Lower ultra-short-term heart rate variability can predict worse mucosal healing in ulcerative colitis.

BACKGROUND: Psychological stress has been proved to be a risk factor for exacerbation for ulcerative colitis (UC). However, traditional approaches of quantifying psychological stress using psychological scales are time-consuming and the results may not be comparable among patients with different educational levels and cultural backgrounds. Alternatively, heart rate variability (HRV) is an indicator for psychological stress and not biased by educational and cultural backgrounds. AIMS: In this study, we try to explore the relationship between psychological stress and UC by analyzing the effect of ultra-short-term HRV on mucosal and histological remission status of UC. METHODS: This is a retrospective case-control study on UC inpatients from 2018 through 2020. Ultra-short-term HRV were calculated using baseline electrocardiography. Patients were divided intocase and control groups according to their Mayo endoscopic scores or histological Geboes scores. Three variables of ultra-short-term HRV (the standard deviation of normal to normal R-R intervals (SDNN), the standard deviation of successive differences between adjacent normal to normal R-R intervals (SDSD), the root mean square of successive differences of normal to normal R-R intervals (RMSSD)) were compared between different groups. And for those variables with significant differences, we built univariate and multivariate logistic regressions to depict the relationship between HRV variables and remission status of UC. RESULTS: All three HRV variables showed significant differences between the mucosal groups. However, none of them showed significant difference between the histological groups. In further logistic regression analyses, smaller RMSSD can predict severe mucosal healing status (OR = 5.21). CONCLUSIONS: Lower ultra-short-term HRV (i.e. smaller RMSSD) is shown to positively correlate with worse mucosal healing status. However, ultra-short-term HRV cannot predict histological healing status according to our data.

Endoscopic treatment can be a viable therapeutic option for esophageal gastrointestinal stromal tumors.

BACKGROUND: Esophageal gastrointestinal stromal tumors(GISTs) are extremely rare. We sought to determine whether endoscopic treatment can be a viable therapeutic option for esophageal GISTs. METHODS: A total of 20 cases with histological diagnosis of esophageal GISTs were obtained from our center between 2008 and 2020. Data on the clinicopathological features and treatment were recorded. RESULTS: There were 9 males (45%) and 11 females (55%) in this study, with a median age of 56 years. The tumors preferentially occurred in the middle and lower parts of the thoracic esophagus (45 and 40%, respectively). The mean size of the tumors was 2.27 cm and mitotic index was no more than 5/50 high power field (HPF) in all patients. In this study, 11 patients received endoscopic treatment and nine patients underwent surgical resection. Tumors ranged from 0.6 to 4 cm in the endoscopic treatment patients and 0.5 to 7 cm in the surgical patients. There were no significant differences in gender, age, symptoms, tumor location, tumor size, mitotic index, and adjuvant imatinib therapy between the endoscopic treatment group and the surgery group (all p > .05). The Kaplan-Meier curve suggested that there was also no significant difference in disease-free survival between the two groups (p = .264). CONCLUSIONS: Endoscopic treatment may be an option for the treatment of esophageal GISTs smaller than 5 cm with a mitotic index no more than 5/50 HPF.

FGF15 promotes hepatic NPC1L1 degradation in lithogenic diet-fed mice.

BACKGROUND: Cholesterol gallstone disease (CGD) is accompanied by biliary cholesterol supersaturation. Hepatic Niemann-Pick C1-like 1 (NPC1L1), which is present in humans but not in wild-type (WT) mice, promotes hepatocyte cholesterol uptake and decreases biliary cholesterol supersaturation. In contrast, intestinal NPC1L1 promotes intestinal cholesterol absorption, increasing biliary cholesterol supersaturation. Ezetimibe (EZE) can inhibit both hepatic and intestinal NPC1L1. However, whether hepatic NPC1L1 can affect CGD progress remains unknown. METHODS: Mice expressing hepatic NPC1L1 (NPC1L1hepatic-OE mice) were generated using Adeno-associated viruses (AAV) gene delivery. The protein level and function of hepatic NPC1L1 were examined under chow diet, high fat-cholesterol diet (HFCD), and lithogenic diet (LD) feeding. Gallstone formation rates were examined with or without EZE treatment. Fibroblast growth factor 15 (FGF15) treatment and inhibition of fibroblast growth factor receptor 4 (FGFR4) were applied to verify the mechanism of hepatic NPC1L1 degradation. RESULTS: The HFCD-fed NPC1L1hepatic-OE mice retained the biliary cholesterol desaturation function of hepatic NPC1L1, whereas EZE treatment decreased biliary cholesterol saturation and did not cause CGD. The ubiquitination and degradation of hepatic NPC1L1 were discovered in LD-fed NPC1L1hepatic-OE mice. Treatment of FGF15 during HFCD feeding and inhibition of FGFR4 during LD feeding could affect the protein level and function of hepatic NPC1L1. CONCLUSIONS: LD induces the ubiquitination and degradation of hepatic NPC1L1 via the FGF15-FGFR4 pathway. EZE may act as an effective preventative agent for CGD.

