectively. Patients’ previous health status, level of disease coping, frequency of abdominal pain episodes, and pain severity were significantly associated with anxiety and depression. Mature coping styles (Problem solving, Seeking for help) had a positive impact on anxiety and depression, while immature coping styles (Self-blame, Fantasy, Repression, Rationalization) had negative effects on anxiety and depression. Conclusion Anxiety and depression were common in patients with CP in China. The factors identified in this study may provide references for the management of anxiety and depression in CP patients.

Background and Aims: Heavy alcohol consumption and genetic factors represent the 2 major etiologies of chronic pancreatitis (CP). However, little is so far known about the clinical features and genetic basis of light-to-moderate alcohol consumption-related CP (LMA-CP). Methods: A cross-sectional analysis was performed on 1061 Chinese CP patients between 2010 and 2015. CP was classified as classical alcoholic CP (ACP; n = 206), LMA-CP (n = 154), and idiopathic CP (ICP; n = 701). Clinical features and genetic characteristics (PRSS1, SPINK1, CTRC, CFTR variant status) were compared between the different groups. Odds ratios (ORs) with 95% confidence intervals were calculated to ascertain the combinatorial effect of alcohol consumption and gene mutation. Results: Compared with ICP, the clinical features of LMA-CP were characterized by higher rates of developing pancreatic stones, pseudocyst, diabetes, and steatorrhea, which were similar to those associated with ACP. The prevalence of CP-related gene variants in LMA-CP was 38.3%, similar to ACP (39.8%), although significantly lower than ICP (56.2%). Alcohol consumption enhanced the risk of a poor clinical outcome, whereas genetic factors amplified alcohol’s effects. Compared with ICP, LMA-CP and ACP were associated with a high risk of pancreatic stones (patients without variants, OR = 2.01 and 2.54; patients with variants, OR = 2.17 and 1.07), pseudocyst (patients without variants, OR = 1.03 and 1.43; patients with variants, OR = 1.67 and 2.14), diabetes mellitus (patients without variants, OR = 0.86 and 1.31; patients with variants, OR = 2.05 and 1.55), and steatorrhea (patients without variants, OR = 1.56 and 2.10; patients with variants, OR = 2.11 and 1.60). Conclusion: Evidence was presented to show that LMA-CP was clinically and genetically similar to ACP but significantly different from ICP. Our findings provide support to the growing view that there is no safe level of alcohol consumption.

Summary: Background: The disease burden of gastrointestinal disease (GD) in China is high, with significant variation across provinces. A comprehensive agreed set of indicators could guide rational resource allocation to support better GD outcomes. Methods: This study collected data from multiple sources, including national surveillance, surveys, registration systems, and scientific research. Literature reviews and Delphi methods were used to obtain monitoring indicators; the analytic hierarchy process was used to determine indicator weights. Findings: The China Gastrointestinal Health Index (GHI) system consisted of four dimensions and 46 indicators. The weight of the four dimensions from high to low included the prevalence of gastrointestinal non-neoplastic diseases and gastrointestinal neoplasms (GN) (0.3246), clinical treatment of GD (0.2884), prevention and control of risk factors (0.2606), and exposure to risk factors (0.1264). The highest indicator weight of GHI rank was the successful smoking cessation rate (0.1253), followed by the 5-year survival rate of GN (0.0905), and the examination rate of diagnostic oesophagogastroduodenoscopy (0.0661). The overall GHI for China in 2019 was 49.89, varying from 39.19 to 76.13 across all sub-regions. The top five sub-regions in the total GHI score were in the eastern region. Interpretation: GHI is the first system designed to monitor gastrointestinal health systematically. In the future, data from sub-regions of China should be used to test and improve the GHI system for its impact. Funding: This research was supported by the National Health Commission of China, the First Affiliated Hospital of Naval Medical University (2019YXK006), and the Science and Technology Commission of Shanghai Municipality (21Y31900100).

Background and AimWith the increasing burden of colorectal cancer (CRC), the practice of colonoscopy is gaining attention worldwide. However, it exhibits distinct trends between developing and developed countries. This study aims to explore its development and identify influencing factors in China.MethodsThe Chinese Digestive Endoscopy Censuses were conducted twice in mainland China under the supervision of health authorities. Information regarding the practice of colonoscopy was collected through a structured online questionnaire. The authenticity of the data was evaluated through logical tests, and a random selection of endoscopic reports underwent manual validation by Quality Control Centers. Potential factors associated with colonoscopy were analyzed using real-world information.ResultsFrom 2012 to 2019, the number of hospitals that performed colonoscopy increased from 3,210 to 6,325 (1.97-fold), and the volume increased from 5.83 to 12.92 million (2.21-fold). The utilization rate rose from 436.0 to 914.8 per 100,000 inhabitants (2.10-fold). However, there was an exacerbation of regional inequality in the adequacy of colonoscopy. Regions with higher incidence of CRC, higher gross domestic product per capita, more average numbers of endoscopists and tertiary hospitals tended to provide more accessible colonoscopy (P

