Maternal inulin supplementation ameliorates prenatal methamphetamine exposure-induced hepatotoxicity and restores gut microbiota in mouse offspring.

Prenatal exposure to methamphetamine (METH) is an issue of global concern due to its adverse effects on offspring, particularly its impact on liver health, an area still not fully understood. Inulin, a recognized prebiotic, is thought to potentially ameliorate these developmental disorders and toxic injuries in progeny. To investigate the effects of prenatal METH exposure on the liver and the role of gut microbiota, we established a murine model, the subjects of which were exposed to METH prenatally and subsequently treated with inulin. Our findings indicate that prenatal METH exposure causes liver damage in offspring, as evidenced by a decreased liver index, histopathological changes, diminished glycogen synthesis, hepatic dysfunction, and alterations in mRNA profiles. Furthermore, it impairs the antioxidant system and induces oxidative stress, possibly due to changes in cecal microbiota and dysregulation of bile acid homeostasis. However, maternal inulin supplementation appears to restore the gut microbiota in offspring and mitigate the hepatotoxic effects induced by prenatal METH exposure. Our study provides definitive evidence of METH's transgenerational hepatotoxicity and suggests that maternal inulin supplementation could be an effective preventive strategy.

[Clinical Value of White Light Image, Endoscopic Ultrasonography and Magnifying Endoscopy with Narrow Band Imaging in Evaluation of Indications for Endoscopic Treatment of Early Gastric Cancer].

OBJECTIVE: To explore the application value of white light image (WLI), endoscopic ultrasonography (EUS) and magnifying endoscopy with narrow band imaging (ME-NBI) in the endoscopic treatment of early gastric cancer (EGC), and to provide basis for decision-making in clinical diagnosis and treatment. METHODS: The clinicopathological data of EGC patients who underwent endoscopic submucosal dissection (ESD) at West China Hospital, Sichuan University between December 2013 and October 2020 were included. The accuracy, sensitivity, specificity, positive predictive value and negative predictive value of EGC invasive depth were compared between WLI and EUS. The role of ME-NBI in predicting the differentiation types of EGC was analyzed. RESULTS: A total of 280 patients (291 lesions) were enrolled in the study. Among them, 199 patients (207 lesions) received EUS and 160 patients (168 lesions) received ME-NBI. The overall accuracy of WLI in diagnosing the invasive depth of EGC was 87.0%, significantly higher than that of EUS (46.4%, P<0.001). When WLI was combined with EUS, the diagnostic accuracy (87.4%) was not significantly improved. The overall accuracy of determining the differentiation degree of EGC with ME-NBI was 92.3% (155/168), and the accuracy of determining undifferentiated EGC with ME-NBI was significantly lower than that of differentiated EGC (41.2% vs. 98.0%, P<0.001). CONCLUSION: In the evaluation of indications for endoscopic treatment of EGC, WLI showed better performance in predicting the invasive depth of EGC, while EUS demonstrated limited value. ME-NBI showed better accuracy for predicting the differentiation degree of most EGC, especially for differentiated EGC.

[Endoscopic Dilation to Treat One Case of Severe Intestinal Stenosis Caused by Endometriosis].

A 46-year-old woman was admitted for repeated abdominal distention and constipation for more than 10 years and further deterioration for 5 years. Colonoscopy showed, in the sigmoid colon, nodular neoplasm protruding into the cavity, resulting in local intestinal stenosis, through which the endoscopy could not pass. Pathological findings of the biopsy sample revealed changes caused by intestinal endometriosis. The patient underwent multiple endoscopic dilatation treatments in our hospital and the interval between recurrences of intestinal stenosis was extended from 6 months to 4 years. Intestinal endometriosis can cause repeated intractable stenosis caused by the infiltration of ectopic glands in the intestinal wall, which usually requires surgical intervention. Herein, we report a case of severe intestinal stenosis caused by endometriosis in the sigmoid colon. Good results have been achieved through endoscopic dilatation treatment. This case suggests that endoscopic dilation has good application value in the treatment of this kind of disease, which needs further exploration and promotion.

[Accuracy of EUS and ME-NBI for Evaluating the Invasion Depth of Early Esophageal Cancer].

