Modeling monocular form deprivation in rabbits using a simulated-cataract intraocular lens

AIM:To establish an animal model of form deprivation amblyopia based on a simulated cataract intraocular lens(IOLs).METHODS:Poly(dimethyl siloxane)-SiO_(2) thin films(PSF)with different degrees of opacity as IOL materials were prepared.The light transmission of the PSF-IOL was measured,and its in vitro biosafety was determined by cell counting kit(CCK)-8 assay using the HLEC-B3 cell line and ARPE-19 cell line.Subsequently,the in vivo safety was determined by implanting the PSF-IOL with 10%wt SiO_(2) into the right eyes of New Zealand white rabbits(PSF-IOL group),and compared with two control groups:contralateral comparison group and normal control(NC)group(Contralateral comparison group:the fellow eye;NC group:a group of binocular normal rabbits without intervention).The flash visual-evoked potentials(F-VEPs)were measured to verify amblyopia.RESULTS:PSFs containing 0,2%,and 10%wt SiO_(2) were successfully constructed.The 0 SiO_(2) PSF was transparent,while the 10%wt SiO_(2) PSF was completely opaque.It was found that PSF did not induce unwanted cytotoxicity in HLECs and ARPE19 cells in vitro.In vitro,PSF-IOL with 10%wt SiO_(2) was also non-toxic,and no significant inflammation or structural changes occurred after four weeks of PSF-IOL implantation.Finally,our IOL-simulated congenital cataract rabbit detected by F-VEPs suggested tentative amblyopia.CONCLUSION:A PSF-IOL that mimics cataracts is created.A novel form deprivation model is created by the IOL-simulated congenital cataract rabbit.It can be developed fast and stable and holds great potential for future study.

XGBoost机器学习模型对乙型肝炎肝硬化诊断的应用价值研究

背景 慢性乙型肝炎病毒感染(chronic hepatitis B virus infection,CHBV)进展成肝硬化是缓慢且容易被忽略的,通过临床常规指标来构建肝硬化无创诊断模型成为研究热点.然而,目前有关肝硬化早期诊断的机器学习模型仍是缺乏的.目的 探讨极限梯度提升机(eXtreme gradient boosting,XGBoost)机器学习模型在乙肝肝硬化无创诊断中的效能.方法 回顾性分析2010-2018年首次就诊于安徽医科大学第一附属医院和第二附属医院感染病科的CHBV患者1087例,按照随机原则以3:1的比例分为训练集和验证集.收集所有研究对象的临床资料并利用XGBoost机器学习模型构建预测模型.同时,计算谷草转氨酶与血小板比率指数(aspartate aminotransferase/platelet ratio index,APRI)、纤维蛋白-4(fibrosis-4 index,FIB-4)评分并与XGBoost机器学习模型进行比较.受试者工作特征曲线下面积(area under curve,AUC)以评估模型区分度,校准曲线(calibration curve,CA)及决策曲线(decision curve analysis,DCA)以评估模型校准度及获益度.结果 共纳入CHBV病例1087例,其中训练集817例,验证集270例.训练集与验证集两组间所有预测变量均无统计学差异(P>0.05).训练集中有103例患者发生肝硬化,肝硬化患者APRI和FIB-4评分明显高于非肝硬化患者(P <0.05).在所有预测因子中血小板的相对重要度最高.训练集和验证集的AUC分别为0.95和0.86(P<0.05),两者Kappa值分别为0.78和0.74,提示模型可重复性较好.CA曲线提示模型预测情况与真实情况拟合情况吻合度较高.训练集和验证集的DCA曲线提示所建立模型能够使患者获得较高的获益度.XGBoost机器学习模型对于肝硬化的效能优于APRI评分和FIB-4评分.结论 本研究利用C H B V患者常见的临床信息构建的XGBoost模型对肝硬化的诊断具有良好的性能,值得临床进一步推广.

