OBJECTIVE:To study the effects of Heishun tablets combined with Rheum palmatum on the pharmacokinetics of hypaconitine in rats. METHODS:Rats were randomly divided into single drug group(Heishun tablets decoction)and drug combi-nation group(Heishun tablets-R. palmatum mixture decoction),with 18 rats in each group. They were given relevant drugs intragas-trically,by 10 g(medicinal materials)/kg of Heishun tablets. 0.3 ml blood samples were collected before(0 h)and 0.083,0.167, 0.333,0.5,0.75,1,1.5,2,3,4,6,8,10 h after medication with 6 rats at each time point,respectively. The blood concentra-tion of hypaconitine was determined by HPLC-MS using palmatine hydrochloride as internal standard. DAS 2.0.1 software was used to calculate pharmacokinetic parameters. RESULTS:The linear range of hypaconitine was 0.102 4-100 ng/ml (r=0.998 7),and the limit of quantification was 0.1 ng/ml. The pharmacokinetic parameters of single drug group vs. drug combination group were as follows as tmax of (0.50 ± 0.086) h vs. (0.75 ± 0.132)h;t1/2 of (9.967 ± 1.123) h vs. (3.708 ± 0.507) h;AUC0-10 h of (26.087 ± 0.672) μg·h/L vs.(6.516 ± 1.135) μg·h/L;cmax of (6.124 ± 2.312) μg/L vs. (1.592 ± 0.051) μg/L. Compared with single drug group,t1/2,AUC0-10 h and cmax of hypaconitine were decreased in drug combination group,with statistical significance (P<0.05). CONCLUSIONS:R. palmatum can inhibit the absorption of hypaconitine in rats,and speed up the elimination of it in rats.

OBJECTIVE:To investigate the role of compatibility on clinical efficacy action of the prescription containing Curcu-ma zedoaria,and to improve the pertinence of drug use by medical staff and clinical efficacy of C. zedoaria. METHODS:By re-viewing relevant literatures,the prescriptions containing C. zedoaria were selected to summarize the effects of compatibility on clini-cal efficacy of C. zedoaria. RESULTS:345 prescriptions containing C. zedoaria were collected,mainly including the compatibility of C. zedoaria with traditional Chinese medicine which promote the circulation of qi,activate blood and remove blood stasis,toni-fy deficiency,warm interior and clear heat. The prescriptions containing C. zedoaria with sparganii often included Rhizoma Sparga-nii and C. zedoaria,involving 219 prescriptions(13.94%). CONCLUSIONS:C. zedoaria have the effects of activating blood stag-nation,promoting the circulation of qi,removing food retention and relieving pain;different compatibility greatly influence the clinical efficacy of C. zedoaria;common couplet medicines are R. Sparganii and C. zedoaria,and it can play the role of activating blood stagnation,promoting the circulation of qi,removing food retention and relieving pain;Common Vladimiria Root combined with Rheum palmatum can promote the circulation of qi and relieve pain. Medical staff should prescribe the prescriptions and use drugs for the compatibility of C. zedoaria based on clinical demands.

Objective To study the value of the technique of "Push-pull traction-relax homingrepeatedly confirmed" in the prevention of bile duct injury in LC. Methods From March 2001-August 2009, we applied this technique in 4800 cases of LC. The technique of "Push-pull traction" showed the structures of in the Calot's triangle. The technique of "relax homing" was to restore the cystic duct,hepatic duct and common bile duct to their original anatomical positions. The technique of "repeatedly confirmed" repeatedly identified the positions of the cystic duct, the common hepatic duct and the common bile duct. Results There was no bile duct injury. Conversion to open surgery happened in 118patients due to difficulties in identifying the Calot's triangle structures, bile duct stones, gallbladder cancer, and gallbladder-duodenal fistula. Conclusions The "Push-pull traction-relax homing-repeatedly confirmed" technique could effectively prevent bile duct injury in LC. The method is simple, easy to master and worthy of promotion.

