Association of polymorphism of tumor necrosis factor-alpha gene promoter region with outcome of hepatitis B virus infection

AIM: To determine whether -238G/A and -857C/T polymorphisms of tumor necrosis factor-alpha (TNF-α), gene promoter and hepatitis B (HB) viral genotypes were associated with outcomes of HBV infection.METHODS: A total of 244 HBV self-limited infected subjects, 208 asymptomatic carriers, and 443 chronic HB patients were recruited to conduct a case-control study.TNF-α -238G/A and -857C/T gene promoter polymorphisms were examined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and HBV genotypes were examined by nested PCR.RESULTS: The positive rate of HBV DNA in asymptomatic carrier group and chronic HB group was 46.6% and 49.9%,respectively. HBV genotype proportion among the asymptomatic carriers was 2.1% for genotype A, 25.8% for genotype B, 68.0% for genotype C, and 4.1% for genotype B+C mixed infection, and 0.9% for genotype A,21.7% for genotype B, 71.5% for genotype C, 5.9% for genotype B+C mixed infection in chronic HB group. There was no significant difference in genotype distribution between the asymptomatic carrier group and chronic HB group (x2 = 1.66, P = 0.647). The frequency of -238GG genotype in self-limited group was 95.1%, significantly higher than 90.7% in chronic HB group and 89.0% in asymptomatic carrier group (P = 0.041 and P = 0.016,respectively).The frequency of TNF-α-857 CC in chronic HB group was 79.7%, significantly higher than 64.4% in asymptomatic carrier group and 70.9% in self-limited group (P＜0.001 and P = 0.023, respectively). A multiple logistic regression analysis revealed that TNF-α-238GA and -857CC were independently associated with chronic HB after gender and age were adjusted.CONCLUSION: TNF-α promoter variants are likely to play a substantial role in the outcome of HBV infection.

Effect of NDC80 in human hepatocellular carcinoma

AIM To investigate the role of nuclear division cycle(NDC)80in human hepatocellular carcinogenesis.METHODS NDC80 gene expression was analyzed by real-time reverse transcription polymerase chain reaction in 47paired hepatocellular carcinoma(HCC)and adjacent tissues.The HCC cell line SMMC-7721 was transfected with lentivirus to silence endogenous NDC80 gene expression,which was confirmed by real-time polymerase chain reaction and western blotting.The effects of NDC80silencing on SMMC-7721 cell proliferation were evaluated by Cellomics Array Scan VTI imaging.Cell cycle analysis and apoptosis were detected with flow cytometry.Colony formation was assessed by fluorescence microscopy.RESULTS NDC80 expression levels in HCC tissues were significantly higher than those in the adjacent tissues.Functional studies demonstrated that NDC80 silencing significantly reduced SMMC-7721 cell proliferation and colony formation.Knockdown of NDC80 resulted in increased apoptosis and cell cycle arrest at S-phase.NDC80 contributed to HCC progression by reducing apoptosis and overcoming cell cycle arrest. CONCLUSION Elevated expression of NDC80 may play a role in promoting the development of HCC.

Association of-238G/A and -857C/T Polymorphisms of Tumor Necrosis Factor-Alpha Gene Promoter Region With Outcomes of Hepatitis B Virus Infection

Objectives To determine whether -238G/A and -857C/T polymorphisms of tumor necrosis factor-alpha （TNF-o0 gene promoter were associated with outcomes of hepatitis B virus infection. Methods A total of 246 HBV self-limited infected subjects and 443 chronic hepatitis B （HB） patients were recruited in this case-control study. TNF-α-238G/A and -857C/T gene promoter polymorphisms were examined by polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP）. Results The frequency of TNF-α-238 GG （90.7%） in chronic HB group was significantly lower than that （95.1%） in self-limited group （P=0.041）. The frequency of TNF-oc-857 CC （79.7%） in chronic HB patients was significantly higher than that （70.9%） in self-limited infected subjects （P=0.021）. Multiple logistic regression analysis revealed that both TNF-oc-238GA and -857CC were independently associated with chronic HB. Conclusions TNF-α promoter variants are likely to play a substantial role in influencing the outcomes of HBV infection.

Detection and Location of a Target in Layered Media by Snapshot Time Reversal and Reverse Time Migration Mixed Method

A target in layered medium can be located by the ridge-like distribution time reversal and reverse time migration(TR-RTM) mixed method. However, this method cannot distinguish between acoustic field distributions of the interface and target for the wider acoustic pulse signals, which may result in inaccurate location of the target. A snapshot TR-RTM mixed method is proposed to solve this problem. The principle of snapshot TR-RTM mixed method is first given. Experiments are then carried out, and a mountain-like acoustic field distribution is obtained by processing experimental data. The results show that the location of the peak is that of the target, and the ratio of the scattered signal and interface reflection signal(signal-to-interference ratio) is improved by about four times after processing. Furthermore, this method can effectively suppress the interface reflection signal and enhance the target scattering signal. Therefore, it can achieve effective detection and location of a target in a layered medium.

