1.Toxicology of polymer pharmaceutical excipients in Sprague-Dawley rats and Beagle dogs
Jinlong DAI ; Xialing LEI ; Yuankeng HUANG ; Jianmin GUO ; Zhisen CHEN ; Wei YANG
Chinese Journal of Comparative Medicine 2025;35(6):50-64
Objective To investigate the effects of the polymer pharmaceutical excipient methoxy poly-ethylene glycol poly-lactic acid(mPEG-PLA)in Sprague-Dawley(SD)rats and Beagle dogs and its toxicological reactions,to provide a reference for its safe clinical use.Methods SD rats and Beagle dogs(male∶female ratios,1∶1)were divided randomly into control group and low,medium,and high dose mPEG-PLA groups(70,210,700 mg/kg).Animals received intravenous mPEG-PLA once a day for 90 days,followed by a 28-day recovery period.Indicators including clinical observations,food intake,body weight,hematology,blood biochemistry,immune function,and pathological examination were recorded.Results Compared with the control group,(1)food intake was decreased(P<0.01)and body weight was increased(P<0.05 or P<0.01)after 90 days of continuous administration,with similar changes in the medium and high dose groups in both rats and dogs.In addition,MONO/MONO%,RBC,MCH,MCHC,HCT,HGB,PLT,TP,ALB,GLB,and Fbg were all decreased(P<0.05 or P<0.01)and coagulation indexes(e.g.,APTT)were increased(P<0.05 or P<0.01).Organ weights and the organ-to-body/brain weight ratios of the liver and spleen were increased(P<0.05 or P<0.01),and histopathology indicated numerous foam-like macrophages in the hepatic sinuses,red spleen pulp,and lymph node medulla.DBIL and TBIL also increased in rats in the high dose group(P<0.05 or P<0.01),while the dogs experienced skin swelling or scabs,abdominal swelling,vomiting,decreased activity,high albuminuria,and ascites,and the renal glomerular cells showed vacuoles.(2)After 28 days of recovery,rats and dogs in the medium and high dose groups showed a few foam-like macrophages in the hepatic sinuses,red spleen pulp,and lymph node medulla,as well as decreased of food intake in dogs.The MCHC,PLT,and TP decreased in dogs in the high dose group(P<0.05),and the liver and spleen weights and organ coefficients in rats increased(P<0.05 or P<0.01),while the MONO%decreased in male rats in the medium dose group(P<0.05).Conclusions Administration of mPEG-PLA 210 and 700 mg/kg for 90 days caused blood mononuclear cells to enter and aggregate in the liver,spleen,lymph nodes,and other tissues in SD rats and Beagle dogs,leading to secondary tissue structural damage.Protein and fibrinogen synthesis and bilirubin metabolism in the liver decreased,leading to abnormal coagulation function,and decreased intravascular colloid osmotic pressure resulted in edema and bleeding.The result suggest that the liver,spleen,kidney,and lymph nodes are target organs for mPEG-PLA toxicity,with dose-dependent and reversible effects and species differences,but no significant sex differences.Clinical monitoring of related organ functions is needed to avoid secondary damage.
