Objective To systematically investigate the effects of Dangmu extract syrup on the growth and development of 4-day-old(postnatal day 4,PND4)Sprague-Dawley(SD)rats and its toxic reactions.Methods According to the whole litter design method,128 young mice(PND2)were randomly divided into negative control group and low,medium and high dose groups.From PND4,the animals were orally given pure water,31 g/kg,93 g/kg and 280 g/kg(calculated as raw herb material)of Dangmu extract syrup,respectively,once daily for 18 consecutive days,with a 15 d of recovery phase.During the study period,the general state,growth and development,nerve reflex function,spontaneous behavior,hematology,coagulation,blood biochemistry,immune function,growth hormone and histopathology of the animals in each group were observed or examined.Results After 18 d of continuous administration,compared with the negative control group,GLU(male and female)in the medium and high dose groups increased(P＜0.05 or P＜0.01),LDH(male and female)and AST(male)in the medium and high dose groups,ALT,AST(female)in the high dose group decreased(P＜0.05 or P＜0.01),RET and percentage of RET(male and female)in the low and high dose groups,RET(male)in the medium dose group increased(P＜0.05 or P＜0.01),spleen mass and the organ-to-body mass ratio(male and female)in the low and high dose groups and female in the medium dose group increased(P＜0.05 or P＜0.01).Splenic nodule structures were formed in all dose groups with large size and number,and there was a dose relationship in the degree of changes.After 15 d recovery period,compared with the negative control group,GLU(female)in the low dose group increased(P＜0.05),ALT,AST,ALP,TG(female)in the medium and high dose groups,GGT,TG,TCHO(male)in the medium dose groups,AST,ALP,TG,LDH(male)in the high dose group decreased(P＜0.05 or P＜0.01),RET(female)and percentage of RET(male)in the high dose group increased(P＜0.05).compared with the 18 d of continuous administration,the spleen structures of the animals in each group were more completely developed and the splenic nodule structures were obvious,but no significant difference was noted in the comparison between groups.No significant drug-related changes were observed in other test result.Conclusions Dangmu extract syrup advanced the development of complete spleen structure in 4-day-old SD rats,accompanied by the enhancement of its hematopoietic function,and at the same time,it caused the animals,blood glucose to rise,the enhancement of glucose metabolism function led to the increase of related enzyme consumption,and led to the decrease of some liver function parameters,and showed a dose correlation.There was no gender difference in the changes,which were reversible after stop administration,and the mechanism of the changes needs to be further explored and confirmed.In the clinical trials,attention should be paid to the control of the dose of the test article,and regular monitoring of the spleen and related blood and clinical chemistry parameters.

Objective:To analyze the chemical components of the Tibetan medicinal material Potentilla anserina L. based on UPLC-Q-EXACTIVE-MS/MS; To establish its fingerprint and content determination method combined with UPLC; To provide the basis for its quality evaluation. Methods:Intelligent UPLC-Q-Exactive-MS/MS combined with literature and PubChem database was used to identify chemical components of Potentilla anserina L. HPLC method was used to establish fingerprints of 12 batches of Potentilla anserina L. Chemical pattern analysis was performed to identify markers of difference. The content of quality markers was quantitatively analyzed. Results:14 chemical components were identified from Potentilla anserina L, including 10 flavonoids, 3 oils and 1 proanthocyanidins; 15 common peaks and 7 chemical components were identified from the fingerprints of Potentilla anserina L.; chemical patterns identified 8 difference markers; the content determination results showed that the contents of catechin, Kaji-ichigoside F1, rosamultin, tormentic acid , pomolic acid and ursolic acid in different batches were among 0.028-0.080 mg/g, 0.144-0.361 mg/g, 0.323-0.630 mg/g, 0.233-0.645 mg/g, 0.214-0.384 mg/g, 0.115-0.203 mg/g, respectively. Conclusion:This study can provide a reference for the study of chemical constituents and pharmacodynamic substances of Potentilla anserina L., and provide a scientific basis for the objective evaluation of the quality of Potentilla anserina L. and the improvement of its quality control.

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.

