Application and Analysis of High-quality Evaluation for Jianwei Xiaoshi Tablets / 中国实验方剂学杂志

Jianwei Xiaoshi tablets， as a common variety of Chinese patent medicine with "one product with many manufacturers"， have many manufacturers and huge market sales. However， the phenomenon about uneven quality and discrepant price is prominent. Based on this， this study was carried out for the quality evaluation of Jianwei Xiaoshi tablets by applying the high-quality evaluation criteria with the quality as core for Chinese patent medicine， which was based on the full production cycle， from the multi-dimension including raw material selection， production process， quality control， post-marketing research and so on. The evaluation results showed that the quality evaluation scores of Jianwei Xiaoshi tablets from different manufacturers varied greatly （ranging from 35 to 66）， indicating that the quality was significantly different. In the actual production， generally inadequate attention was paid to the quality of raw materials， and the quality of raw materials was insufficient with the score ratio of 43%， especially the poor consistency control of them. The role of good manufacturing practice was obvious， and the scores of production process were generally high with the average score ratio of 62%， and the maximum up to 80%. The technological advancement of the manufacturer was outstanding. The score ratio of quality control was only 31% that the internal quality standard of each manufacture almost stayed at the qualified line， which was equal to the national standard， and the consistency of products was insufficient. The post-marketing research was lacking with the score ratio of 37%. Manufacturers with high brand awareness and market share were upper scores， while the others lagged far behind. The results of this evaluation are in line with the overall prediction， which can provide a reference for the high-quality evaluation of Chinese patent medicine， and supply the scientific data for high-quality and high-price application.

Comparative Study on the Current Situation of Pharmacovigilance in Pharmaceutical Manufacturers of Different Scales in Jiangsu Province / 中国药房

OBJECTIVE：To study the current situation of pharmacovigilance work in large ，medium and small-scale pharmaceutical manufacturers in Jiangsu Province ，and to provide reference for the pharmacovigilance development of drug manufacturers with different scales. METHODS ：The situation of pharmacovigilance work in 108 manufacturers in Jiangsu province was investigated through a questionnaire survey and related websites. The pharmacovigilance work （organization，personnel and training，document，computer system ），drug safety monitoring （case report ，regular safety update report ，post-marketing safety research） and drug risk management （signal management ， risk management plan ， risk control measures ， drug safety communication）of different manufacturers were investigated to put forward the suggestions. RESULTS & CONCLUSIONS ：There was no significant difference in the organizational structure （independently established specialized agencies ）among manufacturers of different scales （P＝0.60）. Most of the manufacturers had less than 50％ of the proportion in the independent establishment of specialized institutions for pharmacovigilance. There was significant difference in personnel and training （situation and number of full-time staff in charge ，medical and clinical pharmacy personnel number ），document（formulating training management system ， entrusted management and key monitoring procedures ），computer system （P＜0.05）. There was no difference in the main collection ways of case reports among manufacturers of different scales ；however，the number of independent reports in 2019（P＜ 0.01），the proportion of quality control process for regular safety update reports （P＝0.01），and the proportion of carrying out post-marketing safety research in recent five years （P＜0.01）in large-scale manufacturers were all significantly higher than small- and medium-scale manufacturers. The proportions of large-scale manufacturers （70.00％） and medium-scale manufacturers （84.38％），which considered “lack of technical guidelines ”as an important factor affecting signal management ，were higher than that of small-scale manufacturers （53.57％）（P＝0.01）；the proportions of large-scale manufacturers （60.00％）and medium-scale manufacturers（50.00％），which had carried out risk management plans in the past five years ，were higher than that of small-scale manufacturers（30.36％）（P＝0.04）；the proportion of large-scale manufacturers （50.00％），which adopted the measures in recent 5 year，was higher than medium-scale manufacturers （37.50％）and small-scale manufacturers （25.00％）；the proportions of large-scale manufacturers （70.00％ ） and medium-scale manufacturers （59.38％ ）， which carried out communication for pharmacists，were higher than small-scale manufacturers （32.14％）（P＜0.01）. Large-scale manufacturers outperformed small- and medium-scale manufacturers in terms of pharmacovigilance system ，drug safety monitoring and drug risk management. Large-scale manufacturers had a certain degree of lack of initiative on performing risk management plans ，medium-scale manufacturers on full-time staffs in charge ，and small-scale manufacturers on pharmacovigilance system. So ，it is recommended that large-scale manufacturers take effective control of variety risk as the goal and actively risk management ；medium-scale manufacturers should continuously enhance the awareness of responsibility and improve the investment of resources on pharmacovigilance work ； small-scale manufacturers should pay more attention to improving the pharmacovigilance system and the compliance of specific work.

