Post-marketing evaluation is a process which evaluate the risks and benefits of drug clinical application comprehensively and systematically, scientific and systematic results of post-marketing evaluation not only can provide data support for clinical application of traditional Chinese medicine, but also can be a reliable basis for the supervision department to develop risk control measures. With the increasing demands for treatment and prevention of disease, traditional Chinese medicine has been widely used, and security issues are also exposed. How to find risk signal of traditional Chinese medicine in the early stages, carry out targeted evaluation work and control risk timely have become challenges in the development of traditional Chinese medicine industry.
Drug Evaluation ; methods ; Drugs, Chinese Herbal ; Humans ; Medicine, Chinese Traditional

Objective To investigate the clonal types of Staphylococcus aureus collected from 2004to 2010 in patients with blood stream infection from a Grade A tertiary care hospital in Shanghai as well as the dynamic changes and to detect the variation in antimicrobial resistance and virulence-gene content in different strain types.Methods A total of 103 nonduplicate S.aureus isolates were collected from 2004 to 2010 from inpatients with S.aureus blood stream infection from Shanghai Huashan hospital.Determination of oxacillin MICs and the type of SCCmec gene were used to screen MRSA.Typing of S.aureus isolates was identified by using multilocus sequence typing(MLST) and S.aureus-specific staphylococcal protein A typing(spa typing),PCR was used to detect the antimicrobial resistance and virulence-gene.Results Sixtysix isolates(64.1%) MRSA were detected in 103 nonduplicate S.aureus isolates,and 35 isolates were MRSA with SCCmec type Ⅱ ,Twenty-nine isolates were MRSA with SCCmec type Ⅱ,two isolates were MRSA with SCCmec type Ⅳ,Thirty-seven isolates(35.9%) were MSSA.Thirty-three MRSA isolates were ST5,Twenty-nine MRSA isolates were ST239,two MRSA isolates were ST59,one MRSA isolates was ST641 and one MRSA isolates was ST6.All of the other clones belonged to MSSA.The percentage of ST5 and ST239 were decreased significantly after 2009(ST5 was decreased from 52.9% to 15.4%; ST239 was decreased from 61.1% to 15.4%),and new clonal types MSSA increased significantly(in 2009,the percentage of ST7 was 41.7%; new clonal types such as ST188 and ST15 were detected in 2010).In 2010,it was shown that 84.6% of MSSA were isolated from S.aureus blood stream infection,nineteen isolates(18.4%) harbored mupA gene and 41 isolates(39.8%) harbored qacA/B gene in 103 nonduplicate S.aureus isolates.It was shown that 70.6% ST239 harbored qacA/B gene.Four isolates of ST398 and 1 isolates of ST9were detected which were originally from animal.There was no significant difference of the virulence gene presence in the same strain types except sasX、lukSF and arcA genes,but there were a lot of genes which were restricted to different genomic background.Conclusions The percentage of ST5 and ST239 were decreased and new clonal types of MSSA were increased significantly in S.aureus blood stream infection,antimicrobial resistance and virulence-gene were restricted to different clonal types.

ObjectiveTo investigate the distribution and effect on antibiotic resistance of the novel cell wall anchored protein-encoding gene sasX.MethodsA total of 300 S.aureus isolates were randomly collected from inpatients with S.aureusinfection in ShanghaiHuashanhospitalin 2004, 2007and 2010.Meanwhile,170 S.aureus isolates from the nasal swabs of healthy people were collected as part of a population-based community prevalence study.Typing of S.aureus isolates were identified by using multilocus sequence typing (MLST) and S.aureus-specific staphylococcal protein A typing (spa typing).Determination of oxacillin MICs was used to screen MRSA.PCR and sequencing were used to analyze sasX gene.The effect on antibiotic resistance of sasX gene was detect by disc agar diffusion drug sensitive test.ResultsThe major clonal types of the 300 S.aureus isolates collected from inpatients with S.aureus infection were ST239 ( 110,36.7％) and ST5 (122,40.7％).From 2004 to 2010,the percentage of isolates from inpatients with S.aureus infection was increased from 17％ to 39％,but sasX was only found in 0.59％ of the S.aureus isolates from the nasal swabs of healthy people.The percentage of sasX positive was increased from 47.2％ to 83.8％ in ST239.The percentage of sasX positive MRSA was increased from 26.4％ to 50.8％,but the percentage of sasX positive MSSA was about 10％.Antibiotic resistance of sasX positive strains were higher than that of sasX negative strains.Conclusions SasX gene is mainly detected in nosocomial pathogenic S.aureus and it is a possible virulence factor of S.aureus in hosptal setting.The presence of sasX gene is related to antibiotic resistance.For better understanding the real function of this novel gene,further studies such as expression of the encoded protein should be carried out.

