Objective To screen and establish a method for determining the biological activity of anfibatide.Meth-ods Three methods of light transmittance aggregometry(LTA),whole blood electrical impedance aggregometry,and continuous platelet count method were compared and studied.And the constant platelet counting method was chosen and verified to detect the biological activity of anfibatide.Results The RSD values of anfibatide biological activity detected by LTA,whole blood electri-cal impedance aggregometry,and continuous platelet count method were 10.3%,14.0%,and 3.6%,respectively.RSD of repeat-ability of 6 parallel test articles was 11.0%.The RSD of intermediate precision of 12 test articles for different personnel was 9.8%,and the inhibition rate of anfibatide was linear in the range of 0.3-0.5 U.The correlation coefficient was more than 0.990.The ac-tivity of three batches of anfibatide was determined,and the inhibition rate was 49.9%～53.6%.Conclusion The continuous platelet count method for determining anfibatide activity was established and verified,which can be used for quality control for an-fibatide activity since the precision and detection limit of the method met the requirement for activity assay of biological products.

【Objective】 To explore the geographical environment factors that may affect serum uric acid (UA) of healthy people and explore the change trend of UA reference value at the national scale. 【Methods】 The UA reference values of 607905 healthy people from 565 loci in China were collected, and the correlation between 25 geographical environment factors and UA reference values was analyzed by correlation analysis. CatBoost model was constructed and SHAP value interpretation model was applied to predict the UA reference values of healthy people in counties and cities in China, and the geographical distribution map of UA reference values of healthy people in China was drawn by using ordinary Kriging. 【Results】 A total of 20 indicators, namely, latitude, altitude, annual average temperature, annual average relative humidity, annual precipitation, air temperature annual range, annual average wind speed, percentage of surface soil silt, surface soil bulk density, surface soil gravel content, surface soil organic matter content, surface soil PH, surface soil (clay) cation exchange capacity, surface soil (silt) cation exchange capacity, surface soil base saturation, total surface soil exchange capacity, T-CaCO3, T-CaSO4, surface soil alkalinity, and surface soil salt showed their correlation with UA reference value of healthy people nationwide. The spatial distribution of UA reference values of healthy people across the country differed, manifested as the changing trend of higher in high altitude regions, higher in coastal regions than in inland regions, lower in the mid-eastern region, and higher in Southwest China at similar altitudes. 【Conclusion】 This study lays a foundation for further studies on the mechanism of different influencing factors on UA reference value. CatBoost model was established to provide the basis for establishing reference standards using UA reference values as prognostic factors for hyperuricemia and related chronic diseases in different regions.

Objective To analyze result of the external quality assessment for laboratories of toxicological pathology diagnosis in organizations in China. Methods A total of 86 organizations that participated in the 2020-2021 external quality assessment in laboratory of toxicological pathology diagnosis (hereinafter referred to as "reference units") were selected as research subjects using convenient sampling method, and the assessment results were analyzed. Results The median of total score was 92, and the 0-100 percentiles were 64-100 in these 86 reference units. Among these reference units, 76 were rated as excellent, 10 as qualified, with the excellent and the qualified rate of 88.4% and 11.6%, respectively. No reference unit was rated as unqualified. The rates of excellence of the reference units in public health institutions, pharmaceutical research institutions, drug safety evaluation centers and testing companies were 95.7%, 84.2%, 85.7% and 86.7%, and the qualified rates were 4.3%, 15.8%, 14.3% and 13.3%, respectively. The distribution of excellence and qualification among the four types of reference units showed no statistical difference (P>0.05). The distribution of sample scores according to the three grades of poor, good, and excellent were 4.9%, 20.7%, and 74.5% in public health institutions, 8.6%, 23.7%, and 67.8% in pharmaceutical research institutions, 12.5%, 25.0%, and 62.5% in drug safety evaluation centers, and 5.4%, 17.5%, and 77.1% in testing companies. The proportion of excellence unit in public health institutions was higher than that in pharmaceutical research institutions (P<0.05). Conclusion The overall toxicological pathology diagnostic capabilities in China are good, and various types of reference units demonstrate comparable technical capabilities. However, there is a need for standardization of diagnostic terminology.

OBJECTIVE: To evaluate the diagnostic ability of toxicity pathology in patho-toxicological testing institutions in China. METHODS: The institutions participated in the 2018 Interlaboratory Comparison Activity of Toxicity Pathology Testing(hereinafter referred to as reference unit) were selected as the research subjects. The heart, spleen, skin, soft tissue, liver and mammary gland of SD rats of different groups in the 2-year carcinogenesis test were selected. The femur, knee joint and nose of Beagle dogs in the 4-week toxicity test and a total of 10 pathological tissues were selected as the comparison samples. The pathological diagnosis was carried out by the pathological diagnostic personnel of the reference unit, and the diagnostic results were reported. The expert appointed by the Toxicology and Pathology Committee of Chinese Toxicology Association compared the diagnostic results with the appointed value. RESULTS: A total of 167 pathological diagnostic personnel from 75 reference units in 24 provinces and municipalities participated in the comparison activity. The reference units were mainly distributed in East China, South China and North China, accounting for 77.3%(58/75). Totally 75 reference units fed back 750 effective diagnostic results. The qualified rates of diagnosis on heart, spleen, skin, soft tissue and breast samples were higher than 60.0%. The qualified rates of diagnosis on femur and knee joint, and nose samples were low(30.7% and 6.7%, respectively). There were 1(1.3%), 46(61.4%) and 28(37.3%) reference units rated as unqualified, qualified and excellent, respectively. CONCLUSION: Most of the testing institutions in China have a high level of patho-toxicological diagnostic ability, that can provide reliable diagnostic results for toxicology safety evaluation tests.

