Adult ; Altitude ; Female ; Heart ; physiology ; Humans ; Male ; Occupational Health ; Railroads ; Tibet

Objective To analyse MMACHC mutations for 45 pedigrees with combined methylmalonic aciduria and homocyctinuria by Sanger sequencing, and to discuss the utility of prenatal genetic diagnosis for these pedigrees.Method Peripheral blood was collected from 45 probands and their parents from 2012-2015 in Genetic Counselling Clinic of the First Affiliated Hospital of Zhengzhou University, and the DNA were extracted from the blood.Then the coding sequence of MMACHC gene was amplified by PCR, and the PCR products were further sequenced to detect mutations for each pedigree.For 12 families, chorionic villus sampling was performed on the pregnant women to make prenatal genetic diagnosis.Result There were 14 distinct mutations detected in the 45 pedigrees, and the most frequent mutations are c.609G>A(W203X),c.658-660delAAG(K220del)and c.80A>G (Q27A).Two of those mutations have not been reported before:one is a splicing site mutation c.81+1G>A;while the other is a missense mutation c.665A>G,p.Y222C.Most mutations were found in exon 4.Among the 12 pedigrees who received prenatal diagnosis, 2 fetuses were normal, 7 fetuses were carriers of heterozygous mutation, and the other 3 fetuses were patients with compound heterozygous mutation or homozygous mutation.The couples whose fetuses were normal or carriers continued the gestation, while the couples whose fetuses were patients decided to terminate the pregnancy.After delivery, the outcome of the fetuses was the same as the prenatal diagnose results.Conclusion Two novel mutations of MMACHC were identified and prenatal genetic diagnosis helps to avoid the delivery of combined methylmalonic aciduria and homocyctinuria patients.

Filtering channels carring and subsequent obstruction are the main cause of operation failure after glaucoma filtration surgery. During the process of scarring, human Tenon fibroblasts are transformed into myofibroblasts and secrete a large amount of extracellular matrixproteins. The derangement of the collagen fiber is also observed. A large number of studies have been carried out by domestic and foreign researchers on the treatment of postoperative filtering channel scarring. In this review we summarize the mechanisms of scar formation after glaucoma filtration surgery and corresponding research progress in recent years.

Objective To explore whether extracellular signal-reg-ulated kinase (ERK) signaling pathway is involved in the hypoxia-inducible factor-1α (HIF-1α) expression in the hippocampus of epileptic rats.Methods A total of 208 21-d old SD rats were equally randomized into status epilepticusgroup (SE,n=96),normal control group (NS,n=96) and PD98059 (the ERKsignaling pathway specific inhibitor) treatment group (n=16),respectively; SE rat models of the SE group were induced by intraperitoneal injection of 1％ PTZ (80 mg/kg),and rats of the NS group received injection of normal saline (NS); 0.5,1,1.5,6,12 and 24 h after the inducement,the mRNA and protein expressions of HIF-lα and ERK1/2 in the hippocampus of rats in these two groups were examined by RT-PCR and Westem blotting.For rats in the PD98059 treatment group,PD98059 was intraperitoneally injected 10 minutes before intraperitoneal injection of pentylenetetrazol; 1 h after the inducement,the mRNA expressions of HIF-1α and ERK1/2 in the hippocampus of rats were examined by RT-PCR,while 1.5 h after the inducement,the protein expressions of HIF-1α and ERK1/2 in the hippocampus of rats were examined by Western blotting.The results of the PD98059 treatment group would be compared with those of the SE group.Results Compared with the NS group,the mRNA and protein expressions of HIF-1α and ERK 1/2 in the hippocampus of rats in the SE group after SE increased significantly; the peakexpression time ofERK1/2 mRNA was 1 h after SE (1.112±0.126 h),and the ERK1/2 protein mostly expressed at 1.5 h after SE (1.127±0.155 h).As to HIF-1α mRNA and its protein,the peak expression time was 1.5 h after SE (0.589±0.090 h) and 6 h after SE (0.230±0.052 h),respectively (P＜0.05).Compared with the SE group,the mRNA and protein expressions of HIF-1α and ERK1/2 in the hippocampus of all the rats in the PD98059 treatment group after SE decreased significantly (P＜0.05);positive correlation between HIF-1α and ERK1/2 mRNA in the SE group was noted (r=0.688,P=0.000).Conclusion ERK signaling pathway is activated in the epileptic rats and it participates in the expressionof HIF-1α in the hippocampus.

