Background The pathogenesis of primary open angle glaucoma(POAG) and high myopia are very complex.To construct the regulatory network of virulence genes and relevant genes that involved in pathogenicity are helpful for reveal of the pathogenesis.Objective The aim of this study was to investigate myocilin(Myoc),a gene that contributes to POAG and high myopia in eyes of BXD Recombinant Inbred(BXD RI)mice and construct the regulatory network of Myoc.Methods The affymetrix microarray system was used to detect the differential expression of Myoc in the eyes of C57BL/6J(B6),DBA/2J(D2) and BXD RI mice.Expression quantitative trait loci (eQTL) mapping was performed to construct the regulatory network of Myoc gene.Results The average expression level of the Myoc gene in the BXD strains was 10.83,and the gene exhibited expression levels ranging from 8.39 in BXD55 mice tol 1.43 in B6 mice.The eQTL mapping for the Myoc gene showed a significant likelihood ratio statistic (LRS) of 21.78.The QTL was mapped in chromosome 2,and Myoc was located on chromosome 1,indicating that the Myoc gene was a trans-acting QTL.Olfml2a was identified to be a candidate upstream gene of Myoc by analysis of bioinformatics.Genetic regulatory network analysis demonstrated that a series of genes associated with Myoc probably played roles in the pathogenesis and development of POAG and high myopia.Conclusions The genetical genomics approach provides a powerful tool for constructing pathways that contribute to complex traits,such as POAG and high myopia.

Twenty five patients with incarcerated stone in distal common bile duct were treated with mini-blasting lithotrite under choledochoscope from June 2008 to September 2010.The clinical data of patients were retrospectively analyzed.The successful rate of surgery was 100％.The clearance rate of first procedure was 92％ (23/25),2 cases underwent second procedure and all were successful.There were no severe operative complications including bile duct injury,perforation,hemorrhage or bile leakage.Miniblasting lithotrite is a safe and effective method for treating incarcerated stone in distal common bile duct.

Objective To explore the influence of homocysteine(Hcy)on liver cystathionine-?-synthase(CBS)and methylenetetrahydrofolate reductase(MTHFR)system in apoE-/- mice,and determine the effects of atorvastatin and/or folate/vitamin B12 on liver CBS and MTHFR system.Methods Eighty male 6-week-old apoE-/- mice were randomly divided into two groups:65 mice were fed with a chow diet containing 2%(wt/vol)L-methionine(homomethionine group)and 15 mice were fed with normal saline(control group).Two months later,the 60 mice survived in homomethionine group were subdivided into four groups:group Ⅰ(untreated),Ⅱ(3 mg/kg atorvastatin),Ⅲ(3 mg/kg atorvastatin+2 mg/kg folate+30 ?g/kg vitamin B12)and Ⅳ(2 mg/kg folate+30 ?g/kg vitamin B12).After one month,Western blotting was performed to detect the liver CBS and MTHFR system protein expression in each group.Results The relative expression of liver CBS and MTHFR was significantly lower in group Ⅰ than in control group(P

Objective To study the therapeutic effect of anti-LPS antibody and different antibiotic in treatment and prevention of sepsis a common complication of serious burns.Methods Twenty-nine patients were divied into anti-LPS+antibiotic treatment group and antibiotic treatment group.Plasma endotoxin,serum TNF,IL-6 and IL-8 were detected at different time phase after burn.Results The results showed that the antibodies to LPS could decrease the level of LPS,IL-6,IL-8 and TNF obviously,but some antibiotic couldn't decrease the level of LPS,IL-6,IL-8 and TNF obviously in blood.Impenem was a weak endotoxin inducer and ceftazidime and ciprofloxacin were stronger endotoxin inducers.Conclusion The appropriate selection of antibiotics and anti-LPS antibody has a considerable influence on treating sepsis and its complications after serious burns.

Objective To analyze the association between mtDNA mutations and photodamagc after ultraviolet B (UVB) irradiation. Methods Primary human skin fibroblasts (HSF) and primary human epi- dermal keratinocytes of adult (HEKa) were irradiated by sub-lethal doses of UVB thrice a day for 4-5 days. Thereafter, genomic DNA was extracted from irradiated cells and conventional PCR was applied to detect the frequency rates of 4977 bp and 3895 bp mtDNA deletion. To quantitatively analyze the mutation levels, SYBR Green real-time PCR method was performed. Results In both cell lines, the frequency rates and relative copy number of deletions increased with the cumulative doses of UVB exposure (P<0.05). The prevalence rate of 3895 bp deletion peaked 53.3% and and relative copy number reached (49.63±4.38)×10-5, showing a more intense response to the accumulation of UVB radiation than 4977 bp deletion. In HSF, the minimum cumu- lative dose of UVB radiation was 150 mJ/cm2 for the induction of 3895 bp deletion, and 200 mJ/cm2 for the induction of 4977 bp deletion. It seemed that mtDNA deletion was more readily to be induced by UVB radia- tion in HSF than in HEKa. Conclusions The development and accumulation of mtDNA mutation are intimately related with cumulated UVB dose received by skin cells, and the 3895 bp deletion is more reliable in moni- toring the photodamage caused by UV than 4977 bp deletion. Therefore, the 3895 bp deletion may serve as a biomarker for the detection of photodamagc in skin cells. HSF appear to have an increased susceptibility to UVB radiation, which results in a higher frequency and level of mtDNA mutations compared with HEKa.

