Sialidase NEU1 May Serve as a Potential Biomarker of Proliferation, Migration and Prognosis in Melanoma.

Background: Melanoma is a kind of malignant tumor with high mortality originating from melanocytes. It is urgent to find new molecular biomarkers for prognosis and new treatment methods for melanoma. As an important molecule of sialidase family, neuraminidase-1 (NEU1) has been found to play an important role in regulating the occurrence and progression of tumors, but the role of NEU1 in melanoma is not sure. Methods: The expression level of NEU1 in melanoma and normal tissues was evaluated by analyzing the expression data from ONCOMINE, UALCAN and GEPIA database. The mutation, copy number alteration and gene correlation of NEU1 in melanoma were evaluated by analyzing the melanoma data from cBioPortal database The protein expression levels of NEU1 were further validated by immunohistochemical (IHC) staining data from The Human Protein Atlas database. The melanoma data in TIMER 2.0 database were used to analyze the correlation between NEU1 expression and immune cell infiltration. The proliferative and migratory abilities of melanoma cells were examined by cell proliferation and migration assay in vitro and nude mice. Results: We discovered that NEU1 was highly expressed in melanoma samples compared with normal samples. The alteration frequency of NEU1 in melanoma patients reached 18%, and most of them were "mutation" type. The expression of NEU1 was positively correlated with the overall survival of patients with melanoma. The expression of NEU1 was positively correlated with the expression of proliferation marker CDK2 and epithelial-mesenchymal transition marker CD44 and negatively correlated with the expression of apoptosis marker CASP3 and CASP8. Moreover, the expression level of NEU1 was related to the infiltration of immune cells in melanoma. Knockdown of NEU1 attenuated the in vitro proliferative and migratory abilities of melanoma cells, as well as in vivo tumor progression of melanoma cells. Conclusions: These findings suggest that NEU1 may play a key role in the development of melanoma and may be used as a prognostic target of melanoma.

A Single, Acute Astragaloside IV Therapy Protects Cardiomyocyte Through Attenuating Superoxide Anion-Mediated Accumulation of Autophagosomes in Myocardial Ischemia-Reperfusion Injury.

Myocardial ischemia-reperfusion (I/R) injury, characterized by myocardial cell death (e.g., apoptosis) and generation of reactive oxygen species (ROS) such as superoxide (O2 ·-) and hydrogen peroxide (H2O2), is a serious threat to human health and property. Saponin astragaloside IV (ASIV), extracted from Chinese herbal medicine astragalus, is effective in resolving multiple pathological issues including myocardial I/R injury. Recent studies have shown that autophagy is regulated by ROS and plays an important role in myocardial I/R injury. However, regulation of autophagy by ASIV during myocardial I/R injury and the role of specific ROS involved in the process have been rarely reported. In the present study, we found that SOD2 was downregulated and O2 ·- was upregulated in H2O2-induced H9C2 cardiac myocyte injury in vitro and myocardial I/R injury in vivo, while such alterations were reversed by ASIV. ASIV possessed the ability to alleviate myocardial I/R injury via attenuating I/R-caused autophagosome accumulation. Upregulate of O2 ·- by 2-methoxyestradiol (2-ME) reversed the effect of ASIV-mediated autophagy regulation, which suggested that O2 ·- was vital in this process. In conclusion, our results contribute to understanding the mechanism of ASIV-induced cardioprotective effect.

Nasal nebulization inhalation of budesonide for chronic rhinosinusitis with nasal polyps: A protocol for systematic review and meta-analysis.