Background & Aims: A hybrid allele that originated from homologous recombination between CEL and its pseudogene (CELP), CEL-HYB1 increases the risk of chronic pancreatitis (CP). Although suggested to cause digestive enzyme misfolding, definitive in vivo evidence for this postulate has been lacking. Methods: CRISPR-Cas9 was used to generate humanized mice harboring the CEL-HYB1 allele on a C57BL/6J background. Humanized CEL mice and C57BL/6J mice were used as controls. Pancreata were collected and analyzed by histology, immunohistochemistry, immunoblotting, and transcriptomics. Isolated pancreatic acini were cultured in vitro to measure the secretion and aggregation of CEL-HYB1 protein. Mice were given caerulein injections to induce acute pancreatitis (AP) and CP. Results: Pancreata from mice expressing CEL-HYB1 developed pathological features characteristic of focal pancreatitis that included acinar atrophy and vacuolization, inflammatory infiltrates, and fibrosis in a time-dependent manner. CEL-HYB1 expression in pancreatic acini led to decreased secretion and increased intracellular aggregation and triggered endoplasmic reticulum stress compared with CEL. The autophagy levels of pancreata from mice expressing CEL-HYB1 changed at different developmental stages; some aged CEL-HYB1 mice exhibited an accumulation of large autophagic vesicles and impaired autophagy in acinar cells. Administration of caerulein increased the severity of AP/CP in mice expressing CEL-HYB1 compared with control mice, accompanied by higher levels of endoplasmic reticulum stress. Conclusions: Expression of a humanized form of CEL-HYB1 in mice promotes endoplasmic reticulum stress and pancreatitis through a misfolding-dependent pathway. Impaired autophagy appears to be involved in the pancreatic injury in aged CEL-HYB1 mice. These mice have the potential to be used as a model to identify therapeutic targets for CP.

Neutrophils are the most abundant leukocyte population in the human circulatory system and are rapidly recruited to sites of inflammation. Neutrophils play a multifaceted role in intestinal inflammation, as they contribute to the elimination of invading pathogens. Recently, their role in epithelial restitution has been widely recognized; however, they are also associated with bystander tissue damage. The intestinal epithelium provides a physical barrier to prevent direct contact of luminal contents with subepithelial tissues, which is extremely important for the maintenance of intestinal homeostasis. Numerous studies have demonstrated that transepithelial migration of neutrophils is closely related to disease symptoms and disruption of crypt architecture in inflammatory bowel disease and experimental colitis. There has been growing interest in how neutrophils interact with the epithelium under inflammatory conditions. Most studies focus on the effects of neutrophils on intestinal epithelial cells; however, the effects of intestinal epithelial cells on neutrophils during intestinal inflammation need to be well-established. Based on these data, we have summarized recent articles on the role of neutrophil–epithelial interactions in intestinal inflammation, particularly highlighting the epithelium-derived molecular regulators that mediate neutrophil recruitment, transepithelial migration, and detachment from the epithelium, as well as the functional consequences of their crosstalk. A better understanding of these molecular events may help develop novel therapeutic targets for mitigating the deleterious effects of neutrophils in inflammatory bowel disease.

Increasing attention is being paid to the unique roles gut microbes play in both physiological and pathological processes. Crohn’s disease (CD) is a chronic, relapsing, inflammatory disease of the gastrointestinal tract with unknown etiology. Currently, gastrointestinal infection has been proposed as one initiating factor of CD. Yersinia enterocolitica, a zoonotic pathogen that exists widely in nature, is one of the most common bacteria causing acute infectious gastroenteritis, which displays clinical manifestations similar to CD. However, the specific role of Y. enterocolitica in CD is controversial. In this Review, we discuss the current knowledge on how Y. enterocolitica and derived microbial compounds may link to the pathogenesis of CD. We highlight examples of Y. enterocolitica-targeted interventions in the diagnosis and treatment of CD, and provide perspectives for future basic and translational investigations on this topic.

BackgroundPancreatic cancer (PC) is a highly malignant tumor of the digestive system. As clinical trials involving PC are increasingly being conducted, the transparency of the generated data has become an important issue of concern. In other areas of medicine, clinical trial transparency presents a worrying state of affairs. However, at present, there has been no study examining the transparency of data derived from PC clinical trials.MethodsA comprehensive search was conducted in the ClinicalTrial.gov database for clinical trials investigating pancreatic cancer as of June 2022. We examined the availability of clinical trial results and recorded the characteristics of the trials.ResultsA total of 856 trials were included in this study, of which 668 were completed and 188 were terminated or suspended. The results of 626 trials (73.13%) were available, of these 230 trials (26.87%) did not disclose any information on the trial data in any form. The publication rate for trials with available results was 86.10%, but the report rate on ClinicalTrial.gov was only 39.78%.ConclusionAlthough approximately 90% of clinical trial investigating interventions on patients with PC have published study results, 30% of trials did not report any findings, and the disclosure of trial results from ClinicalTrial.gov was unsatisfactory. In general, there is still room for improvement in the transparency of PC clinical trials.

Peptidylarginine deiminases (PADs) are the only enzyme class known to deiminate arginine residues into citrulline in proteins, a process known as citrullination. This is an important post-translational modification that functions in several physiological and pathological processes. Neutrophil extracellular traps (NETs) are generated by NETosis, a novel cell death in neutrophils and a double-edged sword in inflammation. Excessive activation of PADs and NETs is critically implicated in their transformation from a physiological to a pathological state. Herein, we review the physiological and pathological functions of PADs and NETs, in particular, the involvement of PAD2 and PAD4 in the digestive system, from inflammatory to oncological diseases, along with related therapeutic prospects.

