Hemorrhagic fever with renal syndrome (HFRS) is a category B infectious disease caused by hantaviruses that cause acute kidney injury and has a high mortality rate, and HFRS control has been given a high priority in China. It has been found that hantavirus types are closely associated with selective host transformation and regional adaption, and continue to evolve in the form of gene recombination. The severity of HFRS varies in hantavirus types. In addition, global environmental changes and alteration of host animal behaviors accelerate Hantavirus genome variations, and large-scale land reclamation and infrastructure building increases the likelihood of human contacts with hosts and disease-transmitting vectors, thereby increasing the risk of HFRS development. This review summarizes the main characteristics and influencing factors pertaining to the epidemic process of HFRS, so as to provide insights into effective prevention and control of this infectious disease.

BACKGROUND: Apatite-wollastonite containing glass-ceramic (AWGC) is a kind of good bone repairing materials with excellent bioactivity, which is prepared by traditional melting process.OBJECTIVE: To observe AWGC prepared with sol-gel method and its bioactivity.DESIGN: Design experiment of materials process and in vitro bioactivity experiment.SETTING: College of materials science and Engineering of Sichuan University.MATERIALS: AWGC.METHODS: This experiment was conducted at the laboratory of College of Materials Science and Engineering of Sichuan University between August 2002 and May 2003. AWGC was prepared from sol-gel and followed by heattreating process. Bioactivity was investigated in vitro by immersing in the simulate body fluid (SBF) at 37 ℃ for 7 days . JL-1155 laser particle analyzer, X-ray diffraction, Fourier transform infrared spectroscopy and scanning electron microscope were used for micro-morphological structure analysis.MAIN OUTCOME MEASURES: ①The crystalline structure and microstructure of sol-gel derived glass-ceramic② The apatite forming process in simulate body fluid③ The diameter of the pore of the sol-gel derived apatite/wollastonite glass-ceramicRESULTS: ①Main crystalline phases of the sol-gel derived glass-ceramic materials were hydroxyapatite/fluoroapatite [Ca10(PO4)6(OH, F)] and β-wollastonite[β-CaSiO3]; Microstructure contained many micro-pores of 2-3μ m;② Sol-gel derived AW glass ceramic had excellent bioactivity: plenty of apatite granules were generated on the surface of the material after soaking for 7 days. ③Porous scaffolds possessed good macro-porous structure with the interconnected macro pores of 300-400 μm in diameter;CONCLUSION: Apatite-wollastonite containing glass-ceramic (AWGC)with excellent bioactivity was developed by sol-gel process. The material is expected to be a good candidate for bone-repairing and bone tissue engineering scaffold materials.

Objective:To investigate the effect and mechanism of PAE₂， a polypeptide of Periplaneta americana， in reversing multidrug resistance （MDR） for liver cancer in vivo. Method:Balb/c-nude mice were inoculated with HepG2 and HepG2/ADM cells under the armpits to establish animal models of liver cancer sensitive strains and animal models of MDR respectively. After successful modeling， the nude mice were randomly divided into normal group， HepG2 model group， HepG2/ADM model group， sorafenib group （positive drug control group， ig 30 mg·kg^-1）， HepG2/ADM+PAE₂ （iv） low， medium and high dose groups （50， 100， 200 mg·kg^-1）， HepG2/ADM+PAE₂ （ig） low， medium， and high dose groups （50， 100， 200 mg·kg^-1）， skim cream group （ig 200 mg·kg^-1）， and CⅡ-3 group （ig 200 mg·kg^-1）， all of which received corresponding drug treatment. The body weight and tumor volume of nude mice were measured and recorded every 2 days. The next day after the last administration， tumor tissues of nude mice were taken to record the tumor weight. The effect of P. americana polypeptide PAE₂ on permeability-glycoprotein（P-gp）， lung resistance protein（LRP） ， breast cancer resistance protein（BCRP）， protein kinase C（PKC）， glutathione S-transferase-π（GST-π）， topo-isomerase typeⅡ（ToPoⅡ）， multidurg resistance gene 1（MDR1） and Multidrug resistance-associated proteins（MRP1） of the protein level and gene level expression in tumor tissues were determined by immunohistochemistry （IHC） and real-time quantitative polymerase chain reaction （Real-time PCR）. In addition， both oral and intravenous administration groups were set up at the same time for preliminary study on the basic pharmacokinetic characteristics of P. americana polypeptide PAE₂. Result:After the successful modeling， the body weight of the nude mice was significantly lower than that in the normal mice（P<0.05）. After treatment with corresponding drugs， the body weight increased to a certain extent， but it was still not as good as the normal nude mice. In iv administration， the medium-dose P. americana polypeptide PAE₂ showed the best anti-tumor effect as compared with the model group （P<0.05）， while in oral administration， the anti-effect increased with the increase of the dose， so the high-dose group showed the best effect （P<0.05）. Preliminary crude extract CII-3 had no obvious anti-tumor effect， and skim cream showed a certain anti-tumor effect （P<0.05）. P. americana polypeptide PAE₂ had certain effects on MDR related proteins and enzymes in vivo， mainly by inhibiting the expression of LRP and BCRP in tumor tissues and affecting the expression of these related proteins and genes to different degrees to inhibit intracellular drugs outflow， thereby promoting tumor apoptosis， and the effect was superior to that of the P. americana crude extract CⅡ-3 and skim cream. Conclusion:P. americana polypeptide PAE₂ may reduce the drug efflux， promote intracellular drug accumulation and apoptosis by affecting the expression of related proteins and enzymes that mediate multidrug resistance， thereby exerting a reverse effect on HepG2/ADM cells Balb/c MDR in nude mice.

