Hospital Centralized Monitoring of Post-market Clinical Safety of Naoxintong Capsules in 7 345 Patients / 中国实验方剂学杂志

ObjectiveTo evaluate the clinical safety of Naoxintong （NXT） capsules after marketing， find out the potential risk factors of the drug as soon as possible， and reveal the incidence， nature， and clinical manifestations of the adverse events （ADE） and adverse reactions （ADR） of NXT capsules， so as to provide a basis for safe use of the drug in clinical practice. MethodA prospective， large-sample， multi-center observational cohort study was conducted to monitor all the 7 345 inpatients and outpatients orally taking NXT in 14 hospitals in China from January to December in 2018， with at least one follow-up. The demographic characteristics， disease type， NXT medication， ADR occurrence， characteristics， and prognosis of the patients were collected. SPSS 23.0 was used for single-factor and multivariate logistic regression to predict the influencing factors of ADR. ResultThe male and female patients accounted for similar proportions. There were 5 081 patients （79.40%） aged ≥60 years and 3 153 patients （49.27%） with body mass index （BMI） exceeding the normal standard. There were 344 （5.38%） patients with a history of allergy to medicines and food， 9 （0.14%） patients with a family history of allergy， and 52 （0.81%） patients with a history of allergic diseases. The ADRs associated with NXT occurred in 22 patients， with the incidence of 0.34%. The clinical manifestations of ADR appeared in 31 cases， involving 10 organs/systems， of which gastrointestinal system damage was the most common （17， 54.84%）. All ADRs were mild or moderate. Most ADRs （19， 86.36%） occurred within 4 weeks after administration. The patients with alleviated NXT-associated ADRs accounted for 81.82%. No indicators related to significant increases in ADR risks were found. ConclusionNXT is well tolerated in the general population. The hospital centralized monitoring for the clinical safety of oral Chinese patent drugs based on HIS data and Web tracking and follow-up system is an essential means for the post-market research on the safety of drugs.

Class-imbalance Prediction and High-dimensional Risk Factor Identification of Adverse Reactions of Traditional Chinese Medicine with Centralized Monitoring in Real-world Hospitals / 中国实验方剂学杂志

ObjectiveTo achieve high-dimensional prediction of class imbalanced of adverse drug reaction（ADR） of traditional Chinese medicine（TCM） and to classify and identify risk factors affecting the occurrence of ADR based on the post-marketing safety data of TCM monitored centrally in real world hospitals. MethodThe ensemble clustering resampling combined with regularized Group Lasso regression was used to perform high-dimensional balancing of ADR class-imbalanced data， and then to integrate the balanced datasets to achieve ADR prediction and the risk factor identification by category. ResultA practical example study of the proposed method on a monitoring data of TCM injection performed that the accuracy of the ADR prediction， the prediction sensitivity， the prediction specificity and the area under receiver operating characteristic curve（AUC） were all above 0.8 on the test set. Meanwhile， 40 risk factors affecting the occurrence of ADR were screened out from total 600 high-dimensional variables. And the effect of risk factors on the occurrence of ADR was identified by classification weighting. The important risk factors were classified as follows：past history， medication information， name of combined drugs， disease status， number of combined drugs and personal data. ConclusionIn the real world data of rare ADR with a large amount of clinical variables， this paper realized accurate ADR prediction on high-dimensional and class imbalanced condition， and classified and identified the key risk factors and their clinical significance of categories， so as to provide risk early warning for clinical rational drug use and combined drug use， as well as scientific basis for reevaluation of safety of post-marketing TCM.

Effects of Active Components of Naoxintong Capsule on the Proliferation of HUVEC and Its JAK/STAT Signal Pathway，Vasoactive Substances ，Adhesion Molecules and Inflammatory Factors / 中国药房

