Objective To explore the expression of hypoxia-inducible factor-1?(HIF-1?) protein and its mRNA in cultured cortical neurons after hypoxia,ischemia or hypoxia-ischemia(HI) and explore the possibilities of HIF-1? gene therapy in HI neurons.Methods The in vitro models of HI,pure hypoxia and pure ischemia were established using embryonic day 16-18 rats cortical neurons.Immunohistochemical and in-situ hybridization were performed to examine the expression of HIF-1? protein and its mRNA at different reperfusion time points in neurons.Results The expression of HIF-1? protein was very week in normoxic cultured neurons,but was up-regulated while treated with hypoxia and(or) ischemia.HIF-1? expression reached peak at 4 to 8 h after reperfusion with HI,which were statistically significant higher than that at other time points(Pa=0),and decreased gradually at 12 h.Furthermore,HIF-1? protein expression was significantly higher in HI group compared with that in the pure hypoxia or ischemia group(Pa=0).HIF-1? mRNA reached peak immediately after HI,decreased gradually at 2 h,and returned to the baseline at 8 h after reperfusion.Conclusions HIF-1? expression on cortical neurons is regulated differently with hypoxia,ischemia or HI treatment,HIF-1? gene therapy for HI neurons maybe a useful method in the future studies.

The paper investigates and analyzes the utilization of literature resources by readers in medical college libraries based on questionnaire survey to find out the problems and causes of literature resource construction work in medical college libraries,and puts forward a series of measures to improve and promote the utilization ratio of literature resources in medical college libraries and give full play to the functions of medical college libraries.

Adult ; China ; epidemiology ; GB virus C ; classification ; Hepatitis, Viral, Human ; epidemiology ; virology ; Homosexuality, Male ; Humans ; Male

Background:Pioglitazone may be beneficial in the treatment of psoriasis.However,based on the effectiveness and safety considerations,it has not been widely used.To fully evaluate the strength of evidence supporting psoriasis treatment with pioglitazone,we conducted a meta-analysis of existing published studies.Methods:PubMed,Ovid,Cochrane Library,Google Scholar,and Web of Science databases were systematically searched before February 2019.Randomized controlled trials (RCTs) of pioglitazone administration compared with placebo,administered to patients with psoriasis for at least 10 weeks,and published in English were included.Quality of the included RCTs was identified by the modified Jadad scale.The quality of evidence for each outcome was evaluated using the GRADEpro Guideline Development Tool online software.Primary outcomes were proportion of patents showing psoriasis area and severity index (PASI) score improvement (＞75％) and the mean percent change in PASI score from baseline to the end of treatment.Dichotomous data were analyzed using odds ratios (ORs) corresponding to the 95％ confidence interval (CI),whereas continuous variables,expressed as mean and standard deviation,were analyzed using the mean differences (MD) with the 95％ CI.Results:Six RCTs were analyzed.Meta-analysis showed that pioglitazone reduced the PASI scores in patients with psoriasis compared with the control group when administered at 30 mg per day (P ＜ 0.001,MD =-3.82,95％ CI =-5.70,-1.93) and at 15 mg per day (P =0.04,MD =-3.53,95％ CI =-6.86,-0.20).The PASI-75 of the pioglitazone group was significantly higher than that of the control group at 30 mg per day (P ＜ 0.001,OR =8.30,95％ CI =3.99,17.27) and at 15 mg per day (P =0.03,OR =2.96,95％ CI =1.08,8.06).No statistically significant differences in total adverse events were observed between the groups.There were no significant differences in common adverse reactions such as weight gain and elevated liver enzymes between the two pioglitazone groups.Conclusions:Use of pioglitazone in the current treatment of psoriasis is beneficial.The therapeutic effect of the daily 30 mg dose may be greater than that of the 15 mg dose per day with no significant change in the frequency of adverse reactions.