BACKGROUND: Chronic rhinosinusitis and nasal polyps (CRNP) is a common public health concern for general population, and is thought to negatively impact their quality of life. Although previous studies have reported that nasal nebulization inhalation of budesonide (NNIB) can benefit patients with such condition, its conclusions are still inconsistent. Thus, this study will assess the efficacy and safety of NNIB for the treatment of CRNP. METHODS: To identify any associated studies, we will comprehensively and systematically search Cochrane Library, PubMed, EMBASE, Web of Science, PsycINFO, Cumulative Index to Nursing and Allied Health Literature, Allied and Complementary Medicine Database, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure. We will search all electronic databases from inception to the present with no limitations of language and publication status. Two independent reviewers will undertake selection of study, data collection, and study quality evaluation, respectively. Another reviewer will help to settle down any different opinions between both of them. Study quality will be checked using Cochrane risk of bias tool, and statistical analysis will be performed using RevMan 5.3 software. RESULTS: This study will assess the efficacy and safety of NNIB for the treatment of CRNP through assessing primary outcomes of nasal symptoms and polyp sizes, and secondary outcomes of serum cortisol levels, health-related quality of life, and any expected and unexpected adverse events. CONCLUSION: The results of this study will summarize the up-to-date evidence on assessing the efficacy and safety of NNIB for the treatment of CRNP. STUDY REGISTRATION NUMBER: INPLASY202040108.

Effect of CO2 laser for the management of primary otosclerosis: A protocol for systematic review and meta-analysis.

BACKGROUND: This study will explore the effect and safety of CO2 laser (COL) for the management of patients with primary otosclerosis (PO). METHODS: The following electronic databases will be searched from inception to the present: PUBMED, EMBASE, The Cochrane Library, Web of Science, PsycINFO, Cumulative Index to Nursing and Allied Health Literature, Allied and Complementary Medicine Database, Chinese Biomedical Literature Database, VIP, WANGFANG, and China National Knowledge Infrastructure. No language limitation will be applied. All relevant randomized controlled trials using COL to treat patients with PO will be included. Two researchers will identify studies, collect data and evaluate the risk of bias of each included study independently. Any different views between 2 researchers will be resolved by a third researcher via discussion. Data analysis will be carried out using RevMan 5.3 software. RESULTS: This study will evaluate the effect and safety of COL for the treatment of PO through hearing gain, tinnitus severity, incidence of intraoperative, health-related quality of life, other morbidities, and adverse events. CONCLUSION: This study will provide evidence for the effect and safety of COL in patients with PO. STUDY REGISTRATION NUMBER: INPLASY202040110.

Efficacy of levocetirizine for the treatment of children with allergic rhinitis: A protocol for systematic review and meta-analysis.

BACKGROUND: Although previous studies have reported that levocetirizine is utilized for the treatment of children with allergic rhinitis (AR), its conclusions remain inconsistent. This study aims to evaluate the efficacy and harms of levocetirizine for children with AR. METHODS: Electronic database sources will be undertaken from the beginning to the present: MEDLINE, EMBASE, The Cochrane Library, CINAHL, ACMD, PsycINFO, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure. We will not apply any restrictions to language and publication status. We will only consider randomized controlled trials of levocetirizine for children with AR. Two authors will independently scan literature, select studies, and collect data. Study quality for each included trial will be assessed using Cochrane risk of bias tool, and statistical analysis will be conducted using RevMan 5.3 software. RESULTS: This study will summarize the present evidence to systematically assess the efficacy and harms of levocetirizine for children with AR. CONCLUSION: The findings of this study intent to adequately inform stakeholders or clinicians, as well as to help develop treatment guidelines. STUDY REGISTRATION NUMBER: INPLASY202040111.

Groundwater pollution containing ammonium, iron and manganese in a riverbank filtration system: Effects of dynamic geochemical conditions and microbial responses.

