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Background: Carbon dioxide (CO2) insufflation is increasingly used for endoscopic submucosal dissection (ESD) owing to the faster absorption of CO2 as compared to that of air. Studies comparing CO2 insufflation and air insufflation have reported conflicting results. Objectives: This meta-analysis is aimed to assess the efficacy and safety of use of CO2 insufflation for ESD. Methods: Clinical trials of CO2 insufflation versus air insufflation for ESD were searched in PubMed, Embase, the Cochrane Library and Chinese Biomedical Literature Database. We performed a meta-analysis of all randomized controlled trials (RCTs). Results: Eleven studies which compared the use of CO2 insufflation and air insufflation, with a combined study population of 1026 patients, were included in the meta-analysis (n = 506 for CO2 insufflation; n = 522 for air insufflation). Abdominal pain and VAS scores at 6h and 24h post-procedure in the CO2 insufflation group were significantly lower than those in the air insufflation group, but not at 1h and 3h after ESD. The percentage of patients who experienced pain 1h and 24h post-procedure was obviously decreased. Use of CO2 insufflation was associated with lower VAS scores for abdominal distention at 1h after ESD, but not at 24h after ESD. However, no significant differences were observed with respect to postoperative transcutaneous partial pressure carbon dioxide (PtcCO2), arterial blood carbon dioxide partial pressure (PaCO2), oxygen saturation (SpO2%), abdominal circumference, hospital stay, white blood cell (WBC) counts, C-Reactive protein (CRP) level, dosage of sedatives used, incidence of dysphagia and other complications. Conclusion: Use of CO2 insufflation for ESD was safe and effective with regard to abdominal discomfort, procedure time, and the residual gas volume. However, there appeared no significant differences with respect to other parameters namely, PtcCO2, PaCO2, SpO2%, abdominal circumference, hospital stay, sedation dosage, complications, WBC, CRP, and dysphagia. [ABSTRACT FROM AUTHOR]

Paired-box family member PAX8 encodes a transcription factor that has a role in cell differentiation and cell growth and may participate in the prognosis of hepatocellular carcinoma (HCC). By bioinformatics analysis, we identified several single nucleotide polymorphisms (SNPs) within a newly identified long non-coding RNA (lncRNA) AC016683.6 as expression quantitative trait loci (eQTLs) for PAX8. Hence, we hypothesized that PAX8eQTLs in lncRNA AC016683.6 may influence the HCC prognosis. We then performed a case-only study to assess the association between the two SNPs as well as the prognosis of HCC in 331 HBV-positive HCC patients without surgical treatment. Cox proportional hazard models were used for survival analysis with adjustments for the age, gender, smoking status, drinking status, Barcelona-Clinic Liver Cancer (BCLC) stage, and chemotherapy or TACE (transcatheter hepatic arterial chemoembolization) status. We found that the G allele of rs1110839 and the T allele of rs4848320 in PAX8was significantly associated with a better prognosis compared with the T allele of rs1110839 and the C allele of rs4848320 (adjusted HR = 0.74, 95% CI = 0.61–0.91, P = 0.004 for rs1110839 and adjusted HR = 0.71, 95% CI = 0.54–0.94, P = 0.015 for rs4848320 in the additive model). Furthermore, the combined effect of the variant genotypes for these two SNPs was more prominent in patients with the BCLC-C stage orpatients with chemotherapy or TACE. Although the exact biological function remains to be explored, our findings suggest a possible association of PAX8eQTLs in lncRNA AC016683.6 with the HCC prognosis inthe Chinese population. Further large and functional studies are needed to confirm our findings. [ABSTRACT FROM AUTHOR]