OBJECTIVE：To study the effects of the main active components of Naoxintong capsule （NXTC）on the proliferation of human umbilical vein endothelial cell（HUVEC） and its key protein JAK/STAT signal pathway ， vasoactive substances ，adhesion molecules and inflammatory factors so as to clarify the m echanism of NXTC for promoting blood circulation and removing blood stasis. METHODS ：The effects of different concentration of 12 active components [caffeic acid（1.56-200 μmol/L），ferulic acid （1.56-200 μmol/L），senkyunolide H （3.125-200 μmol/L），n-butylidenephthalide（3.125-200 μmol/L），ligustilide（1.56-200 μmol/L），cryptotanshinone（0.625-80 μmol/L），tanshinol sodium （1.56-200 μmol/L），paeoniflorin （1.56-200 μmol/L），formononetin（1.56-200 μmol/L），salvianolic acid B （1.56-200 μmol/L），catechin（1.56-200 μmol/L）and astragaloside Ⅳ（1.56-200 μmol/L）] on the proliferation of HUVECs were evaluated by CCK- 8 assay. The effects of above active components（3 dose groups ，setting up 0 μmol/L blank control group，hereinafter）on mRNA expression of key proteins JAK 2， STAT3，Akt，ERK in JAK/STAT signal pathway were measured by RT-PCR. The effects of each active component on the expression of PAI- 1，VCAM-1，ICAM-1，VEGF and NF-κB p65 were detected by ELISA. RESULTS ：Ferulic acid （6.25，25-200 μg/mL），senkyunolide H （6.25-200 μmol/L），ligustilide（200 μmol/L），cryptotanshinone（10-80 μmol/L），paeoniflorin（1.56， 6.25，12.5 μmol/L），salvianolic acid B （1.56-12.5 μmol/L，200 μmol/L）and catechin （25 μmol/L）could significantly inhibit the proliferation of HUVECs ；caffeic acid （1.56，12.5 μmol/L），ligustilide（50 μmol/L），trashinol sodium （6.25 μmol/L）and paeoniflorin（1.56，100，200 μmol/L）could significantly promote the proliferation of HUVECs （P＜0.05 or P＜0.01）. Compared with blank control group ，mRNA expression of JAK 2，STAT3 and Akt were decreased significantly in some dose groups of ferulic acid，formononetin，salvianolic acid B and astragaloside Ⅳ（P＜0.05 or P＜0.01）；the expression of PAI- 1 were significantly decreased in some dose groups of caffeic acid ，ferulic acid and n-butylphthalide；the expression of ICAM- 1 and VCAM- 1 were decreased significantly in some dose groups of caffeic acid ，ferulic acid ，n-butenylphthalide，cryptotanshinone，formononetin and catechin；the expression of NF-κB p65 were decreased significantly in some dose groups of ferulic acid ，n-butenylphthalide， formononetin，salvianolic acid B and astragaloside Ⅳ；the expression of VEGF were increased significantly in some dose groups of caffeic acid and catechin （P＜0.05 or P＜0.01）. CONCLUSIONS ：The active components of Naoxintong capsule may play the role of promoting blood circulation and removing blood stasis by inhibiting the expression of JAK/STAT signal pathway key protein mRNA and PAI- 1，ICAM-1，VCAM-1，NF-κB p65 in HUVEC ，and promoting the expression of VEGF.

Classification and Analysis of Set Prescription Preparations Containing Toxic Decoction Pieces in 2015 Edition of Chinese Pharmacopoeia (Part I) / 中国药房

OBJECTIVE: To provide reference for strengthening safe use and supervision of set prescription preparations containing toxic decoction pieces [called "Chinese patent medicine (CPM) containing toxicity" for short] in clinic. METHODS: The CPM containing toxicity in 2015 edition of Chinese Pharmacopoeia (part I) were summarized and analyzed to put forward the suggestion on improving safe use of them in clinic. RESULTS & CONCLUSIONS: A total of 474 CPM containing toxicity are included in 2015 edition of Chinese Pharmacopoeia (part I), accounting for 31. 75％ of set prescription preparations. There are 435 oral preparations (12 preparations both for oral and external use), 38 preparations for external use, one intramuscular injection, accounting for 91. 77％, 8. 02％, 0. 21％ of CPM containing toxicity, respectively. There are 318, 93, 32, 31 set prescription preparations containing 1, 2, 3 or more ingredients toxic decoction pieces, accounting for 67. 09％, 19. 62％, 6. 75％, 6. 54％, respectively. At present, basic research on CPM containing toxicity is weak; the information of the instructions is not perfect; guidance for clinical drug use is absent. It is suggested to strengthen basic research on CPM containing toxicity, develop drug use study among special population, improve rational use of Chinese patent medicine and strengthen post-marketing safety reevaluation so as to guarantee the safety of CPM containing toxicity use in clinic.

Anti-aging Effect Study of Ethyl Acetate Extract from Folygonum multiflora on Caenorhabditis Elegans / 中国药房

OBJECTIVE:To study the lifespan effect of ethyl acetate extract from Polygonum multiflora(EPM)on caenorhab-ditis elegans,and to investigate its anti-aging effect. METHODS:EPM low-concentration,medium-concentration and high- concen-tration groups(25,37.5,50 mg/L,calculated by crude drug)and blank group(0 mg/L)were established to investigate the effects of EPM on the lifespan of caenorhabditis elegans. EPM group(37.5 mg/L)and blank group(0 mg/L)were established to perform re-productive test,acute heat stress test and acute oxidative stress test of caenorhabditis elegans. The effects of EPM on reproductive capacity and pressure stress of caenorhabditis elegans were investigated. RESULTS:The lifespan test,average lifespan of cae-norhabditis elegans in EPM low-concentration,medium-concentration and high-concentration groups were prolonged significantly, compared to blank group(P<0.05 or P<0.01),especially in EPM medium-concentration group. In reproductive test,the number of offspring of caenorhabditis elegans in EPM group on the second and third day were increased significantly,compared to blank group (P<0.05). In acute heat stress test and acute oxidative stress test,average survival time of caenorhabditis elegans in EPM group was prolonged significantly(P<0.05). CONCLUSIONS:37.5 mg/L EPM can retard the aging process of caenorhabditis ele-gans and doesn’t damage the reproductive capacity.

