Polymorphisms in the vitamin D receptor gene and risk of primary biliary cirrhosis: a meta-analysis.

BACKGROUND AND AIM: Primary biliary cirrhosis (PBC) is a chronic and progressive cholestatic autoimmune liver disease. Although many studies have evaluated the association between many functional polymorphisms in the vitamin D receptor (VDR) gene and PBC risk, debates still exist. Our aim is to evaluate the association between VDR gene polymorphisms, including TaqI (rs731236), BsmI (rs1544410), and ApaI (rs7975232), and the risk of PBC by a systematic review. METHODS: We searched literatures in PubMed, SCOPUS, and EMBASE until July 2013. We calculated pooled odds ratios (OR) and 95% confidence intervals (CIs) using a fixed effects model or a random effects model for the risk to PBC associated with different VDR gene polymorphisms. And the heterogeneity assumption decided the effect model. RESULTS: A total of six relevant studies, with 1322 PBC cases and 2264 controls, were included in this meta-analysis. The results indicated that TaqI (rs731236) polymorphism was significantly associated with PBC risk (for T vs t OR = 0.75, 95% CI 0.63, 0.89, Pz = 0.001; TT + Tt vs tt OR = 0.62, 95% CI 0.44, 0.86, Pz = 0.005; OR = 0.74, 95% CI 0.58, 0.94, Pz = 0.016 for recessive model), while ApaI (rs7975232) or BsmI (rs1544410) polymorphism did not. CONCLUSION: Based on current evidences from published studies, the cumulative effect of TaqI polymorphism in VDR was significantly associated with PBC. Larger studies with mixed ethnicity subjects and stratified by clinical and sub clinical characteristics are needed to validate our findings.

Clinical features and prognostic factors of duodenal neuroendocrine tumours: A comparative study of ampullary and nonampullary regions.

BACKGROUND: Duodenal neuroendocrine tumours (DNETs) are rare neoplasms. However, the incidence of DNETs has been increasing in recent years, especially as an incidental finding during endoscopic studies. Regrettably, there is no consensus regarding the ideal treatment of DNETs. Even there are few studies on the clinical features and survival analysis of DNETs. AIM: To analyze the clinical characteristics and prognostic factors of patients with duodenal neuroendocrine tumours. METHODS: The clinical data of DNETs diagnosed in the First Affiliated Hospital of Air Force Military Medical University from June 2011 to July 2022 were collected. Neuroendocrine tumours located in the ampulla area of the duodenum were divided into the ampullary region group; neuroendocrine tumours in any part of the duodenum outside the ampullary area were divided into the nonampullary region group. Using a retrospective study, the clinical characteristics of the two groups and risk factors affecting the survival of DNET patients were analysed. RESULTS: Twenty-nine DNET patients were screened. The male to female ratio was 1:1.9, and females comprised the majority. The ampullary region group accounted for 24.1% (7/29), while the nonampullary region group accounted for 75.9% (22/29). When diagnosed, the clinical symptoms of the ampullary region group were mainly abdominal pain (85.7%), while those of the nonampullary region groups were mainly abdominal distension (59.1%). There were differences in the composition of staging of tumours between the two groups (Fisher's exact probability method, P = 0.001), with nonampullary stage II tumours (68.2%) being the main stage (P < 0.05). After the diagnosis of DNETs, the survival rate of the ampullary region group was 14.3% (1/7), which was lower than that of 72.7% (16/22) in the nonampullary region group (Fisher's exact probability method, P = 0.011). The survival time of the ampullary region group was shorter than that of the nonampullary region group (P < 0.000). The median survival time of the ampullary region group was 10.0 months and that of the nonampullary region group was 451.0 months. Multivariate analysis showed that tumours in the ampulla region and no surgical treatment after diagnosis were independent risk factors for the survival of DNET patients (HR = 0.029, 95%CI 0.004-0.199, P < 0.000; HR = 12.609, 95%CI: 2.889-55.037, P = 0.001). Further analysis of nonampullary DNET patients showed that the survival time of patients with a tumour diameter < 2 cm was longer than that of patients with a tumour diameter ≥ 2 cm (t = 7.243, P = 0.048). As of follow-up, 6 patients who died of nonampullary DNETs had a tumour diameter that was ≥ 2 cm, and 3 patients in stage IV had liver metastasis. Patients with a tumour diameter < 2 cm underwent surgical treatment, and all survived after surgery. CONCLUSION: Surgical treatment is a protective factor for prolonging the survival of DNET patients. Compared to DNETs in the ampullary region, patients in the nonampullary region group had a longer survival period. The liver is the organ most susceptible to distant metastasis of nonampullary DNETs.

