经颅磁刺激参数与结构要件的影响分析

为了进一步探索经颅磁刺激工作机理并改进或研制出新的经颅磁刺激激励源.本文从经颅磁刺激的原理推导出了磁场、感应电流及激励源原理电路电流的表达式,利用大脑-线圈和大脑-线圈-铁芯两种经颅磁刺激模型分析影响因素与头模型各组织的磁场和感应电流分布.对比分析表明电流的性质,线圈半径,线圈激励特性与铁芯对感应电流分布与电磁场分布有着本质的影响.对经颅磁刺激参数及结构要件的研究与分析可用于指导刺激线圈参数及激励源电路参数的设置,以及探索新的激励源制作.     

Focused ultrasound stimulation on meibomian glands for the treatment of evaporative dry eye

Current treatments for meibomian gland dysfunction have several limitations, creating a necessity for other advanced treatment options. The purpose of this study is to determine the effectiveness of focused ultrasound stimulation for the treatment of dry eye disease caused by meibomian gland dysfunction. An in vivo study of nine Dutch Belted rabbits was conducted with focused ultrasound stimulation of the meibomian glands. A customized line-focused ultrasonic transducer was designed for treatment. Fluorescein imaging, Schirmer’s test, and Lipiview II ocular interferometer were used to quantify outcomes from three aspects: safety, tear production, and lipid layer thickness. Both tear secretion and lipid layer thickness improved following ultrasound treatment. Five to 10 min after the ultrasound treatment, the mean values of lipid layer thickness increased from 55.33 ± 11.15 nm to 95.67 ± 22.77 nm (p < 0.05), while the mean values measured with the Schirmer’s test increased from 2.0 ± 2.3 to 7.2 ± 4.3 (p < 0.05). Positive effects lasted more than three weeks. Adverse events such as redness, swelling, and mild burn, occurred in two rabbits in preliminary experiments when the eyelids sustained a temperature higher than 42°C. No serious adverse events were found. The results suggest that ultrasound stimulation of meibomian glands can improve both tear production and lipid secretion. Ultimately, ultrasound stimulation has the potential to be an option for the treatment of evaporative dry eye disease caused by meibomian gland dysfunction.     

Correlation between vaginal microbiota and different progression stages of cervical cancer

The process from high-risk human papillomavirus (HR-HPV) infection to cervical cancer is a continuous and long-term process, but the pathogenesis of the whole process is not completely clear. Here, 59 Chinese women were engaged in this study, and divided into five groups: normal healthy group, HR-HPV infections group, low-grade intraepithelial neoplasia (LSIL) group, high-SIL(HSIL) group, and cervical cancer group. With the occurrence of HR-HPV infection and the development of cervical lesions, the diversity of vaginal microbiota species was increased, and the relative abundance of Lactobacillus (L.), the dominant bacteria in maintaining vaginal microecological balance, was decreased gradually. In contrast, the abundance of Actinobacteria in the four disease groups was significantly higher than that in normal group. Furthermore L. iners may be related to the serious progression of cervical cancer. After analyzing the whole process, we found that Gardnerella(G.), Atopobium(A.) and Dialister(D.) have important effects on both persistent HR-HPV infection and the pathogenesis of cervical cancer. In addition, PICRUSt2 and KEGG results showed that the KEGG pathways enriched by the predicted genes of vaginal microbiota in cancer group included metabolic diseases, endocrine system and immune systems when compared with that in normal group. These findings may provide insights into the pathogenesis of cervical cancer, and help to improve the early detection and prevention of cervical precancerous lesions.     

Mechanical vibration in “double-wound” magnetic field exposure coils

It has been suggested that “double-wound” (bifilar) exposure coils are capable of producing a sham environment in which hum and vibration will be “similar” to the field-exposed condition. We found by direct measurements in a bifilar coil system that vibration amplitude in sham and exposed conditions differed by a factor of 50 when our test system was driven at B = 10 mT. We also found that the normal laboratory environment can include vibrations of an intensity similar to that produced by the exposure system, although not necessarily of similar spectral distribution. © 1996 Wiley-Liss, Inc.     

Genetic association study of intron variants in the forkhead box protein P3 gene in Chinese patients diagnosed with cervical cancer