Objective To systematically investigate the effects of Dangmu extract syrup on the growth and development of 4-day-old(postnatal day 4,PND4)Sprague-Dawley(SD)rats and its toxic reactions.Methods According to the whole litter design method,128 young mice(PND2)were randomly divided into negative control group and low,medium and high dose groups.From PND4,the animals were orally given pure water,31 g/kg,93 g/kg and 280 g/kg(calculated as raw herb material)of Dangmu extract syrup,respectively,once daily for 18 consecutive days,with a 15 d of recovery phase.During the study period,the general state,growth and development,nerve reflex function,spontaneous behavior,hematology,coagulation,blood biochemistry,immune function,growth hormone and histopathology of the animals in each group were observed or examined.Results After 18 d of continuous administration,compared with the negative control group,GLU(male and female)in the medium and high dose groups increased(P＜0.05 or P＜0.01),LDH(male and female)and AST(male)in the medium and high dose groups,ALT,AST(female)in the high dose group decreased(P＜0.05 or P＜0.01),RET and percentage of RET(male and female)in the low and high dose groups,RET(male)in the medium dose group increased(P＜0.05 or P＜0.01),spleen mass and the organ-to-body mass ratio(male and female)in the low and high dose groups and female in the medium dose group increased(P＜0.05 or P＜0.01).Splenic nodule structures were formed in all dose groups with large size and number,and there was a dose relationship in the degree of changes.After 15 d recovery period,compared with the negative control group,GLU(female)in the low dose group increased(P＜0.05),ALT,AST,ALP,TG(female)in the medium and high dose groups,GGT,TG,TCHO(male)in the medium dose groups,AST,ALP,TG,LDH(male)in the high dose group decreased(P＜0.05 or P＜0.01),RET(female)and percentage of RET(male)in the high dose group increased(P＜0.05).compared with the 18 d of continuous administration,the spleen structures of the animals in each group were more completely developed and the splenic nodule structures were obvious,but no significant difference was noted in the comparison between groups.No significant drug-related changes were observed in other test result.Conclusions Dangmu extract syrup advanced the development of complete spleen structure in 4-day-old SD rats,accompanied by the enhancement of its hematopoietic function,and at the same time,it caused the animals,blood glucose to rise,the enhancement of glucose metabolism function led to the increase of related enzyme consumption,and led to the decrease of some liver function parameters,and showed a dose correlation.There was no gender difference in the changes,which were reversible after stop administration,and the mechanism of the changes needs to be further explored and confirmed.In the clinical trials,attention should be paid to the control of the dose of the test article,and regular monitoring of the spleen and related blood and clinical chemistry parameters.

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.

ObjectiveTo provide a reference for the diagnosis of amyloidosis in experimental animals through the pathological diagnosis of systemic amyloidosis in a case of a New Zealand white rabbit. MethodsIn a 6-month repeated ocular toxicity study, an abnormal finding was noted during the routine gross anatomical examination of one New Zealand white rabbit. Its organs were prepared as paraffin sections and stained with hematoxylin-eosin (HE) staining and Congo red staining. The histopathological features were observed under optical and polarized light microscopy. ResultsGross anatomical examination of the animal revealed an enlarged spleen and changes in the color and texture of the lung. HE staining showed that the splenic tissue structure was destroyed, the white pulp of the spleen was surrounded by dense amyloid deposition in the form of nodular rings, along with pressure atrophy of the white pulp. Amyloid deposits were also observed in the submandibular lymph nodes, mesenteric lymph nodes, ileum, sacculus rotundus, vermiform appendix, jejunum, cecum, and rectum. Congo red staining showed that the amyloid deposition in the affected organs appeared salmon-pink, and exhibited characteristic apple green birefringence under polarized light microscopy.Conclusion The histo-pathological features of the New Zealand white rabbit are consistent with the diagnostic characteristics of systemic amyloidosis.

【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.

