Comprehensive analysis of the prognostic and immunological signature of TNFAIP8 family genes in human glioma.

TNFAIP8 family molecules have been recognized for their involvement in the progression of tumors across a range of cancer types. Emerging experimental data suggests a role for certain TNFAIP8 family molecules in the development of glioma. Nonetheless, the comprehensive understanding of the genomic alterations, prognostic significance, and immunological profiles of TNFAIP8 family molecules in glioma remains incomplete. In the study, using the comprehensive bioinformatics tools, we explored the unique functions of 4 TNFAIP8 members including TNFAIP8, TNFAIP8L1, TNFAIP8L2 and TNFAIP8L3 in glioma. The expressions of TNFAIP8, TNFAIP8L1, TNFAIP8L2, and TNFAIP8L3 were notably upregulated in glioma tissues compared to normal tissues. Furthermore, survival analysis indicated that elevated expression levels of TNFAIP8, TNFAIP8L1 and TNFAIP8L2 were correlated with unfavorable outcomes in terms of overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) among glioma patients. Genetic modifications, such as mutations and copy number alterations, within the TNFAIP8 family exhibited a significant association with extended OS, DSS and PFS in individuals diagnosed with glioma. The findings suggest a noteworthy correlation between TNFAIP8 family members and the age and 1p/19q codeletion status of glioma patients. We also found that there were significant relationships between TNFAIP8 family expression and tumor immunity in glioma. Furthermore, functional annotation of TNFAIP8 family members and their co-expressed genes in gliomas was carried out using GO and KEGG pathway analysis. The GO analysis revealed that the primary biological processes influenced by the TNFAIP8 family co-expressed genes included cell chemotaxis, temperature homeostasis, and endocytic vesicle formation. Additionally, the KEGG analysis demonstrated that TNFAIP8 family co-expressed genes are involved in regulating various pathways such as inflammatory mediator regulation of TRP channels, pathways in cancer, prolactin signaling pathway, and Fc gamma R-mediated phagocytosis. Overall, the findings suggest that TNFAIP8 family members may play a significant role in the development of glioma and have the potential to serve as prognostic indicators and therapeutic targets for individuals with glioma.

Human pan-cancer analysis of the predictive biomarker for the CDKN3.

BACKGROUND: Cell cycle protein-dependent kinase inhibitor protein 3 (CDKN3), as a member of the protein kinase family, has been demonstrated to exhibit oncogenic properties in several tumors. However, there are no pan-carcinogenic analyses for CDKN3. METHODS: Using bioinformatics tools such as The Cancer Genome Atlas (TCGA) and the UCSC Xena database, a comprehensive pan-cancer analysis of CDKN3 was conducted. The inverstigation encompassed the examination of CDKN3 function actoss 33 different kinds of tumors, as well as the exploration of gene expressions, survival prognosis status, clinical significance, DNA methylation, immune infiltration, and associated signal pathways. RESULTS: CDKN3 was significantly upregulated in most of tumors and correlated with overall survival (OS) of patients. Methylation levels of CDKN3 differed significantly between tumors and normal tissues. In addition, infiltration of CD4 + T cells, cancer-associated fibroblasts, macrophages, and endothelial cells were associated with CDKN3 expression in various tumors. Mechanistically, CDKN3 was associated with P53, PI3K-AKT, cell cycle checkpoints, mitotic spindle checkpoint, and chromosome maintenance. CONCLUSION: Our pan-cancer analysis conducted in the study provides a comprehensive understanding of the involvement of CDKN3 gene in tumorigenesis. The findings suggest that targeting CDKN3 may potentially lead to novel therapeutic strategies for the treatment of tumors.

Decoding molecular mechanism of species-selective targeting of fungal versus human HSP90 using multiple replica molecular dynamics simulations and binding free energy calculations.

