Jun Cheng, Min Li, Ping Gao, Jin-ling Dong and Qi Wang
Liver steatosis is a pathological hallmark in patients with chronic hepatitis C (CHC). Increased lipid uptake, decreased lipid secretion, increased lipid synthesis and decreased lipid degradation are all involved in pathogenesis of steatosis induced by hepatitic C virus (HCV) infection. Level of low density lipoprotein receptor (LDL-R) and activity of peroxisome proliferator-activated receptor (PPAR) α is related to liver uptake of lipid from circulation, and affected by HCV. Secretion via microsomal triglyceride transfer protein (MTTP), and formation of very low density lipoprotein (VLDL) have been hampered by HCV infection. Up-regulation of lipid synthesis related genes, such as sterol regulatory element-binding protein (SREBP)-1, SREBP-2, SREBP-1c, fatty acid synthase (FASN), HMG CoA reductase (HMGCR), liver X receptor (LXR), acetyl-CoA carboxylase 1 (ACC1), hepatic CB (1) receptors, retinoid X receptor (RXR) α, were the main stay of liver steatosis pathogenesis. Degradation of lipid in liver is decreased in patients with CHC. There is strong evidence that heterogeneity of HCV core genes of different genotypes affect their effects of liver steatosis induction. A mechanism in which steatosis is involved in HCV life cycle is emerging.
Tie-long Zheng, Ping-an Wang, Dian-li Wang, Cheng-fu Sun, Yuan Hong, Qi Wang and Jun Cheng
Objective To observe the biological function of human 3-hydroxyisobutyrate dehydrogenase (HIBADH).
Methods Human 3-hydroxyisobutyrate dehydrogenase (HIBADH, 3-hydroxy-2-methyl propanoate: NAD+ oxidoreductase) recombinant protein was expressed in E. coli BL21, and purified by Ni+ column. The special antisera was obtained from rabbits immunized by this purified antigen. On the distribution of HIBADH, it was found that HIBADH over-expressed in the injured liver cells when serious hepatitis occurred. The phenomenon was confirmed in the animal models of SD rats with acute liver cell injury induced by CCl4, but this phenomenon did not exist in the models induced by endotoxin combined with galactosamine. Further more, HIBADH’s overexpression in liver cells will induce cell necrosis through the pathway of oxidative stress.
Results When the liver cells injured by drug or other chemical materials, HIBADH will be compensationally over-expressed for the deficiency of energy, so liver cells can make enough ATP through brand-chain amino acid catabolism. However, the overexpression of HIBADH will be harmful for liver cells through the product of much more active oxygens which will induce the cell necrosis.
Conclusions HIBADH over-expression is a signal of the liver cell metabolism injury, and it can aggravate the liver cell injury through oxidative stress.
Yi-sheng Zhong, Min-hong Xiang, Wen Ye, Ping Huang, Yu Cheng and You-qin Jiang
Background: Retinal ganglion cells (RGCs) are protected in rats with acute elevated intraocular pressure (IOP) by Erigeron breviscapus (vant.) hand-mazz (EBHM). However, it is unclear whether EBHM has neuroprotective effect on RGCs in animal with chronic elevated IOP.
Objective: Investigate the protective effect of EBHM extract on RGCs in rabbits with chronic elevated IOP.
Methods: Unilateral chronic elevated IOP was produced in rabbits by repeated injection of 2% methylcellulose into the anterior chamber. Secondary degeneration was measured with and without EBHM extract treatment for 60 days. At 60 days, the cells density of the RGCs layer, the thickness of retinal nerve fiber layer (RNFL), and the optic nerve axons were observed and analyzed using an image analysis system. The ultrastructural changes of RGCs and optic nerve axons were observed using transmission electron microscopy.
Results: Compared with their contralateral control eyes with normal IOP, in the retinas of 3-4 mm from the optic disc, the cells density of the RGCs layer in the eyes with chronic elevated IOP was 23.2±6.5 cells (n = 6) and 36.0±8.9 cells (n = 10) per three 400x fields at 60 days in untreated and EBHM-treated group, respectively. The RNFL thickness in eyes with chronic elevated IOP was 3.4±0.4 μm (n = 6) and 5.0±1.0 μm (n = 10) at 60 days in untreated and EBHM-treated group, respectively. The axons number per 15057.8 μm2 in eyes with chronic elevated IOP was 370.4±41.0 (n = 6) and 439.0±50.8 (n = 10) at 60 days in untreated and EBHM-treated group, respectively. The number of the organelles in RGCs plasm appeared decreased and mitochondrion vacuolated in the elevated IOP eyes of EBHM-treated group, while some dispersive mitochondrion and rough surfaced endoplasmic reticulum and ribosome still existed in the RGCs plasm. The myelin sheath plates condensed and degenerated, and the microfilaments and microtubules decreased or disappeared in the elevated IOP eyes, but the axons degeneration in the chronic elevated IOP with EBHM treatment was less than that in the chronic elevated IOP without treatment.
Conclusion: EBHM extract provided a neuroprotective effect on retinal ganglion cells in rabbits with chronic elevated IOP.
Xin Li, Ping Liang, Jie Yu, Xiao-Ling Yu, Fang-Yi Liu, Zhi-Gang Cheng and Zhi-Yu Han
Background. The aim of the study was to evaluate the efficiency and feasibility of contrast-enhanced ultrasound (CEUS) with Sonovue in assessing of renal cell carcinomas (RCCs) following ultrasound (US)-guided percutaneous microwave ablation (MWA).
