Rab31 promotes metastasis and cisplatin resistance in stomach adenocarcinoma through Twist1-mediated EMT.

Stomach adenocarcinoma (STAD) is one of the leading causes of cancer-related death globally. Metastasis and drug resistance are two major causes of failures in current chemotherapy. Here, we found that the expression of Ras-related protein 31 (Rab31) is upregulated in human STAD tissues and high expression of Rab31 is closely associated with poor survival time. Furthermore, we revealed that Rab31 promotes cisplatin resistance and metastasis in human STAD cells. Reduced Rab31 expression induces tumor cell apoptosis and increases cisplatin sensitivity in STAD cells; Rab31 overexpression yielded the opposite result. Rab31 silencing prevented STAD cell migration, whereas the overexpression of Rab31 increased the metastatic potential. Further work showed that Rab31 mediates cisplatin resistance and metastasis via epithelial-mesenchymal transition (EMT) pathway. In addition, we found that both Rab31 overexpression and cisplatin treatment results in increased Twist1 expression. Depletion of Twist1 enhances sensitivity to cisplatin in STAD cells, which cannot be fully reversed by Rab31 overexpression. Rab31 could activate Twist1 by activating Stat3 and inhibiting Mucin 1 (MUC-1). The present study also demonstrates that Rab31 knockdown inhibited tumor growth in mice STAD models. These findings indicate that Rab31 is a novel and promising biomarker and potential therapeutic target for diagnosis, treatment and prognosis prediction in STAD patients. Our data not only identifies a novel Rab31/Stat3/MUC-1/Twist1/EMT pathway in STAD metastasis and drug resistance, but it also provides direction for the exploration of novel strategies to predict and treat STAD in the future.

Helicobacter pylori infection eradication for nonalcoholic fatty liver disease: a randomized controlled trial.

Previous studies have suggested that Helicobacter pylori (H. pylori) infection is associated with nonalcoholic fatty liver disease (NAFLD). The purpose of the present study was to investigate the effect of H. pylori eradication treatment on NAFLD patients. Two hundred NAFLD patients who tested positive for H. pylori infection were randomized into the H. pylori eradication treatment group or the control group. Metabolic and inflammatory parameters and FibroScan were measured in all subjects at baseline and 1 year after treatment. At 1 year after treatment, the decrease in metabolic indicators, such as fasting blood glucose, glycosylated haemoglobin, homeostasis model assessment of insulin resistance (HOMA-IR), triglycerides, body mass index and controlled attenuation parameter values, were more obvious in the treatment group. Moreover, the inflammatory indicators white blood count and high-sensitivity C-reactive protein (hs-CRP) and the inflammatory factors interleukin 6 (IL-6) and tumour necrosis factor-α (TNF-α) were also significantly decreased. H. pylori eradication can further reduce the metabolic indices of NAFLD and the degree of liver steatosis. H. pylori infection may participate in the occurrence and development of NAFLD through its influence on inflammatory factors. Thus, checking for the presence of H. pylori infection in patients at risk of NAFLD may be beneficial.

Hepatic epithelioid hemangioendothelioma after thirteen years' follow-up: A case report and review of literature.

BACKGROUND: Hepatic epithelioid hemangioendothelioma (EHE) is a rare vascular endothelial cell tumor of the liver, consisting of epithelioid and histiocyte-like vascular endothelial cells in mucus or a fibrotic matrix. Immunohistochemistry is usually positive for vascular markers, such as factor VIII-related antigen, CD31, and CD34. Hepatic EHE can have a varied clinical course; treatment includes liver transplantation, liver resection, chemotherapy, and radiation therapy. CASE SUMMARY: A 46-year-old woman with abdominal discomfort and elevated serum carcinoembryonic antigen was found to have multiple low-density lesions in the liver and lung on computed tomography (CT) evaluation. An ultrasound-guided fine needle aspiration biopsy revealed a fibrous stroma with dendritic cells, containing intracellular vacuoles. Immunohistochemical staining found that the tumor cells were positive for CD34, CD31, and factor VIII-related antigen. The patient received four courses of combined chemotherapy and was followed-up for 13 years, at which time the patient was in stable condition without disease progression and a confined neoplasm, as evidenced by CT scans. CONCLUSION: The histology and immunohistochemical characteristics of hepatic EHE are well described. Chemotherapy may be effective in patients with extrahepatic lesions.

Association of serum pepsinogen with degree of gastric mucosal atrophy in an asymptomatic population.

