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AimLong non-coding RNAs (lncRNAs) have been identified to regulate cancers by controlling the process of autophagy and by mediating the post-transcriptional and transcriptional regulation of autophagy-related genes. This study aimed to investigate the potential prognostic role of autophagy-associated lncRNAs in colorectal cancer (CRC) patients.MethodsLncRNA expression profiles and the corresponding clinical information of CRC patients were collected from The Cancer Genome Atlas (TCGA) database. Based on the TCGA dataset, autophagy-related lncRNAs were identified by Pearson correlation test. Univariate Cox regression analysis and the least absolute shrinkage and selection operator analysis (LASSO) Cox regression model were performed to construct the prognostic gene signature. Gene set enrichment analysis (GSEA) was used to further clarify the underlying molecular mechanisms.ResultsWe obtained 210 autophagy-related genes from the whole dataset and found 1187 lncRNAs that were correlated with the autophagy-related genes. Using Univariate and LASSO Cox regression analyses, eight lncRNAs were screened to establish an eight-lncRNA signature, based on which patients were divided into the low-risk and high-risk group. Patients’ overall survival was found to be significantly worse in the high-risk group compared to that in the low-risk group (log-rank p = 2.731E-06). ROC analysis showed that this signature had better prognostic accuracy than TNM stage, as indicated by the area under the curve. Furthermore, GSEA demonstrated that this signature was involved in many cancer-related pathways, including TGF-β, p53, mTOR and WNT signaling pathway.ConclusionsOur study constructed a novel signature from eight autophagy-related lncRNAs to predict the overall survival of CRC, which could assistant clinicians in making individualized treatment.

The aim of this study was to compare the effects of colonic electrical stimulation (CES) and prucalopride on gastrointestinal transit and defecation and to verify the safety of CES in a canine model of constipation.Eight beagles received CES implantation and induction drugs for slow transit constipation (STC). In the STC model, the gastrointestinal transit time (GITT), colonic transit time (CTT), stool frequency and stool consistency were assessed to compare the effects of CES and prucalopride on gastrointestinal transit and defecation. The histocompatibility of the implantable device was evaluated.The individualized parameters for CES varied greatly among the animals, and the GITTs were not significantly shortened by CES or prucalopride; however, both the CES and prucalopride treatment significantly accelerated CTT and improved stool consistency compared with sham stimulation. CES treatment also resulted in significantly higher stool frequency than prucalopride treatment, which did not significantly change the stool frequency. No severe inflammation response was detected in the gross and microscopic appearance around the implants.CES and prucalopride treatment may yield similar short-term effects for improving gastrointestinal transit and stool consistency, and CES outperformed prucalopride treatment in terms of defecation inducement in the short term. There were ideal levels of endurance and histocompatibility for the animals that underwent CES.

To investigate the clinicopathological and molecular features of colorectal cancer (CRC) with synchronous adenoma and to describe features of synchronous adenomas in CRC patients.Single-centre retrospective cohort of 180 patients were included. The clinicopathological and endoscopic data were collected. The expression mismatch repair (MMR) proteins were detected by immunohistochemistry. The determination of microsatellite instability (MSI) was performed by multiple fluorescence PCR, and the mutations of genes were detected by real-time PCR.Among all cases, 49 were diagnosed as CRC with synchronous adenoma, and 131 were diagnosed as solitary CRC. Some of the differences between the groups are: higher incidence was found in male (71.4 vs. 52.6%,Gender, a habit of drinking and other neoplastic diseases are risk factors for the development of a synchronous adenoma. With a low rate of BRAF mutations, the responses to monoclonal antibody and prognosis of patients with synchronous adenomas may be better than that of solitary CRC.

Colon adenocarcinoma (COAD) is one of the most common malignant tumors and has high migration and invasion capacity. In this study, we attempted to establish a multigene signature for predicting the prognosis of COAD patients. Weighted gene co-expression network analysis and differential gene expression analysis methods were first applied to identify differentially co-expressed genes between COAD tissues and normal tissues from the Cancer Genome Atlas (TCGA)-COAD dataset and GSE39582 dataset, and a total of 309 overlapping genes were screened out. Then, our study employed TCGA-COAD cohort as the training dataset and an independent cohort by merging the GES39582 and GSE17536 datasets as the testing dataset. After univariate and multivariate Cox regression analyses were performed for these overlapping genes and overall survival (OS) of COAD patients in the training dataset, a 13-gene signature was constructed to divide COAD patients into high- and low-risk subgroups with significantly different OS. The testing dataset exhibited the same results utilizing the same predictive signature. The area under the curve of receiver operating characteristic analysis for predicting OS in the training and testing datasets were 0.789 and 0.868, respectively, which revealed the enhanced predictive power of the signature. Multivariate Cox regression analysis further suggested that the 13-gene signature could independently predict OS. Among the 13 prognostic genes, NAT1 and NAT2 were downregulated with deep deletions in tumor tissues in multiple COAD cohorts and exhibited significant correlations with poorer OS based on the GEPIA database. Notably, NAT1 and NAT2 expression levels were positively correlated with infiltrating levels of CD8+ T cells and dendritic cells, exhibiting a foundation for further research investigating the antitumor immune roles played by NAT1 and NAT2 in COAD. Taken together, the results of our study showed that the 13-gene signature could efficiently predict OS and that NAT1 and NAT2 could function as biomarkers for prognosis and the immune response in COAD.

