Ⅱ型Waardenburg综合征患儿二例基因诊断分析

目的通过对2例中国云南地区Ⅱ型Waardenburg综合征(WS2)患儿相关基因突变位点的分析,探讨WS2可能的分子生物学致病原因。方法经知情同意,分别于2018年10月和2019年5月对2例WS2先证者及家系成员进行病史采集、体格检查、听力学评估及颞骨CT检查。获取外周血,提取基因组DNA, 高通量测序方法对MITF、PAX3、SOX10、SNAI2、END3、ENDRB、KITLG基因编码区的全部外显子及部分内含子和启动子进行检测,对先证者及其父母进行突变位点的Sanger测序验证分析。结果先证者1检测出MITF基因第7外显子c.641643delGAA突变,导致氨基酸改变p.214delR,为整码移码突变,患儿双亲MITF基因序列测序分析该位点无变异,此位点为自发突变。先证者2检测出MITF基因1~9号外显子大片段杂合缺失,影响蛋白质功能的正常发挥。结论基因诊断是确诊Waardenburg综合征的重要依据,MITF基因c.641643delGAA杂合突变和MITF基因1~9号外显子大片段杂合缺失可能是本研究2例WS2患儿的分子生物学致病原因。     

丙泊酚目标靶控输注用于颅内动脉瘤介入治疗麻醉诱导的临床观察

目的 观察丙泊酚目标靶控输注用于颅内动脉瘤介入治疗麻醉诱导过程中对血流动力学的影响.方法 择期行颅内动脉瘤介入治疗患者90例,按随机数字表法分为三组：对照组（C组）、血浆药物浓度靶控输注组（P组）和效应室药物浓度靶控输注组（E组）,每组30例.C组采用丙泊酚2 mg/kg单次静脉推注;P组设定丙泊酚血浆靶浓度为4μg/ml;E组设定丙泊酚效应室靶浓度为4 μg/m],三组均采用瑞芬太尼浓度为4 ng/ml的血浆靶控输注,静脉推注顺阿曲库铵0.2 mg/kg.持续监测呼气末二氧化碳分压、脑电双频指数、平均动脉压（MAP）、心率（HR）、心电图、脉搏血氧饱和度及生命体征.记录各组患者诱导前（T0）、插管即刻（T1）、插管后1 min （T2）、3 min（T3）、5 min（T4）、10 min（T5）的MAP和HR,记录血流动力学异常发生率及血管活性药物使用情况.结果 三组T0时MAP及HR比较差异无统计学意义（P＞0.05）.三组T1时MAP及HR均显著低于本组T0,差异有统计学意义（P＜0.05）;P组T1时MAP及HR显著低于E组和C组,差异有统计学意义（P＜0.05）.P组使用血管活性药物例数显著低于C组[6.7％（2/30）比40.0％（12/30）],差异有统计学意义（P＜0.01）.结论 丙泊酚血浆药物浓度作为目标靶控输注浓度更适合颅内动脉瘤介入手术患者的麻醉诱导.     

High-content analysis for mitophagy response to nanoparticles: A potential sensitive biomarker for nanosafety assessment

Mitophagy, a selective autophagy of mitochondria, clears up damaged mitochondria to maintain cell homeostasis. We performed high-content analysis (HCA) to detect the increase of PINK1, an essential protein controlling mitophagy, in hepatic cells treated with several nanoparticles (NPs). PINK1 immunofluorescence-based HCA was more sensitive than assays and detections for cell viability and mitochondrial functions. Of which, superparamagnetic iron oxide (SPIO)-NPs or graphene oxide-quantum dots (GO-QDs) was selected as representatives for positive or negative inducer of mitophagy. SPIO-NPs, but not GO-QDs, activated PINK1-dependent mitophagy as demonstrated by recruitment of PARKIN to mitochondria and degradation of injured mitochondria. SPIO-NPs caused the loss of mitochondrial membrane potential, decrease in ATP, and increase in mitochondrial reactive oxide species and Ca²⁺. Blocking mitophagy with PARKIN siRNA aggravated the cytotoxicity of SPIO-NPs. Taken together, PINK1 immunofluorescence-based HCA is considered to be an early, sensitive, and reliable approach to evaluate the bioimpacts of NPs.     

HIV vulnerabilities and coercive sex at same-sex sexual debut among men who have sex with men in Beijing,China

Few studies have examined coercive sex and HIV vulnerabilities among men who have sex with men (MSM) in China. The present study seeks to compare individual characteristics between MSM who did and did not experience coercive sex at their MSM sexual debut and to identify HIV risk factors correlated with coercive sex at MSM sexual debut. In 2007, we recruited 167 MSM in Beijing, China by peer-referred social network sampling. Each participant then completed self-administered questionnaires regarding their sexual experiences and practices. Results show that 14% of participants reported coercive sex at MSM sexual debut, of whom 48% reported recent unprotected anal intercourse (UAI). Coercive sex at MSM sexual debut was significantly associated with UAI [adjusted odds ratio (AOR): 5.38, 95% confidence interval: 1.95–14.87] and lifetime number of male sex partners (AOR: 7.25, 95% CI: 2.39–22.01). Coercive sex is harming MSM in China and should be immediately addressed by researchers, public health officials, and MSM community stakeholders.     

