Objective To investigate the injury of podocyte and its association with proteinuria in IgA nephropathy (IgAN). Method Thirty-five patients of IgA nephropathy with proteinuria more than 1.0 g/24 h were enrolled in the study, and eight cases of renal harmatomaeetomy or renal cancinomaectomy were as controls. Cell cycle regulatory proteins (p21, p27), podocyte-associated molecules (integrin-β1, nephrin, α-actinin 4, nestin), foot process width (FPW) and the amount of podocyte were examined by immunohistochemistry and real-time PCR, respectively. Patients were divided into two groups according to podocyte number per volume (Nv): podocytopenia group (n=15, Nv<52.49×106/μm3) and normal number group (n=20, Nv≥52.49× 106/μm3). Proteinuria was followed up for eighteen months. Results Compared with the controls, podocyte p21 was re-expressed, while the expression of p27 was decreased (0.71±0.12 vs 0.91±0.07, P<0.05) in IgAN. The nestin protein level was markedly decreased in IgAN (13.4%± 0.04% vs 17.6%±0.04%, P<0.05). The mRNA expression of integrin-β1 was significantly increased (12.54±5.20 vs 1.02±0.30, P<0.05), while the amount of nephrin, α-actinin4 remained unchanged. Effacement of foot processes and podocyte detachment from the glomerulax basement membrane were observed in some cases. Nv was significantly less than that of controls (161.27± 225.92 vs 323.22±138.12, P<0.05), which was associated with the Lee's grade of IgA nephropathy. The integrin-β1 mRNA expression and Nv were negatively correlated with baseline proteinuria by univariate analysis (r=-0.840, P=0.034; r =-0.4483, P=0.014, respectively). Proteinuria in podocytopenia group was decreased more slowly than that in normal number group. Conclusions Podocyte injury exsists in IgAN with proteinuria, which manifests alterations in cell cycle regulatory protein and some podocyte-associated molecules, as well as foot process effacement and loss of pedocyte. Podocyte injury may be involved in proteinuria by affecting the progression of proteinuria in IgAN.

Objective To evaluate the clinical value of 6 h 99mTc-diethyl iminodiacetic acid (99mTc-EHIDA) planar hepatobiliary scintigraphy (HBS),6 h tomographic HBS and 24 h planar HBS in diagnosis on biliary atresia(BA).Methods Seventy cases(32 male,38 female) with continuous jaundice received planar and tomographic HBS in Beijing Friendship Hospital from Jan.2005 to Dec.2007.The mean age was 48.7 d (29 d-4 months).According to final diagnosis,all cases were divided into BA group (45 cases) and non-BA group (25 cases).All cases fasted at least 4 hours before HBS.The equipment was 3 head IRIX from Philips company with low energy high resolution collimator.The tracer was 99mTc-EHIDA and the radiochemistry purity was more than 95 percent.The dosage was 7.4 MBq/kg.All diagnosis demonstrated by operation pathology and clinical follow-up.All cases received HBS at 5,10,15,20,30 min and 1,6 h after tracer injection.HBS would ended if radioactivity appeared in gallbladder or intestine.These cases would received tomographic HBS and 24 h HBS if radioactivity did not appear in gallbladder or intestine at 6 h post injection.All these images were analyzed by 2 or more nuclear medicine physicians.Results There were not radioactivity appearing in gallbladder and intestine on planar and tomographic HBS of 27 cases,which suggested the BA.There were radioactivity appearing in gallbladder and intestine on planar and tomographic HBS of 30 cases,which suggested the non-BA.Positive rate of 6 h tomographic HBS was significantly higher than that of 6 h planar HBS and there was significantly difference between the 2 methods.Positive rate of 6 h tomographic HBS was significantly higher than that of 24 h planar HBS and there was significant difference between the 2 methods.Conclusions 99mTc-EHIDA HBS is a noninvasive,safety,valuable examing method and has definitely clinical value in the diagnosis on BA.The clinical value of 6 h tomographic HBS is significantly higher than that of 6 h planar HBS and 24 h planar HBS.

Neuronal calcium (Ca2+) signaling is abnormal in neurodegenerative disorders such as Alzheimer's disease (AD), and Parkinson's disease (PD). The increase in neuronal Ca2 + concentration as a result of normal aging could promote the neurodegenerative process.The role of aberrant neuronal Ca2+ signaling in the pathogenesis of neurodegenerative disorders and aging process was discussed here.