Abstract Psychosocial stress is a vital factor contributing to the pathogenesis and progression of inflammatory bowel disease (IBD). The contribution of intestinal macrophage autophagy to the onset and development of IBD has been widely studied. Herein, we investigated the underlying mechanism of psychosocial stress in an IBD mouse model pertaining to macrophage autophagy. Corticotropin releasing hormone (CRH) was peripherally administrated to induce psychosocial stress. For in vivo studies, dextran sulfate sodium (DSS) was used for the creation of our IBD mouse model. For in vitro studies, lipopolysaccharide (LPS) was applied on murine bone marrow-derived macrophages (BMDMs) as a cellular IBD-related challenge. Chloroquine was applied to inhibit autophagy. We found that CRH aggravated the severity of DSS-induced IBD, increasing overall and local inflammatory reactions and infiltration. The levels of autophagy in intestinal macrophages and murine BMDMs were increased under these IBD-related inflammatory challenges and CRH further enhanced these effects. Subsequent administration of chloroquine markedly attenuated the detrimental effects of CRH on IBD severity and inflammatory reactions via inhibition of autophagy. These findings illustrate the effects of peripheral administration of CRH on DSS-induced IBD via the enhancement of intestinal macrophage autophagy, thus providing a novel understanding as well as therapeutic target for the treatment of IBD.

BackgroundAs a processing method of RNA precursors, alternative splicing (AS) is critical to normal cellular activities. Aberrant AS events are associated with cancer development and can be promising targets to treat cancer. However, no detailed and unbiased study describes the current state of AS of cancer research. We aim to measure and recognize the current state and trends of AS cancer research in this study.MethodsThe Web of Science Core Collection was used to acquire the articles. Utilizing three bibliometric tools (CiteSpace, VOSviewer, R-bibliometrix), we were able to measure and recognize the influence and collaboration data of individual articles, journals, and co-citations. Analysis of co-occurrence and burst information helped us identify the trending research areas related to AS of cancer.ResultsFrom 2012 to 2021, the total number of papers on AS of cancer published in 766 academic journals was 3,507, authored by 20,406 researchers in 405 institutions from 80 countries/regions. Research involving AS of cancer genes was primarily conducted in the United States and China; simultaneously, the Chinese Academy of Sciences, Fudan University, and National Cancer Institute were the institutions with strong research capabilities. Scorilas Andreas is the scholar with the most publications, while the most co-citations were generated by Wang, Eric T. Plos One published the most papers on AS of cancer, while J Biol Chem was the most co-cited academic journal in this field. The results of keyword co-occurrence analysis can be divided into three types: molecular (P53, CD44, androgen receptor, srsf3, esrp1), pathological process (apoptosis, EMT, metastasis, angiogenesis, proliferation), and disease (breast cancer, colorectal cancer, prostate cancer, hepatocellular carcinoma, gastric cancer).ConclusionResearch on AS of cancer has been increasing in intensity over the past decade. Current AS of cancer studies focused on the hallmarks of AS in cancer and AS signatures including diagnostic and therapeutic targets. Among them, the current trends are splicing factors regulating epithelial–mesenchymal transition and other hallmarks, aberrant splicing events in tumors, and further mechanisms. These might give researchers interested in this field a forward-looking perspective and inform further research.

Background: Endoscopic pancreatic stenting is an effective way to relieve the stricture of the pancreatic duct. However, proximal stent migration presents a threat to the patient and a challenge to the doctor. The limited space in the pancreatic duct often prevents the operation of suitable devices for stent removal. Case presentation: A 34-year-old man with painful chronic pancreatitis received endoscopic retrograde cholangiopancreatography (ERCP) and insertion of a pancreatic plastic stent, with 8.5 Fr in diameter and 12 cm in length. A year later, radiography revealed that the proximal end of the stent rested in the pancreatic tail while the distal end rested in the branch duct. Both balloon and rat-tooth forceps were used but failed to retrieve the stent. A week later, a second ERCP was performed. After dilation with a 10-mm balloon, a small amount of bleeding was noticed and a crack appeared in the wall of the branch duct. Consequently, the distal end of the stent was released. Then, rat-tooth forceps was used to grasp the distal end, and the stent was pulled out successfully. Conclusions: For a proximally migrated pancreatic stent stuck at both ends, a strategy of maximum dilation can be used cautiously to retrieve the stent.

