Endovascular Management of Aortic Arch Diseases:Current Status and Future Trends

Treatment of aortic arch(AA)diseases is challenging for surgeons.Conventional open surgery remains the“gold standard”but is associated with significant morbidity and mortality despite improvements in techniques.In the last 2 decades,thoracic endovascular aortic repair(TEVAR)has become the first-line treatment for diseases of the descending aorta,and its indications have expanded gradually.Various strategies have been proposed to preserve supra-aortic branches in TEVAR:hybrid technique,chimney technique,fenestration technique(including custom-made fenestrated or“scalloped”stent grafts,in situ fenestration,and physician-modified fenestration),and branched stent grafts.Though acceptable outcomes of endovascular aortic repair have been documented,the evidence regarding its long-term safety and efficacy is lacking,and concerns remain about the risk of cerebrovascular events,retrograde type-A dissection,endoleaks,and branch occlusion.This review discusses the current status and progress of endovascular repair of the AA,and looks toward future trends.We believe that multidisciplinary collaboration of a“HENDO”team(professionals in hybrid repair,endovascular repair,open surgery,cardiovascular anesthesia,and genetics)is essential for future repair of the AA to provide the optimal treatment.

Multilayer stents, a new progress in the endovascular treatment of aneurysms

Objective To review the recent progress of multilayer stents in treating arterial aneurysms and to draw an initial conclusion about its paradigm. Data sources PubMed database and ELSEVIER database were searched with the keywords ＂cardiatis＂ or ＂multilayer stent＂ for relevant articles from January 2008 to September 2012. Relevant websites （provided by Cardiatis） were also involved in the review process. Study selection Well-controlled, relatively large-scale, retrospective studies as well as meaningful individual cases were all selected as materials. Results A total of 23 articles were involved in this review. The newly introduced Cardiatis muttilayer stent aims at creating an active flow-modulating barrier between normal blood flow and aneurismal sac, which can induce thrombosis within aneurismal sac and preserve collateral circulation at the same time. Currently, it has been applied for complicated aneurysms located in different segments of the arterial system. Conclusion This new concept of multilayer uncovered stent offers a promising alterative in the treatment of arterial aneurysms. However, a further larqe-scale clinical and hemodynamic study is reauired to evaluate the Iona-term effects.

RIPK1 plays a crucial role in maintaining regulatory T-Cell homeostasis by inhibiting both RIPK3-and FADD-mediated cell death

Regulatory T(T_(reg))cells play an essential role in maintaining immune balance across various physiological and pathological conditions.However,the mechanisms underlying T_(reg)homeostasis remain incompletely understood.Here,we report that RIPK1 is crucial for T_(reg) cell survival and homeostasis.We generated mice with T_(reg) cell-specific ablation of Ripk1 and found that these mice developed fatal systemic autoimmunity due to a dramatic reduction in the Treg cell compartment caused by excessive cell death.Unlike conventional T cells,Treg cells with Ripk1 deficiency were only partially rescued from cell death by blocking FADD-dependent apoptosis.However,simultaneous removal of both Fadd and Ripk3 completely restored the homeostasis of Ripk1-deficient Treg cells by blocking two cell death pathways.Thus,our study highlights the critical role of RIPK1 in regulating Treg cell homeostasis by controlling both apoptosis and necroptosis,thereby providing novel insights into the mechanisms of Treg cell homeostasis.

Herbal formula of Bushen Jianpi(补肾健脾方)combined with sorafenib inhibits hepatocellular carcinoma growth by promoting cell apoptosis and blocking the cell cycle

OBJECTIVE:To investigate the efficacy of an herbal formula of Bushen Jianpi(补肾健脾方,BSJP)combined with sorafenib on hepatocellular carcinoma(HCC)in vitro and in vivo,and to study the underlying mechanisms of action.METHODS:BSJP,a mixture of 12 raw herbs,was extracted in 70%alcohol/30%water and freeze-dried into a powder.The in vitro effects of BSJP alone,sorafenib alone,and their combination on cell survival,apoptosis,and cell cycle distribution were evaluated in HCC cell lines HCCLM3,HepG2,and SMMC-7721.The expression of B-cell lymphoma-2(Bcl-2),caspase-3,and caspase-9 in HCCLM3 cells was measured using Western blots after drug administration.The in vivo effects of BSJP and sorafenib were evaluated in a tumor surgical resection model using 4-week old male athymic BALB/c nude mice injected with HCCLM3 cells.Immunohistochemical analysis of tumor tissues was performed to evaluate the effects of BSJP alone,sorafenib alone,and their combination on the expression of caspase-3,caspase-9,and Bcl-2.RESULTS:BSJP decreased the survival rate of HCC cell lines,and the combination of BSJP and sorafenib further decreased the survival rate.BSJP significantly promoted cell apoptosis and blocked cell-cycle progression in HCCLM3,HepG2,and SMMC-7721 cells in a dose-dependent manner.Furthermore,the administration of BSJP and sorafenib inhibited the growth of HCCLM3 cell xenografts in nude mice,with no reduction in body weight.In vivo and in vitro experiments showed that BSJP combined with sorafenib could significantly decrease the expression of Bcl-2.CONCLUSION:Our findings suggest that the herbal formula of BSJP is a potential HCC antitumor agent.

