Ziziphi spinosae semen mainly contains contents of saponins,flavonoids,alkaloids and aliphatic acids.Meanwhile,it has a variety of activities such as sedative-hypnotic,anti-anxiety,anti-depression,nerve protection,cardiovascular and cerebrovascular protection,liver protection,and antioxidant,which is widely used in medicine,food,health food and other fields.The chemical constituents,pharmacological action and clinical application of Ziziphi spinosae semen were systematically summarized in this paper by reviewing the literature,in order to provide theoretical guidance for the sustainable development of the resources and the rational use of Ziziphi spinosae semen.

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.

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.

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.

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.

Objective To investigate the effects of dams-offspring separation on anxiety-like behaviors of dams, and if these anxiety-like behaviors of dams are associated with estrogen receptorα(ERα) and β( ERβ)in some brain regions. Methods Thirty C57BL/6 J female mice were divided into three groups, control group (CG, n= 10,non-isolated group), short-term separation group( SG,/i= 10, dams were separated from their offspring for 15 minuts per day from the second day to the tenth day after childbirth ) and long-term separation group ( LG, n = 10, dams were separated from their offspring for 3 hours per day from the second day to the tenth day after childbirth ). Anxiety-like behaviors of dams were evaluated in an open-field (OF) and elevated plus-maze test ( EPM ). The level of ERα- immunoreactive neurons (ERα-IRs) and ERβ-immunoreactive neurons (ERβ-IRs) in three brain regions including medial preoptic area (mPOA), hypothalamic ventromedial nucleus (VMH) and medial amygdaloid nucleus ( MeA) were analyzed. Results In OF, compared to CG group and SG group, LG group had significantly less time in center area, crossing number and total distance(P<0.001), there were no significant difference between the CG group and SG group( P>0.05 ). In EPM, compared to CG group and SG group, LG group had significantly less percentage of time, distance in open arms and total distance(P<0.001 ). Compared to CG group and SG group, LG group had significantly less ERa-IRs and ERβ-IRs in mPOA, VMH, and MeA(P<0.01). Conclusion Dams that are long-termly separated from their offspring may have anxiety-like behavior, and this behavior may be related to the significant reduction of ERa and ERβ in these brain regions.