Healon~([R])和Viscoat~([R])细胞毒性的比较研究

本实验应用新的组织培养系统培养的兔角膜内皮细胞,对Healon~(R)和Viscoat~(R)的细胞毒性进行了比较研究。发现它们对角膜内皮细胞具有潜在的毒性作用,当细胞暴露于药液3小时后,出现轻度的损害。24小时后,出现严重的细胞损害。两者相比较,Viscoat~(R)对细胞的损害程度比Healon~(R)的轻,提示Viscoat~(R)可替代Healon~(R)用于眼科手术。     

Comparison of Endemic and Epidemic Vesicular Stomatitis Virus Lineages in Culicoides sonorensis Midges

Vesicular stomatitis virus (VSV) primarily infects livestock and is transmitted by direct contact and vectored by Culicoides midges (Diptera: Ceratopogonidae). Endemic to Central and South America, specific VSV lineages spread northward out of endemic regions of Mexico and into the U.S. sporadically every five to ten years. In 2012, a monophyletic epidemic lineage 1.1 successfully spread northward into the U.S. In contrast, the closest endemic ancestor, lineage 1.2, remained circulating exclusively in endemic regions in Mexico. It is not clear what roles virus-animal interactions and/or virus-vector interactions play in the ability of specific viral lineages to escape endemic regions in Mexico and successfully cause outbreaks in the U.S., nor the genetic basis for such incursions. Whole-genome sequencing of epidemic VSV 1.1 and endemic VSV 1.2 revealed significant differences in just seven amino acids. Previous studies in swine showed that VSV 1.1 was more virulent than VSV 1.2. Here, we compared the efficiency of these two viral lineages to infect the vector Culicoides sonorensis (Wirth and Jones) and disseminate to salivary glands for subsequent transmission. Our results showed that midges orally infected with the epidemic VSV 1.1 lineage had significantly higher infection dissemination rates compared to those infected with the endemic VSV 1.2 lineage. Thus, in addition to affecting virus-animal interactions, as seen with higher virulence in pigs, small genetic changes may also affect virus-vector interactions, contributing to the ability of specific viral lineages to escape endemic regions via vector-borne transmission.     

Targeted peptide-modified oxidized mesoporous carbon nanospheres for chemo-thermo combined therapy of ovarian cancer in vitro

Ovarian cancer remains one of serious hazards to human health due to many drawbacks of existing available treatment options. In this study, a multifunctional chemo-thermo combined therapy nanoplatform (OMCNPID) was successfully prepared, which is composed of I₆P₈ peptide as a targeting moiety to interleukin-6 receptors (IL-6Rs), oxidized mesoporous carbon nanospheres (OMCN) as a near infrared (NIR)-triggered drug carrier and doxorubicin (DOX) as a chemotherapeutic drug and fluorescent agent. The synthesized multifunctional nanoplatform displayed high storage capacity for drugs and excellent photothermal properties. Besides, DOX was rapidly released from OMCNPID at the condition of low pH and NIR laser irradiation due to the dissociation of DOX from graphitic cores of OMCN. In vitro experimental results verified that OMCNPID could be markedly taken up by SKOV-3 monolayer cells and tumor spheroids, and revealed a remarkable synergistic chemo-photothermal effect against ovarian cancer. All the results demonstrated that OMCNPID is a pH/NIR dual-stimulus responsive nanoplatform and can achieve efficient chemo-thermo combined therapy.     

Dual IGF1R/IR inhibitors in combination with GD2-CAR T-cells display a potent anti-tumor activity in diffuse midline glioma H3K27M-mutant

BackgroundDiffuse midline gliomas (DMG) H3K27M-mutant, including diffuse intrinsic pontine glioma (DIPG), are pediatric brain tumors associated with grim prognosis. Although GD2-CAR T-cells demonstrated significant anti-tumor activity against DMG H3K27M-mutant in vivo, a multimodal approach may be needed to more effectively treat patients. We investigated GD2 expression in DMG/DIPG and other pediatric high-grade gliomas (pHGG) and sought to identify chemical compounds that would enhance GD2-CAR T-cell anti-tumor efficacy.MethodsImmunohistochemistry in tumor tissue samples and immunofluorescence in primary patient-derived cell lines were performed to study GD2 expression. We developed a high-throughput cell-based assay to screen 42 kinase inhibitors in combination with GD2-CAR T-cells. Cell viability, western blots, flow-cytometry, real time PCR experiments, DIPG 3D culture models, and orthotopic xenograft model were applied to investigate the effect of selected compounds on DIPG cell death and CAR T-cell function.ResultsGD2 was heterogeneously, but widely, expressed in the tissue tested, while its expression was homogeneous and restricted to DMG/DIPG H3K27M-mutant cell lines. We identified dual IGF1R/IR antagonists, BMS-754807 and linsitinib, able to inhibit tumor cell viability at concentrations that do not affect CAR T-cells. Linsitinib, but not BMS-754807, decreases activation/exhaustion of GD2-CAR T-cells and increases their central memory profile. The enhanced anti-tumor activity of linsitinib/GD2-CAR T-cell combination was confirmed in DIPG models in vitro, ex vivo, and in vivo.ConclusionOur study supports the development of IGF1R/IR inhibitors to be used in combination with GD2-CAR T-cells for treating patients affected by DMG/DIPG and, potentially, by pHGG.     

