Specific mitochondrial DNA mutation in mice regulates diabetes and lymphoma development

It has been hypothesized that respiration defects caused by accumulation of pathogenic mitochondrial DNA (mtDNA) mutations and the resultant overproduction of reactive oxygen species (ROS) or lactates are responsible for aging and age-associated disorders, including diabetes and tumor development. However, there is no direct evidence to prove the involvement of mtDNA mutations in these processes, because it is difficult to exclude the possible involvement of nuclear DNA mutations. Our previous studies resolved this issue by using an mtDNA exchange technology and showed that a G13997A mtDNA mutation found in mouse tumor cells induces metastasis via ROS overproduction. Here, using transmitochondrial mice (mito-mice), which we had generated previously by introducing G13997A mtDNA from mouse tumor cells into mouse embryonic stem cells, we provide convincing evidence supporting part of the abovementioned hypothesis by showing that G13997A mtDNA regulates diabetes development, lymphoma formation, and metastasis--but not aging--in this model.     

An update on ECARUCA,the European Cytogeneticists Association Register of Unbalanced Chromosome Aberrations

The European Cytogeneticists Association Register of Unbalanced Chromosome Aberrations (ECARUCA, www.ecaruca.net) is an online database initiated in 2003 that collects and provides detailed, curated clinical and molecular information on rare unbalanced chromosome aberrations. ECARUCA now contains over 4800 cases with a total of more than 6600 genetic aberrations and has over 3000 account holders worldwide. Recently, the ECARUCA web site was renewed, including the presentation of interesting case reports in collaboration with the European Journal of Medical Genetics. This article gives an overview of the current status and future plans of the online ECARUCA database.     

The psychological impact of cryptic chromosomal abnormalities diagnosis announcement

This qualitative study aims to describe the psychological impact of the diagnosis announcement of pathogenic Copy Number Variations (pCNVs). We performed semi-structured interviews of 60 parents of 41 affected children and 5 geneticists who announced the diagnoses. The diagnosis of the best characterized microdeletion syndromes, often defined by patronymic names (e.g. Williams syndrome), is generally made on a clinical basis by geneticists and confirmed by fluorescence in situ hybridization analysis. Chromosomal microarray, on the contrary, can allow the disclosure of rare pCNVs named after cytogenetic formulas, with poorly known clinical consequences: this makes doctors feel less confident with these diagnosis announcements. The disclosure of pCNVs named after cytogenetic formulas does not facilitate the parental mental representation of the disease, leading some parents to call into question the genotype-phenotype correlation or the very notion of a diagnosis. The announcement of inherited pCNVs can increase the feeling of parental guilt; the disclosure of de novo pCNVs can induce a feeling of “breakage” in the mental representation of the parent-child vertical transmission. In conclusion, our study shows that the disclosure of pCNVs has a significant psychological impact: a multidisciplinary approach to the diagnosis announcement, including a psychological support, should be systematically warranted.     

角膜胶原交联术治疗圆锥角膜的疗效和安全性研究

目的：研究角膜胶原交联术治疗圆锥角膜的疗效和安全性。

方法：对2015-04/2018-08在泰国朱拉隆功国王纪念医院行角膜胶原交联术的圆锥角膜患者病历进行回顾性分析。评估术前和术后1a的视力、屈光度、角膜地形图、高阶像差(HOA)、地形图参数和角膜密度。根据患者年龄是否小于24和30岁、基线角膜最大曲率(Kmax)是否小于55 D、基线最佳矫正视力(BCVA)是否小于0.3 LogMAR分组评估年龄、基线Kmax和BCVA对手术疗效的影响。分析术前Kmax、Kmean、平均等效球镜度数(MRSE)、视力、角膜最薄点厚度值、Kmax的变化以及相关参数的变化与角膜密度测量值变化之间的关系。P<0.05具有统计学意义。

