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Examination and assessment of target organ toxicity in toxicologic pathology of preclinical safety evaluation of drugs should combine the results of the gross pathology,histopathology and clinical pathology examination data in a well-considered,stepwise approach.In addition,the nomenclature and diagnostic criteria recommended by INHAND should be used to avoid subjective and inappropriate diagnosis.In this paper,we briefly introduced the basic principles for the examination of organ toxicity in toxicology studies,gross pathology,histopathology,diagnostic approach,procedures,and considerations,international harmonization of diagnostic term and criteria,clinical pathology parameters analysis,results of a well-concerted combination of anatomical and clinical pathology data so as to provide some reference for the examination and assessment of target organ toxicity in toxicologic pathology in the field ofpreclinical safety evaluation of drugs in China.
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Neurotoxicity is one common adverse effect caused by many drugs or compounds.In the early phase of new drug development,it is necessary to screen for neurotoxicants.Neurotoxicity studies in nonhuman primates (NHP) are used to evaluate the neurotoxicity of small-molecule drugs or vaccines that may affect the nervous system across the blood-brain barrier during preclinical safety assessment.Toxicologic pathological evaluation or neuropathological examination is the "gold standard" for the evaluation of drug neurotoxicity in preclinical drug safety studies.In this paper,the majory factors influencing the quality of neuropathology evaluation in toxicology,including the general strategy of neuropathology evaluation,the optimal timing of evaluation,the specific blood-brain barrier in the nervous system,the method of sampling in the histopathology of nerve tissue,and the interference of artificial artifacts in diagnosis of neuropathology,were detailly analyzed in order to provide a reference for setting guidelines of neurotoxicity risk assessment in China and pathologists and toxicologists engaged in nonclinical neurotoxicity studies.
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Computerized system has been played an increasingly important role in preclinical safety evaluation of drugs and has been used directly or indirectly for data acquisition,processing,reporting as well as raw data storage.However,the computerized system has not been widely used in facilities for preclinical safety evaluation of drugs or only some functions of modules of computerized system have been used.Based on the current application status of the computerized system in the facilities for preclinical safety evaluation of drugs in China,this paper briefly introduced the following aspects about validation of computerized system,such as GLP regulatory requirements of validation of the computerized system,validation process of the computerized system,maintenance of validation state of the computerized system,safety precautions of performance of the computerized system,as well as electronic records and electronic signatures with the purpose to provide some references for carrying out and speeding up the validation of computerized system and to further improve the efficiency of the computerized system in facilities for preclinical safety evaluation of drugs in China and to be in line with international practice.
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Toxicologic pathology plays an important role in the safety evaluation of drugs.The results of toxicologic pathology can answer the basic problems of pathological lesions such as location,severity grading,nature and prognosis,etc.Necropsy and gross pathology examination are important aspects of toxicologic pathology assessment.Procedures typically include preparation for the necropsy,euthanasia procedures,identification and recording all gross lesions,collection of tissues listed in the study protocol,determination of organ weight,as well as tissue fixation so as to be ready for the subsequent tissue processing and histopathology examination.All the procedures must be done in a consistent manner and in accordance with standard operating procedures (SOPs).The present paper briefly introduced the principles of necropsy and gross pathology examination for toxicologic pathology in order to standardize the procedures and to lay foundation for the improvement of the histopathology examination in the field of preclinical safety evaluation of drugs of China.
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Objective To develop a laser positioning device for GE OEC850 and Wandong HMC-36 C-arm.Methods The device was composed of two cross-type laser tubes,timing circuit and power source.The optimal 30 cm projection point was determined with laser dual-crossed-line positioning method and considerations on the distance between the tube of GE OEC850 or Wandong HMC-36 C-arm and the image intensifier.Then the projection range was found around 30 cm to define the targeted area.Results The device eliminated the needs of multi times of projection due to improper positioning,decreased the exposure to medical personnel and patient during the operation,prolonged the service life of the tube and reduced the cost for hospital equipment.Conclusion The device behaves well in positioning and easy operation,and thus is worthy promoting clinically.
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Objective To develop a laser positioning device for GE OEC850 and Wandong HMC-36 C-arm.Methods The device was composed of two cross-type laser tubes,timing circuit and power source.The optimal 30 cm projection point was determined with laser dual-crossed-line positioning method and considerations on the distance between the tube of GE OEC850 or Wandong HMC-36 C-arm and the image intensifier.Then the projection range was found around 30 cm to define the targeted area.Results The device eliminated the needs of multi times of projection due to improper positioning,decreased the exposure to medical personnel and patient during the operation,prolonged the service life of the tube and reduced the cost for hospital equipment.Conclusion The device behaves well in positioning and easy operation,and thus is worthy promoting clinically.
