Ethnic disparity in pneumonia-specific mortality among children under 5 years of age in Sichuan Province of Western China from 2010 to 2017.

BACKGROUND: To reveal the ethnic disparity in the pneumonia-specific mortality rates of children under the age of 5 years (PU5MRs) and provide suggestions regarding priority interventions to reduce preventable under-five-years-of-age deaths. METHODS: Data were obtained from the Direct Report System of Maternal and Child Health in Sichuan. The Cochran-Armitage trend test was used to assess the time trend. The Cochran-Mantel-Haenszel test and Chi-square test were used to examine the differences in the PU5MRs among different groups. RESULTS: The PU5MRs in the minority and nonminority counties decreased by 53.7 and 42.3% from 2010 to 2017, respectively. The PU5MRs of the minority counties were 4.81 times higher than those of the nonminority counties in 2017. The proportion of pneumonia deaths to total deaths in Sichuan Province increased from 11.7% in 2010 to 15.5% in 2017. The pneumonia-specific mortality rates of children in the categories of 0-28 days, 29 days-11 months, and 12-59 months were reduced by 55.1, 38.8, and 65.5%, respectively, in the minority counties and by 35.5, 43.1, and 43.7%, respectively, in the nonminority counties. CONCLUSIONS: PU5MRs declined in Sichuan, especially in the minority counties, while ethnic disparity still exists. Although the PU5MRs decreased more for the minority counties as a fraction of all mortality, the absolute number of such deaths were higher, and therefore more children in these counties continue to die from pneumonia than from the non-minority counties. Priority should be given to strategies for preventing and controlling child pneumonia, especially for postneonates, in the minority counties.

Risk factors for recurrence of common bile duct stones after endoscopic biliary sphincterotomy.

Objective Late complications after endoscopic biliary sphincterotomy (EST) include stone recurrence, but no definite risk factors for recurrence have been established. This study was performed to identify the predictors of recurrence and evaluate the clinical outcomes of EST for common bile duct stones. Methods In total, 345 eligible patients who successfully underwent EST were evaluated and followed up. Statistical analysis was performed on patients with recurrence or who had undergone at least 6 months of reliable follow-up to detect the risk factors for recurrence. Results A total of 57 patients (16.52%) developed recurrence of common bile duct stones. The median length of time until recurrence was 10.25 months (range, 6-54.4 months). Univariate analyses showed that the following factors were associated with recurrence: cholecystectomy prior to EST, prior biliary tract surgery, periampullary diverticulum, diameter of the common bile duct (>15 vs. ≤15 mm), quantity of stones, complete stone removal at the first session, and lithotripsy. Multivariate analysis identified two independent risk factors for recurrence: previous biliary tract surgery and lithotripsy. Conclusions EST for common bile duct stones is safe as indicated by patients' long-term outcomes. Patients with a history of biliary surgery or lithotripsy are more prone to recurrence.

Association of SIRT1 gene polymorphism and its expression for the risk of alcoholic fatty liver disease in the Han population.

OBJECTIVE: To investigate the associations between SIRT1 polymorphisms and their expression in patients with alcoholic fatty liver disease (AFLD). METHODS: A total of 268 heavy drinkers were divided into the AFLD group (n = 176) and alcoholic control (n = 92) and 237 light-/non-drinkers into the NAFLD (non-AFLD) group (n = 117) and healthy control (n = 120). The genotyping of SIRT1 (rs33957861, rs11599176, rs12413112 and rs35689145) was detected by the Sequenom MassARRAY iPLEX test. The mRNA and protein expressions of SIRT1 were determined by quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assays (ELISA), respectively. RESULTS: SIRT1 gene rs33957861 and rs11599176 polymorphisms significantly reduce the risk of NAFLD and AFLD, while rs35689145 remarkably increases the risk. Haplotypes of AAAA (rs33957861-rs11599176-rs12413112-rs35689145), AAAA, CAGA and CGAA can appreciably lower the presence of AFLD, but CAAG had an elevated AFLD risk. Besides, in the NAFLD and AFLD groups, a decreased BMI was found in the mutant genotype carriers of rs33957861, rs11599176 and rs12413112, but an increased BMI was observed in the rs35689145 mutant genotype carriers when compared to those with the wild-type homozygous genotype ones. Furthermore, rs33957861 C>T, rs11599176 A>G and BMI were independent risk factors of AFLD. There was no difference among four SNPs of SIRT1 and its mRNA and protein expressions in all groups. CONCLUSION: SIRT1 polymorphisms and their expression were associated with the presence of AFLD, and there was a close relationship among four SNPs and BMI in AFLD patients, but no SNP was related to its expression.

SOX2 Inhibition Promotes Promoter Demethylation of CDX2 to Facilitate Gastric Intestinal Metaplasia.