As a highly evolutionarily conserved molecular chaperone, heat shock protein (HSP90), plays an important role in virulence traits, representing a therapeutic target for the treatment of fungal infections. The close evolutionary relationship between fungi and their human hosts poses a key challenge for the development of selective antifungal agents. In this work, molecular docking, multiple replica microsecond-based molecular dynamics (MD) simulations, and binding free energy calculations were performed to decode molecular mechanism of species-selective targeting of fungal versus human HSP90 triggered by the compound A11. MD simulations reveal that binding of compound A11 to human HSP90 nucleotide-binding domain (NBD) leads to obvious conformational changes relative to fungal HSP90 NBD. Binding free energy calculations show that the binding of compound A11 to fungal HSP90 NBD is stronger than that to human HSP90 NBD. Per residue-based free energy decomposition analysis was used to evaluate the inhibitor - residue interaction profile. The results efficiently identify the hot spot residues that play vital roles in favorable binding of compound A11 to fungal HSP90 NBD. This study is expected to provide a useful guidance for the development of selective inhibitors toward fungal HSP90.Communicated by Ramaswamy H. Sarma.

Circ_0006404 enhances hepatocellular carcinoma progression by regulating miR-624.

Growing studies have demonstrated that circRNAs (circular RNAs) act potential roles in tumor metastasis and progression. However, the expression and function of circ_0006404 in hepatocellular carcinoma (HCC) remain to be investigated. The expression of circ_0006404 and miR-624 was detected by qRT-PCR. CCK-8 assay, flow cytometry, and wound healing were performed to determine cell proliferation, cycle, and migration. The target of circ_0006404 was studied by bioinformatics and luciferase activity analysis. Our data indicated that circ_0006404 was overexpressed in HCC specimens and cells and ectopic expression of circ_0006404 increased HCC cell growth, cycle, and migration. Moreover, we showed that miR-624 was downregulated in HCC specimens and cells and miR-624 expression was negatively correlated with circ_0006404 expression in HCC specimens. Circ_0006404 sponged miR-624 in HCC cell, and the overexpression of circ_0006404 suppressed miR-624 expression in HCC cell. Furthermore, circ_0006404 induced HCC cell growth, cycle, and migration via regulating miR-624. These results elucidated that circ_0006404 facilitated HCC progression and might act as one new biomarker for this carcinoma.

Clinical characteristics of re-hospitalized COVID-19 patients with recurrent positive SARS-CoV-2 RNA: a retrospective study.

At present, it has been noticed that some patients recovered from COVID-19 present a recurrent positive RNA test of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) after being discharged from hospitals. The purpose of the current study was to characterize the clinical features of re-hospitalized patients with recurrent SARS-CoV-2 positive results. From January 12 to April 1 of 2020, our retrospective study was conducted in China. The exposure history, baseline data, laboratory findings, therapeutic schedule, and clinical endpoints of the patients were collected. All the patients were followed until April 10, 2020. Among all COVID-19 patients included in the current study, there were 14 re-hospitalized patients due to recurrent positive tests of SARS-CoV-2 RNA. Fever (11 [78.6%]), cough (10 [71.4%]), and fatigue (7 [50.0%]) were the most common symptoms on the patient's first admission, and less symptoms were found on their second admission. The average duration from the onset of symptoms to admission to hospital was found to be 8.4 days for the first admission and 2.6 days for the second admission (P = 0.002). The average time from the detection of RNA (+) to hospitalization was 1.9 days for the first admission and 2.6 days for the second admission (P = 0.479), and the average time from RNA (+) to RNA (-) was 11.1 days for the first admission and 6.3 days for the second admission (P = 0.030). Moreover, the total time in hospital was 18.6 days for the first admission and 8.0 days for the second admission (P = 0.000). It may be necessary to increase the isolation observation time and RT-PCR tests should be timely performed on multiple samples as soon as possible.

Accessory hepatic vein recanalization for hepatic vein-type Budd-Chiari syndrome.