BACKGROUND: Atrophic gastritis is a precancerous lesion of the stomach. It has been reported that pepsinogen (PG) can reflect the morphology and function of the gastric mucosa, and it is therefore used as a marker for the early diagnosis of atrophic gastritis. AIM: To evaluate the diagnostic value of serum PG for degree of gastric mucosal atrophy in asymptomatic Chinese upon physical examination. METHODS: Medical data were collected from subjects who underwent transnasal gastroscopy between October 2016 and October 2018. For each study subject, serum PG levels and presence of Helicobacter pylori (H. pylori) infection were investigated. Pathology was evaluated using the Operative Link for Gastritis Assessment (OLGA) classification and Operative Link on Gastric Intestinal Metaplasia Assessment (OLGIM) systems. All statistical analyses were carried out using SPSS statistical software. RESULTS: A total of 2256 subjects were enrolled and 1922 cases were finally included in the study. Based on the OLGA grading system, the levels of PGI were slightly decreased, while those of PGII were slightly increased. The PGI/PGII ratio (PGR) was reduced with increasing atrophy. The association between PG and OLGA grading was higher compared with that between PG and the OLGIM grading system. Compared with the OLGA-0 group, a statistically significant difference was observed in the mean age of OLGA-I, III, and IV groups (P < 0.05). In the H. pylori-positive subjects, the PGR levels were notably lower in the OLGA-I, II, and III groups compared with the OLGA-0 group (P < 0.05). H. pylori-positive subjects exhibited significantly higher PGI and PGII serum levels and a significantly lower PGR compared with H. pylori-negative patients in different OLGA groups (P < 0.05). CONCLUSION: Serum PG levels may represent a non-invasive screening marker for gastric mucosal atrophy in asymptomatic subjects.

Therapeutic effects and potential mechanism of dehydroevodiamine on N-methyl-N'-nitro-N-nitrosoguanidine-induced chronic atrophic gastritis.

BACKGROUNDS: Dehydroevodiamine (DHE) is a quinazoline alkaloid isolated from a Chinese herbal medicine, named Euodiae Fructus (Wu-Zhu-Yu in Chinese). This study aimed to investigate the therapeutic effects and potential mechanism of DHE on N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced chronic atrophic gastritis (CAG) based on integrated approaches. METHODS: Therapeutic effects of DHE on serum biochemical indices and histopathology of gastric tissue in MNNG-induced CAG rats were analyzed. MNNG-induced GES-1 human gastric epithelial cell injury model was established. Cell viability and proliferation was quantified by a cell counting kit-8 assay. Cell morphology and mitochondrial membrane potential (MMP) were detected by a high content screening (HCS) assay. Cell migration and invasion were detected by a Transwell chamber. Moreover, UHPLC-Q-TOF/MS was performed to investigate the potential metabolites and signaling pathway affecting the protective effects of DHE on MNNG-induced cell migration and invasion of GES-1. Furthermore, in view of the key role of angiogenesis in the transformation of inflammation and cancer, this study explored relative mRNA and protein expression levels of HIF-1α-mediated VEGF pathway in vivo and in vitro by RT-PCR and Western Blotting, respectively. RESULTS: The results showed that the therapeutic effects of DHE on CAG rats were presented in down-regulation serum biochemical indices and alleviating histological damage of gastric tissue. Besides, DHE has an effect on increasing cell proliferation of GES-1 cells, ameliorating MNNG-induced gastric epithelial cell damage and mitochondrial dysfunction. In addition, DHE could inhibit MNNG induced migration and invasion of GES-1 cells. Cell metabolomics analyses showed that the protective effect of DHE on GES-1 cells is mainly associated with the regulation of inflammation metabolites and energy metabolism related pathways. It was found that DHE has a regulating effect on tumor angiogenesis and can inhibit the relative gene and protein expression of HIF-1α-mediated VEGF signaling pathway. CONCLUSIONS: The present work highlighted the role of DHE ameliorated gastric injury in MNNG-induced CAG rats in vivo and GES-1 cell migration in vitro by inhibiting HIF-1α/VEGF angiogenesis pathway. These results suggest that DHE may be the effective components of Euodiae Fructus, which provides a new agent for the treatment of CAG.

Usefulness of controlled attenuation parameter and liver stiffness measurement for detecting increased arterial stiffness in asymptomatic populations in China.