CD8(+) T cell-mediated cytotoxicity toward Schwann cells promotes diabetic peripheral neuropathy.

BACKGROUND: Damage to Schwann cells has been reported in the development of diabetic peripheral neuropathy (DPN), but how Schwann cells are damaged has not been elucidated. METHODS: The highly expressed proteins in the PBMC of DPN patients were identified through MALDI-TOF/TOF and SELDI protein chip technology. The expression levels of CXCR3 were detected by qPCR and flow cytometric analysis. Transwell migration assay was to investigate the migration of CD8(+) T cells. Western-blot analysis was to detect the levels of p38 MAP kinases pathway related proteins and TNF-α, FasL, and PDL1. RESULTS: Two highly expressed proteins, CXCR3 and p38, were identified. Under high glucose conditions, CXCR3 was elevated in CD8(+) T cells via the activation of p38 MAP kinases. Moreover, CXCL9, CXCL10, and CXCL11 expression were induced in Schwann cells, leading to the recruitment and infiltration of CD8(+) T cells into DPN tissues. Further study demonstrated that Schwann cells promoted activation of CD8(+) T cells and induced expression of TNF-α, FasL, and PDL1 on CD8(+) T cells, in return, CD8(+) T cells induced obvious apoptosis of Schwann cells. CONCLUSION: Our study indicates that CD8(+) T cells mediate cytotoxicity toward Schwann cells and play an important role in the development of DPN.

[The derivation and validation of a prediction rule for differential diagnosis of thyroid nodules].

OBJECTIVE: To set up a prediction rule for the pro-operative differential diagnosis of thyroid nodules and evaluate its clinical value. METHODS: All patients of thyroid nodules underwent thyroid operations in Changzheng hospital from June, 1997 to July, 2012 were included in this study. They were randomly divided into the derivation cohort (2/3) and the validation cohort (1/3). A prediction rule was developed based on the logistic regression model and the scoring system was established in accordance with assigning of the value of each variable ß in the model. The prediction consistency, discriminatory power and diagnostic accuracy were conducted to evaluate the clinical value of the scoring system. RESULTS: A total of 13 980 patients were enrolled in the study with 9195 in the derivation cohort and 4785 in the validation cohort. The prediction rule consisted of 18 variables, which were gender, clinical manifestations including fever, neck sore, neck mass, palpitation and sweating, serum level of thyroid stimulating hormone (TSH) , free triiodothyronine (FT3) , thyroid peroxidase antibody (TPOAb) , thyroglobulin antibody (TgAb) , thyroglobulin (Tg) , calcitonin and carcinoembryonic antigen (CEA) , ultrasonography features including nodules number, location, size, boundaries and ethological patterns and the presence and patterns of lymph nodes. The model showed good calibration consistency (P = 0.437) and discrimination power (area under the receiver operating characteristic curve was 0.928) in the derivation cohort. The sensitivity, specificity, accuracy, positive predictive value, negative predictive value, positive likelihood ratio and negative likelihood ratio of the model were 89.3%, 81.5%, 83.2%, 56.8%, 96.6%, 4.83 and 0.13, respectively. CONCLUSION: The prediction rule and its scoring system established in the study are efficacious for the calibration and discrimination of thyroid nodules in Chinese population, which could be a useful tool for the pro-operative risk stratification.

Relationship between gastric xanthoma, gastric precancerous lesions, and gastric cancer: A retrospective study.

