Objective To understand the epigenetic regulations of P16 during cellular replicative senescence and premature senescence induced by hydrogen peroxide of human embryonic lung fibroblasts(HEFs).Methods The normal HEFs were divided into young cells(22 PDL),mid-aged cells(35 PDL)and replicative senescent cells(49 PDL)during replicative senescence.The synchronously cultured 22 PDL HEFs were exposed for 2 h to 400?mol/L H_2O_2 at half confluence on daily basis.The procedure lasted for 4 consecutive days.And then the treated cells were cultured for another 7 days,called premature senescent cells.The mRNA level of P16 was detected by fluorescence quantitative PCR.The methylation level in the promoter region -846～-639 bp was observed by methylation-specific PCR(MSP).The histone modifications was detected by chromatin immunoprecipitation-QPCR assay,including acetylation for H3,H4 and methylation for H3(Lys4)and H4(Lys20).Results In the process of cellular senescence,the mRNA level of P16 decreased in mid-aged cells,but increased significantly in both replicative and premature senescent cells compared with that of young cells(P

Objective: To detect the alterations of telomerase activity and the expression for oxidative stress responsive genes related with senescence during cellular replicative senescence and hydrogen peroxide-induced premature senescence in human embryonic lung fibroblasts (HELFs) in vitro. Methods: The HELFs were divided into young cells (22 population doubling levels, 22PDL) , mid-aged cells (35PDL) and replicative senes-cent cells (49PDL) and premature senescent cells induced by H₂O₂(premature senescence, PS). The telomerase activity was detected by ELISA assay during cellular replicative and premature senescence. The mRNA level of oxidative stress responsive genes related with senescence for Foxo1, Foxo3, Pdx1, apoA-I and MMP1 was per-formed by RT-Q-PCR separately. Results: The mRNA level for Foxo1, Foxo3, apoA-I and Pdx1 was decreased separately during cellular replicative senescence compared to that in the young-stage cells with statistical signifi-cance (P<0.05). The expression of MMP1 was up-regulated 5.1-fold obviously (P<0.05). In premature senes-cence, the mRNA level was only decreased for Foxo1, Foxo3 and apoA-I, but up-regulated 2.3-fold and 6.2-fold for Pdx1 and MMP1 respcetively vs 22PDL significantly (P<0.05). The telomerase activity in young cells was not detected, and it increased in mid-aged cells and replicative senescence stages during cellular replicative se-nescence as compared to 22PDL with statistical significance (P<0.05). The telomerase activity in premature se-nescence was highly active. Conclusion The expression for genes related with senescence has differences be-tween replicative and premature senescence and hydrogen peroxide modifies their expression levels. The telomer-ase activity has been going up with increased PDLs.

Objective: To explore the key points of diagnosis and treatment of familial Mediterranean fever(FMF). Method: The clinical data of 3 cases with FMF misdiagnosed as Juvenile idiopathic arthritis(JIA)seen from January 2014 to June 2016 in Peking Union Medical College Hospital were retrospectively collected. The clinical manifestations, gene mutation characteristics, treatment and prognosis were also evaluated. Result: Two cases were male and 1 was female. The mean age of onset was 17 months (3 months to 36 months), while the average age of diagnosis was 6 years and 8 months (24 months to 11 years). All the 3 cases presented with periodic fever, red rash and arthritis.Two of them suffered from anemia, 2 of them showed lymphadenopathy, and 1 of them presented with hepatosplenomegaly. All of the 3 cases were diagnosed as JIA by excluding infectious diseases and neoplastic diseases and respondiug poorly to anti-infection treatment, but they benefitted little from glucocorticoids and a variety of immunosuppressive therapy. The mutations of MEFV gene were found in 3 cases by gene detection, and all of them were complex heterozygous mutations. Four reported pathogenic mutations were found: R202Q, E148Q, L110P, P369S. All the 3 cases are currently receiving oral colchicine (in accordance with the initial dose of children under the age of 5 recommended ≤ 0.5 mg/d, 5 to 10 years old children 0.5-1.0 mg/d, 10 years old children and older children 1.0-1.5 mg / d) , and the symptoms were significantly improved. Conclusion The familial Mediterranean fever can be characterized by repeated remittent fever, red rash, arthritis, and is easy to be confused with JIA in clinical manifestation.In this paper, 3 cases were diagnosed as complex heterozygous MEFV gene mutation by gene analysis.During the 6 months follow-up, all of the 3 patients responded well to colchicine.

Cerebral circulation time is defined as the difference between the time to peak of the cavernous sinus segment of the internal carotid artery and the Trolard vein, which is easily obtained in digital subtraction angiography and is closely associated with hemodynamics. Cerebral circulation time can be used to evaluate the outcome of acute ischemic stroke, especially in patients receiving endovascular treatment. This article reviews the evaluation methods of cerebral circulation time and its clinical significance in patients with acute ischemic stroke.