Chronic hepatitis B (CHB) is still a global public health problem, resulting in the high risk of decompensated cirrhosis and hepatocellular carcinoma.At present, there are no single available medications that can induce both potent HBV DNA suppression, and high rates of HBeAg and HBsAg clearance.Therefore, there is great interest in developing combination therapies for patients with chronic HBV infection, which can achieve sustained viral suppression and HBsAg negative inversion after a finite course of treatment leading to clinical cure.This article reviews the current status and advances of combination therapy for CHB.

Biomarker is the measurable change associated with a physiological or pathophysiolog-ical process. Unlike blood which has mechanisms to keep the internal environment homeostatic, urine is more likely to reflect changes of the body. As a result, urine is likely to be a better biomarker source than blood. However, since the urinary proteome is affected by many factors, including diuretics, careful evaluation of those effects is necessary if urinary proteomics is used for biomarker discovery. Here, we evaluated the effects of three commonly-used diuretics (furosemide, F;hydro-chlorothiazide, H; and spirolactone, S) on the urinary proteome in rats. Urine samples were col-lected before and after intragastric administration of diuretics at therapeutic doses and the proteomes were analyzed using label-free liquid chromatography-tandem mass spectrometry (LC-MS/MS). Based on the criteria of P 6 0.05, a fold change P2, a spectral count P5, and false positive rate (FDR) 61%, 14 proteins (seven for F, five for H, and two for S) were identified by Progenesis LC-MS. The human orthologs of most of these 14 proteins are stable in the healthy human urinary proteome, and ten of them are reported as disease biomarkers. Thus, our results suggest that the effects of diuretics deserve more attention in future urinary protein biomarker studies. Moreover, the distinct effects of diuretics on the urinary proteome may provide clues to the mechanisms of diuretics.

Objective To investigate the neuroprotective mechanism of cerebral ischemic preconditioning by detecting the expression changes of hippocampus nuclear factor-κB (NF-κB) and Hesl mRNA after cerebral ischemia-reperfusion in rats.Methods A total of 108 healthy male SD rats were randomly divided into a cerebral ischemia group,a cerebral ischemic preconditioning group,and a sham operation group,and then redivided into 22 h,48 h,72 h,7 d,and 14 d subgroups.Ischemic preconditioning was performed at day 3 before establishing the cerebral ischemia-reperfusion injury model by transient occlusion of right internal carotid artery for 10 min.At each time point after cerebral ischemia-reperfusion,the neurological deficit score and cerebral infarction volume measurement were performed,and the expressions of NF-κB and Hes1 mRNA in the hippocampus were detected by using real-time fluorescence quantitative polymerase chain reaction.Results The neurological function scores and the percentage of cerebral infarction volume in the cerebral ischemic preconditioning goup at each time point were significantly lower than those in the cerebral ischemia-reperfusion group (all P ＜0.05).The expression levels of NF-κB and Hesl mRNAs in each group had progressive reduction with time.Compared with the same time point,it showed that the expression levels of NF-κB and Hes1 mRNAs in the cerebral ischemic preconditioning group and the cerebral ischemia-reperfusion group were significantly higher than those in the sham operation group,the expression level of NF-κB mRNA in the cerebral ischemic preconditioning group was significantly lower than that in the cerebral ischemia-reperfusion group,and the expression level of Hesl mRNA was significantly higher than that in the cerebral ischemia-reperfusion group (all P ＜0.05).Conclusions The upregulation of Hesl and down-regulation of NF-κB may be involved in the neuroprotective mechanisms of cerebral ischemic preconditioning.