OBJECTIVE: To evaluate the relationship between gastric cancer and its precancerous lesions and gastric xanthoma. METHODS: Medical records of 47 736 patients who underwent gastroscopy in our center from January 2020 to December 2021 were reviewed. Patients' age, sex, endoscopic and histopathological findings, and the presence, number and location of gastric xanthoma were recorded. To investigate the detection rate of gastric xanthoma at different stages of gastric lesions, the participants were further divided into the chronic gastritis group (n = 42 758), the precancerous lesion group (n = 3672), and the gastric cancer group (n = 1306), respectively. RESULTS: The overall detection rate of gastric xanthoma was 2.85%, and it was most commonly observed in the gastric antrum (52.50%). In addition, gastric xanthoma was more common in men and more likely to be single lesion. It was most detected in the precancerous lesion group (8.39%), followed by the gastric cancer group (5.44%), and least in the chronic gastritis group (2.29%). Multivariate analysis showed that gastric xanthoma was closely related to precancerous lesions (odds ratio [OR] 3.197, 95% confidence interval [CI] 2.791-3.662, P < 0.001) and gastric cancer (OR 1.794, 95% CI 1.394-2.309, P < 0.001). CONCLUSION: Gastric xanthoma is closely related to gastric precancerous lesions and gastric cancer.

Increased Prevalence of Thyroid Nodules Across Nearly 10 Years in Shanghai, China.

OBJECTIVE: This study aimed to determine whether the prevalence of thyroid nodules (TNs) increased due to modern lifestyles or other factors, despite the advances in screening and diagnostic tools. METHODS: This study included 3474 pairs of participants, who were matched by gender and age (±3 years) from two cross-sectional sampling surveys: (1) the program on the iodine nutritional status and related health status of residents in Shanghai in 2009; (2) the thyroid disease screening program for adults in Shanghai between 2017 and 2018. The prevalence of TNs and thyroid diseases in 2009 and 2017-2018 were compared, and the potential risk factors of TNs were detected. RESULTS: The prevalence of TNs in 2009 was 28.9%: 22.5% in males and 34.5% in females. In 2017, this increased to 43.8%: 37.9% in males and 49.1% in females. The prevalence of TNs significantly increased from 2009 to 2017 (odds ratio, 1.486; 95% confidence interval, 1.238-1.786). In addition, female gender, thyroid disease history, and age were the main risk factors for TNs after adjusting for confounders in the logistic regression across the time period. CONCLUSION: The prevalence of TNs significantly increased across nearly 10 years in Shanghai.

Endoscopic grading of gastric atrophy and histological gastritis staging on risk assessment for early gastric cancer: A case-control study.

OBJECTIVES: To assess the predictive value of endoscopic grading of gastric atrophy using Kimura-Takemoto classification, histological grading systems of operative link on gastritis assessment (OLGA) and operative link on gastric intestinal metaplasia (OLGIM) on risk stratification for early gastric cancer (EGC) and other potential risk factors of EGC. METHODS: A single-center, case-control study was retrospectively conducted including 68 patients with EGC treated with endoscopic submucosal dissection and 68 age- and sex-matched control subjects. Kimura-Takemoto classification, OLGA and OLGIM systems, and other potential risk factors were evaluated between the two groups. RESULTS: Of the 68 EGC lesions, 22 (32.4%) were well differentiated, 38 (55.9%) were moderately differentiated, and 8 (11.8%) were poorly differentiated, respectively. Multivariate analysis revealed O-type Kimura-Takemoto classification (adjusted odds ratio [AOR] 3.282, 95% confidence interval [CI] 1.106-9.744, P = 0.032) and OLGIM stage III/IV (AOR 17.939, 95% CI 1.874-171.722, P = 0.012) were significantly related to a higher risk of EGC. Especially, O-type Kimura-Takemoto classification within 6-12 months before EGC diagnosis (AOR 4.780, 95% CI 1.650-13.845, P = 0.004) was independently associated with EGC risk. Areas under the receiver operating characteristic curve of the three systems for EGC were comparable. CONCLUSIONS: Endoscopic Kimura-Takemoto classification and histological OLGIM stage III/IV are independent risk factors for EGC, which may reduce the need for biopsies in risk stratification of EGC. Further multicenter prospective studies of large sizes are needed.

Efficacy and safety of triple therapy containing berberine hydrochloride, amoxicillin, and rabeprazole in the eradication of Helicobacter pylori.