PURPOSE: To explore the clinical efficacy and long-term outcomes of accessory hepatic vein (AHV) recanalization as a means of treating hepatic vein (HV)-type Budd-Chiari syndrome (BCS). METHODS: Between January 2011 and December 2018, a total of 46 symptomatic HV-type BCS patients were treated by AHV recanalization in our hospital. The technical and clinical success of this treatment, as well as associated long-term patient prognosis was assessed herein. RESULTS: The AHV recanalization approach was technically successful in 100% of patients, without any instances of complications associated with the operation. This procedure was 95.7% (44/46) clinically successful and resultant. AHV re-obstruction occurred in 12 patients. The cumulative primary one-, two-, and five-year patency rates were 77.3%, 71.7%, and 71.7%, respectively. The secondary cumulative one-, two-, and five-year patency rates were 97.7, 87.1, and 87.1%, respectively. The five-year patency rates did not differ significantly between patients treated with balloons and stents (p = .674). Based on Cox-regression analysis, younger age was an independent predictor of re-obstruction (p = .005). The cumulative one-, two-, and five-year survival rates were 97.7, 92.2, and 92.2%, respectively. CONCLUSIONS: AHV recanalization is a safe and effective treatment for HV-type BCS.

Stent with radioactive seeds strand insertion for malignant hilar biliary obstruction.

PURPOSE: This study aimed to assess clinical efficacy and long-term patient outcomes in individuals with malignant hilar biliary obstruction (MHBO) that had been treated via insertion of a stent with a radioactive seed strand (RSS). MATERIAL AND METHODS: A total of 84 MHBO patients were treated via either normal stent insertion (n = 48) or stent with RSS insertion (n = 36) from January 2015 to December 2018. RESULTS: The technical success rates of normal stent insertion and stent with RSS insertion were 93.8% (45/48) and 97.2% (35/36), respectively (p = .632), with clinical success rates of 93.3% (42/45) and 100% (35/35), respectively (p = .252). In these two patient groups, 11 and seven patients, respectively, suffered from stent dysfunction (p = .637). In the normal and RSS groups, median stent patency was 165 and 225 days, respectively (p < .001). All patients in the present study died due to tumor progression, with median survival times of 188 and 250 days in the normal and RSS stent groups, respectively (p < .001). CONCLUSION: Relative to normal stent insertion, combined stent with RSS insertion can effectively prolong both stent patency and patient survival in patients with MHBO.

Irradiation stent insertion for inoperable malignant biliary obstruction: a meta-analysis of randomized controlled trials.

The purpose of the study was to compare the relative clinical efficacies of irradiation stent (IRS) and conventional stent (CVS) insertions for the treatment of patients with malignant biliary obstruction (MBO). Pubmed, Embase, and Cochrane Library databases were searched for relevant randomized controlled trials (RCTs) from the date of inception through to August 2020. Data analysis was performed using RevMan v5.3. This meta-analysis included eight RCTs which included a total of 319 patients who had undergone IRS insertion, and 328 who had undergone CVS insertion. No significant differences in pooled Δ total bilirubin values (MD 0.34; P = 0.92), incident rates of cholangitis (P = 0.47), hemobilia (P = 0.60), or pancreatitis (P = 0.89) were detected between two groups. The rate of stent dysfunction was significantly lower in the IRS group compared to the CVS group (22.2% vs. 37.7%, P = 0.02). The pooled stent patency (P < 0.00001) and survival (P < 0.00001) were significantly longer in the IRS group compared to the CVS group. Significant heterogeneity was detected in the endpoints of rate of stent dysfunction (I2 = 52%; P = 0.08) and survival (I2 = 77%; P = 0.0005). Subgroup analysis was performed based on the different IRS types and showed significantly longer survival in the IRS group based on both types of IRS. Funnel plot analyses did not detect any evidence of publication bias. This meta-analysis included eight RCTs which included a total of 319 patients who had undergone IRS insertion, and 328 who had undergone CVS insertion. No significant differences in pooled Δ total bilirubin values (MD 0.34; P = 0.92), incident rates of cholangitis (P = 0.47), hemobilia (P = 0.60), or pancreatitis (P = 0.89) were detected between 2 groups. The rate of stent dysfunction was significantly lower in the IRS group compared to the CVS group (22.2% vs. 37.7%, P = 0.02). The pooled stent patency (P < 0.00001) and survival (P < 0.00001) were significantly longer in the IRS group compared to the CVS group. Significant heterogeneity was detected in the endpoints of rate of stent dysfunction (I2 = 52%; P = 0.08) and survival (I2 = 77%; P = 0.0005). Subgroup analysis was performed based on the different IRS types and showed significantly longer survival in the IRS group based on both types of IRS. Funnel plot analyses did not detect any evidence of publication bias. Our meta-analysis demonstrates that IRS insertion can prolong stent patency and the survival of patients with MBO compared to CVS insertion.