重组人生长激素对裸鼠肝癌移植瘤生长转移的实验研究

目的:研究重组人生长激素(recombinant hunman growth hormone,rhGH)对裸鼠肝癌移植瘤生长和转移能力的影响及相关信号转导通路的变化。方法:通过RNA干扰技术抑制MHCC-97H肝癌细胞中胰岛素样生长因子-1受体(insulin-like growth factor-1 receptor,IGF-1R)的表达。建立裸鼠皮下和原位肝癌移植模型;研究IGF-1R基因沉默前后,rhGH对裸鼠肝癌移植瘤成瘤、生长和转移的影响,并用Western印迹法检测PI-3K信号转导通路中,信号分子AKT的蛋白表达和磷酸化水平。结果:注射rhGH可使荷瘤裸鼠体重明显增加,肝癌原位移植瘤体积显著增大(P0.05)。IGF-1R基因沉默后,裸鼠皮下移植瘤的成瘤率、原位肝癌接种模型中的肝癌移植瘤体积均显著减小(P0.05)。对PI-3K信号通路的研究显示,rhGH能显著促进MHCC-97H肝癌细胞信号分子AKT磷酸化,IGF-1R沉默后AKT磷酸化水平明显降低(P<0.05)。结论:rhGH在体内具有显著促进荷瘤裸鼠体重增加及移植瘤生长的作用;但并不促进肝癌的转移。IGF-1R基因沉默后,rhGH对裸鼠移植瘤的成瘤和促生长作用明显减弱。而PI-3K信号通路在rhGH促肝癌生长中发挥重要的介导作用。     

口腔固有条件对全口义齿满意度的影响

目的探讨无牙颌患者口腔固有条件对全口义齿修复效果的影响及与全口义齿满意度的关系。方法随机选取97例行全口义齿修复的患者,根据口腔固有条件分成三组,修复后的1个月和6个月分别填写全口义齿满意度调查问卷,进行统计分析。结果戴用全口义齿1个月后,口腔固有条件Ⅰ级组Ⅱ级组较Ⅲ级组全口义齿满意度高,有统计学意义;戴用全口义齿6个月后,三组的满意度均有一定提高,三组间满意度无明显差异。结论无牙颌患者的口腔固有条件会部分影响全口义齿的修复效果。     

河南省65～74岁年龄组牙列缺损或缺失情况流行病学抽样调查分析

目的:获取河南省老年人牙列缺损、缺失情况的基本资料。方法:采用分层、不等比、多阶段、整群抽样的方法,对全省范围内65～74岁年龄组老年人牙列缺损、缺失情况进行流行病学抽样调查。结果:受调查的2320人中,牙列缺损者为1219人,占52.54%;义齿修复者为641人,占牙列缺损者的52.58%;牙列缺失率为21.98%,修复率为71.18%。结论:与全国平均水平相比,河南省老年人牙列缺损率较低,牙列缺失率较高。     

胰头癌全胰腺系膜切除的争论与进展

区域性淋巴结清扫对病人预后是否受益,切除远站的淋巴结是否会增加术后的并发症,一直受到人们质疑.胰腺癌周围神经丛浸润十分常见,胰内神经丛浸润可蔓延至胰外神经丛,是导致切缘阳性的重要因素,因而整块切除腹膜后组织包括部分神经丛应作为胰头癌手术的一个基本组成部分.全胰腺系膜切除（total mesopancreas excision,TMpE）理念的提出,要求包括神经、毛细血管及淋巴结在内的所有软组织的廓清,在不增加手术并发症和死亡的基础上,可提高RO切除率,有助于改善病人预后.     

Mothers' questionnaire of preschoolers' language and motor skills: a validation study

Objective Parent questionnaires of child motor and language skills are useful in many contexts. This study validates one such measure, the Preschool Child Development Inventory (PCDI), a mother‐answered standardized measure of motor (fine and gross) and language (expression and comprehension) skills of 3–6‐year‐old children. Methods Eighty‐one mothers answered the inventory and their children were concurrently tested on six verbal subtests of WPPSI‐R^IS. Results The six language and motor subtests of the PCDI revealed the predicted convergent and divergent correlations with the verbal subtests of the WPPSI‐R^IS. As predicted, the motor subtests diverged and the language subtests converged with the expected WPPSI‐R^IS subtests. Principal components analysis of all the measures (the PCDI and the WPPSI‐R^IS subtests) revealed two components, verbal and motor in content. Conclusions The findings support the validity of a mother‐answered inventory to assess language and motor development. It is pointed out that such inventories are a viable brief and cost effective alternative to individual testing, both to supplement such measures in clinical practice and as main information in research, for example on determinants of development. Some suggestions are made for future research and applications.