Clonorchis sinensis Co-infection Could Affect the Disease State and Treatment Response of HBV Patients.

Clonorchis sinensis (C. sinensis) is considered to be an important parasitic zoonosis because it infects approximately 35 million people, while approximately 15 million were distributed in China. Hepatitis B virus (HBV) infection is a major public health issue. Two types of pathogens have the potential to cause human liver disease and eventually hepatocellular carcinoma. Concurrent infection with HBV and C. sinensis is often observed in some areas where C. sinensis is endemic. However, whether C. sinensis could impact HBV infection or vice versa remains unknown.Co-infection with C. sinensis and HBV develops predominantly in males. Co-infected C. sinensis and HBV patients presented weaker liver function and higher HBV DNA titers. Combination treatment with antiviral and anti-C. sinensis drugs in co-infected patients could contribute to a reduction in viral load and help with liver function recovery. Excretory-secretory products (ESPs) may, in some ways, increase HBV viral replication in vitro. A mixture of ESP and HBV positive sera could induce peripheral blood mononuclear cells (PBMCs) to produce higher level of Th2 cytokines including IL-4, IL-6 and IL-10 compared to HBV alone, it seems that due to presence of ESP, the cytokine production shift towards Th2. C. sinensis/HBV co-infected patients showed higher serum IL-6 and IL-10 levels and lower serum IFN-γ levels.Patients with concomitant C. sinensis and HBV infection presented weaker liver function and higher HBV DNA copies. In co-infected patients, the efficacy of anti-viral treatment was better in patients who were prescribed with entecavir and praziquantel than entecavir alone. One possible reason for the weaker response to antiviral therapies in co-infected patients was the shift in cytokine production from Th1 to Th2 that may inhibit viral clearance. C. sinensis/HBV co-infection could exacerbate the imbalance of Th1/Th2 cytokine

Design and Implementation of Probe Driver Teleoperative Force Feedback System

The basic need of neurosurgery is to insert the probe into the key hole linearly for performing functional neurosurgery, trigeminal neuralgia surgery, biopsies, deep brain stimulation, and stereo-EEG. Recently, tele-robotic systems have been introduced to assist surgeon during invasive procedures to obtain desired results. In this paper, a linear probe driving tele-operative system with force feedback is proposed. The proposed system is highly accurate, stable, and safe and provides haptic transparency to the surgeon during its operation. The master slave architecture, control system and software application are designed to inject and eject probe driving trials. The experiments are performed on a piecewise linear Plasticine model. The accuracy, stability, repeatability of the system and haptic force feedback fidelity are discussed in the results.  DOI : http://dx.doi.org/10.11591/telkomnika.v12i6.527

Impact of anti-<i>C</i>. <i>sinensis</i> treatment on antiviral therapies in co-infected patients.

<p>Elevated liver transaminases (including AST, ALT and TB) and HBV DNA copies in the plasma of co-infected patients were detected after receiving combination treatment ETV and PZQ or not. (A) AST and (B) ALT and (C) TB were measured in plasma. (D) HBV DNA levels were measured by RT-PCR. Symbols show individual measurements within the patient groups, and the graphs show the means ± SD. Asterisks indicate statistically significant differences between NONPZQ and PZQ groups, as measured by paired, two-tailed Student's t-test (*<i>p</i> <0.05, ** <i>p</i> <0.01)</p

Detection of HBV-DNA copies in PBMC culture supernatant.

<p>HBV DNA was detected by FQ-PCR in the supernatant of the PBMCs incubated with mixtures of ESP and HBV positive serum or HBV positive serum only, or ESPs only. Medium alone served as a control. Asterisks indicate statistically significant differences between HBV positive sera only and mixtures of HBV positive sera and ESPs, as measured by paired, two-tailed Student's t-test (** <i>p</i> <0.01).</p

mRNA levels of Th1 and Th2 cytokines secreted by stimulated PBMCs.

<p>Total RNAs from PBMCs stimulated by mixtures of ESP and HBV positive serum, HBV positive serum only, or ESPs only were extracted for reverse transcription using cytokine gene-specific primers for Th1 cytokine (A) including IL-2 and IFN-γ and Th2 cytokines (B) including IL-4, IL-6 and IL-10 and human β-actin. The relative expression of each cytokine was detected by quantitative real-time RT-PCR and normalized relative to β-actin expression. Medium only served as a control. Data are shown as the mean ± SEM (*<i>p</i> <0.05, ** <i>p</i> <0.01, *** <i>p</i> <0.001).</p

Primer sequences for quantitative real-time PCR.

<p>Primer sequences for quantitative real-time PCR.</p

Clinical characteristics of the study cohort.

<p>Clinical characteristics of the study cohort.</p

Cathepsin-facilitated invasion of BMI1-high hepatocellular carcinoma cells drives bile duct tumor thrombi formation

Abstract Bile duct tumor thrombosis (BDTT) is a complication mostly observed in patients with advanced hepatocellular carcinoma (HCC), causing jaundice and associated with poor clinical outcome. However, its underlying molecular mechanism is unclear. Here, we develop spontaneous preclinical HCC animal models with BDTT to identify the role of BMI1 expressing tumor initiating cells (BMI1high TICs) in inducing BDTT. BMI1 overexpression transforms liver progenitor cells into BMI1high TICs, which possess strong tumorigenicity and increased trans-intrahepatic biliary epithelial migration ability by secreting lysosomal cathepsin B (CTSB). Orthotopic liver implantation of BMI1high TICs into mice generates tumors and triggers CTSB mediated bile duct invasion to form tumor thrombus, while CTSB inhibitor treatment prohibits BDTT and extends mouse survival. Clinically, the elevated serum CTSB level determines BDTT incidence in HCC patients. Mechanistically, BMI1 epigenetically up-regulates CTSB secretion in TICs by repressing miR-218-1-3p expression. These findings identify a potential diagnostic and therapeutic target for HCC patients with BDTT