Background: Accumulating evidence has demonstrated that the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a part of Lewy body inclusions and involves the pathogenesis of Parkinson’s disease (PD). However, it remains unknown whether or not genetic variation at the GAPDH locus contributes to the risk for PD. Methods: A total of 302 sporadic PD patients and 377 control subjects were recruited in our study for assessing two single nucleotide polymorphisms (rs3741918 and rs1060619) in the GAPDH gene. Both allelic association and additive models were used to analyze association between GAPDH variants and risk for PD. Results: Both polymorphisms were significantly associated with risk for PD after correction by Bonferroni multiple testing. The minor allele of rs3741918 was associated with decreased risk of sporadic PD (allelic contrast, OR = 0.74, 95% CI: 0.59–0.93, corrected P = 0.028; additive model, OR = 0.73, 95% CI: 0.58–0.92, corrected P = 0.018). While for the rs1060619 locus, the minor allele conferred increased risk for PD (allelic contrast, OR = 1.41, 95% CI: 1.14–1.75, corrected P = 0.007; additive model, OR = 1.43, 95% CI: 1.15–1.79, corrected P = 0.002). Conclusion: Our study indicates that GAPDH variants confer susceptibility to sporadic PD in a Chinese Han population, which is consistent with the role of GAPDH protein in neuronal apoptosis. To our knowledge, this is the first study of genetic association between GAPDH locus and risk for PD in the Chinese population. [ABSTRACT FROM AUTHOR]

Background: Idiopathic Parkinson disease (PD) is a common neurodegenerative disease that seriously hinders limb activities and affects patients’ lives. We performed a meta-analysis aiming to systematically review and quantitatively synthesize the efficacy and safety of traditional Chinese medicine (TCM) as an adjunct therapy for clinical PD patients. Methods: An electronic search was conducted in PubMed, Cochrane Controlled Trials Register, China National Knowledge Infrastructure, Chinese Scientific Journals Database and Wanfang data to identify randomized trials evaluating TCM adjuvant therapy versus conventional treatment. The change from baseline of the Unified Parkinson’s Disease Rating Scale score (UPDRS) was used to estimate the effectiveness of the therapies. Results: Twenty-seven articles involving 2314 patients from 1999 to 2013 were included. Potentially marked improvements were shown in UPDRS I (SMD 0.68, 95%CI 0.38, 0.98), II (WMD 2.41, 95%CI 1.66, 2.62), III (WMD 2.45, 95%CI 2.03, 2.86), IV (WMD 0.32, 95%CI 0.15, 049) and I-IV total scores (WMD 6.18, 95%CI 5.06, 7.31) in patients with TCM plus dopamine replacement therapy (DRT) compared to DRT alone. Acupuncture add-on therapy was markedly beneficial for improving the UPDRS I–IV total score of PD patients (WMD 10.96, 95%CI 5.85, 16.07). However, TCM monotherapy did not improve the score. The effectiveness seemed to be more obvious in PD patients with longer adjunct durations. TCM adjuvant therapy was generally safe and well tolerated. Conclusions: Although the data were limited by methodological flaws in many studies, the evidence indicates the potential superiority of TCM as an alternative therapeutic for PD treatment and justifies further high-quality studies. [ABSTRACT FROM AUTHOR]

