论著

基于孟德尔随机化以及 Meta 分析方法评估 CX3CL1 表达水平与系统性红斑狼疮的因果关系

Causal relationship between CX3CL1 expression levels and systemic lupus erythematosus based on Mendelian randomization and Meta-analysis

:1491-1500
 
      目的   采用两样本孟德尔随机化以及Meta分析研究趋化因子C-X3-C基序配体1(CX3CL1)表达水平与系统性红斑狼疮(SLE)发病风险的因果关系。方法   获取CX3CL1表达水平与SLE的全基因组关联研究(GWAS)数据,将单核苷酸多态性(SNP)作为工具变量并选择敏感的SNPs进行分析。通过逆方差加权法(IVW)、加权中位数法(WM)、MR-Egger回归法进行两样本MR分析,以OR值评估CX3CL1表达水平与SLE之间的因果关系,并对结果进行异质性和多效性检验。最后利用R软件Meta包进行Meta分析。利用coloc包进行共定位分析。结果   纳入9个SLE作为结局变量,其中4个变量ebi-a-GCST90018917(OR=2.14,95%CI:1.50~3.06),ebi-a-GCST003156(OR=2.25,95%CI:1.00~5.06),ebi-a-GCST90014238(OR=3.02,95%CI:1.54~5.94),finn-b-SLE_NOS(OR=1.81,95%CI:1.01~3.22)表明CX3CL1表达水平与SLE之间存在因果关系。关于 OR 95% CI 的森林图显示 SLE 患者的CX3CL1表达水平显著高于健康人群(OR=1.87,95%CI:1.53~2.29,P<0.001)。共定位分析结果提示CX3CL1表达水平和SLE表型之间有共享的遗传变异位点(rs170364)。结论  CX3CL1表达水平与SLE存在正向因果关系,CX3CL1表达水平的升高使得SLE的发病风险升高。
       Objective  To investigate the causal  relationship  between CX3CL1 levels and the  risk of  systemic lupus erythematosus(SLE)using two-sample Mendelian randomization and Meta-analysis methods.Methods  Genome-Wide Association Study(GWAS)data for CX3CL1 levels and SLE were obtained.Single nucleotide polymorphisms(SNPs)were used as instrumental variables,and sensitive SNPs were selected for analysis.Two-sample Mendelian  randomization was performed using the inverse variance weighted(IVW)method,weighted median(WM)method,and MR-Egger  regression to evaluate the causal relationship between CX3CL1 levels and SLE,with OR values assessing this relationship.Heterogeneity and pleiotropy tests were conducted on the results.Meta-analysis was performed using the Meta package in R software,and colocalization analysis was conducted using the coloc package.Results  Nine SLE outcomes were included as outcome variables,with four variables(ebi-a-GCST90018917[OR=2.14,95%CI:1.50-3.06],ebi-a-GCST003156[OR=2.25,95%CI:1.00-5.06],ebi-a-GCST90014238[OR=3.02,95%CI:1.54-5.94],finn-b-SLE_NOS[OR=1.81,95%CI:1.01-3.22])indicating a causal relationship between CX3CL1 expression levels and SLE.The forest plot for OR 95%CI showed that CX3CL1 expression levels in SLE patients were significantly higher than in healthy individuals(OR=1.87[95%CI:1.53-2.29],P<0.001).Colocalization analysis suggested that there was shared genetic variation sites(rs170364)between CX3CL1 expression levels and SLE phenotype.Conclusions  There is a positive causal relationship between CX3CL1 expression levels and SLE,with increased CX3CL1 levels elevating the risk of developing SLE.
综述

可注射水凝胶药物递送系统在肿瘤治疗中的应用

The application of injectable hydrogels as drug delivery systems in tumor treatment

:1035-1044
 
       肿瘤治疗仍然是生物医学研究的一个突出领域。围绕各种化学治疗(化疗)药物和其他治疗药物的不良反应和靶向疗效的研究推动了各种药物载体的发展。这些载体聚焦于提高肿瘤部位的药物浓度,最大限度地减少全身不良反应,并改善治疗效果。在已报道的递送系统中,可注射水凝胶由于其微创的药物递送特性,已成为化疗药物体内递送的重要载体形式。文章系统地总结了可注射水凝胶的类型和特征,并进一步概括了可注射水凝胶装载药物的方式,同时深入讨论可注射水凝胶在治疗肿瘤的各种药物的递送应用。文章对原位注射水凝胶在治疗肿瘤方面存在的潜在性挑战和可能的解决方案提供了动态前瞻性的参考。可注射的水凝胶作为药物传递系统用于肿瘤治疗具有良好的发展前景。
       Tumor treatment remains a prominent area of biomedical research.The  researches surrounding the adverse 
reactions and targeted efficacy of various chemotherapy drugs and other therapeutic drugs have driven the development of various drug carriers.These carriers focus on increasing drug concentration at tumor site,minimizing systemic adverse reactions,and improving treatment outcomes.In the reported delivery systems,injectable hydrogels have become an important carrier for the delivery of chemotherapeutic drugs in vivo due to their minimally invasive characteristics.This review systematically summarized the types and characteristics of injectable hydrogels,and further summarized their drug loading methods.At the same time,the application of injectable hydrogels in the delivery of various drugs for tumor treatment was discussed in depth.This  review provides dynamic and prospective reference for the potential challenges and possible solutions of the in situ injectable hydrogels for tumor therapy.Injectable hydrogels as drug delivery systems are with good prospects for tumor treatment.
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