Increased risk of herpes zoster infection in patients with inflammatory bowel disease: a meta-analysis of cohort studies.

Previous studies have shown increased risk of herpes zoster (HZ) infection in patients with inflammatory bowel disease (IBD). The aim of this study is to better characterize this possible association by conducting a meta-analysis. A comprehensive search of relevant literature until April 30, 2019, was performed. Data on HZ infection and medications in patients with IBD and controls were extracted. The relative risk (RR) and 95% confidence interval (CI) were calculated. Subgroup analyses were performed to assess the source of heterogeneity. Seven cohort studies were included that involved more than 1,000,000 participants. The RR of HZ infection in patients with Crohn's disease (CD) compared with non-CD patients was 1.74 (95% CI 1.57-1.92, p < 0.001). The pooled RR of HZ infection in patients with ulcerative colitis (UC) compared with non-UC was 1.40 (95% CI 1.31-1.50, p < 0.001). Subgroup analyses revealed that age, race, and publication year contribute to heterogeneity. We also found that steroid users were at increased risk of HZ in CD (OR = 1.78, 95% CI 1.10-2.88). Steroid users and anti-TNFα users were at increased risk of HZ in UC, with RRs of 1.99 (95% CI 1.64-2.42) and 2.29 (95% CI 1.52-3.45), respectively. Begg's test and Egger's test suggested no publication bias. There was a 74% increased risk of HZ infection in patients with CD and 40% increased risk of HZ infection in patients with UC compared with that in non-IBD. IBD patients with high risk of HZ infection may benefit from an HZ vaccine.

Dysregulated Up-Frameshift Protein 1 Promotes Ulcerative Colitis Pathogenesis Through the TNFR1-NF-κB/MAPKs Pathway.

BACKGROUND: Ulcerative colitis (UC) is an idiopathic colonic mucosal disease, and its pathogenesis has not been fully understood. Up-frameshift protein 1 (UPF1) is a potential molecule for UC predicted by a computational approach. AIM: The present study aimed to validate the underlying mechanism of UPF1 in UC. METHODS: UPF1 expression was detected by qRT-PCR, western blotting, and immunohistochemistry in dextran sulfate sodium-induced colitis in mice. To simulate the intestinal inflammation microenvironment, NCM460 human colonic epithelial cells were exposed to a mixture of inflammatory mediators. The potential mechanism involving TNFR1-NF-κB/MAPKs pathway activation was addressed by western blotting, reporter gene assays, and siRNA (siUPF1) or UPF1-expressing plasmid pENTER-transfected cells. RESULTS: UPF1 was downregulated in colonic epithelial cells of colitic mice, and in vitro, contrary to the mRNA levels of the associated cytokines enhanced in the UPF1 dysregulation group within stimulatory factors, most relevant cytokines were significantly decreased in UPF1 overexpression group. Mechanistically, the increased expression of tumor necrosis factor receptor 1 (TNFR1) was found in NCM460 cells pre-treated with siUPF1, with the activation of IKK/NF-κB and MAPKs pathways, including JNK/AP-1 and P38, but not the ERK1/2 pathway. Moreover, the repression of TNFR1 required the interaction of UPF1 with the promoter. CONCLUSION: UPF1, which negatively regulated the transcription of TNFR1, is a novel factor regulating intestinal inflammation. The downregulation of UPF1 activated the TNFR1-dependent NF-κB/MAPKs pathway, and promoting inflammatory responses in colon might act as a causal role in UC.