2.Toxicology of polymer pharmaceutical excipients in Sprague-Dawley rats and Beagle dogs
Jinlong DAI ; Xialing LEI ; Yuankeng HUANG ; Jianmin GUO ; Zhisen CHEN ; Wei YANG
Chinese Journal of Comparative Medicine 2025;35(6):50-64
Objective To investigate the effects of the polymer pharmaceutical excipient methoxy poly-ethylene glycol poly-lactic acid(mPEG-PLA)in Sprague-Dawley(SD)rats and Beagle dogs and its toxicological reactions,to provide a reference for its safe clinical use.Methods SD rats and Beagle dogs(male∶female ratios,1∶1)were divided randomly into control group and low,medium,and high dose mPEG-PLA groups(70,210,700 mg/kg).Animals received intravenous mPEG-PLA once a day for 90 days,followed by a 28-day recovery period.Indicators including clinical observations,food intake,body weight,hematology,blood biochemistry,immune function,and pathological examination were recorded.Results Compared with the control group,(1)food intake was decreased(P<0.01)and body weight was increased(P<0.05 or P<0.01)after 90 days of continuous administration,with similar changes in the medium and high dose groups in both rats and dogs.In addition,MONO/MONO%,RBC,MCH,MCHC,HCT,HGB,PLT,TP,ALB,GLB,and Fbg were all decreased(P<0.05 or P<0.01)and coagulation indexes(e.g.,APTT)were increased(P<0.05 or P<0.01).Organ weights and the organ-to-body/brain weight ratios of the liver and spleen were increased(P<0.05 or P<0.01),and histopathology indicated numerous foam-like macrophages in the hepatic sinuses,red spleen pulp,and lymph node medulla.DBIL and TBIL also increased in rats in the high dose group(P<0.05 or P<0.01),while the dogs experienced skin swelling or scabs,abdominal swelling,vomiting,decreased activity,high albuminuria,and ascites,and the renal glomerular cells showed vacuoles.(2)After 28 days of recovery,rats and dogs in the medium and high dose groups showed a few foam-like macrophages in the hepatic sinuses,red spleen pulp,and lymph node medulla,as well as decreased of food intake in dogs.The MCHC,PLT,and TP decreased in dogs in the high dose group(P<0.05),and the liver and spleen weights and organ coefficients in rats increased(P<0.05 or P<0.01),while the MONO%decreased in male rats in the medium dose group(P<0.05).Conclusions Administration of mPEG-PLA 210 and 700 mg/kg for 90 days caused blood mononuclear cells to enter and aggregate in the liver,spleen,lymph nodes,and other tissues in SD rats and Beagle dogs,leading to secondary tissue structural damage.Protein and fibrinogen synthesis and bilirubin metabolism in the liver decreased,leading to abnormal coagulation function,and decreased intravascular colloid osmotic pressure resulted in edema and bleeding.The result suggest that the liver,spleen,kidney,and lymph nodes are target organs for mPEG-PLA toxicity,with dose-dependent and reversible effects and species differences,but no significant sex differences.Clinical monitoring of related organ functions is needed to avoid secondary damage.
3.Changes in hematological parameters of long-term high-frequency platelet donors
Zhongwen YAN ; Dong LIN ; Lihua WANG ; Qundi YE ; Liuyun YIN ; Qi ZENG ; Zhisen HUANG
Chinese Journal of Blood Transfusion 2022;35(12):1216-1220
【Objective】 To understand the effect of long-term high-frequency platelet donation on the health, safety and platelet quality of blood donors. 【Methods】 From August 2020 to July 2022, blood donors who donated platelets for single collection in the station were selected as two groups: those who donated for 20-29 times and those who donated for 30-44 times. Such 14 test indexes as red blood cell count (RBC), hemoglobin (Hb), hematocrit (Hct), mean corpuscular volume (MCV), platelet count (Plt), white blood cell count (WBC), large platelet ratio (P-LCR), lymphocyte (LYM) , neutrophil (NE), mean hemoglobin content (MCH), mean hemoglobin concentration (MCHC), platelet specific volume (PCT), mean platelet volume (MPV) and platelet distribution width (PDW) were grouped and statistically analyzed for 5 times in each group. In addition, blood donors who have donated platelets more than 100 times in the station were chosen; the changes of their 5 parameters as RBC, Hb, Hct, PLT and WBC, as well as the correlation with the total number of platelet donations were analyzed through statistical analysis of the first 100 donations(10 donations/group). 【Results】 During 2 years, the hematological parameters were similar between 20-29 donation group(n=30) and 30-44 donation group(n=11) (P>0.05). For donors with donations≥100 occasions, RBC, Hb, Hct and WBC were negatively correlated with the number of blood donations, while Plt was positively correlated. There were significant differences in Hb, Hct, WBC and Plt among groups (P<0.05). Hb, Hct and WBC showed a downward trend, while Plt showed an upward trend. 【Conclusion】 With the increase of blood donations and units of blood donated, some changes in hematological parameters are observed among long-term high-frequency platelet donors. Monitoring and health education should be strengthened to ensure the safety and quality of blood donors.
