Association of non-HDL-C/apoB ratio with long-term mortality in the general population: A cohort study.

Background: In general, the identification of cholesterol-depleted lipid particles can be inferred from non-high-density lipoprotein cholesterol (non-HDL-C) concentration to apolipoprotein B (apoB) concentration ratio, which serves as a reliable indicator for assessing the risk of cardiovascular disease. However, the ability of non-HDL-C/apoB ratio to predict the risk of long-term mortality among the general population remains uncertain. The aim of this study is to explore the association of non-HDL-C/apoB ratio with long-term all-cause and cardiovascular mortality in adults of the United States. Methods: This retrospective cohort study was a further analysis of existing information from the National Health and Nutrition Examination Survey (NHANES). In the ultimate analysis, 12,697 participants from 2005 to 2014 were included. Kaplan-Meier (K-M) curves and the log-rank test were applied to visualize survival differences between groups. Multivariate Cox regression and restricted cubic spline (RCS) models were applied to evaluate the association of non-HDL-C/apoB ratio with all-cause and cardiovascular mortality. Subgroup analysis was conducted for the variables of age, sex, presence of coronary artery disease, diabetes and hypertriglyceridemia and usage of lipid-lowering drugs. Results: The average age of the cohort was 46.8 ± 18.6 years, with 6215 (48.9%) participants being male. During a median follow-up lasting 68.0 months, 891 (7.0%) deaths were documented and 156 (1.2%) patients died of cardiovascular disease. Individuals who experienced all-cause and cardiovascular deaths had a lower non-HDL-C/apoB ratio compared with those without events (1.45 ± 0.16 vs. 1.50 ± 0.17 and 1.43 ± 0.17 vs. 1.50 ± 0.17, both P values < 0.001). The results of adjusted Cox regression models revealed that non-HDL-C/apoB ratio exhibited independent significance as a risk factor for both long-term all-cause mortality [hazard ratio (HR) = 0.51, 95% confidence interval (CI): 0.33-0.80] and cardiovascular mortality (HR = 0.33, 95% CI: 0.12-0.90). Additionally, a significant sex interaction was discovered (P for interaction <0.05), indicating a robust association between non-HDL-C/apoB ratio and long-term mortality among females. The RCS curve showed that non-HDL-C/apoB ratio had a negative linear association with long-term all-cause and cardiovascular mortality (P for non-linearity was 0.098 and 0.314). Conclusions: The non-HDL-C/apoB ratio may serve as a potential biomarker for predicting long-term mortality among the general population, independent of traditional risk factors.

Elevated MIR100HG promotes colorectal cancer metastasis and is associated with poor prognosis.

mir-100-let-7a-2-mir-125b-1 cluster host gene (MIR100HG), which is located on chromosome 11q24.1, is a polycistronic microRNA host gene. MIR100HG overexpression in colorectal cancer (CRC) has been demonstrated to be associated with cetuximab resistance; however, the role of MIR100HG in CRC metastasis remains unclear. The present study aimed to investigate the impact of aberrant MIR100HG expression on metastasis and prognosis in patients with CRC. The results from reverse transcription-quantitative PCR demonstrated that MIR100HG expression was higher in CRC tissues compared with in corresponding normal mucosa tissues. In particular, MIR100HG expression was higher in advanced CRC compared with in early stage CRC. Furthermore, the results from Kaplan-Meier analysis followed by a log-rank test revealed that patients with CRC and high MIR100HG expression exhibited poorer disease-free survival and overall survival compared with patients with CRC and lower MIR100HG expression. Furthermore, results from in vitro Transwell assays and in vivo animal assays demonstrated that upregulated MIR100HG expression promoted CRC cell migration and invasion and the formation of liver metastatic colonies in mice. In conclusion, the present study demonstrated that MIR100HG overexpression may contribute to the progression of CRC and may predict a poorer prognosis in patients with CRC. MIR100HG may therefore be considered as a novel therapeutic target and a prognostic biomarker in patients with CRC.

Facile synthesis of Pt-decorated Ir black as a bifunctional oxygen catalyst for oxygen reduction and evolution reactions.