The Elastic Contact and Stability Analysis of an Inertial Micro-Switch with a Spring Stationary Electrode.

A mechanical trigger inertial micro-switch with spring stationary electrode is proposed and fabricated by surface micromachining. The elastic contact process and stability performance are evaluated through experimental tests performed using a drop hammer. The test results show that the contact time is about 110 µs and 100 µs when the threshold acceleration is 480 g and the overload acceleration is 602 g, respectively. The vibration process of the electrodes is explained through an established physical mode. The elastic contact process is analyzed and discussed by Finite Element Analysis (FEA) simulations, which indicated that the contact time is about 65 µs when the threshold acceleration is 600 g. At the same time, this result also proved that the contact time could be extended effectively by the designed spring stationary electrode. The overload acceleration (800 g) has been applied to the Finite-Element model in ANSYS, the contact process indicated that the proof mass contacted with stationary electrode three times, and there was no bounce phenomenon during contact process, which fully proved that the stable contact process can be realized at high acceleration owing to the designed elastic stationary electrode.

Hepatitis C Virus Infection Is Positively Associated with Gallstones in Liver Cirrhosis.

AIM: To elucidate the prevalence and risk factors of gallstone disease (GD) among patients with liver disease and explore their association with the aetiology and severity of hepatic injury. METHODS: We analysed 4,832 subjects of hepatic injury induced by one of the following aetiologies: hepatitis B virus (HBV) infection, hepatitis C virus (HCV) infection, excessive alcohol consumption. The risk factors significantly associated with GD were analysed using stepwise logistic regression analysis, the influence of aetiology and severity of liver disease on the prevalence of GD were assessed by multiple logistic regression analysis adjusting for confounding factors. RESULTS: Three thousand forty eight patients were of positive HBV surface antigen alone with a prevalence of GD of 18.6%, 526 were tested as positive Anti-HCV alone with a prevalence of GD of 22.4%, and 1,258 were identified with excessive alcohol consumption patterns with a prevalence of GD of 13.5%. In each aetiological category, the prevalence of GD increased by age. Stepwise logistic regression analysis showed that age, female, low-density lipoprotein-cholesterol (LDL-Cho), family history of GD, HBV infection, HCV infection, chronic hepatitis and cirrhosis were independent factors associated with GD. After adjusting for age, LDL-Cho and family history of GD, the prevalence of gallstone disease was significantly associated with HCV-related cirrhosis in both genders, HBV-related cirrhosis in males and alcohol-related cirrhosis in females compared with patients with less severe liver disease [corrected]. After adjusting for gender, age, LDL-Cho and family history of GD, patients with HCV-related cirrhosis (OR 2.66, 95% CI 1.49-3.84) but not HBV-related cirrhosis (OR 1.52, 95% CI 0.73-1.82) were more likely to have GD compared with alcohol-related cirrhosis. CONCLUSION: HCV infection is positively associated with gallstone formation especially in those with cirrhosis patients.

Helicobacter pylori induces increased expression of the vitamin d receptor in immune responses.

BACKGROUND: Vitamin D receptor (VDR) is a member of the nuclear receptor family of transcription factors that play a critical role in innate immunity. This study examined the role of VDR in gastric innate immune defence against the gastric pathogen Helicobacter pylori. MATERIALS AND METHODS: Seventeen H. pylori-infected patients and sixteen controls participated in the study. The GES-1 cells were transfected with siRNA or incubated with or without 1α,25(OH)2 D3 (100 nmol/L) then infected with H. pylori. VDR, cathelicidin antimicrobial protein (CAMP), and cytokine mRNA expression levels in normal and H. pylori-infected gastric mucosa and GES-1 cells was determined by qRT-PCR and correlated with the histopathologic degree of gastritis. Bactericidal activity was measured by using a colony-forming unit assay. RESULTS: Vitamin D receptor mRNA expression levels were significantly upregulated in H. pylori-infected patients and positively correlated with chronic inflammation scores. There was a significant positive correlation between VDR and CAMP mRNA expression in H. pylori-positive gastric mucosa. VDR siRNA reduced H. pylori-induced CAMP production and conversely increased IL-6 and IL8/CXCL8 expression levels. The vitamin D agonist 1α,25(OH)2 D3 increased CAMP expression and reduced cytokine activation in GES-1 cells infected with H. pylori. 1α,25(OH)2 D3 could enhance the intracellular killing of the replicating bacteria, but the presence of siVDR and siCAMP led to a decline in its bactericidal ability. CONCLUSIONS: The expression of VDR and CAMP in the gastric epithelium is up-regulated in the case of H. pylori infection; thus, VDR plays an important role in gastric mucosa homeostasis and host protection from H. pylori infection.