ABSTRACT Maintaining the health of seafarers is a difficult task during long-term voyages. Little is known about the corresponding changes in the gut microbiome-host interaction. This study recruited 30 seafarers undertaking a 6-month voyage and analyzed their gut microbiota using 16S rRNA gene sequencing. Fecal untargeted metabolomics analysis was performed using liquid chromatography-mass spectrometry. Significant changes in the composition of the gut microbiota and an increased ratio of Firmicutes/Bacteroidetes at the end (day 180) of the 6-month voyage, relative to the start (day 0), were observed. At the genus level, the abundances of Holdemanella and Plesiomonas were significantly increased, while the abundance of Bacteroides was decreased. Predicted microbial functional analysis revealed significant decreases in folate biosynthesis and biotin metabolism. Furthermore, 20 differential metabolites within six differentially enriched human metabolic pathways (including arginine biosynthesis, lysine degradation, phenylalanine metabolism, sphingolipid metabolism, pentose and glucuronate interconversions, and glycine, serine, and threonine metabolism) were identified by comparing the fecal metabolites at day 0 and day 180. Spearman correlation analysis revealed close relationships between the 14 differential microbiota members and the six differential fecal metabolites that might affect specific human metabolic pathways. This study adopted a multi-omics approach and provides potential targets for maintaining the health of seafarers during long-term voyages. These findings are worthy of more in-depth exploration in future studies. IMPORTANCE Maintaining the health of seafarers undertaking long-term voyages is a difficult task. Apart from the alterations in the gut microbiome and fecal metabolites after a long-term voyage, our study also revealed that 20 differential metabolites within six differentially enriched human metabolic pathways are worthy of attention. Moreover, we found close relationships between the 14 differential microbiota members and the six differential fecal metabolites that might impact specific human metabolic pathways. Accordingly, preventative measures, such as adjusting the gut microbiota by decreasing potential pathobionts or increasing potential probiotics as well as offsetting the decrease in B vitamins and beneficial metabolites (e.g., d-glucuronic acid and citrulline) via dietary adjustment or nutritional supplements, might improve the health of seafarers during long-term sea voyages. These findings provide valuable clues about gut microbiome-host interactions and propose potential targets for maintaining the health of seafarers engaged in long-term sea voyages.

Background and Aims: Actual behaviors of drugs in the upper GI tract are not well elucidated. We assess the feasibility of magnetically controlled capsule endoscopy (MCE) in direct and real-time visualization of oral drug behaviors in the stomach. Methods: From November 2019 to December 2019, 9 patients with a recent history of upper GI symptoms and 10 healthy volunteers were enrolled in this study. Participants swallowed magnetically controlled capsules to examine the whole stomach. After baseline examination, participants ingested dyed sucralfate gel, and MCE recorded the adhesion time, retention time, and distribution area of sucralfate gel. Outcomes included behaviors of sucralfate gel, safety, and satisfaction assessment of the procedures. Results: Adhesion time of sucralfate gel in the abdominal symptoms group was significantly shorter than in the healthy control group (23.76 ± 1.37 minutes vs 31.96 ± 3.09 minutes; P = .032), whereas retention time was longer (98.85 ± 13.94 minutes vs 63.93 ± 8.57 minutes; P = .043). The distribution area of sucralfate gel in the abdominal symptoms group was significantly larger than in healthy control group in cardia (24.29 ± 7.39 vs 9.18 ± 4.06; P < .0001), fundus (18.90 ± 7.08 vs 8.49 ± 4.10; P = .0015), and pylorus (4.64 ± 2.72 vs 0.94 ± 0.90; P = .0019). No adverse events were observed. All participants had a high degree of satisfaction. Conclusions: MCE is a feasible and noninvasive tool for direct and real-time visualization of drug behaviors (eg, sucralfate gel) in the stomach. (ClinicalTrials.gov. ID: NCT04327869.)

ObjectiveThe pathogenesis of chronic pancreatitis (CP) is not completely clear. With further studies, smoking is toxic to the pancreas. This study classified smoking-related CP as a new etiology of CP and defined the cutoff of smoking.DesignPatients with CP admitted from January 2000 to December 2013 were included in the study. The characteristics were compared between smoking patients, drinking patients, and a group of patients who never smoke or drink (control group). The cumulative rates of steatorrhea, diabetes mellitus (DM), pancreatic pseudocyst (PPC), pancreatic stone, and biliary stricture after the onset of CP were calculated, respectively.ResultsA total of 1,324 patients were included. Among them, 55 were smoking patients, 80 were drinking patients, and 1,189 were controls. The characteristics of smokers are different from the other two groups, especially in age at the onset and diagnosis of CP, initial manifestation, and type of pain. The development of DM (P = 0.011) and PPC (P = 0.033) was significantly more common and earlier in the smokers than in the other two groups. Steatorrhea also developed significantly more in the smokers than in the controls (P = 0.029). Smokers tend to delay the formation of pancreatic stones and steatorrhea.ConclusionThe clinical characteristics of smoking-related CP is different from CP of other etiologies. A new type of CP, smoking-related CP, was put forward. Smoking-related CP should be separated from idiopathic CP and defined as a new independent subtype of CP different from alcoholic CP or idiopathic CP.

Abstract Background Although the number of existing cases of coronavirus disease 2019 (COVID-19) in China has been decreasing since late February 2020, the number of confirmed cases abroad is surging. Improving public knowledge of COVID-19 is critical to controlling the pandemic. This study aimed to determine China’s public knowledge of COVID-19 and the attitudes towards control measures. Methods A cross-sectional study was conducted over 48 h from 22:30 29 February 2020 to 22:30 2 March 2020 based on a self-administered web-based questionnaire. The survey was conducted on the WeChat network. Exponential non-discriminative snowball sampling was applied. The questionnaire was voluntarily completed by WeChat users. The questionnaire covered basic demographic information, public knowledge of the epidemiological and clinical characteristics of COVID-19, psychological state, and attitudes towards the overall control measures. The primary outcome was the China’s public knowledge of COVID-19 and the attitudes towards control measures and secondary outcome was the psychological state of the public during this pandemic. Results The study included 10,905 participants and 10,399 valid questionnaires were included for analysis. Participants with tertiary education, younger participants and healthcare workers had better overall knowledge than other participants (all P