Serum Soluble Vascular Endothelial Growth Factor Receptor 1 as a Potential Biomarker of Hepatopulmonary Syndrome

Background and Aims:The results of basic research implicate the vascular endothelial growth factor(VEGF)family as a potential target of hepatopulmonary syndrome(HPS).However,the negative results of anti-angiogenetic therapy in clinical studies have highlighted the need for markers for HPS.Therefore,we aimed to determine whether VEGF family members and their receptors can be potential biomarkers for HPS through clinical and experimental studies.Methods:Clinically,patients with chronic liver disease from two medical centers were enrolled and examined for HPS.Patients were divided into HPS,intrapulmonary vascular dilation[positive contrast-enhanced echocardiography(CEE)and normal oxygenation]and CEE-negative groups.Baseline information and perioperative clinical data were compared between HPS and non-HPS patients.Serum levels of VEGF family members and their receptors were measured.In parallel,HPS rats were established by common bile duct ligation.Liver,lung and serum samples were collected for the evaluation of pathophysiologic changes,as well as the expression levels of the above factors.Results:In HPS rats,all VEGF family members and their receptors underwent significant changes;however,only soluble VEGFR1(sFlt-1)and the sFlt-1/placental growth factor(PLGF)ratio were changed in almost the same manner as those in HPS patients.Furthermore,through feature selection and internal and external validation,sFlt-1 and the sFlt-1/PLGF ratio were identified as the most important variables to distinguish HPS from non-HPS patients.Conclusions:Our results from animal and human studies indicate that sFlt-1 and the sFlt-1/PLGF ratio in serum are potential markers for HPS.

Detection and Location of a Target in Layered Media without Prior Knowledge of Medium Parameters

Without prior knowledge of medium parameters,a method is proposed to detect and locate a target in layered media.Experiments were carried out for liquid/liquid and solid/liquid layered media,and the location of a target in them was obtained using three methods combined,i.e.,the least-square method,the method of finding minimum dispersal degree of target distribution,and the snapshot time reversal and reverse time migration mixed method.The medium parameters,i.e.,the acoustic velocities of upper and lower media as well as the thickness of the upper medium,were inversed simultaneously.The results show that the position of target is consistent with its actual position.Thus,the detection and location of a target in layered media are achieved without prior knowledge of medium parameters,and it overcomes the difficulty that the common time reversal method only detects the target,but cannot locate it.

Relationships of body composition and adipocytokines with outcomes in metastatic castration-resistant prostate cancer patients receiving docetaxel chemotherapy

We evaluated the relationships of body composition and serum adipocytokine levels with progression-free survival(PFS)and overall survival(OS)in metastatic castration-resistant prostate cancer(mCRPC)patients receiving docetaxel.The medical records of mCRPC patients who received docetaxel between January 2011 and December 2015 at Fudan University Shanghai Cancer Center(Shanghai,China)were reviewed.The following body composition parameters were calculated using computed tomography:skeletal muscle index(SMI),visceral adipose tissue index(VATI),and subcutaneous adipose tissue index(SATI).Pretreatment serum adipocytokine levels,including interleukin 6,insulin,leptin,monocyte chemoattractant protein-1,adiponectin,and resistin,were measured using the multiplex bead-based immunoassays.Cox regression and Kaplan–Meier methods were used for survival analyses.Of the 453 mCRPC patients initially identified,105 were included in the analysis.High VATI group patients had longer PFS(median,10 months vs 7 months,P=0.008)and OS(median,24 months vs 15 months,P=0.017),compared with low VATI group patients.SMI and SATI were not significantly associated with PFS or OS.Of the six detected adipocytokines,only leptin was associated with mCRPC prognosis.High leptin group patients had shorter PFS(median,7 months vs 12 months,P=0.0018)and OS(median,17 months vs 22 months,P=0.042),compared with low leptin group patients.Multivariate analysis showed that a high VATI was an independent protective factor for PFS and OS,while a high leptin level was an independent risk factor for PFS and OS.Therefore,VATI and serum leptin levels could provide important information concerning mCRPC prognosis.

Facile synthesis of suvorexant,an orexin receptor antagonist,via a chiral diazepane intermediate

A facile synthesis of suvorexant, an orexin receptor antagonist, is described. The key intermediate 6 was prepared from R-3-aminobutyric acid through protection, condensation, deprotection, cyclization, and hydrogenation steps. The title product was obtained with a total yield of 31% （〉99% ee） after eight linear steps using commercially available raw materials.

High Q,high frequency,high overtone bulk acoustic resonator with ZnO films

Bulk acoustic wave resonators with piezoelectric films have been widely explored for the small size and high quality factor(Q) at GHz.This paper describes a high overtone bulk acoustic resonator(HBAR) based on Al/ZnO/Al sandwich layers and c-axis sapphire substrate.ZnO film with high quality c-axis orientation has been obtained using DC magnetron sputtering.The fabricated HBAR presents high Q at the multiple resonances from a 0.5-4.0 GHz wide band with a total size(including the contact pads) of 0.6 mm×0.3 mm×0.4 mm.The device exhibits the best acoustic coupling at around 2.4 GHz,which agrees with the simulation results based on the one-dimensional Mason equivalent circuit model.The HBAR also demonstrates Q values of 30 000,25 000,and 6500 at 1.49,2.43,and 3.40 GHz,respectively.It is indicated that the HBAR has potential applications for the low phase noise high frequency oscillator or microwave signal source.