肿瘤免疫检查点抑制剂相关的肝毒性

肿瘤免疫检查点抑制剂治疗为肿瘤患者带来生存获益的同时,也面临了许多挑战,例如免疫介导的肝毒性的发生。深入了解免疫检查点抑制剂治疗肿瘤过程中导致肝损伤的发生情况、可能机制、危险因素等,有助于更好地临床管理。     

Specific alterations in plasma proteins during depressed,manic, and euthymic states of bipolar disorder

Bipolar disorder (BD) is a common psychiatric mood disorder affecting more than 1-2% of the general population of different European countries. Unfortunately, there is no objective laboratory-based test to aid BD diagnosis or monitor its progression, and little is known about the molecular basis of BD. Here, we performed a comparative proteomic study to identify differentially expressed plasma proteins in various BD mood states (depressed BD, manic BD, and euthymic BD) relative to healthy controls. A total of 10 euthymic BD, 20 depressed BD, 15 manic BD, and 20 demographically matched healthy control subjects were recruited. Seven high-abundance proteins were immunodepleted in plasma samples from the 4 experimental groups, which were then subjected to proteome-wide expression profiling by two-dimensional electrophoresis and matrix-assisted laser desorption/ionization-time-of-flight/time-of-flight tandem mass spectrometry. Proteomic results were validated by immunoblotting and bioinformatically analyzed using MetaCore. From a total of 32 proteins identified with 1.5-fold changes in expression compared with healthy controls, 16 proteins were perturbed in BD independent of mood state, while 16 proteins were specifically associated with particular BD mood states. Two mood-independent differential proteins, apolipoprotein (Apo) A1 and Apo L1, suggest that BD pathophysiology may be associated with early perturbations in lipid metabolism. Moreover, down-regulation of one mood-dependent protein, carbonic anhydrase 1 (CA-1), suggests it may be involved in the pathophysiology of depressive episodes in BD. Thus, BD pathophysiology may be associated with early perturbations in lipid metabolism that are independent of mood state, while CA-1 may be involved in the pathophysiology of depressive episodes.     

死亡结构域相关蛋白及其在宫颈病变中的研究进展

宫颈癌对妇女健康构成严重威胁,人乳头瘤病毒感染与宫颈病变及宫颈癌的发生密切相关。关于宫颈癌发生发展的机制仍在研究中。近年研究发现一种多功能核蛋白,即死亡结构域相关蛋白(death domain associated protein,Daxx),其与细胞内蛋白或病毒蛋白相互作用,参与调节细胞凋亡、转录调控、抗病毒等细胞活动,在不同途径中发挥不同的生理或病理作用。通过对Daxx功能及其作用机制的研究有助于进一步阐明宫颈癌发生发展的机制,有助于发现新的预防和治疗方法。综述Daxx的一般特性和研究现况及其在宫颈病变的研究进展。     

利用CNV-seq技术产前诊断Pallister-Killian综合征胎儿一例

应用拷贝数变异测序(copy number variation sequencing,CNV-seq)技术鉴别来源不明的胎儿标记染色体,明确其遗传物质的来源,并探讨此技术在产前诊断中的应用价值。讨论Pallister-Killian综合征(Pallister-Killian syndrome,PKS)的临床特征及遗传学特点,提高对此类罕见染色体疾病的认识。该病例因在妊娠中期超声发现胎儿异常而行羊水穿刺进行CNV-Seq检测,同时分析胎儿和父母的核型。羊水CNV-Seq结果示该样本12号染色体p13.33-p11.1处检测到拷贝数为3.5、片段大小为34.70 Mb的嵌合重复区域;羊水染色体核型结果为47,XY,+i(12)(p10)[58]/46,XX[42],综合上述结果考虑为PKS。通过结合超声结果,综合应用染色体G显带核型分析和CNV-seq技术能准确确认染色体异常片段来源,在产前有效诊断PKS患者。     

D6S1043、D12S391基因座与主动攻击行为的关联研究

目的:探讨D6S1043、D12S391基因座的基因多态性对主动攻击行为的影响。方法:应用聚合酶链反应技术结合毛细管电泳法对114例男性主动攻击行为者(研究组)及120名健康男性(对照组)进行D6S1043、D12S391基因座的基因型及等位基因检测,分析D6S1043、D12S391基因座多态性与主动攻击行为的相关性。结果:研究组D6S1043基因座中12~19基因型频率(13.16%)明显高于对照组(1.67%)(P0.05);两组等位基因频率差异无统计学意义;两组D12S391基因座的基因型及等位基因频率差异无统计学意义。结论:D6S1043基因座中12~19基因型可能主动攻击行为有关。