1.Validation of zebrafish embryo toxicity evaluation method
Jia CHANG ; Liang LU ; Yan CHANG
Chinese Journal of Pharmacology and Toxicology 2014;(2):290-295
OBJECTIVE In this study,nine different levels of known teratogenic embryos toxic com-pounds (aceta minophen,methi mazole,indo metacin,methotrexate,ascorbic acid,isoniazid,penicillin G,saccharin ,5-fluorouracil )were used to validate the established evaluation method of zebrafish e mbryo develop mental toxicity in our laboratory via zebrafish e mbryonic develop ment toxicity tests. METHODS By water bath method,zebrafish embryos of post-fertilization 2 h (2 hpf)were exposed to different concentrations of compounds.Observe and record the nu mber of malformations and dead e mbryo in 24,48,72,144 hpf.After three parallel experiments,get EC50 ,LC50 through software and calculate the teratogenic indices (TI =LC50 /EC50 )of the positive drug and recorded it as teratogens.If there is no teratogenic index recorded it as non-teratogens.Co mpare the results with the existing animal experiments and clinical trials to obtain the sensitivity and specificity.RESULTS Based on the results, exposure to aceta minophen (TI =2.07),methi mazole (TI =2.91 ),indo methacin (TI =1 .67),5-flu-orouracil (TI =8.31 ),methotrexate (TI =1 .31 ),showed various levels of teratogenic effects,and the corresponding TI′s were calculated.Methi mazole appeared more obvious skeletal deformities;indo m-ethacin toxicity is mainly reflected in abnormal heart,blood circulation and other endpoints;5-FU at lower doses that result in higher mortality rates,but also took place over the lacking of pig mentation;aceta min-ophen for the heart,liver and other target organ toxicity,pericardial cyst;methotrexate appears signifi-cant so mites,skeletal deformity.Since the IT′s for ascorbic acid,isoniazid,penicillin G,saccharin can-not be calculated,these compounds are considered to show negative results,indicating that the data fro m the nine compounds in zebrafish test are consistent with traditional animal experiments and clinical information,the sensitivity of 100% and specificity of 100%.CONCLUSION Though validation test,it has been de monstrated that the established zebrafish embryos develop mental toxicity evaluation method can be applied to early screening of drug toxicity.
2.Effect of Relative Humidity on the Concentrations of Formaldehyde and Ammonia in Indoor Air After Decoration
Shudui JIA ; Dou CHANG ; Sheng WANG
Journal of Environment and Health 1993;0(01):-
Objective To observe the effect of relative humidity on indoor concentrations of formaldehyde and ammonia. Methods 12 currently decorated rooms were randomly divided into 3 groups, 4 rooms involved in each, in which the average relative humidity of rooms were 55%,65% and 75% respectively. The concentrations of formaldehyde, ammonia were monitored every two days for 9 consecutive days according to GB/T18204.26 -2000 and GB/T18204.25-2000. Results The concentrations of formaldehyde and ammonia decreased gradually with the prolongation of the experimental period. The concentrations of formaldehyde in the rooms of 55%,65% and 75% relative humidity groups decreased significantly after the 5th, 3rd, 3rd day of the experiment compared with those in the same group at the 1st day of the experiment respectively(P
4.Identification of a Pair of Toxin-antitoxin (TA) Gene in the Chromosome of Cyanobacteria Synechocystis sp. PCC6803
Jia-Ning CHANG ; De-Gang NING ;
Microbiology 1992;0(01):-
Chromosomally encoded toxin–antitoxin (TA) systems are thought to result in growth arrest and eventual cell death upon exposure to environmental stress in E. coli. In the chromosome of cyanobacteria Synechocystis sp. PCC6803, the genetic organization of a 360 bp open reading frame (ORF), slr0664, and another small ORF of 256 bp, ssr1114, is similar to that of TA system. The predicted protein encoded by slr0664 is homologous to RelE, but neither homologue of ssr1114 nor ssr1114-encoding protein was found in TA system. To see whether slr0664 encodes a toxin protein, ssr1114 encodes an antitoxin, an expressing plasmid containing promoter Plac and PBAD, was constructed. In this construct, Both slr0664 and ssr1114 were controlled by Plac and PBAD, respectively. Expression of slr0664 in Escherichia coli results in the inhi-bition of bacterial growth, the expression of ssr1114 neutralize the toxicity of slr0664 expression. These re-sults show that slr0664 is toxin gene and ssr1114 is antitoxin gene, both ssr1114 and slr0664 constitute achromosomal TA system in Synechocystis sp. PCC6803.
