Objective To examine the association of 18 single nucleotide polymorphisms (SNPs) in 4 DNA repair genes (BLM,WRN,ERCC6 and OGG1) with age-related cataract (ARC) in a Han Chinese population from Jiangsu Eye Study and to determine the possible functional consequence of the SNPs to DNA damage.Methods Together 18 SNPs in 4 DNA repair genes were genotyped in 789 ARC patients and 531 normal controls from Jiangsu Eye Study.The Comet assay was conducted to assess the extent of DNA damage in peripheral lymphocytes of the selected subjects.Results The results showed that WRN-rs11574311 was initially associated with ARC in general,cortical and mixed cataracts (P =0.003,OR =1.49;P =0.001,OR =1.68 and P ＜0.000 1,OR=2.08),BLM-rs1063147 with nuclear cataracts (P =0.03,OR =1.31),WRN-rs2725383 with cortical cataracts (P =0.01,OR =1.49),WRN-rs4733220 and WRN-rs2725338 with mixed cataracts (P =0.04,OR =0.74 and P =0.003,OR =0.60).However,after Bonferroni corrections,WRN-rs11574311 was still associated with cortical and mixed cataracts,as well as WRN-rs2725338 with mixed cataracts.The difference in DNA damage of peripheral lymphocytes with SNP types did not approach statistical significance among groups (all P ＞ 0.05).Conclusion WRN genes may have a vital role in ARC pathogenesis and exert a different action in ARC subtypes,which may be associated with different risk factors and mechanisms.

OBJECTIVETo investigate the expressions of mRNA and protein of p38, Osx, PI3K, Akt1 in the rats bone with chronic fluorosis.

METHODSDental fluorosis were observed and the fluoride contents in the urine and bone were detected by fluorin-ion selective electrode. The morphologic changes and ultrastructure of rats' bone were observed by light and electronic microscopy. The expressions of protein and mRNA of p38, Osx, PI3K and Akt1 were detected by immunohistochemistry and real-time PCR, respectively. The contents of BALP and BGP in serum were detected by ELISA.

RESULTSThe rates of dental fluorosis in the fluorosis rats were increased, and the fluoride contents in bone and urine of the fluorosis rats were increased compared to the control group, the difference was statistically significant (P < 0.05). The bone trabeculae thickness and density and the thickness of bone cortex in fluorosis rats were remarkably increased, the space of bone trabeculae was reduced, and in accordance with the matching morphometrical indices, the difference was statistically significant (P < 0.05) as compared with the control rats. The contents of BALP [(54.61 ± 2.27) U/L] and BGP [(2.38 ± 0.16) µg/L]in the fluoride groups were higher than those in the control group, the difference was statistically significant (P < 0.05). Ultrastructurally, the broadening of the osseouslacuna was observed. The reduced protuberances of the osteocytes, the unclear organelle structure, pyknosis, karyotheca increasation and edged chromatin were also observed. Compared to the control group, the expressions of protein and its mRNA of p38, Osx, PI3K and Akt1 were higher in the fluorosis rats than those in the control rats, and the difference was statistically significant (P < 0.05). There is no any expression of p38, Osx, PI3K and Akt1 in the osteocytes in fluorosis rats.

CONCLUSIONSThe over-expression of p38, Osx, PI3K and Akt1 in bone tissue of fluorosis rats may relate to the accumulation of fluorine in the body. The bone injury mainly occur in the stage of the differentiation and proliferation. The upregulation of P38MARK signal path and PI3K/Akt1 signal path may be involved in the pathogenesis of bone injury caused by fluoride.