GBM Propensity Score Weighting for Causal Inference Research / 世界科学技术-中医药现代化

Objective In observational studies or non-randomized design,the researchers' ability to make causal inferences from data was hampered by confounding factors.This study used this method to analyze a group of observational medical data in order to instruct relevant medical personnel to carry out their own causal inference studies.Methods At present,the four main types of propensity scoring methods:matching,stratification,inverse probability weighting and covariate adjustment have been widely used in the study of causal inference.Propensity score method can theoretically eliminate the bias of the observable confounding factors,so that the treatments variables are close to the result of random assignment design,thus,it is estimated that the treatment factor has a causal effect on the outcome.Results Considering the advantages of the inverse probability weighting method over other methods,this paper summarizes the applicable conditions for the estimate of causal effect,particularly illustrates the use of a modern nonparametric statistical technology--Generalized Boosted Models (GBM) and its advantages and disadvantages.Conclusion When there is a lot of different types of confounding factors,and uncertain functional forms for their associations with treatment selection in linear,non-linear or interaction effect,and other issues,GBM propensity score weighting method can overcome the obstacles in the process of accurately estimating propensity score.

Study on 10 409 cases of post-marketing safety Danhong injection centralized monitoring of hospital / 中国中药杂志

<p><b>OBJECTIVE</b>To study Danhong injection adverse reactions (ADR) incidence, nature and clinical performance, provide the basis for the clinical safety of drugs.</p><p><b>METHOD</b>Multi-center, a large sample of hospitals focused on monitoring method.</p><p><b>RESULT</b>Danhong injection ADR for the rapid onset and ease the quick recovery, the rate was 0. 682% , the newly discovered ADR constipation, sweating, tinnitus, irritability, joint disease, erythema, venous pain, phlebitis, local numbness, pain, weakness, gastrointestinal ulcer bleeding, vasospasm, cyanosis.</p><p><b>CONCLUSION</b>Danhong injection adverse reactions are type A adverse reactions occasionally, centralized monitoring of hospital medicine injection method is to carry out post-marketing safety re-evaluation of appropriate methods.</p>

Comparative study on four kinds of assessment methods of post-marketing safety of Danhong injection / 中国中药杂志

<p><b>OBJECTIVE</b>To study the adverse reaction of Danhong injection with four kinds of methods, central monitoring method, chart review method, literature study method and spontaneous reporting method, and to compare the differences between them, explore an appropriate method to carry out post-marketing safety evaluation of traditional Chinese medicine injection.</p><p><b>METHOD</b>Set down the adverse reactions' questionnaire of four kinds of methods, central monitoring method, chart review method, literature study method and collect the information on adverse reactions in a certain period. Danhong injection adverse reaction information from Henan Province spontaneous reporting system was collected with spontaneous reporting method. Carry on data summary and descriptive analysis.</p><p><b>RESULT</b>Study the adverse reaction of Danhong injection with four methods of central monitoring method, chart review method, literature study method and spontaneous reporting method, the rates of adverse events were 0.993%, 0.336%, 0.515%, 0.067%, respectively. Cyanosis, arrhythmia, hypotension, sweating, erythema, hemorrhage dermatitis, rash, irritability, bleeding gums, toothache, tinnitus, asthma, elevated aminotransferases, constipation, pain are new discovered adverse reactions.</p><p><b>CONCLUSION</b>The central monitoring method is the appropriate method to carry out post-marketing safety evaluation of traditional Chinese medicine injection, which could objectively reflect the real world of clinical usage.</p>

Effects of Decoction Equipment on Yield of Cinnaldehydum from Cinnamomun cassia / 中国药房

OBJECTIVE: To compare the yield of cinnaldehydum from Cinnamomum cassia by TCM decoction machine or stainless steel pot at different decoction time, and to determine the appropriate decoction method of C. cassia. METHODS: The content of cinnaldehydum from C. cassia was determined by HPLC. T-test of data and results was conducted. RESULTS: At different decocting time, the yield of cinnaldehydum from C. cassia by TCM extraction machine was higher than by stainless steel pans (P