Analysis of Material Basis and Mechanism of Sangjiang Ganmao Injection in Treatment of Common Cold Based on UPLC-Q-Orbitrap HRMS and Network Pharmacology / 中国实验方剂学杂志

Objective:To explore the material basis and mechanism of Sangjiang Ganmao injection （SG） in the treatment of common cold by ultra-performance liquid chromatography-quadrupole/electrostatic field orbitrap high resolution mass spectrometry （UPLC-Q-Orbitrap HRMS） and network pharmacology. Method:UPLC-Q-Orbitrap HRMS was used to identify the chemical components of SG with mobile phase of acetonitrile （A）-0.1% formic acid aqueous solution （B） for gradient elution （0-10 min， 4%-15%A； 10-35 min， 15%-30%A； 35-45 min， 30%-33%A； 45-55 min， 33%-60%A； 55-58 min， 60%A）， flow rate of 0.2 mL·min^-1， electrospray ionization （ESI） and scanning range of <italic>m</italic>/<italic>z</italic> 100-1 500 under positive and negative ion modes. Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and GeneCards 5.0 database were used to screen and predict the potential targets of chemical components in SG， STRING 11.0 database and Cytoscape 3.7.2 software were used to construct protein-protein interaction （PPI） network model， gene ontology （GO） analysis and pathway analysis were performed on potential targets by Metascape 3.5， Reactome database and Kyoto Encyclopedia of Genes and Genomes （KEGG）， Cytoscape 3.7.2 software was used to build the network of "herbs-ingredients-key targets". Result:A total of 54 components in SG were identified， and 80 potential targets of SG for treatment of common cold were predicted and screened based on this. SG exerted therapeutic effects by acting on targets such as interleukin （IL）-6， tumor necrosis factor （TNF） and IL-10， and signaling pathways such as IL-17 signaling pathway， TNF signaling pathway and interaction of cytokine receptors. Conclusion:SG may interfere with the expression of inflammatory cytokines by acting on related targets and pathways such as inflammation and immune system， and regulate the immune function of the body as a whole， thereby exerting a therapeutic effect.

Effects of Different Processed Methods on Anti-gouty Arthritis and Cardiotoxicity of Aconiti Radix / 中国实验方剂学杂志

Objective:To study the effects of different processing methods on the anti-gouty arthritis and cardiotoxicity of Aconiti Radix， and to explore the possible attenuation and synergism mechanism of these different processing methods. Method:The swelling degree of knee joint， levels of inflammatory factors ［interleukin （IL） -1<italic>β</italic>， IL-18， tumor necrosis factor （TNF）-<italic>α</italic>］ and the activities of liver energy metabolism-related enzymes ［Ca²⁺-Mg²⁺-adenosine triphosphatase （ATPase）， Na⁺-K⁺-ATPase， succinate dehydrogenase （SDH）］ in rats with gouty arthritis were used as indicators to evaluate the effects of pharmacopoeia steaming Aconiti Radix， pharmacopoeia boiling Aconiti Radix， Jianchang faction processed Aconiti Radix， Zhang faction processed Aconiti Radix and raw Aconiti Radix. The activity of creatine kinase （CK）， lactate dehydrogenase （LDH） and the content of B-type natriuretic peptide （BNP） were used as indexes to evaluate the cardiotoxicity of Aconiti Radix and its different processed products. Result:In the anti-gouty arthritis test， compared with the blank group， the knee joint of the model group was significantly swollen （<italic>P</italic><0.01）， the levels of IL-1<italic>β</italic>， IL-18， and TNF-<italic>α</italic> in serum were significantly increased （<italic>P</italic><0.01）， and the Ca²⁺-Mg²⁺-ATPase activity was significantly decreased （<italic>P</italic><0.01）. Compared with the model group， raw Aconiti Radix and the four processed products could reduce knee joint swelling and decrease IL-1<italic>β</italic>， IL-18， and TNF-<italic>α</italic> levels in serum of rats. The activity of Ca²⁺-Mg²⁺-ATPase in the liver of rats from the pharmacopoeia steaming Aconiti Radix group was significantly higher than that in the model group （<italic>P</italic><0.01）， and there was no statistical difference in other groups. In the cardiotoxicity test， compared with the blank group， the activities of CK and LDH were significantly increased and the level of BNP was significantly increased in the raw Aconiti Radix group and the pharmacopoeia steaming/boiling Aconiti Radix groups （<italic>P</italic><0.01）. In terms of LDH activity and BNP content， the Zhang faction and Jianchang faction processed Aconiti Radix groups were significantly lower than those in the raw Aconiti Radix group （<italic>P</italic><0.01）. In the CK activity， the Zhang faction processed Aconiti Radix group was significantly lower than that in the raw Aconiti Radix group （<italic>P</italic><0.01）. Conclusion:Raw Aconiti Radix and the four processed products have certain anti-inflammatory effects， but there are some differences among different indicators. There are significant differences in cardiotoxicity between the raw products and processed products of Aconiti Radix， and the cardiotoxicity of Jianchang faction and Zhang faction processed products was the weakest.