DNA Methylation and Transcription of HLA-F and Serum Cytokines Relate to Chinese Medicine Syndrome Classification in Patients with Chronic Hepatitis B

Objective:To explore the molecular bases of Chinese medicine(CM) syndrome classification in chronic hepatitis B(CHB) patients in terms of DNA methylation,transcription and cytokines.Methods:Genome-wide DNA methylation and 48 serum cytokines were detected in CHB patients(DNA methylation:15 cases;serum cytokines:62 cases) with different CM syndromes,including dampness and heat of Gan(Liver) and gallbladder(CHB1,DNA methylation:5 cases,serum cytokines:15 cases),Gan stagnation and Pi(Spleen) deficiency(CHB2,DNA methylation:5 cases,serum cytokines:15 cases),Gan and Shen(Kidney) yin deficiency(CHB3,DNA methylation:5 cases,serum cytokines:16 cases),CHB with hidden symptoms(HS,serum cytokines:16 cases) and healthy controls(DNA methylation:6 cases).DNA methylation of a critical gene was further validated and its mRNA expression was detected on enlarged samples.Genome-wide DNA methylation was detected using Human Methylation 450 K Assay and further verified using pyrosequencing.Cytokines and mRNA expression of gene were evaluated using multiplex biometric enzyme-linked immunosorbent assay(ELISA)-based immunoassay and reverse transcription-quantitative polymerase chain reaction(RT-qPCR),respectively.Results:Totally 28,667 loci,covering 18,403 genes were differently methylated among CHB1,CHB2 and CHB3(P<0.05 and|△β value|> 0.17).Further validation showed that compared with HS,the hg19 CHR6:29691140 and its closely surrounded 2 CpG loci were demethylated and its mRNA expressions were significantly up-regulated in CHB1(P<0.05).However,they remained unaltered in CHB2(P>0.05).Levels of Interleukin(IL)-12 were higher in CHB3 and HS than that in CHB1 and CHB2 groups(P<0.05).Levels of macrophage inflammatory protein(MIP)-1αand MIP-1β were higher in CHB3 than other groups and leukemia inhibrtory factor level was higher in CHB1 and HS than CHB2 and CHB3 groups(P<0.05).IL-12,MIP-1α and MIP-1β concentrations were positively correlated with human leukocyte antigen F(HLA-F)mRNA expression(R;=0.238,P<0.05;R;=0.224,P<0.05;R;=0.447,P<0.01;respectively).Furthermore,combination of HLA-F mRNA and differential cytokines greatly improved the differentiating accuracy among CHB1,CHB2 and HS.Conclusions:Demethylation of CpG loci in 5’ UTR of HLA-F may up-regulate its mRNA expression and HLA-F expression was associated with IL-12,MIP-1α and MIP-1β levels,indicating that HLA-F and the differential cytokines might jointly involve in the classification of CM syndromes in CHB.(Registration No.ChiCTR-RCS-13004001)

DNA Methylation and SNPs in VCX are Correlated with Sex Differences in the Response to Chronic Hepatitis B

The study was conducted to explore the mechanisms of sex differences in the response to chronic hepatitis B(CHB)in terms of DNA methylation,SNP genotype,and gene expression.Genomic DNA was isolated from peripheral blood mononuclear cells(PBMCs)of CHB patients and healthy controls and evaluated using the Human Methylation 450 K Assay.The DNA methylation level at hg37 chromosome(CHR)X:7810800 was further validated using pyrosequencing.SNP genotypes,VCX mRNA expression of PBMCs,and plasma VCX protein concentration were further examined using SNaPshot,RT-qPCR,and Western blot,respectively.Results showed that a total of 5529 CpG loci were differentially methylated between male and female CHB patients.DNA methylation level and CC+CT frequency at CHR X:7810800,VCX mRNA expression of PBMCs,and plasma VCX protein concentration were higher in female than in male CHB patients.The CHR X:7810800 locus was hypermethylated in CHB patients with CC+CT genotypes in comparison with those with the TT genotype.In cases of CC-f CT genotypes,VCX mRNA expression was negatively correlated with the DNA methylation level.CHB patients with higher levels of HBV DNA,AST,and GGT or higher GPRI scores exhibited lower VCX expression.In conclusion,SNPs and DNA methylation at the CHR X:7810800 locus cooperatively regulate VCX expression in CHB.The upregulated VCX expression in female CHB patients might represent a mechanism of protection from more severe liver dysfunction and extensive fibrosis,as observed in male CHB patients.