Bench-scale experiments were conducted to investigate the effect of hydraulic loadings and influent concentration on the migration and biotransformation behavior of three groundwater pollutants: ammonium (NH4 +), iron (Fe2+) and manganese (Mn2+). Columns packed with aquifer media collected from a river bank filtration (RBF) site in Harbin City, NE China were introduced synthetic groundwater (SGW) or real groundwater (RGW) were at two different constant flow rates and initial contaminant concentrations to determine the impact of system conditions on the fate of the target pollutants biotransformation. The results showed that the biotransformation rate of Fe2+ Mn2+, and NH4 + decreased by 8%, 39% and 15% under high flow rate (50 L d-1) compared to low flow rate (25 L d-1), which was consistent with the residence-time effect. While the biotransformation rate of Fe2+ Mn2+, and NH4 + decreased by 7%, 14% and 9% under high influent concentration compared to original groundwater. The 16S rRNA analysis of the aquifer media at different depths after experiments completion demonstrated that the relative abundance of major functional microbes iron oxidizing bacteria (IOB) and manganese oxidizing bacteria (MnOB) under higher flow rate and higher influent concentration decreased 13%, 14% and 25%, 24%, respectively, whereas the ammonium oxidizing bacteria (AOB) and nitrite oxidizing bacteria (NOB) exhibited minimal change, compared to the lower flow rate. Above all results indicated that both high flow rate and high concentration inhibit the biotransformation of NH4 +, Fe2+ and Mn2+. The biotransformation of Fe2+ and Mn2+ occurs primarily in the 0-40 cm and 20-60 cm depth intervals, respectively, whereas the NH4 + biotransformation appears to occur relatively uniformly throughout the whole 110cm column. The biotransformation kinetics of NH4 + in RGW and SGW, Mn2+ in RGW at different depths accords with the first order kinetics model, while Fe2+ in RGW and SGW, Mn2+ in SGW presented more complicated biotransformation process. The results should improve understanding of the transport and fate of common groundwater pollutants in riverbank filtration and other groundwater recharge environments.

The spatial variations of correlation between microbial diversity and groundwater quality derived from a riverbank filtration site, northeast China.

To identify the relationship between microbial communities and groundwater quality parameters, especially typical groundwater contaminants including ammonium (NH4+), iron (Fe2+), and manganese (Mn2+), groundwater samples and aquifer media were collected from a riverbank filtration (RBF) site in Harbin city, northeast China. The structures of the microbial communities of aquifer media at different depths were illustrated through 16S rRNA sequencing using the Illumina MiSeq platform, and the correlation between microbial communities and water quality parameters was quantitatively demonstrated by redundancy analysis (RDA). The results revealed that the diversity of microbial communities decreased along the groundwater flow path at the south bank of Songhua river. The richness and diversity in the unsaturated zone (0-5 m) were significantly higher than those in the saturated zone (5-50 m) because of physiochemical properties of aquifer media and the redox environment in the RBF system. Core taxa, which were significantly related to the biotransformation behavior of iron, manganese, and ammonium, were Pseudomonas, Acinetobacter, Ochrobactrum, Sphingobium, and Sphingomonas. RDA results indicated that the critical physiochemical parameters that significantly influenced the composition of microbial communities were different in the saturated and unsaturated zones, and the total organic carbon (TOC), electrical conductivity (EC), nitrate (NO3-), and manganese (Mn2+) levels were the four principal factors affecting the function and composition of microbial communities in the whole RBF system. Proteobacteria, Sphingomonadales, and Sphingobium were the dominant bacteria at the phylum, order, and genus levels with 39.8%, 59.2%, and 65.3% contribution to the overall groundwater quality, respectively. The results obtained from this study should improve the understanding of the relationship between the structure of microbial communities (especially, bacteria related to the biotransformation of NH4+, Fe2+, and Mn2+) and physiochemical parameters.

Effect of colloids on non-Fickian transport of strontium in sediments elucidated by continuous-time random walk analysis.

