Active targeted Janus nanoparticles enable anti-angiogenic drug combining chemotherapy agent to prevent postoperative hepatocellular carcinoma recurrence.

Surgery is one of the main effective strategies for the treatment of solid tumors, but high postoperative recurrence is also the main cause of death in current cancer therapy. The prevention of postoperative hepatocellular carcinoma (HCC) recurrence is a clinical problem that needs to be solved urgently. At present, there are still some problems to be solved, such as, how to achieve free drugs to target the site of surgical resection; develop a strategy for the simultaneous administration of multiple drugs to inhibit postoperative recurrence; and provide the appropriate animal model that mimics the process of postoperative HCC recurrence. In this study, we used a facile and reproducible method to successfully prepare amphiphilic Janus nanoparticles (JNPs). In order to improve targeting of the JNPs to residual HCC cells after surgery, we modified the side of gold nanorods (GNRs) with lactobionic acid (LA), thus creating LA-JNPs. This provided an active and targeted co-delivery system for hydrophilic and hydrophobic drugs in separate rooms, thus avoiding mutual effects. Next, we established two models to simulate postoperative HCC recurrence: a subcutaneous postoperative recurrence model based on patient-derived tumor xenograft (PDX) tissues and a postoperative recurrence model of orthotopic HCC. By applying these models, the enhanced permeability and retention effect (EPR) based tumor targeting and LA based active targeting can jointly promote the enrichment and uptake of JNPs at tumor site. LA-JNPs represented an efficient targeting system for the co-delivery of Sorafenib/Doxorubicin with an optimized anti-recurrence effect and significantly improved the survival of mice during treatment for postoperative recurrence.

Research progress of novel drug delivery system for STING agonist / 中国药理学通报

Stimulator of interferon genes(STING)is a key protein in cGAS-STING signaling pathway and plays an important role in immune response mediated by the exogenous or endogenous DNA.This review describes the biological function of STING, the process of cGAS-STING pathway, the classification and administration of STING agonists, and summarizes the currently reported drug delivery systems.The delivery of STING agonists through appropriate drug carriers can overcome the lack of difficult entry, easy enzymatic hydrolysis, short half-life and poor targeting, improve the body's innate and adaptive immunity, and enhance the therapeutic effect of drugs.In conclusion, this paper mainly reviews the research progress of drug delivery system for STING agonists to provide basis for the development of drug delivery system and promote the clinical transformation and application of STING agonists.

Study on Therapeutic Effect and Related Mechanism of Fuyou Granule on Precocious Puberty in SD Female Rats / 中国实验方剂学杂志

Objective:To study the effect and related mechanism of Fuyou granule on danazol-induced precocious puberty model in rats. Method:Totally 21 cages of SD female rats were randomly divided into normal group， model group， Leuprorelin（0.1 g·kg^-1） and Fuyou mixture group（37.9 g·kg^-1）， and high-dose， mid-dose and low dose Fuyou granule<italic> </italic>groups（17.0，8.5，4.3 g·kg^-1）. Rats at 5 days of age were given a single subcutaneous injection of 300 μg danazol to establish the precocious puberty model. After 10 days of modeling， drug intervention was started. Vaginal opening was examined at the age of 20 days， and the gonadal development was observed by hematoxylin-eosin （HE） staining. The levels of serum luteinizing hormone （LH）， follicle-stimulating hormone （FSH） and estradiol （E₂） were determined by radioimmunoassay. The mRNA expressions of hypothalamic gonadotropin releasing hormone （GnRH）， Kiss-1， G protein-coupled receptor 54 （GPR54） were detected by Real-time fluorescent quantitative polymerase chain reaction （Real-time PCR）， and the expression of GnRH cells in the hypothalamus was detected by immunohistochemistry. Result:Compared with the normal group， the vaginal opening of the model group was significantly earlier， and the uterus and ovarian coefficients were significantly increased （<italic>P</italic><0.05）， indicating that the danazol-induced precocious puberty model was successfully established. The expression levels of GnRH， Kiss-1， and GPR54 also increased significantly （<italic>P</italic><0.05）， indicating that the danazol model can activate the HPG axis in advance， thereby inducing precocious puberty<bold>. </bold>Compared with the model group， the mid-dose Fuyou granule group significantly delayed the time of vaginal opening （<italic>P</italic><0.01）， high-dose Fuyou granule group<italic> </italic>significantly reduced uterine wall thickness and uterine coefficient （<italic>P</italic><0.05，<italic>P</italic><0.01）， mid-dose group reduced ovarian coefficient and uterine wall thickness （<italic>P</italic><0.05）. All the three dosage groups of Fuyou granule significantly reduced the content of serum hormones E₂， LH and FSH （<italic>P</italic><0.05，<italic>P</italic><0.01）， reduced the expression levels of hypothalamic GnRH， Kiss-1 and GPR54 mRNA （<italic>P</italic><0.05）， and decreased the expression of GnRH cells （<italic>P</italic><0.05）. Conclusion:Fuyou granule can achieve therapeutic precocity by regulating the Kiss-1/GPR54 system and down-regulating the expression of GnRH to inhibit the activation of the HPG axis.