OBJECTIVE: To estimate the effectiveness and safety of triple therapy containing berberine, amoxicillin, and rabeprazole in the eradication of Helicobacter pylori (H. pylori). METHODS: This prospective, randomized controlled, open-label, noninferiority trial included treatment-naive patients with H. pylori infection who were randomly allocated at a ratio of 1:1 into the berberine triple therapy group (berberine hydrochloride 300 mg thrice daily, amoxicillin 1 g twice daily, and rabeprazole 10 mg twice daily) or standard bismuth-containing quadruple therapy group (amoxicillin 1 g twice daily, rabeprazole 10 mg twice daily, clarithromycin 500 mg twice daily, and bismuth tartrate 200 mg twice daily) for 14 days. Negative 13 C/14 C-urea breath test at 4 weeks after completion of the therapy was regarded as successful eradication. RESULTS: Altogether 262 and 262 patients received berberine triple therapy and bismuth-containing quadruple therapy, respectively. Both intention-to-treat (79.8% vs 80.9%, P = 0.742) and per-protocol analyses (83.6% and 85.1%, P = 0.636) showed comparable eradication rate between the two groups, indicating a noninferior eradication rate (the lower limit of the 95% confidence interval over -10% [-7.9% and -7.87%, respectively]). Adverse events more commonly occurred in the bismuth-containing quadruple-therapy group (8.8% vs 16.0%, P = 0.012), while patient compliance and symptom improvement of the two regimens were comparable. CONCLUSION: Triple therapy containing berberine, amoxicillin and rabeprazole is noninferior to bismuth-containing quadruple therapy in the initial treatment for H. pylori eradication.

Association of two polymorphisms within and near SOCS3 gene with obesity in three nationalities in Xinjiang province of China.

AIM: SOCS3 gene plays an important role in the pathogenesis of obesity in animal models, but the data from human studies are relatively limited. To address this issue, a genetic association analysis on nationalities with different genetic background living in the similar environmental conditions was performed. METHODS: Two thousand seven hundred eleven subjects were randomly recruited from the Kazakh, Uygur and Han nationalities in Xinjiang of China. SNP polymorphisms rs4969168 and rs9892622 within or near the SOCS3 gene were genotyped using TaqMan-MGB™ assay. Association study between the two polymorphisms and obesity-related traits (body mass index [BMI]; waist-to-hip ratio [WHR]; weight; height, waist, and hip measurements) was conducted. RESULTS: Significant association was found between rs4969168 and the obesity-related traits, including BMI (25.32 ± 3.49 kg/m(2) for AA, 24.60 ± 3.70 kg/m(2) for AG, 24.39 ± 3.42 kg/m(2) for GG, P=0.042), weight (65.58 ± 11.42 kg for AA, 63.50 ± 11.30 kg for AG, 62.00 ± 10.78 kg for GG, P=0.011) in the Han nationality, but not in the Kazakh or Uygur nationalities. Rs9892622 was significantly associated with BMI, WHR, and WAIST in the Uygur males. Rs9892622 was also associated with BMI in Kazakh males. Linear regression analysis verified the above findings. However, neither of the two polymorphisms was associated with obesity-related traits in the total population. CONCLUSION: The polymorphism rs4969168 within or near the SOCS3 gene has a significant effect in the Han nationality, while rs9892622 was associated with obesity in Uygur and Kazakh nationalities in Xinjiang of China.

[Observation on therapeutic alliance with UDCA and glucocorticoids in AIH-PBC overlap syndrome].

OBJECTIVE: To observe the efficacy of ursodeoxycholic acid (UDCA) combined with glucocorticoids in the treatment of autoimmune hepatitis-primary biliary cirrhosis (AIH-PBC) overlap syndrome. METHODS: 19 patients with AIH-PBC overlap syndrome were divided randomly into two groups: initiate combined group and initiate UDCA-monotherapy group. Biochemical responses and pathological features before and after treatment were analyzed retrospectively with student's t test, Wilcoxon rank sum test and Fisher's exact method. RESULTS: In the initiate combination group, biochemical responses in terms of AIH features (ALT decline to normal, IgG is less than or equal to 16 g/L) and PBC features (ALP decline ≥ 40% or to normal) were achieved. In UDCA-monotherapy group, no statistical difference existed in biochemical responses before adding glucocorticoids, whereas the levels of ALT, AST, GLB and IgG decreased significantly when combined with glucocorticoids. No statistical difference of rates of biochemical responses eixted between the two groups, whereas variance could be seen in different pathological stages. Alleviation of inflammatory infiltration after therapy appeared in 3 patients. CONCLUSION: Combination therapy of UDCA with glucocorticoids could be suitable for AIH-PBC overlap syndrome. Early treatment is of benefit for achieving better biochemical response and pathological improvement.