Understanding the influence of colloids on radionuclide migration is of significance to evaluate environmental risks for radioactive waste disposals. In order to formulate an appropriate modelling framework that can quantify and interpret the anomalous transport of Strontium (Sr) in the absence and presence of colloids, the continuous time random walk (CTRW) approach is implemented in this work using available experimental information. The results show that the transport of Sr and its recovery are enhanced in the presence of colloids. The causes can be largely attributed to the trap-release processes, e.g. electrostatic interactions of Sr, colloids and natural sediments, and differences in pore structures, which gave rise to the varying interstitial velocities of dissolved and, if any, colloid-associated Sr. Good agreement between the CTRW simulations and the column-scale observations is demonstrated. Regardless of the presence of colloids, the CTRW modelling captures the characteristics of non-Fickian anomalous transport (0 < ß < 2) of Sr. In particular, a range of 0 < ß < 1, corresponding to the cases with greater recoveries, reveal strongly non-Fickian transport with distinctive earlier arrivals and tailing effects, likely due to the physicochemical heterogeneities, i.e. the repulsive interactions and/or the macro-pores originating from local heterogeneities. The results imply that colloids can increase the Sr transport as a barrier of Sr sorption onto sediments herein, apart from often being carriers of sored radionuclides in aqueous phase. From a modelling perspective, the findings show that the established CTRW model is valid for quantifying the non-Fickian and promoted transport of Sr with colloids.

Apportionment and evolution of pollution sources in a typical riverside groundwater resource area using PCA-APCS-MLR model.

Comparative analysis was performed of changing groundwater quality over ten years (2006-2016) by source apportionment and spatial distribution characteristics. This shallow groundwater in a typical riverside groundwater resource area was studied using principal component analysis (PCA) and factor analysis (FA), coupled with the absolute principal-component-score multiple-linear-regression (APCS-MLR) receptor model. The relationship among land-use types, hydro-chemical composition, and evolution of the quality of groundwater from natural and anthropogenic sources was demonstrated. The results showed that water-rock interaction, agricultural fertilizer, and domestic and industrial wastewater were responsible for the evolution of contamination in the groundwater. The major potential pollution sources that had significant effect on groundwater quality variables were categorized into three groups: heavy metals (iron, manganese), nutrients (ammonia nitrogen, nitrite and nitrates), and organic pollution (chemical oxygen demand). The APCS-MLR model considered the average contribution of each different potential pollution source to these categories separately. The potential pollution sources in the groundwater presented an obvious spatial distribution with an area of high concentration distributed mainly in the western and northwestern areas downstream from the Songhua River. The variation of land use type and evolution of the spatial distribution of the pollution sources in the groundwater showed good consistency. Eventually, PCA /FA coupled with APCS-MLR became a versatile tool for comprehensive source apportionment of groundwater.

[Seasonal Variation Characteristics of Pollution Risk in a Riverside Source Area Based on Source Apportionment].

Riverbank filtration is internationally accepted as a safe new method for extracting drinking water. This paper describes the structure and characteristics of pollution sources in the Hulan water source area of Harbin during wet and dry seasons, based on groundwater pollution sources apportionment technology. Pollution risk of the water source area was also assessed using the pollution sources-pathway-receptor model. Impacts on water quality safety under the collective effects of seasonal changes and human activities were then analyzed. Results showed that groundwater pollution sources have different spatial distribution characteristics based on pollution source apportionment during wet and dry seasons, with four principal influencing factors:①water-rock interaction caused by exploitation of water sources, ② natural geological processes resulting from dissolution of iron manganese minerals, and pollution by ③ nitrogen and ④ organics in response to human activities. Pollution risk assessment showed that water sources were at low risk during both wet and dry seasons. However, the south area of the water source area showed high groundwater pollution risk during the wet season, while other high-risk areas were mainly distributed around the riverbanks and densely populated areas during the dry season. These findings indicate that human activities greatly influence groundwater pollution risk during the dry season; accordingly, this season should be the focus of integrated water quality management and control for the water source area.

The safety of catheter ablation for premature ventricular contractions in patients without structural heart disease.

