Hypoxia-inducible factor(HIF) plays a key role in the adaptation of tumour cells under hypoxic circumstance,there are some advances in the literatures regarding HIF as an important target for anticancer agents and gene therapy.In this review,the molecular mechanism and clinical significance of compounds targeting on hypoxia- inducing factor was summarized.

T),resulting in His to Leu(CAT→CTT) substituted at codon 435(H435L).No mutation was identified in the patient's parents.HT occurred in the patient during following-up.Conclusion H435L mutation in exon 10 of TR? gene leads to resistance to thyroid hormone.Meanwhile,consistent RTH might lead to HT.

Objective: To establish a mice model of congenital heart disease transposition of great arteries in order to provide a research reference for the occurrence and development of transposition of great arteries. Methods: A total of 20 pregnant ICR mice at 8-10 weeks of age were divided into 2 groups: Control group, the mice received a single dose of DMSO 70 mg/kg at 8.5 days of gestation,n=5 and Experiment group, the mice received a single dose of all-trans retinoic acid 70 mg/kg at 8.5 days of gestation,n=15. All animals were treated for 18 days and then the embryos were taken to observe cardiac morphology under stereomicroscope. Results: Compared with Control group, Experiment group had obviously increased occurrence rates of premature delivery, abortion and embryo absorption, and 61.2% phenotype for transposition of great arteries; meanwhile, combining with non-heart defect phenotypeas exophthalmos and spinal malformation. Conclusion: All-trans retinoic acid may induce transposition of great arteries in mice embryos, which is a feasible animal model in experimental research.

Objective To evaluate the effect of N- acetylcysteine(NAC) on lipopolysaccharide (LPS) - sensitized neonatal rats with hypoxic- ischemic brain damage(HIBD) and possible mechanism except the antioxidant. Methods With the total number of 98 Wistar pups at postnatal day 8 of either sex was used in this study. There were 86 pups which were divided into three groups to evaluate the brain injury:vehicle group ( n = 29) ,low dose (25 mg/kg) ( n = 31 ) and high dose NAC (200 mg/kg) ( n - 26) treatment group. The pups were injected with LPS(0.1 mg/kg)intraperitoneally 3 days before hypoxic- ischemic(HI) insult. Multiple dose of NAC (25 mg/kg or 200 mg/kg) or vehicle was injected intraperitoneally before and after HI. Brain injury was evaluated 7 days after HI. For the Caspase - 3 activity and immunoblotting analysis, the samples were collected at 24 h after HI treated either with vehicle or high dose NAC ( n = 6 per group). Results The brain injury volume was significantly reduced by high dose NAC (200 mg/kg) treatment compared with that of vehicle (77% reduction, P ＜ 0.001 ). The tissue loss was reduced 67 % ( P ＜ 0.001 ) in high dose NAC treated group compared with that of vehicle. However,there was no significant reduction of brain injury in the low dose NAC treatment group compared with vehicle group. Caspase - 3 like activity measurement showed that the activity decreased 53 % after high dose NAC treatment ( P ＜ 0. 001 ) compared with that of vehicle treatment. The immunoblots showed that the active form of Caspase - 3, 17 kDa band, was abolished by the high dose NAC treatment. Conclusions NAC treatment attenuate LPS - sensitized neonatal HI brain injury is dose dependent. The neuroprotective effect involves Caspase - 3 inhibition.

Objective To analyze the current status of mental symptoms and related influencing factors in patients with schizophrenia, and to provide reference for helping patients achieve better home rehabilitation. Methods Cluster extraction was done of 371 home schizophrenia patients registered in the community, and follow-up surveys were carried out for general demographic data, family status, current status of the disease, and treatment status.Univariate and multivariate logistic regression analysis was used for each factor in affecting the patient′s mental symptoms. Results All of the 371 patients completed follow-up surveys, and 121 patients with positive psychotic symptoms (positive rate 32.61%).Univariate analysis showed that differences in the economic situation, course of illness(years), risk behavior level, self-knowledge, hospitalization and working status were statistically significant (P < 0.05), while differences in gender, age, education level, marital status, disease course, family history were not.And there was no significant difference in the disability identification, monitoring status, medication compliance, and free medication (P>0.05).Multivariate logistic analysis showed that complete self-knowledge(OR=0.488, 95%CI:0.284-0.838), and participation in work(OR=0.469, 95%CI:0.257-0.857) were protection factors (P < 0.05). Conclusion The service management of patients with schizophrenia at home should be strengthened, regular follow-up and nursing care mechanisms should be improved, and patients with positive mental symptoms should be actively mobilized for hospitalized treatment.Improving the patient′s self-knowledge and helping patients improve their ability to work and work is the key to preventing mental symptoms in patients with schizophrenia.