Microsecond molecular dynamics simulations reveal the allosteric regulatory mechanism of p53 R249S mutation in p53-associated liver cancer.

The tumor suppressor p53, a transcription factor, plays a critical role in many cellular processes, including DNA repair and apoptosis and cell cycle arrest. Missense mutations in the p53 have closely related to human cancer. R249S mutation at the p53 core DNA binding domain (DBD) is frequently observed in hepatocellular carcinoma. This mutation is away from the p53 DBD-DNA binding interface. However, how the R249S mutation causes the structural changes of p53 DBD that lead to weak the binding of p53 mutant to DNA has not been clearly understood. Here, microsecond-scale molecular dynamics (MD) simulations of p53 DBD in the wild type (WT) and R249S mutated states in the absence of DNA binding were performed to explore the effect of the R249S mutation on the conformational dynamics of p53 DBD. The R249S mutation does not cause the global conformational changes, and it only affects the local domains at the mutation site and the DNA binding interface, particularly at the S1-S2 turn. The allosteric effects of the S1-S2 turn induced by the R249S mutation lead to the extension of the S1-S2 turn into the ß-strands, which in turn interferes with the binding of DNA at the major groove. The results can help decipher the allosteric regulatory mechanism by which the R249S mutation of p53 DBD affects the p53 DBD-DNA interactions.

Self-Expanded Metallic Stent Insertion for Hilar Cholangiocarcinoma: Comparison of Unilateral and Bilateral Stenting.

Purpose: This study aims to ascertain the relative outcomes in patients with hilar cholangiocarcinoma (HCCA) undergoing either unilateral or bilateral self-expanded metallic stent (SEMS) insertion. Materials and Methods: In this retrospective single-center study, 93 patients with HCCA were treated through percutaneous insertion of either unilateral or bilateral SEMS during January 2012 to December 2018. We compared technical success, clinical success, and long-term outcomes of the treatment method. Results: Overall, 51 and 42 patients were treated through unilateral and bilateral SEMS insertion, respectively, with technical success rates of 92.2% (47/51) and 95.3% (40/42), respectively, (P = .859). No patients experienced any procedure-related complications, with unilateral and bilateral clinical success rates of 95.7% (45/47) and 97.4% (38/39), respectively, (P = 1.000) and with comparable adverse event rates between these groups (3/47 vs. 5/40; P = .541). Moreover, 8 and 3 patients treated with unilateral and bilateral stents exhibited stent dysfunction, respectively, (P = .183). In unilateral and bilateral groups, median patency rates were189 and 198 days, respectively, (P = .887). During the follow-up period, all patients died, with respective mean overall survival rates of 222 and 202 days for those treated using unilateral and bilateral stents (P = .755). Both Bismuth type III HCCA (P = .025) and a lack of chemotherapy (P = .000) correlated with reduced survival in univariate and multivariate regression analyses. Conclusion: Insertion of unilateral and bilateral SEMS exhibits similar clinical efficacy and long-term outcomes in patients with HCCA.

Development of a Novel Magnetic Brake Shoe for Mine Hoists Based on Nano-Fe3O4 and Nd-Fe-B Additive.

