Baicalin induces ferroptosis in bladder cancer cells by downregulating FTH1

Ferroptosis is a non-apoptotic regulated cell death caused by iron accumulation and subsequent lipid peroxidation. Currently, the therapeutic role of ferroptosis on cancer is gaining increasing interest. Baicalin an active component in Scutellaria baicalensis Georgi with anticancer potential various cancer types; however, the effects of baicalein on bladder cancer and the underlying molecular mechanisms remain largely unknown. In the study, we investigated the effect of baicalin on bladder cancer cells 5637 and KU-19-19. As a result, we show baicalin exerted its anticancer activity by inducing apoptosis and cell death in bladder cancer cells. Subsequently, we for the first time demonstrate baicalin-induced ferroptotic cell death in vitro and in vivo, accompanied by reactive oxygen species (ROS) accumulation and intracellular chelate iron enrichment. The ferroptosis inhibitor deferoxamine but not necrostatin-1, chloroquine (CQ), N-acetyl-l-cysteine, l-glutathione reduced, or carbobenzoxy-valyl-alanyl-aspartyl-[O-methyl]-fluoromethylketone (Z-VAD-FMK) rescued baicalin-induced cell death, indicating ferroptosis contributed to baicalin-induced cell death. Mechanistically, we show that ferritin heavy chain 1 (FTH1) was a key determinant for baicalin-induced ferroptosis. Overexpression of FTH1 abrogated the anticancer effects of baicalin in both 5637 and KU19-19 cells. Taken together, our data for the first time suggest that the natural product baicalin exerts its anticancer activity by inducing FTH1-dependent ferroptosis, which will hopefully provide a prospective compound for bladder cancer treatment.     

抗IgE单克隆抗体治疗难治性鼻窦炎伴鼻息肉三例

鼻息肉是鼻腔和鼻窦黏膜最常见的慢性变态反应相关疾病之一,难治性鼻窦炎伴鼻息肉常合并哮喘,手术和药物治疗都很难控制病情。奥马珠单克隆抗体是人源性IgE单克隆抗体,国外已有应用IgE单克隆抗体治疗鼻息肉,特别是哮喘合并鼻息肉的报道。本研究对3例哮喘合并慢性鼻窦炎伴鼻息肉（CRSwNP）的患者采用奥马珠单克隆抗体治疗,随访1...     

逆转录病毒载体介导人GM－CSF基因转染肿瘤细胞

应用逆转录病毒载体ｐＺＩＰＮｅｏＳＶ（Ｘ）介导人ＧＭ－ＣＳＦ基因转染肿瘤细胞获得表达。经Ｌｉｐｏｆｅｃｔｉｎ将含有人ＧＭ－ＣＳＦ基因的重组逆转录病毒载体ｐＺＩＰ－ＧＭ转染兼性病毒包装细胞系ＰＡ３１７，继之用病毒收获液感染人肝癌细胞ＳＭＭＣ７７２１和人胃癌ＢＧＣ－８２３，经ＧＭ－ＣＳＦ依赖细胞株ＴＦ１测活和双抗体夹心法ＥＬＩＳＡ测定表明：人ＧＭ－ＣＳＦ基因在人肿瘤细胞中获得稳定高效表达。为进─步建立ＧＭ－ＣＳＦ的转基因治疗模型提供了基础。     

Gene therapy by membrane-expressed superantigen for alpha-fetoprotein-producing hepatocellular carcinoma

Staphylococcus enterotoxin A (SEA) is a powerful immunostimulant, which can stimulate T cells bearing certain T-cell receptor beta-chain variable regions, when bound to major histocompatibility complex II molecules. In vivo administration of intact superantigen in sufficient therapeutic amounts risks unwanted cytotoxicity against normal cells. In this study, we used SEA fused with CD80 transmembrane region (named as SEAtm) driven by alpha-fetoprotein (AFP) enhancer/promoter to reduce toxicity and to improve safety and efficiency in the application of SEA. We demonstrated that SEAtm by adenovirus from the AFP enhancer/promoter (AdAFPSEA) could be expressed on the surface of AFP-producing cell line Hepa1-6 instead of non-AFP-producing cell lines. Hepa1-6 infected by recombinant adenovirus stimulated proliferation of splenocytes and activated CD4(+) and CD8(+) T cells in vitro. After AdAFPSEA was injected into the subcutaneously established hepatoma in vivo, the expression of SEA was detected in tumor tissues, which subsequently induced tumor-specific cytotoxic T cells in spleen. Moreover, hepatocellular carcinoma (HCC) xenografts were suppressed by treatment with AdAFPSEA and the survival time of treated mice was prolonged. These findings suggest that membrane-expressed SEA by adenovirus from AdAFPSEA can generate stronger local and systemic antitumor responses against HCC.     