Research Progress on Multi-material and Multi-process Processing of Aconiti Radix / 中国实验方剂学杂志

Aconiti Radix is a kind of medicinal material with great toxicity, which has more than 2 000 years of clinical application history, in the folk, there are often poisoning accidents caused by improper processing. The main processing purpose of Aconiti Radix in the early period was to reduce the toxicity with simple procedure and single excipient. Since the Song dynasty, with the deepening of physicians' cognition of processing and the theory of medicinal properties, the application of procedures and materials in the processing of Aconiti Radix began to become complicated, and the scope of clinical application was further expanded. In modern times, the processing technology of Aconiti Radix is mainly based on steaming and boiling, which is quite different from the traditional processing method with multiple materials and multiple processes. Based on the characteristics of many kinds of materials and processes, this paper discusses the change in processing methods of Aconiti Radix from the perspective of excipients and processes, as well as modern processing research, in order to lay a scientific foundation for exploring the effects of many kinds of materials and processes on the quality of Aconiti Radix and revealing its processing mechanism, and provide basis and reference for establishing a more reasonable and scientific processing method for Aconiti Radix in the future.

Research progress of SDF-1α/CXCR4 axis in the treatment of ischemic stroke with stem cells / 药学学报

Stroke is the leading cause of death in Chinese currently, characterized by high incidence, high morbidity and high mortality, of which ischemic stroke accounted for 87%. However, it still lacks the ideal treatment. Stem cells are a class of cells with self-renewal ability and high differentiation potential. Stem cell transplantation breaks the irreversibility of nerve injury to post-stroke infarct area. However, stem cells also requiring specific chemokines to promote their directional migration to the injured tissue site after transplanted. Stromal cell-derived factor-1α (SDF-1α) is one of the typical chemokines. SDF-1α and its specific receptor CXCR4 can induce its migration, increase its proliferation and promote angiogenesis. In this paper, the role of SDF-1α/CXCR4 axis in the treatment of ischemic stroke in stem cells is reviewed in order to provide a theoretical basis for enhancing the efficacy of stem cell transplantation in the treatment of ischemic stroke.

Therapeutic effect of PCI combined tirofiban hydrochloride on aged ASTEMI patients and its influence on cardiac function and myocardial microcirculation indexes / 心血管康复医学杂志