Reversal of the immunosuppressive tumor microenvironment by nanoparticle-based activation of immune-associated cells.

Immunotherapy that activates the host immune system to reverse immunosuppression has emerged as a new generation of cancer treatment in both preclinical studies and clinical trials. Although immunotherapy has shown significant achievements in the treatment of various cancers, it faces challenges that limit its further evolution such as poor permeation and modest responsiveness. The development of nanoparticle drug delivery system has provided an opportunity to overcome these drawbacks and to achieve optimized immunotherapy. Based on the research of our group, we here introduce the new strategies being employed using nanoscale intelligent drug delivery systems to enhance the effects of cancer immunotherapy. We also provide a perspective on the further possible application of nanoparticles in more effective antitumor immunotherapy.

Effect of pH value of pretreatment environment of plasma samples on matrix effects in HPLC-MS/MS analysis of stilbene compounds / 中国药学杂志

OBJECTIVE: To evaluate the effects of the pH condition in which the plasma samples were prepared on the matrix effects of HPLC-MS/MS analysis of stilbene compounds.

Realgar nanometer suspension inducing apoptosis of Siha cell and its effect on expression of HPVE6/E7 oncogene / 中国中药杂志

<p><b>OBJECTIVE</b>To study the growth-inhibitory and apoptosis-inducing effects of realgar nanometer suspension in human carcinoma cervical cell Siha line, and the effect on HPV16E6/E7 oncogene expression.</p><p><b>METHOD</b>A " micro-jet efflux" strategy was used for the preparation of realgar nanometer suspension. Siha cells were treated with various concentrations (6.25, 12.5, 25, 50 mg x L(-1)) of realgar nanometer suspension for different hours (12, 24, 48, 72 h). The effect of realgar nanometer suspension on Siha cell growth suppression was detected by MTT method. Special morphological changes of apoptosis were observed by light and transmission electron microscopy (TEM) and DNA fragments electrophoresis. The apoptotic rates were quantified by flow cytometry (FCM). The expression of HPV16E6/E7 mRNA was assayed by RT-PCR.</p><p><b>RESULT</b>After being treated with 25-50 mg x L(-1) realgar nanometer suspension for 48, 72 h, the survival of Siha cells decreased, and the rate of apoptosis markedly increased. With TEM and DNA electrophoresis, the special morphological changes were found. The apoptotic rates of Siha cells treated with realgar nanometer suspension were significantly higher than those in the control group (P < 0.01). G0-G1 phase arrest appeared following the treatment with realgar nanometer suspension in 25 and 50 mg x L(-1) 48 h. RT-PCR assay revealed that realgar nanometer suspension reduced HPV16E6/E7 gene expression.</p><p><b>CONCLUSION</b>Realgar nanometer suspension can inhibit the proliferation of human carcinoma cervical cell Siha line and induce the cell apoptosis. The mechanism may be related to the down-regulation of HPV16E6/E7 oncogene expression.</p>

Epidemiological investigation on natural infection to Borna disease virus (BDV) among horses in Yili,Xinjiang / 中华流行病学杂志

Objective To investigate the epidemiological pattern of Borna disease virus (BDV)infection in horses and to analyze the phylogenetic tree of derived BDV in Yili, Xinjiang. Methods We established a modified nested RT-PCR (nRT-PCR) to detect BDV p24 segment in peripheral blood mononuclear cells (PBMCs) and brain tissues of 120 horses in Yili, Xinjiang. Positive products were analyzed by sequencing and homology analysis. Results The positive rate of BDV infection was 2.5% in both PMBCs and brain tissues at the same time. The gene sequence revealed in positive PCR samples was more than 93 % ,identical to that of BDV derived from horses in other countries. We also noticed a high degree of identity ( >98 % ) to standard strain He/80 in gene sequence of positive PCR samples. Conclusion Our study found the presence of BDV natural infection in horses in Yili. The endemic BDV had a high degree of identity to standard strain He/80.