The aim of this study was to investigate the effects of forkhead box protein P3 (FOXP3) intron single nucleotide variants (SNVs) in high‐risk human papilloma virus (HR‐HPV) infection and cervical cancer (CC) malignant lesions. We performed FOXP3 genotyping in 350 patients with CC and 350 healthy controls using the ImLDR multiple single nucleotide polymorphism genotyping technology. The heterozygous mutation TC in rs2294021 decreased the risk of HR‐HPV infection and CC malignant lesions (TC vs. TT: OR = 0.71, 95% CI = 0.51–0.99); the dominant model TC+CC and allele C in rs2294021 decreased the risk of CC malignant lesions (TC+CC vs. TT: OR = 0.69, 95% CI = 0.50–0.95; C vs. T: OR = 0.78, 95% CI = 0.63–0.97). The heterozygous mutation GA, dominant model GA+AA and allele A in rs3761549 also decreased the risk of HR‐HPV infection and CC malignant lesions (GA vs. GG: OR = 0.70, 95% CI = 0.51–0.96; GA+AA vs. GG: OR = 0.69, 95% CI = 0.51–0.94; A vs. G: OR = 0.75, 95% CI = 0.58–0.96). Patients with CC and HR‐HPV infection carrying rs2294021 TC and rs3761549 GA had lower expression of FOXP3 protein. Haplotype analysis revealed that T‐C‐A decreased the risk of HR‐HPV infection. Furthermore, we found a significant association between immune cells infiltration and prognosis in patients with CC. Our findings demonstrated that rs2294021 and rs3761549 variants may protect against HR‐HPV and CC malignant lesions by downregulating FOXP3 and that FOXP3 was associated with immune cells infiltration, which affected the prognosis of CC.     

BMI1基因下调使宫颈癌和子宫内膜癌对紫杉醇敏感

目的 研究B细胞特异性莫洛尼鼠白血病病毒插入位点1（BMI1）基因对宫颈癌及子宫内膜癌增殖浸润及紫杉醇耐受的影响及其机制。方法 首先利用Cbioportal、TCGA和CPTAC数据库分析BMI1基因在宫颈癌和子宫内膜癌中的突变及表达情况。接着对人宫颈癌组织样本和人子宫内膜癌组织样本中BMI1的蛋白质表达水平进行免疫组化分析。采用蛋白质印迹法（Western blot)检测BMI1敲低后宫颈癌及子宫内膜癌细胞中BMI1下游调控因子的蛋白质水平变化。此外,通过细胞功能实验研究了BMI1在宫颈癌HeLa及子宫内膜癌HEC-1-A细胞中的功能。最后,通过实验评估siBMI1联合紫杉醇治疗的协同抗生长作用。结果 数据库分析结果显示,BMI1在1.5%的子宫颈癌患者及1.9%的子宫内膜癌的患者中存在不同程度的扩增、错义及剪接突变。此外,高mRNA水平的BMI1与宫颈癌的病理类型相关,且高蛋白质水平的BMI1与子宫内膜癌的病理类型和肿瘤分级及较低的生存率相关。进一步的免疫组化分析发现,与正常组织相比,宫颈癌和子宫内膜癌组织中BMI1蛋白水平表达升高,且与肿瘤的病理分化及浸润深度相关。药物敏感性实验显示,BMI1过表达导致HeLa及HEC-1-A细胞对多种抗癌药物的敏感性下降,其中包括紫杉醇。为了进一步分析BMI1与紫杉醇耐受的关系,通过Western blot检测BMI1敲除后HeLa及HEC-1-A细胞中BMI1下游因子的蛋白质水平变化。结果显示,抗凋亡相关蛋白Bcl-2随着BMI1的敲低而表达水平下降,而促凋亡相关蛋白BAX则显著升高。此外,细胞功能实验结果显示,体外过表达BMI1可促进HeLa及HEC-1-A细胞的增殖和迁移,且BMI1低表达的HeLa及HEC-1-A细胞对紫杉醇更敏感。结论 BMI1在宫颈癌和子宫内膜癌患者的肿瘤组织中过表达,BMI1的下调通过调控凋亡通路使CC和EC细胞对紫杉醇更加敏感。     

The levels of leukemia inhibitory factor mRNA in a Schwann cell line are regulated by multiple second messenger pathways

Axotomy of sympathetic and sensory neurons leads to changes in their neuropeptide phenotypes. These changes are mediated in part by the induction of leukemia inhibitory factor (LIF) by nonneuronal cells. In the present study, we identified satellite/Schwann cells as a possible source of the injury-induced LIF. Using a Schwann cell line, SC-1 cells, we examined mechanisms of LIF induction. LIF mRNA levels increased rapidly when the cells were treated with 8-(4-chlorophenylthio)adenosine 3',5'-cyclic monophosphate, phorbol 12-myristate 13-acetate (PMA), or A23187. Among these reagents, PMA was the most efficacious. Inhibition of protein kinase C (PKC) by GF-1 09203X significantly reduced the PMA-induced LIF mRNA levels. As PKC is known to activate the extracellular signal-regulated kinase (ERK) signaling pathway, the involvement of this pathway in the PMA-stimulated induction of LIF mRNA was examined. Phosphorylation of ERKs was increased following PMA treatment in SC-1 cells. Moreover, inhibition of ERK kinase activity by PD98059 dramatically reduced PMA-stimulated phosphorylation of ERKs and induction of LIF mRNA. These results indicate that LIF mRNA levels can be regulated by ERK activation via stimulation of PKC in Schwann cells.