Objective To develop an animal model of minimal persistent inflammation(MPI)in allergic rhinitis guinea pigs and to investigate its significance.Methods Sixty male Hartley guinea pigs were divided into four groups:group A(positive control group),B(MPI model group),C(negative group) and D(bland group)respectively,with fifteen animals in each group.Guinea pigs from group A,B and C were sensitized intraperitoneally by injection of suspension of ovalbumin(OVA)and aluminum hydroxide in 0.9%physiological saline.Then,repeated local booster sensitization with different concentration of OVA suspension(1%and 0.01%)or physiological saline into the nasal cavity of those guinea pigs were performed.For group D,physiological saline was used only.Symptoms(sneezing)of guinea pigs after intercellular adhesion molecule 1(ICAM-1)in the nasal epithelial cells were also examined.Results When challenged with l%OVA.the sneezing number of guinea pigs in group B was increased markedly than that in group D(P<0.05).However,there was no difference between group B,A and C(P>0.05).When challenged with 0.01% OVA,the symptom of snee~ng almost disappeared in group B just like that in group D and there was no difference between the two groups(P>0.05). Besides,there was still more EOS infiltrated in the nasal mucosa of guinea pigs in group B than that in group D(P<0.05).There was no expressed in group B.Condusions MPI models have been established successfully through long term challenge with lower density of OVA in the sensitized guinea pigs.which will provide us witll a new method for further research in the mechanism and treatment of allergic rhinitis.

Objective To establish an animal model of minimal persistent inflammation(MPI)of allergic rhinitis in guinea pigs and to investigate the changes of nasal mucosa.The expression of transforming growth factor-β1(TGF-β1)and matrix metalloproteinases-9(MMP-9)were discussed. Methods Thirty male Hartley guinea pigs were randomly divided into two groups:MPI model group and control group randomly,with fifteen animals in each group.Guinea pigs from MPI model group were sensitized intraperitoneally by injection of suspension of ovoalbumin(OVA)and aluminum hydroxide in 0.9%physiological saline.Then.repeated local booster sensitization with low concentration of OVA suspension into the nasal cavity was performed to establish MPI models.Alcian blue-periodic acid-Schiff(AB-PAS)staining and Masson's trichrome(MT)staining were used to determine the number of goblet cells and collagen deposition within the basement membrane of epithelium.The expression and distribution of TGF-β1 and MMP-9 in nasal mucosa were estimated by double immunofluorescence under a confocal laser scan microscopy system.Results Compared with the control group,the increased goblet cells(t=13.720,P＜0.05)in nasal epithelium together with the increased collagen fibrils(t=4.542,P＜0.05)within the basement membrane of epithelium were observed in the MPI model group.There was nearly no expression of TGF-β1 in the control group and the expression of MMP-9 was only found in the epithelium cell.In contrast,there was significantly higher expression of TGF-β1 and MMP-9(t=25.218,P＜0.05)in nasal mucosa of MPI model group than that in control group.TGF-β1 mainly expressed in the epithelium cell,the infiltrated inflammatory cell and extracellular matrix,while MMP-9 expressed in the epithelium cell and the infiltrated inflammatory cell.Conclusions Long time MPI in allergic rhinitis resulted in some changes of tissue remodeling in nasal mucosa.TGF-β1 and MMP-9 may play an important role in disease progression.

Objective To probe into the level and influencing factors of community stroke patients′health behaviors so as to provide evidence for health guidance of community stroke. Methods The health promoting lifestyle profile ( HPLPⅡ) and self-designed general information questionnaire were conducted in 200 stroke patients in the community in 2013 July to 2014 March, and the results of surveys had been analyzed. Results Stroke patients with HPLP Ⅱ score was (121. 43 ± 13. 71) score, and 74% patients had unhealthy lifestyle. The influencing factors of health behavior were gender, education background, income, BMI, smoking, regular diet and regular check-up. Conclusions Stroke patients were in poor health behavior level, so the medical care personnel should focus on patients with smoking, diet, not regular recheck and other bad habits according to different gender, education and income to promote their lifestyle.

OBJECTIVETo elucidate the effect of targeted gene modulation of peroxisome proliferator activated receptor gamma (PPARg) on hepatocellular apoptosis in nutritional fibrotic steatohepatitis in mice. C57BL/6J mice were fed with high fat, methionine-choline deficient (MCD) diet for 8 weeks to induce fibrotic steatohepatitis. Mice fed the MCD diet were treated with adenovirus carrying PPARg (Ad-PPARg), adenovirus-beta-galactosidase (Ad-LacZ), Ad-PPARg plus PPARg agonist rosiglitazone, or PPARg antagonist 2-chloro-5-nitro- benzanilide (GW9662), respectively. H and E stain was performed for observation of hepatocellular apoptosis, hepatic steatosis, inflammation and fibrosis in the liver sections. The expression levels of mRNA and protein of PPARg and apoptosis related genes, Fas, Fas Ligand (FasL), B cell lymphoma/leukemia-2 (Bcl-2), Bcl-2 associated X protein (Bax) and cysteine-containing aspartate-specific proteases-3 (caspase-3) were detected by real-time RT-PCR and Western blot assay, respectively.