Long non-coding RNAs (lncRNAs) were reported to have the potential in maintaining genome instability, but the identification of lncRNAs related to genome instability and their prognostic value have not been largely explored in colon cancer. In this study, we obtained 155 genome instability-associated lncRNAs based on somatic mutation profiles in colon cancer from The Cancer Genome Atlas (TCGA) database. Functional enrichment analysis revealed the possible roles of genes co-expressed with those lncRNAs involved in some cancer, genome instability and immune related biological processes. Combined with overall survival data, a seven-lncRNA signature was established for prognosis prediction. According to the risk score calculated by this signature, high-risk patients characterized by high somatic mutation count, high microsatellite instability, significantly poorer clinical outcomes and specific tumor immune infiltration status compared with low-risk patients. The lncRNA signature was validated to be an independent prognostic indicator with good predictive performance in TCGA cohort. Furthermore, the prognostic value of the ZNF503-AS1 in lncRNA signature was confirmed in another independent dataset from Gene Expression Omnibus database. In summary, the genome instability-associated lncRNA signature in this study could be a promising tool for effectively predicting survival outcomes in colon cancer.

IntroductionFunctional constipation (FC) is a common digestive system disease, with an uptrend in morbidity and mortality, resulting in huge social and economic losses. Although the guidelines recommend lifestyle intervention as a first-line treatment, lifestyle intervention is not widely used in clinic. Inulin can be used as the basic material of functional food. Clinical studies have shown that inulin supplementation is associated with increased frequency of bowel movements, but has certain side effects. Therefore, the efficacy and safety of inulin in the treatment of FC need to be further evaluated.Methods and analysisWe will search Medline, Web of Science, Embase, China National Knowledge Infrastructure Database, Wanfang Database and China Biomedical Literature Database. We will also search the China Clinical Trial Registry, the Cochrane Central Register of Controlled Trials and related conference summaries. This systematic review will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RevMan V.5.3.5 will be used for analysis.Ethics and disseminationThis systematic review will evaluate the efficacy and safety of inulin supplementation for the treatment of FC. All included data will be obtained from published articles, there is no need for the ethical approval, and it will be published in a peer-reviewed journal. Due to lack of a new systematic review in this field, this study will combine relevant randomised controlled trials to better explore the evidence of inulin supplementation in the treatment of FC and guide clinical practice and clinical research.PROSPERO registration numberCRD42020189234.

Pancreatic adenocarcinoma (PAAD) is an extremely lethal disease worldwide. Brain-derived neurotrophic factor (BDNF) is a critical member of the neurotrophin polypeptide superfamily that plays an important role in multiple cancers. However, the association among BDNF expression, tumor immunity, and PAAD prognosis remains unclear. BDNF expression and its influence on patient prognosis were explored based on The Cancer Genome Atlas, Cancer Cell Line Encyclopedia, Genotype-Tissue Expression, and Kaplan-Meier plotter. Gene set enrichment analysis was performed to understand the biological roles of BDNF. The role of BDNF in tumor-infiltrating immune cells was determined using the Tumor Immune Estimation Resource database and the single-sample gene set enrichment analysis and xCell algorithm. The correlation among BDNF and chemokines, chemokine receptors, chemotherapeutic efficacy, and immune checkpoints was analyzed based on RStudio. BDNF expression was remarkably higher in PAAD compared to their paired normal tissues, and high BDNF expression was associated with unfavorable prognosis. Enrichment analysis revealed that BDNF was significantly enriched in major oncogenic pathways in PAAD. BDNF expression was positively correlated with immune infiltration, especially Th2 cells. Moreover, BDNF expression was positively correlated with Th2 cell-related chemokine/chemokine receptors, indicating that BDNF might modulate the migration of Th2 cells in PAAD. We also found that BDNF expression was correlated with high chemotherapeutics sensitivity and highly expressed immune checkpoints, making it a valuable biomarker in predicting the therapeutic benefits for chemotherapy and immunotherapy in cancer patients. In summary, BDNF might affect patient prognosis by interacting with tumor-infiltrating Th2 cells, thus serving as a potential prognostic biomarker in PAAD.