Objective To explore the effects of recombinant human growth hormone(rhGH) on the serum levels of cytokines in severely burned patients.Methods Thirty-six burn patients were en-rolled in the study and were randomly divided into 3 groups according to the rhGH dosage used,i.e. small(0.3IU?kg -1 ?d -1 ,A),large(0.6IU?kg -1 ?d -1 ,B) dose groups and control group(C,with normalsaline).The rhGH was administered beginning from 3 postburn days(PBDs) and lasted for 20 days.The dynamic changes in the serum levels of TNF-?,IL-6,IL-8 and LPS at different time points were observed.Results When compared with these in C group,the serum levels of TNF-?,IL-6 in A,B groups were decreased,especially in B group with earlier decrease and bigger range(P0.05).Conclusions rhGH might decrease the production of postburn inflammatory mediators.The clinical application of rhGH might be a supplementary measure in preventing and ameliorating postburn SIRS and MODS in severely burned patients.

OBJECTIVE:To observe therapentic efficacy of bevacizumab combined with irinotecan+leucovorin+fluorouracil (FOLFIRI)plan in the treatment of advanced colon cancer,toxic reaction and patients'survival rate. METHODS:A total of 113 patients with advanced colon cancer admitted to the oncology department in our hospital from Jan. 2010 to Aug. 2014 were random-ized into observation group 1(40 cases),observation group 2(39 cases)and control group(34 cases). Three groups received FOLFIRI;observation group 1 and 2 were additionally given Bevacizumab injection 5 and 7.5 mg/kg 14 d as a treatment course, for 8 cycles. Clinical efficaices as well as the positive rate of VEGF-A,immune indexes(the proportion of CD3+,CD3+CD4+,CD3+CD8+ in T cell subset)before and after treatment,the incidence of toxic reaction,1-year and 2-year survival rates were compared among 3 groups. RESULTS:The total response rate of observation group 1 and 2 were significantly higher than control group,and the positive rate of VEGF-A in observation group 1 and 2 were significantly lower than control group,with statistical significance (P<0.05). The proportion of CD3+,CD3+CD4+ and CD3+CD8+ in 3 groups were significantly lower than before treatment,but ob-servation group 1 and 2 were significantly higher than control group,with statistical significance(P<0.05). The incidence of grade hypertension(grade 3-4)in observation group 1 and control group were lower than observation group 2;the incidence of leucope-nia(grade 3-4)in observation group 1 and 2 were significantly lower than control group,with statistical significance(P<0.05). There was no statistical significance in 1-year survival rate among 3 groups(P>0.05). 2-year survival rate of observation group 1 and 2 were significantly higher than control group,with statistical significance(P<0.05). CONCLUSIONS:For advanced colon cancer,different doses of bevacizumab combined with FOLFIRI have significant synergistic effect,can effectively inhibit VE-FG-A,play a role of immune protection and anti-toxic side effects,and prolong the survival time. The incidence of hypertension in patients treated with low-dose bevacizumab is relatively lower and the safety is better.

Objective To investigate the effect of bifidobacteria on dextran sulphate sodium(DSS)- induced acute ulcerative colitis in mice.Methods Thirty BALB/C mice were randomly divided into nor- mal control group (n=10),0501 strain group (n=10) and c122 strain group (n=10).Fifty BALB/ C mice received 5% dextran sulphate sodium(DSS) for 7 days to induce ulcerative colitis.The mice were then divided to model group,negative control group(perfused with 0.9 NaCl solution ),positive control group(perfused with SASP of 20 mg/ml),DSS + 0501 strain group(perfused with 1?10~9 CFU/ml bifidobacteria 0501 strain solution and DSS + c122 strain group (perfused with 1?10~9 CFU/ml bifidobacteria c122 strain solution).All mice were sacrificed 9 days later.The colon specimens were measure by histoehemical staining with H-E.The expressions of interleukin-10 (IL-10) and its protein were detected by RT-PCR and immunohistochemistry respectively.Results The degree of colon inflam- mation in mice both in DSS+ 0501 strain and DSS+ c122 strain groups were aggravated and expressions of IL-10 mRNA and protein were reduced compared to model group.No colon inflammation was found in 0501 strain and c122 strain groups.Conclusion Some strain of bifidobaeteria may aggravate colon in- flammation in mice when mucosal harrier is destroyed.

