Parental origin of mutation and the risk of breast cancer in a prospective study of women with a BRCA1 or BRCA2 mutation

The objective is to estimate the risk of breast cancer in women who carry a deleterious BRCA1 or BRCA2 mutation, according to parental origin of mutation. We conducted a cohort study of women with a BRCA1 mutation (n = 1523) or BRCA2 mutation (n = 369) who had not been diagnosed with breast or ovarian cancer. For each woman, the pedigree was reviewed and the origin of the mutation was assigned as probable paternal or maternal. The hazard ratio (HR) for developing breast cancer in the follow‐up period was estimated for women with a paternal mutation compared to a maternal mutation. The risk of breast cancer was modestly higher in women with a paternal BRCA1 mutation compared to women with a maternal BRCA1 mutation (HR = 1.46; 95% CI = 0.99–2.16) but the difference was not significant (p = 0.06). The parental mutation origin did not affect the risk in women with a BRCA2 mutation. Our results are consistent with the hypothesis that there is an increased risk of breast cancer among women with a paternally inherited BRCA1 mutation compared to a maternally inherited mutation. However, the data are not sufficiently compelling to justify different screening recommendations for the two subgroups.     

Translational cell biology of highly malignant osteosarcoma

Highly malignant osteosarcoma (HMO) is the most frequent malignant bone tumor preferentially occurring in adolescents and children with a second more flat peak in patients over the age of 60. The younger patients benefit from combined neoadjuvant chemotherapy with 65–70% 5-year survival rate. In patients with metastatic HMO the 5-year survival rate is consistently poor with approximately 30%. In the last several years strategies for target therapies have been developed by using next generation sequencing (NGS) for defining targetable molecular factors. However, it has so far been challenging to establish an effective target therapy for so-called ‘orphan tumors’ without recognizable driver mutations, including HMO. The molecular genetic studies using NGS have shown that HMOs are genomically unstable tumors with highly complex chaotic karyotypes. Before the background of this genetic complexity more investigations should be performed in the future for defining targetable biological factors. As the prognosis could not be improved for 40 years one may expect improvements for patients only by gaining a deeper understanding of the cell and molecular biology of HMO. The cell of origin of HMO is being clarified now. The majority of studies indicate that an osteoblastic progenitor cell is probably the cell of origin of HMO and not an undifferentiated mesenchymal stem cell. This means that the established histopathological definition of HMO through verification of osteoid production by the osteoblastic cells is well justified and will probably be the cornerstone for a precise differential diagnosis of HMO also in the years to come.     

肾综合征出血热患者血清C反应蛋白测定的临床意义

目的：探讨 C 反应蛋白(CRP)在肾综合征出血热(HFRS)的诊断意义。方法收集96例各病期 HFRS 患者血清,以30例发热待查患者(发热待查组)及30例体检健康者(健康对照组)为对照,测定血清 CRP、丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、肌酸激酶(CK)、乳酸脱氢酶(LDH)、肌酐(Cr)水平。结果各病期 HFRS 患者 CRP 水平均低于发热待查组,差异均有统计学意义(P <0.05);CRP 在 HFRS 患者各病期的变化趋势与 AST、CK、LDH、Cr 基本一致。结论CRP 对鉴别HFRS 与普通发热待查有重要临床意义。     

Localization of cardiac arrhythmias: conventional noninvasive methods

Noninvasive localization of the accessory pathway (AP) in patients with the Wolff-Parkinson-White syndrome and of the site of origin of ventricular tachycardia (VT) is reviewed. 12-lead electrocardiography (ECG) is the most readily available method for localization of both the AP and the site of VT origin. Many published ECG criteria are introduced. The application of body surface potential mapping, vectocardiography, nuclear phase imaging, echocardiography, computed tomography, nuclear magnetic resonance, and signal-averaged ECG in the localization of these arrhythmogenic substrates is also described. We believe that ECG is the most sensitive noninvasive method for AP localization as well as being convenient and simple; it may be used as the only noninvasive method for the initial evaluation. The left lateral AP, which occurs with an incidence of more than 40%, could be localized preoperatively by noninvasive methods only. For localization of the site of VT origin, none of the noninvasive methods is accurate enough for guiding the surgical and catheter-mediated ablative therapies so far.Abbreviations AP accessory pathway - ARVD arrhythmogenic right ventricular dysplasia - BSPM body surface potential mapping - LFW left free wall - LAW left anterior wall - LLW left lateral wall - LPW left posterior wall - LPS left posteroseptal - NMR nuclear magnetic resonance - PS posteroseptal - RFW right free wall - RAS right anteroseptal - RAW right anterior wall - RLW right lateral wall - RPW right posterior wall - RPS right posteroseptal - VPB ventricular premature beats     

Analysis of antioxidant prenylflavonoids in different parts of Macaranga tanarius,the plant origin of Okinawan propolis