Background: Obesity has become a serious public health issue. The role of Helicobacter pylori (H. pylori) infection in overweight or obesity is inconsistent and controversial. It is very necessary to conduct a systematic review and meta-analysis for determining whether H. pylori infection was associated with risk of overweight/obesity. Methods: Four databases (PubMed, Web of Science, The Cochrane Library, and EMBASE) will be searched from the inception to January 15, 2019. All observational studies (including cross-sectional, case-control or longitudinal studies) reporting the association between H. pylori infection and overweight/obesity will be included. The primary outcome was the presence and incidence of overweight/obesity in conjunction with H. pylori infection. Study selection, data extraction, and assessment of quality will be conducted independently by 2 reviewers. RevMan 5.3 and STATA 14.0 software will be used for data synthesis. Results: The results of this study will provide a better understanding of the role of H. pylori infection in overweight/obesity among overall population. Conclusion: This systematic review and meta-analysis will generate evidence of the association between H. pylori infection and overweight/obesity, and the findings of this study will be published in a peer-reviewed journal. PROSPERO registration number: CRD42019121939

Mitochondrial homeostasis is closely associated with liver cancer progression via multiple mechanisms and is also a potential tumour-suppressive target in clinical practice. However, the role of mitochondrial fission in liver cancer cell viability has not been adequately investigated. Matrine, a type of alkaloid isolated from Sophoraflavescens, has been widely used to treat various types of cancer. However, the molecular effect of matrine on mitochondrial homeostasis is unclear. Therefore, the aim of the current study was to determine the role of mitochondrial fission in cell apoptosis, viability, migration and proliferation of HepG2 cells in vitro. The effect of matrine on mitochondrial fission and its mechanism were also explored. The results of our study showed that HepG2 cells treated with matrine had reduced viability, an increased apoptotic rate, a blunted migratory response, and impaired proliferation capacity. At the molecular level, matrine treatment activated mitochondrial fission, which promoted mitochondrial dysfunction, caused cellular oxidative stress, disrupted cellular energy metabolism and initiated cell apoptotic pathways. However, blockade of mitochondrial fission abolished the deleterious effects of matrine on HepG2 cells. Further, we demonstrated that the Mst1-JNK signalling axis was required for matrine-modulated mitochondrial fission. Matrine-mediated mitochondrial dysfunction was reversed by inhibiting Mst1-JNK pathways. Together, our results demonstrated that mitochondrial fission could be a potential upstream tumour-suppressive signal for liver cancer by modifying mitochondrial function and cell death. By contrast, matrine exerted an anticancer function in liver cancer by activating mitochondrial fission mediated by Mst1-JNK pathways.

Matrine is a natural alkaloid isolated from the root and stem of the legume plant Sophora. Its anti-proliferative and pro-apoptotic effects on several types of cancer have been well-documented. However, the role of matrine in regulating mitochondrial homeostasis, particularly mitophagy in liver cancer apoptosis, remains uncertain. The aim of our study was to explore whether matrine promotes liver cancer cell apoptosis by modifying mitophagy. HepG2 cells were used in the study and treated with different doses of matrine. Cell viability and apoptosis were determined by MTT assay, TUNEL staining, western blotting, and LDH release assay. Mitophagy was monitored by immunofluorescence assay and western blotting. Mitochondrial function was assessed by immunofluorescence assay, ELISA, and western blotting. The results of our study indicated that matrine treatment dose-dependently reduced cell viability and increased the apoptotic rate of HepG2 cells. Functional studies demonstrated that matrine treatment induced mitochondrial dysfunction and activated mitochondrial apoptosis by inhibiting protective mitophagy. Re-activation of mitophagy abolished the pro-apoptotic effects of matrine on HepG2 cells. Molecular investigations further confirmed that matrine regulated mitophagy via the PINK1/Parkin pathways. Matrine blocked the PINK1/Parkin pathways and repressed mitophagy, whereas activation of the PINK1/Parkin pathways increased mitophagy activity and promoted HepG2 cell survival in the presence of matrine. Together, our data indicated that matrine promoted HepG2 cell apoptosis through a novel mechanism that acted via inhibiting mitophagy and the PINK1/Parkin pathways. This finding provides new insight into the molecular mechanism of matrine for treating liver cancer and offers a potential target to repress liver cancer progression by modulating mitophagy and the PINK1/Parkin pathways.