Comparative study on chronic multiple organ injury in normal rats caused by high dose of Tripterygium Glycosides Tablets from 6 different manufacturers / 中国中药杂志

The aim of this paper was to compare different effects of Tripterygium Glycosides Tablets from 6 different manufacturers on multiple organ injuries in rats and to explore mechanism of hepatotoxicity preliminarily from the perspective of apoptosis and oxidative stress. Rats were randomly divided into the groups normal, Zhejiang, Hunan, Hubei, Shanghai, Jiangsu and Fujian(7 groups with 16 rats in each group, sex in half). Rats were given Tripterygium Glycosides Tablets at 144 mg·kg~(-1)·d~(-1)(16 times the clinical equivalent dose) once a day according to its corresponding group like rats in Zhejiang group was given Tripterygium Glycosides Tablets from Zhejiang manufactures continuously for 20 days with the life and death situation of mice to be observed, then rats were executed to detect various indicators. RESULTS:: showed that 8 female rats in Zhejiang group died after 15 days of administration, the serum NEUT of rats in Hubei, Fujian and Shanghai groups was significantly lower than that of normal rats. The serum AST, ALT and/or TBiL levels were increased in all rats, and serum BUN and/or CRE levels of rats were also increased in Hunan, Hubei, Fujian and Shanghai groups. In dosage groups, testicular and ovarian coefficients of rats were reduced, the number of sperm were significant decreased while the rate of sperm malformation increased and sperm dynamics parameters of normal, especially in Jiangsu and Zhejiang groups. Liver histopathology and apoptosis of liver cells were observed in dosage groups, especially in Jiangsu and Hubei groups. In liver, Nrf2, HO-1 and Bcl-2 were inhibited and the protein expression level of Bax were increased simultaneously in dosage groups. These results showed that all Tripterygium Glycosides Tablets from 6 manufacturers could lead to chronic multiple organ injuries with disparate specialties in rats, and Jiangsu and Zhejiang groups were more toxic. It could be the mechanism promoting mitochondrial mediated Bax/Bcl-2 cell apoptosis signaling pathway and negatively regulating Nrf2/HO-1 oxidative stress signaling pathway that Tripterygium Glycosides Tablets from 6 different manufacturers resulted in chronic liver injury, the results above were for reference only in subsequent study.

Effects of Tripterygium Glycosides Tablets from 6 different manufacturers on acute liver injury of normal mice / 中国中药杂志

The aim of this paper was to compare the performance of acute liver injury in mice induced by Tripterygium Glycosides Tablets from 6 different manufacturers,and to explore the toxicity mechanism from the perspective of oxidative stress and apoptosis preliminarily. Male or female mice were randomly divided into normal group,Zhejiang group,Hunan group,Hubei group,Shanghai group,Jiangsu group and Fujian group. Mice in Tripgerygium Glycosides Tablets groups were given 16 times the clinical equivalent dose( 300 mg·kg-1) Tripgerygium Glycosides Tablets by oral administration for one time,mice were executed in 24 h after lavaged.Then the visceral brain coefficient of the organ was calculated. Histopathological changes of liver were observed by hematoxylin-eosin staining. Td T-mediated d UTP nick-end labeling was used to detect the apoptosis of the liver cells and the protein content of oxidative stress related factors in liver homogenate. Nuclear transcription factor E2-related factor( Nrf2) and heme oxygenase-1( HO-1) as well as mitochondrial mediated apoptosis-related protein expression levels of Bax and Bcl-2 in hepatic tissue were measured by Western blot.Within 24 hours of administration,6 male mice in Jiangsu group and 2 female mice in Zhejiang group were dying; compared with normal ones,liver coefficients of mice in Zhejiang,Shanghai,Jiangsu and Hunan groups were significantly increased,thymus coefficients in the first two groups were significantly reduced,as well as the lung coefficients of Fujian group mice,the rest was normal. In addition to Hubei group,serum AST,ALT or ALP levels of mice were increased,while TBi L were not being affected. Histopathological changes and apoptosis of liver cells were observed in all mice,and the degree of severity was ranked as Jiangsu,Zhejiang,Shanghai,Hunan,Hubei and Fujian group. All Tripterygium Glycosides Tablets increased the MDA and reduced the content of T-SOD,CAT or GSH in liver tissue while inhibited Nrf2,HO-1 and Bcl-2,increased the protein expression level of Bax( except Hunan group). Tripgerygium Glycosides Tablets from 6 manufacturers all resulted in liver function damage and liver histopathological changes,especially in Jiangsu,Hubei and Fujian,and the mechanism may related to inhibit Nrf2/HO-1 oxidative stress pathway and activate Bax/Bcl-2 apoptosis pathway to mediate lipid peroxidation and induce liver cell apoptosis. Triptolide A may be one of the main toxic components of Tripgerygium Glycosides Tablets that causing drug-induced liver injury. This study was conducted on normal mice with super dose medication,so the relevant results are for reference only.

Analysis of the Reasons for Drug Shortage and Countermeasure Study in Medical Institutions of Sichuan Province from the Perspective of Manufacturers and Distribution Enterprises / 中国药房

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.