Objective:To analyze the antioxidant prenylilavonoids in different parts of Macaranga tanarius(M.tanarius)(Euphorbiaceae)including the leaf,petiole,stem,leaflet,flower and fruit(only in female plant),and to evaluate their antioxidant properties.Methods:Methanol extracts of each part of M.tanarius were prepared and five prenylilavonoids in them were quantitatively analyzed using HPLC.The fruits from female plant were further separated into seed,pericarp,and glandular trichome.After the quantitative analyses of prenylflavonoids in each part of M.tanarius,antioxidant activity of the extracts was evaluated by 2,2-diphenyl-l-picryI-hydrazyl(DPPH)radical scavenging assay.Results:The leaf of M.tanarius contained two prenylflavonoids as main components in both male and female plants.Both flowers(male and female)contained five kinds of prenylflavonoids.In the petiole,stem and leaflet of both male and female plants,the prenylflavonoids were not delected or their amounts were very low.Five kinds of prenylflavonoids were detected in the seed,pericarp and glandular trichome of female M.tanarius.In particular,the glandular trichome had the highest level of total prenylflavonoids(235 mg/g of fresh plant).DPPH radical scavenging activity of all parts was more than 30%.Conclusions:We found that different parts of M.tanarius contained antioxidant prenylflavonoids.In particular,not only the glandular trichome but also the leaf contained prenylflavonoids,which indicated that M.tanarius may be developed as a functional plant,because the leaves of this plant can be easily collected.     

From the Cover: Early Holocene chicken domestication in northern China

Chickens represent by far the most important poultry species, yet the number, locations, and timings of their domestication have remained controversial for more than a century. Here we report ancient mitochondrial DNA sequences from the earliest archaeological chicken bones from China, dating back to ∼10,000 B.P. The results clearly show that all investigated bones, including the oldest from the Nanzhuangtou site, are derived from the genus Gallus, rather than any other related genus, such as Phasianus. Our analyses also suggest that northern China represents one region of the earliest chicken domestication, possibly dating as early as 10,000 y B.P. Similar to the evidence from pig domestication, our results suggest that these early domesticated chickens contributed to the gene pool of modern chicken populations. Moreover, our results support the idea that multiple members of the genus Gallus, specifically Gallus gallus and Gallus sonneratii contributed to the gene pool of the modern domestic chicken. Our results provide further support for the growing evidence of an early mixed agricultural complex in northern China.In his epochal work on domestication, Darwin suggested that domestic chicken (Gallus gallus domesticus) originated from red jungle fowl (Gallus gallus gallus) ∼4,000 y B.P. in the Indus Valley (1). However, more recent evidence, based on both mitochondrial (mt) and nuclear DNA (2–4), refutes a monophyletic origin of G. g. domesticus. Analyses of large-scale mtDNA datasets (5) strongly suggest that chickens were domesticated multiple times in different parts of Asia, including regions in South Asia, Southwest China, and Southeast Asia. Although some of the earliest chicken bones have been discovered in northern China, dating to over 10,000 B.P. at the Nanzhuangtou site and to over 7,000 B.P. at several other sites (e.g., Cishan and Peiligang), northern China has not yet been suggested as a center of chicken domestication for two main reasons. First, it is unclear if the discovered bones really represent domesticated rather than wild members of the genus Gallus (6), and second, northern China is currently a semiarid steppe, and therefore does not provide suitable habitat for jungle fowl, the wild ancestor of domestic chicken. However, abundant remains of tropical animal and plant species excavated at the Cishan and Nanzhuangtou sites show that northern China was much warmer and more humid, with much more extensive forest coverage during the early Holocene (7, 8), providing a potentially suitable habitat for jungle fowl at this time. Moreover, previous studies have revealed northern China as a center for both early pig domestication (9) and the earliest millet domestication (10, 11) already by 10,000 B.P., showing that agriculture existed in this region at the time to which the earliest chicken bones date.Previous studies (9, 12, 13) have shown that ancient DNA analyses can be informative with regard to determining the places of domestication for a species. The time, region, and pattern of chicken domestication in particular regions over the world have also been worked out using ancient DNA analysis (14–17). However, the oldest chicken sequences analyzed to date are only around 4,000 y old, substantially postdating the beginning of chicken domestication.Therefore, we chose 39 ancient chicken bones from three archaeological sites in the area of the Yellow River (Cishan, Nanzhuangtou, and Wangyin), representing the earliest sites for chicken bones both in northern China and worldwide, and one younger archaeological site in the middle area of the Yangtze River (Jiuliandun Chu Tombs) for ancient DNA analyses (Fig. 1 and Table S1.Open in a separate windowFig. 1.Examples of ancient chicken bones and localities of all investigated samples. (A) Map of China showing the location of the four archaeological sites (red dots). (B) Typical ancient chicken bones unearthed in northern China. (C) Close-up of the Yellow River area from which the samples originate. The sites are marked with yellow dots with white asterisks.

Table 1.

Summary of ancient samples analyzed

胶原蛋白基再生医疗产品质量控制

由于胶原蛋白具有良好的生物相容性、可降解性、生物活性及可加工性等,作为再生医疗产品中重要的生物材料,被广泛应用于神经、骨、软骨、肌腱、韧带、血管植入物和皮肤修复中。为了保证胶原蛋白基再生医疗产品的安全和有效,有必要建立适当的质量控制体系。本文重点从原材料、产品性能、病毒去除/灭活、包装和灭菌等方面来探讨胶原蛋白基再生医疗产品质量控制的考虑要点,为该类产品的研发、生产及监管提供技术参考。