Alkaline Phosphatase ; blood ; Animals ; Bone and Bones ; metabolism ; pathology ; ultrastructure ; Fluoride Poisoning ; metabolism ; pathology ; Fluorides ; metabolism ; urine ; Fluorosis, Dental ; metabolism ; pathology ; Immunohistochemistry ; Microscopy, Electron, Transmission ; Osteocalcin ; blood ; Phosphatidylinositol 3-Kinases ; genetics ; metabolism ; Proto-Oncogene Proteins c-akt ; genetics ; metabolism ; RNA, Messenger ; metabolism ; Rats ; Rats, Sprague-Dawley ; Real-Time Polymerase Chain Reaction ; Signal Transduction ; Sodium Fluoride ; toxicity ; Transcription Factors ; genetics ; metabolism ; p38 Mitogen-Activated Protein Kinases ; genetics ; metabolism

Objective To study the dynamic changes of Omi/HtrA2 in the cytoplasm of cerebral parietal cortex in neonatal rats with hypoxic-ischemic brain damage (HIBD),and explore the role of Omi/HtrA2 in HIBD.Methods Seven-day-old SD rats were randomly assigned to sham-operated group and vehicle group; and HIBD models were established by the Rice and CHEN Hui-jin methods.Each group was further divided into 4 subgroups (n=8) according to the observation time points (6,12,24and 72 h).In each subgroup,the turnover ability and dextrorotatory ability when their tails were gripped were observed before the experiment and 1 h after hypoxic-ischemia (HI).The appearance of the brain was observed,and the protein levels of Omi/HtrA2 in the brain tissues or homogenates were examined by immunohistochemistry and Western blotting.Results (1) Changes of behavior of the rats:before the experiment,all rats were healthy; 1 h after HI,the rats in sham-operated group were still healthy,while out of 32 rats which bared HI injury,18 could not turn themselves over,20 became dextrorotatory when their tails were gripped and 14 exhibited both behavior problems.(2) General examination of the brain:the ligated brain hemisphere in the vehicle group showed obvious pallor and edema at 24 h; the two brain hemispheres in sham-operated group showed no pathological change.(3) Western blotting results showedthat the protein levels of Omi/HtrA2 in the vehicle group were significantly higher than those in the sham-operated group at each observation time points (P＜0.05); the expressions of Omi/HtrA2 in the vehicle group began to increase at 6 h,peaked at 24 h after HI insult and decreased thereafter.(4) By immunohistochemistry,it showed that the Omi/HtrA2 positive cells in cytoplasm and membrane of cerebral cortex in the vehicle group peaked at 24 h after HI insult and decreased thereafter; the quantity of positive cells in the vehicle group was larger than that in the sham-operated group (P＜0.05).Conclusion The levels of Omi/HtrA2 in the cerebral cortex increase after HI insult in neonatal rats,showing time-difference expression,which may play important roles in cell apoptosis induced by HIBD.

OBJECTIVETo study the feasibility and technical parameters of posterior transarticular screw fixation in the thoracic spine.

METHODSSince September 2009 to December 2009, 20 thoracic cadaveric spines (12 males and 8 females) were dissected. The lateral masses and pedicles were exposed carefully. After the entrance point of transarticular screws was determined, posterior transarticular screws implantation was performed under direct visualization into T(1,2), T(5,6) and T(9,10). Then CT scan was performed. On the CT scan,the angle and length of the transarticular screw trajectory were measured.

RESULTSThe thoracic transarticular screw trajectory were caudal tilting in the sagittal plane and lateral tilting in the coronal plane with successful placement. There was little differences between different segmental of thoracic vertebrae of the angle, but without significance (P > 0.5). The average angles of the screws were (52.6 +/- 5.9) degrees caudal tilting in the sagittal plane and (12.4 +/- 2.9)0 lateral tilting in the coronal plane. The average trajectory lengths were (22.5 +/- 1.9) mm. There was significant differences statistically among T(1,2), T(5,6) and T(9,10) (P < 0.01).

CONCLUSIONPosterior transarticular screw fixation is feasible. Transarticular screw fixation in the thoracic spine affords an alternative to standard pedicle screw placement for thoracic stabilization.