Objective: Recent studies suggest that not only is constipation a clinical marker of premotor phase in Parkinson’s Disease (PD), but is also correlated with the duration and severity. Some reports indicated that inflammatory from gut dysbiosis might be involved in the pathogenesis of PD, but the correlation between them remains poorly understood. This study aims to investigate how the presence of constipation affects the dopamine level of nigrostriatal system and whether gastrointestinal (GI) inflammation is involved in the brain-gut axis. Methods: Clinical materials, serum inflammatory factors, and datum of dopamine level including 84 cases and 83 controls, were collected consecutively and randomly from November 1, 2017 to October 31, 2018. Dopamine levels of nigrostriatal system were detected by [18F]-DTBZ radiotracer (18F-AV-133). Data analysis was conducted by variance, covariance analysis, bicorrelation, partial correlation, chi-square analysis and logistic regression. Results: The mean age of cases was older than that of controls, and male predominance was also observed (P0.05). The dopamine levels of putamen and caudate nucleus, especially in the dorsal part of putamen, were significantly decreased in cases than that in controls (P0.05). Conclusion: The presence of constipation may increase the severity of motor symptoms and decrease dopamine levels of nigrostriatal system in PD. Inflammatory factors may be involved in the brain-gut axis of PD.

Objective: Gastrointestinal (GI) hemorrhage is serious during the acute phase and is reported to be related to an increased risk of death during the acute phase of acute ischemic stroke in particular. Our study was designed to investigate the relationship between GI hemorrhage and the mortality of acute ischemic stroke, assessing the influence of cerebrovascular risk factors, brain herniation and oral anticoagulation on the onset of GI hemorrhage. The identified risk factors for the occurrence of GI hemorrhage help to elucidate their respective roles in the mortality of acute ischemic stroke. Methods: A total of 15993 consecutive patients with acute ischemic stroke, including 216 cases and 15777 controls, were enrolled in the study from October 2010 to December 2018. Basic clinical and examination data were collected at the time of study enrollment. GI hemorrhage was diagnosed according to the presence of clinical features and endoscopy. Chi-square test and multiple logistic regressions were conducted to explore the associations between the GI hemorrhage occurrence and known risk factors. Kaplan-Meier was used to assess the influence of GI hemorrhage on the age of mortality of acute ischemic stroke. Results: GI hemorrhage cases among patients with acute ischemic stroke accounted for 1.35%. Male patients with ischemic stroke were more likely to have GI hemorrhage than their female counterparts (odds ratio (OR): 1.79; P = 0.000). Patients with atrial fibrillation (AF) had a higher incidence of GI hemorrhage than their counterparts without AF (3.03% vs. 1.20%; P < 0.05). Use of oral anticoagulants was related to increased risk for GI hemorrhage (OR: 1.96; P = 0.00). After adjusting for age and sex, both AF and oral anticoagulant use maintained associations with increased risk for GI hemorrhage (2.59-times and 2.02-times risk respectively; P = 0.00). Patients with hyperlipidemia had a lower incidence of GI hemorrhage than their counterparts without hyperlipidemia (0.62% vs. 1.60%; P < 0.05). Hyperlipidemia was associated with a reduced risk of GI hemorrhage (OR: 0.38, 95% confidence interval (CI): 0.25-0.58; P = 0.00), even after adjusting for age and sex (OR: 0.41; P = 0.00). Patients with brain herniation had a 6.54-times increased risk for GI hemorrhage (P = 0.00). GI hemorrhage was associated with 10.98-fold risk for mortality of acute ischemic stroke (P = 0.00). There was an interaction between GI hemorrhage and brain herniation and increased 26.91-fold risk for the mortality after acute ischemic stroke (P = 0.00). Conclusion: AF, oral anticoagulant use, brain herniation and male sex increase GI hemorrhage risk, while hyperlipidemia reduces risk. GI hemorrhage itself increases the risk for mortality of acute ischemic stroke. The interaction between GI hemorrhage and brain herniation increased the risk for the mortality after acute ischemic stroke.

Introduction Functional constipation (FC) is one of the common gastrointestinal disorders that affects people of almost every age. Persistent FC significantly affects quality of life and well-being along with economic burden on patients as well as health care system. Therapeutic efficacy of currently used treatment strategies becomes limited shortly after their discontinuation as constipation occurs again as a result of inappropriate dietary habits. Previous studies have revealed that light vegetarian diet (LVD) can significantly improve both typical and atypical subtypes of major traditional Chinese medicine (TCM) FC syndrome such as gastrointestinal damp-heat syndrome. This protocol aims at exploratorily investigating effectiveness and safety of LVD following a rigorous clinical trial. Methods and design Total 92 patients in each of the 2 subtypes will be recruited in China-Japan Friendship Hospital for participating in this prospective, placebo-controlled, randomized trial and exploratory study. The patients in each subtype will be randomly divided into 4 groups according to 1:1:1:1 ratio with allocation concealment, which are drug + diet group, drug group, placebo + diet group and placebo group. Patients in the group with diet intervention will be required to strictly follow the LVD. The study will continue for a period of 28 days, including a drug or placebo supervised intervention and a 14th-day telephone follow-up. During the intervention, patients will be required to record a designed diary for controlling the diet quality (DQ) and analyzing the defecation. The study will focus investigation of complete spontaneous bowel movements (CSBM) per week as its primary outcome and constipation-related symptom rating scale (CSS), TCM syndrome scale (TCMSS), 48-hour gastrointestinal transit time (48-hour GITT), high resolution anorectal manometry (HRAM) and fecal flora detection (FFD) will be included in secondary outcomes. Furthermore, the study will also determine safety, DQ and compliance indicators. Ethics and dissemination This study has been approved by China-Japan Friendship Hospital clinical research ethics committee (No. 2017-46-1). A SPIRIT checklist is available for this protocol. Trial registration number ChiCTR1800019686 in Chinese Clinical Trial Registry (WHO ICTRP member).