Background/Aims: Single-balloon enteroscopy (SBE) has been widely used in diagnosing small bowel disease. We conducted this study to systematically appraise its technical and clinical performance. Methods: Studies on SBE published by September 2018 were systematically searched. Technical and clinical performance data were collected and analyzed with descriptive or meta-analysis methods. Results: In total, 54 articles incorporating 4,592 patients (6,036 procedures) were included. Regarding technical parameters, the pooled insertion depths (IDs) for anterograde and retrograde SBE were 209.2 cm and 98.1 cm, respectively. The pooled retrograde ID in Asian countries was significantly greater than that in Western countries (129.0 cm vs 81.1 cm, p

Abstract Background A full spectrum of video capsule endoscopy (VCE) adverse events over the past two decades has not been evaluated. We aimed to determine pooled rates, predictors and temporal-trend of VCE adverse events over the past two decades. Methods Systematic search of PubMed and EMBASE for English-language publications reporting VCE adverse events (January 1, 2000 to March 31, 2019). Data were extracted independently by two investigators. Pooled VCE adverse event rates were calculated using the random or fixed model as appropriate. Predictors and temporal-trend of each adverse event were performed by meta-regression analyses. Results In total, 402 studies were identified, including 108,079 VCE procedures. Rate of retention, swallow disorder, aspiration, technical failure, and procedural adverse events were 0.73% (95% confidence interval [CI] 0.59–0.89%), 0.75% (95% CI 0.43–1.13%), 0.00% (95% CI 0.00–0.00%), 0.94% (95% CI 0.65–1.28%), 0.67% (95% CI 0.32–1.10%), respectively; incomplete examination rate of esophagus, stomach, small bowel, and colon were 9.05%, 7.69%, 12.08%, 19.19%, respectively. Patency capsule reduced retention rate by 5.04%, whereas known inflammatory bowel disease increased retention rate by 4.29%. Elder was the risk and protective factor for small bowel incomplete examination (0.30%) and swallow disorder (− 0.72%), respectively. Rates of retention and small bowel incomplete examination significantly declined over time (P = .0006 and P

BackgroundPreoperative sarcopenia is a prognostic risk factor for gastric cancer (GC). This study aimed to determine whether radiomic sarcopenia features on computed tomography (CT) could be used to diagnose sarcopenia preoperatively, and whether they could be used to accurately predict the postoperative survival and complication prognosis of patients with GC.MethodsWe retrospectively analyzed data of 550 patients with GC who underwent radical gastrectomy. The patients were divided into training (2014–2016) and validation (2017–2019) cohorts. We established a radiomics-based diagnosis tool for sarcopenia. Thereafter, univariate and multivariate analyses of diagnostic factors were carried out. Receiver operator characteristic (ROC) curves and area under the curve (AUC) were used to compare different diagnostic models. The Kaplan–Meier method was used to estimate the survival curve.ResultsRadiomic sarcopenia correlated with complications and long-term survival. Skeletal muscle index, grip strength, and walking speed were correlated with postoperative complications in both cohorts (AUCs: 0.632, 0.577, and 0.614, respectively in the training cohort; 0.570, 0.605, 0.546, respectively, in the validation cohort), and original sarcopenia was more accurate than any of these indicators. However, radiomic sarcopenia has a higher AUC in predicting short-term complications than original sarcopenia in both groups (AUCs: 0.646 vs. 0.635 in the training cohort; 0.641 vs. 0.625 in the validation cohort). In the training cohort, the overall survival time of patients with original sarcopenia was shorter than normal patients (hazard ratio, HR = 1.741; 95% confidence interval [CI], 1.044–2.903; p = 0.031). While radiomic sarcopenia had a greater prognostic significance, the overall survival time of patients with radiomic sarcopenia was significantly worse than normal patients (HR, 1.880; 95% CI, 1.225–2.885, p = 0.003).ConclusionExtracted sarcopenia features based on CT can predict long-term survival and short-term complications of GC patients after surgery, and its accuracy has been verified by training and validation groups. Compared with original sarcopenia, radiomic sarcopenia can effectively improve the accuracy of survival and complication prediction and also shorten the time and steps of traditional screening, thereby reducing the subjectivity effects of sarcopenia assessment.

Summary: Background: Functional constipation (FC) is an intractable disease that carries large financial burden as well as emotional and physical stress. We aimed to assess the efficacy and safety of the newly developed smartphone-controlled vibrating capsule (VC) in patients with FC. Methods: From December 2018 to February 2020, we did a multicenter, blinded, placebo-controlled randomised trial in six top general hospitals in China focusing on patients aged 18 to 80 with FC. Patients were randomly assigned in a 1:1 ratio to receive VCs or placebo treatment for six weeks (two capsules per week) after a two-week baseline period. The primary outcome was the responder rate, defined as the proportion of patients with an increase of at least one complete spontaneous bowel movement (CSBM) per week during treatment compared to baseline in the full analysis set. This trial is registered with ClinicalTrials.gov, number NCT04671264, and is completed. Findings: 107 patients aged from 18 to 74 were randomly assigned to receive VC (n = 53) or placebo treatment (n = 54). The responder rate in the VC group was significantly higher than that in the placebo group (64·2% vs. 35·8%; difference, 27·7% [95% CI, 10·4–45·1]; P = 0·005). More patients in the VC group reported weekly CSBMs ≥ 1 for at least four weeks during treatment (difference, 22·7% [95% CI, 8–46]; P = 0·022) and follow-up period (difference, 17.3% [95% CI, 0–35]; P = 0·048). The mean Patient Assessment of Constipation-Symptoms score and Patient Assessment of Constipation-Quality of Life score differed significantly from the baseline in both groups (all P