OBJECTIVE：To initially evaluate the safety of ceritinib after it is marketed ，and to provide reference for the rational use of drug. METHODS The report odd ratio method and proportional reporting ratio method were used to mine the signals of ceritinib-related adverse events from FDA adverse event reporting system （FAERS）during the second quarter of 2014 to the third quarter of 2019. The patients ’gender，age，body weight ，daily dose and course of treatment were collected. SPSS 26.0 software was used to test the number of ADR cases of this system group and other system groups by chi square test. RESULTS ：A total of 10 318 ADR reports with ceritinib as the first suspicious drug were collected ， and 236 ADR signals of seretinib were excavated. After excluding the ineffective treatment ，187 ADR signals were obtained ，involving 16 systems. Inaddition to those mentioned in the drug instructions ，the signals also included various nervous disease ，blood and lymph system disease ，infections and infectious disease ，etc.，such as hand-foot-genital syndrome ，mutation of anaplatic lymphoma kinase gene. Among them ，the ADR reports of gastrointestinal diseases were the most （576 cases）. Compared with ADR of other systems ，gender，age，body weight，daily dose and treatment course had significant effects on ADR of gastrointestinal diseases （P＜0.05）. Most of the patient with gastrointestinal ADR after using ceritinih were female （59.9％），45 years old and above （70.3％），body weight ≤65 kg （68.1％），daily dose 451-750 mg/d（50.2％），and medication duration less than 3 months（75.7％）. CONCLUSIONS ：The risk of gastrointestinal ADR in female patients over 45 years old and with body weight less than 65 kg after using seretinib is relatively high. This kind of ADRs are also related to daily dose ，and most of which occur within 3 months. Therefore ，great importance should be attached to drug monitoring during clinical use.

OBJECTIVE： To investigate the reasons for drug shortage in medical institutions of Sichuan province and put forward relevant countermeasures， and to provide reference for establishing supply security mechanism of drug shortage. METHODS： Questionnaire survey was conducted to investigate drug shortage in 78 medical institutions of the province during Jan. 2015-Jun. 2017. Traceability investigation was conducted from manufacturers and distribution enterprises involved in drug shortage. Questionnaire survey and field investigation were combined to analyze the reasons for drug shortage in Sichuan province and put forward countermeasures. RESULTS： Totally 78 questionnaires were sent out to medical institutions with recovery rate and effective rate of 100％. A total of 206 drugs were reported by 78 medical institutions， involving 240 specifications for shortage in total. Totally 140 questionnaires and 68 questionnaires were distributed to the manufacturers and distribution enterprises involved in drug shortage， and the recovery rate and effective rate were all 100％. Combined with the field survey， survey results of shortage drugs of 212 specifications were obtained. From the perspective of manufacturers， the most important factors causing drug shortage were the increase of production cost （66.51％） and circulation cost（26.88％）. From the perspective of distribution enterprises，the main factors causing drug shortage were insufficient supply of drugs（75.47％），inventory management（16.51％） and price inversion（11.32％）. CONCLUSIONS： Main reasons of drug shortage from manufacturers and distribution enterprises include the increase of production cost and circulation cost， drug price inversion， inventory management and bidding procurement. It is suggested that measures should be taken to improve the bidding and pricing system of drugs， mobilize the enthusiasm of enterprises； improve the early warning mechanism of drug shortage on the enterprises， strengthen information communication； establish the mechanism of drug shortage reserve， organize the emergency production of drug for shortage； strengthen the management of drug shortage supply chain， purify the unhealthy atmosphere in the market； improve the emergency disposal methods of drug shortage， and improve the supply guarantee ability of drug shortage. Departments cooperate to reduce the emergence of drug shortage and ensure the continuous access to safe and effective drugs in clinic.

OBJECTIVE： To investigate the situation and reasons of drug shortage in some medical institutions from Sichuan province. METHODS： A questionnaire survey was conducted among 78 medical institutions in Sichuan province by stratified random sampling. The situation of drug shortage were collected from Jan. 2015 to Jun. 2017， mainly including the basic information of medical institutions， drug shortage situation， specific drug shortage information and the reasons for drug shortage. Descriptive analysis of the information collected by the questionnaire was carried out， and Logistic regression analysis of the data by SPSS 20.0 software was adopted to find out the key factors affecting drug shortage. RESULTS & CONCLUSIONS： Totally 78 medical institutions include 13 third-level hospitals， 22 second-level hospitals and 43 primary medical institutions （10 community health service centers， 33 township health centers）. A total of 78 questionnaires were sent out， and the recovery rate and effective rate both were 100％. Among them， 68 medical institutions reported 206 shortage drugs totally， involving 240 specifications. The prices of more than 88.34％ of the shortage drug were less than 50 yuan. Main types of shortage drugs included anti-infective drugs， central nervous system drugs and cardiovascular system drugs， and most of them were purchased directly through internet. The proportion of temporary shortage （shortage time＜3 months） and long-term shortage （shortage time＞12 months） was relatively high （more than 68％ in total）. Drug supply and medical institutions’own factors were two main causes of drug shortage. Logistic regression analysis showed that main factors affecting the time of drug shortage were hospital drug purchase process， location of medical institution and drug purchase price. The main factors affecting the specifications of drug shortage in medical institutions were the process of drug purchase， the limitation of hospital purchase catalogue， primary or non-primary medical institution， comprehensive or specialized hospitals. It is suggested that medical institutions in this region can reduce the drug shortage caused by their own reasons by building a platform for drug information management， optimizing drug purchase catalogues and plans， strengthening the management of pharmacy inventory and establishing a regulatory system for distribution enterprises.