In recent studies, vibration-controlled transient elastography (FibroScan) has been reported as an alternative noninvasive approach for measuring liver steatosis and fibrosis. The present study aimed to investigate the feasibility of FibroScan controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) in the detection of increased arterial stiffness in asymptomatic populations in China.A retrospective cohort recruiting 4747 asymptomatic patients with no underlying causes of liver disease and having FibroScan and brachial-ankle pulse wave velocity (baPWV) during wellness check-up was covered. Nonalcoholic fatty liver disease (NAFLD) was defined as a CAP ≥238 dB/m. NAFLD with significant fibrosis was defined as an LSM ≥7.3 kPa in the presence of NAFLD. Increased arterial stiffness was determined as a BaPWV ≥1.4m/second.Among the 4747 study participants, 1596 subjects (33.6%) suffered from increased arterial stiffness. The prevalence of increased arterial stiffness progressively increased across CAP quartiles and LSM quartiles in NAFLD (23.5%, 30.8%, 38.3%, 43.7%, P < .001 and 33.1%, 36.8%, 40.4%, 48.2%, P < .001, respectively). After conventional cardiovascular risk factors were adjusted (age, sex, overweight, diabetes mellitus, hypertension, hypercholesterolemia, and current smoking habits), multivariate logistic regression analysis revealed that CAP (odd ratio [OR] = 1.005; 95% confidence interval [CI]: 1.003-1.006; P < .001), NAFLD (OR = 1.427; 95% CI: 1.212-1.681; P < .001), LSM in NAFLD (OR = 1.073; 95% CI: 1.023-1.125; P = .003), and significant fibrosis in NAFLD (OR = 1.480; 95% CI: 1.090-2.010; P = .012) were independently associated with increased arterial stiffness. Furthermore, in a multivariate logistic regression analysis, OR (95% CI) for the maximal vs. the minimal quartile of CAP was 1.602 (1.268-2.024), and that of LSM in NAFLD was 1.362 (1.034-1.792) after adjustment for the above-mentioned risk factors. Notably, NAFLD and significant fibrosis in NAFLD were significantly correlated only with increased arterial stiffness in subjects without hypertension or diabetes mellitus after adjustment for the above-mentioned risk factors.CAP-defined NAFLD and LSM-defined significant fibrosis in NAFLD showed significant and independent relationships with increased arterial stiffness even after adjustment for conventional cardiovascular risk factors, which can be conducive to stratifying relative risk of subjects having undergone screening assessment for cardiovascular disease.

The associations among Helicobacter pylori infection, white blood cell count and nonalcoholic fatty liver disease in a large Chinese population.

Reported relationships among Helicobacter pylori infection, white blood cell (WBC) count and nonalcoholic fatty liver disease (NAFLD) are inconsistent and controversial. We, therefore, conducted a cross-sectional study to investigate the associations among the presence of NAFLD, WBC count and H pylori infection, as diagnosed using the C-urea breath test (UBT).This study included 20,389 subjects enrolled at the International Health Care Center of the Second Affiliated Hospital of the Zhejiang University School of Medicine from January 2015 to December 2015. All participants underwent a C-UBT for the diagnosis of H pylori infection and ultrasonography for NAFLD as well as a blood test to determine WBC count. Multivariate logistic regression was then performed to evaluate the relationship among H pylori infection, WBC count and NAFLD.H pylori infection was detected in 38.49% (7,848/20,389) of the subjects via the UBT, and NAFLD was present in 37.24% (7,592/20,389) of the subjects. The prevalence of H pylori infection was higher in the NAFLD group than in the control group (41.25% vs 36.85%, P <.001). Significant differences were found between various WBC quartiles and H pylori infection, age, gender, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), high-sensitivity C-reactive protein (HS-CRP), glycosylated hemoglobin (HbA1c), triglyceride (TG), low-density lipoprotein (LDL-C), fasting blood glucose (FPG), homeostasis model assessment of insulin resistance (HOMA-IR), and smoking. Multivariate logistic regression revealed that the combination of H pylori infection and WBC count (odds ratio [OR] = 1.067, 95% confidence interval [CI]: 1.014, 1.093; P = .007; OR = 1.165, 95% CI: 1.023, 1.488; P <.001; OR = 1.183, 95% CI: 1.085, 1.559; P <.001, respectively) was positively associated with NAFLD.H pylori infection and WBC count may contribute to the pathogenesis of NAFLD.

Ileocecal endometriosis and a diagnosis dilemma: a case report and literature review.

Bowel endometriosis affects between 3.8% and 37% of women with endometriosis. The evaluation of symptoms and clinical examination are inadequate for an accurate diagnosis of intestinal endometriosis. We describe the case of a 41-year-old woman who presented to our hospital because of six months of recurrent abdominal pain, vomiting and diarrhea, without previous history of bowel disease. Physical examination revealed a palpable 3 cm × 5 cm mass in the right lower quadrant abdomen. Laboratory tests showed slightly elevated levels of CA19-9 and CA125. Small bowel computer tomography scanning revealed an ileocecal mass with bowel wall thickening and luminal narrowing. Small bowel endoscopy identified a deep longitudinal ulcer and mucosal edema in the distal ileum. All these findings supported the diagnosis of Crohn's disease. The patient underwent a laparotomy, which identified a 5 cm × 5 cm ileocecal mass with severe mucosal edema and luminal stricture in the distal ileum. Histopathological examination confirmed a diagnosis of ileocecal endometriosis without other areas involved. After one-year follow-up, there was no recurrence of the symptoms.