Reactive oxygen species up-regulates SOCS-3 in 3T3-L1 adipocytes

We investigated the effect of increased intracellular reactive oxygen species(ROS) on SOCS-3 expression in 3T3-L1 adipocytes. Increased intracellular ROS levels in 3T3-L1 adipocytes were achieved by two methods of exposure to H2O2 and the occurrence of oxidative stress in cells was assessed by flow cytometry . Expression of SOCS-3 mRNA and that of some adipokines were measured by real time PCR. The level of SOCS-3 protein was determined by western blot. The effect of the antioxidant alpha-lipoic acid was also investigated. Both the relatively mild increased intracellular ROS and the acute but transient increased ROS elevated the levels of SOCS-3 mRNA and protein in 3T3-L1 adipocytes, acompanied with elevated levels of TNF-α mRNA and resistin mRNA and the decreased levels of adiponectin mRNA and secretory adiponectin in culture medium. α-lipoic acid could attenuate the effects of ROS on 3T3-L1 adipocytes. We hypothesized that in mature 3T3-L1 adipocytes, SOCS-3 could be upregulated directly by the induction of increased intracellular ROS and to some extent which was up-regulated by adipokine modulation.

     

BAY 11-7082, a nuclear factor-κB inhibitor,induces apoptosis and S phase arrest in gastric cancer cells

Background

Inhibitors of nuclear factor (NF)-κB pathway have shown potential anti-tumor activities. However, it is not fully elucidated in gastric cancer.

Methods

Firstly, we screened the inhibitory effect of pharmacologic NF-κB inhibitors on cell viability of human gastric cancer cells via CCK-8 assay. Next, cell apoptosis, cell cycle distribution, and mitochondrial membrane potential after BAY 11-7082 treatment were detected by annexin V staining, propidium iodide staining, TUNEL, and JC-1 assays in human gastric cancer HGC-27 cells. Expression of regulatory factors for apoptosis and cell cycle were measured by western blot. Finally, human gastric cancer xenograft model was established to verify the anti-tumor effects of BAY 11-7082 in vivo. Cellular apoptosis and growth inhibition in subcutaneous tumor section were detected by TUNEL and immunohistochemistry assays.

Results

BAY 11-7082 exhibited rapid and potent anti-tumor effects on gastric cancer cells in vitro within a panel of NF-κB inhibitors. BAY 11-7082 induced rapid apoptosis in HGC-27 cells through activating the mitochondrial pathway, as well as down-regulation of Bcl-2 and up-regulation of Bax. BAY 11-7082 also induced S phase arrest through suppressing Cyclin A and CDK-2 expression. Xenograft model confirmed the anti-tumor effects of BAY 11-7082 on apoptosis induction and growth inhibition in vivo.

Conclusions

Our results demonstrated that BAY 11-7082 presented the most rapid and potent anti-tumor effects within a panel of NF-κB inhibitors, and could induce cellular apoptosis and block cell cycle progression both in vitro and in vivo, thus providing basis for clinical application of BAY 11-7082 in gastric cancer cases.     

一体化PET/MR结合统计参数图辅助^11C-PIB显像的半定量分析及其临床应用

目的 研究一体化PET/MR结合统计参数图(SPM)辅助^11C-匹兹堡化合物B(PIB)用于β-淀粉样蛋白(Aβ)PET显像半定量分析的准确性,探索其用于认知障碍的诊断及鉴别诊断的可行性.方法 回顾分析2018年1月至2019年9月在华中科技大学同济医学院附属协和医院PET中心进行^11C-PIB PET/MR扫描,临床最终确诊的13例阿尔茨海默病(AD)患者[男4例,女9例;年龄(59.2±5.8)岁]和10例血管性认知障碍(VCD)患者[男9例,女1例;年龄(59.5±11.5)岁].结合三维T1加权成像(3D T1WI)对^11C-PIB PET图像分别进行脑区手动勾画和SPM辅助半自动分割,获得8个关键脑区(大脑白质、纹状体、丘脑、后扣带回、额叶皮质、后顶叶皮质、颞叶外侧皮质和枕叶皮质)与小脑皮质的标准摄取值比值(SUVR).对2种方法所获结果进行Pearson相关分析;采用两独立样本t检验、配对t检验分析数据.结果 AD组与VCD组患者的年龄和简易精神状态检查量表(MMSE)评分[(19.7±4.7)和(21.7±3.8)分]差异均无统计学意义(t值:0.095和1.098,均P>0.05).除丘脑外(r=0.179,P=0.413),分割法和勾画法在其余7个关键脑区获得的SUVR均有良好的相关性(r值:0.678~0.893,均P<0.05).AD组8个关键脑区的SUVR均明显高于VCD组(1.519~2.055与1.105~1.618;t值:2.799~11.582,均P相似文献   

Correction to: Associations between serumIL-8 and knee symptoms,joint structures,and cartilage or bone biomarkers in patients with knee osteoarthritis

Clinical Rheumatology - There were overlaps between the article recently published in this journal [1] and the previous publications from the authors’ group [2-4] that they did not cite.]