5.Clinical efficacy of different doses of budesonide/formoterol in the treatment of an acute exacerbation of chronic obstructive pulmonary disease in patients
Jinhu JIA ; Caihong CHANG ; Yulin GAO
Chinese Journal of Primary Medicine and Pharmacy 2021;28(5):660-665
Objective:To investigate the clinical efficacy of different doses of budesonide/formoterol in the treatment of an acute exacerbation of chronic obstructive pulmonary disease in patients.Methods:A total of 200 inpatients with an acute exacerbation of chronic obstructive pulmonary disease graded C/D by global initiative for chronic obstructive lung disease (GOLD) staging system who received treatment in Jiuquan City People's Hospital, China from January to December in 2019 were included in this study. They were randomly divided into a control group and a treatment group ( n = 100/group). Based on anti-infection and expectorant treatment, the treatment group was given inhalation therapy (higher dose budesonide/formoterol, 320 μg/9 μg), while the control group was identically given inhalation therapy (lower dose budesonide/formoterol, 160 μg/4.5 μg), with a total course of 9 days in each group. Before treatment and at 5 and 9 days of treatment, procalcitonin (PCT), high-sensitivity C-reactive protein (hs-CRP), fractional exhaled nitric oxide (FeNO), percentage of eosinophils (EO%), partial pressure of oxygen (PaO 2), lactic acid, interleulin-6 (IL-6), forced expiratory volume in 1 second (FEV 1), the ratio of FEV 1/ forced vital capacity (FVC) were monitored in each group. COPD assessment test (CAT) score, modified Medical Research Council (mMRC) dyspnea score, 6-minute walking test (6MWT), and symptom improvement were determined in each group. Results:Before treatment, there were no significant differences in PCT and PaO 2 between the control and treatment groups (both P > 0.05). There were significant differences in PCT, PaO 2, FeNO, hs-CRP, E0 (%), IL-6, FEV 1, FEV 1/FVC, 6MWT, mMRC, cough, expectoration, shortness of breath and CAT score measured at 5 days of treatment between the treatment and control groups ( t = 2.416, 3.289, 3.982, 4.871, 3.332, 4.098, 5.253, 6.214, 3.843, 7.268, 5.387, 7.392, 5.398, 6.349, all P < 0.05). There were significant differences in PCT, PaO 2, FeNO, hs-CRP, E0 (%), IL-6, FEV 1/FVC, FEV 1, 6MWT, mMRC, cough, expectoration, shortness of breath and CAT score measured at 9 days of treatment between the treatment and control groups ( t = 2.508, 4.032, 2.948, 3.527, 3.118, 5.251, 5.325, 6.338, 2.907, 6.289, 3.246, 2.084, 2.151, 2.527, all P < 0.05). At 5 days of treatment, lactic acid level in the observation group was significantly lower than that in the control group ( t = 4.341, P < 0.05). At 9 days of treatment, there was no significant difference in lactic acid level between the control and observation groups ( t = 1.173, P > 0.05). There was no significant difference in the incidence of adverse reactions between the control and treatment groups [4%(4/100) vs. 5%(5/100), P > 0.05]. Conclusion:Inhalation of high doses of budesonide/formoterol can greatly improve pulmonary function, 6MWT performance, decrease mMRC and CAT scores, alleviate cough, expectoration, shortness of breath, and decrease serum levels of FeNO, hs-CRP, E0(%), IL-6 and other inflammatory factors. Inhalation of higher doses of budesonide/formoterol exhibits better efficacy in the treatment of an acute exacerbation of chronic obstructive pulmonary disease in patients than inhalation of lower doses of budesonide/formoterol.
6.Alteration of the expression of cartilage matrix molecule in the cartilage by the chondrocytes from rabbit temporomandibular joint with experimental osteoarthritis and its response to interleukin-1?
Jia CHANG ; Xuchen MA ; Dalon MA
Journal of Peking University(Health Sciences) 2003;0(05):-
Objective: To study the effect of interleukin 1(IL 1?) on the metabolism of osteoarthritic and normal mature condylar chondrocytes in temporomandibular joints, and investigate the role of IL 1? in the pathogenesis of temporomandibular joint osteoarthritis. Methods: The primary generation of osteoarthritic and normal condylar chondrocytes cultured in the monolayer condition was treated with 20 ?g?L -1 recombined human interleukin 1? (rhIL 1?), and then collected to be detected with RT PCR method for the cellular metabolism including mRNA expression of type Ⅱ collagen, aggrecan, collagenase, insulin like growth factor 1 (IGF 1), and transforming growth factor?1(TGF?1). Results: The normal mature condylar chondrocytes showed the obviously decreased mRNA expression of type Ⅱ collagen and aggrecan after the intervention of exogenous IL 1?, but less influence could be found for the collagenase expression. The osteoarthritic condylar chondrocytes exhibited the decreased mRNA expression of type Ⅱ collagen and collagenase under the effect of IL 1?, while the cellular mRNA expression of aggrecan didn’t change obviously. The intervention of exogenous IL 1? didn't show an obvious influence on the cellular expression of endogenous growth factors such as IGF 1 or TGF ?1 for both the normal and osteoarthritic condylar chondrocytes cultured in vitro. Conclusion: IL 1? could not only disturb the expression of cartilage matrix molecules by the normal condylar chondrocytes, which lead to the lesion of condylar cartilage, but also worsen the abnormal cartilage matrix environment within the osteoarthritic condylar cartilage.