Selective synthesis of three-dimensional ZnO@Ag/SiO2@Ag nanorod arrays as surface-enhanced Raman scattering substrates with tunable interior dielectric layer

We describe the synthesis of three-dimensional(3D) multilayer ZnO@Ag/SiO2@Ag nanorod arrays by the physico–chemical method. The surface-enhanced Raman scattering(SERS) performance of the 3D multilayer Zn O@Ag/SiO2@Ag nanorod arrays is studied by varying the thickness of dielectric layer SiO2 and outer-layer noble Ag. The 3D Zn O@Ag/SiO2@Ag nanorod arrays create a huge number of SERS "hot spots" that mainly contribute to the high SERS sensitivity. The great enhancement of SERS results from the electron transfer between ZnO and Ag and different electromagnetic enhancements of Ag nanoparticles(NPs) with different thicknesses. Through the finite-difference time-domain(FDTD) theoretical simulation, the enhancement of SERS signal can be ascribed to a strong electric field enhancement produced in the 3D framework. The simplicity and generality of our method offer great advantages for further understanding the SERS mechanism induced by the surface plasmon resonance(SPR) effect.

A human-specific insertion promotes cell proliferation and migration by enhancing TBC1D8B expression

Human-specific insertions play important roles in human phenotypes and diseases.Here we reported a 446-bp insertion(Insert-446)in intron 11 of the TBC1D8B gene,located on chromosome X,and traced its origin to a portion of intron 6 of the EBF1 gene on chromosome 5.Interestingly,Insert-446 was present in the human Neanderthal and Denisovans genomes,and was fixed in humans after human-chimpanzee divergence.We have demonstrated that Insert-446 acts as an enhancer through binding transcript factors that promotes a higher expression of human TBC1D8B gene as compared with orthologs in macaques.In addition,over-expression TBC1D8B promoted cell proliferation and migration through“a dual finger”catalytic mechanism(Arg538 and Gln573)in the TBC domain in vitro and knockdown of TBC1D8B attenuated tumorigenesis in vivo.Knockout of Insert-446 prevented cell proliferation and migration in cancer and normal cells.Our results reveal that the human-specific Insert-446 promotes cell proliferation and migration by upregulating the expression of TBC1D8B gene.These findings provide a significant insight into the effects of human-specific insertions on evolution.

Thyroid function of twin-pregnant women in early pregnancy

Background: Serum human chorionic gonadotrophin (hCG) is higher in twin than that in singleton pregnancies. As hCG stimulates the thyroid to produce more free thyroxine (FT4), which may lead to decreased thyroid-stimulating hormone (TSH) levels, the reference ranges of thyroid-related indicators may differ between singleton and twin pregnancies in the first trimester. This study aimed to establish reference ranges for thyroid-related indicators in early twin pregnancies and to compare them with singleton pregnancies. Methods: Data of 820 twin-pregnant women were extracted from the established database of all pregnant women who delivered at Peking University First Hospital from October 2013 to May 2018;160 who met National Academy of Clinical Biochemistry criteria were included to establish TSH and FT4 reference ranges. We screened 480 (3:1 paired) women with singleton pregnancies from the same database as controls. The Mann-Whitney test for TSH and FT4 levels was applied for comparisons between singleton and twin pregnancies. Results: First-trimester reference ranges (4–12 gestational weeks) for twin pregnancies were: TSH 0.69 (0.01–3.35) mIU/L and FT4 16.38 (12.45–23.34) pmol/L. Median TSH was significantly lower at 7 to 12 gestational weeks than that at 4 to 6 gestational weeks (0.62 vs. 0.96 mIU/L, Z =-1.964, P = 0.049);FT4 was not significantly different between the two groups. Compared to singleton pregnancies, median TSH was significantly lower (0.69 vs. 1.27 mIU/L, Z =-6.538, P = 0.000), and FT4 was significantly higher (16.38 vs. 14.85 pmol/L, Z =-7.399, P = 0.000) in twin pregnancies in the first trimester. Conclusions: Specific reference ranges for thyroid-related indicators for twin pregnancies are needed to avoid a misdiagnosis of thyroid dysfunction. Moreover, establishment of separate reference ranges for 4 to 6 and 7 to 12 gestational weeks in twin pregnancies may be considered.