Objective To explore the effects of different doses of contrast agent (CA) on types of time-signal intensity curves (TICs) and semi-quantitative parameters after dynamic contrast-enhanced MRI (DCE-MRI) on Walker 256 murine breast tumor model.Methods A total of 12 rats burdened Walker256 breast cancer models were established and divided into 3 groups randomly, 4 in each group.Routine MR and DCE-MRI scans of the rats using Bruker Pharmascan 7T MR scanner were performed.Doses for the 3 groups were 0.2, 0.3, and 0.5 mmol/kg, respectively.MR data, TICs types and semi-quantitative parameters from each different dose group were statistically studied and compared to observe the differences.Results Tumors were enhanced significantly after injection.The types of TICs in all tumors were the Ⅲ pattern which was not influenced by CA doses.Semi-quantitative parameters of first enhancement (Efirst), maximal enhancement (Emax), washout enhancement (Ewash), and signal enhancement ratio (SER) showed statistical differences among the three dose groups (P＜0.05).Semi-quantitative parameters of time to peak (Tpeak) and washout velocity (Vwash) showed no statistical differences among the three dose groups (P＞0.05).Mean signal intensity of each group was highly negatively linear correlated with scan times after the peak (r=-0.972, P=0.000;r=-0.971, P=0.000;r=-0.989, P=0.000).The washout slope (slopewash) showed no statistical differences among the three groups (P＞0.05).Conclusions Injection doses of CA didn't change the TIC type, Tpeak, Vwash, and Slopewash.These parameters are comparable among different medical centers and can be considered as prior parameters to monitor the efficacy of neoadjuvant chemotherapy.

This article compares and analyzes the content and theoretical structure of the concept of pathogenesis from the national textbooks of Basic Theory of Chinese Medicine and Diagnostics in Chinese Medicine from the first to the ninth version.The authors consider the mechanism as the main content of pathogenesis concept in contemporary Chinese medicine.During the construction of this concept,the concept of pathology has a profound influence,wh ich differs a lot from the emphasis on key in ancient pathogenesis content,mainly reflected in clinical diagnosis and treatment ideas transferring from dealing with key issues to dealing with abstract concept.This change is associated with the impact of western medicine on modern Chinese medicine,emphasizing the mechanism and so on,so that the ancient Xiang (象) concept is marginalized.

Objective To establish a mouse model of kidney-yin and kidney?yang deficiency after oral administra?tion of hydrocortisone, and to explore the related evaluation factors. Methods The model was established by oral adminis?tration of hydrocortisone to induce kidney?yin and kidney?yang deficiency in mice. The survival and body weight of the mice were observed. The serum content of adrenal cortical hormone ( ACTH) , cortisol ( Cor. ) in the hypothalamic?pituitary?ad?renal (HPA) axis, and thyroid stimulating hormone (TSH), triiodothyronine (T3), thyrox (T4) in the hypothalamic?pi?tuitary?thyroid (HPT) axis, follicle?stimulating hormone (FSH), estradiol (E2), testosterone (T) in the hypothalamic?pituitary?gonadal ( HPG) axis were determined by radioimmunoassay. Results The body weight of kidney?yin and kidney?yang mice were decreased, the serum ACTH, Cor, TSH, T3, T4 contents were decreased, the serum FSH, E2, T contents were increased in the kidney?yang deficiency model mce ( P<0. 01 ) , and those parameters in the kidney?yin deficiency model mice were changed in opposite direction. Conclusions It is found that the hormone levels of ACTH, Cor, TSH, T3, T4, FSH, E2 and T in kidney deficiency mice are changed, and cortisol can be used as an important index to evaluate the model of kidney deficiency induced by glucocorticoid.

OBJECTIVETo establish an HPLC method for determination the contents of quercitrin in Polygonum capitatum and Relinqing granules.

METHODThe samples were analyzed on a Diamonsil C18 colunm (4.6 mm x 250 mm, 5 microm) eluted with the mobile phase consisted of methanol-1% HAc-THF. The flow rate was 1.0 mL x min-m. The detection wavelength was set at 258 nm and the column temperature was 25 degrees C.

RESULTThe calibration curve was linear in the range of 0. 081 64-0.4084 microg (r = 0.99997). The average recovery rate of quercitrin in P. capitatum was 102.3% (RSD 0.99%), and was 102.7% (RSD 2.2%) in Relinqing granules.

CONCLUSIONThe method is reliable and specific with good repeatability, and can be used for the quality control of P. capitatum and Relinqing granules. It can provide a science bases for the planting of polygonum capitatum.