Endoscopic ultrasound-guided lauromacrogol injection for treatment of colorectal cavernous hemangioma: Two case reports.

BACKGROUND: Colorectal cavernous hemangioma is a rare vascular malformation resulting in recurrent lower gastrointestinal hemorrhage, and can be misinterpreted as colitis. Surgical resection is currently the mainstay of treatment, with an emphasis on sphincter preservation. CASE SUMMARY: We present details of two young patients with a history of persistent hematochezia diagnosed with colorectal cavernous hemangioma by endoscopic ultrasound (EUS). Cavernous hemangioma was relieved by several EUS-guided lauromacrogol injections and the patients achieved favorable clinical prognosis. CONCLUSION: Multiple sequential EUS-guided injections of lauromacrogol is a safe, effective, cost-efficient, and minimally invasive alternative for colorectal cavernous hemangioma.

Effect of hepatic NPC1L1 on cholesterol gallstone disease and its mechanism.

Cholesterol gallstone disease (CGD) is associated with bile cholesterol supersaturation. The Niemann-Pick C1-like 1 (NPC1L1), the inhibitory target of ezetimibe (EZE), is a critical sterol transporter of cholesterol absorption. Intestinal NPC1L1 facilitates the absorption of cholesterol, whereas hepatic NPC1L1 promotes cholesterol uptake by hepatocytes and reduces bile cholesterol supersaturation. The potential of hepatic NPC1L1 to prevent CGD has yet to be established due to its absence in the mice model. In this study, we generated mice expressing hepatic NPC1L1 using adeno-associated virus (AAV) gene delivery. The biliary cholesterol saturations and gallstone formations were explored under chow diet and lithogenic diet (LD) with or without EZE treatment. The long-term (8-week) LD-fed AAV-mNPC1L1 mice exhibited no significant differences in biliary cholesterol saturation and gallstone formation compared to WT mice. EZE effectively prevented CGD in both WT and AAV-mNPC1L1 mice. Mechanistically, prolonged LD feeding induced the degradation of hepatic NPC1L1, whereas short-term (2-week) LD feeding preserved the expression of hepatic NPC1L1. In conclusion, our findings suggest that hepatic NPC1L1 is unable to prevent CGD, whereas EZE functions as an efficient bile cholesterol desaturator during CGD development.

[Double balloon endoscopy in diagnosis of patients with obscure gastrointestinal bleeding].

OBJECTIVE: To assess the diagnostic value of double balloon endoscopy (DBE) for obscure gastrointestinal bleeding (OGIB) METHODS: The data of 103 OGIB patients who underwent DBE from January 2007 to September 2010 in the First Affiliated Hospital, Zhejiang University School of Medicine were retrospectively analyzed. RESULTS: DBE was successfully performed in all 103 patients without complications. Of 103 patients, 66(64.1 %) had positive DBE findings and 28 had surgery procedures(27.2 %). Ninety-four patients finally acquired positive diagnosis, including small intestine tumor(31.1 %), angiodysplasia(22.3 %), exulceratio simplex(9.7 %), Crohn's disease(6.8 %), diverticulum(4.9 %), abdominal purpure(4.9 %), etc. Lesions occurred more frequently in proximal small intestine than in distal small intestine (56.3 % Compared with 30.1 %, P<0.001). CONCLUSION: DBE is a safe, effective and reliable procedure for the diagnosis of OGIB.

Design, Simulation, and Fabrication of a New Three-Axis Inertial Switch with a Triangular Movable Electrode Structure.