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By reviewing the reports of clinical study on herbs of promoting the circulation of Qi to remove blood stasis in treating adenomyosis in recent years, therapeutic mechanism and clinical effects of the treatment were summed up, in order to provide literature reference for the therapy.
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Objective To analyze genetic characteristics of HIV isolated from men who have sex with men(MSM) in Beijing and predict the epidemic trend in this population.Methods All of the HIV gene sequences in our laboratory obtained from MSM in Beijing were used,which were aligned with all of the HIV gene sequences from MSM and other populations in China downloaded from Los Alamos HIV Database.Phylogenetic trees were constructed by using software PhyML 3.0,based on which the relationships of prevalent HIV strains between Beijing MSM and other populations in China were further explored.The evolution rate,the time of most recent common ancestor (tMRCA),the epidemic parameters,the reproductive number (R0) were calculated by using software BEAST to predict HIV evolution and epidemic characteristics.Results Multiple HIV subtypes,including subtype B,CRF01_AE and CRF07_BC,were found to be prevalent among MSM in Beijing.In ML tree constructed based on strains from the whole country,three clusters including B-1,CRF01_AE-1,and CRF01_AE-2 were found among the MSM in Beijing (accounting for 40％).At least three independent introduction of B 1 cluster strains into Beijing MSM were found,which were at March 1991 (July 1984-February 1997),January 1994 (January 1989-January 1998),April 1991 (August 1984-January 1996).For CRF01_AE strains,two clusters including CRF01_AE-1 and CRF01_AE-2 were introduced into the population at December 2000 (March 1998-January 2003) and December 2001 (January 2000-July 2003) respectively.The population epidemiology of HIV in Beijing MSM was reconstructed based on sequences.The CRF01_AE-1 cluster spread more quickly than the other two clusters,and the evolution rate was higher.Conclusion Multiple HIV subtypes were found prevalent among MSM in Beijing.Although subtype B strain was introduced into Beijing MSM earlier than CRF01_AE strain,CRF01_AE strain increased more quickly than subtype B strain.More research and control of the CRF01_AE prevalence will be helpful for prevention and control of HIV epidemic in MSM in Beijing.
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<p><b>OBJECTIVE</b>To observe the clinical efficacy of Bushen Huoxue Sanyu Decoction (BHSD) in treatment of adenomyosis (AM) patients.</p><p><b>METHODS</b>Seventy AM patients of Shen deficiency blood stasis syndrome (SDBSS) were randomly assigned to two groups, the CM treatment group (50 cases) and the Mirena group (20 cases). Patients in the CM treatment group were treated with BHSD, one dose per day. Levonorgestrel intrauterine system (Mirena) was placed in the uterine cavity of those in the Mirena group. The therapeutic course for all was 3 months. Changes of dysmenorrhea, menstrual quantity, SDBSS, CM syndrome, uterine volume, and serum CA125 levels were observed before and after treatment.</p><p><b>RESULTS</b>Compared with before treatment in the same group, scores for dysmenorrhea integral, scores for menstrual quantity, scores for SDBSS, and scores for CM syndrome all decreased in the two groups after treatment (P < 0.01). Compared with before treatment in the same group, the uterine volume was reduced after treatment in the two groups (P < 0.05) and serum carbohydrate antigen CA125 levels decreased between the two groups (P < 0.05, P < 0.01). Compared with the Mirena group, scores for dysmenorrhea integral increased and scores for SDBSS decreased in the CM treatment group (P < 0.01, P < 0.05). There was no statistical difference in the uterine volume or serum carbohydrate antigen CA125 levels (P > 0.05).</p><p><b>CONCLUSIONS</b>BHSD could effectively alleviate main symptoms of AM patients of QSBSS such as dysmenorrhea, profuse menstrual blood volume, and increased uterine volume, and lower scores for QSBSS and the total score for CM syndrome.</p>
Subject(s)
Female , Humans , Adenomyosis , Drug Therapy , Drugs, Chinese Herbal , Pharmacology , Therapeutic Uses , Dysmenorrhea , Levonorgestrel , Therapeutic UsesABSTRACT
Isolated pulmonary amyloidosis is a very rare disease. We retrospectively reviewed the records of patients with pathologically proven isolated pulmonary amyloidosis treated at our hospital from 1990 to 2011. There were 9 males and 4 females with a mean age of 54.7 years [range, 45-72 years] and the mean course of disease was 46.5 months [range, 5 months-15 years]. The most common symptoms were cough [10/13], expectoration [8/13], hemoptysis [4/13], chest tightness [12/13], dyspnea [10/13], chest pain [3/13], fever [5/13], and body weight loss [2/13]. Radiological findings included tracheal stenosis [2/13], bronchial stenosis with atelectasis [5/13], pulmonary nodules [3/13], lung consolidation [1/13], and lymph node enlargement with pleural effusion [2/13]. Treatments included endotracheal stenting, endoscopic resection of tracheal and bronchial lesions, lung resection, and drug therapy with glucocorticoids, antineoplastic agents, or antibiotics. Four patients died of the disease within 1 year of diagnosis, 2 died of pneumonia at 3-4 years after original treatment, and the remaining patients are alive with follow-up ranging from 3 to 15 years. Isolated pulmonary amyloidosis is a rare disease with a relatively high mortality and its various manifestations make diagnosis challenging. Surgical resection of lesions and chemotherapy tend to be effective treatments