Objective This study was performed to investigate impaired vagal activity to meal in patients with functional dyspepsia (FD) with delayed gastric emptying (GE). Methods Eighty-five patients were studied. GE parameters, including those in the overall and proximal stomach, were measured by GE functional tests at the Department of Nuclear Medicine. Autonomic nervous function was tested by spectral analysis of heart rate variability (HRV). The vagal activity and sympathetic activity were analyzed by recording the power in the high-frequency component (HF), low-frequency component (LF), and LF/HF ratio. Results Overall and proximal GE were delayed in 47.2% and 50.9% of the patients, respectively. Spectral analysis of HRV showed that the HF in patients with delayed proximal GE was significantly lower and that the LF/HF ratio was significantly higher than those in patients with normal proximal GE after a meal. Conclusion Delayed proximal GE might be caused by disrupted sympathovagal balance as a result of decreased vagal activity after a meal. Improvement in vagal activity may constitute an effective treatment method for patients with FD.

To evaluate visceral sensitivity, gut barrier function and autonomic nerve function (ANF) in patients with diarrhea-predominant irritable bowel syndrome (IBS-D), and to explore their roles in IBS-D pathophysiology. Methods: A total of 46 IBS-D patients (IBS-D group) were selected from the Department of Gastroenterology of China-Japan Friendship Hospital from October 2015 to March 2016, and 20 healthy volunteer were served as a control group (HC group). Clinical and psychological symptoms were evaluated by questionnaire, and visceral sensitivity to rectal balloon distention, gut barrier function and autonomic nerve function (ANF) were examined. The difference in the above-mentioned indexes were compared between the 2 groups, and the correlations in the parameters were analyzed in the IBS-D group. Results: The scores of IBS symptom severity scale (IBS-SSS), Hamilton anxiety scale (HAMA), Hamilton depression scale (HAMD) and visceral sensitivity index (VSI) were significantly higher in the IBS-D group than those in the HC group (P0.01). In the visceral sensitivity test, maximum tolerable threshold in the IBS-D group was significantly decreased compared to that in the HC group (P0.01); there was no significant difference in first sensation threshold and defecating sensation threshold between the two groups (P0.05). As gut barrier function markers, the serum diamine oxidase (DAO) and d-lactate were significantly increased in the IBS-D group (P0.05). In ANF test, the total score and parasympathetic score as well as the proportion of abnormal scores in the IBS-D group were significantly higher than those in the HC group (P0.05). In IBS-D group, the HAMA, VSI and serum DAO were positively correlated with IBS-SSS (r=0.528, 0.575, 0.507; P0.01), while the 3 visceral sensitivity thresholds were negatively correlated with IBS-SSS (r= -0.636, -0.476, -0.697; P0.01); in addition to the IBS-SSS, the HAMA, HAMD, VSI and serum DAO were also significant negatively correlated with the visceral sensitivity thresholds (all P0.05); no significant correlations were found between the ANF and the other parameters. Conclusion: IBS-D patients show psychological symptoms, visceral hypersensitivity, impaired gut barrier function and abnormal ANF characterized by parasympathetic dysfunction; the former 3 factors are all associated with disease severity, and thus may play vital roles in IBS-D pathophysiology.目的：评价腹泻型肠易激综合征(diarrhea-predominant irritable bowel syndrome，IBS-D)患者的内脏敏感性、肠屏障功能和自主神经功能(autonomic nerve function，ANF)，探索它们在IBS-D病理生理学中的作用。方法：以2015年10月至2016年3月就诊于中日友好医院消化内科的46例IBS-D患者(IBS-D组)和20例健康志愿者(对照组)为研究对象，采用问卷评估其临床及精神心理症状，并检测内脏敏感性、肠屏障功能及ANF，比较两组上述各指标的差异，并分析IBS-D组中各指标间的相关性。结果：IBS-D组的病情尺度调查表(IBS symptom severity scale，IBS-SSS)、汉密尔顿焦虑量表(Hamilton anxiety scale，HAMA)、汉密尔顿抑郁量表(Hamilton depression scale，HAMD)和内脏敏感指数(visceral sensitivity index，VSI)评分均显著高于对照组(P0.01)。内脏敏感性检测中，IBS-D组对直肠扩张刺激的最大耐受阈值显著低于对照组(P0.01)，初始感觉阈值和持续排便阈值两组差异无统计学意义(P0.05)。肠屏障功能血清标志物二胺氧化酶(diamine oxidase，DAO)和D-乳酸在IBS-D组中均显著升高(均P0.05)。IBS-D组的ANF总分和副交感计分以及两者的异常比例均显著高于对照组(均P0.05)。在IBS-D组各指标相关性分析中，HAMA，VSI和血清DAO与IBS-SSS呈显著正相关(分别r=0.528，0.575，0.507；P0.01)，3个内脏感觉阈值均与IBS-SSS呈显著负相关(分别r=–0.636， –0.476，–0.697，P0.01)；与内脏感觉阈值呈显著负相关的指标除IBS-SSS外，还有HAMA，HAMD，VSI和血清DAO(均P0.05)；ANF与其他指标间未发现关联。结论：IBS-D患者存在精神心理异常、内脏高敏感、肠屏障受损和以副交感神经功能异常为主的ANF失调，前三者均与病情程度相关，可能在IBS-D病理生理学中发挥了重要作用。.