Chromatography, High Pressure Liquid ; methods ; Drugs, Chinese Herbal ; analysis ; chemistry ; Polygonum ; chemistry ; Quercetin ; analogs & derivatives ; analysis ; chemistry ; Reproducibility of Results

The development of multifunctional nanocontrast agents with high sensitivity, high specificity, and low toxicity so that they can precisely localize tumors and reflect tumor biological information in real time is the core of promoting the development of tumor molecular imaging technology and realizing early and precise tumor diagnosis. Polydopamine (PDA) nanomaterials are bionanomaterials with a structure extremely similar to that of natural melanin. They can be easily fabricated and functionalized, and can achieve controlled assembly of functional molecules such as contrast components and targeting ligands via metal coordination, π-π stacking, electrostatic adsorption, and other methods. They have good biocompatibility and biodegradability, show great potential for clinical translation, and have been widely used in molecular imaging of tumors. In this review paper, the preclinical studies of PDA nanoparticles are reviewed as well as the synthesis methods, functionalized modification, and assembly strategies of PDA nanoparticles and their applications in tumor molecular imaging. The development trends of PDA are also presented to promote their application in the field of tumor molecular imaging.

Objective To investigate the influence of early growth response gene-1 (EGR1) on the autophagy of host cells following infection with human T cell leukemia virus type 1 (HTLV-1).MethodsA HTLV-1-positive cell line MT2 was co-cultured with HeLa cells for 24 h to construct the virus early infection model.Immunoblotting assay was used to detect the expression of HTLV-1 core protein p19 and EGR1.Luciferase reporter gene analysis was used to detect the transcriptional activity of 5′-regulatory sequence of EGR1 at different time points after co-culturing.An effective small interfering RNA (siRNA) targeting EGR1 was screened out and transfected into HeLa cells by Lipofectamine 2000.Then the transfected HeLa cells were co-cultured with the HTLV-1-positive cell line MT2 for 24 h.Immunoblotting assay was used to detect HTLV-1 core protein p19, EGR1 and autophagy-related protein LC3.Real-time PCR was performed to detect viral load.Autophagosome was analyzed by immunofluorescence after co-culturing.Results The expression of EGR1 and the transcriptional activity of pEGR1-luc gradually increased after co-culturing HeLa cells with MT2 cells for 8 h (P<0.01).The expression of EGR1 was positively correlated with host cell autophagy following HTLV-1 infection.The effective siRNA for silencing the expression of EGR1 was obtained and named as siE2.The viral load, the expression of HTLV-1 core protein p19 and the proportion of LC3B/LC3A in the co-culture model were markedly down-regulated by RNA interference with siE2, which was concomitant with a persistent decrease of intracellular autophagosome (P<0.01).Conclusion EGR1 is associated with host cell autophagy and viral replication in HTLV-1 infection.

Objective:To investigate the impact of China's Mental Health Law on the work of psychological counseling in colleges and universities, and to explore ways to improve the law. Methods: Totally 12 heads of college and university counseling centers in Beijing were conducted with semi-structured interviews. The average age of the interviewees was (40 ±7) years old, with master or doctor degrees in psychology or related disciplines. The method of content analysis was used to analyze the interviewees' understanding of the " Mental Health Law". Results: All of the 12 interviewees had gained some understanding of the "Mental Health Law", and accordingly amended the regulation of their counseling centers. Also, interviewees suggested the positive and negative impacts brought by the law, such as enhancing practitioners' legislative sense, clarifying their responsibilities and boundaries as college and university counseling, as well as difficulties to distinguish psychotherapy and psychological counseling, ambiguity in the legality of working with students who were diagnosed with mental disorders. Moreover, interviewees threw out suggestions on improving the law from the aspect of industry standard, supervision department and vocational qualification. Conclusion: The execution of "Mental Health Law" improves practitioners' legislative sense, clarifies their responsibility. Nevertheless, it does not clearly distinguish psychotherapy from psychological counseling, and be lack of regulation on the psychological counseling industry.