Whether pancreatic extracorporeal shock wave lithotripsy (ESWL) is safe for patients with autosomal dominant polycystic kidney disease (ADPKD) is unclear. A woman in her early 30s was admitted to our hospital because of intermittent upper abdominal pain and recurrent pancreatitis. The imaging results confirmed the diagnosis of pancreatic stones and ADPKD. We performed pancreatic ESWL using a third-generation lithotripter to pulverize the pancreatic stones. A maximum of 5000 shock waves was delivered per therapeutic session. A second session of ESWL was performed the next day. The patient developed no adverse events or complications related to pancreatic ESWL. Three years after treatment, the patient had developed no relapse of pancreatitis or abdominal pain. Shock waves do not lead to complications such as hematuria, cyst rupture, or deterioration of the inner bleeding of renal cysts. Multiple kidney cysts are not a contraindication for pancreatic ESWL.

BackgroundColon cancer is one of the most frequent malignancies and causes high mortality worldwide. Exploring the tumor-immune interactions in the tumor microenvironment and identifying new prognostic and therapeutic biomarkers will assist in decoding the novel mechanism of tumor immunotherapy. BGN is a typical extracellular matrix protein that was previously validated as a signaling molecule regulating multiple processes of tumorigenesis. However, its role in tumor immunity requires further investigation.MethodsThe differentially expressed genes in three GEO datasets were analyzed, and BGN was identified as the target gene by intersection analysis of PPIs. The relevance between clinical outcomes and BGN expression levels was evaluated using data from the GEO database, TCGA and tissue microarray of colon cancer samples. Univariable and multivariable Cox regression models were conducted for identifying the risk factors correlated with clinical prognosis of colon cancer patients. Next, the association between BGN expression levels and the infiltration of immune cells as well as the process of the immune response was analyzed. Finally, we predicted the immunotherapeutic response rates in the subgroups of low and high BGN expression by TIS score, ImmuCellAI and TIDE algorithms.ResultsBGN expression demonstrated a statistically significant upregulation in colon cancer tissues than in normal tissues. Elevated BGN was associated with shorter overall survival as well as unfavorable clinicopathological features, including tumor size, serosa invasion and length of hospitalization. Mechanistically, pathway enrichment and functional analysis demonstrated that BGN was positively correlated with immune and stromal scores in the TME and primarily involved in the regulation of immune response. Further investigation revealed that BGN was strongly expressed in the immunosuppressive phenotype and tightly associated with the infiltration of multiple immune cells in colon cancer, especially M2 macrophages and induced Tregs. Finally, we demonstrated that high BGN expression presented a better immunotherapeutic response in colon cancer patients.ConclusionBGN is an encouraging predictor of diagnosis, prognosis and immunotherapeutic response in patients with colon cancer. Assessment of BGN expression represents a novel approach with great promise for identifying patients who may potentially benefit from immunotherapy.

Abstract Background Despite pancreatic extracorporeal shock wave lithotripsy (P-ESWL) is a minimally invasive treatment for pancreatic stones, complications exist. Case presentation A 37-year-old male was diagnosed with chronic pancreatitis and admitted to our hospital for recurrent acute pancreatitis. After the first P-ESWL session, the patient complained of a new type of pain different from the previous pain pattern. Computerized tomography and colonoscopy were arranged and colonic hematoma was found. Since the patient had stable vital signs, no special treatment was given focusing on the colonic hematoma. Five days later, P-ESWL treatment was repeatedly performed for four consecutive days. Two days after the last P-ESWL session, the patient underwent endoscopic retrograde cholangiopancreatography. At the three-month follow up visit, the colonic hematoma disappeared and pancreatic stones decreased significantly. Conclusions To the best of our knowledge, colonic hematoma after P-ESWL for pancreatic stones has never been reported. Here, we present the only case of colonic hematoma after P-ESWL, which was coincidentally found in more than 6000 P-ESWL sessions in our hospital. As the symptoms of colonic hematoma are mild, we believe the incidence of colonic hematoma has been underestimated. Many people with colonic hematoma after P-ESWL may be undiagnosed or misdiagnosed. Treatment for colonic hematoma depends on whether there is severe clinical state. Exploration of more precise location method for pancreatic stones may reduce the probability of P-ESWL complication.

