CIMP-positive glioma is associated with better prognosis: A systematic analysis.

BACKGROUND: CpG island methylator phenotype (CIMP) was closely related to the degree of pathological differentiation of tumors, and it's an important determinant of glioma pathogenicity. However, the molecular and pathological features of CIMP-positive glioma have not been fully elucidated. In addition, CIMP have been reported to be a useful prognostic marker in several human cancers, yet its prognostic value in gliomas is still controversial. Therefore, we aimed to evaluate gene mutations and pathological features of CIMP-positive glioma and explore the prognostic value of CIMP in gliomas. METHODS: We comprehensively searched PubMed, Embase, and MEDLINE for studies describing gene mutations, pathological features and overall survival of gliomas stratified by CIMP status. Odds ratios (OR), hazard ratios (HR), and their 95% confidence intervals (CI) were used to estimate the correlation between CIMP and the outcome parameters. RESULTS: Twelve studies with 2386 gliomas (1051 CIMP-positive and 1335 CIMP-negative) were included. Our results showed that CIMP was more frequent in isocitrate dehydrogenase 1 (IDH1)-mutated gliomas (OR 229.07; 95% CI 138.72-378.26) and 1p19q loss of heterozygosis (LOH) gliomas (OR 5.65; 95% CI 2.66-12.01). Pathological analysis showed that CIMP was common in low-malignant oligodendroglioma (OR 5.51; 95% CI 3.95-7.70) with molecular features including IDH1 mutations and 1p19q LOH, but rare in glioblastoma (OR 0.14; 95% CI 0.10-0.19). However, CIMP showed no obvious correlation with anaplastic oligoastrocytomas (OR 1.57; 95% CI 1.24-2.00) or oligoastrocytomas (OR 0.79; 95% CI 0.35-1.76). Concerning the prognosis, we found that CIMP-positive gliomas had longer overall survival (HR 0.57; 95% CI 0.97-0.16) than CIMP-negative gliomas. CONCLUSIONS: CIMP could be used as a potential independent prognostic indicator for glioma.

Rev-erbα can regulate the NF-κB/NALP3 pathway to modulate lipopolysaccharide-induced acute lung injury and inflammation.

Progressive lung injury and pulmonary inflammation can be induced by an intraperitoneal injection of lipopolysaccharide (LPS). Interleukin-1ß (IL-1ß) is a key pro-inflammatory cytokine that can further exaggerate inflammation, which is cleaved and activated by the NALP3 inflammasome. Although the nuclear receptor Rev-erbα attenuates the level of LPS-induced pulmonary inflammation, the mechanism remains unclear. In this study, we investigated the influence of LPS-induced production of IL-1ß and Rev-erbα on the development of lung inflammation. Herein, we demonstrate that Rev-erbα reduces IL-1ß production and lung injury following an intraperitoneal injection of LPS, which is dependent on the NF-κB/NALP3 pathway. Thus, Rev-erbα is able to decrease the extent of acute lung injury by regulating IL-1ß production. This mechanism may represent a potential novel therapeutic approach for lung injury.

Feasibility of laparoscopic gastrectomy for patients with Siewert-type II/III adenocarcinoma of the esophagogastric junction: A propensity score matching analysis.

BACKGROUND/AIM: The feasibility of using laparoscopic gastrectomy for the treatment of Siewert-type II/III adenocarcinoma of the esophagogastric junction (AEG) has not been addressed. This study aimed to comparatively evaluate the short- and long-term effects on laparoscopic versus open surgery using (propensity score matching) PSM for Siewert-type II/III AEG. METHODS: We retrospectively collected data from the patients with Siewert-type II/III AEG who were treated in our cancer center between January 2013 and December 2015. Patients undergoing laparoscopic gastrectomy and open gastrectomy were matched via PSM. The cumulative 2-year Overall survival (OS) rate of patients in the two cohorts was estimated by Kaplan-Meier plots. Multi-variable analysis using a Cox regression model was conducted to identify independent risk factors. RESULTS: A total of 963 patients with Siewert-type II/III AEG were included, of which 132 cases were in the laparoscopic gastrectomy group, and 831 cases were in the open gastrectomy group. After regrouping with PSM, 132 patients in the laparoscopic gastrectomy group were balanced with 264 similar patients in the open gastrectomy group. As expected, the laparoscopic gastrectomy group had significantly longer operation times, but less blood loss. Furthermore, the two groups showed similar results for post-operative complications, duration of hospital stay and 2-year OS rate. Combined organ resection was an independent risk factor for 2-year OS rate. CONCLUSION: This study suggests that laparoscopic gastrectomy may serve as a safe and feasible treatment for Siewert-type II/III AEG and achieve similar oncologic outcomes as open gastrectomy.

HBsAg/ß2GPI activates the NF­κB pathway via the TLR4/MyD88/IκBα axis in hepatocellular carcinoma.