Ulcerative colitis (UC) is a chronic non-specific inflammatory bowel disease, listed as a modern refractory disease by the World Health Organization, which is difficult to recover, whereas it is easy to be attacked repeatedly. UC pathogenesis is closely related to gut microbiota dysbiosis. The gut microbiota interacts with bile acids (BAs), short-chain fatty acids (SCFAs), tryptophan, and other metabolism, immune system, intestinal barrier, etc., which regulate each other and affect the occurrence and development of UC. The active ingredients of traditional Chinese medicine (TCM), single herb and its extracts, and formulae can effectively alleviate UC symptoms by regulating the diversity, structure, composition, and metabolites of gut microbiota. In this review, the TCM based on the regulation of gut microbiota in the treatment of UC and its related mechanism for nearly three years was summarized.

Hepatic fibrosis (HF) is a self-healing pathological process after all kinds of chronic liver injuries and can cause diseases such as liver cirrhosis and liver cancer. The Wnt signaling pathway is highly conserved in species evolution and widely exists in invertebrates and vertebrates, and many studies have confirmed that the Wnt signaling pathway is closely associated with the development and progression of HF. This article reviews the mechanisms of the classical and non-classical Wnt signaling pathways in regulating hepatic stellate cells, hepatic macrophages, and hepatic progenitor cells, so as to provide new ideas for subsequent studies on the mechanism of the Wnt signaling pathway in regulating HF and further exploration of therapeutic targets that can reverse HF.

A novel series of benzyl urea analogues based on the structural modification of sorafenib were synthesized. Their in vitro antitumor activities against MX-1, HepG2, Ketr3 and HT-29 were evaluated using the standard MTT assay. While several target compounds showed inhibitory activity against multiple cancer cell lines, compound 9 was of particular interest, demonstrating IC50 values (5.69-13.6 micromol x L(-1)) comparable to those of sorafenib. Furthermore, compounds 20 and 23 showed more potent inhibitory activity against HT-29 and MX-1 when compared to sorafenib. In particular, compound 20 bearing the N-3-pyridyl moiety not only exhibited greater inhibitory activity against HT-29 cell line (IC50 3.82 micromol x L(-1)), but also had improved solubility at pH 7.2, is worthy of further investigation as a lead to identify novel antitumor agents.

To research the structure-activity relationship (SAR) of glycinamide-bearing compounds that used as inhibitors of dipeptidyl peptidase IV (DPP-IV), P32/98 and compound A were chosen as the leading compounds, heterocycles containing nitrogen atom were introduced to form amide, and different residues on a-position of carbonyl were designed. The nineteen designed compounds were synthesized by a simple route and were evaluated as inhibitors of DPP-IV. All of the structures were characterized by 1H NMR and HRMS. The preliminary SAR result was obtained.

Aim To determine the effect of SYL934 , a novel immunosuppressant, on skin allograft rejec-tion. Methods HTRF-IP1 assay was used to evaluate the agonistic activity of SYL934-P, the active form of SYL934 in vivo, on S1P1 and S1P3 in vitro. SD rat peripheral blood lymphocytes ( PBL ) test and heart rate test was used to assess the in vivo immunosuppres-sive effect and heart rate effect of SYL934 . Mice skin graft transplantation experiment was used to observe the effect of SYL934 on skin allograft refection. ResultsSYL934-P selectively activated S1 P1 but not S1 P3 in vitro. Single orally administration of SD rats with
SYL934 decreased the PBL significantly and played an obviously immunosuppressant role, but did not affect the heart rate. Daily orally administration of mice with SYL934 significantly increased the survival rate of al-lografts of skin slice in mice. Conclusion SYL934 has great selectivity in vitro and good activity in vivo, which indicated it potential use as an anti-rejection drug in skin transplantation.

Syl948 is a synthesized selective S1P1 agonist with novel structure. HTRF-IP1 test indicated that Syl948-P, the active form of Syl948 in vitro, has strong activity against S1P1 (EC50: 83 +/- 16 nmol x L(-1)), but its effect on S1P3 was very weak (EC50: 1 026 +/- 90 nmol x L(-1)). In SD rats, oral administration of Syl948 10 mg x kg(-1) significantly decreased the peripheral blood lymphocytes (PBL), with the maximal PBL inhibition rate of 63%, which was as similar as equal dose of fingolimod (FTY720). Oral administration of Syl948 10 mg x kg(-1) had no effect on heart rate of SD rats, which was better than FTY720. Daily oral administration with Syl948 (2 or 4 mg x kg(-1)) significantly prolonged the survival time of the allografts of skin slice on mice. In summary, the above results demonstrated that Syl948 has great selectivity in vitro and good activity in vivo, which indicated its potential use as an anti-rejection drug in skin transplantation.

A novel series of fingolimod analogues containing diphenyl ether moiety were designed and synthesized based on the modification of immunosuppressive agent fingolimod used in the treatment of multiple sclerosis. Compounds were evaluated in vivo for lymphopenic activity and heart rate affection. Most compounds showed moderate lymphopenic activity. It is worth noting that compounds 6c, 6d and 14c-14e showed considerable immunosuppressive activities comparable to fingolimod. And compound 14e had no effect on heart rate.