The animal laboratory of pharmaceutical and biological product inspection and testing institutions undertakes important basic support tasks for testing and scientific research work.This article summarizes the management experience accumulated in the operation of our institution's CNAS-CL06 quality management system,providing reference for similar institutions in operation to ensure the scientific nature of animal experimental data.In order to ensure the scientific nature of animal experimental data,the experimental animal institution has successfully passed the CNAS accreditation of the experimental animal institution,and has completed rectification on time during on-site supervision and evaluation.At the same time,regular self inspections of the system have been carried out in accordance with the"Quality and Capability Accreditation Guidelines for Experimental Animal Breeding and Use Institutions"(CNAS-CL06).During the self inspection process,we examined issues while improving the content of the system.Starting from animal procurement,occupational health and safety,animal disease treatment and care,and facility operation emergency drills,we enriched the content of the quality management system,ensured the continuous and effective operation of the system,and ensured the effectiveness and standardization of animal experiment data.At the same time,we contributed to the management ideas of our institution in sharing animal experiment platforms,provide hardware and software support for the construction of cloud platforms for animal experiments.This article aims to explore and form a quality management model for the experimental animal industry based on practical work,being focused in the standardization strategy,continue to deepen the reform of standardization work,and give full play to the basic and strategic role of standardization in the modernization of the animal experiments system.

OBJECTIVE To explore the effects of intensive pharmaceutical intervention led by clinical pharmacists on hypertension patients with medium and high risk of ischemic stroke. METHODS The hypertension outpatients with medium and high risk of ischemic stroke， who were assessed by the modified Framingham stroke scale in Zhengzhou People’s Hospital from Oct. 2019 to Apr. 2020， were randomly divided into control group and intervention group， with 200 cases in each group. Patients in the control group received conventional treatment without pharmaceutical intervention； on the basis of conventional treatment， patients in the intervention group received 12-month intensive pharmaceutical intervention （grading management of compliance+ regular follow-up， involving medication education and guidance， blood glucose， blood pressure， blood lipid management and healthy life guidance） provided by clinical pharmacists. The blood glucose indexes， blood lipid indexes， blood pressure compliance rate， medication compliance， 10-year stroke risk and stroke incidence were compared between two groups at baseline and 12 months after enrollment. RESULTS After 12 months of enrollment， the level of low-density lipoprotein cholesterol （LDL-C） in intervention group was significantly lower than that in the same group at baseline， and the levels of fasting blood glucose， glycosylated hemoglobin， total cholesterol and LDL-C in intervention group were significantly lower than those in control group at the same time points （P＜0.05 or P＜0.01）. The compliance rate of blood pressure and medication compliance in intervention group were significantly higher or better than those in control group （P＜0.01）. There were 12 and 15 patients in control group and intervention group turned into low-risk ones respectively， and the proportion of high-risk patients in intervention group was significantly lower than that in control group（P＜0.01）， while the proportion of medium-risk patients was significantly higher than that in control group（P＜0.05）； the incidence of stroke in intervention group was significantly lower than that in control group （1.0% vs. 4.5%， P＜0.05）. CONCLUSIONS The pharmaceutical intensive intervention led by clinical pharmacists can reduce blood glucose and blood lipid levels of hypertensive outpatients， improve their blood pressure compliance rate and medication compliance， and help reduce the risk of stroke.

Objective To study the relationships between differences in tumorigenicity and immu-nogenetic backgrounds of nude mice. Methods According to the Chinese Pharmacopoeia, positive and neg-ative groups were set up in both Laboratory A and B with ten nude mice in each group. Organ tissues were collected for clinicopathological analysis. Blood samples were collected and detected using flow cytometry. DNA was extracted and analyzed with 23 STR markers. Results The positive group of Laboratory B was in-valid (7/10 tumor formation). The two laboratories showed no significant difference in the results of patho-logical analysis, but had significant differences in CD25, CD8, CD4, Th1 and Th2. There were 13 and 18 polymorphic sites respectively found in nude mice of Laboratory A and B. Further analysis of the non-tumor-bearing nude mice in Laboratory B positive group revealed that CD25, Th2, D3Mit29 and D5Mit48 were the specific indexes. Conclusion Differences in tumorigenicity might be related to the diversity of immunoge-netic backgrounds of nude mice.

Objective To strengthen the quality control management and enhance the detection capacity of the experimental animal quality control laboratoriesin our country through the detection of serum esterase-1 (Es-1) in the experimental mice.Methods The samples were prepared according to the standard procedure, and then were randomly numbered and distributed to participating units by cold-chain transport.Before the deadline, the participants submitted the results and the copies of original records.When the results were completely consistent with the standard results,the results were regarded as satisfactory, otherwise were unsatisfactory.Results A total of 11 laboratories participated in this program, of which 10 laboratories were regarded as satisfactory (90.9%) and one laboratory obtained unsatisfactory result (9.1%).Conclusions The results of this proficiency testing project demonstrate that the overall detection level of Es-1 in laboratory mice is highof the participating laboratories.However, more attention still should be paid to standard specifications and some test details.