OBJECTIVE: To assess the accuracy of endoscopic ultrasound (EUS) and magnifying endoscopy with narrow-band imaging (ME-NBI) in evaluating the invasion depth of early esophageal carcinoma. METHODS: Patients who underwent endoscopic resection for early esophageal cancer from March 2013 to October 2017 were enrolled. The EUS and ME-NBI results were compared with the pathology results. RESULTS: A total of 392 lesions from 333 patients were assessed, including 83 mild and moderate dysplasia, 72 severe dysplasia, 235 squamous cell carcinoma, and 2 adenosquamous carcinoma. About 308 lesions were given EUS only, 7 had ME-NBI only, 77 underwent both EUS and ME-NBI. EUS resulted in a 43.9% accuracy for the 385 lesions, with poor consistency (Kappa=0.1) with the pathology results. But higher accuracy (68.2%) was found for lesions infiltrating into the submucosa of the lesions, compared with 40.5% for lesions contained within the mucosa (P=0.001). ME-NBI resulted in a 72.6% accuracy for the 84 lesions, with a medium consistency (Kappa=0.4). The accuracy for lesions contained within the mucosa was 91.0%, compared with 16.7% for lesions infilrtrating into the submucosa (P=0.001). EUS and ME-NBI for the 77 lesions demonstrated an accuracy of 42.9% for the EUS and 84.3% for the ME-NBI (P=0.001). CONCLUSIONS: ME-NBI has higher accuracy than EUS in evaluating the invasion depth of early esophageal carcinoma.

[Expression and its clinical significance of AMP-activated protein kinase in esophageal squamous cell carcinoma].

OBJECTIVE: To investigate the expression and its possible function of AMP-activated protein kinase (AMPK) in the occurrence of esophageal squamous cell carcinoma (ESCC). METHODS: The tissue samples were collected from 40 fresh ESCC and 40 normal esophagus, and the expression of AMPK downstream substrates p-ACC and ACC were tested by Western-blot, then the correlations of p-ACC and ACC expression to the clinicopathologic characterisics were analyzed. RESULTS: The expression of p-ACC in ESCC was lower than that in normal tissues, with significant statistical difference (P < 0.05). The down-regulation ratio of p-ACC in poorly-differentiated ESCC was 81.8% (9/11), which was significantly higher than that in moderately and well-differentiated ESCC (3.5%, 1/29). There was no correlation of p-ACC down-regulation with age, gender, TNM stage and lymph node metastasis (P > 0.05). CONCLUSION: The expression of p-ACC was down-regulation in ESCC, and the down-regulation is associated with tumor cell differentiation.

Development and validation of a model to determine risk of refractory benign esophageal strictures.

BACKGROUND: Current research has identified several risk factors for refractory benign esophageal strictures (RBES), but research is scarce on the prediction of RBES in benign esophageal strictures patients. Meanwhile, the long-term outcomes of RBES remain unclear. The aim of this study was to develop and validate a model to determine the progression of RBES in patients with benign esophageal strictures. And we also explored the long-term outcomes and safety in patients with RBES. AIM: To develop and validate a model to determine the progression of RBES in patients with benign esophageal strictures, based on the demographic data and endoscopic findings. METHODS: A total of 507 benign esophageal stricture patients treated by dilation alone or in combination with stenting were retrospectively enrolled between January 2009 and February 2018. The primary outcome was to establish a risk-scoring model predicting RBES in benign esophageal strictures. The secondary outcome was to explore the clinical effectiveness and adverse events in patients with RBES. RESULTS: In the study, age, etiology, and number and length of strictures were the independent risk factors for the refractory performance of benign esophageal strictures. According to risk factors of benign esophageal strictures, a risk-scoring model for predicting RBES in benign esophageal strictures was established: The risk score ranged from 0 to 8 points, and the risk scores were divided into low risk (0-2 points), intermediate risk (3-5 points), and high risk (6-8 points). The proportions of RBES in the corresponding risk categories were 1.0%, 12.2%, and 76.0%, respectively. Among 507 patients, 57 had RBES (39 males; median age, 60 years). The success rate of dilation treatment (51.2%, 21/41) was higher than that of stent placement (37.5%, 6/16). CONCLUSION: In this study, 11.3% (57/507) patients had RBES at our hospital. The risk-scoring model predicting RBES in benign esophageal strictures could predict the long-term outcome of patients with strictures ahead.

Lactobacilli inhibit interleukin-8 production induced by Helicobacter pylori lipopolysaccharide-activated Toll-like receptor 4.