Pt-Decorated Ir black (Pt@Ir) nanoparticles with two varying Pt mass fractions (Pt4@Ir96 and Pt16@Ir84) were generated by a facile method in water with the aid of Ir black. The Pt@Ir nanoparticles were investigated as a bifunctional oxygen catalysts for both the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) in acidic medium. Benefiting from the good dispersion of ultrafine Pt nanodots on the Ir black surface and the synergistic effect between the Pt and underlying Ir atoms, Pt@Ir nanoparticles have exhibited outstanding ORR activity and comparable OER performance in comparison with commercial Ir black. In particular, Pt16@Ir84 shows an ORR mass activity of 2.6 times that of commercial Pt black and exhibits much better bifunctional performances than a mixture of Pt black and Ir black with a Ir/Pt mass ratio of 50/50 (Pt50Ir50). Our work highlights the effectiveness of decorating Ir black with Pt nanodots to fabricate bifunctional oxygen catalysts.

Suppression of miR-21-3p enhances TRAIL-mediated apoptosis in liver cancer stem cells by suppressing the PI3K/Akt/Bad cascade via regulating PTEN.

BACKGROUND: TNF-related apoptosis-inducing ligand (TRAIL) functions as a selective apoptosis-inducing ligand in cancer cells with normal cells remaining unaffected; however, resistance limits its anticancer properties. Cancer stem cells (CSCs) are involved in the treatment of resistant cancer cases including liver cancer (LC). The aim of this study was to look into the approaches for increasing the sensitivity of liver cancer stem cells (LCSCs) toward TRAIL. METHODOLOGY: PLC, HepG2 and Huh7 LC cell lines were used in this study. Quantitative reverse transcription PCR (qRT-PCR) analysis was done for evaluating the expression of miR-21-3b. Fluorescent-activated cell-sorting equipment was used for separation and identification of LCSCs and non-LCSCs. The cells were transfected with RNA along with miR-21-3p mimics, anti- miR-21-3p, miR-NC and the phosphatase and tensin homologue (PTEN) siRNA. MTT assay for cell viability, Luciferase assay for luciferase activity, Western blots for the expression of proteins and flow cytometry for the measurement of ROS and apoptosis, respectively, were carried out. Tumor xenografts nude mice were used for tumor growth in vivo. RESULTS: We found that miR-21-3p was overexpressed in LCSCs compared to non-LCSCs and that the suppression of miR-21-3p along with anti-miR-21-3p enhanced the sensitivity of LCSCs to TRAIL-mediated apoptosis. We further found that miR-21-3p regulated the expression of PTEN in Huh7-LCSCs directly and that the suppression of miR-21-3p enhanced the levels of PTEN. The study confirmed that inhibition of the PI3K/Akt/Bad signaling pathway was involved in enhancing TRAIL-mediated apoptosis of LC cells. CONCLUSION: The study suggested that overexpression of miR-21-3p suppresses the sensitivity to TRAIL in LCSCs. This study concludes that the suppression of miR-21-3p is a potential approach for enhancing the sensitivity of LC cells toward TRAIL by PI3K/Akt/Bad cascade via the miR-21-3p/PTEN axis.

[Risk analysis of the canceration of colorectal large polyps].