碱性成纤维生长因子在膀胱移行细胞癌中的免疫组化研究

目的：探讨碱性成纤维生长因子（bFGF）在磅脱移行细胞癌（BTCC）中表达的意义。方法：应用免疫组化ABC法对33例BTCC及12例正常膀胱组织中bFGF抗原进行检测。结果：bFGF在正常移行细胞呈阴性表达．在肿瘤细胞、血管内皮细胞、肌细胞中呈阳性表达,且在肿瘤细胞中的过表达率与不同病理分级、临床分期密切相关（P＜0．05）,在单发与多发,初发与复发组间无显著性差异（P＞0．05）。结论：bFGF在BTCC浸润转移过程中起重要作用,可为综合治疗提供新途径。     

Complete Genome Sequence of Herpes Simplex Virus 2 Strain G

Herpes simplex virus type 2 (HSV-2) is a common causative agent of genital tract infections. Moreover, HSV-2 and HIV infection can mutually increase the risk of acquiring another virus infection. Due to the high GC content and highly repetitive regions in HSV-2 genomes, only the genomes of four strains have been completely sequenced (HG52, 333, SD90e, and MS). Strain G is commonly used for HSV-2 research, but only a partial genome sequence has been assembled with Illumina sequencing reads. In the current study, we de novo assembled and annotated the complete genome of strain G using PacBio long sequencing reads, which can span the repetitive regions, analyzed the ‘α’ sequence, which plays key roles in HSV-2 genome circulation, replication, cleavage, and packaging of progeny viral DNA, identified the packaging signals homologous to HSV-1 within the ‘α’ sequence, and determined both termini of the linear genome and cleavage site for the process of concatemeric HSV-2 DNA produced via rolling-circle replication. In addition, using Oxford Nanopore Technology sequencing reads, we visualized four HSV-2 genome isomers at the nucleotide level for the first time. Furthermore, the coding sequences of HSV-2 strain G have been compared with those of HG52, 333, and MS. Moreover, phylogenetic analysis of strain G and other diverse HSV-2 strains has been conducted to determine their evolutionary relationship. The results will aid clinical research and treatment development of HSV-2.     

ICP-MS用于羌活药材亲缘关系的分析研究

目的:对6个具有代表性的不同产地、不同采收期的羌活药材中无机元素的含量进行测定,通过数学统计软件分析,确立不同采收期羌活药材无机元素含量差别和不同产地羌活药材的亲缘关系,为建立中药微量元素与药效之间的关系打下一定的基础。方法:药材经微波消解仪消解处理后,利用电感耦合等离子体质谱对其微量元素进行检测。结果:测得羌活药材质荷比在2～260之间元素含量。结论:经数学软件统计后,以59种经过筛选的无机元素作为特征值,聚类统计后得不同采收期药材无机元素对羌活药材含量差异影响不大,但不同产地对羌活药材含量差异影响较大。本溪和贵州产的羌活药材被聚为一类,其次是湖南产羌活,再次是新疆伊犁产,丹东、四川产的羌活药材被聚为另一类。通过相关文献查阅和调研,湖南、新疆伊犁、本溪和贵州产的羌活药材亲缘关系较为接近,丹东和四川产的羌活药材亲缘关系较为接近。     

应用Bayesian反馈法预测阿替洛尔药代动力学参数及血药浓度

应用Bayesian反馈法,预测21例高血压病人口服阿替洛尔的个体药动学参数及稳态血药浓度C_(pss),并与经典药动学方法估算的结果比较。本法的T_(1/2)为(6.0±1.7)h,Vd为(1.43±0.13)L/kg,CL为(172±34)ml·h~(-1)·kg~(-1);经典法的T_(1/2)为(6.8±2.4)h,Vd为(1.45±0.56)L/kg,CL为(164±85)ml·h~(-1)·kg~(-1)。两者无显著性差异(P>0.05),两法所测得C_(pss)有较好相关性(r=0.993)。     

Off-pump Coronary Endarterectomy and Bypass Grafting in Patients With Diffuse Coronary Artery Disease

Coronary artery bypass grafting (CABG) and percutaneous coronary intervention are effective therapeutic modalities for patients with ischemic heart disease. However, many patients referred for CABG nowadays had experienced failed percutaneous intervention…     

心先安治疗肺心病心衰疗效分析

心先安注射注，化学名环磷腺苷甲胺，为新型环磷腺苷酸类药，药理试验表明，本药具有扩张心脑外周血管，增加冠脉流量，增加心肌收缩力，改善心输出量，减少心肌耗氧量，降低外周阻力不致反射性加快心率等作用，临床上用于治疗病窦综合征，冠心病，心绞痛或洋地黄中毒病人更为适用我院于2003年10月～2005年5月应用江苏万邦生化医药股份有限公司提供的心先安注射液治疗肺心病心衰患者45例，收到了良好疗效，作一临床总结。