Objective:To explore therapeutic effect of percutaneous coronary intervention(PCI)combined tirofiban hydrochloride on aged patients with acute ST elevation myocardial infarction(ASTEMI)and its influence on cardiac function and myocardial microcirculation.Methods:A total of 90 aged ASTEMI patients undergoing PCI in our hospital from Jul 2013 to Mar 2016 were selected.According to hospitalization order,they were randomly and e-qually divided into pure PCI group and combined treatment group(received tirofiban based on pure PCI group), both groups were treated for one month.ST segment regression degree,corrected TIMI frame count(CTFC)and TIMI flow grade after PCI,contrast agent acoustic peak intensity in myocardial microcirculation(PI)and serum CK-MB peak concentration before and after PCI,LVEF,LVEDd and LVEDV before and six months after PCI, and incidence rate of adverse events were measured and compared between two groups.Results:Compared with pure PCI group after PCI,there were significant rise in ST segment regression degree[(43.8 ± 7.1)% vs.(66.2 ± 8.2)%],TIMI flow grade[(2.1 ± 0.5)grade vs.(2.9 ± 0.6)grade]and PI[(7.1 ± 1.1)vs.(8.6 ± 1.2)],and sig-nificant reductions in CTFC[(27.3 ± 8.0)frame vs.(18.9 ± 6.6)frame],and serum CK-MB peak level[(296.5 ± 58.1)U/L vs.(199.3 ± 32.4)U/L]in combined treatment group,P= 0.001 all.Compared with pure PCI group on six months after PCI,there was significant rise in LVEF[(54.2 ± 8.3)% vs.(61.1 ± 8.0)%],and signifi-cant reductions in LVEDd[(48.1 ± 7.7)mm vs.(41.3 ± 8.1)mm]and LVEDV[(85.4 ± 10.6)mm3vs.(80.2 ± 10.4)mm3]in combined treatment group,P<0.05 or <0.01.Total incidence rate of adverse events of com-bined treatment group was significantly lower than that of pure PCI group(8.89% vs.26.67%),P=0.001.Con-clusion:PCI combined tirofiban hydrochloride can significantly improve myocardial microcirculation and cardiac function with low incidence rate of cardiovascular adverse events.The mechanism may be related to improving effect of tirofiban hydrochloride on myocardial microcirculation.

Synthesis and evaluation of 2-cyano-3, 12-dioxooleana-1, 9(11)-en-28-oate-13β, 28-olide as a potent anti-inflammatory agent for intervention of LPS-induced acute lung injury / 中国天然药物

The present study was designed to synthesize 2-Cyano-3, 12-dioxooleana-1, 9(11)-en-28-oate-13β, 28-olide (1), a lactone derivative of oleanolic acid (OA) and evaluate its anti-inflammatory activity. Compound 1 significantly diminished nitric oxide (NO) production and down-regulated the mRNA expression of iNOS, COX-2, IL-6, IL-1β, and TNF-α in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Further in vivo studies in murine model of LPS-induced acute lung injury (ALI) showed that 1 possessed more potent protective effects than the well-known anti-inflammatory drug dexamethasone by inhibiting myeloperoxidase (MPO) activity, reducing total cells and neutrophils, and suppressing inflammatory cytokines expression, and thus ameliorating the histopathological conditions of the injured lung tissue. In conclusion, compound 1 could be developed as a promising anti-inflammatory agent for intervention of LPS-induced ALI.

Research progress of JAK-3 kinase and its inhibitors / 药学学报

JAK-3, a member of the Janus kinase family, is a protein tyrosine kinase, which plays an important role in the JAK-STAT signaling pathway. Previous studies showed that regulation of JAK-3's activity plays a crucial role in the treatment of diseases such as rheumatoid arthritis. Many reports have been published with a focus on selective JAK-3 inhibitors, some of which showed excellent JAK-3 selectivity and inhibitory activities. Among the JAK-3 inhibitors reported, tofacitinib has satisfactory therapeutic benefits in the clinical trials, and has been approved for treatment of patients with rheumatoid arthritis. However, some JAK-3 inhibitors exhibited moderate to severe side effects, which need to be controlled by drug improvement. In order to pave the way for improvement of current JAK-3 inhibitors and development of new JAK-3 inhibitors, we provide an outline of the structure of JAK-3 and strategies in development of its inhibitors.