OBJECTIVE: To analyze the risk factors of carcinogenesis of large colorectal polyps (diameter ≥ 10 mm) found by colonoscopy. METHODS: Clinicopathological and follow-up data of 418 consecutive patients who were diagnosed as colorectal polyps with diameter≥10 mm by colonoscopy at two endoscopy centers of the Affiliated Wuxi Second People's Hospital, Nanjing Medical University (n=207) and Zhongshan Hospital, Fudan University (n=211) from January 2015 to December 2016 were retrospectively collected. High-grade intraepithelial neoplasia and cancer were defined as malignancy in this study. Chi square test was used for univariate analysis, and logistic regression was used for multivariate analysis (in patients with multiple polyps, if the pathological findings were all low grade intraepithelial neoplasia, one polyp with the largest diameter was selected to enter the model; in patients with high grade intraepithelial neoplasia, one polyp of high grade intraepithelial neoplasia with the largest diameter was selected to enter the model). Associated risk factors of malignancy were analyzed. RESULTS: Among the 418 patients, 278(66.5%) were male and 140(33.5%) were female, with mean age of (58.7±10.2) (range 15-87) years old. Of 398 patients undergoing endoscopic treatment with resected 456 polyps, 142 cases with 150 polyps were malignant, including 134 polyps of high-grade intraepithelial neoplasia and 16 polyps of intra-mucosal cancer. The other 20 patients showed negative elevation signs after endoscopic submucosal injection and were transferred to surgery, of whom 20 polyps were resected. Histological examination of these 20 polyps indicated invasive cancer. Univariate analysis showed that age ≥ 50 years [40.5% (150/370) vs. 25.0% (12/48), χ² =4.323, P=0.041], multiple polyps [77.5%(31/40) vs. 34.7%(131/378), χ² =12.900, P=0.001], polyp locating at rectum [59.0%(36/61) vs. 32.3%(134/415), χ² =22.736, P=0.000], polyp diameter ≥31 mm [74.1%(20/27) vs. 33.4%(150/449), χ² =36.493, P=0.000] and tubular villous adenoma [67.4%(120/178) vs. 16.8%(50/298), χ² =71.810, P=0.000] were associated with malignancy. Multivariate analysis showed that age ≥ 50 years(OR=2.473, 95%CI:1.209-5.058, P=0.013), multiple polyps (OR=2.472, 95%CI: 1.300-4.702, P=0.006), polyp locating at rectum (OR=1.253, 95%CI: 1.091-1.439, P=0.001) and the polyp diameter ≥31 mm (OR=1.500, 95%CI:1.196-1.881, P=0.000) were independent risk factors for malignancy of large colorectal polyps. The mean follow-up time was (9.6±4.2) months. During the follow-up period, 86 patients (20.5%) who received endoscopic resection developed recurrent adenoma which all were successfully removed by colonoscopic polypectomy. Two patients(0.5%) developed colon cancer 6 months after endoscopic resection and both underwent radical surgery and chemotherapy. Their previous pathology from endoscopic resection was tubular villous adenoma and high grade intraepithelial neoplasia. All the patients were alive during the follow-up period. CONCLUSIONS: Age ≥50 years old, multiple polyps, polyps locating at rectum and polyps with diameter ≥ 31 mm are the risk factors of malignancy. Emphasized examination should be recommended for those with the above mentioned risk factors to avoid missed diagnosis and misdiagnosis. The choice of endoscopic treatment must be reasonable for curative resection.

The role of regulatory B cells in digestive system diseases.

INTRODUCTION: The past decade has provided striking insights into a newly identified subset of B cells known as regulatory B cells (Bregs). In addition to producing antibody, Bregs also regulate diseases via cytokine production and antigen presentation. This subset of B cells has protective and potentially therapeutic effects. However, the particularity of Bregs has caused some difficulties in conducting research on their roles. Notably, human B10 cells, which are Bregs that produce interleukin 10, share phenotypic characteristics with other previously defined B cell subsets, and currently, there is no known surface phenotype that is unique to B10 cells. METHODS: An online search was performed in the PubMed and Web of Science databases for articles published providing evidences on the role of regulatory B cells in digestive system diseases. RESULTS AND CONCLUSIONS: Abundant evidence has demonstrated that Bregs play a regulatory role in inflammatory, autoimmune, and tumor diseases, and regulatory B cells play different roles in different diseases, but future work needs to determine the mechanisms by which Bregs are activated and how these cells affect their target cells.

A promoter polymorphism in the hMLH1 gene (-93G/A) associated with sporadic colorectal cancer.

Colorectal cancer (CRC) is a worldwide problem for public health. mutL homolog 1 (MLH1) is a key component of the mismatch repair system, and the MLH1-93G/A polymorphism (rs1800734) is predicted to affect MLH1 protein expression, suggesting that the polymorphism may be associated with the cancer risk; however, the results concerning this have been inconsistent. In order to investigate the possible correlation between human (h)MLH1-93G/A polymorphism and the development and progression of sporadic CRC (SCRC) in China, the genotypes of hMLH1-93G/A were detected by the TaqMan MGB probe method in 312 SCRC patients and 300 healthy controls, and immunohistochemical staining was also performed to measure the expression of hMLH1 in cases with different alleles among the SCRC patients and normal controls. It was observed that the A/A genotype and A allele significantly increased the risk of developing Duke's stage C+D CRC and lymphatic metastasis. hMLH1 expression of the A allele was lower than that of the G allele in CRC. By contrast, there was no statistically significant difference in hMLH1 expression for the A allele and the G allele in the normal controls. These results suggested that hMLH1-93G/A polymorphism may not be associated with the overall risk of CRC, but that the hMLH1-93A/A genotype and A allele are associated with the progression of CRC.