7.Transplantation of mesenchymal stem cells and gelatin porous microcarriers into normal rat heart tissue
Jing CHANG ; Han LEI ; Fengpeng JIA
Journal of Third Military Medical University 1988;0(06):-
Objective To investigate the feasibility of transplantation of human fetal liver-delivered mesenchymal stem cells(HFMSCs) and porous microcarries into normal heart tissue and whether it can improve heart function and regeneration of heart tissue.Methods SD rats were divided into HFMSCs injection group(n=9),microcarrier injection group(n=9) and control group(n=4),in which 80-100 ?l Perfadex with HFMSCs or gelatin porous microcarriers or pure Perfadex was injected into the wall of left ventricle.Heart function was evaluated by UCG before and 7 d after transplantation.On day 7,14,the survival of HFMSCs was tested by fluorescent in situ hybridization(FISH),regeneration or cardiac differentiation by immunohistological staining against desmin,tropomyosin and lectin,cellular immune response by the infiltration of macrophages,and lymphocyte reaction to HFMSCs by mixed lymphocyte culture(MLC) in vitro.Results Seven days after injection,the HFMSCs survived and improved the heart function,though no sign of differentiation into cardiomyocytes was seen.On day 14,a large amount of macrophages infiltrated into injection sites,and MLC showed prominent enhancement of proliferation of lymphocytes,when no transplanted cells were detected in the myocardium.On day 7,14,the microcarriers retained their round shape at the injection sites and were attatched by a large quantity of cells which were proven not cardiomyocytes or capilaries by immunohistological staining.Conclusion Transplantation of HFMSCs into normal heart improves heart function by short-period survival without differentiation,but the transplanted cells disappeared because of immune reaction.Transplantation of porous microcarriers into normal heart could not improve heart function either by regeneration of heart tissue or capilaries.
8.The effect of spironolactone on the expression of TGF-?_1 , PDGF-BB and ?-SMA in hepatic fibrosis tissues in rats
Ai JIA ; Xinming CHANG ; Yingtao ZHANG ; Yingchao LI ; Ying CHANG
Journal of Xi'an Jiaotong University(Medical Sciences) 1982;0(01):-
Objective To investigate the preventive effect of spironolactone on hepatic fibrosis. Methods Ninety SD rats were randomly divided into three groups. Control group consisted of 8 rats that , fed by normal food, were injected with peanut oil subcutaneously. Model group consisted of 42 rats whose liver fibrosis was induced by compound factors. Spiro nolactone-prevention group consisted of 40 rats that were given 100 mg?kg -1 spironolactone per day, by the same methods of making models as those of the model group. At the end of weeks 2, 4, 6 and 8, 8 rats were randomly taken out of model group and spironol actone group and then were sacrificed. The expressions of TGF- ? 1 , PDGF- BB and ? -SMA in hepatic tissues were detected with immunohistochemical met hods. Results The expressions of TGF- ? 1 , PDGF-BB a nd ? -SMA in spironolactone group decreased greatly than those in model gro up ( P
10.Study of HPV Infection, P53 Gene Mutation and Expression in Cervical Carcinoma
Huifang LI ; Yanli CHANG ; Na LI ; Sumin YANG ; Zongzhi JIA
Progress in Biochemistry and Biophysics 2001;28(2):214-217
P53 gene (exon7~8) mutatins and p53 proteins and HPV 6,11,16,18-DNA were examined in 49 cervical carcinoma by immunohistochemistry, polymerase chain reaction (PCR) and single strand conformation polymorphism (SSCP) in order to investigate their role and mutual relation and clinical significance in the onco genesis of cervical carcinoma. The results showed that first, p53 proteins posit ive rate was 48.98%, and not outstandingly related to the differentiation and the invasive degree of cervical carcinoma(P>0.05); the defects of P53 gene (exon7~8) were not found but P53 (exon7~8) mutations were detected in 7 of 49(14.29%) cervical carcinoma; then, HPV16-DNA positive rate was much higher than HPV6,11,18-DNA positive rate respectively(P<0.001),and the different HPV-DNA was simultaneously tested in one cerv ical carcinoma; last, not all cases of P53 mutations had p53 proteins posi tive, but the cases of P53 mutations and p53 proteins negative certainly had HPV infections, and HPV positive cases were much more than its negative one in the cases of p53 proteins positive(P<0.001). These results proved that the oncogenesis of cervical carcinoma is mainly associated with HPV16 infections, and second related to P53 (exon7~8) mutations. p53 proteins positive results from P53 mutations or/and HPV infections in cervical carc inoma.