Adult ; Bone Screws ; Feasibility Studies ; Female ; Humans ; Image Processing, Computer-Assisted ; Joints ; surgery ; Male ; Radiography, Thoracic ; Thorax ; Tomography, X-Ray Computed

Objective To investigate the prevalence and associated risk factors for pterygium among people aged 50 years and above in Funing County,Jiangsu Province.Methods A cluster random sampling method was performed,the subjects aged 50 years or above were randomly selected from 30 survey sites in Funing County,Jiangsu Province.Questionnaires,visual acuity tests,the examinations of eye surface,anterior segment,fundus examinations were conducted.Pterygium was diagnosed and graded clinically by slit lamp examination.The risk factors were acquired from questionnaires and analyzed by the multivariate logistic regression analysis.This study protocol was approved by Ethic Committee of Affiliated Hospital of Nantong University (NO.2010-05).Written informed consent was obtained from each subject prior to entering study cohort.Results A total of 6 145 persons aged 50 years and above were enumerated,and actually 5 947 (96.8％) participants were examined.Among them,1 950 cases were diagnosed as pterygium in either eye and 1 228 cases were diagnosed as pterygium in binoculus,which was equivalent to the 32.79％ [95％ confidence interval(CI):31.60％-33.98％] of pterygium in either eye and 20.65％ (95％ CI:19.62％-21.68％) in bilateral pterygium.Among 2467 male subjects,838 were diagnosed as pterygium (33.97％,95％ CI:32.10％-35.84％).Among 3480 female subjects,1 112 were diagnosed as pterygium (31.95％,95％ CI:30.40％-33.51％).There was no significant difference in the prevalence of pterygium between genders (P =0.135).Multivariate Logistic analysis showed that,older age (50 ～ ＜60 years:odds ratio [OR] =1.00;60 ～ ＜70 years:OR=1.54,P＜0.001;70 ～ ＜80 years,OR=1.83,P＜0.001;≥80 years:OR=1.99,P＜0.001),low educational level (no education:OR =1.00;＜primary:OR =0.87,P =0.031;primary education:OR =0.72,P =0.002;≥ secondary education:OR =0.63,P =0.002),farmer occupations (OR =1.34,P =0.020),and long outdoor work time (OR =1.13,P =0.026) were independent risk factors for pterygium.Gender,marriage,income,hypertension,diabetes,smoking and alcohol use history were not associated with pterygium (all at P＞0.05).Conclusions The prevalence of pterygium in Funing County is 32.79％ in people aged 50 years and above.The high prevalence of pterygium may be associated with older age,low education level and long outdoor work time.

OBJECTIVE: To evaluate the benefits and toxicities of different corticosteroid regimes in preventing relapse in children with steroid sensitive nephrotic syndrome (SSNS). METHODS: MEDLINE (Jan. 1963-Mar. 2007), elsevier (Jan. 1997-Aug. 2006), OVID databank (Jan. 1993-Aug. 2006), Springer databank (Jan. 1994-March 2007), the Cochrane Controlled Trials Register (Cochrane Library, Issue Feb. 2006), Cochrane Renal Group Specialised Register (Jul. 2006), EMBASE (Jan. 1980-Mar. 2007) and CNKI (Jan. 1994-Mar. 2007) etc, were searched by the terms primary nephrotic syndrome, glucocorticoid, corticosteroid, steroid, prednisone, methylprednisolone, dexamethasone and children etc for the human clinical trials about glucocorticoid (GC) administration in primary nephrotic syndrome (PNS) (aged 3 months to 18 years), controlled or semi-controlled ones, including unpublished documents from scientific meetings and theses, and similar documents listed in the references of the above documents were also included. All the studies were evaluated strictly according to Jadad Standard, and the Meta-analysis were adopted. Review manager 4.2 software was used to analyze the data. The odds ratio was calculated for the relapse rate and side effect from the initial episode to the end of follow-up between the patients treated with corticosteroids and the controls. RESULTS: Totally 12 trials with 868 subjects meeting the criteria were included in this review. A Meta-analysis of 7 trials, which compared between 2 months of prednisone and 3 months or more in the first episode, showed that longer treatment duration significantly reduced the risk of relapse at 12-24 months (RR=0.70,95% CI:0.60-0.89),without an increase of side effect. There was a negative linear relationship between the duration of treatment and risk of relapse (r2 =0.66, P=0.05). CONCLUSION (1) Children in their first episode of SSNS should be treated for at least 3 months of GC. The therapeutic effect of patients in the primary nephrotic syndrome treated with GC for 12 weeks was prior to that for 8 weeks, compared with that in the controls. It could reduce the relapse rate of half year, the longer treatment duration in the NS patients at the first relapse was, the lower relapse risk was.(2) Compared with alternative GC administration, standard GC administration can reduce the side effects; Course more than 1 year of GC administration can reduce the 2-year relapse rate. Hence in children who relapse frequently, multicentre, well-designed experiments should be adopted.
Child ; Drug Resistance ; Glucocorticoids ; pharmacology ; therapeutic use ; Humans ; Nephrotic Syndrome ; drug therapy