BACKGROUND: The brake is an important safety protection device for mine hoists, in which the performance of the brake shoe affects directly the safe operation of the hoist system. In order to solve problems such as high wear rate and unstable friction coefficient of brake shoe under high temperature, this paper indicated that adding magnetic powder to the composite material of traditional mine hoist's brake shoe will be a creative and effective approach to improve its properties. METHODS: Based on relevant China patents of the authors, several new formulas of brake shoe material were designed in the presence of Nano-Fe3O4 and Nd-Fe-B, and the methods of both preparation and performance testing of the magnetic brake shoes were introduced. The experiment of formula design was carried out by uniform prescription design, and the friction coefficient and wear rate of each kind of brake shoes made through different formulas were measured. Furthermore, the formula was optimized by application of fuzzy comprehensive evaluation method and analytic hierarchy process. RESULTS: Compared with ordinary formulas, the optimized formula is higher totally and changes more steadily as well. Its wear rate is far lower than the national standard. Namely, its comprehensive properties are better. Few relevant patents to the topic have been reviewed and cited. CONCLUSION: This paper proved that it is practically valuable and feasible to improve the properties of hoist brake shoes by adding magnetic powder to its composite material.

Protective effects of alpinetin on lipopolysaccharide/d-Galactosamine-induced liver injury through inhibiting inflammatory and oxidative responses.

Alpinetin, a type of novel plant flavonoid derived from Alpinia katsumadai Hayata, has been reported to have anti-inflammatory effects. The aim of this investigation was designed to reveal the protective effects of alpinetin on Lipopolysaccharide (LPS)/d-galactosamine (D-Gal)-induced liver injury in mice. Alpinetin (12.5, 25, 50 mg/kg) were given 1 h before LPS and D-Gal treatment. 12 h after LPS and D-Gal treatment, the liver tissues and serum were collected. Our results showed that alpinetin treatment improved liver histology, indicating a marked decrease of inflammatory cell infiltration and restore hepatic lobular architecture. Alpinetin also inhibited liver myeloperoxidase (MPO) activity and malondialdehyde (MDA) level. Furthermore, LPS/D-Gal-induced tumor necrosis factor-α (TNF-α) and Interleukin-1ß (IL-1ß) production were dose-dependently inhibited by alpinetin. Alpinetin also attenuated LPS/D-Gal-induced expression of phospho-NF-κB p65 and phospho-IκBα. In addition, alpinetin was found to increase the expression of nuclear factor E2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). In conclusion, these findings suggested that alpinetin inhibited liver injury through inhibiting NF-κB and activating the Nrf2 signaling pathway.

Mesenchymal stem cells inhibited development of lung cancer induced by chemical carcinogens in a rat model.

Mesenchymal stem cells (MSCs) may play a significant role in carcinogenesis; however, data have shown that MSCs can both promote and inhibit tumor growth. We investigated the effect of MSCs on the development of lung cancer in a rat model. Bone marrow-derived MSCs were isolated from male Wistar rats and fluorescently labeled. Genotoxic carcinogens 3-methylcholanthrene (MCA) and diethylnitrosamine (DEN) were instilled into the left lung lobes of female rats to induce tumors. Labeled male MSCs were infused into the female rats via tail vein, and the rats were sacrificed on days 3 and 7. MSC survival and distribution were detected by PCR and fluorescence, respectively. Labeled MSCs aggregated at the injection site in the left lobe (MCA/DEN-treated) on day 3 but not the untreated right lobe. Survival of the MSCs in vivo was confirmed by detection of the male SRY gene in lung tissues by PCR at day 3; however, by day 7, lung tissues were SRY-negative. Next, carcinogen-treated rats were divided into two groups and infused with normal MSCs (experimental group) or PBS (control group) every week for 10 weeks, then sacrificed. Cell proliferation in lung tissues was calculated by Ki67 and PCNA expression. Eighty-percent (8/10) of rats in the control group had tumors, while none of the rats in the experimental group had tumors. There was no difference in cell proliferation in lung tissues between the groups. Therefore, bone marrow-derived MSCs prevented development of carcinogen-induced lung cancer in a rat model. Additional studies are needed to determine mechanism.