Background Using an adjustable stimulator with a wide range of stimulation parameters, the aims of this study were 1) to investigate the effects of long-term gastric electrical stimulation (GES) on appetite and differential food cravings for three different foods and 2) to investigate the effects of GES on plasma gastrointestinal peptide concentrations. Methods The study was performed in eight Beagle dogs implanted with one pair of serosal electrodes. They were followed during GES and sham GES sessions in a crossover design. GES was conducted using a series of individualized parameters. Food intake and food cravings were observed to evaluate the effects of long-term GES. Enzyme-linked immunosorbent assay was used to measure the plasma concentrations of gastrointestinal peptides. Results Dogs on GES for three months ate significantly less food than those on sham GES for three months (p < 0.05). A significant change in food cravings was induced by GES. Dogs with GES ate significantly less high-fat food. However, there was no significant difference in consumption of high-carbohydrate food or balanced food between the periods of GES and sham GES. The plasma concentrations of ghrelin, peptide YY3-36, and glucagon-like peptide 1 did not differ significantly between the periods of GES and sham GES. Conclusions Food intake and food craving were changed significantly by adjustable GES. GES may be used for treating obesity by changing food preferences. Further clinical studies are necessary to highlight the effect of adjustable GES on eating behavior.

To improve the therapeutic effects of gastric electrical stimulation (GES) for obesity, an animal experiment was conducted using a new type of stimulators. Proper parameters of GES were selected, and the impacts of GES on the food intake and gastric accommodation of canines were observed. Eight beagle dogs were operated on, and GES was performed on them. Firstly, GES was performed to determine the right parameters according to symptoms. Secondly, the so selected parameters were used in a 3-day GES procedure, during which process food intake, body weight, and symptoms were recorded. Thirdly, the gastric capacities before and after GES with different pulse widths were measured by means of a barostat. The selected parameters varied for each dog, with the pulse widths ranging from 0.3 to 6 ms. The food consumption after GES dropped significantly as compared with the amount observed in the sham stimulation. Tolerance to stimulation could be observed during GES. The post-GES gastric fundus capacity increased evidently in comparison with the capacity before GES, suggesting significant distention as compared with sham stimulation. Given an increment of 2 ms in the pulse width twice, the gastric capacity continued to distend each time. GES featuring pulse trains with wider and individualized pulse widths could inhibit food consumption of dogs. The stimulation parameters should be selected individually and adjusted periodically. GES of this mode could also increase the fasting gastric capacity with certain dose-related effects. The new type of stimulators may be more suitable for the treatment of human obesity than traditional stimulators.

Objective The effect of acute retrograde gastric electrical stimulation (RGES) on food intake, gastric accommodation, and gastric emptying in obese patients was investigated. Methods Simple obesity patients underwent RGES or sham stimulation. The maximum food intake volume was determined and the total calorie of consumed food was calculated. Gastric emptying was determined by 99m-diethylenetriaminepentaacetic acid scintigraphy. Results Sixteen obese patients were studied, with a median BMI of 32.1 (IQR, 31.2, 33.8) kg/m2. The median gastric emptying time was 106.1 (IQR, 81.8, 122.4) min with sham stimulation and 113.0 (IQR, 83.7, 124.8) min with RGES (P = 0.352). The mean maximum satiety food intake was 580 (IQR, 510, 725) mL with sham stimulation and 490 (IQR, 385, 590) mL with RGES (P = 0.003). No statistically significant difference was noted between sham stimulation and RGES in the 1 and 2-h food retention rate. The total calories of maximum satiety food intake with sham stimulation were 985.2 (IQR, 842.5, 1063.1) kcal and 759.9 (IQR, 547.9, 784.9) kcal with RGES (P = 0.007). Conclusions Acute RGES reduces calorie intake by decreasing gastric accommodation in obese subjects.

