Correlation of matrix metalloproteinase－2, －9, tissue inhibitor－1 of matrix metalloproteinase and CD44 variant 6 in head and neck cancer metastasis

This study aimed to explore the molecular mechanism in tumor invasion and metastasis. The expression of matrix metalloproteinase 2, 9 (MMP 2, MMP 9), tissue inhibitor 1 of matrix metalloproteinase (TIMP 1), cell adhesion molecule 44 variant 6 (CD44v6), HER2/neu and p53 was investigated in 154 patients with head and neck squamous cell carcinoma (SCC) by ABC and ImmunoMax immunohistochemical method. Their clinical relevance and correlation were analysed. The expression of MMP 2, MMP 9, TIMP 1, CD44v6, HER2/neu and p53 was found in cancer cells in 87.01%, 85.71%, 68.18%, 98.05%, 55.19% and 50.65% cases respectively. Linear regression and correlation analysis revealed that there was close positive relationship ( P <0.05) between the expression of MMP 2 and MMP 9, TIMP 1 and CD44v6, HER2/neu and MMP 9, MMP 2 and p53. Up regulation of MMP 2 was accompanied by advanced T stage ( P <0.01) . There was also a trend of MMP 2 expression being related with tumor metastasis. Increased expression of HER2/neu was found in patients with tumor recurrence( P <0.05). The expression of TIMP 1 was higher in laryngeal cancer than that in pharyngeal cancer, and higher in keratinizing and non keratinizing SCC than that in basaloid SCC( P <0.05). These findings suggested that MMP 2 and MMP 9, HER2/neu and MMP 9, MMP 2 and p53 had a coordinate function in aggression of tumor; that MMP 2 had a more important function than MMP 9 in tumor invasion and metastasis; and that HER2/neu might serve as a biomarker for poor prognosis in HNSCC.

VTCN1调控结肠癌细胞长链非编码RNA和mRNA的全基因表达谱分析

目的·探讨含V-set域T细胞激活抑制因子(V-set domain containing T cell activation inhibitor 1,VTCN1)在结肠癌中对下游长链非编码RNA(long noncoding RNA,lncRNA)和mRNA的调控作用。方法·利用慢病毒质粒在结肠癌细胞株SW1116中过表达VTCN1,抽提RNA并测序,与阴性对照组比较分析差异表达的lncRNA和m RNA,并任意选取差异表达的lncRNA(3条)和mRNA(2条)进行实时定量PCR(qRT-PCR)验证RNA测序结果的准确性。通过BLAST2GO和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)分析预测这些差异表达lncRNA和m RNA的相关功能。利用线上平台GEPIA18(Gene Expression Profiling Interactive Analysis)分析差异表达lncRNA与结直肠癌患者生存期的相关性。结果·通过RNA测序在过表达VTCN1的SW1116细胞中发现了167条差异基因,包括39条lncRNA和128条m RNA。qRT-PCR检验结果与RNA测序结果变化趋势一致。生物信息学分析结果显示这些受VTCN1调控的差异基因可能参与了内质网中的蛋白处理、mRNA监控信号通路。另外,在过表达VTCN1的结肠癌细胞中明显上调的3条lncRNA(DNAJC9-AS1、HCG27和RP11-339B21.13),同时也是预测结直肠癌患者总生存期的独立因子。结论·在结肠癌细胞中VTCN1对下游多条lncRNA和mRNA具有调控作用,这些lncRNA和mRNA可能参与了内质网中的蛋白处理和mRNA监控信号通路。

Effects of Incretin-based Therapies on Weight-related Indicators among Patients with Type 2 Diabetes: A Network Meta-analysis

Objective To evaluate the effects of incretin-based therapies on body weight as the primary outcome,as well as on body mass index(BMI)and waist circumference(WC)as secondary outcomes.Methods Databases including Medline,Embase,the Cochrane Library,and clinicaltrials.gov(www.clinicaltrials.gov)were searched for randomized controlled trials(RCTs).Standard pairwise meta-analysis and network meta-analysis(NMA)were both carried out.The risk of bias(ROB)tool recommended by the Cochrane handbook was used to assess the quality of studies.Subgroup analysis,sensitivity analysis,meta-regression,and quality evaluation based on the Grading of Recommendations Assessment,Development,and Evaluation(GRADE)were also performed.Results A total of 292 trials were included in this study.Compared with placebo,dipeptidyl-peptidase IV inhibitors(DPP-4 Is)increased weight slightly by 0.31 kg[95%confidence interval(CI):0.05,0.58]and had negligible effects on BMI and WC.Compared with placebo,glucagon-like peptide-1 receptor agonists(GLP-1 RAs)lowered weight,BMI,and WC by-1.34 kg(95%CI:-1.60,-1.09),-1.10 kg/m2(95%CI:-1.42,-0.78),and-1.28 cm(95%CI:-1.69,-0.86),respectively.Conclusion GLP-1 RAs were more effective than DPP-4 Is in lowering the three indicators.Overall,the effects of GLP-1 RAs on weight,BMI,and WC were favorable.