AIM: To investigate the effect of Lactobacillus bulgaricus (LBG) on the Toll-like receptor 4 (TLR4) pathway and interleukin-8 (IL-8) production in SGC-7901 cells treated with Helicobacter pyloriSydney strain 1 lipopolysaccharide (H pyloriSS1-LPS). METHODS: SGC-7901 cells were treated with H pyloriSS1-LPS in the presence or absence of pretreatment for 1 h with viable LBG or supernatant recovered from LBG culture MRS broth (LBG-(s)). Cellular lysates were prepared for Western blot with anti-TLR4, anti-transforming growth factor beta-activated kinase 1 (TAK1), anti-phospho-TAK1, anti-nuclear factor kappaB (NF-kappaB), anti-p38 mitogen-activated protein kinase (p38MAPK), and anti-phospho-p38MAPK antibodies. The amount of IL-8 in cell culture medium was measured by ELISA. RESULTS: H pyloriSS1-LPS up-regulated the expression of TLR4, stimulated the phosphorylation of TAK1, subsequently enhanced the activation of NF-kappaB and the phosphorylation of p38MAPK in a time-dependent manner, leading to augmentation of IL-8 production in SGC-7901 cells. Viable LBG or LBG-(s) pretreatment attenuated the expression of TLR4, inhibited the phosphorylation of TAK1 and p38MAPK, prevented the activation of NF-kappaB, and consequently blocked IL-8 production. CONCLUSION: H pyloriSS1-LPS induces IL-8 production through activating TLR4 signaling in SGC-7901 cells and viable LBG or LBG-(s) prevents H pyloriSS1-LPS-mediated IL-8 production via inhibition of the TLR4 pathway.

[Effects of Lactobacilli on regulating NF-kappaB activation and IL-8 secretion in SGC7901 cell impacted by Helicobacter pylori].

OBJECTIVE: In vitro to investigate the regulation effects of Lactobacillus acidophilus ATCC4356 and L. bulgaricus (LB) on the activation of NF-kB and IL-8 secretion of SGC7901 cell, which Helicobacter pylori induced. METHODS: SGC7901 cell was cultured to reach the exponential growth phase, then adjusted to cell concentration (2.5 x 10(5)/mL), and planted into six shadow mask and incubated for 24 hours. Until reaching exponential growth phase, the cultured ATCC4356 and LB were adjusted to different concentration to incubation with SGC7901 cell together for one hour, and then added H. pylori into them for culturing 3 hours. For the contrast analysis of result, the experiment subgroups were designed as follow: normal control, H. pylori stimulating group (H. pylori group), ATCC4356 intervention group (ATCC4356 group) and LB intervention group (LB group). The nuclear factor-kB of SGC7901 cell was detected by immunohistochemistry. The release of IL-8 in cells was detected by ELISA. RESULTS: The percentage of NF-kB p65 positive nuclei-stained cell and the secreting level of IL-8 from cells in H. pylori group significantly increased compared with those in control group (P < 0.01). When the Lactobacillus concentration was 3 x 10(6) cfu/mL, 3 x 10(7) cfu/mL and 3 x 10(8) cfu/mL respectively, the percentage of NF-kB p65 positive nuclei-stained cell of ATCC4356 group was significantly decreased compared with that of H. pylori group (P < 0.01). When the Lactobacillus concentration was 3 x 10(6) cfu/ mL and 3 x 10(7) cfu/mL respectively, the IL-8 secretory volume of cells of ATCC4356 group could be significantly decreased compared with that of H. pylori group (P < 0.01). When the Lactobacillus concentration was 3 x 10(6) cfu/ mL, 3 x 10(7) cfu/mL and 3 x 10(8) cfu/mL respectively, the percentage of NF-kB p65 positive nuclei-stained cell of LB group was significantly decreased compared with that of H. pylori group (P < 0.05). When the Lactobacillus concentration was 3 x 10(7) cfu/mL or 3 x 10(8) cfu/mL respectively, the cell IL-8 secretory volume of LB group was significantly decreased compared with that of H. pylori group (P < 0.05). However, if the level of Lactobacillus concentration showed too high, the ATCC4356 and LB might have no above mentioned inhibitory action, the percentage of NF-kB p65 positive nuclei-stained cell and the level of IL-8 secretion of cells in those experiment groups significantly increased compared with those in H. pylori group. CONCLUSION: In some concentration range, both ATCC4356 and LB can inhibit the cell inflammatory reaction induced by H. pylori, but if the concentration is too high, they may make the inflammatory reaction become more serious. These can explain in partial why lactobacillus as primary common bacterium maintains the proper proportion concentration is very important for the keeping on microecological balance in stomach.