RESULTSMice fed with MCD diet for 8 weeks showed severe hepatic injury including steatosis, hepatocellular apoptosis, inflammatory infiltration and fibrosis, concomitancy with enhanced expression of pro-apoptosis genes, Fas, FasL, Bax and caspase-3 and increased expression of anti-apoptosis gene Bcl-2, by comparing with the control group. The mRNA expression levels of these genes were 3.59+/-0.35 vs 1.11+/-0.37, 4.37+/-1.03 vs 1.09+/-0.33, 4.27+/-0.48 vs 1.03+/-0.10, 4.93+/-0.67 vs 1.12+/-0.24 and 3.95+/-0.34 vs 1.20+/-0.19, and LSD-t values were 2.49, 3.28, 3.25, 3.80 and 2.75, as compared with the control group, P is less than 0.01; the protein expression levels were 1.96+/-0.07 vs 0.45+/-0.07, 0.53+/-0.07 vs 0.22+/-0.02, 1.32+/-0.06 vs 0.59+/-0.03, 1.51+/-0.23 vs 0.36+/-0.09 and 0.57+/-0.01 vs 0.29+/-0.01, and LSD-t values were 1.51, 0.31, 0.73, 1.14 and 0.28, P is less than 0.01. Administration of PPARg agonist rosiglitazone and/or Ad-PPARg significantly ameliorated hepatic steatosis, hepatocellular apoptosis, necro inflammation and fibrosis. These effects were associated with repressed expression of pro-apoptosis genes and up-regulated expression of anti-apoptosis gene. After rosiglitazone treatment, the mRNA expression levels were 3.78+/-0.58, 3.66+/-0.83, 3.04+/-0.37, 2.54+/-0.62 and 4.42+/-0.42, and LSD-t values were 0.18, 0.71, 1.23, 2.39 and 0.46, as compared with MCD group, the P values were 0.627, 0.241, less than 0.01, less than 0.01 and 0.278, the protein expression levels were 1.06+/-0.03, 0.30+/-0.01, 0.70+/-0.05, 1.19+/-0.30 and 0.90+/-0.01, and LSD-t values were 0.90, 0.23, 0.62, 0.31 and 0.34, the P values were less than 0.01, less than 0.01, less than 0.01, 0.122, less than 0.01. After Ad-PPARg treatment, the mRNA expression levels were 2.31+/-0.16, 2.71+/-0.23, 2.52+/-0.27, 1.79+/-0.32 and 5.97+/-0.72, and LSD-t values were 1.28, 1.66, 1.75, 3.13 and 2.02, as compared with MCD group, P is less than 0.05; the protein expression levels were 1.73+/-0.07, 0.43+/-0.04, 1.01+/-0.08, 1.31+/-0.10 and 1.56+/-0.04, and LSD-t values were 0.23, 0.10, 0.30, 0.20 and 0.99, with P values equal 0.009, 0.01, less than 0.01, 0.322 and less than 0.01.

CONCLUSIONSThis study provided evidences for the protective role of activation and overexpression of PPARg in ameliorating hepatocellular apoptosis in mice with hepatic fibrosing steatohepatitis.

Animals ; Apoptosis ; Liver ; metabolism ; pathology ; Liver Cirrhosis ; metabolism ; pathology ; Male ; Mice ; Mice, Inbred C57BL ; PPAR gamma ; metabolism

BACKGROUND: C-telopeptide and N-telopeptide cross-linked collagen type Ⅰ (CTx and NTx, respectively) are specific biochemical bone markers that can reflect bone formation and resorption. OBJECTIVE: To analyze the association of CTx with disuse osteoporosis. METHODS: Male Sprague-Dawley rats, weighing 180-220 g, were randomly divided into control and disuse osteoporosis groups. Right hind limbs of the rats in the disuse osteoporosis group were immobilitzed for 4 weeks by ankle-tail fixation to establish the rat model of disuse osteoporosis. Peritoneal venous blood was collected before and after modeling, and the femur was then removed to measure the serum CTx level and bone mineral density of the bilateral femurs. RESULTS AND CONCLUSION: The serum CTx level did not differ significantly between groups before modeling (P > 0.05). At 4 weeks after modeling, the serum CTx level in the disuse osteoporosis group was significantly higher than that in the control group and at baseline (P <0.01). The serum CTx level showed no significant change in the control group before and after modeling (P > 0.05). The increment of serum CTx in the disuse osteoporosis group exhibited a negative correlation with the bone mineral density of the bilateral femurs (r=0.426, P < 0.01). The bone mineral density of the right femur in the disuse osteoporosis group was significantly lower than that of the left one in the disuse osteoporosis group and the right one in the control group (P < 0.01), and there was no significant difference in the bone mineral density between left and right femurs in the control group (P > 0.05). These results imply that the model of disuse osteoporosis by ankle-tail fixation is established successfully. Disuse osteoporosis can promote the production of CTx further reducing bone mineral density; CTx is positively correlated with the degree of bone loss, so it can be used for therapeutic assessment and diagnosis of osteoporosis.

rats.