BackgroundHigh myopia is one of leading causes of blindness,so far the pathogenesis remains unclear.Two single-nucleotide polymorphisms (SNPs) of rs6885224 and rs12716080 in CTNND2 gene were recently found to be associated with high myopia in Singaporean Chinese.But whether these SNPs are related with the pathogenesis of high myopia in Han Chinese is worth studying,Objective This study was to investigate the relationship between the genetic variations of the CTNND2 gene and high myopia in Han Chinese.MethodsA case-controlled association study was designed.Nine hundred and thirty-three individuals with high myopia and 1227age- and gender-matched normal subjects were included in this study.The 5 ml of periphery blood was obtained from all subjects for the extraction of genomic DNA.The target DNA was amplified using PCR and purified by the SNaPshot method.Four SNPs rs12716080,rs917012,rs6885224 and rs16901340 in the CTNND2 gene were genotyped.This study was approved by the Ethic Committee of Sichuan Provincial People Hospital.Written informed consent was obtained from each subject before his/her enrollment.Results The frequencies of the genotypes rs6885224,rs12716080,rs917012,rs16901340 SNPs were in Hardy-Weinberg equilibrium (HWE) ( P=0.181,0.085,0.732,0.313,0.264,0.663,0.084,0.196).There were no significant differences in genotypes frequency distribution ( in turn P =0.654,0.406,0.828,0.403 ) and allele frequency distribution of the CTNND2 gene ( in turn P =0.377,0.209,0.743,0.198) between the high myopia group and normal control group.The haplotypes (TA and GA)frequencies of rs12716080 and rs917012 in the high myopia group were significantly different from those of the normal control group(TA:0.784 vs.0.719;GA:0.087 vs.0.136) (x2 =6.115,P=0.013 ;x2 =6.634,P=0.010),but those of GG were similar between the high myopia group and normal control group ( 0.123 vs.0.143,x2 =0.889,P =0.346). ConclusionsThe SNPs rs12716080,rs917012,rs6885224 and rs16901340 in CTNND2 gene were not responsible for high myopia,however,the haplotypes of rs12716080 and rs917012 are susceptible for high myopia in Han Chinese.

Objective:To conduct health economic evaluation of Chinese population-based screening and opportunistic testing strategies for the prevention of Helicobacter pylori ( H. pylori)-related diseases. Methods:The Markov models of H.pylori infection caused non-ulcer dyspepsia, peptic ulcer (PU) and gastric cancer were established. The cost and effects of the population-based screening, opportunistic testing, and non-intervention strategies in 100 000 population of our country were simulation calculated. Wilcoxon signed rank test was used for statistic analysis. Single factor sensitivity analysis was performed to analyze the impact of single parameter uncertainty on cost-effectiveness. Probability sensitivity was used to analyze the impact of common uncertainty of all parameters on cost-effectiveness. Results:Compared with opportunistic testing strategy and non-intervention strategy, the total cost of population-based screening strategy was reduced by 0.43 million yuan(-6.63 million yuan to 7.19 million yuan) and 4.45 million yuan(-8.60 million yuan to 27.93 million yuan), quality adjusted life years (QALY), life years and asmptomatic months were prolonged by 888.00 (479.86 to 1 574.10) and 3 032.78 (1 756.04 to 5 007.84), 651.82 (294.73 to 1 211.94) and 1 868.64 (1 045.88 to 3 148.34), 28 381.91 (19 109.54 to 43 736.72)and 102 537.13 (58 649.18 to 176 868.77) respectively, gastric cancer, deaths from gastric cancer, deaths from PU and deaths from various causes were reduced by 115 cases(52 cases to 232 cases) and 464 cases(266 cases to 803 cases), 74 cases(33 cases to 148 cases) and 260 cases(149 cases to 453 cases), 46 cases(25 cases to 72 cases) and 369 cases(210 cases to 710 cases), 80 cases(42 cases to 126 cases) and 501 cases(331 cases to 772 cases) respectively, and the differences were statistically significant ( Z=1.99, 10.54, 27.39, 27.39, 27.37, 27.39, 27.39, 27.39, 27.21, 27.28, 27.22, 27.28, 27.38, 27.39, 27.39 and 27.39, all P<0.05). Compared with the non-intervention strategy, the opportunistic testing strategy reduced the total cost by 3.89 million yuan(-2.79 million yuan to 18.18 million yuan), QALY, life years and asymptomatic months were prolonged by 1 764.77 (888.70 to 3 406.62), 1 044.16 (524.46 to 1 912.75) and 62 568.69 (30 054.07 to 129 892.76) respectively, gastric cancer, deaths from gastric cancer, deaths from PU and deaths from various causes were reduced by 311 cases(164 cases to 563 cases), 164 cases (87 cases to 301 cases), 325 cases(162 cases to 644 cases) and 399 cases(234 cases to 684 cases) respectively, and the differences were statistically significant ( Z=14.20, 27.39, 27.38, 27.39, 27.25, 27.25, 27.39 and 27.39, all P<0.01). The results of singlefactor sensitivity analysis showed that the uncertainty of any parameter did not affect the cost-effectiveness of three strategies. The results of probability sensitivity analysis indicated that the probability of cost-effectiveness advantage of the population-based screening strategy was 100% and the common uncertainty of all parameters had no effect on cost-effectiveness. Conclusions:For preventing H.pylori-related diseases, the population-based screening strategy has the lowest average cost and the best average effect. However, non-intervention strategy has the highest average cost and the worst average effect. Population-based screening strategy is worthy of promotion throughout China, and opportunistic testing strategy has a higher clinical practical value.