Objective To understand the characteristics of minipigs infected withJapanese encephalitis virus(JEV).Methods After the brain tissues were treated, the pig brain tissue treatment solution was inoculated with BHK21 cells.Then, virus culture,indirect immunofluorescence assay, neutralization test, electron microscopic observation, and reverse transcription-polymerase chain reaction (RT-PCR) amplification of the new isolate E segment and PrM segment nucleotide sequence were performed and the genotype was identified.Results BHK21 cells were inoculated into 25 pigbrain tissues.Among them, three tissue-treated fluid couldinduce shrinkage and aggregation of BHK21 cells, and immunofluorescence staining showed strong green fluorescence response.The results of neutralization test showed that the neutralization titer of these three new isolates was 1:64, and the size of the virus particles was about 40nm under the electron microscope.The homology of both RT-PCR product sequencing results and E-segment of vaccine strain were 95%.Three new isolates were type GIII JEV.Conclusion The results ofthisstudydemonstrate that there is G III type Japanese encephalitis virus infection in the minipig farm.

Objective:To discuss the clinical characteristics,diagnosis and treatment experience of a case of lateral ectopic thyroid.Methods:The patient with lateral ectopic thyroid was diagnosed by thyroid color ultrasound and single-photon emission computed tomography(SPECT)-CT examination.The right thyroidectomy and the thyroid tissue in cervical section Ⅳ of the patient were removed by received the operation.The pathological examination after operation was performed.The daily usage of euthyrox after operation was 50 μg.Results:The patient recovered well,who accepted 10 months follow-up with normal life and stable condition,and had no recurrence and metastasis.Conclusion:The mechanism of lateral ectopic thyroidy is not clear yet,the surgical treatment can result in good effectiveness and better prognosis.

Objective To establish a rapid, simple, sensitive, and specific multiplex real-time PCR method for quantitative detection of Campylobacter jejuni, Salmonella and Shigella in tree shrews.Methods Specific primers and probes were designed, according to the HipO gene of Campylobacter jejuni, inV gene of Salmonella and ipaH gene of Shigella.The primers were confirmed by single pathogen quantitative PCR, and the sensitivity and specificity of the multiplex PCR were analyzed.Finall, the samples of experimental tree shrews were detected by this multiplex PCR method.Results The PCR element of TaqMan-MGB real-time PCR assay was able to quantitatively amplify the Campylobacter jejuni, Salmonella or Shigella.Appropriate standard amplification curves of Campylobacter jejuni, Salmonella and Shigella in the multiplex quantitative PCR were obtained.The sensitivity of this method was 1×103 ng/μL.There was no false positive detection from other bacterial strains.Conclusions This multiplex quantitative real-time PCR method has good application and development prospects in the detection of microorganisms in tree shrews.

Objective To compare and analyze the genetic structure of NIH mice bred in Unites A and B, using microsatellite technology.Methods Thirty SPF 8-week old outbred NIH mice (half male and half female) of each population were randomly chosen from the Units A and B, respectively.PCR amplification and STR scan were performed to determine the genetic characteristics of two outbred populations using microsatellite loci, and the population genetic structure was analyzed with statistical software Popgene 1.32.Results In the NIH mouse population form the Unit A, 74 alleles were obtained, with an average heterozygosity of 0.3108 and polymorphism information content of 0.2637.In the NIH mouse population from the Unit B, 76 alleles were obtained, with an average heterozygosity of 0.3257 and polymorphism information content of 0.2777.The inter-population comparison showed that genetic differentiation coefficient Fst was 0.3932, the genetic identity was 0.3971, and the genetic distance was 0.9235.The population difference was significant.Conclusions There is serious genetic differentiation between the two NIH mice populations,resulting in the formation of two different closed populations.

Objective To screen the markers of chromosome 12, which is vacant in the Beijing local standard DB11/T828.3-2011 for genetic quality control of miniature pigs in Beijing, and to study the applicability of the local standard by comparison of two different methods for evaluation of the genetic quality of the same population.Methods According to the literature, we selected four pairs of microsatellite markers of chromosome 12 and studied the polymorphism through monitoring the genetic quality of two populations of China Agricultural University miniature pigs.We screened the highly polymorphic markers of chromosome 12, combined them with the microsatellite primers of the standard 18 pairs of chromosomes to establish the whole chromosome method.We compared and analyzed the applicability of the local standard DB11/T828.3-2011 through monitoring the genetic quality of the same population of miniature pigs with different method.The data were processed and analyzed using software Popgen32.Results All the screened four pairs of microsatellite markers of chromosome 12 were highly polymorphic (PIC>0.5).The local standard showed a chromosome coverage of 94.7%, stability of amplification of 96.0%, and certified that the China Agricultural University miniature pig III was qualified, while the China Agricultural University miniature pig I was not qualified.When the markers of chromosome 12 were added, the whole chromosome method showed result of 100% chromosome coverage and 96.6% amplification stability, both of the two populations of pigs were certified as qualified.Conclusions The four screened markers of chromosome 12 are all highly polymorphic, and provide a support for supplement of the local standard DB11/T828.3-2011.

Objective To analyze and evaluate the population genetic quality of 3 subbreeds of China Agricultural University miniature pigs in Beijing.Method According to the local standard DB11/T828.3 -2011, 25 pairs of microsatellite primers were used in 3 subbreeds of China Agricultural University miniature pigs, and software Popgen32 was used to process the data.Results 24 microsatellite loci shared 130, 122 and 138 alleles in the China Agricultural University miniature pigs I, II, III, respectively. The average heterozygosity was 0.6759, 0.5967 and 0.6779, respectively, while the average polymorphism information content ( PIC) was 0.6344, 0.5540 and 0.6403, respectively. The genetic distance between China Agricultural University miniature pig II and III was 0.4251, while the genetic distance between China Agricultural University miniature pig I and II was 0.2084.Conclusions In the 3 subbreeds, China Agricultural University miniature pigs II and III have genetic stability and genetic diversity, and both of which satisfy with the genetic characteristics of closed colony laboratory animal.