Chronic hepatitis B virus (HBV) infection remains one of the leading causes of hepatocellular carcinoma (HCC) globally. However, the mechanism underlying the mediation by HBV surface proteins (HBsAgs) of the early steps in the virus life cycle and following HCC development is unclear. ß­2­glycoprotein I (ß2GPI) specifically interacts with HBsAg and demonstrates high expression during the earliest stages of hepatitis B virus infection. In the present study, the assessment of HCC and adjacent tissues revealed that the levels of mRNA and protein of ß2GPI were highly expressed in HBV­related HCC. Previous studies have reported that HBsAg activates the nuclear factor (NF)­κB pathway via interaction with ß2GPI in HCC. However, the underlying mechanism of how the interaction between HBsAg and ß2GPI confers activation of the NF­κB pathway is still unclear. The HBsAg is comprised of three carboxyl­co­terminal HB proteins. In the present study, immunofluorescence assay and EMSA consistently revealed that a combination of recombinant small HBV surface antigen (rSHB) and ß2GPI can significantly activate the NF­κB signaling pathway. Another study from our team revealed that high expression of ß2GPI enhanced HBsAg binding to cell surfaces and its interaction with Annexin II. However, Annexin II is not a transmembrane protein. Therefore, by a knockdown experiment with TLR2, TLR4 or MyD88 siRNAs using cells with co­incubated HBsAg/ß2GPI, certain aspects of the mechanism through which the HBsAg/ß2GPI complex activates the NF­κB pathway through the Toll­like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/IκBα axis were explained. In the present study, we identified the functional domain of HBsAg co­interaction with ß2GPI for the activation of NF­κB and revealed the mechanism of the HBsAg/ß2GPI­activated NF­κB pathway which could contribute to the treatment of HBV­related HCC. A novel finding of the present study is that HBsAg can bind to ß2GPI. We first identified the functional domain of HBsAg with ß2GPI to activate NF­κB. Second, by siRNA knockout experiments, we identified the downstream molecules involved in the activation of NF­κB induced by ß2GPI/HBsAg. In addition, we found that HBsAg/ß2GPI activated the NF­κB pathway through the phosphorylation of Ser32/36 by IκBα.

Diagnostic value of nailfold videocapillaroscopy in systemic sclerosis secondary pulmonary arterial hypertension: a meta-analysis.

BACKGROUND: Microvascular changes play a decisive role in systemic sclerosis (SSc) and occur early in the course of the disease. Pulmonary arterial hypertension (PAH) represents one of the main clinical expressions of the vascular changes in SSc, and the abnormal changes, especially capillary density and capillary width, are detectable at nailfold videocapillaroscopy (NVC). AIMS: To investigate the differences in capillary nailfold changes in SSc patients with and without PAH and to estimate the early diagnostic value of NVC in SSc secondary PAH (SSc-PAH). METHODS: A comprehensive literature search of MEDLINE and PUBMED was performed to identify published studies without language restrictions. The methodological quality of the included studies was evaluated. The pooled specificity, sensitivity, positive likelihood rate, negative likelihood rate, diagnostic odds ratio, area under the curve and Q value were found using Meta-Disc version 1.4 software packages. Finally, seven studies were included in this meta-analysis. RESULTS: The meta-analysis demonstrated that the diagnostic odds ratio, area under the curve and Q value were 5.84 (95% confidence interval: 1.95-17.54), 0.79 and 0.72 respectively. It indicated that the microvascular changes detected at NVC were significant in SSc-PAH and especially showed significantly lower capillary density and higher capillary width. CONCLUSION: The NVC may be a valuable tool for the early diagnosis of SSc-PAH. It can detect the early microvascular changes associated with the risk of PAH and has a significant role in the early prediction of SSc-PAH.

Accelerated senescence of renal tubular epithelial cells is associated with disease progression of patients with immunoglobulin A (IgA) nephropathy.

The aim of this study is to determine the potential correlation between the accelerated senescence of renal tubular epithelial cells (RTECs) and the disease progression of patients with immunoglobulin A nephropathy (IgAN). A total of 108 IgAN patients with different Lee's pathologic grades were enrolled. Additionally, 18 patients with renal resection were recruited as controls. Cellular senescence was evaluated by senescence-associated ß-galactosidase (SA-ß-gal) staining and an immunohistochemical analysis of p21 and p16 protein expression. The expression of type III collagen (Col III) and fibronectin (FN) in renal interstitium and the levels of serum total and low-density lipoprotein (LDL) cholesterol, serum creatinine concentration (SCr), and 24-h urinary protein excretion were evaluated also. SA-ß-gal staining and the expression of p16 and p21 were increased significantly in renal biopsy specimens obtained from grades I-II IgAN patients compared with controls (P < 0.05). The expression of these senescence-associated markers increased gradually with disease progression and correlated with the renal morphologic changes and the expression of Col III and FN in renal interstitium in IgAN patients. A correlation analysis showed that the expressions of p16, p21, and SA-ß-gal staining were associated significantly with blood pressure and renal function (P < 0.05), but not with patient age, body mass index (BMI), LDL cholesterol level, or 24-h urinary protein value (P > 0.05). Our results indicated that the RTECs in IgAN patients exhibited features of accelerated senescence, which were unrelated to mechanisms associated with normal aging. Cellular senescence was associated closely with IgAN disease progression, which suggested the accelerated senescence of RTECs may contribute to this progression.