Lamb's tripe extract and vitamin B12 capsule plus celecoxib reverses intestinal metaplasia and atrophy: A retrospective cohort study.

BACKGROUND: Chronic atrophic gastritis (AG) with intestinal metaplasia (IM) significantly increases the risk of gastric cancer. Some medicines have showed definite therapeutic effects in AG and IM regression. AIM: To validate the efficacy of Lamb's tripe extract and vitamin B12 capsule (LTEVB12) initial therapy and celecoxib rescue therapy for IM and AG. METHODS: A total of 255 patients were included to receive LTEVB12 initial therapy (2 capsules each time, three times daily for 6 mo) in hospital in this study. The patients with failure of IM regression continued to receive celecoxib rescue therapy (200 mg, once daily for 6 mo). After each therapy finished, the patients underwent endoscopy and biopsy examination. The regression efficiency was assessed by the operative link on gastritis assessment (OLGA) and the operative link on the gastric intestinal metaplasia assessment (OLGIM) staging system. Logistic regression analysis was applied to identify factors associated with the curative effect. RESULTS: For LTEVB12 initial therapy, the reversal rates of IM and AG were 52.95% and 48.24%, respectively. Analogously, for celecoxib rescue therapy, the effective rates for IM and AG were 56.25% and 51.56%, respectively. The IM regression rate of complete therapy was up to 85.03%. In different OLGA and OLGIM stages of IM patients, therapeutic efficiency showed a significant difference in each group (P < 0.05). For both therapies, patients with high stages (III or IV) of both the OLGA and OLGIM evaluation systems showed a higher IM or AG regression rate than those with low stages (I or II). Among patients with high stages (OLGIM III and IV), the IM regression rate was above 70% for each therapy. Eating habits, fresh vegetable intake, and high-salt diet were identified as independent factors for the IM reversal effect of LTEVB12 therapy, especially high-salt diet (odds ratio = 1.852, P < 0.05). CONCLUSION: Monotherapy could reverse IM and AG. LTEVB12 initial therapy and celecoxib rescue therapy significantly increase the regression effect. IM may not be the point of no return among gastric precancerous lesions.

Bile reflux is an independent risk factor for precancerous gastric lesions and gastric cancer: An observational cross-sectional study.

OBJECTIVE: To identify whether bile reflux on endoscopy and other related variables are risk factors for precancerous gastric lesions and gastric cancer (GC). METHODS: A multicenter, cross-sectional and observational study was conducted in five centers in China from June to October 2019, 1162 patients were recruited and divided into the chronic gastritis (CG), the precancerous lesion (low-grade intraepithelial neoplasia and intestinal metaplasia), and GC groups (including high-grade intraepithelial neoplasia). All participants underwent detailed interviews, endoscopy and biopsy, and completed questionnaires. Odds ratio and 95% confidence interval were calculated with multivariate logistic regression models with or without adjustment for Helicobacter pylori infection. RESULTS: We recruited 668 patients with CG, 411 with precancerous lesions and 83 with GC. By comparing the CG and precancerous lesion groups, independent risk factors for cancerous gastric lesions were the grade of bile reflux, patient's age, dietary habits and family history of GC. Similar results were obtained when comparing the CG and GC groups. In addition, bile reflux was confirmed as an independent risk factor for progression from precancerous lesions to cancer. CONCLUSIONS: Bile reflux on endoscopy as well as age, dietary habits and a family history of GC were independent risk factors for the development of precancerous gastric lesions and GC.

The presence of NAFLD in nonobese subjects increased the risk of metabolic abnormalities than obese subjects without NAFLD: a population-based cross-sectional study.