Patients and methods. Seventy-nine patients (60 males and 19 females) with 83 lesions (mean size 3.2±1.6 cm) were treated by US-guided percutaneous MWA. The CEUS results of the third day after the ablation were compared with the synchronous contrast-enhanced computed tomography (CT)/magnetic resonance imaging (MRI) results and biopsy pathological results. The follow-up was performed by CEUS and CT/MRI after 1, 3, 6 months and every 6 months subsequently. The combination of clinical follow-up results and CT/MRI imaging findings was the reference standard of CEUS results for evaluating the therapeutic effect. The identification of residual or recurrence tumour was assessed by two blinded radiologists.
Results. On the third day after MWA, CEUS showed 68 of 83 lesions (68/83, 81.9%) successfully ablated and 15 of 83 (18.1%) with residual tumours. Among residual tumours, 13 (86.7%) were confirmed by contrast-enhanced CT/MRI findings and biopsy results. The sensitivity, specificity, accuracy, positive and negative predictive value of CEUS evaluating the short-term MWA effectiveness were 100%, 97.1%, 97.6%, 86.7% and 100%, respectively. During the six years follow-up (median 26 months), the CEUS showed recurrence in 7 patients, and six of them achieved consistent results on CEUS and CT/MRI imaging. The sensitivity, specificity, accuracy, positive and negative predictive value for CEUS evaluating long-term MWA effectiveness were 85.7%, 98.7%, 97.6%, 85.7% and 98.7%, respectively.
Conclusions. The post-procedural CEUS demonstrated as an effective and feasible method in evaluating a therapeutic effect of RCCs following MWA.
Ming-hui Li, Yao Xie, Yao Lu, Guo-hua Qiu, Lu Zhang, Ge Shen, Li-wei Zhuang, Ju-long Hu, Jian-ping Dong, Cai-qin Mu, Lei-ping Hu, Li-jun Chen, Xing-hong Li, Min Yang, Yun-zhong Wu, Hui Zhao, Shu-jing Song, Jun Cheng and Dao-zhen Xu
Objective To investigate the effects of individualised treatment with peginterferon alpha-2a (40 kD) plus ribavirin in Chinese patients with CHC.
Methods Total of 297 consecutive Chinese patients were enrolled, including 250 naïve cases and 47 cases who were previously treated. Treatment duration was determined according to viral genotypes, prior treatment history and viral responses at week 4, 12 and 24.
Results Totally, 235 patients (79.1%) completed treatment and 186 (87.3%) achieved SVR. And 219 out of 289 (75.8%) patients achieved HCV RNA negative at week 4 (RVR) and 259 of 276 (93.8%) at week 12. Among the 164 patients with RVR who completed follow-up, 158 (96.3%) achieved SVR. Patients with RVR had lower baseline viral loads than patients without RVR (P = 0.034). The positive predictive value (PPV) of RVR for SVR was 90.7% (OR 2.10 vs. non-RVR, 95% CI: 0.50 - 8.7). Similar outcomes were observed among patients with HCV undetectable at week 12.
Conclusions Complete viral suppression by week 4 is associated with a high rate of treatment success in treatment naïve and experienced patients receiving individualized CHC therapy.
Wen Xie, Hong Zhao, Yu Chen, Qin Zhang, Wei Lu, Wei Liu, Ai-rong Hu, Han-wei Li, Ping Feng, Ming-sheng Chen, Cun-jin Mei, Xiao-lin Guo, Xiao-hu Zhao, Jiang-bin Wang, Zheng-qin Fan, Jian-he Gan, Qing Xie and Jun Cheng
Obejective Ademetionine 1,4-butanedisulfonate [S-adenosyl-L-methionine (SAMe)/Transmetil®, Abbott] has been available in China for more than 15 years, and it has been shown to reduce serum bilirubin and transaminase levels in viral hepatitis (VH) patients. However, no large-scale studies have focused on the impact of SAMe treatment regimen on reducing the serum total bilirubin (TBil) in VH patients with intrahepatic cholestasis (IHC). The primary purpose of this study was to evaluate the effectiveness of intravenous SAMe (Transmetil®) treatment in reducing the serum TBil by 50%.
Methods This retrospective, multi-center, cross-sectional medical record review involved patients aged ≥18 years. Records of 1 280 hospitalized VH patients at 16 sites diagnosed with IHC who had received intravenous SAMe 1 000 mg or 2 000 mg q.d. for at least 7 days from January 1, 2006 to June 30, 2009, were screened and 905 records were randomly selected.
Results The safety set (SS) included 834 patients and the full analysis set 826 patients. TBil levels after 14 days injection treatment were available for 763 patients. TBil decreased ≥ 50% versus baseline after 14 days treatment in 288 (37.7%) patients (95% CI 34.3%, 41.2%). Twenty-nine non-serious adverse events (non-SAEs) were reported in 19 (2.3%) patients, and 29 SAEs were reported in 10 patients (1.2%). All adverse events (AEs) were considered unrelated to the study drug.
Conclusions This retrospective study shows that intravenous SAMe administration in VH patients with IHC is associated with significant reduction of TBil levels in more than 30% of patients 14 days after treatment initiation.