The adverse reaction monitoring is important in warning the risks of traditional Chinese medicines at an early stage, finding potential quality problems and ensuring the safe clinical medication. In the study, efforts were made to investigate the risk signal mining techniques in line with the characteristics of traditional Chinese medicines, particularly the complexity in component, processing, compatibility, preparation and clinical medication, find early risk signals of traditional Chinese medicines and establish a traditional Chinese medicine safety evaluation system based on adverse reaction risk signals, in order to improve the target studies on traditional Chinese medicine safety, effective and timely control risks and solve the existing frequent safety issue in traditional Chinese medicines.
China ; epidemiology ; Drug Evaluation ; Drug-Related Side Effects and Adverse Reactions ; epidemiology ; etiology ; Drugs, Chinese Herbal ; adverse effects ; therapeutic use ; Humans ; Product Surveillance, Postmarketing

Objective To observe the changes of immunological parameters and the effects of intravenous immunoglobulin (IVIG) in children with idiopathic thrombocytopenic purpura (ITP),schonlein-Henoch purpura(HSP) and mucocutaneoas lymph node syn-drome(kawasaki disease, KD).Methods T cell subsets and serum immunoglobulins and complements were measured with the flow cytometry and enhanced trubidimetric immunoassay. Routine therapy combined with IVIG. Results CD3+ CD4+ T cells were de-creased in children with ITP accompanied by increased serum IgG;Serum IgA and CD3+ T cells were increased in children with HSP; CD3+ CD8+ T cells were decreased in children with KD. Clinical features were markedly improved after treatment with IVIG. It was noted that the incidence of damage to coronary artery decreased after the use of IVIG. Conclusions T cell subsets, serum immunoglobulins should undergo the clinical routine examinations in ITP,HSP and KD. Early administration of IVIG might be important to improve disease prognosis and shorten its course of treatment in children with three kinds of immunology related diseases.

Objective To explore the best treatment strategy of pyogenic brain abscesses.Methods Clinical data of 45 patients(34 males and 11 females,ages ranged from 7 to 76 years,averaged 42.6 years) with brain abscess treated from January 1999 to March 2008 were retrospectively analyzed.Among the 45 patients,there were 40 with single brain abscess and 5 with multiple brain abscess;43 with unilocular abscess and 2 with multilocular abscess.19 patients accepted the conservative treatment with the third generation cephalosporin,16 were treated with stereotactic puncture of abscess,8 treated with stereotactic puncture and drainage,and microsurgical excision was performed in 5 patients.Results Of the 19 patients treated with conservative method,16 were cured,no recurrence was found during the follow-up period(from 6 months to 5 years) in 13 patients,and another 3 were deteriorated and accepted stereotactic operation.All the stereotactic operations were carried successfully out in 24 patients(including 3 cases after expectant treatment failure) and only one patient needed another stereotactic aspiration two weeks later because of abscess recurrence after the initial operation.Epileptic seizure was found in one patient at the end of stereotactic procedure.Total removal of brain abscess was performed by microsurgical craniotomy in 5 patients.At the time of discharge,clinical symptoms disappeared or were improved remarkably,and CT or MRI re-examination disclosed the disappearance or obviously diminution of abscess in all patients.No abscess recurred during the follow-up period(from 4 months to 3 years,average 14 months) in 22 patients.Conclusion A set of treatment strategy of pyogenic brain abscesses has been proposed and stereotactic operation seems to be the most appropriate surgical choice.

