Angiolymphoid Hyperplasia with Eosinophilia ; pathology ; Forehead ; pathology ; Humans ; Male ; Middle Aged ; Parotid Gland ; pathology

Objective To study the effect of injured podocytes on glomerular maturation and its underlying mechanism in neonatal mice.Methods Single i.p.injection with puromycin aminonucleoside (PA,0.1 mg/g BW) was given to ICR neonatal mice at day 1 after birth (1 dpp). Littermates injected with normal saline (NS) were used as control.Animals were examined for urine protein,blood pressure,kidney weight/body weight (KW/BW),renal histology at 2,4,8,12, 30,60 and 90 dpp (n=6～9 for each group).Immunohistochemistry and quantitative RT-PCR were performed to examine the expression of WT-1,CD31,VEGF,Flk-1,Ang-1,Ang-2,Tie-1 and Tie-2.Results Mice with PA injection had lower kidney weight and body weight at all time points as well as lower KW/BW at 4,8,12 dpp when compared with NS controls.Electron microscopy revealed nearly complete foot process effacement and segmental microvillous transformation as early as 1 day after PA injection.PA-injected kidneys showed fewer capillary loops and decreased maturation index as well as less CD31-positive endothelium in cortical glomeruli at 12 dpp. Glomerular mesangial injury and developing glomerulosclerosis along with proteinuria were noted in PA-injected kidneys starting from 30 dpp.Significantly increased systolic blood pressure was detected at 60 dpp in PA mice.Compared with NS injection,PA injection significantly induced decreased mRNA expression of Flk-1 and Tie-2 as well as increased expression of Ang-1,without obvious changes of VEGF at 2 dpp.Conclusions Podocytes in neonatal kidney of ICR mice are susceptible to PA. Such podocyte injury can alter the expression of VEGF and angiopoietin system in glomeruli,leading to abnormal development of glomerular capillaries,and subsequent proteinuria,hypertension and glomerulosclerosis.

Objective To assess the characteristic of normal tension glaucoma (NTG) patients with mild cogni?tive impairment (MCI). Methods This study included twenty-six cases of normal tension glaucoma patients who were diagnosed at ophthalmology department of Peking University Third Hospital. All the participants were examined by us?ing the scales of Montreal Cognitive Assessment (MoCA), mini-mental state examination(MMSE), clinical dementia rat?ing (CDR), activities of daily living (ADL), Hamilton anxiety scale (HAMA), Hamilton depression scale (HAMD), Pitts?burgh Sleep Quality Index (PSQI) and polysomnography (PSG). The patients were then divided into Group with MCI (16 cases) and Group without MCI (19 cases). Results There was no difference between the two groups in gender, age, edu?cation, depression, anxiety and body mass index (BMI) (P>0.05), but significant difference in MoCA scores (P<0.05). The incidence rate of sleep disorder of PSQI in was 28.6%(10/35 patients) of total NTG patients, 43.8%(7/16 patients) in Group with MCI, and 15.8% (3/19 patients) in Group without MCI, respectively. The PSQI score was higher in Group with MCI than in Group without MCI (P<0.05). Sleep efficiency was higher in Group without MCI than in Group with MCI (P<0.05), but no difference was found between the two groups in six other indexes of PSQI (P>0.05). The in?cidence rate of sleep structure disorder of PSG in all the NTG patients was 85.7%(30/35 patients), 87.5%(14/16 pa?tients) in Group with MCI, and 84.2%(16/19 patients) in Group without MCI. Sleep time of NREM-N3 was significant?ly shorter in Group with MCI than in Group without MCI (P<0.05), but no difference was found between those groups in total sleep time, sleep efficiency, sleep latency and REM time (P>0.05). Conclusion NTG patients with mild cogni?tive impairment are more prone to sleep disorders, especially sleep structure disturbance and short NREM-N3 time may affect cognitive function.