[Clinical value of the narrow-band imaging combined with endoscopic submucosal dissection for gastric high grade intraepithelial neoplasia].

OBJECTIVE: To determine the feasibility, safety and short-time efficacy of narrow-band imaging (NBI) combined with endoscopic submucosal dissection (ESD) for treating gastric high grade intraepithelial neoplasia (HGIN). METHODS: Clinical data of 78 patients with gastric HGIN diagnosed by gastroscope and pathology undergoing NBI combined with ESD at Wuxi No.2 People's Hospital and Zhongshan Hospital of Fudan University from January 2014 to December 2015 were retrospectively analyzed. Their clinicopathological and follow-up data were analyzed. RESULTS: There were 47 males and 31 females aged from 38 to 85 years old. Preoperative NBI showed that lesions of all the 78(100%) patients had clear resection margin, and 91%(71/78) lesions had abundant vessels in the central depression area. One case was converted to open abdominal operation due to intra-operational perforation, 77(98.7%) gastric HGIN lesions were successfully dissected under ESD, including 74 cases(94.9%) of en bloc dissection, and other 3 cases with severe adhesion of submucosa whose lesion wound after ESD was treated with argon plasma coagulation(APC). The mean maximum diameter of the lesion size was (1.2±0.8) cm. The average operation time was(48±21) minutes. Delayed hemorrhage occurred in 5 cases(6.4%) who were also treated successfully by endoscopic hemostasis. Postoperational pathology revealed en bloc dissection rate was 91.0%(71/78), positive rate of resection margin was 3.8%(3/78), and healing dissection rate was 89.7%(70/78). Thirty-two lesions (41.0%) remained the diagnosis as HGIN, 6 lesions(7.7%) were diagnosed as low grade intraepithelial neoplasia, and 40 lesions (51.3%) were diagnosed as adenocarcinoma. Fifty-seven cases were followed up for 12 months, 21 cases were followed up for 6 months, and there was no recurrence in those 3 patients with positive margin. Two cases (2.6%) relapsed and were diagnosed as adenocarcinoma by repeat pathology examination. CONCLUSION: NBI combined with ESD for diagnosis and treatment of gastric HGIN is safe and effective, and can achieve en bloc complete resection of the lesions with a low complication rate.

Role of high-mobility group box 1 protein in inflammatory bowel disease.

High-mobility group box 1 (HMGB1) protein is a nuclear non-histone DNA-binding protein. It is released into the extracellular milieu and mediates inflammatory responses, which contribute to the pathogenesis of numerous inflammatory diseases, including inflammatory bowel disease (IBD). An online search was performed in PubMed and Web of Science databases for articles providing evidence on the role of HMGB1 in IBD. HMGB1 plays an important role in IBD pathogenesis. Application of HMGB1 antagonists reduced inflammatory reactions and ameliorated colitis in rodent models, which may provide new insights into the diagnosis and treatment of IBD.

Optimization of physicochemical properties and safety profile of novel bacterial topoisomerase type II inhibitors (NBTIs) with activity against Pseudomonas aeruginosa.

Type II bacterial topoisomerases are well validated targets for antimicrobial chemotherapy. Novel bacterial type II topoisomerase inhibitors (NBTIs) of these targets are of interest for the development of new antibacterial agents that are not impacted by target-mediated cross-resistance with fluoroquinolones. We now disclose the optimization of a class of NBTIs towards Gram-negative pathogens, especially against drug-resistant Pseudomonas aeruginosa. Physicochemical properties (pKa and logD) were optimized for activity against P. aeruginosa and for reduced inhibition of the hERG channel. The optimized analogs 9g and 9i displayed potent antibacterial activity against P. aeruginosa, and a significantly improved hERG profile over previously reported analogs. Compound 9g showed an improved QT profile in in vivo models and lower clearance in rat over earlier compounds. The compounds show promise for the development of new antimicrobial agents against drug-resistant Pseudomonas aeruginosa.