Up to date, there are two types of drugs approved to treat hepatitis B: interferons and nucleos (t) ide analogues. However, the therapies are limited in the clinical context because of the negative side effects of interferon-α and the development of substantial viral resistance to nucleos (t) idic inhibitors. Therefore, new drugs with novel structures and mechanisms are needed. In this article, the drugs approved by FDA or the European Commission for treating chronic hepatitis B virus infection, as well as those under clinical trials, and several compounds in preclinical studies are reviewed. Additionally, some potential targets and strategies to combat chronic hepatitis B virus infection are discussed.

ObjectiveTo investigate the relationship between the polymorphisms of the promoter of a disintegrin and metalloproteinase 10(ADAM10) gene and sporadic Alzheimer's disease (SAD).Methods The promoter of ADAM10 gene in 10 controls and 10 SAD patients was sequenced.Three variations were found,then these variations in 298 SAD patients (SAD group) and 315 healthy controls (control group)were genotyped by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).ResultsThree polymorphisms were found in the promoter of ADAM10 gene: -279G/A (rs653765),- 630G/T( rs514049 ) and - 921GAGA/- ( rs33926666 ).For - 921GAGA/-,there were significant differences in genotype ( GAGA/GAGA:138 (46.3％ ),GAGA/-:155(52.0％),-/-:5(1.7％))and allele frequencies (GAGA:431 (73.6％),-:165 (27.7％) ) between SAD and control (genotype:x2 =34.130,P =0.000; allele:x2 =25.972,P =0.000). For - 279G/A,there were significant differences in genotype and allele frequencies between SAD and control in the subjects without ApoEε4 allele (genotype:x2 =8.734,P=0.013; allele:x2 =5.129,P=0.024). -279G and -921GAGA were relatively protective allele types for SAD,and they were not in linkage disequilibrium.ConclusionThe polymorphisms - 279G/A and - 921GAGA/- of ADAM10 are associated with SAD.Allele G or genotype G/G of -279G/A and the GAGA/GAGA genotype or the GAGA allele of -921GAGA/- might have a protective effect on SAD.

Rheumatoid arthritis(RA)is a serious autoimmune disease.Type Ⅱ collagen induced murine arthritis(CIA)displays polyarthritis and causes chronic and destructive joint damages,which is similar to RA in many aspects.CIA is widely used for the research on RA pathogenesis and drug discovery.In this review,we discussed the establishment of CIA and the key factors participating in the CIA pathogenesis.

Objective To determine the risk factors and clinical features of mild vascular cognitive impairment due to subcortical small vessel disease (mVCI-SSVD).Methods Detailed demographic data,vascular risk factors, past and present history were collected and carefully neurological examination, National Institutes of Health Stroke Scale (NIHSS), as well as Hachinski ischemic score (HIS) were performed on 56 mVCI-SSVD patients.Further, the demographic data and vascular risk factors of mVCI-SSVD patients were compared with those of 80 normal control subjects.Results Proportions of smoking (39.3% (22/56)), hypertension (67.9% (38/56)), and diabetes (25.0% (14/56)) were higher in the patient group than in the normal control group (21.3% (17/80) , 47.5% (39/80), 11.3% (9/80)).Odds ratio (2.32(95% CI 1.05-5.13),2.15 (95% CI 1.02-4.54),2.26(95% CI 0.86-5.92)) between the two groups was statistically significant (P value: 0.039, 0.045, 0.047).There was no difference in terms of hyperlipidemia and cardiac disease between groups.Fifty percent (28/56) mVCI-SSVD patients had a clear stroke history.Twenty-six point eight percent (15/56) patients developed the cognitive impairment with an acute onset.Neurological focal signs presented in 20 patients (35.7%).Twenty four (42.9%) patients with HIS ≤ 4 points.Thirty eight cases (67.9%) scored 0 on NIHSS.Conclusions Current study suggested that smoking, hypertension, and diabetes may be risk factors for mVCI-SSVD.While hyperlipidemia and cardiac disease do not increase the risk of mVCI-SSVD.Unlike mVCI caused by large vessel disease, about half mVCI-SSVD patients lack of stroke history.Most patients show a relatively insidious onset and free of significant neurological focal signs.

Objective To investigate the CT and MRI features of the autoimmune pancreatitis (ALP).Methods CT and MRI data of fourteen patients with AIP who were confirmed by histology and/or steroid therapy were retrospectively analyzed.Ten patients underwent CT examination, and seven patients underwent MRI, while three patients underwent both CT and MRI examinations.Results It was showed that diffuse (n =11 ) or local ( n = 3 ) enlargement of pancreas.CT features showed that the hypoattenuation pancreatic lesions on unenhanced CT (n = 10);segmental pancreatic duct could be seen in five patients;stenosis of common bile duct in the head of pancreas was observed in 5 patients;the capsule-like structure around lesions was seen in seven patients.Delayed homogeneous enhancement was showed on enhanced CT.MRI features included homogeneous ( n = 3) and heterogeneous ( n = 4) hyperintense on T1 WI with fat-suppression images and homogeneous ( n = 3 )and heterogeneous (n =4) hyperintense on T2WI with fat-suppression images.Pancreatic duct could be seen in four patients.MRCP showed pancreatic duct stenosis in the head of pancreas ( n = 1 ) and segmental pancreatic duct (n = 2).Stenosis of common bile duct in the head of pancreas was showed in 5 cases.The capsule-like structure around lesions was showed in seven patients.No pancreatic calcification was revealed, and no significant pancreatic duct dilation was detected ( ＞3 mm) in all 14 patients.Conclusions The CT and MRI manifestations of AIP had characteristic features such as sausage-like changes of the pancreas, capsule-like structure around the lesions, diffuse or local pancreatic duct stricture, and stenosis of common bile duct in the bead of pancreas.