BACKGROUND: Patients with frequent premature ventricular contractions (PVCs) are often symptomatic. Catheter ablation was usually indicated to eliminate symptoms in patients with PVCs-induced cardiomyopathy. Currently, PVCs-ablation is also applied for patients with PVCs and no structural heart diseases (SHD); however, the safety and efficacy of ablation in these patients remains unclear. METHODS: In this retrospective study, data from patients who underwent ablation for PVCs from January 2010 to December 2016 at our hospital was retrieved. Predictors of complications and acute procedural success were evaluated. RESULTS: A total of 1231 patients (mean age 47.8 ± 16.8 years, 59% female) were included. The overall complication rate was 2.7%, and the most common complication was hydropericardium. Two ablation-related mortalities occurred. One patient died of coronary artery injury during the procedure and the other died from infectious endocarditis. Location (left ventricle and epicardium) was the main predictor of complications, with right ventricular outflow tract (RVOT) predicting fewer complications. The acute procedural success rate was 94.1% in all patients. The main predictor of acute procedural success was RVOT origin, while an epicardial origin was a predictor of procedural failure. CONCLUSION: Locations of left ventricle and epicardium were predictors of procedural complications for patients with PVCs. Therefore, ablation is not recommended in these patients. For other origins of PVCs, particularly RVOT origin, ablation is a safety and effective treatment.

Spectroscopic characterization of DOM and the nitrogen removal mechanism during wastewater reclamation plant.

The performance of the Sha-he wastewater reclamation plant was evaluated in this study. To remove residual nitrogen after Anaerobic-Anoxic-Oxic (A2O) treatment, three multistage Anoxic-Oxic (A/O) were added to investigate the nitrogen removal efficiency and its mechanism. In addition, the constituents and evolution of dissolved organic matter (DOM) during wastewater reclamation was also investigated using a method combining fluorescence spectroscopy with fluorescence regional integration (FRI). The results suggested that multistage A/O treatment can effectively improve the nitrogen removal ability under low concentrations of carbon sources. The total nitrogen (TN) exhibits significantly positive correlation with fulvic acid-like materials and humic acid-like materials. The correlation coefficient for TN and fulvic acid-like substances (R2 = 0.810, P < 0.01) removal was greater than that of humic acid-like substances (R2 = 0.636, P < 0.05). The results indicate that nitrogen removal may be achieved with the fulvic-like and humic-like substances, and the removal effects were higher by fulvic acid-like substances than humic-like substances, mostly due to that the latter were relatively more difficult to be utilized as carbon source during the nitrogen removal process. The effluent water quality of biological treatment reached the first grade A standard of "Cities sewage treatment plant pollutant discharge standard" (GB18918-2002). In addition, the effluent from the membrane bioreactor reached the "Standards of reclaimed water quality" (SL368-2006).

Neutral merocyanine dyes: for in vivo NIR fluorescence imaging of amyloid-ß plaques.

Two neutral merocyanine-based near-infrared fluorescent probes were for the first time developed through rational engineering of the classical cationic cyanine scaffold IR-780 for in vivo imaging of amyloid-ß plaques. In vivo NIRF imaging revealed that the probe could penetrate the blood-brain barrier and efficiently differentiate the living transgenic and wild-type mice.

Effects of ZNF139 on gastric cancer cells and mice with gastric tumors.

Gastric cancer (GC) is the fourth most common type of cancer, worldwide. The major molecular factors associated with the pathogenesis of GC remain unclear. Previous studies found that zinc finger proteins are highly abundant in human eukaryotes and tissues, and play an important role in maintaining normal cellular functions and have an association with tumor initiation. In the current study, interference technology was used to silence the ZNF139 protein, a zinc finger protein that was previously found to be closely associated with GC. The results showed that cell viability and proliferation were inhibited in the Znf139-knockdown of GC cells. Additional study found that the expression levels of B cell lymphoma-2 (Bcl-2) and survivin messenger RNAs and proteins were downregulated in Znf139-silenced cells, indicating that cells expression Znf139 are able to induce the growth of tumor cells by mediating the apoptosis pathway. Further in vivo experiments showed that Znf139 knockdown downregulated the expression levels of Bcl-2 and survivin in mice. Overall, the in vitro and in vivo findings of the present study indicate that ZNF139 may be actively involved in the progression of GC.