Background Over 90% of pancreatic stones are radiopaque and can be treated with endoscopy or surgery. However, radiolucent stones are different than radiopaque stones in nature and formation, and therefore, treatment varies. Case presentation: A 25-year-old woman was admitted because of recurrent acute pancreatitis. Imaging examinations confirmed the diagnosis of chronic pancreatitis (CP), and which revealed the existence of radiolucent stones. Endoscopic retrograde cholangiopancreatography (ERCP) was performed and abundant protein-like radiolucent stones were extracted. Three 10F, 7-cm plastic stents were placed. However, the stents were completely occluded by radiolucent stones 1 month later. A nasopancreatic tube was then inserted and flushed regularly, but protein-like stones formed continuously. After multidisciplinary consultation, the following conservative treatment strategy was applied: 1) no more endotherapy; 2) a diet with 40% to 50% of calories from fat was recommended; 3) no pancreatic enzyme replacement therapy; and 4) regular exercise. The above advice aimed to stimulate the secretion of pancreatic fluid to achieve auto-flushing of the pancreatic duct and prevent protein-like stones from depositing. No acute pancreatitis recurred during the 5-year follow-up. Conclusions This strategy was effective for auto-flushing the pancreatic duct in patients with radiolucent pancreatic stones after the main pancreatic duct stricture was resolved.

Abstract Background Autoimmune factor was regarded as one of the risk factors in the pathogenesis of chronic pancreatitis (CP), especially for autoimmune pancreatitis (AIP). However, whether autoimmune factor plays a role in non-AIP CP or not was unknown. Methods Hospitalized patients with non-AIP CP from January 2010 to October 2016 were detected for 22 autoantibodies at the time of hospital admission. Autoantibodies with frequency > 0.5% were enrolled to calculate the frequency in historial healthy controls through literature search in PubMed. Differentially expressed autoantibodies were determined between patients and historial healthy controls, and related factors were identified by multivariate logistic regression analysis. Results In a total of 557 patients, 113 cases were detected with 19 kinds of positive autoantibodies, among them anti-β2-glycoprotein I (β2-GPI) antibody was most frequent (9.16%). Compared with historial healthy controls, the frequencies of serum β2-GPI and anti SS-B antibody in patients were significantly higher, while frequencies of anti-smooth muscle antibody and anticardiolipin antibody were significantly lower (all P

Abstract Background The clinical significance of SPINK1 intronic variants in chronic pancreatitis has been previously assessed by various approaches including a cell culture-based full-length gene assay. A close correlation between the results of this assay and in silico splicing prediction was apparent. However, until now, a clinical diagnostic pipeline specifically designed to classify SPINK1 intronic variants accurately and efficiently has been lacking. Herein, we present just such a pipeline and explore its efficacy and potential utility in potentiating the classification of newly described SPINK1 intronic variants. Results We confirm a close correlation between in silico splicing prediction and results from the cell culture-based full-length gene assay in the context of three recently reported pathogenic SPINK1 intronic variants. We then integrated in silico splicing prediction and the full-length gene assay into a stepwise approach and tested its utility in the classification of two novel datasets of SPINK1 intronic variants. The first dataset comprised 16 deep intronic variants identified in 52 genetically unexplained Chinese chronic pancreatitis patients by sequencing the entire intronic sequence of the SPINK1 gene. The second dataset comprised five novel rare proximal intronic variants identified through the routine analysis of the SPINK1 gene in French pancreatitis patients. Employing a minor allele frequency of > 5% as a population frequency filter, 6 of the 16 deep intronic variants were immediately classified as benign. In silico prediction of the remaining ten deep intronic variants and the five rare proximal intronic variants with respect to their likely impact on splice site selection suggested that only one proximal intronic variant, c.194 + 5G > A, was likely to be of functional significance. Employing the cell culture-based full-length gene assay, we functionally analyzed c.194 + 5G > A, together with seven predicted non-functional variants, thereby validating their predicted effects on splicing in all cases. Conclusions We demonstrated the accuracy and efficiency of in silico prediction in combination with the cell culture-based full-length gene assay for the classification of SPINK1 intronic variants. Based upon these findings, we propose an operational pipeline for classifying SPINK1 intronic variants in the clinical diagnostic setting.

Background/Aims: Endoscopic retrograde cholangiopancreatography (ERCP) in Billroth II gastrectomy patients is technically demanding and factors affecting its technical difficulty have not yet been clarified. This study aimed to investigate the outcomes of ERCP in Billroth II gastrectomy patients and identify potential factors affecting its technical failure. Patients and Methods: A large retrospective study of 308 consecutive patients (391 procedures) with Billroth II gastrectomy—who underwent ERCP from January 2002 to December 2016—was conducted. The outcomes of ERCP and potential factors affecting its technical failure were analyzed. Results: The success rate of duodenal ampullary access, selective duct cannulation and the accomplishment of expected procedures was 81.3% (318/391), 86.5% (275/318) and 97.3% (256/263), respectively, and the technical success rate was 70.3% (275/391). The overall ERCP-related complication rate was 15.3% (60/391). The multivariate analysis indicated that first-time ERCP attempt [odds ratio (OR) 4.29, 95% confidence interval (CI) 2.34–7.85, P < 0.001], Braun anastomosis (OR 3.65, 95% CI 1.38–9.64, P < 0.009), and no cap-assisted gastroscope (OR 3.05, 95% CI 1.69–5.51, P < 0.001) were significantly associated with technical failure. Conclusions: ERCP is safe, effective and feasible for Billroth II gastrectomy patients. Previous ERCP history, absence of Braun anastomosis and the use of a cap-assisted gastroscope are the predictive factors for its technical success.