OBJECTIVETo investigate the expressions of STAT5 phosphorylation in CD34(+)CD38(-)CD123(+) bone marrow cells of the patients with myelodysplastic syndromes (MDS), and then evaluate the level of activation of STAT5 associated with cell proliferation in MDS clone cells.

METHODSThe bone marrow mononuclear cells (BMMNC) were extracted from 36 MDS patients and 14 normal controls. The mean fluorescence intensities (MFI) of phosphorylated STAT5(P-STAT5) in CD34(+)CD38(-)CD123(+) and CD34(+)CD38(-)CD123(-)cells, with or without the stimulation of 10 U/ml EPO, were examined by flow cytometry (FCM).

RESULTSWithout stimulation, the P-STAT5 MFI in CD34(+)CD38(-)CD123(+) cells of low/high risk MDS patients was 113.71 ± 67.22/173.05 ± 102.78, which was significantly higher than that of CD34(+)CD38(-)CD123(-) cells (58.84 ± 27.51/68.99 ± 50.42, P < 0.01, P < 0.05) and the normal controls CD34(+)CD38(-)CD123(-) cells (63.06 ± 21.06, P < 0.05), there was no significant difference between the CD34(+)CD38(-)CD123(-) cells of MDS patients and the normal control CD34(+)CD38(-)CD123(-) cells; With the EPO stimulation, the P-STAT5 MFI in CD34(+)CD38(-)CD123(+) cells of low/high risk MDS patients was 144.04 ± 58.11/239.45 ± 152.05, which was significantly higher than that of CD34(+)CD38(-)CD123(-) cells (68.41 ± 25, 10/64.21 ± 23.43, P < 0.01) and the normal controls CD34(+)CD38(-)CD123(-) cells (75.21 ± 27.02, P < 0.01), there was no significant difference between the CD34(+)CD38(-)CD123(-) cells of MDS patients and the normal control CD34(+)CD38(-)CD123(-) cells; The P-STAT5 MFI in the CD34(+)CD38(-)CD123(+) cells of low/high risk MDS patients with or without EPO stimulation were 21.80/28.86, which was significantly higher than that of CD34(+)CD38(-)CD123(-) cells (7.42/5.50, P < 0.01, P < 0.05) and the normal controls CD34(+)CD38(-)CD123(-) cells (6.39, P < 0.05), there was no significant difference between the CD34(+)CD38(-)CD123(-) cells of MDS patients and the normal controls CD34(+)CD38(-)CD123(-) cells; There was no significant difference of P-STAT5 MFI with or without EPO stimulation and the increased P-STAT5 MFI between the CD34(+)CD38(-)CD123(+) cells of low and high risk MDS.

CONCLUSIONSTAT5 associated with cell proliferation was activated in CD34(+)CD38(-)CD123(+) bone marrow cells in MDS, which had more significant reactions to EPO than CD34(+)CD38(-)CD123(-) cells, indicating that CD34(+)CD38(-)CD123(+) bone marrow cells might be the real malignant MDS clone cells in MDS.

Adult ; Aged ; Aged, 80 and over ; Antigens, CD34 ; metabolism ; Bone Marrow Cells ; cytology ; metabolism ; Cell Proliferation ; Cells, Cultured ; Female ; Flow Cytometry ; Humans ; Male ; Middle Aged ; Myelodysplastic Syndromes ; metabolism ; pathology ; Phosphorylation ; STAT5 Transcription Factor ; metabolism

OBJECTIVETo investigate the clinicopathologic characteristics of childhood renal diseases.

METHODSA retrospective analysis of 1316 renal biopsies performed over the past 20 years was performed.