[Responses of ecosystem services value to land use change in national nature reserves in Xinjiang, China].

With GIS and RS technology, characteristics of land use change and ecosystem services value of different years in six national nature reserves in Xinjiang, China were analyzed with remote sensing image of the year 2000-2010. Results showed that the area of water body and grassland decreased while the area of forest, farmland, wetland, unused land and construction land increased in 2000-2010. Variation rate of land use change in 2000-2005 was faster, as 2.4-6.3 times as that in 2005-2010. The total ecosystem services value mostly consisted of that of water body, grassland and forest, accounting for 93% approximately. During the study, the values of all kinds of the ecosystem services increased except for grassland and water body, the total ecosystem services value increased firstly and then decreased, and overall emerged as a reducing trend with the rate of 1.2%. In the process of the development of the west regions, it is necessary to pay more attention to the protection of natural resources and ecosystem restoration, so as to achieve sustainable development of resources, environment and social economy in the western regions.

Association between Ras association domain family 1A promoter methylation and esophageal squamous cell carcinoma: a meta-analysis.

RASSF1A has been reported to be a candidate tumor suppressor in esophageal squamous cell carcinoma (ESCC). However, the association between RASSF1A promoter methylation and ESCC remains unclear. Eligible studies were identified through searching PubMed, Medline, Web of Science, and the China National Knowledge Infrastucture database. Studies were pooled and odds ratios (ORs) with corresponding confidence intervals (CIs) were calculated. Funnel plots were also performed to evaluate publication bias. Twelve studies involving 859 cases and 675 controls were included in this meta-analysis. A significant association was observed between RASSF1A methylation and ESCC overall (OR = 11.7, 95% CI: 6.59-20.9, z=8.36, P<0.00001). Subgroup analysis showed that the OR for heterogeneous tissues was 5.35 (95% CI = 2.95-9.71) while for autologous tissues it was 16.0 (8.31-30.96). For patient sample size, the OR for the <50 subgroup was 9.92 (95% CI = 2.88-34.2) and for the 50 case group was 13.1 (95% CI = 6.59-25.91). The OR for a relationship between RASSF1A methylation and TNM stages was 0.27 (95% CI=0.10-0.77), whereas there were no significant differences in RASSF1A methylation in relation to gender and differentiation among ESCC cases. This meta-analysis suggests a significant association between RASSF1A methylation and ESCC.

Source apportionment of sediment PAHs in the Pearl River Delta region (China) using nonnegative matrix factorization analysis with effective weighted variance solution.

Considering the advantages and limitations of a single receptor model, in this study, a combined technique of nonnegative matrix factorization analysis with effective weighted variance solution (NMF-EWV) was proposed for source apportionment. Utilizing NMF, major linear independent factor loadings with nonnegative elements were extracted to identify potential pollution sources. Then, these physical reasonable factor loadings were regarded as source profiles to apportion contributions using effective weighted variance solutions. Evaluation results indicated that the NMF-EWV method reproduced the source profiles well, and got a reasonable apportionment results for the synthetic dataset. The methodology of the NMF-EWV was also applied to recognize sources and apportion the contributions of polycyclic aromatic hydrocarbons (PAHs) collected from freshwater and marine sediments in the Pearl River Delta (PRD) region which is one of the most industrialized and economically significant regions of China. Apportionment results showed that traffic tunnel made the largest contribution (46.49%) for the freshwater PAH sediments in the PRD, followed by coal residential source (29.61%), power plant (13.45%) and gasoline engine (10.45%). For the marine sediments, traffic tunnel was also apportioned as the largest source (57.61%), followed by power plant (22.86%), gasoline engine (17.71%) and coal residential source (1.82%). Traffic-related sources were the predominant reasons for PAH pollution in that region.

Source apportionment for sediment PAHs from the Daliao River (China) using an extended fit measurement mode of chemical mass balance model.