Metabolic products and pathway of neferine in rat liver / 药学学报

The present study utilized LC-MS and HPLC approaches to characterize the metabolites of neferine in rat liver after an oral administration of 20 mg x kg(-1), and investigated the involvement of CYP450 isoforms in the metabolism of neferine by their selective inhibitors in vitro, separately. In positive ionization mode, besides neferine, four metabolites (M1-M4) were detected. M2 (the major metabolite) and M4 were identified as liensinine and isoliensinine by comparison with reference substances. Moreover, according to the analysis of metabolic rule of parent drug (neferine), M1 and M3 may be desmethylliensinine and desmethyl-isoliensinine, respectively. Furthermore, the metabolism of neferine in rat liver microsomes showed that the percentage inhibition of the major metabolism (liensinine) formation was 80.5% by quinidine (10 micromol x L(-1), selective CYP2D1 inhibitor) and 25.7% by ketoconazole (1 micromol x L(-1), selective CYP3A1 inhibitor). Neferine was mainly metabolized by CYP2D1 or CYP3A1 to liensinine, isoliensinine, desmethyl-liensinine and desmethyl-isoliensinine.

Determination of three alkaloids in total alkaloids exfracts from Lotus plumule by RP-HPLC / 中国中药杂志

<p><b>OBJECTIVE</b>To develop a RP-HPLC method for determination of three alkaloids in total alkaloids exfracted from Lotus plumule.</p><p><b>METHOD</b>A Hypersil C18 column was used with the mobile phase of methanol-phosphate (73:27, pH 9.0) at the detection wavelength of 230 and 286 nm. The flow rate was 1 mL min(-1).</p><p><b>RESULT</b>The linear range was 20-700 microg mL(-1), the recovery of three alkaloids were 97.9%, 98.4% and 98.1%. The RSD of intra-day and inter-day was 0. 24% -4. 83%. Different groups of samples were determined by this method. The result showed that the extraction method with methanol was prior to the extraction method with alcohol.</p><p><b>CONCLUSION</b>The method is simple, rapid and suitable for the determination of three alkaloids in total alkaloids exfracted from L. plumule.</p>

Study on corresponding areas the liver and lung channels in brain with fMRI / 中国针灸

<p><b>OBJECTIVE</b>To explore distribution of the Liver and Lung Channels in the brain so as to provide imaging basis for construction of channel theory in the brain.</p><p><b>METHODS</b>Sixty healthy student volunteers were randomly divided into a Liver Channel group (I) and a Lung Channel group (II), and the each group was further divided into five subgroups with 6 volunteers in each subgroup, based on five-shu-point principles which, were Dadun (LR 1, I 1), Xingjian (LR 2, I 2), Taichong (LR 3, I 3), Zhongfeng (LR 4, I 4), Ququan (LR 8, I 5), Shaoshang (LU 11, II 1), Yuji (LU 10, II 2), Taiyuan (LU 9, II 3), Jingqu (LU 8, II 4), and Chize (LU 5, II 5), respectively. In order to observe the brain activating patterns during acupuncture at the different acupoints, functional magnetic resonance imaging (fMRI) technique was adopted. All image data were then analyzed with SPM 2 software. The statistical parameter gram was composed of the pixel P < 0.01, and anatomic location was made according to Talairach coordinate, attaining experimentally activated areas, and the commonly activated area of five-shu-point of each channel was considered as the brain distribution of the Liver and Lung Channels.</p><p><b>RESULTS</b>The common areas activated by the five-shu-points of the Liver Channel were homolateral Brodmann area (BA) 34, BA 47, red nucleus, contralateral BA 19, BA 30, BA 39, the superior parietal lobule, cerebellum decline, and bilateral BA 3 and culmen. The common areas activated by the five-shu-points of the Lung Channels included homolateral BA 2, BA 18, BA 35, and contralateral BA 9 and substania nigra.</p><p><b>CONCLUSION</b>There are relatively specific corresponding brain areas for the Liver and Lung Channels, indicating that there is possible relatively specific connection between channels and the brain.</p>