Aim To investigate the effect of intrathecal injection of CCR2 antagonist on pain behaviours,spinal astrocytes activation in the spinal cord in a rat model of bone cancer pain. Methods Forty female SD rats weighing 150 ~180 g were randomly divided into five groups ( n=8 each ):(Ⅰ) sham group;(Ⅱ) sham +RS102895 group;(Ⅲ) bone cancer pain group;(Ⅳ) bone cancer pain + DMSO group;(Ⅴ) bone cancer pain+RS102895 group. Rats received i. t. injections of either RS102895 (3 g·L-1 ) 10 μl or 10%DMSO 10 μl at the time of 10-12 days after the operation. Bone cancer was induced by intra-tibial inoculation of 1 × 105 Walker 256 breast cancer cell. Mechanical hind paw withdrawal threshold test was performed one day before and at 3rd,6th,9th, 10th,11th and 12th days after surgery. Immunofluorescence was used to observe the activation of the spinal astrocytes. Results Compared with group Ⅰ, the rats in bone cancer pain group appeared obvious mechanical hyperalgesia (Ⅲ、Ⅳ、Ⅴ) ,the volume,shape and mean optical den-sity ( MOD) of spinal astrocytes could be seen obvious-ly increased,groupⅡhad no obvious statistical signifi-cance (P>0. 05). Compared with group Ⅳ ,i. t. in-jections of RS102895 increased the paw mechanical withdrawal threshold, suppressed the action of astro-cytes,reduced the MOD of spinal astrocytes. Conclu-sion CCR2 might participate in the formation of bone cancer pain via activating spinal astrocytes. CCR2 will be a potential target for the treatment of bone cancer pain.

AIM:To observe the effect of Jingzhui Wentong (JZWT) Capsule (Ramulus Cinnamomi,Radix et Rhizoma clematidis,Radix Puerariae Lobatae,Radix Dipsaci,etc.) on somesthetic evoked potential (SEP),behavior and pathology of rat's cervical radiculitis induced by formalin. METHODS:Experiments were carried out:(1) 60 SD rats were divided randomly into 6 groups:control,model and Jingfukang groups,the high,moderate and low dose groups of JZWT Capsule. Rats of these groups were given water,Jingfukang or JZWT Capsule respectively,and SEP was tested after operation and 14 days after drugs were given to rats. At the same time,the animal behavior was observed daily. (2) 144 SD rats were divided into the same groups and given the same drugs as before. The nerve roots were taken out for pathological observation after 4,7,14,and 21 days with drug administration. RESULTS:In each drug group,the normal SEP was obviously restored,symptoms of encroached nerve were notably lightened,inflammatory reaction and proliferation tissue of mimic cervical radiculitis were more obviously alleviated than that in the model group of rat. CONCLUSION:JZWT Capsule can reduce significantly pathology change of mimic cervical radiculitis in rats,and promote the recovery of nerve function.

The regulation of immune response is affected by several factors in order to maintain homeostasis.Indoleamine 2,3-dioxygenase(IDO) is a tryptophan-catabolizing enzyme expressed by different types of APC,including macrophages and dendritic cells.IDO activity leads to regulatory effects on T cells,which are mediated by tryptophan depletion in specific local tissue microenvironments,the production of proapoptotic metabolites,and inhibition of T-cell clone proliferation through regulatory T cells.IDO plays an important role in protecting the allogeneic fetus from rejection,the development of autoimmune diseases,allograft rejection,and cancer.So regulation of IDO activity may offer a novel drug-based strategy to treat immune-related diseases.

isointensity on arterial phase and hyperintensity on DWI. The combination of DWI and Gd-DTPA-enhanced MR imaging may help to accurately diagnose HCCs.

Objective To investigate the value ofin vivo proton MR spectroscopy(1H-MRS)in the assessment of large focal hepatic tumors.Methods Fifty-three consecutive patients with 54 large(no less than 4 cm in dimneter)hepatic tumors and 19 normal volunteers were:included in this study.MRS of the 25 HCC confirmed by pathological examination,the choline-to-lipid mtios(Cho/Lip)were measured by dividing the peak area of choline at 3.2 ppm and lipid at 1.3 ppm.Differences in the ratios of normal liver,benign tumors and HCC were analyzed by Dunnett-t test.The sensitivity and specificity prof'des of 1H-MRS in the diagnosis of HCC were determined by plotting receiver operating characteristic(ROC)curves.Results The mean Cho/Lip ratios for normal liver(n=17),benign tumor(n=8),and HCC(n=25)were 0.07±0.04,0.11 ±0.06 and 0.55±0.17,respectively(F=6.58,P＜0.05).A significant statistical difference was found in the mean Cho/Lip ratios between HCC and benign liver tumors or normal liver(t=2.99,2.32;P＜0.05).But there wag no difference between benign hepatic tumors and norlnal liver(t=1.53,P＞0.05).The ROC curve showed proton MRS had moderate discriminating ability in diagnosing HCC.The area under the curve was 0.77. If 0.1 was chosen ns the cut-off value for diagnosing HCC with MRS,the sensitivity and specificity for HCC were 80.0%and 62.59b,respectively.Conclusion In vivo proton MRS is technically feasible for the evaluation of focal hepatic lesions,and may be useful in the diagnosis and differential diagnosis of HCC by providing metabolic ifformafion.