BACKGROUND: With lifestyle modification and over-nutrition, the prevalence of nonalcoholic fatty liver disease (NAFLD) has been increasing annually. Here we aimed to assess the updated prevalence of NAFLD, and to evaluate the association of NAFLD with metabolic abnormalities according to gender, body mass index and age. METHODS: A population-based cross-sectional study was conducted in Shanghai from December 2016 to July 2017. With a three-stage stratified sampling strategy, 3,717 eligible participants were enrolled for the analysis. RESULTS: In total, 1,217 subjects (32.7%) had NAFLD. Among them, 400 (16.3%) of the nonobese and 817 (65.0%) of the obese subjects had NAFLD. The prevalence of NAFLD was increased according to the quartiles of age and waist circumference (WC) in the nonobese subjects. Females with nonobese NAFLD had 1.6-, 2.6-, 2.0-, 2.3- and 3.3-fold higher risks for metabolic syndrome, diabetes mellitus, hyperglycemia, hypertriglycerdemia (high TG) and low high-density lipoprotein cholesterol than obese subjects without NAFLD, respectively. Males had comparable metabolic profiles in both groups, except for a 2.0-fold higher risk of high TG in nonobese NAFLD subjects compared with obese subjects without NAFLD. More impressively, the homeostasis metabolic assessment insulin resistance index was comparable between the two groups. CONCLUSIONS: The increase of age and WC had significant impact on the risk of NAFLD in nonobese subjects. The presence of NAFLD in nonobese subjects increased the risk of metabolic diseases than obese subjects without NAFLD, especially in female.

Mechanistic study of endogenous skin lesions in diabetic rats.

Pathological and physiological changes in dermal tissue in a rat model of diabetes mellitus (DM) were investigated. Sixteen male 8-week-old Sprague-Dawley rats were randomized into two groups of eight, the DM group (Group DM) and the normal control group (Group (NC) normal control). Group DM rats were injected with streptozotocin (STZ) intraperitoneally at a dose of 65 mg/kg body weight. Group NC rats were injected with the same volume of citric acid buffer. All rats were sacrificed 12 weeks later. The impact of exposure to (AGE) advanced glycation end products-modified human serum albumin (AGE-HSA) on epidermal cells and ECV304 cells was evaluated in cell culture experiments. The diabetic rats exhibited changes in skin tissue, including a decrease in thickness, disappearance of the multilayer epithelium structure, degeneration of collagen fibres and an increase in the infiltration of inflammatory cells, in addition to a significant increase in skin glucose and AGEs. Moreover, diabetic rats had increased plasma glycosylated protein (GSP) and malondialdehyde (MDA) and decreased plasma glutathione (GSH). The percentage of epidermal cells in S phase was similar between the two group rats; however, there was a marked decrease in the G2/M phase in Group DM. Additionally, exposure of ECV304 cells to AGE-HSA led to a time-dependent and dose-dependent increase in apoptosis. Therefore, the high glucose in the skin tissue, coupled with the accumulation of toxic substances such as AGEs, promote the dysfunction of dermal cells and/or the matrix. This may be a significant mechanism of diabetes-induced early-stage endogenous skin damage.

[A two-year follow-up study on the efficacy of ursodeoxycholic acid on primary biliary cirrhosis in different stages].

OBJECTIVE: To assess the therapeutic effect of primary biliary cirrhosis(PBC) in different stages with ursodeoxycholic acid (UDCA). METHODS: 91 patients with PBC were divided into 4 periods based on levels of liver test and symptoms. Clinical manifestations, biochemical changes and pathological changes were observed for 2 years on UDCA therapy. RESULTS: The levels of alkaline phosphatase (ALP) and glutamyltranspetidase (GGT) at the second PBC period were declined by 51.9% and 67.3% respectively after a 6-month UDCA therapy. The biochemical responses were 81.25% (Paris criteria) and 93.75% (Barcelona criteria). The levels of ALP and GGT at the third PBC period were declined by 48.8% and 46.6% after 6 months of UDCA therapy, and the biochemical responses were 36.84% (Paris criteria) and 57.89% (Barcelona criteria). Symptoms like fatigue, pruritus and jaundice after UDCA therapy were better than before. Same results also appeared at the fourth period. 11 patients in different periods underwent pathological examinations before and after UDCA therapy and no progression found in the first and the second periods, however difference found in the third and the fourth periods with the lymphocyte infiltration was less than before UDCA treatment. CONCLUSION: Good biochemical responds appear in patients at the second, third and forth periods after UDCA therapy, in which the second period is best. Symptoms could be improved after UDCA treatment. Early UDCA therapy is benefit for slowing down the progression of liver pathology.