Objective To study the macrophage colony-stimulating factor(M-CSF)expression levels of serum and synovial fluids from patients with spondyloarthropathy(SPA)and its contribution to the pathogen- esis of SpA.Methods Eleven SpA synovial tissue samples were compared to those from peripheral blood mononuclear cells(PBMC)of 10 normal subjects using a 1176 gene array.M-CSF was detected in both serum samples and synovial fluids by enzyme linked immunosorbent assay(ELISA).Two groups of AS subjects were tested.The first group consisted of 41 ankylosing spondylitis(AS)patients who had not been treated with bio- logics.The second group consisted of 13 subjects whose serum samples were collected before and 14 weeks af- ter initiation of infliximab.These were compared to serum samples from 28 normal subjects,and synovial fluid samples from 15 SpA patients.Results Expression of M-CSF could be detected in both serum samples and synovial fluids.The concentration of M-CSF in the group of 41 AS patients not treated with biologics correlated with the Bath Ankylosing Spondylitis Disease Activity Index(BASDAI)values(r=0.41,P=0.004).Treatment of infliximab in AS patients led to a significant decrease in the values of BASDAI(P=0.000 07),but no signif- icant change in the serum M-CSF values.Conclusion M-CSF is a promising candidate for research on the mechanisms of SpA and its signaling on pathway in SpA is different from tumor necrosis factor(TNF)-?,and it may provide new basis for developing new anti-biologics for SpA.

Objective:To determine whether ox-LDL (oxdized low-density lipoprotein) is highly deposited on the uremic vessel wall and its influence on the vascular remodeling. Methods: Segments of radial arteries were obtained from 21 uremic subjects during the operation of A-V fistula prior to hemodialysis. Segments of internal thoracic arteries of similar diameter were obtained from patients with benign chest tumors as control.The vascular lesions and ox-LDL, CD68,MCP-1, eNOS,ET-1, PCNA,FN on the vessel wall were determined by means of H-E stain and immunohistochemistry. Results： With H-E stain,atherosclerotic plaques were found in the radial arteries of 4 uremic patients. The middle layer of the arteries in uremic patients were obviously thickened, and the T/D　(thickness of the wall/external diameter) ratio was significantly higher than those in control group(P<0.01). ox-LDL,CD68,MCP-1, ET-1, PCNA,FN on the vessel wall in uremic patients were much higher than those in control group (P<0.01). Moreover, ox-LDL on the vessel wall was positively related to the expression of other above mentioned substances on the vessel wall (P<0.01). Whereas the expression of eNOS on the vessel wall was lower than control group (P<0.01),and was negatively related to ox-LDL on the vessel wall(P<0.01). Conclusion: ox-LDL is an important factor contributing to uremic vascular remodeling by increasing the migration,adhesion and infiltration of monocyte,the proliferation of vascular smooth muscle cell and dysfunction of endothelia.

Objective:To determine whether ox-LDL (oxdized low-density lipoprotein) is highly deposited on the uremic vessel wall and its influence on the vascular remodeling. Methods: Segments of radial arteries were obtained from 21 uremic subjects during the operation of A-V fistula prior to hemodialysis. Segments of internal thoracic arteries of similar diameter were obtained from patients with benign chest tumors as control.The vascular lesions and ox-LDL, CD68,MCP-1, eNOS,ET-1, PCNA,FN on the vessel wall were determined by means of H-E stain and immunohistochemistry. Results： With H-E stain,atherosclerotic plaques were found in the radial arteries of 4 uremic patients. The middle layer of the arteries in uremic patients were obviously thickened, and the T/D　(thickness of the wall/external diameter) ratio was significantly higher than those in control group(P<0.01). ox-LDL,CD68,MCP-1, ET-1, PCNA,FN on the vessel wall in uremic patients were much higher than those in control group (P<0.01). Moreover, ox-LDL on the vessel wall was positively related to the expression of other above mentioned substances on the vessel wall (P<0.01). Whereas the expression of eNOS on the vessel wall was lower than control group (P<0.01),and was negatively related to ox-LDL on the vessel wall(P<0.01). Conclusion: ox-LDL is an important factor contributing to uremic vascular remodeling by increasing the migration,adhesion and infiltration of monocyte,the proliferation of vascular smooth muscle cell and dysfunction of endothelia.