Glycosylation of ent-kaurene derivatives and an evaluation of their cytotoxic activities / 中国天然药物

AIM@#To discover more active and water-soluble derivatives of tetracyclic diterpenoids containing an exo-methylene cyclopentanone or an α-methylenelactone moiety.@*METHODS@#All of the key intermediates were synthesized from stevioside, and the target compounds were obtained through glycosylation of the 4-carboxyl group. The cytotoxicity of the target compounds against six human cancer cell lines, HepG2, Bel-7402, A549, U251, MCF-7 and MDA-MB-231, were evaluated by the MTT assay.@*RESULTS@#Compound 1b was more effective than the positive control adriamycin against the HepG2, Bel-7402, A549, MCF-7, and MDA-MB-231 cell lines with IC50 values of 0.12, 0.91, 0.35, 0.08, and 0.07 μmol·L(-1), respectively. Moreover, compound 3c exhibited the most potent and selective cytotoxic activity against the HepG2 cell line (IC50, 0.01 μmol·L(-1)).@*CONCLUSION@#Compounds 1b and 3c could be considered as potential anticancer candidates for further study.

TcpC induces apoptosis of macrophages through promoting ROS production / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the effects of Toll/interleukin 1 receptor domain-containing protein(TcpC)on macrophages and its mechanisms.</p><p><b>METHODS</b>Murine macrophage J774A cells were co-cultured with TcpC producing wild type E. coli strain CFT073 (TcpC(wt)) or tcpc gene-deleted CFT073 mutant (TcpC(mut)) in Transwell system, respectively. Apoptosis of J774A cells co-cultured with TcpC(wt) or TcpC(mut) was analyzed by Annexin/PI double staining. The levels of reactive oxygen species (ROS) in J774A cells were determined by DCFH-DA staining after treatment with TcpC(wt) or TcpC(mut) at 6 h, 12 h,24 h or 36 h. After the ROS was scavenged by N-acetylcysteine (NAC), the changes of J774A cell apoptosis were also examined. The expression of caspase-3 in J774A cells co-cultured with TcpC(wt) or TcpC(mut) in the presence or absence of 0.1 mmol NAC was detected by Western blot.</p><p><b>RESULTS</b>J774A cells co-cultured with TcpC(wt) for 24 h or 36 h showed significantly increased apoptosis (27.39% ± 4.05% and 28.45% ± 4.55%,respectively) when compared to control group (7.96% ± 1.63% and 10.55% ± 1.44%,P<0.01) or TcpC(mut) group (11.45% ± 2.77% and 19.26%± 2.89%,P<0.01). Levels of ROS in J774A cells treated with TcpC(wt) for 24 h (108.8 ± 9.73) or 36 h (100.3 ± 10.11) were significantly higher than those in control group (56.8 ± 4.11 and 52.8 ± 4.42,P<0.01) or TcpC(mut) (69.7 ± 5.66 and 62.6 ± 4.56, P < 0.01). The pro-apoptotic effects of TcpC(wt) on J774A cells were reversed by 0.1 or 1 mMol NAC treatment. Expression of caspase-3 in J774A cells co-cultured with TcpC(wt) (0.43 ± 0.04) decreased significantly when compared to control group (0.75 ± 0.08,P<0.05) or TcpC(mut) group (0.80 ± 0.12,P<0.05). However,total caspase-3 expression was restored in J774A cells co-cultured with TcpC(wt) in the presence of 0.1 mmol NAC (0.80 ± 0.09).</p><p><b>CONCLUSION</b>TcpC can promote ROS production in macrophages,hereby inducing macrophage apoptosis.</p>