Occupational semi-quantitative risk assessment in a crane manufacturing enterprise / 预防医学

Objective To evaluate occupational health risk at sites in a crane manufacturing enterprise and to provide the basis for occupational risk management and worker'health.Methods A crane manufacturing enterprise was selected and investigated for occupational health.Singapore occupational semi-quantitative risk assessment technique was used to evaluate the exposure risk in workers and compared with classification and occupational exposure limits of occupational hazards at workplaces.Results Benzene, toluene, xylene, manganese, butyl alcohol, butyl acetate, welding fume, silica dust, grinding wheel dust, noise were occupational hazard at the crane manufacturing sites.Results showed 3.28% of all the chemical substance analyzed in our study by Singapore occupational semi-quantitative risk assessment technique were high risk, and 8.2% were moderate risk, and 55.74% were low risk and 32.78% were negligible risk.The risk level of dip coating, welding, bob-weight, coremaking, sand mixing, shakeout were between moderate to high.The job grading of occupational chemical substance were correspondingly: harmless, 98.36%;slight, 1.64%.The results of the two methods were significantly different(P<0.05).Conclusion Singapore occupational semi-quantitative risk assessment technique could be used in evaluating the risk level of workplaces.However, this technique is limited in evaluating the risk level of physical factor such as noise and heat and should be combined with National Occupational Standards.

The quality of life and its influencing factors among assembly line workers in manufacturers of Zhongshan City / 中国职业医学

OBJECTIVE: To investigate the current situation of the quality of life and its related factors among assembly line workers in manufacturers of Zhongshan City. METHODS: By cluster sampling method,1 485 assembly line workers from five manufacturing enterprises of Zhongshan City were selected as study subjects. The quality of life was measured by SF-36 scale. RESULTS: The dimension scores of physical functioning,physical role,body pain,general health,vitality,and social function of 1 485 workers were higher than those of normal people in Sichuan and Hangzhou( P < 0. 01). The score of emotional function dimension were higher than those of normal people in Sichuan( P < 0. 01). But the dimension score of mental health was lower than those of the normal people of Sichuan and Hangzhou( P < 0. 01). The multiple linear regression analysis result indicated that the quality of life of assembly line workers was influenced by monthly income,night shift,occupational hazard protection device and regular physical exercise( P < 0. 05). CONCLUSION: The mental health score of assembly line workers in manufacturers was low. The overall score was influenced by employment status and physical exercise.

Quality Comparison of Counting Culture Medium of Drugs Microbial Limit Test from Different Manufacturers / 中国药房

OBJECTIVE:To compare the quality of fungus and bacteria counting culture medium of drug microbial limit test among different manufacturers.METHODS:Culture medium for 7 kinds of nutrient agars and 5 kinds of sodium rose red bengal agars for sale or self-made were enrolled in study.The content of water and nitrogen,pH value were determined.The number of microcolonies which were recovered from 5 kinds of representative bacterial strains was calculated,and the size and number of microcolonies were compared.RESULTS:Physicochemical index of culture medium,the size and number of microcolonies were different among different manufacturers.CONCLUSION:The quality of culture medium is different among different manufacturers,which is associated with physicochemical index.

The Role of the Epidemiological Causality of the Association between Smoking and Lung Cancer / 한국역학회지

It is generally accepted that acknowledgment of the causality of the association between smoking and lung cancer plays a crucial role in imposing liability on tobacco manufacturers in tobacco-related cases. However, acknowledgment of the epidemiological causality of the association is merely a precondition to putting liability on tobacco manufacturers; it does not play a crucial role. Smokers smoke manufactured tobacco by their right to choose according to their self-decision; therefore, it is not reasonable to place all liability concerning lung cancer on tobacco manufacturers. This paper studies the dual structure of the causality of the association between tobacco manufacturing and smoking as well as smoking and lung cancer. It can be understood that tobacco manufacturers must be held liable for lung cancer caused by smoking when there was intentional concealment or insufficient provision of information on the harmfulness of tobacco and the addictiveness of nicotine. The epidemiological causality of the association is the minimum scientific and legal precondition to placing liability on tobacco manufacturers for lung cancer caused by smoking. However, striving for protection and promotion of national health by, for instance, promoting antismoking programs, the epidemiological causality of the association adequately plays a social role when viewed from a public health perspective.

Civil Liability of Pharmaceutical Manufacturers and Medical Institution in Medication Misadventures / 中国药房

OBJECTIVE:To provide references for the accountability of civil liability induced by different causes.METHODS:Literature retrieval and case study were applied to analyze the civil liability of pharmaceutical manufacturers and medical institution in medication misadventures.RESULTS & CONCLUSIONS:At present it is difficult for patients who suffered from medication misadventures caused by drug quality defects,drug adverse reaction or medication errors to claim.The main reasons are imperfect relevant law system and the vacancy of compensation mechanism of drug-induced injury events.It is suggested to establish technology institution for evaluating medication misadventures,state relief and compensation system and encourage pharmaceutical manufacturers to buy products liability insurance.