The metalloproteinases/disintegrins in the snake venom act as platelet aggregation inhibitor by an antagonism against integrin on platelet through its RGD sequence and may play other important role in cell-cell fusion, cell matrix interaction and other cellular function. Ussurin is a new metalloproteinase/disintegrin that was cloned from Gloydius ussuriensis. Poly (A+) RNA was purified from the total RNA preparation from venom gland of a single G. ussuriensis using the poly (A+) tract-mRNA isolation system. A cDNA library was constructed with the SMART PCR cDNA library construction kit. The cDNA library was screened and the positive clones were selected. The full-length cDNA of Ussurin was obtained. The cDNA encoding the Ussurin precursor has a 51bp 5'-UTR, the open reading frame of Ussurin and a 490 bp 3'-UTR, the open reading frame of Ussurin cDNA nucleotide sequence is 1434 bp and codes for 478 amino acids with a predicted molecular mass of 53.2 kD and an isoelectric point of 5.37. There is no potential N-glycosylation site in the deduced sequence region. Its deduced amino acid sequence consists of four region, a signal sequence of 18 amino acid residues, a zymogen pro-peptide of 171 amino acid residues with a cysteine switch motif (PK-MCGVT) in it, a central metalloproteinase domain of 201 amino acid residues containing a conserved zinc-chelating sequence (HEXXHXXGXXH) and a methionine-turn CIM involving zinc banding also, a space sequence between metalloproteinase domain and disintegrin domain of 15 amino acid residues with a conserved T392, T397, S400, which is specific residues of the P-II snake venom metalloproteinases, a disintegrin domain of 73 amino acid residues with a characteristic RGD region and six-disulfide bonds. Ussurin belongs to P-II class. The cDNA sequence and deduced amino acid sequence of Ussurin precursor were compared with homologous sequence in the GenBank database, the result reveals high degree of homology in sequence and organization pattern of domain with metalloproteinase/disintegrin gene family of other snake species. Compared with the alignment of amino acid sequence of metalloproteinase/disintegrin member, hypervariable regions of this member were revealed, besides they share higher homologous in the zymogen domain. It suggests that the hypervariable regions are the counterparts directly suitable for interacting with different domain of receptors, different receptors or substrates.
Amino Acid Sequence ; Animals ; Base Sequence ; Cloning, Molecular ; Disintegrins ; chemistry ; genetics ; metabolism ; Metalloproteases ; chemistry ; genetics ; metabolism ; Molecular Sequence Data ; Sequence Alignment ; Viper Venoms ; enzymology ; genetics ; Viperidae ; genetics ; metabolism

OBJECTIVETo study the relationship between a G/T substitution at position -88 of myxovirus resistance-1 gene (MxA) and the self-limiting or chronic infection of HBV.

METHODSBlood samples from 100 patients with self-limiting HBV infection (positive anti-HBs and anti-HBc) and from 340 patients with chronic HBV infection were collected. MxA-88 G/T polymorphism was typed using a protocol based on competitively differentiated-polymerase chain reaction. For statistical analysis, odds ratio and chi-square test were used.

RESULTSThe detective rate of G/G genotype (low expression genotype) of MxA-88 G/T was 50.2% (221/440), those of T/T genotype (high expression genotype) and G/T heterozygous genotype were 5.5% (24/440) and 44.3% (195/440). Compared to patients with chronic infection, patients with self-limiting infection had lower frequency of G/G genotype (41.0% vs 52.9%, P < 0.05) or G allele (62.5% vs 75.9%, P < 0.01) and had higher frequency of T/T genotype (16.0% vs 2.4%, P < 0.01) or T allele (37.5% vs 24.1%, P < 0.01), but there was no significant difference in the G/T heterozygous genotype.

CONCLUSIONSMxA gene -88 G/T polymorphism influences the natural outcomes of HBV infection to some extent. This SNP of MxA gene may be used as a clinical prognostic marker of HBV infection.