To minimize the selection uncertainties of source profiles and obtain the higher model performance, an extended fit measurement mode for chemical mass balance model (EFMM-CMB) was proposed and applied to estimate source contributions for sediment PAHs from the Daliao River around which is the important industrial bases with oil, chemical and steel factories in the northeast part of China. Based on least squares fitting method, EFMM-CMB initially calculated the fit measurement index to every one of the possible combinations that can be made from the source profiles. Any successful applications of the fitting method were ranked according to performance measures, and then determined by maximizing an overall fitting index for a unique solution. Apportionment results from two case scenarios showed that the values of performance measures for EFMM-CMB were better to that for CMB8.2 results. With species selection of high molecular weight PAHs, power plant (45.75%), biomass burning (29.34%) and traffic tunnel (10.59%) were identified as the major sources of sediment PAHs from the Daliao River region.

Gene silencing of ß-catenin by RNAi inhibits proliferation of human esophageal cancer cells by inducing G0/G1 cell cycle arrest.

OBJECTIVES: The aim of the present study was to explore mechanisms underlying the effects of down-regulating ß-catenin expression on esophageal carcinoma (EC) cells. METHODS: Cell cycle distribution and apoptosis were determined using flow cytometry and annexin V apoptosis assay, respectively. Transmission electron microscopy (TEM) was used to examine changes in ultrastructure, while expression of cyclin D1 protein and mRNA was detected by western blot and real-time PCR. Proliferating cell nuclear antigen (PCNA) and extracellular signal-regulated kinase (ERK) 1/2 were evaluated by Western blot analysis. PCNA labeling index (LI) was determined by immunocytochemistry. RESULTS: Compared with pGen-3-con transfected and Eca-109 cells, the percentage of G0/G1-phase pGen-3-CTNNB1 transfected cells was obviously increased (P<0.05), with no significant difference among the three groups with regard to apoptosis (P>0.05). pGen-3-CTNNB1 transfected cells exhibited obvious decrease in cyclin D1 mRNA and protein expression (P<0.05) and the ultrastructure of Eca-109 cells underwent a significant change after being transfected with pGen-3-CTNNB1, suggesting that down-regulating ß-catenin expression can promote the differentiation and maturation. The expression of PCNA and the ERKI/2 phosphorylation state were also down-regulated in pGen-3-CTNNB1 transfected cells (P<0.05). At the same time, the PCNA labeling index was decreased accordingly (P<0.05). CONCLUSION: Inhibition of EC Eca-109 cellproliferation by down-regulating ß-catenin expression could improve cell ultrastructure by mediating blockade in G0/G1 through inhibiting cyclin D1, PCNA and the MAPK pathway (p-ERK1/2).

[Mutation analysis of the HBV reverse transcriptase in nucleos(t)ide-treated patients with chronic HBV infection].

OBJECTIVE: To characterize genotypic resistance within HBV RT region in chronic hepatitis B (CHB) patients with nucleos(t)ide analogue (NA) treatment. METHODS: Serum samples of 229 CHB patients with NA treatment were obtained. Full-length HBV RT sequences were amplified, sequenced and analyzed, on the following NA resistant (NAr) mutations belonging to different NAr pathways. RESULTS: Among 229 HBV isolates, 14.41% (33/229) and 85.59% (196/229) were genotype B and C, respectively; and the patients with HBV genotype C may be more susceptible to develope resistant mutations than patients with HBV genotype B(chi2 = 2.95, P < 0.05). NAr mutations were detected in 63 CHB patients. Mutations were not found at rtI169, rtT184, rtA194 or rtS202. RtM204 mutations were detected at the highest frequency among 63 mutants (40/63, 63.49%) and found to display 11 combination mutation patterns, in which rtM204I were associated with rtL80I/V and rtL180M, and rtM204V were associated with rtL1l80M, respectively. Conclusions There are complicated mutation patterns in the HBV RT region for chronic hepatitis B (CHB) patients with nucleos(t)ide analogue (NA) treatment. RtM204V/I mutation was the highest.