Increasing Diverticulosis in an Aging Population: A Colonoscopy-Based Study of 5-Year Trends in 26 463 Patients in Northern China.

BACKGROUND Because such data are scarce in northern China, the purpose of this study was to determine trends in diverticulosis over the past 5 years. MATERIAL AND METHODS A total of 26 463 patients (27 558 examinations, including 1095 repeated colonoscopies) performed between January 2011 and December 2015 were reviewed respectively. The distributions of diverticulosis were recorded, which were classified as right-sided, left-sided, and bilateral type. The trends in diverticulosis were analyzed in terms of aging and yearly increase. Additionally, associations of the occurrence of diverticulosis with age (≤39, 40-59, and ≥60 years) and sex were determined using a logistic regression model. RESULTS We identified 1045 patients with colonic diverticulosis, with an overall prevalence of 3.8% (1045/27 558). A preponderance of right-sided diverticulosis was demonstrated, accounting for 72.9% (693/951) of included subjects. The proportion of colonic diverticulosis increased significantly (P<0.001 for trend), from 2.78% (112/4028) in 2011 to 4.98% (309/6208) in 2015. The proportion of patients of all age groups with diverticulosis increased significantly (P<0.001 for trend) in correlation with yearly increase. There was a greater proportion of diverticulosis, regardless of the distribution, in patients aged ³60 than in younger age groups (P<0.001 for trend). Multivariate analysis showed older age and male sex (P<0.001) were independent risk factor for diverticulosis. CONCLUSIONS Colonic diverticulosis has been increasing in northern China, where rapid aging is ongoing.

Red blood cell distribution width to platelet ratio levels in assessment of histologic severity in patients with primary biliary cholangitis.

We aimed to investigate the relationship between the histologic severity and red blood cell distribution width to platelet ratio (RPR) in patients with primary biliary cholangitis (PBC). One hundred and seven consecutive patients with liver biopsy-proven and as yet treatment-naïve PBC were enrolled as the primary and validation cohort. The histologic stages were divided into early stage (Scheuer's stage 1 & 2) and late stage (Scheuer's stage 3 & 4). The overall patient demographics, clinical manifestations, hematological tests and biochemical profile were retrospectively collected from our database. Both groups were compared in terms of RPR, aspartate aminotransferase-to-platelet ratio index (APRI), fibrosis index based on the 4 factors (FIB-4) and AST/ALT ratio (AAR). Of the 77 patients in the primary cohort, a total of 24 (31.2%) had early stage PBC, whereas 53 (68.8%) represented late stage. Patients with late stage PBC showed significantly higher red blood cell distribution width (15.5 vs. 14.1%, p = .016), RPR (0.15 vs. 0.09, p < .001), direct bilirubin (32.4 vs. 12.9 µmol/L, p = .041), FIB-4 (3.41 vs. 6.34, p = .001) and significantly lower platelet (132.8 vs. 185.8 × 109/L, p = .002). The area under the curve, cut-off value, sensitivity, specificity, positive predictive value, negative predictive value for determining late stage were 0.74, 0.14, 49.1%, 95.8%, 96.3% and 46.0%, respectively. Additionally, high RPR may also serve as a prognostic indicator for 18-month mortality. In conclusion, RPR can be used as a non-invasive and effective predictor of histologic severity in patients with PBC.

Prognostic nomogram incorporating neutrophil-to-lymphocyte ratio for early mortality in decompensated liver cirrhosis.

BACKGROUND: Neutrophil-to-lymphocyte ratio (NLR) is a marker of systemic inflammation. However, its predictive utility of 30-day mortality remains elusive in decompensated cirrhotics. AIMS: We aimed to combine NLR and other variables associated with early mortality of cirrhotics with acute insults in to a predictive nomogram. METHODS: We retrospectively analyzed 352 decompensated cirrhotics. The 30-day mortality was regarded as primary outcome. Multivariate Cox analysis was performed, and a NLR-based nomogram was developed. The performance of nomogram was determined in terms of its calibration, discrimination and clinical usefulness. Serum cytokines were evaluated by Milliplex cytokine assay. RESULTS: On multiple analysis, independent factors for early mortality were albumin, MELD and NLR, which were all selected into the nomogram. The nomogram showed good discrimination, with a concordance index of 0.88. Calibration of the nomogram predicted survival corresponding optimally with the actual outcomes. Decision curve analysis indicated our nomogram was useful in clinical practice. Among circulating cytokines we investigated, IL-6 and IL-8 were substantially elevated in cirrhotics compared to healthy subjects. High NLR was positively correlated with the expression of IL-6 and IL-8. CONCLUSION: The proposed nomogram incorporating NLR offered an individualized predictive tool for 30-day mortality in decompensated cirrhotics. The escalating value of NLR likely implicated excessive inflammatory response.

Sex differences in risk factors of uncomplicated colonic diverticulosis in a metropolitan area from Northern China.