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Objective To investigate the mechanism and significance of low density nitric oxide (NO) in-halation combined with urokinase (UK) in treatment of pulmonary thromboembolism in swine. Method PIE model was estabhshed in 12 healthy infant swines, which were subsequently assigned to UK group or UK+NO ter establishment of the PIE model;in the UK+NO group, swines received continuous NO inhalation of 10 ppm NO for two hours in addition to administration of UK no done in the UK+NO group. Volume of physiological dead space (VDphy), volume of alveolar dead space (VDalv), intrapoulmonary shunt (Qs/Qt), mean ptdmonary arteri-al pressure (PAP), systolic blood pressure (SBP), heart rote (HR), cardiac output (CO), arterial blood pH val-ue, arterial partial pressure of carbon dioxide (PaCO2) and arterial partial pressure of oxygen (PaO2) were mea-sured at 30 min before and 0 min, 30 min, 60 rain, 120 min and 180min after establishment of pulmonary em-bolism.All date were analyzed by ANOVA (SNK-q test),and P<0.05 was considered as significantly differet. Results After PE, VDphy, VDalv, Qs/Qt and PAP of both groups increased markedly compared with the pre-PE values (P<0.01), but the post-PE PAP showed a tendency of decline as time passed. Post-PE PaO2 of both groups decreased significantly (P<0.05 and P<0.01). There were no significant differences in HR, SBP, CO, pH or PaCO2 between pre-PE and post-PE (P>0.05). Both pre- and Post-PE PAP of UK+NO group were markedly less than those of the UK group (P<0.05 and P<0.01). No significant difference was found in other measurements between the two groups. Conclusions UK combined with low density NO inhalation may lower pul-monary arterial pressure promptly to alleviate PIE without distur bance in hemodynamics or gas exchange status and without pulmonary raterial pressure rebound.
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Objective To investigate the mechanism and significance of low concentration nitric oxide (NO) inhalation in the treatment of pulmonary thromboembelism in swine. Method The pulmonary thromboem-bolism(PTE) model was made in 15 healthy infantile swines which were subsequently assigned to either control group (n = 8) or NO group (n = 7). Swines of the control group were not treated with any medicine, while 10 ppm of NO was administered by continuous inhalation for 2 hours to swines of NO group. Volume of physiological dead space (VDphy), volume of alveolar dead space (VDalv), intrapulmonary shunt (Qs/Qt), mean pulmonary arterial pressure (PAP), systolic blood pressure (SBP), heart rate (HR), cardiac output (CO), arterial blood pH (pH), arterial partial pressure of carbon dioxide (PaCO2) and arterial partial pressure of oxygen (PaO2) were measured 30 min before and 0 min, 30 min, 60 min, 120 min and 180 min after establishment of VIE. Results The post-FIE VDphy, VDalv, Qs/Qt and PAP in both groups increased markedly after PTE compared with the cor-responding pre-PTE measurements (P < 0.01). Post-FIE PaO2 of both groups decreased significandy (P <0.05 and P <0.01), while significance difference was found between pre- and post-PTE HR, SBP, CO, pH or PaCO2 in neither groups (P > 0.05). Both post-PTE PAP and VDalv in NO group were markedly lower(P <0.05 and P <0.01) and beth PaCO2 and PaO2 were much higher than those of the control group (P <0.05). No signi-fieant difference were found in other measurements between two groups. Conclusions Pulmonary arterial pressure may be lowered, alveoli dead space may be reduced and PaCO2 increased by low concentration NO inhalation for the treatment of PIE without decline in haemodynamic status.
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Under the socialist market-oriented economic system, state-owned hospitals need to overcome many problems in their traditional management system. The authors discuss a series of issues, including the property right involved in the reform of the management system of state-owned hospitals; the relationships between nonprofit hospitals run by the government and ways of handling them; the conditions of using the corporation management structure in hospitals; the responsibilities of the government in the framework of medical services and the form in which the government supervises state-owned hospitals. Lastly, the authors put forward suggestions from the perspective of policy-making on the reform of the management system of state-owned hospitals.