ABSTRACT
Chronic hepatitis B virus (HBV) infection is a primary cause for liver cancer. And the main challenge of curing hepatitis B is the elimination of the stable covalently closed circular DNA (cccDNA) of the viral genome. The formation of HBV cccDNA requires the filling of single-stranded region and the ligation of nicks in relaxed circular DNA (rcDNA) strands. Previously, our group reported that proliferating cell nuclear antigen (PCNA) was involved in the formation of HBV cccDNA. However, the underlying mechanism of the conversion of HBV rcDNA to cccDNA is poorly understood. In the present study, we aim to explore the mechanism by which PCNA contributes to the conversion of HBV rcDNA to cccDNA. Our data showed that PCNA was involved in the process of HBV rcDNA repair. The knockout of PCNA by the CRISPR/Cas9 system remarkably blocked the conversion of HBV rcDNA to cccDNA, while the ectopic expression of PCNA could effectively rescue the event (P<0. 001). Knockout of PCNA significantly slowed down the conversion kinetics of HBV rcDNA to cccDNA (P<0. 01). Mechanically, the DNA binding domain of PCNA was required for the process of HBV rcDNA repair to cccDNA (P<0. 01). Thus, we conclude that PCNA confers the conversion of HBV rcDNA to cccDNA by its DNA binding domain. Clinically, PCNA might serve as a novel target for antiviral therapy.
ABSTRACT
<p><b>OBJECTIVE</b>To evaluate safety and efficacy of preoperative administration of enteral nutrition support in gastric cancer patients at risk of malnutrition.</p><p><b>METHODS</b>A single center randomized controlled clinical trial was performed in 60 gastric cancer patients in West China Hospital from May to October 2012. Thirty patients were given enteral nutrition support(Ensure(R)) manufactured by Abbott Laboratories for ten consecutive days before surgical operation in the treatment group, and 30 patients were given an isocaloric and isonitrogenous homogenized diet in the control group for 10 days as well. The laboratory parameters of nutritional status and hepatorenal function were observed and compared between the two groups on admission, preoperative day 1 and postoperative day 3, respectively. Clinical observations, such as nausea and vomiting, were carried out until patients were discharged.</p><p><b>RESULTS</b>Before the intervention, there were no significant differences in the baseline characteristics between the two groups. The levels of serum albumin [(33.9±5.6) g/L vs. (31.0±5.3) g/L, P<0.05], and hemoglobin[(103.4±7.7) g/L vs.(96.6±10.5) g/L, P<0.01] were significantly improved in the treatment group on postoperative day 3. However, the levels of body mass index, lymphocyte count, liver and renal function, serum glucose, sodium, and potassium were not significantly different between the two groups(all P>0.05). Moreover, two patients with nausea and one with vomiting in each group were found. In clinical observation period, no severe treatment-related adverse event were observed.</p><p><b>CONCLUSION</b>The enteral supplement with Ensure(R) in gastric cancer patients at risk of malnutrition during preoperative period is effective and safe, which is superior to homogenized diet and an appropriate choice for gastric cancer patients with nutritional risk.</p>