Lymph node metastasis is the main mode of metastasis of thyroid papillary carcinoma.In the central compartment lymph node dissection,the lymph node posterior to right recurrent laryngeal nerve is hidden because of its deep anatomical position,which is easy to be missed during the operation and becomes one of the factors that affect the recurrence of thyroid papillary carcinoma.The metastasis rate of lymph node posterior to right recurrent laryngeal nerve is 10％-30％,which is related to the tumor size,location and other factors,and its position in the surgical treatment of thyroid cancer is increasingly prominent.

Objective: To investigate the antigenic epitope prediction method of hemagglutinin (HA) protein of influenza A (H1N1) virus. Methods: BALB/c mice were conventionally immunized with influenza H1N1 vaccine. The splenocytes from the immunized mouse were fused with SP2/0 mouse myeloma cell line, and then the antigen-specific monoclonal antibodies (mAbs) were obtained by screening hybridoma supernatants. ELISA blocking test was used to detect the blocking result of each monoclonal antibody, which was labeled by horseradish peroxidase (HRP). The light and heavy chain variable region genes of each antibody were cloned, the amino acid sites of the antibody-binding HA antigen epitope were predicted by computer simulation. Results: Three hybridoma cell lines of stable secreting anti-H1N1 influenza virus HA protein were obtained.Three mAbs were divided into two categories by ELISA blocking tests, which were divided into two categories according to preliminary results of computer simulation. Conclusions ELISA blocking test and computer simulation prediction can prove each other in predication of the antigenic epitopes of HA protein of H1N1 influenza virus.

Objective:To systematically review the efficacy and safety of acid-suppressive therapy including proton pump inhibitors (PPI) and histamine 2 receptor antagonists (H2RA) and compare with those of placebo or blank control in the postoperative patients with stress ulcer bleeding (SUB) to provide evidence-based reference for clinical practice.Methods:The Cochrane library,Medline,Embase,CBM,CNKI,VIP,Wan Fang Data,clinicaltrials.gov,ISRCTN Register and WHO ICTRP were searched.Only randomized controlled trials (RCTs) of acid-suppressive therapy compared with placebo or blank control for postoperative stress ulcer bleeding were selected with bleeding rate,mortality,adverse drug reactions,gastric juice pH and length of stay as the indices.After the quality evaluation and data extraction,Meta-analysis was performed by using Stata12.0 statistics software.The results were expressed as relative risk(RR) and its corresponding 95% confidence interval(CI).Funnel plot and Eggers test were used to determine the publication bias;and then Grade approach was applied to assess the confidence in the evidence for each outcome.Results:Totally 15 trials enrolling 971 patients were selected,and acid-suppressive therapy was more effective than placebo or blank control in reducing the risk of stress ulcer bleeding,overt upper gastrointestinal bleeding and clinical important bleeding(RR 0.29,95% CI:0.19-0.45;RR 0.25,95%CI:0.10-0.64;RR 0.36,95%CI:0.17-0.77)(moderate),however,there was no statistical significance in the incidence of occult bleeding,mortality and adverse drug reactions (RR 0.79,95%CI:0.41-1.50;RR 0.49,95%CI:0.17-1.38;RR 0.78,95%CI:0.33-1.85,very low confidence).The subgroup analysis of drug classification,operation types and administration juncture showed that the incidence of SUB using PPI (RR=0.27) was lower than that using H2RA (RR=0.33);that of heart surgery (RR=0.20) was lower than that of general surgery (RR=0.31) and neurosurgery(RR=0.37);that of postoperative administration (RR=0.26) was lower than that of preoperative administration (RR=0.23).Conclusion:Acid-suppressive drugs seem to be more effective than placebo or blank control in reducing the risk of bleeding without significant increase of the risk of mortality or adverse drug reactions.The robustness of the conclusion is limited because of the low quality of the trial methodology,incomplete outcome indicators and lack of safety indices for pneumonia and clostridium diffcile-associated infection.Trials with high-quality and larger sample size are still needed to verify its clinical effects.