BACKGROUND: Gastric intestinal metaplasia (IM) is regarded as a premalignant lesion, conferring risks for gastric cancer development. An intestinal transcription factor, CDX2, plays a vital role in establishing and maintaining IM. SOX2, an HMG-box transcription factor, is expressed in normal gastric mucosa and downregulated in IM. Therefore, it is important to elucidate the mutual interaction of SOX2 and CDX2 in gastric IM. AIMS: This study aims to evaluate the negative correlation between SOX2 and CDX2 in mRNA expression and promoter methylation and to illuminate the effect of SOX2 on the promoter methylation of CDX2. METHODS: Immunohistochemistry, real-time PCR and methylation-specific polymerase chain reaction assays were performed to evaluate the expression and promoter methylation of SOX2 and CDX2 in IM tissues from patients. SOX2 knockdown and CDX2 overexpression were performed in GES-1 cells to further clarify the relationship between SOX2 and CDX2. RESULTS: A negative correlation between SOX2 and CDX2 was found in 120 gastric IM specimens. Additionally, significant DNA demethylation of CDX2 promoter in clinical IM specimens was observed concomitantly with partial methylation of the SOX2 promoter. Furthermore, SOX2 knockdown in GES-1 cells triggered promoter demethylation of CDX2. Finally, the phenotype shift of gastric intestinal metaplasia in GES-1 cells, marked by MUC2 expression, was effectively induced by the combination of SOX2 RNAi and CDX2 overexpression. CONCLUSIONS: Aberrant DNA methylation of SOX2 and CDX2 genes contributes to the development of IM. Notably, SOX2 may play a role in establishing and maintaining the methylation status of the CDX2 gene in gastric tissues and cells.

Risk and cause of interval colorectal cancer after colonoscopic polypectomy.

BACKGROUND: To investigate the cause and risk of interval colorectal cancer (ICC) in patients undergoing surveillance colonoscopy within 5 years after colonoscopic polypectomy. PATIENTS AND METHODS: We retrospectively analyzed data (endoscopy, pathology, demography) of patients who received surveillance colonoscopy within 5 years after colonoscopic polypectomy. RESULTS: Among 1,794 patients undergoing surveillance colonoscopy within 5 years after colonoscopic polypectomy, 14 suffered from ICC. The mean follow-up time was 2.67 years and the incidence density of ICC was 2.9 cases per 1,000 person-years. 50% of ICCs were found in patients in whom adenomas had been incompletely removed by endoscopic therapy, 36% were missed cancers, and 14% were new cancers. Age >60 years (OR 2.97, 95% CI 2.31-3.82) was significantly associated with interval cancer on the surveillance colonoscopy as were advanced adenoma (OR 1.28, 95% CI 1.01-1.62), the presence of villous (HR 1.38, 95% CI 1.03-1.85) and high-grade dysplasia (OR 1.61, 95% CI 1.07-2.42). CONCLUSIONS: Among patients undergoing surveillance colonoscopy within 5 years after polypectomy, the incidence density of ICC was 2.9 cases per 1,000 person-years. The majority of interval cancers originated from incomplete resection of advanced adenomas and missed cancers, which can be prevented by improving endoscopic techniques and selecting an appropriate follow-up time interval.

Five-year risk of colorectal neoplasia after normal baseline colonoscopy in asymptomatic Chinese Mongolian over 50 years of age.

BACKGROUND: After normal colonoscopy, the 5-year risk of colorectal neoplasia is sufficiently low for asymptomatic people over 50 years of age. In China, the incidence of colorectal carcinoma of Mongolian people is higher than that of Han people. The aim of this study was to assess the 5-year risk of colorectal neoplasia after normal colonoscopy in asymptomatic Chinese Mongolian population. PATIENTS AND METHODS: A cohort of asymptomatic Chinese Mongolian people (≥50 years old) were recruited and followed up with colonoscopy 5 years after colonoscopy. Baseline colonoscopy and follow-up colonoscopy findings were categorized based on the most advanced lesions: no adenoma, nonadvanced adenoma, and advanced adenoma. Five-year risk of colorectal neoplasia in these people was assessed according to the rates of no baseline adenoma and advanced adenoma at the end of 5 years. RESULTS: A total of 480 of the 538 recruited people underwent follow-up colonoscopy at the end of 5 years. In people with no baseline adenoma, 27.3 % (82/301) was found to have any adenoma, and 1.7 % had advanced adenoma at follow-up colonoscopy. The risk of an advanced adenoma did not differ significantly between people with no adenoma at baseline and those with nonadvanced adenoma (relative risk (RR), 1.06; 95 % confidence interval (CI), 0.19-6.07). Advanced adenoma at baseline colonoscopy was the independent risk factor for advanced adenoma recurrence, compared with no adenoma at baseline (RR, 8.25; 95 % CI, 1.90-35.77). CONCLUSION: The risk of advanced adenoma is low 5 years after the normal baseline colonoscopy, even in asymptomatic Chinese Mongolian population over 50 years of age.

The role of small molecular weight compounds to increase vacuolation induced by VacA toxin in vitro.