?AIM:To compare the coherence and difference on the fundus examination made with two kinds of optical coherence tomography ( OCT): Angio-OCT and fourier domain-optical coherence tomography ( FD-OCT) .?METHODS:Using Angio-OCT and FD-OCT to measure the retinal nerve fiber layer ( RNFL ) thickness, optic parameters, and ganglion cell complexes ( GCC ) thickness from 20 subjects respectively.The coherence was tested with Pearson's correlation coefficient, the difference was tested with paired Student t testing.?RESULTS:The total correlation of the RNFL thickness, optic parameters, GCC thickness made with two kinds of OCT was between 0.7-0.8;the RNFL thickness, optic disk area etc.made with the Angio-OCT were lower than those made with FD-OCT except for the GCC thickness.?CONCLUSION: The results made with two kinds of OCT from the same subject has certain coherence, but cannot be compared directly.

ObjectiveTo investigate the correlation of serum 25-hydroxy vitamin D［25(OH)D］ level with the severity of infantile cholestatic hepatopathy (ICH). MethodsA total of 121 infants with ICH who were admitted or referred to Liver Research Center in our hospital from July 2015 to December 2017 were enrolled, and according to the presence or absence of liver cirrhosis, these infants were divided into liver cirrhosis group with 26 infants and non-liver cirrhosis group with 95 infants. The two groups were compared in terms of age, sex ratio, 25(OH)D, liver function parameters ［total bilirubin (TBil), direct bilirubin (DBil), total protein (TP), albumin (Alb), alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), alkaline phosphatase (ALP), total bile acid (TBA), and prothrombin time (PT)］, serological markers of liver fibrosis ［procollagen Ⅲ peptide (PⅢNP), laminin (LN), hyaluronic acid (HA), and type Ⅳ collagen (C-Ⅳ)］, and indices associated with vitamin D metabolism (Ca and P). The independent samples t-test or the Mann-Whitney U test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups. A binary logistic regression analysis was used to investigate the factors associated with the development of liver cirrhosis. ResultsOf all 121 infants, 107 (88.43%) had vitamin D deficiency, and all 26 infants with liver cirrhosis had vitamin D deficiency. Compared with the non-liver cirrhosis group, the liver cirrhosis group had significant reductions in the serum levels of 25(OH)D and Alb (Z=3.029, t=2.294, P＜0.05) and significant increases in the levels of DBil, AST, GGT, HA, and C-Ⅳ(Z=3.032, 2.026, 3.439, 3.143, and 2.247, P＜0.05), while there were no significant differences in the other indices between the two groups (all P＞0.05). The multivariate logistic regression analysis showed that 25(OH)D (odds ratio ［OR］=0.865, 95% confidence interval ［CI］: 0.755-0.922, P=0.038), GGT(OR=1.002, 95%CI: 1.000-1.004, P=0.039), and HA (OR=1.004, 95%CI: 1.000-1.008, P=0.034) were associated with liver cirrhosis in infants with ICH. ConclusionSerum 25(OH)D has a certain clinical value in predicting the severity of hepatocyte damage and the development of early liver cirrhosis in infants with ICH.

Objective To observe the protective effects of Toll-like receptor(TLR)-4 siRNA against acute liver injury in mice induced by lipopolysaccharide(LPS)and D-galactosamine(D-GalN).Methods One hundred and fifty C57BL/6 male mice were divided into 5 groups: phosphate buffered solution(PBS)pretreatment group,negative control plasmid pretreatment group,TS4 pretreatment group,TS6 pretreatment group and TS7 pretreatment group.Acute liver injury was induced in mice by intraperitoneal coinjection of LPS(10 ng/g)and D-GalN(1 mg/g).In vivo delivery of siRNA was performed via the tail vein by hydrodynamic injections(50 μg siRNA dissolved in 1 mL PBS)24 h and 48 h before coinjection of LPS and D-GalN. Expression of TLR-4 in liver tissues was measured by immunohistochemistry.The changes of TLR-4,tumor necrosis factor(TNF)-α and macrophage nflammatory protein(MIP)-2 mRNA levels in liver tissues were determined by reverse transcriptasepolymerase chain reaction(RT-PCR)analysis.MIP-2 and TNF-α concentrations in the sera of mice were determined by enzyme-linked immunosorbent assay(ELISA). Levels of alanine transaminase (ALT) and aspartate transaminase(AST) in serum were measured by standard autoanalyzer techniques. Liver pathological changes were observed by haematoxylin-eosin staining, while cell apoptosis levels in liver were determined by terminal deoxynucleotidyl-mediated-dUTP nick end labeling (TUNEL)assay. The difference of survival rates in 5 groups was analyzed by Fisher's exact probability test.ResultsPretreatment with TLR-4 siRNA down-regulated the TLR-4 mRNA and protein expressions,and significantly decreased the mortality and liver injury caused by coinjection of LPS and D-GalN in C57BL/6 mice.TLR-4 siRNA significantly down-regulated the TNF-α and MIP-2 mRNA expression and cytokine levels as determined by RT-PCR and ELISA,respectively. TLR-4 siRNA abrogated hepatocyte necrosis and inflammatory infiltration and also remarkably reduced serum concentrations of transaminases. The percentage of TUNEL-positive hepatocytes was significantly reduced in TLR-4 siRNA pretreatment group(TS4 pretreatment group: 0.065±0.015 vs PBS pretreatment group; 0.346±0.062,P＜0.05).ConclusionIt suggest that inhibition of TLR-4 expression by TLR-4 siRNA may provide potential application value for preventing liver injury.