Background Gastric electrical stimulation (GES) has been proposed as a promising therapeutic option in treating obesity for 20 years. Currently, the available device of GES cannot meet the clinical needs. The purpose of this study is to verify the effect of a new type of adjustable gastric electrical stimulator in reducing food intake and body weight. Methods Eight beagle dogs randomly followed GES and sham GES for 3 months in a crossover design. Parameters were adjusted and individualized during the experiment. Symptoms of GES were recorded, and the effective parameters were selected. Resistance to GES was assessed. Food intake and body weight were measured to evaluate the effect of GES. Results The effective parameters were varied among the dogs. Resistance to GES was observed in different periods in dogs. Parameters needed to be adjusted every 10.2 ± 2.1 days during the period of GES. Food intake during GES for 3 months was significantly reduced than that during sham GES of 3 months (P

Baicalin, a flavonoid isolated from Scutellaria baicalensis Georgi, has shown a wide range of anti-inflammatory, antioxidative, antiviral, and antitumor properties. However, the molecular mechanism of how baicalin exerts its effects, especially on inflammation regulation, has not been fully investigated. In this article, we report the effects of baicalin on the mouse macrophage cell line RAW264.7. Our results demonstrate that baicalin inhibits the production of inflammatory factors interleukin-6 and tumor necrosis factor-alpha upon lipopolysaccharide stimulation of macrophages. We observed that baicalin inhibits STAT3 activation through retarding its expression and phosphorylation. Interestingly, baicalin treatment promotes the elevation of miR-124 in lipopolysaccharide-treated macrophages. Overexpression of the miR-124 mimic in RAW264.7 reduced STAT3 expression and phosphorylation. Furthermore, inhibition of miR-124 attenuated the dysregulation of STAT3 and reduction of inflammatory factors upon baicalin treatment. Our results revealed the molecular mechanism that baicalin attenuates pro-inflammatory cytokine production through miR-124-STAT3 signaling pathway, suggesting that miR-124 is an important modulator in regulating anti-inflammation by baicalin in macrophages.

Background: The aim of this study was to investigate the visceral sensation to gastric stimulation and its correlation with the stimulation-induced alterations in gastric accommodation and gastric emptying. Methods: The study was performed in 12 healthy human controls. Gastric stimulation was performed using bipolar electrodes attached to the mucosa of the distal stomach under endoscopy. Experiments were conducted on 3 consecutive days to investigate the effects of gastric stimulation with various parameters on visceral sensation, maximum intake of water and gastric emptying of solids. Results: 1) The stimulation energy was 265.6 ′ 134.9 smA 2 for the first sensation and 2,020.0 ′ 865.1 smA2 for the maximum tolerance, and there was a large variation among the subjects; 2) Gastric stimulation with stimulation energy less than 50% of that required to induce the first sensation significantly reduced the maximum intake of water and delayed gastric emptying of solids without inducing symptoms; 3) The stimulation energy of the first sensation was significantly correlated with the stimulation-induced reduction in water intake (r=-0.80, P=0.02) and the stimulation-induced prolongation of gastric emptying (r=-0.78, P=0.003). That is, the inhibitory effects of gastric stimulation were more obvious in those subjects who were viscerally more sensitive to gastric stimulation. Conclusions: Gastric stimulation via the distal stomach reduces gastric accommodation and delays gastric emptying. These inhibitory effects are correlated with the visceral sensitivity of the individual to gastric stimulation. It is worthy to further investigate whether the outcome of the implantable gastric stimulation (IGS) therapy for obesity may be predicted from the visceral sensitivity of the patient to temporary gastric stimulation using endoscopically placed mucosal electrodes.

Purpose. To investigate the prevalence and some related factors about irritable bowel syndrome (IBS) in medical students.Methods. A cross-sectional study was carried out from February 2014 to Jun 2014 in Beijing University of Chinese Medicine, Beijing, China. All participants were asked to completed self-administered questionnaires.Results.Seven hundred and sixty-seven medical students (23.26±2.88years, 25.6% males) completed the survey. The prevalence of IBS was 33.3%, with a high prevalence in women (36.1%). Among the IBS patients, 112 cases were IBS-M (43.9%) and 77.6% had moderately severe IBS. There were no statistical differences between control group and IBS patients in anxiety and depression scores (P>0.05). The total score of Pittsburgh sleep quality index (PSQI) was significantly higher for medical students with IBS and 35.5% of IBS patients had severe sleep disorder; the scores of child trauma questionnaire (CTQ) and student-life stress inventory (SLSI) were also higher in IBS patients. Sex and sleep disorder were independently associated with IBS (OR, 1.914, 95%CI, 1.281–2.860; OR, 1.143, 95%CI, 1.074–1.216).Conclusion. Our study has many valuable findings and they may provide valuable suggestions for the necessary intervention and treatment measures towards medical students.