Objective To prepare the 99Tcm-survivin mRNA antisense peptide nucleic acid (PNA)and investigate its value as a gene imaging agent in tumor bearing mice and early diagnosis in tumor.Methods Survivin mRNA antisense PNA and mismatch PNA were synthesized.Four amino acids (Gly- (D)Ala-Gly-Gly) and Aba (4-aminobutyric acid) were linked to the 5' end of PNA.Gly- (D)Ala-Gly-Gly served as a chelating moiety for strong chelation of 99Tcm and Aba acted as a spacer to minimize the steric hindrance.PNAs were labeled with 99Tcm by the ligand-exchange method.The labeling efficiency and radiochemical purity were measured by HPLC and ITLC methods.There were five BALB/c nude mice bearing human lung carcinoma ( A549 ) in each of antisense PNA and mismatch PNA groups.Gene imaging of 99Tcm-survivin mRNA antisense and mismatch PNAs were performed at 1,2 and 4 h post the injection,respectively,and the T/NT ratio was measured by the method of ROI.The statistical comparisons of average values were performed with the two-group t-test for independent sample by SPSS 13.0.Results The product kept stable in vitro.The labeling efficiency of 99Tcm-survivin mRNA antisense PNA was (95.48 ±1.92)％ and more than 85％ after the incubation for24 h in serum.The radiochemical purity was ＞ 95％.The labeling efficiency of mismatch PNA was similar to the antisense PNA.99Tcm-survivin mRNA antisense PNA was especially uptaken by tumor lesion,and its accumulation reached the top at 4 h post the injection.T/NT ratios at 1,2,and 4 h were 2.70 ± 0.28,3.44 ± 0.35,4.21 ± 0.63,respectively.In the comparison,the T/NT ratio of 99Tcm-survivin mRNA mismatch PNA at 4 h (3.12 ±0.50) was significantly lower (t =2.918,P =0.019).Conclusions 99Tcm-survivin mRNA antisense PNA has high labeling efficiency,good stability and no need of purification.Its characteristic of especial uptake by tumor lesion provides the potential value in early diagnosis of tumor.

Objective To investigate the present prevalence state of children's Kaschin-Beck disease (KBD) in Xinghai county of Qinghai province,a relative active KBD area in 2009,and to investigate their nutritional selenium level of local children and the T-2 toxin contamination level in their staple food.Methods Right hand X-ray photographs of children aged 7 - 12 in Shang,Zhong and Xia villages of Tangnaihai countryside in Xinghai county were taken.X-ray diagnosis was carried out according to the Diagnostic Criteria of Kashin Beck Disease (GB 16003-1995 ).Selected samples (children's hair,drinking water and their staple food) were collected according to X-ray film taken.Selenium contents in hair,drinking water and staple food samples were measured by 2,3-diaminonaphthalene fluorescence,and T-2 toxin in staple food sample was detected with enzyme-linked immunosorbent assay(ELISA) kits.ResultsTotal X-ray detection rate of children KBD was 12.20％(31/254) and KBD positive rate of children in Xia village was up to 14.97％(22/147),Shang village was up to 9.52％(6/63),and Zhong village was up to 6.82％ (3/44).The selenium level in children's body and outer environment was very low,namely,the selenium content in hair,drinking water,wheat and flour was (0.250 ± 0.136)mg/kg,(0.156 ± 0.046)μg/L,(0.0045 ± 0.0030)mg/kg,and (0.0067 ± 0.0116)mg/kg,respectively.The T-2 toxin level was relatively high in children's staple food,which was (78.91 ± 46.17)μg/kg in wheat and (47.47 ± 46.47)μg/kg in flour.Conclusions In relative active KBD areas of Xinghai county of Qinghai province,the children's selenium nutritional level is low,and the T-2 toxin contamination level in their staple food is relatively high,which is consistent with the distribution of local children's KBD.

BACKGROUNDMultiple epiphysis dysplasia (MED) is a common skeletal dysplasia with a significant locus heterogeneity. In the majority of clinically defined cases, mutations have been identified in the gene encoding cartilage algometric matrix protein (COMP).

METHODSFive patients were included in the study. Linkage analysis and mutation analysis of the COMP gene were conducted in the patients and their family members.

RESULTSWe have identified a novel mutation in axon 14 of COMP gene in the family.

CONCLUSIONSThis mutation produced a severe MED phenotype with marked short stature, early onset osteoarthritis, and remarkable radiographic changes. Our results extended the range of disease-causing mutations in COMP gene and contributed more information about relationship between mutations and phenotype.

Adolescent ; Asian Continental Ancestry Group ; Cartilage Oligomeric Matrix Protein ; genetics ; Female ; Humans ; Male ; Osteochondrodysplasias ; genetics ; Pedigree ; Point Mutation ; genetics

OBJECTIVETo study the effects of maternal folate deficiency on fetal growth and development and the methylation profiles of insulin-like growth factor system in the offspring rats.