TcpC induces apoptosis of human vascular endothelial cells and its mechanisms / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the effects of TcpC on human umbilical vascular endothelial cells (HUVECs) and its mechanisms.</p><p><b>METHODS</b>HUVECs were co-cultured with TcpC secreting wild-type E. coli strain CFT073 (TcpC(wt)) or tcpc gene-deleted CFT073 mutant strain (TcpC(mut)) in transwell system,respectively. Apoptosis of HUVECs was analyzed by Annexin-V/PI double staining. Mitochondrial membrane depolarization was detected by JC-1 staining. Expression of apoptosis-related proteins in HUVECs was determined by Western blot.</p><p><b>RESULTS</b>HUVECs showed morphological changes after co-cultured with TcpC(wt) for 24 h: the cells became detached and cell debris increased,and cell number was also decreased when compared to HUVECs co-cultured with TcpC(mut). The apoptosis of HUVEC cells co-cultured with TcpC(wt) for 24 h significantly increased,compared to that of control group and TcpC(mut) group (60.1% 9.7% compared with 9.0% 1.3% and 16.9% 0.4%,respectively, P<0.05); meanwhile the mitochondrial depolarization of HUVECs co-cultured with TcpC(wt) was significantly increased,compared to that in control and TcpC(mut) groups (64.5% 0.9% compared with 14.5% 2.1% and 15.6% 3.3%, respectively,P<0.05). Cleavage of PARP and inhibition of Mcl-1 and XIAP expression were seen in HUVECs co-cultured with TcpC(wt),but not in groups of control and TcpC(mut).</p><p><b>CONCLUSION</b>TcpC secreted from CFT073 can induce apoptosis of HUVECs through mitochondrial pathway, in which PARP is cleaved and Mcl-1 and XIAP expressions are inhibited.</p>

Research progress of the biological characteristics of IkappaB kinase and its inhibitors / 药学学报

The NF-kappaB pathway regulates the expression of over 150 target genes, e.g., cytokines, chemokines, leukocyte adhesion molecules and inducible effector enzymes. Consequently, it plays a crucial role in innate and adaptive immune responses, inflammatory response, stress responses, apoptosis and so on. IkappaB kinase (IKK) is the key of this pathway, and it owns a special structure which consists of catalytic subunit and regulatory subunit. Naturally, the activation of IKK needs the interaction of the two subunits and phosphorylation by its upstream kinases. Actually, there are two methods of activation of the NF-kappaB pathway, and both of the methods need the IKK complex. Given to the crucial role of IKK, researchers have isolated and synthesized amounts of IKK inhibitors, and these provide a great convenience to develop novel anti-inflammatory and anti-tumor drugs.

Role of Wnt/β-catenin signaling in aging of mesenchymal stem cells of rats / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the role of Wnt/β-catenin signaling in aging of mesenchymal stem cells (MSCs) of rats.</p><p><b>METHODS</b>Serum samples were collected from young (8 ≈ 12 w) and aged (64 ≈ 72 w) SD rat. Four experiment groups were assigned: young rat serum (YRS), YRS+Wnt 3a, old rat serum (ORS) and ORS+DKK1 groups. Immunofluorescence and Western blotting were used to detect the expression of intracellular β-catenin. The senescence-associated changes were examined with SA-β-galactosidase staining. The proliferation ability was tested by MTT assays. The survived and apoptotic cells were determined by AO/EB staining. The expressions of γ-H2A. X and p53 protein were detected by immunofluorescence and Western blotting. RT-PCR was used to detect the expression of p53 and p21 mRNA.</p><p><b>RESULTS</b>Compared with the YRS group, the intracellular expression of β-catenin in the ORS group was significantly increased,especially in the nuclei of MSCs. After treatment of DKK1 in ORS, the γ-catenin expression was reduced. The number of SA-β-galactosidase positive MSCs was significantly higher in the YRS+Wnt 3a group than that in the YRS group (P<0.01), and the proliferative and survival ability of MSCs was significantly decreased in the YRS+Wnt 3a group. The number of SA-β-galactosidase positive MSCs in the ORS+DKK1 group was significantly decreased compared with that in ORS group (P <0.01), and the proliferative and survival ability of MSCs was significantly increased in the ORS+DKK1 group. The expression of γ-H2A.X, p53 and p21 was markedly increased in the ORS group than that in YRS group, however, after treatment with Wnt/β-catenin signaling inhibitor DKK1, the expression of γ-H2A.X, p53 and p21 was significantly decreased compared with that in the ORS group.</p><p><b>CONCLUSION</b>Results suggest that the Wnt/β-catenin signaling is activated in the MSCs cultured with ORS and excessive activation of Wnt/β-catenin signaling can promote MSCs aging. The DNA damage response and p53/p21 pathway may be main mediators of MSC aging induced by excessive activation of Wnt/β-catenin signaling.</p>