结果：共155例患者185眼纳入研究,其中119例男性,36例女性。根据Amsler-Krumeich进行分类,1期和2期占优势(分别为37.84%和35.14%)。术后1a,平均裸眼视力(UCVA)提高0.1 LogMAR(P<0.05)。与基线BCVA较好组(术前BCVA<0.3 LogMAR)相比,基线BCVA较差组(术前BCVA≥0.3 LogMAR)术后BCVA改善大于0.2 LogMAR的眼数较多(78.26% vs 21.74%,P<0.05)。平均Kmax比基线下降2.36 D(P<0.05)。术前Kmax≥55 D的患眼术后Kmax下降超过2.0 D的眼数占比73%。距角膜顶点6 mm处角膜HOA下降0.40(P<0.05)。术后1mo～1a,0～6 mm区角膜密度测量值持续增加。术后1a,角膜密度的增加与最薄点厚度的减少呈线性相关。表面变异指数、高度非对称性指数、圆锥角膜指数、高度轴偏心指数在术后1a时下降(P<0.05)。术后1a,手术成功率为90.24%。术后1wk、1、3、6mo、1a角膜混浊发生率分别为11.35%、30.27%、15.67%、10.27%、2.16%。无角膜水肿发生,但有1例无菌性角膜炎患者。

结论：角膜胶原交联术可有效治疗圆锥角膜,使角膜变平、重塑,提高视力、HOA和角膜形态指数,晚期圆锥角膜Kmax也明显降低。     

FS-LASIK与FS-LASIK联合快速角膜胶原交联术矫正高度近视术后早期屈光度及角膜高阶像差比较

目的：比较飞秒激光辅助的准分子激光原位角膜磨镶术(FS-LASIK)与FS-LASIK联合快速角膜胶原交联术(FS-LASIK Xtra)矫正高度近视术后早期屈光度及角膜高阶像差变化特点,评估两种术式矫正高度近视的早期效果。

方法：回顾性病例对照研究。纳入2019-04/2020-04在我院进行FS-LASIK Xtra及FS-LASIK的高度近视患者42例84眼,每组各21例42眼,术后随访3mo,比较两组患者术后裸眼视力(UCVA)、等效球镜(SE)、散光度及角膜高阶像差。

结果：FS-LASIK Xtra组患者术后1d UCVA(LogMAR)低于FS-LASIK组(P<0.01),其余时间点两组间比较均无差异(P>0.05)。两组患者术后SE均较术前明显降低,术后3mo,FS-LASIK Xtra组有38眼(90%)、FS-LASIK组有41眼(98%)术眼SE在±1.00D以内。两组患者术后均有35眼(83%)的术眼残余散光在0.50D以内。两组术后3mo角膜总高阶像差、球差、彗差及三叶草差均较术前增大,FS-LASIK Xtra组总高阶像差及三叶草差大于FS-LASIK组(均P<0.05)。

结论：FS-LASIK与FS-LASIK Xtra矫正高度近视在术后早期均具有较好的有效性和可预测性,术后早期角膜总高阶像差均增加,且行FS-LASIK Xtra增加更显著。     

Chromosomal losses and gains in meningiomas: Comparative genomic hybridization (CGH) study of the whole genome

Abstract

We investigated chromosomal aberrations in meningiomas using newly developed comparative genomic hybridization (CGH) technique and compared the results with the proliferating potential of the tumors. This technique permits the entire genome to be surveyed in one session of experiments. Our results revealed chromosomal aberrations in 5 out of 10 (50%) of the tumor samples studied. Losses of the distal parts of chromosome 1p (5 out of 10) and 22q (3 out of 10) were the two most frequent chromosomal aberrations. Losses and/or gains in other regions were only sporadic. The MIB-1 staining indices (MIB-511 %) were 1.9 ± 0.9% (mean ± SD) in benign (n = 8)1 4.5% in atypical (n = 1)1 and 11.7% in anaplastic (n = 1) meningiomas. The comparison of MIB-51 between the tumors with (2.3 ± 0.6%) and without (7.6 ± 0.3%) chromosomal aberrations demonstrated a trend towards an increased MIB-51 in meningiomas with chromosomal aberrations (p < 0.07) by unpaired 5tudent1s t-test. This study suggests that alterations in chromosomes 1p and 22q could be a primary focus of further detailed assessment of tumorigenesis and in understanding the biological behavior of meningiomas. [Neural Res 1998; 20: 612-616]     