Background: Previous meta-analyses reported that probiotics improve the effectiveness of Helicobacter pylori (H. pylori) eradication during antibiotic therapy, while results regarding a possible reduction of side effects remained inconclusive. Moreover, the effectiveness of different strains of probiotics has not been studied so far. It is further conceivable that probiotics will produce additional effects only if antibiotics are relatively ineffective. Methods: This meta-analysis includes eligible randomized controlled trials examining effects of probiotics supplementation on eradication rates (ER) and side effects, published up to May 2014. Sub-group analysis was performed to compare different probiotic strains and antibiotic therapies with different effectiveness in controls (ER <80% vs.>80%). Publication bias was assessed with funnel plots and Harbord's test. The quality of the trials was assessed with the Cochrane risk of bias tool. Results: Thirty-three RCTs involving a total of 4459 patients met the inclusion criteria in case of eradication rates of which 20 assessed total side effects in addition. Overall, the pooled eradication rate in probiotics supplementation groups was significantly higher than in controls (ITT analysis: RR 1.122, 95% CI 1.086–1.159, PP analysis: RR 1.114, 95% CI 1.070–1.159). Sub group-analysis could, however, confirm this finding only for four individual strains (Lactobacillus acidophilus, Lactobacillus casei DN-114001, Lactobacillus gasseri, and Bifidobacterium infantis 2036) and for relatively ineffective antibiotic therapies. There was a significant difference between groups in the overall incidence of side effects (RR 0.735, 95% CI 0.598–0.902). This result was, however, only confirmed for non-blinded trials. Conclusions: The pooled data suggest that supplementation with specific strains of probiotics compared with eradication therapy may be considered an option for increasing eradication rates, particularly when antibiotic therapies are relatively ineffective. The impact on side effects remains unclear and more high quality trials on specific probiotic strains and side effects are thus needed. [ABSTRACT FROM AUTHOR]

The mechanisms leading to dopaminergic neuronal loss in the substantia nigra of patients with Parkinson disease (PD) remain poorly understood. We recently reported that aberrant DNA replication mediated by DNA polymerase-β (DNA pol-β) plays a causal role in the death of postmitotic neurons in an in vitro model of PD. In the present study, we show that both proliferating cell nuclear antigen (PCNA) and DNA pol-β are required for MPP+-induced neuronal death. PCNA binds to the catalytic domain of DNA pol-β in MPP+-treated neurons and in post-mortem brain tissues of PD patients. The PCNA-DNA pol-β complex is loaded into DNA replication forks and mediates DNA replication in postmitotic neurons. The aberrant DNA replication mediated by the PCNA-DNA pol-β complex induces p53-dependent neuronal cell death. Our results indicate that the interaction of PCNA and DNA pol-β contributes to neuronal death in PD. [ABSTRACT FROM AUTHOR]

Background: The molecular mechanism between Helicobacter pylori (H. pylori) infection and gastric cancer remained largely unknown. In this study, we determined the role of miRNA in H. pylori induced gastric cancer. Methods and Results: We found that miR-204 was decreased in H. pylori positive tissues by qRT-PCR. Knockdown of miR-204 enhanced the invasion and proliferation ability of gastric cancer cells in vitro. Luciferase assay revealed that SOX4 was target gene of miR-204, which was found up-regulated in H. pylori positive tissues. Down-regulation of miR-204 and over-expression of SOX4 promoted epithelial-mesenchymal transition process. Conclusion: Taken together, our findings demonstrated that miR-204 may act as a tumor suppressor in H. pylori induced gastric cancer by targeting SOX4. [ABSTRACT FROM AUTHOR]

Objective: Genetic polymorphisms of Toll-like receptors (TLRs) may influence the effects of H. pylori infection and play important roles in gastric carcinogenesis. The aim of this study was to determine whether the polymorphisms of TLR4 and TLR9 are associated with susceptibility to gastric carcinoma and its prognosis. Methods: This study consisted of 314 patients with gastric cancer and 314 healthy controls. The polymorphisms were assessed using polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) analysis. Survival was analyzed by Kaplan–Meier survival curves. Results: No variant genotypes of TLR4+896A/G, TLR4+1196C/T, or TLR9 -1237T/C were detected. For TLR9 -1486 T/C, multiple logistic regression analyses revealed that compared with the TT homozygote, patients with both the TC variant (adjusted odds ratio (OR) = 1.47, 95% confidence interval (CI) = 1.04–2.10) and the CC variant (adjusted OR = 1.63, 95% CI = 1.01–2.64) had higher risks of gastric cancer. Further stratification analyses revealed that an increased risk of gastric cancer associated with C carriers was evident among females (adjusted OR = 1.84, 95%CI = 1.02–3.33), in younger subjects aged less than 60 years old (adjusted OR = 1.86, 95%CI = 1.15–3.00), and subjects with H. pylori infection (adjusted OR = 1.53, 95% CI = 1.03–2.27). We also observed a significant association between C carriers and noncardia gastric cancer (adjusted OR = 1.51, 95% CI = 1.03–2.20). In addition, we demonstrated that the C carrier genotype and H. pylori infection may have a synergistic effect and conferred an OR of 2.44 for developing gastric cancer. TLR9 -1486C was also identified as an independent marker of poor survival of carcinoma. Conclusions: Our results suggest that TLR9 -1486C carriers are associated with an increased risk and poor prognosis of gastric carcinoma in the Chinese population. [ABSTRACT FROM AUTHOR]

