介导肿瘤多药耐药的ATP结合盒转运体的研究进展

多药耐药（MDR）是阻碍肿瘤化疗成功的一大障碍,其机制之一就是耐药的肿瘤细胞高表达三磷酸腺苷（ATP）结合盒（ABC）转运体。依据此机制提出克服肿瘤细胞耐药的策略即开发外排转运体抑制剂,以期逆转MDR。最近的研究发现肿瘤干细胞也可能是通过表达外排转运体天然耐药,这就提供了一个新的抗癌药物作用靶点。对介导肿瘤细胞多药耐药的ABC转运体及其抑制剂的开发作一综述。     

Selective enrichment of sialylated glycopeptides with a d-allose@SiO2 matrix

Abnormal sialylation of glycoprotein is associated with different kinds of cancers and neurodegenerative diseases. However, analysis of low abundance sialylated glycopeptides (SGPs) from complex biological samples is still a big challenge. To solve the problem, materials with high SGPs enrichment selectivity should be designed and prepared. Inspired by the saccharide–saccharide interaction in life systems, a d-allose@SiO₂ (ABS) material was prepared and applied in SGPs enrichment under hydrophilic interaction liquid chromatography (HILIC) mode. Fourier-transform infrared (FTIR) spectroscopy, scanning electron microscope (SEM), and nitrogen adsorption experiment results proved that the ABS matrix was successfully synthesized. The SGPs enrichment selectivity of ABS matrix was evaluated with Nano Electrospray Ionization Quadrupole Time-of-Flight Mass Spectrometry (Nano ESI Q-TOF/MS). The results indicated that the SGPs enrichment selectivity was notably higher with the ABS matrix (24 SGPs) than the commercially available Sepharose CL-6B (9 SGPs) and TiO₂ (8 SGPs), taking digests of fetuin/bovine serum albumin (BSA) (1 : 10, w/w) as the test sample. The SGPs enrichment performance of ABS matrix was further validated by the interference, recovery rate, and reproducibility evaluation experiments. In the end, the ABS matrix was applied in the analysis of real biosample (HeLa cell lysates). Totally 301 SGPs with 277 glycosylation sites from 186 glycoprotein were successfully characterized by taking HeLa S3 cell lysate as target sample in two replicated experiments. The results indicated that the ABS matrix had great potential to be applied in the enrichment of SGPs from complex biological samples.

Abnormal sialylation of glycoprotein is associated with different kinds of cancers and neurodegenerative diseases.     

三维斑点追踪技术评价冠状动脉病变严重程度

目的 探讨三维斑点追踪成像（3D-STI）技术评价冠状动脉粥样硬化性心脏病（简称冠心病）患者冠状动脉病变程度的价值。方法 收集103例疑似冠心病患者,参考冠状动脉造影结果,根据冠状动脉Gensini评分,将其分为病变组（n=79）和正常组（Gensini评分0分,n=24）,病变组又分为轻度（Gensini评分<25分,n=40）、中度（Gensini评分25~50分,n=26）和重度（Gensini评分>50分,n=13）3个亚组。应用3D-STI技术获得左心室三维整体纵向应变（3D-GLS）、三维整体周向应变（3D-GCS）、三维整体面积应变（3D-GAS）和三维整体径向应变（3D-GRS）,比较2组间和3个亚组间的差异。绘制ROC曲线,评价3D-STI参数评价冠状动脉正常或轻度病变（Gensini评分<25分）与中重度病变（Gensini评分≥25分）的效能。结果 病变组3D-GLS、3D-GCS、3D-GAS及3D-GRS均低于正常组（P均<0.05）。病变组内轻度、中度与重度亚组间各应变参数总体差异均有统计学意义（P均<0.05）。ROC曲线结果显示,AUC由大到小依次为3D-GLS（0.929）、3D-GCS（0.873）、3D-GRS（0.853）和3D-GAS（0.819）。结论 3D-STI技术用于评价冠心病患者冠状动脉病变严重程度具有一定价值。     

高频超声评价2型糖尿病患者下肢周围神经病变临床观察

目的探讨高频超声用于评价2型糖尿病合并周围神经病变患者下肢股神经和隐神经异常改变的临床价值。方法共81例2型糖尿病患者分为无周围神经病变组(40例)和合并周围神经病变组(41例),通过彩色多普勒超声观察股神经和隐神经内部回声及连续性,测量并比较神经宽径、厚径和横截面积。结果正常对照组受试者股神经和隐神经横切面扫描呈略高回声,内部呈细小筛网格状,纵切面扫描内部呈条状低回声和平行线样排列的条状略高回声;无周围神经病变组患者内部回声略减低,细小筛网格状结构模糊,纵切面条状低回声结构欠清晰;合并周围神经病变组患者内部回声明显减低,细小筛网格状结构显示不清,纵切面条状低回声结构模糊。与正常对照组相比,糖尿病组患者股神经宽径(均P=0.000)、厚径(P=0.023,0.036)和横截面积(均P=0.000)增大;隐神经宽径(P=0.010,0.014)、厚径(均P=0.001)和横截面积(P=0.002,0.004)增大;合并周围神经病变组患者股神经和隐神经厚径(P=0.048,0.012)和横截面积(P=0.031,0.034)较无周围神经病变组增大。结论高频超声可以清晰地显示2型糖尿病合并周围神经病变患者股神经和隐神经主干内部回声及各径线的异常改变,为临床诊断提供客观依据,具有重要临床意义。     

