Objective To establish a research protocol to clarify the characteristic changes in major functional activities and cellular processes involved in bone marrow during aging using RNA sequencing,and to identify potential targets for aging prediction and intervention.Methods Bone marrow cells were extracted from the bilateral tibiae and femurs of three C57BL/6J male mice aged 2,10,and 18 months,respectively.After red blood cell lysis,RNA was extracted for sequencing analysis.Results The result of gene expression and Venn analysis showed that gene expression levels were predominantly down-regulated from 2～10 months,but mainly up-regulated from 10～18 months.Gene expression thus changed from mainly down-regulation to mainly up-regulation during maturation and development in mice.Kyoto encyclopedia of genes and genomes and gene set enrichment analyses indicated that bone marrow tissues in mice at different ages showed significant expression differences in the"immune system""development and regeneration""transport and catabolism""cell growth and death"and other pathways.Specifically,inflammatory,cytoskeletal,and DNA repair pathways showed sustained activation,contrasting with progressive hematopoietic decline and fluctuating immune regulation.Enriched pathway screening revealed interactions among differentially expressed genes,such us upregulated genes Bmpr1a and Inhba,downregulated genes Dntt and Ccnd1,and downregulated genes Col1a1,Col1a2,Fcgr1,Fyn,Lgmn,Ctsl,Ctsk,Ctss,Gnail,Myl4,and Ccr5,involved in HSCs homeostasis,cell cycle,DNA repair,immune regulation,and apoptosis.Conclusions This study provides data on gene expression changes at the transcriptional level and offers a research strategy to explore the major characteristic changes in bone marrow during aging in mice.The result identify aging-related genes and signaling pathways,thus providing new strategies for delaying aging and preventing aging-related diseases.

Objective To establish a research protocol to clarify the characteristic changes in major functional activities and cellular processes involved in bone marrow during aging using RNA sequencing,and to identify potential targets for aging prediction and intervention.Methods Bone marrow cells were extracted from the bilateral tibiae and femurs of three C57BL/6J male mice aged 2,10,and 18 months,respectively.After red blood cell lysis,RNA was extracted for sequencing analysis.Results The result of gene expression and Venn analysis showed that gene expression levels were predominantly down-regulated from 2～10 months,but mainly up-regulated from 10～18 months.Gene expression thus changed from mainly down-regulation to mainly up-regulation during maturation and development in mice.Kyoto encyclopedia of genes and genomes and gene set enrichment analyses indicated that bone marrow tissues in mice at different ages showed significant expression differences in the"immune system""development and regeneration""transport and catabolism""cell growth and death"and other pathways.Specifically,inflammatory,cytoskeletal,and DNA repair pathways showed sustained activation,contrasting with progressive hematopoietic decline and fluctuating immune regulation.Enriched pathway screening revealed interactions among differentially expressed genes,such us upregulated genes Bmpr1a and Inhba,downregulated genes Dntt and Ccnd1,and downregulated genes Col1a1,Col1a2,Fcgr1,Fyn,Lgmn,Ctsl,Ctsk,Ctss,Gnail,Myl4,and Ccr5,involved in HSCs homeostasis,cell cycle,DNA repair,immune regulation,and apoptosis.Conclusions This study provides data on gene expression changes at the transcriptional level and offers a research strategy to explore the major characteristic changes in bone marrow during aging in mice.The result identify aging-related genes and signaling pathways,thus providing new strategies for delaying aging and preventing aging-related diseases.

Objective To establish interferon-induced transmembrane protein 3(Ifitm3)knockout mice and to explore the effects of Ifitm3 on the proliferation and differentiation of adult neural stem cells of mice(aNSCs).Methods IFITM3 knockout mice were established by the CRISPR/Cas9 method and identified by genotype identification and Western Blot.The differences between Ifitm3-knockout mice and wild-type mice were analyzed by hematoxylin-eosin(HE)staining and flow cytometry.The aNSCs of wild-type mice and Ifitm3-knockout mice were isolated and cultured,the number and size of neurospheres were detected,The ability of aNSCs to proliferate and differentiate were detected by quantitative reverse-transcription polymerase chain reaction,Western Blot,and immunofluorescence.Results Ifitm3-knockout mice were successfully established.The mice developed normally,and there were no obvious abnormalities either histopathologically or the immune system.In vitro experiments showed that Ifitm3 knockout inhibited the self-renewal potential of aNSCs,led to a decrease in the proliferation ability of aNSCs,and inhibited the differentiation of aNSCs into immature neurons and astrocytes.Conclusions This study finds that a lack of IFITM3 result in the ability of aNSCs to proliferate and differentiate decreased,IFITM3 may regulate the function of aNSCs.

Objective To evaluate the safety,effectiveness and clinical factors of re-intervention of transjugular intrahepatic porto-systemic shunt (TIPS).Methods A retrospective study of safety and longterm outcomes of TIPS was made in 771 patients from August 1994 to August 2010.The 625 patients had follow-up data.The patients who received TIPS once,twice,and more than twice were divided into group 1,group 2 and group 3,respectively.Clinical symptoms,survival rate and restenosis rate of each group were analyzed.Clinical influencing factors of re-intervention effect were discussed.Results The success rate of first intervention was 98.2％ (757/771),the death rate was 0.7％ (5/757) and severe complication rate was 2.5％ (19/757).The success rate of re-intervention was 98.7％ (457/463),no death and severe complications occurred.The restenosis rate in group 3 decreased significantly than group 1 ( x2 =7.908,P ＜0.05 ) in the first year of TIPS.The restenosis rates in group 2 and group 3 were lower than group 1 from 2 to 5 years of TIPS ( x2 values were 27.046,25.724,37.002 and 19.046,respectively,P ＜ 0.05 ). The survival rate in group 3 was higher than group 1 (x2 =9.114,P＜0.05)and group 2 was higher than group 1 ( x2 =4.929,P ＜ 0.05 ) in the first year of TIPS,while there was no statistical difference between group 2 and group 3 ( x2 =2.678,P ＞ 0.05).The patients in group 2 and group 3 also had higher survival rates than group 1 from 2 to 5 years of TIPS (x2 value were 41.314,26.920,13.692 and 6.713,respectively,P ＜ 0.05 ).19.4％ (79/406)of patients who received re-intervention had symptom recurrence and shunt stenosis or occlusion. 11.6％ (47/406) of patients had symptom recurrence with portal hypertension signs,62.8％ (255/406) had shunt stenosis or occlusion with portal hypertension signs.Conclusions Restenosis or occlusion of TIPS,symptom recurrence and portal hypertension signs were important factors for re-intervention.Re-intervention of TIPS was safe and effective,and could improve the survival rate of patients with TIPS.