OBJECTIVETo probe into periostin's role in the pathological mechanism of hyperplasic scars, by examining the expression of periostin in hyperplasic scar tissues. To investigate the correlations between periostin and TGF-beta1, TGF-beta R I, TGF-beta R II.

METHODSRT-PCR was used to assess the mRNA expression levels of TGF-beta1, TGF-beta R I, TGF-beta R II in three kinds of tissues, which are keloid (K), hypertrophic scar (HS) and normal skin (SK). The protein expression of periostin was measured with Western blotting.

RESULTSThe mRNA level of periostin in K was higher than that in SK. The mRNA expression of TGF-beta1 in K was higher than that in HS and SK. The mRNA level of TGF-beta R I in K was higher than that in HS and SK. The significances above all was at P < 0.01. The protein expression level of periostin in HS increased, compared with that in SK (P < 0.05). Periostin was related to TGF-beta1 positively (P <0.01).

CONCLUSIONSThe periostin's expression is increased in keloids. Periostin is a cicatrix specific gene. Periostin appears to play an important role in the formation of keloids, which is related to TGF-beta1 closely.

Adult ; Cell Adhesion Molecules ; metabolism ; Cicatrix, Hypertrophic ; metabolism ; pathology ; Female ; Humans ; Keloid ; metabolism ; pathology ; Male ; Receptors, Transforming Growth Factor beta ; metabolism ; Transforming Growth Factor beta1 ; metabolism

OBJECTIVETo probe into the mechanism of fibrillin 1 in pathologic scar, by examining the expressions of fibrillin 1 and TGF-beta1 as well as their correlations in the tissues of keloid, hypertrophic scar and normal skin.

METHODSThe tissues of keloid, hypertrophic scar and normal skin were tested. RT-PCR was used to assess the mRNA expression levels of the aimed genes. The distribution of fibrillin 1 in scars and normal skin was examined by immunohistochemistry staining.

RESULTSThe mRNA level of fibrillin 1 in keloid (0.802 +/- 0.116) was increased by 218.25% (P < 0.01) than that in normal skin (0.252 +/- 0.067). The expression of the gene in hypertrophic scar (0.628 +/- 0.144) was higher by 149.21% (while, P > 0.05) than that in normal skin. The expression of TGF-beta1 in keloid and hypertrophic scar were more than that in normal skin. The expression of fibrillin 1 was related to that of TGF-beta1 positively (r = 0.820, P < 0.01). Fibrillin 1 protein was stained positively in basic membranes, endothelial cells, fibroblasts and extracellular matrix of skin tissues. In dermal, the protein levels of fibrillin 1 in keloid (0.117 +/- 0.042) was decreased than those in normal skin (0.185 +/- 0.043) and hypertrophic scar (0.181 +/- 0.048), the inhibition rates were 36.76%, 35.36% respectively (both P < 0.01).

CONCLUSIONSThe expression of fibrillin 1 in keloid was changed and related to the expression of TGF-beta1 positively, which appears that fibrillin 1 was a cicatrix specific gene. Fibrillin 1 might play an important role in the formation of keloid.

Cicatrix, Hypertrophic ; metabolism ; pathology ; Fibrillin-1 ; Fibrillins ; Humans ; Keloid ; metabolism ; pathology ; Microfilament Proteins ; metabolism ; RNA, Messenger ; genetics ; Transforming Growth Factor beta1 ; genetics ; metabolism