The effect of acute retrograde gastric electrical stimulation (RGES) on food intake, gastric accommodation, and gastric emptying in obese patients was investigated.Simple obesity patients underwent RGES or sham stimulation. The maximum food intake volume was determined and the total calorie of consumed food was calculated. Gastric emptying was determined by (99m) -diethylenetriaminepentaacetic acid scintigraphy.Sixteen obese patients were studied, with a median BMI of 32.1 (IQR, 31.2, 33.8) kg/m(2) . The median gastric emptying time was 106.1 (IQR, 81.8, 122.4) min with sham stimulation and 113.0 (IQR, 83.7, 124.8) min with RGES (P = 0.352). The mean maximum satiety food intake was 580 (IQR, 510, 725) mL with sham stimulation and 490 (IQR, 385, 590) mL with RGES (P = 0.003). No statistically significant difference was noted between sham stimulation and RGES in the 1 and 2-h food retention rate. The total calories of maximum satiety food intake with sham stimulation were 985.2 (IQR, 842.5, 1063.1) kcal and 759.9 (IQR, 547.9, 784.9) kcal with RGES (P = 0.007).Acute RGES reduces calorie intake by decreasing gastric accommodation in obese subjects.

A new type of gastric electrical stimulator (GES) was introduced. After the stimulator was implanted in beagle dogs, its stimulating effects and the pathological changes at the implant site were observed to study the safety and efficacy of stimulator as well as the tissue compatibility of the materials used. The results showed that, this type of stimulator was safe and capable of inhibiting food intake of the dogs, and that the materials used had good tissue compatibility.

Obesity is one of the most prevalent health problems in the world with a lack of satisfactory therapies and gastric electrical stimulation has recently been proposed for the treatment of obesity. The aim of this study was to investigate the effects of retrograde gastric pacing (RGP) on food and water intake, and gastric emptying in humans. RGP with a tachygastrial frequency of 9 cycles/min was performed via a pair of submucosal gastric electrodes implanted 5 cm above the pylorus in 12 subjects. The water load test, food intake test and scintigraphic gastric emptying test were performed to assess the efficacy of RGP. RGP resulted in a 13% reduction in the consumption of water, a 16% reduction in food intake and a 15% increase in gastric retention of a solid meal. No significant symptoms were recorded with RGP using the parameters used for the water-load, food intake and scintigraphic gastric emptying tests. Acute RGP at a tachygastrial frequency results in a significant reduction of water and food intake and a delay in gastric emptying without inducing any unacceptable symptoms. It is worthy to explore its therapeutic potential for obesity.

AIM: To investigate the visceral response to acute retrograde gastric electrical stimulation (RGES) in healthy humans and to derive optimal parameters for treatment of patients with obesity. METHODS: RGES with a series of effective parameters were performed via a bipolar mucosal electrode implanted along the great curvature 5 cm above pylorus of stomach in 12 healthy human subjects. Symptoms associated with dyspepsia and other discomfort were observed and graded during RGES at different settings, including long pulse and pulse train. Gastric myoelectrical activity at baseline and during different settings of stimulation was recorded by a multi-channel electrogastrography. RESULTS: The gastric slow wave was entrained in all the subjects at the pacing parameter of 9 cpm in frequency, 500 ms in pulse width, and 5 mA in amplitude. The frequently appeared symptoms during stimulation were satiety, bloating, discomfort, pain, sting, and nausea. The total symptom score for each subject significantly increased as the amplitude or pulse width was adjusted to a higher scale in both long pulse and pulse train. There was a wide diversity of visceral responses to RGES among individuals. CONCLUSION: Acute RGES can result in a series of symptoms associated with dyspepsia, which is beneficial to the treatment of obesity. Optimal parameter should be determined according to the individual sensitivity to electrical stimulation.

The heat-labile enterotoxin (LTc) isolated from chicken enterotoxigenic Escherichia coli was purified to homogeneity and its molecular and antigenic properties were compared with those of purified LTs from porcine and human enterotoxigenic Escherichia coli (LTp, LTh). The A subunit of LTc was identical to that of LTp and the B subunit of LTc was identical to that of LTh but not that of LTp, in mobility on SDS-polyacrylamide gel electrophoresis. Ouchterlony tests demonstrated that LTc is antigenically identical to LTh but not with LTp. The pI point and amino acid composition of LTc were also compared and the results suggest that chicken enterotoxigenic E. coli produced an LT similar to LTh.