Correlation of interferon-lambda 4 ss469415590 with the hepatitis C virus treatment response and its comparison with interleukin 28b polymorphisms in predicting a sustained virological response: a meta-analysis.

BACKGROUND: Interferon-lambda 4 (IFNL4) ss469415590 is a newly discovered polymorphism that could predict the treatment response in hepatitis C virus (HCV)-infected patients. This meta-analysis was performed in order to clarify its specific effect on the treatment response and to compare it with interleukin 28b (IL28B). METHOD: The commonly used literature databases were searched. Meta-analyses were performed with fixed/random-effects models using Stata 12.0. The sustained virological response (SVR) rate was summarized using R software. Publication bias was examined through Egger's test. RESULTS: A total of seven studies were finally included in this meta-analysis. IFNL4 ss469415590 was demonstrated to be associated with SVR (odds ratio (OR) 3.83, 95% confidence interval (CI) 3.22-4.56, p<0.001). Asians had a higher likelihood of achieving SVR than Caucasians (OR=7.36 vs. 3.54). When stratifying all the patients according to HCV genotype, a significant association was observed in HCV genotype 1 patients (OR 4.5, 95% CI 2.91-6.95, p<0.001). In HCV genotype 2/3 patients, the favorable TT/TT genotype patients tended to have a statistically higher SVR rate than the non-TT/TT genotype patients (84.4% vs. 78.3%, p=0.058). Compared with IL28B rs12979860 (OR 3.45) and rs8099917 (OR 3.50), ss469415590 TT/TT genotype patients showed a slightly higher probability of achieving a SVR (OR 3.61 calculated from studies investigating both IFNL4 and rs12979860; OR 4.86 for studies investigating both IFNL4 and rs8099917). Furthermore, ss469415590 showed a slightly higher predictive value than rs12979860 using the diagnostic test tool (area under the curve=0.71 vs. 0.70). IFNL4 was also correlated with rapid virological response (RVR) (OR 4.35, 95% CI 1.43-13.20, p=0.01), viral clearance (OR 0.31, 95% CI 0.24-0.39, p<0.001), and HCV susceptibility (OR 0.76, 95% CI 0.65-0.89, p=0.001). CONCLUSIONS: IFNL4 ss469415590 is significantly associated with SVR in HCV genotype 1 patients, irrespective of race; there is a tendency towards an association in HCV genotype 2/3 patients. Comparable to IL28B, IFNL4 is correlated with natural viral clearance and HCV susceptibility, additionally IFNL4 ss469415590 has a slightly higher predictive performance over IL28B polymorphisms in regard to SVR.

A Review on the Research Progress of Nano Organic Friction Materials.

BACKGROUND: Traditional organic friction materials are difficult to adapt to people's growing technical requirements for stability, safety, comfort and environmental protection in the braking process. With the rapid development of nanotechnology, the brake's organic friction materials meet new opportunities. This article aims to review the research progress of organic friction materials that have applied nanotechnology. METHODS: The research progress of nano organic friction materials was reviewed from four aspects in this article. Firstly, this article outlined the development history of friction materials. Secondly, two preparation methods of the nano organic friction material were summarized as by nano modifying of matrix material and by adding nanoparticles into friction material. Thirdly, it was indicated that the nano organic friction material has generally better mechanical, physical properties and tribological performance than traditional organic friction materials. And the main factors that affect the friction and wear performance were analyzed. Finally, the main existing problems in this field were summarized. RESULTS: It was pointed out that the nano organic friction material may be an important developing trend of friction materials. It was also pointed out that the dispersion of nanoparticles must be a key process during preparation. What is more, the improvement mechanisms of performance by nano modifying were explained. And it was considered at the end that the functional friction material with magnetism or self-adsorption may be a leading developoing direction of nano organic friction materials in the future. CONCLUSION: The findings of this review confirm the excellent performance of nano organic friction materials. It is concluded that the development of a new functional friction material by using the special effect of nanoparticles will be an important developing trend. Few relevant patents to the topic have been reviewed and cited.