Adult ; Biomarkers ; Female ; GTP-Binding Proteins ; biosynthesis ; genetics ; Genotype ; Hepatitis B, Chronic ; genetics ; Humans ; Male ; Myxovirus Resistance Proteins ; Polymorphism, Single Nucleotide ; genetics ; Prognosis

OBJECTIVETo determine whether there are differences in both the right hepatic vein (RHV) morphology and the size of the angle between the inferior vena cava and the RHV in patients with membranous obstruction of the inferior vena cava (MOVC),in healthy individuals and in patients with cinhosis (HLC), in order to help guide development of an effective interventional treatment program.

METHODSConsecutive patients (n=248) were divided into the following three groups: group A (control; n=94), group B (MOVC patients; n=68), group C (HLC patients; n=86). The angle between the hepatic vein and inferior vena cava was measured and defined as the T value. The morphology of the RHV was classified as N, U, or I. The difference of the constituent ratio was compared among the three groups for the T value and the angle type.Measurement data was calculated as x ± s,and groups were compared using one-way ANOVA; count data was calculated as relative number, and groups were compared using the chi-square test.

RESULTSThe average T value of group B was significantly higher than that of group A (56.1 ± 13.7 vs. 49.3 ± 7.8, P=0.010) and of group C (vs. 51.5 ± 10.0, P < 0.001); the difference was statistically significant (F=8.750, P < 0.001), but there was no significant difference between the groups A and C.N-type proportion of B group was 48.5% (33/68), greater than that of group A(16.0%,15/94) and C (16.3%, 14/86), x² = 20.1, x² =18.6.U-type proportion of B group was 11.8% (8/68), smaller than that of groups A (28.7%,27/94) and C (37.2%, 32/86), 2 2 = 6.70, x² =12.8, and the differences were statistically significant (P < 0.01). For groups A and C, the N and U types were not significantly different.

CONCLUSIONThe angle between the RHV and the inferior vena cava in MOVC patients is morphologically different from that in healthy humans, with the angle value in MOVC patients being slightly larger. However, this difference is irrelevant to cirrhosis.

Hepatic Veins ; Humans ; Vena Cava, Inferior

OBJECTIVETo study the methylation status of p73 gene promoter in patients with myelodysplastic syndrome (MDS) and explore its significance with clinical prognosis.

METHODSMethylation of p73 promoter was detected in bone marrow cells from 135 MDS patients and 13 healthy controls by methylation-specific PCR (MSP). The results of MSP were confirmed by bisulfite sequencing. The expression of p73 mRNA was detected by real-time quantitative PCR. Primary bone marrow cells from MDS patients were treated with decitabine, the changes of p73 methylation status and p73 mRNA expression were measured. The role of p73 methylation in the prognosis of MDS and the correlated clinical data were explored.

RESULTSp73 hypermethylation was present in 37.04% of MDS cases and patients with high risk MDS (RAEB-1 and RAEB-2) exhibited a significantly higher frequency of p73 methylation than that of low risk MDS (58.8% vs 29.7%, P = 0.002). The expression of p73 mRNA in the methylated group was decreased compared to that of the unmethylated group (P = 0.032). Decitabine treatment decreased the level of p73 methylation and increased the level of p73 transcripts. Patients with p73 methylation progressed rapidly to AML (P < 0.001) and had shorter survival (P = 0.002) than those who did not have p73 methylation. In the multivariate Cox regression model, BM blast and p73 methylation status emerged as independent prognostic factor for overall survival and leukemia free survival.

CONCLUSIONp73 gene methylation is common in patients with MDS and may indicate poor prognosis. p73 may be a therapeutic target in MDS.

Aged ; Case-Control Studies ; DNA Methylation ; DNA-Binding Proteins ; genetics ; Female ; Humans ; Male ; Middle Aged ; Myelodysplastic Syndromes ; genetics ; Nuclear Proteins ; genetics ; Prognosis ; Promoter Regions, Genetic ; Tumor Protein p73 ; Tumor Suppressor Proteins ; genetics