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

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

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.

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.

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 investigate the clinical efficacy of coronary renal shunt via splenic vein for portal hypertension (PHT) after splenectomy.Methods The retrospective descriptive study was adopted.The clinical data of 5 patients with PHT who were admitted to the People's Hospital of Ningxia Autonomous Region from August 2012 to April 2015 were collected.Operative procedures:two procedures of coronary renal shunt via splenic vein (SV) were carried out after primary splenectomy.Procedure 1:the SV was freed from the residual end to the right for 5-6 cm in length and end-to-side spleno-renal shunt was carried out.The anterior wall of superior mesenteric vein (SMV) was exposed beneath the pancreatic neck and dissected behind the neck upward until the upper edge of the SV and its confluence with the left gastric vein (LGV) were exposed.The SV was ligated with clip between portal vein (PV) and LGV to let blood flow from LGV drain through the whole course of SV to left renal vein (LRV).Procedure 2:the peritoneum at the inferior border of the pancreas was incised,and the junctions of the SV and SMV and junctions of the SV and LGV were exposed.The inferior mesenteric vein (IMV) was divided between ligations.Dissection of the SV was carried out to the left for 3-4 cm in length and was divided.Its distal end was tied and proximal stump anastomosed to LRV by the end-to-side anastomosis.The SV was ligated with clip between PV and LGV.The right gastric and gastroepiploic vessels were ligated at the junction of the antrum and the body,and from this point,the hepatogastric ligment and the omentum were divided upward and downward respectively to completely separate the venous flow between the hepatointestinal area and the stomach in the two procedures.Patients took oral enteric-coated aspirin and warfarin after operation.(1) Intraoperative observation indicators included surgical procedures,operation time,volume of blood loos and free portal pressure (FPP).(2) Postoperative observation indicators included recovery of patients,time to anal exsufflation,time for diet intake,time of abdominal drainage,duration of hospital stay and occurrence of complications.(3)The follow-up using telephone interview and outpatient examination was performed to detect the changes of platelet (PLT),portal vein thrombosis (PVT),patency of spleno-renal vein anastomosis,oral anticoagulants and gastroesophageal varices up to October 2015.Measurement data with skewed distribution were analyzed by M (range).Results (1)Intraoperative observation indicators:5 patients underwent successful coronary renal shunt via splenic vein.Two patients received procedure 1 and 3 patients received procedure 2.Operation time and volume of blood loss were 226 minutes (range,195-298 minutes) and 425ml (range,235-820 mL).FPP was 3.46 kPa (range,2.69-4.61 kPa) before spleen resection,2.69 kPa (range,2.11-3.07 kPa) after spleen resection,2.98 kPa (range,2.30-3.36 kPa) after spleno-renal anastomosis,respectively.(2) Postoperative observation indicators:5 patients had good recovery,and time to anal exsufflation,time for fluid diet intake,time of abdominal drainage removal and duration of hospital stay were respectively 3 days (range,2-4 days),3 days (range,2-4 days),5 days (range,4-9 days) and 14 days (range,10-17 days).Of 5 patients,1 was complicated with pleural effusion and atelectasis and 1 with serum tumescence of incision.(3) Follow-up situations:5 patients were followed up for a median time of 18 months (range,6-36 months).The level of postoperative PLT was continuously growing,and the dose of oral warfarin was increased according to the level of growing PLT.The follow-up results of procedure 1 in 2 patients:1 patient was followed up for 36 months and complicated with splenic vein thrombosis at postoperative month 6,and underwent transcatheter hepatic arterial chemoembolization (TACE) due to primary liver cancer at postoperative month 12,and then no special treatment was conducted due to splenic vein occlusion and sever esophageal varices without red-color sign or bleeding at postoperative month 36.The other patient was followed up for 24 months,and didn't undergo special treatment due to mild hepatic encephalopathy with a level of blood ammonia of 76 μmol/L at postoperative month 3,and then was found to have mild esophageal varices at postoperative month 18 by computed tomography (CT) and gastroscopy.Three patients using procedure 2 were followed up at month 6,12,18,with increased body mass index (BMI) and without occurrence of peritoneal effusion and hepatic encephalopathy,and they were complicated with mild gastroesophageal varices by reexamination of CT angiography and gastroscopy at postoperative month 6.Conclusion Coronary renal shunt via splenic vein for PHT after splenectomy could relieve hypersplenism and reduce selectively vein decompression of gastroesophageal varices.

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 .