BACKGROUND:Atorvastatin has been shown to reduce bone loss and fracture, but its effects on implant osseointegration remain unknown.
OBJECTIVE:To investigate the effects of atorvastatin on implant osseointegration in osteoporotic rats and the underlying mechanisms.
METHODS:Forty-eight Sprague-Dawley rats were randomized into sham-surgery, ovariectomy, and atorvastatin (10 and 20 mg/kg per day) treatment groups, respectively. Al rats received ovariectomy and implant surgery except those in the sham-surgery group. Bone mineral density of the lumbar vertebra, osseointegration ratio and pul-out strength of implants were measured after 12-week treatment.Levels of bone formation and resorption markers in osteoblasts treated with atorvastatin were determined by ELISA. Wnt pathway-relatedgene expression was detected by RT-PCR.
RESULTS AND CONCLUSION:Bone mineral density, osseointegration ratio and pul-out strength of implants were significantly increased in 20 mg/kg per day of atorvastatin treatment group compared with ovariectomy group (P< 0.05). Levels of alkaline phosphatase, osteocalcinand osteoprotegerinwere significantly increased in osteoblasts treated with atorvastatinin vitro(P<0 .05), and the level of osteoclast differentiation factor RANKL was significantly inhibited (P< 0.05). Meanwhile, atorvastatin significantly promoted the mRNA expression of low-density lipoprotein associated protein 5and β-catenin, and inhibited the mRNA expression of dickkopfWnt signal pathway inhibitor 1and sclerostin. Our results suggest that atorvastatin promotes implant osseointegration in osteoporotic rats by activating Wnt/β-catenin signal pathway.

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 evaluate the effect of various iterative reconstruction methods on phase analysis of gated myocardial perfusion imaging (MPI). Methods Thirty consecutive patients scanned by the Philips CardioMD system were recruited into this study. The gated SPECT (GSPECT) data were reconstructed with filtered backprojection (FBP),maximum likelihood expectation maximization (MLEM),three-di-mensional (3D) resolution recovery MLEM (AST),attenuation corrected (AC) MLEM,AC and 3D Monte Carlo scatter corrected (ACSC) MLEM methods. Parameters of left ventricular ( LV ) dyssynchrony ( phase standard deviation and histogram bandwidth) were measured using the software SyncTool. Paired t-test was used to compare the differences of the LV dyssynchrony indices between FBP and MLEM,AC MLEM,ACSC MLEM,AST respectively. Results The phase standard deviations of stress GSPECT MPI for FBP,MLEM,AC MLEM,ACSC MLEM,and AST were 11.6°,10.9°,11.2°,11.6°,11.4° respectively;while the histogram bandwidths were 35.7°,34.3°,35.1°,36.9°,35. 1 ° respectively. The phase standard deviations of rest GSPECT MPI for FBP,MLEM,AC MLEM,ACSC MLEM and AST were 15.2°,14. 5°,15.4° ,15. 4°,14.8° respectively; while the histogram bandwidths were 47.3°,46.4°,46.4° ,47.9°,46.1 ° respectively. No statistical significance was observed between the FBP and various iterative reconstruction methods for both the stress and rest GSPECT MPI study (t:-1. 179 to 1.554,P＞0.05 forall). Conclusion The standard FBP reconstruction method is accurate enough for the measurement of LV dyssynchrony indices using the widely used clinical software SyncTool.

OBJECTIVETo evaluate the clinical effect of endotracheal lavage with porcine pulmonary surfactant (PS) in term neonates with severe meconium aspiration syndrome (MAS).

METHODSA total of 136 full-term infants with severe MAS who were admitted to the neonatal intensive care unit between January 2010 and June 2013 were randomly and equally divided into PS lavage and PS injection groups. In the PS lavage group, patients were treated with endotracheal lavage using 3-5 mL of diluted PS (12 mg/mL) each time, and the PS injection group was given PS by intratracheal injection at the first dose of 200 mg/kg. Blood gas, oxygenation index (OI), and PaO2/FiO2 (P/F) of the two groups were evaluated before and 2, 12, 24, and 48 hours after the treatment, and the duration of mechanical ventilation, complication rate, and cure rate were compared between the two groups.