Objective:To establish a new approach to synthesis of diethyl N-[4-[(2,4-diaminopyrido [3,2-d]pyrimidin-6-yl)methylamino]benzoyl]-L-glutamate.Methods:Target compound (5) was syn-thesized by the use of (2,4-dioxo-tetrahydropyridopyrimidin-6-yl) methyl acetate (1) as starting material via hydrolysis, chlorination, condensation with diethyl (p-aminobenzoyl)glutamate and aminolysis.Re-sults:A new approach to synthesis of diethyl N-[4-[(2,4-diaminopyrido[3,2-d]pyrimidin-6-yl)methyl-amino]benzoyl]-L-glutamatewas established .This synthetic route has hydrolysis reaction , chlorination, diethyl N-( p-aminobenzoyl )-L-glutamate condensation reaction and ammonolysis reaction .The total yield is 36.7%.The structures of those compounds have identified by 1 H nuclear magnetic resonance , 13 C nu-clear magnetic resonance and mass spectrometry .This synthetic route avoid the unstable brominated re-action product and improves the harsh condition of ammonolysis reaction .Conclusion:The new synthetic route has improved the reaction condition and the stability of the intermediate , and increased the extent of the derivative compounds , which has great significance to anti-folic acid of anti-tumor inhibitor synthesis .

Protein tyrosine phosphatase (PTP) 1B is a potential target for the treatment of diabetes and obesity. Phosphotyrosine (pTyr) is the substrate for PTP1B dephosphorylation. Malonic acid moiety was used herein as a mimic of the phosphate group in pTyr, and novel malonic acid derivatives 1-7 were designed, synthesized and evaluated as PTP1B inhibitors. Results from enzymatic assays indicated that compounds 3 and 4 exhibited potent inhibition against human recombinant PTP1B with IC50 values of 7.66 and 1.88 micromol x L(-1), respectively.

Traditional Chinese medicine Polygoni Multiflori Radix is dried roots of Polygonaceae Polygortum multiflorum Thunb. Its clinical application records were first discovered in literatures of the Tang dynasty. The origins, efficacy, toxicity, processing and taboos of Polygoni Multiflori Radix have been discussed in many ancient herb literatures. In recent years, with the increase in the public awareness in health, Polygoni Multiflori Radix admits preparations have been more widely applied in the treatment and prevention of diseases. However, there have been more and more reports about Polygoni Multiflori Radix induced liver injury, the safety of Polygoni Multiflori Radix has increasingly attracted attention of the society. In this paper, the authors summarized and analyzed the toxicity and medication risk factors of Polygoni Multiflori Radix recorded in ancient herb literatures, and proposed that more attention shall be given to the effect of the planting and processing methods on the components and toxicity of Polygoni Multiflori Radix in safety studies, which provides clues for the further studies.
China ; Drugs, Chinese Herbal ; adverse effects ; history ; History, Ancient ; Humans ; Medicine in Literature ; Medicine, Chinese Traditional ; history ; Polygonum ; adverse effects ; Risk Assessment

The renal toxicity and mutagenicity of aristolochic acid (AA) as well as its carcinogenicity on upper urinary tract transitional epithelial cells have been widely known. Since 2003, drug regulatory departments have successively cancelled the quality standards for AA-containing medicines such as Aristolochiae Radix, Aristolochiae Manshuriensis Caulis and Aristolchiae Fangchi Radix, and adopted measures for strengthening regulation and revising package insert or quality standards for other AA-containing medicines, including Aristolochia Cinnabarina Radix, Aristolochiae Fructus, Aristolochiae Mollissimae Herba, in order to control its safety risk. In recent years, domestic and foreign studies on AA have mainly involved action mechanism and clinical performance of AA toxicity, early-stage diagnosis and treatment method. In this paper, authors gave a brief summary and evaluation on risk factors for using AA-containing medicines, and offered measures and suggestions for preventing and controlling AA toxicity.
Animals ; Aristolochia ; adverse effects ; chemistry ; Aristolochic Acids ; analysis ; therapeutic use ; toxicity ; Drug Therapy ; Drug-Related Side Effects and Adverse Reactions ; epidemiology ; etiology ; Drugs, Chinese Herbal ; analysis ; therapeutic use ; toxicity ; Humans