RESULTSOf the 1316 patients, 383 (29.09% ) were diagnosed as nephrotic syndrome, 291 (22.00%) as acute nephritis syndrome, 224 (17.21%) as isolated hematuria, 209(15.87%) as purpura nephritis, and 96 (7.30% ) as hepatitis B virus-associated nephritis . Mesangial proliferation was the most common pathological change (756 cases; 57.45%), followed by IgA nephropathy (113 cases; 8.59%), endothelial capillary proliferation(112 cases; 8.51%), membranous nephropathy (66 cases; 5.02%), and various minor and minimal changes (59 cases; 4.48%). Alport syndrome, congenital nephrotic syndrome, thin basement membrane nephropathy, fibrillary glomerulopathy disease, and Fabry disease were confirmed by electronic microscopy. IgA, IgM and C1q nephropathy were definitely diagnosed using immune histochemistry or immunofluorescent. A diagnosis of primary glomerular disease was made in 69.53% of the cases (915 cases); secondary glomerular disease was noted in 26.14% (344 cases). Of the 915 cases of primary glomerular disease, 375 (41.0%) had nephrotic syndrome. Secondary glomerular disease due to purura nephritis was common (209/344; 60.8%).

CONCLUSIONSPrimiary glomerular disease predominates in children. Nephrotic syndrome is the most common clinical diagnosis. Mesangial proliferation is the most common pathological patterns in children with renal disease.

Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Infant, Newborn ; Kidney ; pathology ; Kidney Diseases ; pathology ; Kidney Glomerulus ; pathology ; Male ; Renal Insufficiency ; pathology ; Retrospective Studies

Aim To explore the effect and mechanism of the artesunate(ART)on hepatocellular carcinoma(HCC).Methods The cell lines MHCC-97H and HCC-LM3 were used to be detected.MTT and clone formation were used to determine the cell proliferation;Wound healing was used to detect the cell migration;Transwell was used to test the cell invasion.Flow-cy-tometry was used to detect cell apoptosis and cell cy-cle.RNA-seq and qRT-PCR was used to detect the genes expression.Results The proliferation,migra-tion and invasion of treated cells were obviously inhibi-ted(P＜0.01).Moreover,the apoptosis rate in-creased significantly,so did the proportion of G2/M cells.Transcriptomic analysis identified GADD45A as a potential target of ART through RNA-sequencing da-ta,and suggested that ART might induce apoptosis and cell cycle arrest through regulating the expression of GADD45A.In addition,the results of mechanism studies and signaling analysis suggested that GADD45A had interaction with its upstream gene NACC1(nucle-us accumbens associated 1).Moreover,after ART treatment,the expressions of GADD45A and NACC1 were changed significantly.Conclusion ART may be a potential drug to resist HCC by affecting the expres-sion of GADD45A and its upstream gene NACC1,which provides a new drug,a new direction and a new method for the clinical treatment of HCC.

PLA-α-asarone nanoparticles were prepared by using organic solvent evaporation method, and their in vivo distribution and brain targeting after intranasal administration were studied as compared with intravenous administration. The results showed that brain targeting coefficient of PLA-α-asarone nanoparticles after intranasal and intravenous administration was 1.65 and 1.16 respectively. The absolute bioavailability, brain-targeting efficiency and the percentage of nasal-brain delivery of PLA-α-asarone nanoparticles were 74.2%, 142.24 and 29.83%, respectively after intranasal administration. The results of fluorescence labeling showed that the fluorescent intensity of coumarin-6 in the brain tissue was the highest after intranasal administration of PLA-α-asarone fluorescent nanoparticles, achieving the purpose of brain-targeted drug delivery. The fluorescent intensity of coumarin-6 in liver tissue after intravenous administration of PLA-α-asarone nanoparticles was much higher than that after intranasal administration, indicating that intranasal administration of PLA-α-asarone nanoparticles could decrease drug-induced hepatotoxicity. In addition, the fluorescent intensity of coumarin-6 in lung tissue was weaker after intranasal administration, which solved the shortcomings of intranasal administration of α-asarone dry powder prepared by airflow pulverization method. In vivo studies indicated that PLA-α-asarone nanoparticles after intranasal administration had a stronger brain targeting as compared with intravenous administration.