As the world's most populated and rapidly aging country, there is limited information on sex-related differences in factors regarding uncomplicated colonic diverticulosis in China. We aimed to investigate sex differences in individual risk factor in a northern metropolis. Patients with colonic diverticulosis who underwent indicated colonoscopy were queried with respect to medical history and demographic features. Demographic information, life style factors and co-morbidities were retrieved from a prospective dataset. Multiple regression analyses were performed to determine precipitating factors of diverticula. Of 4,386 enrolled patients, colonic diverticulosis were detected in 218 cases (4.97%). Multiple logistic regression analysis implicated increasing age (OR = 1.05, 95%CI 1.03-1.06, P < 0.001), red meat ≥100 g/d (OR = 2.53, 95%CI 1.72-3.70, P < 0.001), smoking (OR = 2.14, 95%CI 1.05-4.33, P = 0.035), rheumatologic diseases (OR = 3.38, 95%CI 1.09-10.5, P = 0.035) and NSAIDs (OR = 2.11, 95%CI 1.12-3.97, P = 0.020) were significantly associated with diverticulosis in men, whilst advancing age (OR = 1.03, 95%CI 1.01-1.05, P = 0.013), BMI (OR = 1.12, 95%CI 1.04-1.19, P = 0.001), smoking (OR = 10.2, 95%CI 2.81-37.4, P < 0.001), rheumatologic diseases (OR = 8.04, 95%CI 3.05-21.2, P < 0.001), hypertension (OR = 1.76, 95%CI 1.01-3.06, P = 0.047), colonic polyps (OR = 3.12, 95%CI 1.82-5.36, P < 0.001) and antihypertensive medications (OR = 2.99, 95%CI 1.66-5.39, P < 0.001) in women. In conclusion, it is pivotal to take account of differentially sex-related factors in regard to the development of uncomplicated colonic diverticulosis.

Does neutrophil-to-lymphocyte ratio predict 1-year mortality in patients with primary biliary cholangitis? Results from a retrospective study with validation cohort.

OBJECTIVES: Neutrophil-to-lymphocyte ratio (NLR) has been used to predict prognosis in various liver diseases, but its role in primary biliary cholangitis (PBC) is not clarified. We aimed to investigate the prognostic usefulness of NLR for 1-year mortality in PBC. METHODS: The study recruited a retrospective cohort with 88 patients with PBC and a prospective validation cohort with 63 participants who were followed-up for 1 year. NLR and other laboratory measurements were analysed by multivariate regression model for identifying independent factors for early mortality. The cut-off threshold of NLR was determined by calculating the area under the receiver operating characteristics curve (AUROC) and used in a subsequent Kaplan-Meier survival analysis. RESULTS: Univariate and multivariate analyses showed that Mayo Risk Score (MRS), serum creatinine and NLR were independent indicators for mortality. NLR yielded significantly higher AUROC (0.86) than those of platelet-to-lymphocyte ratio (0.58, p=0.03), but comparable with MRS (0.87, p=0.88). Spearman's correlation analysis represented a positive correlation between escalating NLR and aggravating Child-Pugh grade (r=0.44, p<0.001). Patients with NLR <2.18 exhibited higher survival (with 100% sensitivity and 67.1% specificity) within 1 year follow-up duration, and NLR ≥2.18 was indicative of higher mortality (log-rank test, p<0.001). In addition, these results were internally confirmed by a validation cohort. CONCLUSION: NLR is closely related to short-term mortality in patients with PBC.

Analysis of the learning curve for peroral endoscopic myotomy for esophageal achalasia: Single-center, two-operator experience.

BACKGROUND AND AIM: Peroral endoscopic myotomy (POEM) has emerged as an advanced technique for the treatment of achalasia, and defining the learning curve is mandatory. METHODS: From August 2011 to June 2014, two operators in our institution (A&B) carried out POEM on 35 and 33 consecutive patients, respectively. Moving average and cumulative sum (CUSUM) methods were used to analyze the POEM learning curve for corrected operative time (cOT), referring to duration of per centimeter myotomy. Additionally, perioperative outcomes were compared among distinct learning curve phases. RESULTS: Using the moving average method, cOT reached a plateau at the 29th case and at the 24th case for operators A and B, respectively. CUSUM analysis identified three phases: initial learning period (Phase 1), efficiency period (Phase 2) and mastery period (Phase 3). The relatively smooth state in the CUSUM graph occurred at the 26th case and at the 24th case for operators A and B, respectively. Mean cOT of distinct phases for operator A were 8.32, 5.20 and 3.97 min, whereas they were 5.99, 3.06 and 3.75 min for operator B, respectively. Eckardt score and lower esophageal sphincter pressure significantly decreased during the 1-year follow-up period. Data were comparable regarding patient characteristics and perioperative outcomes. CONCLUSION: This single-center study demonstrated that expert endoscopists with experience in esophageal endoscopic submucosal dissection reached a plateau in learning of POEM after approximately 25 cases.

Identification of immediate early response protein 2 as a regulator of angiogenesis through the modulation of endothelial cell motility and adhesion.