微创软通道技术与外科开颅治疗大量基底节去脑出血疗效比较

目的探讨微创软通道技术与外科开颅手术治疗高血压性大量基底节区脑出血的临床疗效比较。方法采用回顾性分析方法,收集我院神经ICU及神经外科收治的大量基底节脑出血（70—100mL）手术治疗患者85例,其中外科开颅组40例和微创手术组45例。对两组治疗效果进行回顾性分析。结果两组患者术后2周GCS评分、术后3个月死亡率、mRs评分,无显著性差异P〈0．05。住院住院费用,及住院天数,微创手术组显著优于外科开颅组,两者具有显著性差异（P〈0．05）。结论对于大量基底节区脑出血患者而言,微创手术与去骨瓣手术疗效无差异,但是较去骨瓣手术减少住院天数以及住院费用。故微创手术是外科去骨瓣手术的较好的替代方案。     

多房囊性肾细胞癌与复杂性肾囊肿的CT鉴别

目的:探讨多房囊性肾细胞癌(MCRCC)与复杂性肾囊肿(CRC)的CT特点,为疾病的鉴别诊断提供依据。方法:回顾性分析66例MCRCC与CRC患者的CT特征,包括肿物直径、分隔、钙化、结节等。结果:17.4%的MCRCC、46.5%的CRC显示钙化(P=0.038);69.5%的MCRCC、21.1%的CRC有分隔(P=0.000);26.1%的MCRCC、4.7%的CRC有结节(P=0.032);38.1%的MCRCC、10.5%的CRC有囊壁强化(P=0.029);MCRCC组肿物直径CRC组(P=0.007);logistic回归显示多分隔(P=0.011)、囊壁强化(P=0.039)为独立预测因子。结论:钙化、分隔、结节、肿物直径在两组鉴别上具有意义;多分隔、囊壁强化是两组鉴别最有价值的特征。     

Dioscin protects against diabetic nephropathy by inhibiting renal inflammation through TLR4/NF-κB pathway in mice

Diabetic nephropathy (DN) is a chronic kidney disease caused by the long-term loss of renal function, which occurs in 20% - 40% of all diabetes and is also the primary cause of end-stage renal diseases. DN is related with other lethal diseases, particularly cardiovascular diseases, leading to an increased risk of death. Therefore, an effective treatment for DN is required. Here we tested the protective effect of dioscin in a mouse model of streptozocin (STZ)-induced DN. First, STZ was intraperitoneally injected into C57BL/6 J mice and TLR4^-/- mice respectively, on a daily basis for 5 days to induce diabetes. Dioscin was then orally administered into diabetic mice daily for 8 weeks. Our results show that STZ injection effectively induced diabetes in mice as indicated by the increased blood glucose levels in C57BL/6 J mice, whereas it did not cause diabetes in TLR4^-/- mice. Dioscin significantly ameliorated STZ-induced renal damage via reducing inflammatory responses in diabetic mice and antagonizing the activation of TLR4/NF-κB pathway and the production of inflammatory cytokines. In conclusion, our study highlights the potential of dioscin as a novel approach to treat DN in diabetic patients.     

Asxl1在炎性微环境中对成骨细胞增殖分化的作用

背景:研究表明Asxl1的缺失可导致骨质发育不全、骨质缺损类疾病的发生,但目前在根尖周炎环境下该因子与骨破坏之间的关系暂无相关报道。目的:探讨炎性微环境下Asxl1对成骨细胞增殖分化的影响。方法:实验选用脂多糖刺激MC3T3-E1细胞建立体外炎性微环境,通过CCK-8实验筛取脂多糖最佳质量浓度和最佳作用时间,然后用20 mg/L脂多糖刺激MC3T3-E1细胞24 h,免疫荧光检测Asxl1的蛋白表达水平,Real Time-PCR检测Asxl1 mRNA的表达水平。为进一步验证Asxl1基因在炎性微环境中影响成骨细胞的增殖与分化,脂多糖刺激形成炎性微环境后转染Asxl1-SiRNA 24 h,采用CCK-8检测细胞增殖活性,RealTime-PCR检测Asxl1及成骨相关基因ALP和RUNX2 mRNA的表达水平。结果与结论:①脂多糖刺激MC3T3-E1细胞后,Asxl1蛋白和mRNA表达水平呈降低趋势;②脂多糖刺激MC3T3-E1细胞后,转染Asxl1-SiRNA 24 h,细胞增殖活性下降趋势明显,Asxl1基因及成骨相关基因ALP和RUNX2 mRNA的表达水平明显降低;③结果提示,Asxl1可能通过参与炎性反应过程,影响成骨细胞的增殖与分化,进而参与骨破坏进程。     

Collagen scaffolds modified with CNTF and bFGF promote facial nerve regeneration in minipigs

Most experiments of peripheral nerve repair after injury have been conducted in the rodent model but the translation of findings from rodent studies to clinical practice is needed partly because the nerve regeneration must occur over much longer distances in humans than in rodents. The reconstruction of long distance nerve injuries still represents a great challenge to surgeons who is engaged in peripheral nerve surgery. Here we used the functional nerve conduit (collagen scaffolds incorporated with neurocytokines CNTF and bFGF) to bridge a 35 mm long facial nerve gap in minipig models. At 6 months after surgery, electrophysiology assessment and histological examination were conducted to evaluate the regeneration of peripheral facial nerves. Based on functional and histological observations, the results indicated that the functional collagen scaffolds promoted nerve reconstruction. The number and arrangement of regenerated nerve fibers, myelination, and nerve function reconstruction was better in the CNTF + bFGF conduit group than the single factor CNTF or bFGF conduit group. The functional composite conduit, which exhibited favorable mechanical properties, may promote facial nerve regeneration in minipigs effectively.