Expression and significance of Clara cell secretory protein in injury lungs of Kunming mice after n-hexane long-term inhalation / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To observe the expression of Clara cell secretory protein(CCSP) in the Kunming mouse model of n-hexane long-term inhalation, and to discuss the functions of Clara cell in injury lung induced by n-hexane.</p><p><b>METHODS</b>24 healthy mice were randomly divided into 4 groups: one control group and three n-hexane groups (4 w, 8 w and 12 w), 6 each group. Primary concentration of n-hexane was 17.6 g/m3, 8 hours per day, 6 d per week. After inhalation, n-hexane concentration of blood from celiac artery was detected. The lungs were embedded with paraffin and HE staining in the routine. The ratio of Clara cells with CCSP reaction in bronchiole and the number of macrophage cells with lysozyme reaction were determined by immuno-histochemistry.</p><p><b>RESULTS</b>In the poisoning groups, the average n-hexane concentration of blood was significantly higher than that of the control group (P < 0.01). There were apparent pathologic damages in lungs of the poisoning mice. In poisoning 4 w, 8 w and 12 w groups, the ratio of Clara cells was significantly decreased [(73.33 +/- 4.21)%, (60.98 +/- 4.94)%, (34.04 +/- 2.33)% in terminal bronchiole, and (75.44 +/- 7.91)%, (58.54 +/- 4.86)%, (33.35 +/- 2.67)% in respiratory bronchiole] as compared with the control mice [(80.26 +/- 6.43)% and (81.74 +/- 7.75)%, P < 0.05 or P < 0.01], meanwhile the numbers of macrophage cells were gradually increased [(21.39 +/- 7.41), (28.54 +/- 10.73), (48.97 +/- 19.55) per microscopic field at 200x] in poisoning mice than those in control mice [(7.84 +/- 3.12) per microscopic field at 200x, P < 0.05 or P < 0.01].</p><p><b>CONCLUSION</b>In injury lungs after n-hexane inhalation, Clara cells are the target cells of n-hexane toxicity effect. Clara cells play an extensive protective role in lung inflammation.</p>

Classification and synthesis of ubiquitin-proteasome inhibitor / 药学学报

The inhibition of protein degradation through the ubiquitin-proteasome pathway is a recently developed approach to cancer treatment which extends the range of cellular target for chemotherapy. This therapeutic strategy is very interesting since the proteasomes carry out the regulated degradation of unnecessary or damaged cellular proteins, a process that is dysregulated in many cancer cells. Based on this hypothesis, the proteasome complex inhibitor Bortezomib was approved for use in multiple myeloma patients by FDA in 2003. Drug discovery programs in academy and the pharmaceutical industry have developed a range of synthetic and natural inhibitors of the 20S proteasome core particle that have entered human clinical trials as significant anti-cancer leads. The main results from the use of proteasome inhibition in cancer chemotherapy, the structure of several proteasome inhibitors and their synthesis is going to be reviewed in this paper.

Progress in small-molecule inhibitors of Bcl-2 family proteins / 药学学报

Apoptosis is an essential factor in keeping homeostasis of the organism. Apoptosis is regulated by a series of cytokines. Bcl-2 family proteins are key regulators of apoptosis. The Bcl-2 family includes both anti- and pro-apoptotic proteins with opposing biological functions. Their interaction regulates the transmission of the apoptosis signal. High expression of anti-apoptotic members such as Bcl-2 and Bcl-xL are commonly found in human cancers. In recent years, following the disclosing of the crystal structures of Bcl-2 family proteins, researchers have paid attention to the development of the small molecule inhibitors of Bcl-2 family proteins. This article reviews the progress in this field from the view of drug design.