Recent advances of miRNAs in the development and clinical application of gastric cancer.

Gastric cancer (GC) is one of the most common malignant tumors. The mechanism of how GC develops is vague, and therapies are inefficient. The function of microRNAs (miRNAs) in tumorigenesis has attracted the attention from many scientists. During the development of GC, miRNAs function in the regulation of different phenotypes, such as proliferation, apoptosis, invasion and metastasis, drug sensitivity and resistance, and stem-cell-like properties. MiRNAs were evaluated for use in diagnostic and prognostic predictions and exhibited considerable accuracy. Although many problems exist for the application of therapy, current studies showed the antitumor effects of miRNAs. This paper reviews recent advances in miRNA mechanisms in the development of GC and the potential use of miRNAs in the diagnosis and treatment of GC.

Efficacy and safety of fecal microbiota transplantation by washed preparation in patients with moderate to severely active ulcerative colitis.

OBJECTIVE: We aimed to evaluate the short-term efficacy and safety of fecal microbiota transplantation (FMT) by washed preparation for moderate to severely active UC. METHODS: An open-label prospective trial was conducted in an inflammatory bowel disease (IBD) tertiary referral center from April 2016 to March 2018. Patients with moderate to severely active UC were randomly assigned to undergo FMT thrice on day 1, 3 and 5 by nasojejunal tube (NJT) or transendoscopic enteral tubing (TET). The primary end-point was a clinical response at week 2 post-FMT. The secondary end-points were clinical and endoscopic remission at week 12 post-FMT, safety and disease progression. RESULTS: Of the nine patients included, 77.8% (7/9) achieved a clinical response at week 2. And 55.6% (5/9) and 33.3% (3/9), respectively, achieved clinical remission and endoscopic remission at week 12. In two patients who had no response to FMT, one switched to anti-tumor necrosis factor-α therapy, and the other underwent a colectomy. FMT was delivered through NJT in 44.4% (4/9) of the patients, while TET was used in 55.6% (5/9). The clinical outcomes did not differ significantly based on the delivery route (P > 0.05). Adverse events, all mild and self-limiting, were observed in 33.3% (3/9) of the patients. CONCLUSIONS: FMT by washed preparation appears to be a safe and effective adjunct therapy for moderate to severely active UC during a short-term follow-up. The efficacy did not differ significantly between the NJT or TET delivery routes. Further randomized controlled studies are needed to confirm these findings.

A randomized, multicenter and noninferiority study of amoxicillin plus berberine vs tetracycline plus furazolidone in quadruple therapy for Helicobacter pylori rescue treatment.

OBJECTIVE: Helicobacter pylori (H. pylori) infection is closely associated with gastric ulcers and gastric adenocarcinomas. We aimed to assess the efficacy and safety of a quadruple regimen with amoxicillin plus berberine vs tetracycline plus furazolidone in rescue therapy for H. pylori eradication. METHODS: We conducted a randomized, open-label, multicenter, noninferiority trial. Patients with previous treatment failures recruited from five centers were randomized (1:1) to receive a regimen with esomeprazole and bismuth plus either berberine and amoxicillin (the BA group) or tetracycline and furazolidone (the TF group) for 14 days. Their H. pylori infection status was confirmed 4-8 weeks after treatment. The primary outcome was the eradication rate. The secondary outcomes included the rates of symptom improvement, compliance, and adverse events. This study was registered at ClinicalTrials.gov (NCT03609892). RESULTS: Altogether 658 participants were consecutively enrolled. An intention-to-treat analysis demonstrated that the two regimens achieved a similar eradication rate (76.3% vs 77.5%; P = 0.781). The per-protocol analysis reached a similar result (81.5% vs 85.0%; P = 0.278). The eradication rate reached in the BA group was greater than the pre-established margin of noninferiority, at -10% (the lower bounds of the 95% CI were -7.66% and -9.43%, respectively). The rate of adverse events was lower for the BA group than the TF group (18.5% vs 26.1%, P = 0.024). Rates of compliance and symptom improvement were similar for the two therapies. CONCLUSION: The efficacy of both regimens in rescue treatment for H. pylori eradication was satisfactory, 14-day BA-based quadruple therapy is noninferior to the TF-based therapy.