Sitagliptin counteracts seasonal fluctuation of glycemic control

AIM:To assess the effect of sitagliptin therapy on seasonal fluctuation of glycemic control in Japanese type 2 diabetic patients.METHODS:Participating patients(age:29-80 years) had been treated with conventional oral antidiabetic agents and/or diet and exercise therapy for over 6 mo.From December 2009,35 patients were additionally prescribed oral sitagliptin starting from 50 mg once daily,while 19 patients taking-glucosidase inhibitors were switched to sitagliptin.Twenty-four patients who refused sitagliptin formed the control group.Changes of mean monthly hemoglobin A 1c(HbA 1c) during the "winter holiday season" were compared between groups using Student's t-test(2008-2009 vs 2009-2010).Statistical significance was accepted at P < 0.05.Multivariate analysis was performed to assess whether sitagliptin use was associated with deterioration or improvement of glycemic control.RESULTS:Both add-on sitagliptin and switching from-glucosidase inhibitors to sitagliptin prevented the seasonal deterioration of glycemic control and tended to improve HbA 1c.Multivariate analysis revealed that both adding and switching to sitagliptin were negatively correlated with deterioration of glycemic control.In 44 patients who continued sitagliptin therapy for another year,elevation of HbA 1c was suppressed without adverse effects.CONCLUSION:Sitagliptin is a suitable oral agent for preventing deterioration of glycemic control during the winter holiday season.

免疫检查点抑制剂治疗驱动基因阳性晚期非小细胞肺癌的研究进展

免疫检查点抑制剂(immune checkpoint inhibitors,ICIs)已成为晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)的重要治疗方法,但其在驱动基因阳性患者中的疗效仍存在争议。现有研究显示:ICIs的疗效可能与不同的驱动基因类型、程序性死亡蛋白-配体1(programmed cell death-ligand 1,PD-L1)表达水平、肿瘤突变负荷(tumor mutational burden,TMB)等相关,同时可能需要参考其他因素,如临床特征、免疫细胞密度等。ICIs单药或联合治疗可能会在一部分驱动基因阳性NSCLC患者中发挥作用,但仍需要进一步研究来筛选出这些患者,这或许是晚期NSCLC治疗未来发展的一个重要方向。

D-D、PS、FⅤ、t-PAI-C预测产妇分娩后血栓前状态及血栓发生的价值

目的探究D-二聚体(D-D)、蛋白S(PS)、凝血因子(F)Ⅴ、组织纤溶酶原激活物-纤溶酶原激活物抑制剂-1复合物(t-PAI-C)预测产妇分娩后血栓前状态(PTS)及血栓发生的价值。方法选择2021年9月—2022年8月分娩产妇122例,术后均进行超声检查,根据是否发生PTS,分为阳性组(n=53)及阴性组(n=69),比较2组的D-D、PS、FⅤ、t-PAI-C水平,分析4项指标对PTS的预测价值。根据术后是否发生静脉血栓栓塞(VTE)分为VTE组(n=21)及未发生组(n=101),比较2组D-D、PS、FⅤ、t-PAI-C水平,分析4项指标对VTE诊断价值。结果阳性组的D-D、FⅤ、t-PAI-C水平均高于阴性组,PS水平低于阴性组,差异有统计学意义(P<0.05);采用ROC曲线分析,4项指标联合预测产后PTS的AUC为0.985,均高于单一的D-D、PS、FⅤ及t-PAI-C的0.795、0.837、0.815、0.824(P<0.05);VTE组D-D、FⅤ、t-PAI-C水平均高于非VTE组,PS水平低于非VTE组,差异有统计学意义(P<0.05);D-D、PS、FⅤ、t-PAI-C联合对VTE诊断的灵敏度、特异度、准确率分别为85.71%、92.08%、90.98%,Kappa值为0.711。结论D-D、PS、FⅤ、t-PAI-C联合检测有助于预测产后PTS发生,并为VTE诊断提供参考,有助于临床防治PTS及VTE的发生。

多基因突变在不同种族人群深静脉血栓形成中的研究现状

静脉血栓栓塞症是指血液在静脉系统中凝聚后形成的一种半固体栓子,其原因是纤维蛋白溶解和血栓形成之间平衡的破坏。凝血因子V Leiden突变(FVL),凝血酶原G20210A(FⅡG20210A),5,10-亚甲基四氢叶酸还原酶(MTHFR),纤溶酶原激活物抑制药-1(PAI-1)等基因多态性是可以用于评估VTE患病风险的常见的分子生物标记物。鉴于FVL,FⅡG20210A,MTHFR,PAI-1等基因突变存在地域性差异,本文就不同种族间这四种基因多态性的国内外研究进展作一综述。