OBJECTIVE: To explore the non-neoplastic hepatic lesions in SD rats at different ages. METHODS: The specificpathogen free SD rats were collected from the blank control groups used in subacute toxicity tests,subchronic toxicity tests and chronic toxicity combined with carcinogenic tests for safety evaluation. At the end of each experiment,i. e. week 10,19,56 and 108(assigned into four groups: 10,19,56 and 108 weeks,each contained 100 rats with each sex),rats were executed. The liver organ coefficient was calculated,the pathological examination was performed,and the non-tumorous lesions in the liver were analyzed. RESULTS: The liver organ coefficients at the age of 19,56,108 weeks were lower than that of 10 weeks(P < 0. 05); those at the age of 56 and 108 weeks were lower than that of 19 weeks(P < 0. 05),and that of 108 weeks was greater than of 56 weeks(P < 0. 05). Among the 10-week-old,19-week-old,56-week-old and 108-week-old groups,the types of non-neoplastic hepatic lesions detected in the female rats were 6,6,13 and 15 respectively,meanwhile those in the male rats were 6,6,13 and 15 respectively. Both male and female rats,the incidences of hepatocyte fatty degeneration,edema and hepatic infiltration of inflammatory cells were significantly increased with the increase of age in each group(P < 0. 05). The incidences of intrahepatic bile duct proliferation and intrahepatic bile duct fibrosis in rats at the age of 56 and 108 weeks were higher than those at the age of 10 and 19 weeks(P < 0. 008).Moreover,the frequency of hepatic sinus expansion lesions in rats at the age of 108 weeks was higher than those of 19 weeks(P < 0. 008). CONCLUSION: Spontaneous non-neoplastic lesions in the liver of SD rats were common,primarily demonstrated as hepatocyte fatty degeneration,edema and infiltration of inflammatory cells. The incidences of lesions increased with the increase of age.

OBJECTIVE: To explore the spontaneous non-tumor lesion of kidney and its correlation with different age and sex in SD rats. METHODS: Eight hundred specific pathogen free SD rats were collected from the blank control groups used in subacute toxicity tests,subchronic toxicity tests and 1 or 2 years of chronic toxicity combined with carcinogenic tests. Rats were randomly divided into 4 groups with 10,19,56 or 108 weeks of experimental periods. Each group consisted of 100 female and 100 male rats. The renal tissues were collected at the end of each experiment,and the renal organ coefficients were calculated. The pathological non-tumor changes of the kidneys were analyzed. RESULTS: The renal organ coefficients in female rats at the age of 56 and 108 weeks were both lower than that of 10 and 19 weeks( P < 0. 008). The renal organ coefficient of male rats at the age of 56 weeks was lower than that of 10 and 19 weeks( P < 0. 008). The renal organ coefficient of male rats at the age of 108 weeks was higher than that of 56 weeks( P < 0. 008). The renal organ coefficient of male rats at the age of 108 weeks was higher than that of female rats of 108 weeks( P < 0. 008). The incidence of renal tubular calcium salt deposition,interstitial inflammatory cell infiltration and renal tubular dilatation in the female rats at the age of 108 weeks were higher than those in the male rats at the age of 108 weeks( P < 0. 05). The chronic progressive nephropathy incidence of female rats at the age of 108 weeks was lower than that of male rats aged 108 weeks( P < 0. 01).The renal tubular calcium salt deposition incidence of female rats aged 56 weeks was higher than that of male rats aged 56weeks( P < 0. 01). CONCLUSION: The spontaneous non-tumor lesions in the kidney of SD rats were common. The incidence of some lesions was different in the same age group with different sex.

OBJECTIVE: To observe the diagnostic capacity and its influencing factors in the toxicologic pathology diagnostic laboratories in China. METHODS: Inter-laboratory comparison of toxicologic pathology diagnosis was cosponsored by Chinese Society of Toxicology-Toxicologic Pathology Specialty Section and Guangdong Province Hospital for Occupational Disease Prevention and Treatment. Nine digital slices of digestive system lesions were screened as comparison samples,and the reference institution with toxicologic pathology diagnostic laboratories completed the diagnosis within the prescribed time. According to the three grades of “excellent”,“satisfaction”and “dissatisfaction”,the evaluation was carried out.RESULTS: A total of 74 reference institution participated in this comparison,which distributed in 20 provinces and 4 municipalities and 156 pathologists. The reference institutions were mainly distributed in North China,Southern China and East China. There was an average of 2 pathologists per laboratory,and in the quantity of academic title,the junior,intermediate,and senior was 15,70 and 46 persons respectively. Parasitic hepatocyte cysts( 97. 3%),adenocarcinoma of small intestine( 95. 9%) and polyarteritis nodosa of the pancreas( 89. 2%) had the highest rate of “excellent”grade,while the duodenal gland inflammation( 67. 6%),foam cell aggregation in colonic propria( 40. 5%) and hepatoma adenoma( 32. 4%) had the highest rate of dissatisfaction grade in the evaluation of single case. In the overall evaluation,reference laboratories reached the “excellent”grade and the “satisfaction”grade were 78. 4% and 21. 6% respectively.The number of pathologists provided by each reference laboratory had impacts on the overall evaluation level and the single case evaluation( neoplastic lesions) in the evaluation of single case( P < 0. 05). The types of the reference laboratory,the regional distribution and the grade of the academic title had no effect on the diagnostic ability( P > 0. 05). CONCLUSION: The reference laboratory is superior in diagnosing the digestive system lesions in the inter-laboratory comparison activity.The number of pathologists in the reference laboratory is one of the influencing factors of its diagnostic ability.