METHODSTwenty-two Sprague-Dawley female rats were randomly assigned to two groups: a folate deficient group (n=12) and a control group (n=10). They were fed with folate deficient and normal diet respectively. Dams were mated after 2 weeks of feeding. Eight female rats from each group were pregnant. On the 20th day of gestation, the fetuses were delivered by caesarean section. Thirty-two fetal rats from each group were randomly selected and the body length and weight were measured. Eight fetal rats from each group were randomly selected and ELISA was used to measure the level of folate content, IGF-1 and IGFBP-3 in the fetal brain and liver. Three fetal rats from each group were randomly selected and methylated DNA immunoprecipitation sequencing (MeDIP-Seq) was used to detect the methylation level of insulin-like growth factor system in the fetal brain and liver. ELISA was used to measure the level of IGF-1 and IGFBP-3 in the maternal serum from both groups.

RESULTSThe mean fetal length and weight were lower in the folate deficient group than in the control group (P<0.05). The levels of IGF-1 and IGFBP-3 in the maternal serum, as well as folate content and IGFBP-3 in the fetal brain and liver were significantly lower in the folate deficient group than in the control group (P<0.05). The methylation levels of IGF-1R, IGF-2R, IGFBP-2, IGFBP-5, IGFBP-6 and IGFBP-7 in the fetal brain were higher in the folate deficient group than in the control group (P<0.05). The methylation levels of IGF-1R, IGF-2R, IGFBP-3 and IGFBP-5 in the fetal liver were higher in the folate deficient group than in the control group. The methylation of IGF-2 gene showed a significant reduction in the folate deficient group (P<0.05).

CONCLUSIONSMaternal folate deficiency may cause retardation of growth and development of the offspring, which is possibly associated with the changes of methylation profiles of insulin-like growth factors.

Animals ; Brain ; metabolism ; DNA Methylation ; Female ; Fetal Development ; Fetus ; metabolism ; Folic Acid Deficiency ; metabolism ; Insulin-Like Growth Factor Binding Protein 3 ; blood ; Insulin-Like Growth Factor I ; analysis ; Liver ; metabolism ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo explore the relationship between serum creatinine (Scr) reference values in healthy adults and geographic factors and provide evidence for establishing Scr reference values in different regions.

METHODSWe collected 29 697 Scr reference values from healthy adults measured by 347 medical facilities from 23 provinces, 4 municipalities and 5 autonomous regions. We chose 23 geographical factors and analyzed their correlation with Scr reference values to identify the factors correlated significantly with Scr reference values. According to the Principal component analysis and Ridge regression analysis, two predictive models were constructed and the optimal model was chosen after comparison of the two model's fitting degree of predicted results and measured results. The distribution map of Scr reference values was drawn using the Kriging interpolation method.

RESULTSSeven geographic factors, including latitude, annual sunshine duration, annual average temperature, annual average relative humidity, annual precipitation, annual temperature range and topsoil (silt) cation exchange capacity were found to correlate significantly with Scr reference values. The overall distribution of Scr reference values featured a pattern that the values were high in the south and low in the north, varying consistently with the latitude change.

CONCLUSIONThe data of the geographic factors in a given region allows the prediction of the Scr values in healthy adults. Analysis of these geographical factors can facilitate the determination of the reference values specific to a region to improve the accuracy for clinical diagnoses.

ObjectiveTo investigate the value of 99Tcm labeled survivin mRNA antisense peptide nucleic acid (PNA) as an imaging agent in the specific diagnosis for carcinoma.MethodsSurvivin mRNA antisense PNA was labeled directly with 99Tcm by the ligand-exchange method.Twenty nude mice with lung carcinoma A549 xenografts were randomly divided into 4 groups.Three groups were used for biodistribution study and one group was used for imaging study.Other twenty mice infected by staphylococcus aureus underwent the same procedure.The biodistribution and imaging of 99Tcm-survivin mRNA antisense PNA was studied at 1,2 and 4 h respectively after the intravenous injection in nude mice bearing lung carcinoma A549 xenografts or inflammation models.SPSS 13.0 was used in the study and all data were analyzed by t test.ResultsBiodistribution results showed that the highest radioactivity was found in the liver,and then in the kidney.Four hours after the administration of the imaging agent,the radioactivity ratios of target-tonon target (T/NT,tumor or inflamumatory lesions to the contralateral regions) in tumor model group were significantly higher than those in inflammation model group ( 3.69 ± 1.13 vs 2.03 ± 0.47,t =3.01,P =0.02 ).Tumors were clearly visible in the tumor model groups at 0.5 h and still clearly seen at 4 h after the injection of antisense PNA.On the contrary,inflammatory lesions could not be seen clearly.Conclusion 99Tcm labeled survivin mRNA antisense PNA can be used to distinguish tumor from inflammation and it may provide a new feasible method for specific tumor diagnosis.