Probiotics in the treatment of peptic ulcer infected by helicobacter pylory and its safety.

This paper aimed to study the curative effect of probiotics in the treatment of peptic ulcer (PU) infected with Helicobacter Pylory (H. Pylory). A total of 132 cases of patients with PU infected by H. Pylory who were received and treated by department of gastroenterology from Binjiang Hospital, Guangxi from May 2013 to 2014 were recruited in the study. They were divided into observation group and control group based on random number table, 66 cases in each group. Patients in observation group were given probiotics combined with triple therapy while patients in control group were treated by traditional triple therapy. After one-month treatment, all the patients were examined by (14)C urea breath test for checking the treatment condition of H. Pylory and reviewed by gastroscope for checking union of ulcer. In addition, clinical effect and improvement of digestive tract symptom were compared between two groups. It was found that, the content of (14)C urea detected by breath test was 95.15 dpm/mmol ± 8.34 dpm/mmol in observation group after treatment; eradication rate of H. Pylory was 87.9%; symptom remission rate was 97%; adverse reaction rate was 4.5%; total effective rate of clinical treatment was 97%; while in control group, the content of (14)C urea was 100.3 dpm/mmol ± 10.34 dpm/mmol, eradication rate was 63.6%, symptom remission rate was 93.9%, adverse reaction rate was 18.2%, and total effective rate was 83.3%. These results demonstrated that, the symptom remission rate of the observation group and the control group was not obvious, but the content of (14)C urine, eradication rate of H. Pylory, incidence of adverse reaction and total effective rate were of significant significance in two groups (P<0.05). In conclusion, probiotics combined with triple therapy for treating PU infected by H. Pylory can greatly improve the eradication rate of H. Pylory and increase recovery rate of patients, with less adverse reaction. Therefore, the method is worth for promotion.

Efficacy of poly-unsaturated fatty acid therapy on patients with nonalcoholic steatohepatitis.

AIM: To examine whether poly-unsaturated fatty acid (PUFA) therapy is beneficial for improving nonalcoholic steatohepatitis (NASH). METHODS: In total, 78 patients pathologically diagnosed with NASH were enrolled and were randomly assigned into the control group and the PUFA therapy group (added 50 mL PUFA with 1:1 ratio of EHA and DHA into daily diet). At the initial analysis and after 6 mo of PUFA therapy, parameters of interest including liver enzymes, lipid profiles, markers of inflammation and oxidation, and histological changes were evaluated and compared between these two groups. RESULTS: At the initial analysis, in patients with NASH, serum levels of alanine aminotransferase (ALT) and aspartase aminotransferase (AST) were slightly elevated. Triglyceride (TG), total cholesterol (TC) and low-density lipoprotein cholesterol levels, markers of systemic inflammation [C-reactive protein (CRP)] and oxidation [malondialdehyde (MDA)], as well as fibrosis parameters of type IV collagen and pro-collagen type III pro-peptide were also increased beyond the normal range. Six months later, ALT and AST levels were significantly reduced in the PUFA group compared with the control group. In addition, serum levels of TG and TC, CRP and MDA, and type IV collagen and pro-collagen type III pro-peptide were also simultaneously and significantly reduced. Of note, histological evaluation showed that steatosis grade, necro-inflammatory grade, fibrosis stage, and ballooning score were all profoundly improved in comparison to the control group, strongly suggesting that increased PUFA consumption was a potential way to offset NASH progression. CONCLUSION: Increased PUFA consumption is a potential promising approach for NASH prevention and reversal.

The Role of Phosphorylated Cx43 on PKC Mediated Ser368 in Lung Injury Induced by Seawater Inhalation.