Reevaluate the effect of G-480 point mutation that determines the neurovirulence of type I vaccine polioviruses / 病毒学报

Whole genome sequencing of 9 type I circulating vaccine-derived polioviruses (cVDPVs) isolated in Guizhou Province in China revealed that reverse mutations did not occur in G-480 and U-525 which are known as the most important neurovirulence determinate sites, while other known neurovirulence determinate sites such as A-2438, A-2795, C-6203 and G-7441 did revert to Mahoney type. 5 type I cVDPVs were selected for neurovirulence test on PVR-Tg21 transgenic mice which express human poliovirus receptor gene based on their different nucleotide sequences, they all showed higher neurovirulence than P1/Sabin strain, and the neurovirulence of CHN8184 and CHN8229-1. 1 were comparable to that of wild type P1/Mahoney. The neurovirulence of CHN8229-1.1, CHN8229-2 and CHN8229-3 presented a trend of decreasing, but still laid in high level. There were 7 nucleotide mutations between CHN8229-1.1 and CHN8229-2, and only 2 between CHN8229-2 and CHN8229-3 in their whole genomes, but the neurovirulence among them were relatively different, showing that there must be some unknown neurovirulence determinate sites among these mutations. Computer predicted RNA secondary structure of stem-loop V of the poliovirus 5' NCR of Guizhou type I cVDPVs was relatively stable. In the situation that no reverse mutation occurred in G-480, some type I cVDPVs already showed high neurovirulence nearly equal to P1/Mahoney, it meant that the effect of G-480 point mutation that determined neurovirulence of P1/Sabin strain has been overestimated, G-480 was not the only important site to determine neurovirulence in P1/Sabin strain, others also may play the very important role. More details are needed to elucidate the mechanism of attenuation in type I polioviruses.

Feasibility study of enforcing immunization certificate check before primary school or kindergarten enrollment in Guizhou Province, China / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To study the feasibility of enforcing immunization certificate check before children enroll in primary schools or kindergartens in Guizhou Province.</p><p><b>METHODS</b>Quantitative and qualitative studies were conducted. The multi-stage and cluster sampling approach was adopted for the quantitative part of the study. A questionnaire was designed and 996 children and their keepers were interviewed. Principals, doctors or teachers of the primary schools, directors and child care nurses of kindergarten, and staff of immunization agencies were invited to take part in 12 focus group discussions; meanwhile, face-to-face individual in-depth interviews with 16 officials of the Health, Education and Governmental Departments at various levels were conducted.</p><p><b>RESULTS</b>The total number of subjects was 996. 16.7% of the children in the study completed all the procedures of the National Immunization Programme. 34.3% of them had immunization certificates while the remainder 44.7% registered in immunization agencies. Factors, including the migrant children, doubt about vaccine efficiency, mother's occupation and educational background, knowledge of the National Immunization Programme on targeted vaccines, played an important role in obtaining or not immunization certificates. 95% of the keepers interviewed thought the immunization certificates were useful; 94.8% of them considered the check was critical while only 3.6% of them thought it unnecessary. The first reason from those who found it unnecessary was that they feared that repeated immunization might affect their children's health. The second reason was the cost of immunization, which some of them could not afford to pay. However, the Health Department expressed a favorable attitude to the checking scheme. Though the Education Department agreed that the scheme was essential, they worried that it would affect the enrollment rate.</p><p><b>CONCLUSION</b>In spite of the difficulty in administering immunization certificate check, the effort would be rewarding for raising the immunization coverage rate among the children in Guizhou Province.</p>