A new three-axis inertial switch is proposed. The triangle-structured movable electrode is designed to improve the inertial switch's dynamic response performance, especially the movable electrode's dynamic stability performance. The static mechanical analysis indicated that the displacement of the movable electrode to the fixed electrode in the sensitive direction is the minimum when the acceleration is applied to this designed inertial switch. The dynamic simulation analysis showed that the threshold of the designed inertial is about 235 g. The threshold in the non-sensitive direction is about 240 g, 270 g, 300 g, and 350 g when the directions of applied acceleration deviate 15°, 30°, 45°, and 60° from the sensitive direction, respectively. These results indicated that the designed inertial could resist the impact in non-sensitive directions and improve the stability in sensitive directions. The prototype of the inertial switch was fabricated and tested successfully. The testing results indicate that the threshold of the fabricated inertial switch is about 219 g. The test results verify the dynamic stability performance of the designed inertial switch.

Gastric metastasis presenting as submucosa tumors from renal cell carcinoma: A case report.

BACKGROUND: Gastric metastasis from renal cell carcinoma (RCC) is an extremely rare clinical entity. Due to an easily neglected RCC history, nonspecific symptoms and under-recognized endoscopic presentation may lead to a potential diagnostic pitfall in daily clinical practice. CASE SUMMARY: We present a case of metastatic gastric tumors arising from RCC 5 years after radical nephrectomy. Simultaneous, multifocal metastases to the gallbladder, pancreas and soft tissue were observed. One year previously, a solitary submucosal discoid tumor with a central depression was detected in the gastric fundus in a 65-year-old man. Endoscopic ultrasonography (EUS) showed a 1.12 x 0.38 cm lesion originating from the deeper mucosal layers with partially discontinuous submucosa. One year later, the endoscopic findings of the lesion showed various changes. A large lesion of the protruding type (2.5 cm × 2 cm) was found in the fundus at the same location. EUS showed a heterogeneous mass that involved the mucosa and submucosal layer. In addition, two small similar submucosal lesions 0.4-0.6 cm in size were detected. These lesions had a central depression, surface mucosal congestion and thickened vessels. The two adjacent lesions in the fundus were resected by endoscopic submucosal dissection. Based on the postoperative pathological analysis, the patient was diagnosed with gastric metastasis from RCC. CONCLUSION: Gastric metastasis from RCC should be considered in patients with a history of RCC irrespective of the time interval involved.

Levofloxacin susceptibility testing for Helicobacter pylori in China: comparison of E-test and disk diffusion method.

BACKGROUND: The aims of this study were to compare disk diffusion with E-test method for levofloxacin susceptibility testing of Helicobacter pylori and standardized breakpoints for disk diffusion as a stable and reliable method for determining qualitative levofloxacin susceptibility. MATERIALS AND METHODS: We determined the levofloxacin susceptibility of 45 H. pylori strains isolated from Chinese patients by the E-test method. Disk diffusion was evaluated as an alternative method to determine susceptibility and compared with the E-test results by linear regression analysis. RESULTS: The minimum inhibitory concentration (MIC) values tested by E-test method ranged from 0.047 to 32 µg/mL. Resistance to levofloxacin was detected in 16 (35.6%) isolates. The levofloxacin disk zone sizes obtained by disk diffusion method correlated well (r² = .877) with the MICs obtained by E-test method. As a consequence of regression analysis, isolates with inhibition diameters < 12 mm were considered resistant to levofloxacin. There was 100% agreement between the two methods for levofloxacin, applying the regression-based breakpoints. CONCLUSIONS: The disk diffusion method is equivalent to the E-test method for testing levofloxacin susceptibility of H. pylori strains; it is more practical and inexpensive, and it is suitable for the analysis of a small number of isolates compared with the E-test method.

The Design, Simulation and Fabrication of an Omnidirectional Inertial Switch with Rectangular Suspension Spring.

An omnidirectional inertial switch with rectangular spring is proposed in this paper, and the prototype has been fabricated by surface micromachining technology. To evaluate the threshold consistency and stability of omnidirectional inertia switch, the stiffness of rectangular suspension springs is analyzed. The simulation result shows that the coupling stiffness of the rectangular spring suspension system in the non-sensitive direction is a little more than that in the sensitive direction, which indicated that the omnidirectional switching system's stability is reinforced, attributed to the design of rectangular springs. The dynamic response simulation shows that the threshold of the omnidirectional inertial switch using the rectangular suspension spring has high consistency in the horizontal direction. The prototype of an inertial switch is fabricated and tested successfully. The testing results indicate even threshold distribution in the horizontal direction. The threshold acceleration of the designed inertial switch is about 58 g in the X direction and 37 g in the Z direction; the contact time is about 18 µs.