Background and Aims: Osteopontin, SDF-1a, and MMP-2 are important secreted molecules involved in the pathophysiology of human hepatocellular carcinoma (HCC). This study investigates the effect of the SDF-1a/CXCR4 axis on expression and activity of MMP-2 induced by osteopontin. Methods: The expression of CXCR4, SDF-1a, MMP-2 and their associated cellular signaling cascades, involving Akt and MAP Kinases, were determined by Western blotting. The activities of MMP-2 and MMP-9 were assayed by gel zymography. The role of the osteopontin receptors integrin avb3 and CD44v6 was evaluated using neutralizing antibodies. We also established CXCR4-deficient SMMC7721 cell lines by transfection with miRNA-CXCR4 plasmids and determined cell invasion activity in a transwell assay. Results: In comparison with untreated cells, recombinant human osteopontin (rhOPN) up-regulated CXCR4, SDF-1a, and MMP-2 expression about 5-, 4-, and 6-fold on the protein levels through binding to integrin avb3 and CD44v6 in hepatocellular carcinoma cells (SMMC7721 and HepG2). Inhibition of the SDF-1a/CXCR4 axis down-regulated the rhOPNinduced MMP-2 expression and activity. rhOPN also activated Akt, p38 and JNK. Down-regulation of CXCR4 decreased the rhOPN-induced invasion in SMMC7721 cells. Conclusion: These results indicate that rhOPN up-regulates MMP-2 through the SDF-1a/CXCR4 axis, mediated by binding to integrin avb3 and CD44v6 and activating the PI-3K/Akt and JNK pathways in HepG2 and SMMC7721 cells. Therefore, the osteopontin-SDF-1a/CXCR4-MMP-2 system may be a new therapeutic target for treating HCC progression. [ABSTRACT FROM AUTHOR]

Background: Carbon dioxide (CO2) insufflation is increasingly used for endoscopic submucosal dissection (ESD) owing to the faster absorption of CO2 as compared to that of air. Studies comparing CO2 insufflation and air insufflation have reported conflicting results., Objectives: This meta-analysis is aimed to assess the efficacy and safety of use of CO2 insufflation for ESD., Methods: Clinical trials of CO2 insufflation versus air insufflation for ESD were searched in PubMed, Embase, the Cochrane Library and Chinese Biomedical Literature Database. We performed a meta-analysis of all randomized controlled trials (RCTs)., Results: Eleven studies which compared the use of CO2 insufflation and air insufflation, with a combined study population of 1026 patients, were included in the meta-analysis (n = 506 for CO2 insufflation; n = 522 for air insufflation). Abdominal pain and VAS scores at 6h and 24h post-procedure in the CO2 insufflation group were significantly lower than those in the air insufflation group, but not at 1h and 3h after ESD. The percentage of patients who experienced pain 1h and 24h post-procedure was obviously decreased. Use of CO2 insufflation was associated with lower VAS scores for abdominal distention at 1h after ESD, but not at 24h after ESD. However, no significant differences were observed with respect to postoperative transcutaneous partial pressure carbon dioxide (PtcCO2), arterial blood carbon dioxide partial pressure (PaCO2), oxygen saturation (SpO2%), abdominal circumference, hospital stay, white blood cell (WBC) counts, C-Reactive protein (CRP) level, dosage of sedatives used, incidence of dysphagia and other complications., Conclusion: Use of CO2 insufflation for ESD was safe and effective with regard to abdominal discomfort, procedure time, and the residual gas volume. However, there appeared no significant differences with respect to other parameters namely, PtcCO2, PaCO2, SpO2%, abdominal circumference, hospital stay, sedation dosage, complications, WBC, CRP, and dysphagia.