4.Characteristics and related factors of adverse reactions to blood donation among medical students
Zhenxing WANG ; Shaobin CHEN ; Zhisen HUANG ; Guowei HAN ; Zhu′an SU
Chinese Journal of Blood Transfusion 2021;34(8):891-894
【Objective】 To analyze the related factors and countermeasures of adverse reactions to whole blood donation(ARBD) for medical student donors, so as to further reduce the incidence of ARBD. 【Methods】 The demographic data of medical/non-medical student donors and those suffered from ARBD from 2016 to 2018 were retrospectively analyzed, and the relationship between ARBD and age, gender, frequency of blood donation, blood volume, blood type, pulse, ALT, blood pressure, hemoglobin, etc. was statistically analyzed. 【Results】 The incidence of ARBD in all medical student donors from 2016 to 2018 was 1.16%, lower than that of non-medical students (1.51%). The ARBD rate(2.30%) of senior medical students (> 20 years old) was significantly lower than that of non-medical students (3.93%) and higher than that of junior medical students (≤20 years old)(0.70%). The ARBD rate of novel medical student donors was 1.27%, lower than that of novel non-medical students (2.12%) (P<0.05). Male medical students(1.68%) were more likely to develop ARBD than females(0.78%), donations within 200 mL(55%) than 300mL(0.26%) and 400mL(0), Hb<120 g/L(13.04%) than Hb≥120 g / L( 1.10% ), and blood type A(1.70%) than type O (0.88%) (P<0.05). Logistic regression analysis showed that blood volume and blood type were related factors. ARBD was more likely to occur in Type A blood than type O, and was more likely to occur when blood volume was lower. ARBD occurred frequently during phlebotomy, due to mental stress(75%) and hunger(8.92%)(P<0.05), while 96.43% of ARBD could recover within 10 minutes. 【Conclusion】 Novel, male, older than 20 years, Hb<120 g / L, blood type A and donation unit ≤200 mL were main risks for ARBD in medical student donors. Popularizing the knowledge of voluntary blood donation and strengthening pre-donation communication are important measures to prevent ARBD.
5.Research on the P-CMM-based appraisal and improvement of recruitment practice system of a tertiary hospital
Zhisen BAN ; Kun YANG ; Ying QU ; Yu HUANG ; Tao LUO
Chinese Journal of Hospital Administration 2020;36(10):850-853
Objective:To improve the recruitment management process of public hospitals and enhance the quality of recruitment.Methods:Through the introduction of the people capability maturity model(P-CMM), the recruitment practice system of a tertiary hospital was evaluated. The evaluation scoring was expressed as the average score±standard deviation( ± s), and the scorer′s reliability index was expressed as Kendall coefficient. Results:According to the P-CMM recruitment practice standards, a total of 16 level-1 indicators and 35 level-2 indicators were set up. Among them, there were 7 standard projects and 9 gap projects, with reasons for the gaps analyzed.Conclusions:It is necessary to enhance the strategic vision of the recruitment process, systematically implement hospital post management, build a recruitment platform based on multi-party participation, and scientifically analyze the recruitment process to further improve the recruitment quality of public hospitals.
6.Therapeutic effect of sodium aescinate on severe acute pancreatitis in rats
Xin HUANG ; Zhisen MAO ; Congyao TANG
International Journal of Traditional Chinese Medicine 2014;36(2):125-127
Objective To investigate the therapeutic effect of sodium aescinate (SA) on severe acute pancreatitis (SAP) in rats.Methods SAP model was induced by intraductal administration of 5% taurocholic acid sodium salt.SD rats were then randomly divided into 3 groups (n =16),namely sham,model and SA group (5 mg/kg).Drugs or saline(10 ml/kg) were administered via caudal vein 30 min post-operation.The serum amylase was measured with spectrophotometer and pancreatic histological changes were observed under microscope 6 h and 12 h post-operation,respectiveiy.Results Pancreatic histological grades in the model group were (9.42 ± 1.06) and (18.30± 2.18) 6 h and 12 h post-operation,respectively,which showed significant differences (P<0.01) compared with the sham group [(0.55 ±0.20) and 0,respectively].SA evidently reduced the severity of pancreatic pathology and improved the tissue inflammation in rats with SAP.Pancreatic histological grades were (7.85±1.33) and (12.75±1.69)in the SA group 6 h and 12 h post-operation,respectively,which had significant differences compared with the model group (P<0.05).Serum amylase levels in model group were (2612 ± 59) U/L and(3004±687)U/L6 h and 12 h post-operation,respectively,which showed significant differences (P < 0.01) compared with the sham group [(928 ± 271) and (890± 295) U/L,respectively].Serum amylase levels were reduced to (1790± 336) U/L and (2093 ± 298) U/L in the SA group 6 h and 12 h post-operation,respectively.SA markedly inhibited the level of serum amylase compared to the model group (P<0.01).Conclusion SA could protect rats with SAP effectively.

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