Synthesis and bioactivity of 2-arylimino-4-thiazolidones / 药学学报

<p><b>AIM</b>To synthesize a series of 2-arylimino-4-thiazolidone derivatives and 2-imidazolino [2,3-b]-4-thiazolidone in order to get some novel potent compounds with nitric oxide synthases (NOS) inhibitory activity.</p><p><b>METHODS</b>The target compounds were prepared by reaction of N-chloroacetyl-1,2,3,4-tetrahydroisoquinoline or N-chloroacetylphthalimide with substituted thioureas, their NOS inhibitory activity were measured.</p><p><b>RESULTS AND CONCLUSION</b>The 15 new compounds were synthesized and most of the reaction yields were over 65%. The structures of new compounds were identified by IR, 1H NMR, MS and elemental analyses. Bioassay indicated that, most of 15 new compounds synthesized had confirmed bioactivities inhibition against NOS.</p>

Study on an epidemic caused by the vaccine-derived poliovirus circulation in Guizhou province, 2004 / 中华流行病学杂志

<p><b>OBJECTIVE</b>To study the circulating vaccine-derived poliovirus (cVDPVs) that occurred in Zhenfeng county, Guizhou province in 2004 and to discover wild-poliovirus, vaccine-derived poliovirus (VDPVs) and other vaccine-associated poliovirus which could cause clinical poliomyelitis.</p><p><b>METHODS</b>Field epidemiological studies at the epidemic area and collecting acute flaccid paralysis (AFP) case and contact stool specimen for virus identification and nucleotide sequencing. Analysis on data related to annual reports on stool specimens surveillance which involved AFP case and contacts in the resent years in Zhenfeng county.</p><p><b>RESULTS</b>Type-I VDPVs had been isolated from 2 AFP cases and 3 contact stool specimen in Wanlan village of Zhenfeng. After the first cVDPVs case was identified, there were 3 cases identified of having other vaccine-associated poliovirus of type-I or type-II in the 5 case of AFP that met the criteria of clinical poliomyelitis. The result of virological surveillance on polio showed that the EV isolation rate (55.1%) of Zhenfeng county was higher than the rate from the whole province of the same year (23.2%). The poliovirus (PV) isolation rate (36.8%) was obviously higher in 2004 than in the previous years. In the 16 PVs strains, the type-I accounted for 43.8% which was significantly higher than the average level (18.3%) from the whole province.</p><p><b>CONCLUSIONS</b>Data indicated that the type-I VDPVs had been circulating (cVDPVs) in Zhenfeng county in Guizhou province. Clinical poliomyelitis was caused by non-VDPVs. The increased PV infection and the decreasing rate of vaccination in the general population were responsible for the epidemic of type-I cVDPVs at this time. Monitoring and evaluation on the rate of routine immunization program and prediction of the trend of epidemic should be strenthened.</p>

Synthesis of isothioureas derived from tetrahydroisoquinoline and NOS inhibitory activity / 药学学报

<p><b>AIM</b>To get some novel potent compounds with NOS inhibitory activity, a series of new compounds of isothioureas derived from 1,2,3,4-tetrahydroisoquinoline were synthesized.</p><p><b>METHODS</b>1,2, 3,4-Tetrahydroisoquinol-2-yl was introduced into the structure of isothioureas, the NOS inhibitory activity of the new compounds synthesized were measured.</p><p><b>RESULTS AND CONCLUSION</b>Twenty-two isothiourea derivatives of [alkyl(or aryl) imino] (1,2,3,4-tetrahydroisoquinol-2-yl) methyl alkyl thioethers (I) and S-alkyl-1-phenyl-3-[4-(1,2,3,4-tetrahydroisoquinol-2-yl) methane] phenyl isothioureas (II) were synthesized from thioureas by S-alkylation with alkyl halides, and their structures were identified by IR, 1H NMR, MS and elemental analysis. The preliminary biological test showed that the part of type I (1-9 and 1-13) had higher NOS inhibitory activity than that the control aminoguanidine (AG), but the type II had weak ability to inhibit NOS.</p>