Background: Cytochrome P450 2E1 (CYP2E1), an ethanol-inducible enzyme, has been shown to metabolically activate various carcinogens, which is critical for the development and progression of cancers. It has demonstrated that CYP2E1 polymorphisms alter the transcriptional activity of the gene. However, studies on the association between CYP2E1 polymorphisms (PstI/RsaI or DraI) and gastric cancer have reported conflicting results. Thus, the aim of the present study was to investigate whether CYP2E1 polymorphisms is associated with the development and progression of gastric cancer and its prognosis in Chinese patients., Methods: A case-control study was conducted in which CYP2E1 PstI/RsaI and DraI polymorphisms were analyzed in 510 Chinese patients with gastric cancer and 510 age- and sex- matched healthy controls by PCR-RFLP. Odds ratios were estimated by multivariate logistic regression, and the lifetime was calculated by Kaplan-Meier survival curves. In addition, a meta-analysis was also conducted to verify the findings., Results: For CYP2E1 PstI/RsaI polymorphism, C2C2 homozygotes (OR = 2.15; CI: 1.18-3.94) and C2 carriers (OR = 1.48; CI: 1.13-1.96) were associated with an increased risk of gastric cancer when compared with C1C1 homozygotes. Both C1C2 and C2C2 genotypes were associated with advanced stage, but not the grade of gastric cancer. Moreover, C2C2 genotype was identified as an independent marker of poor overall survival for gastric cancer. However, there was not any significant association between CYP2E1 DraI polymorphism and the risk of gastric cancer. In the meta-analysis, pooled data from 13 studies confirmed that the CYP2E1 PstI/RsaI polymorphism was associated with a significantly increased risk of gastric cancer., Conclusion: CYP2E1 PstI/RsaI polymorphism is associated with increased risk of development, progression and poor prognosis of gastric cancer in Chinese patients. Pooled data from 13 studies, mainly in Asian countries, are in agreement with our findings.

Background: Gastric cancer is one of the most common and lethal malignant cancers worldwide, and numerous epidemiological studies have demonstrated that Helicobacter pylori (H. pylori) infection plays a key role in the development of gastric carcinomas. Our previous studies showed that aquaporin 3 (AQP3) is overexpressed in gastric carcinoma and promotes the migration and proliferation of human gastric carcinoma cells, suggesting that AQP3 may be a potentially important determinant of gastric carcinoma. However, the role of AQP3 in H. pylori carcinogenesis is unknown., Methods: The AQP3 protein and H. pylori were detected in human gastric tissues by immunohistochemistry and modified Giemsa staining respectively. AQP3 knockdown was obtained by small interfering (si) RNA. Western blot assays and RT-PCR were used to evaluate the change of AQP3 in the human gastric cancer AGS and SGC7901 cell lines after co-culture with H. pylori. Sprague Dawley rats were orally inoculated with H. pylori to establish a rat model colonized by H. pylori., Results: The present study found that AQP3 expression correlated with H. pylori infection status in gastric cancer tissues and corresponding normal mucosa, and H. pylori co-culture upregulated AQP3 expression in human gastric adenocarcinoma cells in vitro via the extracellular signal-regulated kinase signaling pathway. H. pylori infection also increased AQP3 expression in gastric mucosa colonized by H. pylori in a Sprague Dawley rat model., Conclusions: These findings provide further information to understand the mechanism of H. pylori carcinogenesis and a potential strategy for the treatment of H. pylori-associated gastric carcinoma.