Efficacy and safety of dulaglutide monotherapy compared with glimepiride in Chinese patients with type 2 diabetes: Post-hoc analyses of a randomized, double-blind, phase III study.

AIMS/INTRODUCTION: To investigate the efficacy/safety of dulaglutide once-weekly monotherapy versus glimepiride in Chinese patients with type 2 diabetes. MATERIALS AND METHODS: This was a post-hoc analysis of a Chinese randomized, double-blind, non-inferiority, phase III study. Patients (n = 572) with inadequate glycemic control received dulaglutide 1.5 mg (n = 189) or 0.75 mg (n = 194) once-weekly or glimepiride (1-3 mg/day; n = 189) for 26 weeks. The primary objective of the study was to investigate the non-inferiority of dulaglutide 1.5 mg versus glimepiride by the change from baseline to week 26 in glycated hemoglobin (non-inferiority margin 0.4%). RESULTS: Dulaglutide 1.5 mg and 0.75 mg were non-inferior (P < 0.001) and superior (P ≤ 0.002) versus glimepiride for the change in glycated hemoglobin from baseline to week 26. The least-squares mean differences (95% confidence interval) versus glimepiride were dulaglutide 1.5 mg, -0.53% (-0.74, -0.32) and dulaglutide 0.75 mg, -0.32% (-0.53, -0.12). Significantly more patients attained glycated hemoglobin <7.0% at week 26 in the dulaglutide 1.5 mg (71.7%) versus the glimepiride (57.5%; P = 0.005) group. The decrease from baseline to week 26 in fasting blood glucose was significantly more pronounced in both the dulaglutide groups versus the glimepiride group (P < 0.01). The overall incidence and rate of hypoglycemia were lower in both of the dulaglutide groups versus the glimepiride group. At week 26, bodyweight had increased from baseline in the glimepiride group and decreased from baseline in both dulaglutide groups. The most frequent gastrointestinal drug-related adverse events with dulaglutide were diarrhea, abdominal distension, nausea and vomiting. CONCLUSIONS: These findings support once-weekly dulaglutide monotherapy as a treatment for Chinese patients with early stage type 2 diabetes.

The relationship between gastric cancer, its precancerous lesions and bile reflux: A retrospective study.

OBJECTIVE: To evaluate the relationship between gastric cancer (GC) and precancerous lesions and bile reflux. METHODS: Medical records of 30 465 participants who underwent gastroscopy between January and December 2018 in our center were reviewed. Their age, sex, time of endoscopy, endoscopic/histologic diagnosis and grade of bile reflux were recorded. The participants were further divided into the chronic gastritis group (n = 27 807), a precancerous lesion group (n = 1943) and a GC group (n = 715). The χ2 tests and hierarchical analyses were performed. RESULTS: Patients aged 18-27 years had a higher bile reflux rate than those aged 28-37 and 68-75 years (P < 0.001), while it did not differ between patients aged <50 years and those over 50 years (P = 0.639). It was lower in men than in women (P < 0.001). The bile reflux rate did not differ in terms of months, seasons and half of the year (all P > 0.05), but differed between morning and afternoon when they underwent the endoscopy (P = 0.000). There was an interrelationship between the severity of gastric mucosal disease and bile reflux grade (r = 0.171). After excluding the effects of sex, age and time of endoscopy on bile reflux, bile reflux rate in chronic gastritis and precancerous lesions was lower than in gastric cancer (P < 0.01). CONCLUSIONS: Bile reflux may be a risk factor for gastric cancer and precancerous lesions. A high grade of bile reflux may be associated with the progression of gastric mucosal diseases.