VacA is a vacuolation protein toxin secreted by Helicobacter pylori. Many compounds have been implicated in the regulation of VacA toxin activity. In this study, regulation of cell vacuolation induced by VacA was observed with the addition of glycine, glycine hydrochloride, xylitol, and taurine by neutral red dye uptake assay using gastric human epithelial cell cultures. Glycine, xylitol, and taurine increased cell vacuolation significantly after 48h (p<0.05), with their effect apparent in a wide concentration range (0.2mM to about 100mM). Changes were sharp in respect of concentration and showed little dose-response characteristics. In contrast, upregulation of glycine hydrochloride on cell vacuolation in weak acidic extracellular pH was much retarded with VacA activity not initiated until 72h. In addition, our results showed that cell vacuolation was highest when the pH was 6.8. The increase in vacuolation was gentle in weak acidic extracellular pH and the increase dose-dependent with a Pearson correlation coefficient (r) of 0.986 from 0.2 to 6.25mM. In this concentration range and at the same time point, the pH decrease was negatively correlated with vacuolating activity (r=0.922, p<0.01). In conclusion, our study showed that three small molecular compounds can increase vacuolation induced by VacA toxin in vitro.

Recurrence and surveillance of colorectal adenoma after polypectomy in a southern Chinese population.

BACKGROUND AND AIM: Repeat colonoscopy is often performed within a short time after polypectomy due to the fear that colorectal adenomas were missed during the initial colonoscopy or that new adenomas have developed. The aim of this study was to estimate the actual recurrence rate of adenoma and its association with the length of the surveillance interval after polypectomy in a southern Chinese population. METHODS: A total of 1,356 patients undergoing endoscopic polypectomy and completing three or more surveillence colonoscopies between 1976 and 2007 were retrospectively analyzed. The recurrence rates of adenoma and advanced adenoma and surveillance intervals after polypectomy were identified based on the features of adenomas detected on initial colonoscopy. RESULTS: The recurrence rates of advanced adenoma in patients with non-advanced adenoma on the initial colonoscopy were 0.9, 3.9, 5.8, and 29.2% during surveillance intervals of 1-3, 3-5, 5-10, and 10-20 years post-initial colonoscopy; for patients with advanced adenoma on the initial colonoscopy, the recurrence rates were 3.8, 13.1, 34.7, and 52.0% during the same surveillance intervals, respectively. Older age (p < 0.05 for trend) and male sex [hazard ratio (HR) 2.11, 95% confidence interval (CI) 1.27-3.53] were significantly associated with recurrence for advanced adenoma, as were the size and number of baseline adenoma (p < 0.05 for trend), tubulovillous, villous adenoma (HR 2.57, 95% CI 1.24-5.32), and high-grade dysplasia (HR 1.61, 95% CI 1.07-2.42). When 5% of patients had recurring advanced adenoma, the surveillance interval was estimated to be 6.9 (95% CI 6.3-12.2) years in the low-risk group and 3.0 (95% CI 2.7-3.2) years in the high-risk group. CONCLUSIONS: Among our patient group, the recurrence of advanced adenoma after polypectomy increased with the length of the surveillance interval. Based on our results, a 3-year follow-up of patients after polypectomy could be effective in preventing the recurrence of advanced adenoma in high-risk patients.

Effect of NaCl and Helicobacter pylori vacuolating cytotoxin on cytokine expression and viability.

AIM: To determine whether Helicobacter pylori (H pylori) vacuolating cytotoxin (VacA) regulates release of pro-inflammatory cytokines (IL-1beta, IL-8, TNF-alpha, and IL-6) or alters gastric epithelial cell viability and to determine whether NaCl affects these VacA-induced changes. METHODS: Vacuolating activity was determined by measuring the uptake of neutral red into vacuoles of VacA-treated human gastric epithelial (AGS) cells. AGS cell viability was assessed by direct cell counting. Specific enzyme-linked immunosorbent assays (ELISA) and reverse transcriptase-polymerase chain reaction(RT-PCR) were performed to examine the effects of H pylori VacA and NaCl on cell pro-inflammatory cytokine production in AGS cells. Immunohistochemical staining of gastric tissue from Mongolian gerbils was used to confirm VacA-induced pro-inflammatory cytokine production and the effects of NaCl on this VacA-induced response. RESULTS: Addition of VacA alone reduced AGS cell viability (P < 0.05), and this reduction was enhanced by high doses of NaCl (P < 0.05). VacA alone induced expression of TNF-alpha, IL-8 and IL-1beta, while NaCl alone induced expression of TNF-alpha and IL-1beta. Changes in mRNA levels in the presence of both VacA and NaCl were more complicated. For the case of TNF-alpha, expression was dose-dependent on NaCl. IL-6 mRNA was not detected. However, low levels of IL-6 were detected by ELISA. Positive immunohistochemical staining of IL-1, IL-6, and TNF-alpha was found in gastric tissue of H pylori-infected gerbils fed with either a normal diet or a high salt diet. However, the staining of these three cytokines was stronger in H pylori-infected animals fed with a 5 g/kg NaCl diet. CONCLUSION: VacA decreases the viability of AGS cells, and this effect can be enhanced by NaCl. NaCl also affects the production of pro-inflammatory cytokines induced by VacA, suggesting that NaCl plays an important role in H pylori-induced gastric epithelial cell cytotoxicity.