RESULTSCompared with the PS injection group, the PS lavage group had significantly higher PaO2 and P/F ration and significantly lower PaCO2 and OI at 12, 24, and 48 hours post-treatment (P<0.01), a significantly shorter duration of mechanical ventilation (P<0.01), a significantly smaller amount of PS (P<0.01), a significantly lower complication rate (P<0.05), and a significantly higher cure rate (97% vs 88%; P<0.05).

CONCLUSIONSCompared with the intratracheal injection of PS, endotracheal lavage with diluted PS in term neonates with severe MAS can increase ventilation and oxygenation efficiency, shorten the duration of mechanical ventilation, reduce the complication rate, and increase the cure rate, indicating that this method is a safe and effective therapeutic strategy.

Animals ; Humans ; Infant, Newborn ; Meconium Aspiration Syndrome ; drug therapy ; Pulmonary Surfactants ; administration & dosage ; Swine ; Therapeutic Irrigation ; Trachea

OBJECTIVETo explore the molecular genetic mechanism of complicating depression in asthma by detecting two gene polymorphisms of 5-hydroxytryptamine transporter (5-HTTLPR/Stin2) gene.

METHODSOne hundred fifty-six adults with asthma were collected, and divided into group of asthma with depression (HAMD score > or = 8) and group of asthma without depression or single asthma (HAMD score <8) according to the score of Hamilton depression scale (HAMD). A total of 508 adults with depression alone and 433 healthy individuals were enrolled as controls. The target gene fragments containing the polymorphic regions of 5-HTTLPR and Stin2 were amplified by polymerase chain reaction (PCR). The amplified fragments were then analyzed using agarose gel electrophoresis (AGE) and motored molecular imaging system.

RESULTSThe frequencies of genotype and allele distribution of the Stin2 polymorphism showed that males with genotype Stin2.12/Stin2.10 and allele Stin2.10 had higher risk for asthma than the others (Stin2.12/Stin2.10: OR = 2.291, 95% CI: 1.195 and 4.390; Stin2.10: OR = 1.942, 95% CI: 1.069-3.527). No significant difference was found in the frequencies of genotype and allele distribution of the 5-HTTLPR locus between the asthma and healthy control groups and the two stratified by gender.

CONCLUSIONThe Stin2 polymorphism may play a role in the onset of male asthma. There might be association between the genetic pathogenesis of asthma and depression.

Adult ; Alleles ; Asthma ; epidemiology ; genetics ; Case-Control Studies ; Comorbidity ; Depression ; epidemiology ; genetics ; Female ; Genome-Wide Association Study ; Genotype ; Humans ; Male ; Polymorphism, Genetic ; Serotonin Plasma Membrane Transport Proteins ; genetics

Background: and Purpose Mutations in the FIG4 gene have been linked to amyotrophic lateral sclerosis (ALS) type 11 in Caucasian populations. The purpose of this study was to identify FIG4 variants in a cohort of 15 familial ALS (FALS) indexes and 275 sporadic ALS (SALS) patients of Han Chinese origin. Methods: All 23 exons of FIG4 were sequenced using targeted next-generation sequencing.An extensive literature review was performed to detect genotype-phenotype associations of FIG4 mutations. Results: No FIG4 variants were identified in the FALS patients. One novel heterozygous missense variant (c.352G>T [p.D118Y]) and one novel heterozygous nonsense variant (c.2158G>T [p.E720X]) in FIG4 were identified in two SALS patients. The p.E720X variant is interpreted as likely pathogenic while the p.D118Y variant is a variant of uncertain significance. The patient carrying the p.E720X mutation developed lower-limb-onset slowly progressive ALS, and survived for 11.5 years. The patient harboring the FIG4 p.D118Y variant also presented with progressive ALS, with the score on the ALS Functional Rating Scale–Revised (ALSFRS-R) decreasing by 0.4 per month. The rate of decrease in the ALSFRS-R scores from symptom onset to diagnosis seemed to be lower in the patients carrying FIG4 variants than the no-FIG4-mutation ALS patients in this study. Conclusions Our findings suggest that ALS patients carrying FIG4 mutations are not common in the Chinese population and are more likely to exhibit slow progression.