Human immediate early response 2 (IER2) has been characterized as a putative nuclear protein that functions as a transcription factor or transcriptional co­activator in the regulation of cellular responses, and may be involved in the regulation of tumor progression and metastasis. Data from our previous gene expression profile of the human microvascular endothelial cells during capillary morphogenesis showed a significant alteration of IER2 expression, suggesting that IER2 may participate in the regulation of the endothelial cell morphogenesis and angiogenesis. The aim of the present study was to investigate the role of IER2 in cell motility, cell­matrix adhesion and in vitro capillary­like structures formation of the human umbilical vein endothelium cells (HUVECs). IER2 was constitutively expressed in HUVECs, and lentiviral­mediated depletion of IER2 significantly reduced the cell motility, cell­matrix adhesion and capillary­like structures formation of HUVECs. Results also showed that depletion and overexpression of IER2 altered the actin cytoskeleton rearrangement in HUVECs. Furthermore, results from western blot analysis showed that the activity of the focal adhesion kinase (FAK) can be regulated by IER2. These results indicated that IER2 regulates endothelial cell motility, adhesion on collagen type I matrix and the capillary tube formation, as the result of the regulation of the actin cytoskeleton rearrangement presumably via a FAK­dependent mechanism.

Modulation of tumor cell migration, invasion and cell-matrix adhesion by human monopolar spindle-one-binder 2.

Human monopolar spindle-one-binder 2 (hMOB2) is a member of the hMOB family of proteins, and it has been reported to regulate the nuclear-Dbf2-related kinase (NDR) activation. However, the function of hMOB2 expression in tumor cell adhesion and motility has not been addressed. Herein, the lentiviral-mediated overexpression and the knockdown of hMOB2 in HepG2 and SMMC-7721 cells was established. It was demonstrated that overexpression of hMOB2 significantly reduced the cell motility and enhanced the cell-matrix adhesion, while the hMOB2 knockdown decreased not only the cell motility, but also the cell-matrix adhesion. Immunofluorescence results showed that both hMOB2 overexpression and knockdown altered assembly of the focal adhesions and the actin cytoskeleton rearrangement. Furthermore, the focal adhesion kinase (FAK)-Src-paxillin signal pathway activated by hMOB2 was confirmed to be involved in controlling the cell motility and the cell-matrix adhesion. These results demonstrated that the altered cell-matrix adhesion and cell motility induced by hMOB2 expression was caused by the assembly of focal adhesions as well as the actin cytoskeleton rearrangement through the activation of the FAK-Src-paxillin signal pathway, unveiling a novel mechanism of cell motility and cell-matrix adhesion regulation induced by hMOB2 expression.

Apigenin induces the apoptosis and regulates MAPK signaling pathways in mouse macrophage ANA-1 cells.

Apigenin is a naturally occurring plant flavonoid that possesses antioxidant, anti-cancer and anti-inflammatory properties. However, there are few reports has been done on the ability of apigenin to induce apoptosis in macrophages. In this study, mouse macrophage ANA-1 cells were incubated with different concentrations of apigenin. The cell viability was determined by an MTT assay. The cell apoptosis were analyzed by flow cytometric analysis. Apoptosis were also analyzed using a TUNEL assay and a DNA ladder. The level of intracellular ROS was detected using a dichlorofluorescein -diacetate probe. The expression levels of apoptosis-related proteins were detected by western blot analysis. The results showed that apigenin decreased the viability of ANA-1 cells and induced apoptosis in a dose- and time-dependent manner. Apigenin increased the level of intracellular ROS, downregulated the expression of Bcl-2 and upregulated the expression of caspase-3 and caspase-8 in ANA-1 cells. Furthermore, apigenin downregulated the expression of phospho-ERK and phospho-JNK, upregulated the expression of phospho-p38 and had no significant effect on the expression of Bax, ERK, JNK and p38. The results suggested that apigenin induced cell apoptosis in mouse macrophage ANA-1 cells may via increasing intracellular ROS, regulating the MAPK pathway, and then inhibiting Bcl-2 expression.

Decreased miRNA-148a is associated with lymph node metastasis and poor clinical outcomes and functions as a suppressor of tumor metastasis in non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide, and only 15% of lung cancer patients live more than 5 years. microRNAs (miRNAs) are endogenously expressed non-coding RNAs, and dysregulation of miRNAs is a common feature in human cancers including lung cancer. In this study, we describe the epigenetic regulation of miRNA-148a and its prognostic value in NSCLC. Due to hypermethylation of the miRNA­148a encoding region, the expression levels of miRNA-148a were decreased in NSCLC tissues and cells. Decreased miRNA­148a expression was associated with lymph node metastasis, advanced clinical stage and shortened disease-free survival and overall survival in NSCLC, and was an independent prognostic factor for overall survival in multivariate analysis. In vitro, overexpression of miRNA-148a significantly suppressed the migratory and invasive abilities of A549 and H1299 lung cancer cells. Enforced expression of miRNA-148a in lung cancer cell lines resulted in a significant reduction in the expression of DNMT1. This, in turn, led to a decrease in DNA methylation of the tumor-suppressor gene E-cadherin and induced an increase in the protein levels of E-cadherin. By understanding the function and molecular mechanism of miRNA-148a in NSCLC, miRNA-148a may have therapeutic potential to suppress lung cancer metastasis.