Seawater aspiration may result in acute lung injury/acute respiratory distress syndrome (ALI/ARDS), which is characterized by pulmonary inflammation and lung edema that closely related to pulmonary barrier dysfunction and intracellular communication. The aim of the present research was to explore the role of connexion 43 (Cx43) in seawater aspiration-induced ALI/ARDS. The results from in vivo experiments showed that seawater inhalation led to increased expression of p-PKC and phosphorylated Cx43 (p-Cx43), which were followed by protein rich fluid leakage and TNF-α and IL-1ß secretion. Besides, the results from in vitro tests proved that the expression of p-PKC directly influenced phosphorylation state of Cx43 and its function, which could further affect the inflammatory factors secretion and intercellular communication. In conclusion, seawater aspiration causes p-Cx43 expression by PKC pathway, which is involved in the on come and development of pulmonary inflammation and lung edema.

miR-709 up-regulated in hepatocellular carcinoma, promotes proliferation and invasion by targeting GPC5.

OBJECTIVES: Hepatocellular carcinoma (HCC) is one of the most common cancers and is a significant leading cause of cancer-related deaths worldwide. Emerging evidence has shown that microRNAs (miRNAs) are associated with cancer development and progression. However, up to now little has been known concerning the role of miR-709 in HCC. MATERIALS AND METHODS: Real-time RT-PCR was performed to detect expression of miR-709 in HCC cell lines and tissues. To further understand its role in HCC, we restored its expression in HepG2 cell line through transfection with miR-709 mimics or inhibitors. CCK-8 proliferation assay, migration assay and invasion assay were used to detect functional roles of miR-709. Luciferase assay and western blotting were performed to detect the target gene of miR-709. RESULTS: We found that miR-709 was highly expressed in HCC tissues and in HCC cell lines by qRT-PCR. Re-expression of miR-709 in HCC cells remarkably promoted cell migration and invasiveness in vitro. Subsequent investigation revealed that glypican-5 (GPC5) was a direct and functional target of miR-709 in HCC cells where overexpression of miR-709 impaired GPC5-induced inhibition of proliferation and invasion. Finally, analysis of miR-709 and GPC5 levels in human HCC tissues revealed that miR-709 inversely correlated with GPC5 expression. CONCLUSIONS: These results suggest that miR-709 may positively regulate invasion and metastasis of HCC through targeting GPC5.

IL-28B polymorphisms correlated with treatment response in HCV-4 mono-infected patients: a meta-analysis.

BACKGROUND: The role of interleukin 28B (IL-28B) polymorphisms played in hepatitis C virus (HCV) infection has been gradually explicit, especially in HCV genotype 1, 2 and 3. However, no confirmative conclusion was acquired in genotype 4 HCV patients. Thus we conducted this meta-analysis. METHODS: We searched the commonly used databases both in English and Chinese. Meta-analysis was performed in fixed/random effects models using STATA 12.0 or R software. Publication bias was examined through Egger's test and Begg's funnel plot. RESULTS: In total, 11 studies were included in this meta-analysis, encompassing 1284 patients who were mono-infected with HCV-4 and received Peg-interferon (Peg-IFN) plus Ribavirin (Rbv). Around 53.0% patients would achieve sustained virologic response (SVR), 36.6% achieve rapid virologic response (RVR) and 62.4% achieve end of treatment response (ETR). Egyptian patients had a higher rate achieving SVR than non-Egyptian patients (56.3% vs. 47.8%). IL-28B rs12979860 CC genotype not only favored SVR (OR = 3.95, 95%CI = 3.03-5.16), regardless of citizenship, but also favored RVR (OR = 3.82, 95%CI = 2.46-5.95) and ETR (OR = 4.22, 95%CI = 2.81-6.34). IL-28B rs8099917 genotype TT also correlated with SVR (OR = 3.41, 95%CI = 1.92-6.07), but might not with RVR. IL-28B rs12980275 might still correlate with SVR, but warrant more studies to validate. CONCLUSIONS: The favorable IL-28B rs12979860 genotype is a statistically significant predictor of SVR, RVR and ETR in HCV-4 monoinfected patients treated with Peg-IFN plus Rbv. Rs8099917 might predict SVR but not RVR. Egyptian HCV-4 patients would achieve better outcomes than non-Egyptian patients when treated with standard care.