The Analysis of the Influence of Threshold on the Dynamic Contact Process of a Fabricated Vertically Driven MEMS Inertial Switch.

In this work, to evaluate the influence of the threshold on the dynamic contact process, five models (number 1, 2, 3, 4, 5) with different thresholds were proposed and fabricated with surface micromachining technology. The contact time and response time were used to characterize the dynamic contact performance. The dynamic contact processes of the inertial switches with gradually increasing thresholds were researched using analytical, simulation, and experimental methods. The basic working principle analysis of the inertial switch shows that the contact time of the inertial switch with a low-g value can be extended by using a simply supported beam as the fixed electrode, but the high-G inertial needs more elasticity for fixed electrode. The simulation results indicate that the response time and contact time decrease with the increment in the designed threshold. Prototypes were tested using a dropping hammer system, and the test result indicates that the contact time of the inertial switch with a fixed electrode of the simply supported beam is about 15 and 5 µs when the threshold is about 280 and 580 g, respectively. Meanwhile, the contact time can be extended to 100 µs for the inertial switch using a spring as the fixed electrode when the threshold is about 280 and 580 g. These test results not only prove that the spring fixed electrode can effectively extend the contact time, but also prove that the style of the fixed electrode is the deciding factor affecting the contact time of the high-G inertial switch.

Association between Helicobacter pylori infection and nonalcoholic fatty liver disease: a systemic review and meta-analysis.

Although clinical studies have shown possible links of Helicobacter pylori infection with the development of nonalcoholic fatty liver disease (NAFLD), the results remain controversial. The aim of this meta-analysis is to investigate the association between H. pylori infection and NAFLD. A comprehensive search of relevant studies was performed up to November 2018. Data on H. pylori infection in NAFLD patients and controls were extracted. Odds ratio (OR) and 95% confidence interval (CI) were calculated using a random-effects model. Twelve studies involving 27 400 NAFLD patients and 60 347 controls were included. The pooled overall OR of H. pylori infection in NAFLD patients compared with controls was 1.36 (95% CI: 1.22-1.53, I=89.6%, P=0.000). Meta-regression and subgroup analysis showed that the sample size and the case-control ratio may have accounted for some of the heterogeneity. When stratified by publication year, the diagnostic method used for H. pylori, and Newcastle-Ottawa Scale scores, the OR remained significant. However, possible publication bias was observed. Of the 12 studies, six had carried out multivariable analysis after adjusting for potential confounders. The pooled results from these studies still indicated a higher risk of NAFLD in patients infected with H. pylori (OR=1.17, 95% CI: 1.01-1.36, I=72.4%, P=0.003). There is a 36% increased risk of NAFLD in patients with H. pylori infection. Further studies are warranted to investigate whether eradication of H. pylori is useful in the prevention and treatment of NAFLD.

Correction: Exploration of Serum Proteomic Profiling and Diagnostic Model That Differentiate Crohn's Disease and Intestinal Tuberculosis.

[This corrects the article DOI: 10.1371/journal.pone.0167109.].

Multiple gastric angiolipomas: A case report.

BACKGROUND: Angiolipoma is a benign tumor and is generally found in subcutaneous tissues. Angiolipomas are rare in the gastrointestinal tract, including the stomach. Preoperative diagnosis of the tumor is difficult, although there are several radiological examinations such as computed tomography and endoscopic ultrasound. CASE SUMMARY: We report a 24-year-old Chinese man with multiple gastric angiolipomas, with a positive stool occult blood examination. Endoscopic biopsy only showed nonspecific inflammation. Histological examination of the specimen by endoscopic snare resection showed that the tumor consisted of adipose tissues and blood vessels. We also performed a literature review. After the use of proton pump inhibitor, the fecal occult blood test was negative. Due to the difficulty of resecting multiple lesions in the stomach completely and the benign characteristics of angiolipoma, we chose to have regular upper gastrointestinal endoscopy evaluation of the lesion. No evidence of significant change in lesion size was detected after 3-years follow-up. CONCLUSION: Gastric angiolipoma is rare, and benign neoplasm should be considered when lesions occur submucosally in the gastrointestinal tract.