无创基因检测在胎儿染色体非整倍体诊断中的应用

目的 评价无创基因检测在胎儿染色体非整倍体诊断中的临床应用价值.方法 选取253例高龄孕妇,在知情同意的原则下采集外周血血浆,对其血浆中胎儿游离DNA进行检测;并与实验孕妇的羊水染色体核型分析结果进行比对验证.结果 本试验对253例样本进行了孕妇血浆胎儿游离DNA检测,检出21-三体阳性病例3例,检出18-三体阳性病例1例,与染色体核型分析的结果一致.结论 无创基因检测可以用于胎儿染色体拷贝数异常的检测,具有无创、灵敏度高、特异性强等优点,在胎儿染色体拷贝数异常疾病的产前检测中具有临床实际应用的价值.     

Protective effect of Alstonia scholaris Linn. R. Br. against Bleomycin induced chromosomal damage in cultured human lymphocytes,in vitro

It is both interesting and necessary to identify and develop nontoxic radioprotective compounds. Bleomycin (BLM), a known radiomimetic drug was used as a clastogen in the present study. The possible protective effects against BLM (15?μg/ml) induced clastogenicity by aqueous and methanolic extracts from Alstonia scholaris bark, stem and leaves were compared. The treatment of bark extracts significantly (p?2 assay was performed. Lymphocyte cultures from 12 healthy volunteers were exposed to aqueous (50?μg/ml) and methanolic (50?μg/ml) extracts of A. scholaris bark alone as well as in combination with Bleomycin under two different growth phases, G₀ and G₂. There was a statistically significant reduction (p?2 phase as compared to respective cultures exposed at G₀ phase. The highest level (p?2 phase than those at G₀ phase. This indicated that there could be certain compound(s) present in aqueous bark extracts which enhance DNA repair capacity. Therefore, the bark of A. scholaris could be further utilized to identify and bring out front line radio protective agents in the market with effective formulations.     

Assessment of the cytotoxicity and genotoxicity properties of Uvaria chamae P. Beauv (Annonaceae) and Morinda lucida Benth (Rubiaceae) in mice

The toxicity profile of medicinal plants is an important preclinical requirement in the development of phytomedicines. The cytotoxic and genotoxic effects of the leaf of Uvaria chamae P. Beauv (Annonaceae) and stem bark of Morinda lucida Benth (Rubiaceae) were investigated in order to provide information on their safety as antimalarial plants. The methanol extract of U. chamae and ethanol (70%) extract of M. lucida were separately orally administered (125, 250, and 750?mg/kg/day) to mice for 10 consecutive days. Cyclophosphamide (50?mg/kg, single dose) and distilled water were used as positive and negative controls, respectively. The mice were injected with colchicine (0.04%) intra-peritoneally 24?h after the last administration of the extracts and the bone marrows harvested. Giemsa-stained slides of bone marrow cells were microscopically assessed for dividing cells to determine the mitotic index (MI) and scored for chromosomal aberrations (CA) according to standard methods. chamae exhibited dose-dependent cytotoxicity. At 750?mg/kg, the MI was significantly (p?M. lucida was not significantly different (p?>?0.05) from that of the negative control. The total CA observed from treatment with both plants at all doses were significantly (p?U. chamae showed both cytotoxicity and genotoxicity while M. lucida exerted only genotoxic effect. Nevertheless, the two plants should be used with caution in antimalarial therapy.