Abstract Background Pediatric patients always suffer from chronic pancreatitis (CP), especially those with steatorrhea. This study aimed to identify the incidence of and risk factors for steatorrhea in pediatric CP. To our best knowledge, there is no pediatric study to document the natural history of steatorrhea in CP. Methods CP patients admitted to our center from January 2000 to December 2013 were enrolled. Patients were assigned to the pediatric (

Abstract Background Endoscopic ultrasonography (EUS)-guided drainage has become the first-line therapy for late peri-pancreatic fluid collection (PFC). Double pigtail plastic stents (DPPS) and lumen-apposing metal stents (LAMS) are commonly used for PFC drainage. Recently, a multi-institutional consensus on PFC drainage has recommended that LAMS should be the standard care for patients with walled-off necrosis (WON). However, given the poor quality of evidence, we aim to perform a large-scale randomized controlled trial to determine whether LAMS is superior to DPPS for WON drainage. Methods/design The study is an open-label, prospective, parallel-group, superiority, multicenter randomized controlled trial. Two hundred and fifty-six patients with WON who will attend 18 tertiary hospitals in China will be randomly allocated to the LAMS or DPPS group before the procedure. The primary endpoint is the clinical success at one month after drainage (reduction in the size of WON to

Abstract Background Pancreatic extracorporeal shock wave lithotripsy (P-ESWL) is the first-line therapy for large pancreatic duct stones. Although it is a highly effective and safe procedure for the fragmentation of pancreatic stones, it is still not complication-free. Just like endoscopic retrograde cholangiopancreatography (ERCP), pancreatitis is the most common complication. To date, nonsteroidal anti-inflammatory drugs (NSAIDs) have proven to be the only effective prophylactic medication for post-ERCP pancreatitis and the European, American and Japanese Society for Gastrointestinal Endoscopy guidelines have recommended prophylactic rectally administered indomethacin for all patients undergoing ERCP. Given the little research about effective prevention for post P-ESWL pancreatitis, we aim to determine whether rectally administered indomethacin can reduce post-ESWL-pancreatitis. Methods/design The RIPEP study is a prospective, randomized, double-blinded, placebo-controlled trial. One thousand three hundred and seventy patients with chronic pancreatitis and pancreatic stones (>5 mm in diameter) treated with P-ESWL at Changhai Hospital will be randomly allocated to rectally administered indomethacin or placebo therapy before the procedure. The primary endpoint is the incidence of post-ESWL pancreatitis. Secondary endpoints include the severity of pancreatitis, occurrence rate of asymptomatic hyperamylasemia and other complications. Discussion The RIPEP trial is designed to show that rectally administered indomethacin reduces the development and severity of post-ESWL pancreatitis and benefits patients treated with P-ESWL. Trial registration ClinicalTrials.gov, ID: NCT02797067 . Registered on 17 November 2016.

Abstract Constipation, mainly manifesting as abdominal discomfort and painful defecation, is considered as a chronic disorder. Due to a lack of effective therapy, it imposes a significant economic burden and greatly impacts patients’ quality of life which prompt searches for new, original approaches. Based on the research of vibrating capsule (VC) carried out by Ron et al., we investigated the safety and efficacy of an innovative, multi-mode VC in terms of its effect on defecation in animal studies. The parameters associated with different operation modes of VCs can be detected and adjusted by smartphone controlled external configuration device (ECD). The results of blood tests, physiological parameters, CT scan and pathological examination showed no significant abnormality, which undoubtedly confirmed the safety of VCs. For efficacy studies, defecation frequency of beagles increased after administration of these capsules without influence on stool characters. Meanwhile, the mean time of capsule evacuation tended to be reduced while showing no significant difference between different modes. In summary, this study elucidates the safety and effectiveness of VC in prompting the passage of gastrointestinal walls thus greatly increasing the defecation frequency. This study innovatively displays the promising application of VC in the treatment of constipation.

Abstract Background SPINK1 (serine protease inhibitor, kazal-type, 1), which encodes human pancreatic secretory trypsin inhibitor, is one of the most extensively studied genes underlying chronic pancreatitis. Recently, based upon data from qualitative reverse transcription-PCR (RT-PCR) analyses of transfected HEK293T cells, we concluded that 24 studied SPINK1 intronic variants were not of pathological significance, the sole exceptions being two canonical splice site variants (i.e., c.87 + 1G > A and c.194 + 2T > C). Herein, we employed the splicing prediction tools included within the Alamut software suite to prioritize the ‘non-pathological’ SPINK1 intronic variants for further quantitative RT-PCR analysis. Results Although our results demonstrated the utility of in silico prediction in classifying and prioritizing intronic variants, we made two observations worth noting. First, we established that most of the prediction tools employed ignored the general rule that GC is a weaker donor splice site than the canonical GT site. This finding is potentially important because for a given disease gene, a GC variant donor splice site may be associated with a milder clinical manifestation. Second, the non-pathological c.194 + 13T > G variant was consistently predicted by different programs to generate a new and viable donor splice site, the prediction scores being comparable to those for the physiological c.194 + 2T donor splice site and even higher than those for the physiological c.87 + 1G donor splice site. We do however provide convincing in vitro evidence that the predicted donor splice site was not entirely spurious. Conclusions Our findings, taken together, serve to emphasize the importance of functional analysis in helping to establish or refute the pathogenicity of specific intronic variants.