Objective To study classification of vascular sign of tiny ground glass nodules-like lung adenocarcinoma in HRCT, and explore its value to differentiate benign from malignant of the ground glass nodules(GGN).Methods 87 patients with tiny ground glass nodules-like lung adenocarcinoma examined on HRCT were retrospectively evaluated.According to the new pathological classification standard of lung adenocarcinoma,they were divided into three groups:(1)pre-invasive group(n=25),including 14 cases of atypical adenomatous hyperplasia(AAH)and 11 cases of adenocarcinoma in situ(AIS);(2)minimally invasive adenocarcinoma (MIA)group(n=35);(3)invasive adenocarcinoma(IAC)group(n=27).The lesions were divided into three types according to the grinding of glass composition proportion:Type A,pure ground glass nodules(pGGN);Type B,mixed ground glass nodules (mGGN)which contained glass composition≥50%;Type C,mGGN which contained glass composition < 50%.The vascular sign of GGN were divided into four types:Type 1,without vessels passing through the GGN,or vessels passing by GGN;Type 2,intact vessels passing through GGN,but vascular morphology is normal;Type 3,single vessels passing through GGN,and distorted,stiff vessels seen within GGN;Type 4,two or more vessels passing through GGN,and branches between vessels formed in GGN,and the diameter of vessel was irregular,partial enlargement.The relationship among the size of the GGN,content of the grinding of glass proportion and the vascular sign of GGN were analyzed both in axial images and reconstruction images.Results There were significant differences in size among the three groups(P=0.032,P=0.000,P=0.000).There were significant differences between content of the grinding of glass proportion and classification of vascular sign of GGN(P=0.000).Type 1 and type 2 vascular sign were dominant in the infiltrating former group,a total of 24 cases(96%).The incidence of type 3 and type 4 vascular sign in MIA group and IAC group was 60% and 74% respectively,and there were significant differences with the infiltrating former group(P=0.000,0.000).Further analysis indicated that type 3 was more commonly seen in MIA with comparison to type 4 which was more likely seen in IAC,the difference was statistically significant(P=0.043).Conclusion To study HRCT vascular sign of tiny ground glass nodules-like lung adenocarcinoma can improve the ability of the GGN benign and malignant diagnosis,provide reliable basis for clinical diagnosis and treatment.

Aim To observe the effect of BAPTA-AM on extracellular acid-induced autophagy in rat articular chondrocytes and its possible mechanisms.Methods Rat articular chondrocytes were isolated from Sprague-Dawley rats and incubated with different pH medium. The states of autophagy were examined by acridine or-ange (AO ) staining .Moreover,the expressions of LC3 ,Beclin-1 ,ULK1 ,CaMKKβ,AMPK and mTOR were detected using Western blot or quantitative real-time PCR (qRT-PCR ). Intracellular calcium ([Ca2+]i )was analyzed by a Ca2+-imaging method. Results Compared with pH 6.0 group,BAPTA-AM could significantly decrease the activation of autophagyinduced by acid exposure,and the expressions of autophagy markers including LC3 Ⅱ,Beclin1 and ULK1were also decreased,accompanied with reduced acidinduced [Ca2 +]i influx,decreased proteins expressionof CaMKKβand phosphorylatedAMPK,and increasedphosphorylation of mTOR.Conclusion BAPTAAMcan significantly restrain acidinduced autophagy in ratarticular chondrocytes,the mechanism of which may beassociated with decreased Ca2 + influx.

BACKGROUND:Polyurethane has good mechanical and physical characteristics and is extensively used in
clinical and experimental studies, but its hydrophobicity and histocompatibility are not ideal, which limits its use in tissue engineering as a biomaterial scaffold to some extents.
OBJECTIVE:To observe the hydrophilicity of polyurethane membrane grafted with silk fibroin and glutin and its compatibility with human hypopharyngeal cel s.
METHODS:The changes in hydrophilicity of polyurethane membrane grafted with silk fibroin and glutin were detected by contact angle measurements. Human hypopharyngeal fibroblasts were cultured in vitro on
polyurethane membrane, silk fibroin-polyurethane membrane, glutin-polyurethane membrane and tissue culture plate. Cel compatibility was compared using cytometry and cel morphology obsevation.
RESULTS AND CONCLUSION:Hydrophilicity of silk fibroin-or glutin-polyurethane membranes significantly increased (P<0.01). The hydrophilicity of silk fibroin-polyurethane membrane was higher than that of
glutin-polyurethane membrane (P<0.01). The number of cel s on the tissue culture plate was the most. The number of human hypopharyngeal fibroblasts on the silk fibroin-or glutin-polyurethane membrane was higher
than that on the polyurethane membrane, especial y on the silk fibroin-polyurethane membrane. These suggested that hydrophilicity and cel compatibility of silk fibroin-or glutin-polyurethane membrane were elevated.