The centrally projecting Edinger–Westphal nucleus—I: Efferents in the rat brain

The oculomotor accessory nucleus, often referred to as the Edinger–Westphal nucleus [EW], was first identified in the 17th century. Although its most well known function is the control of pupil diameter, some controversy has arisen regarding the exact location of these preganglionic neurons. Currently, the EW is thought to consist of two different parts. The first part [termed the preganglionic EW—EWpg], which controls lens accommodation, choroidal blood flow and pupillary constriction, primarily consists of cholinergic cells that project to the ciliary ganglion. The second part [termed the centrally projecting EW—EWcp], which is involved in non-ocular functions such as feeding behavior, stress responses, addiction and pain, consists of peptidergic neurons that project to the brainstem, the spinal cord and prosencephalic regions. However, in the literature, we found few reports related to either ascending or descending projections from the EWcp that are compatible with its currently described functions. Therefore, the objective of the present study was to systematically investigate the ascending and descending projections of the EW in the rat brain. We injected the anterograde tracer biotinylated dextran amine into the EW or the retrograde tracer cholera toxin subunit B into multiple EW targets as controls. Additionally, we investigated the potential EW-mediated innervation of neuronal populations with known neurochemical signatures, such as melanin-concentrating hormone in the lateral hypothalamic area [LHA] and corticotropin-releasing factor in the central nucleus of the amygdala [CeM]. We observed anterogradely labeled fibers in the LHA, the reuniens thalamic nucleus, the oval part of the bed nucleus of the stria terminalis, the medial part of the central nucleus of the amygdala, and the zona incerta. We confirmed our EW–LHA and EW–CeM connections using retrograde tracers. We also observed moderate EW-mediated innervation of the paraventricular nucleus of the hypothalamus and the posterior hypothalamus. Our findings provide anatomical bases for previously unrecognized roles of the EW in the modulation of several physiologic systems.     

连花清瘟胶囊治疗病毒性感冒的有效性与安全性观察

目的观察连花清瘟胶囊治疗病毒性感冒的疗效及安全性。方法将临床确诊为病毒性感冒的200例患者随机分为两组。治疗组100例采用连花清瘟胶囊口服治疗方案,对照组100例采用强效感冒片口服治疗方案,疗程各为3天。结果治疗组有效率明显高于对照组（P〈0.05）,副反应无明显差异（P〉0.05）。结论连花清瘟胶囊治疗病毒性感冒效果显著,无严重不良反应。     

LIM-domain proteins,LIMD1, Ajuba,and WTIP are required for microRNA-mediated gene silencing

In recent years there have been major advances with respect to the identification of the protein components and mechanisms of microRNA (miRNA) mediated silencing. However, the complete and precise repertoire of components and mechanism(s) of action remain to be fully elucidated. Herein we reveal the identification of a family of three LIM domain-containing proteins, LIMD1, Ajuba and WTIP (Ajuba LIM proteins) as novel mammalian processing body (P-body) components, which highlight a novel mechanism of miRNA-mediated gene silencing. Furthermore, we reveal that LIMD1, Ajuba, and WTIP bind to Ago1/2, RCK, Dcp2, and eIF4E in vivo, that they are required for miRNA-mediated, but not siRNA-mediated gene silencing and that all three proteins bind to the mRNA 5′ m⁷GTP cap–protein complex. Mechanistically, we propose the Ajuba LIM proteins interact with the m⁷GTP cap structure via a specific interaction with eIF4E that prevents 4EBP1 and eIF4G interaction. In addition, these LIM-domain proteins facilitate miRNA-mediated gene silencing by acting as an essential molecular link between the translationally inhibited eIF4E-m⁷GTP-5^′cap and Ago1/2 within the miRISC complex attached to the 3′-UTR of mRNA, creating an inhibitory closed-loop complex.     

Local control of a disorder-order transition in 4E-BP1 underpins regulation of translation via eIF4E

The molecular mechanism underpinning regulation of eukaryotic translation initiation factor eIF4E by 4E-BP1 has remained unclear. We use isothermal calorimetry, circular dichroism, NMR, and computational modeling to analyze how the structure of the eIF4E-binding domain of 4E-BP1 determines its affinity for the dorsal face of eIF4E and thus the ability of this regulator to act as a competitive inhibitor. This work identifies the key role of solvent-facing amino acids in 4E-BP1 that are not directly engaged in interactions with eIF4E. These amino acid residues influence the propensity of the natively unfolded binding motif to fold into a conformation, including a stretch of α-helix, that is required for tight binding to eIF4E. In so doing, they contribute to a free energy landscape for 4E-BP1 folding that is poised so that phosphorylation of S65 at the C-terminal end of the helical region can modulate the propensity of folding, and thus regulate the overall free energy of 4E-BP1 binding to eIF4E, over a physiologically significant range. Thus, phosphorylation acts as an intramolecular structural modulator that biases the free energy landscape for the disorder-order transition of 4E-BP1 by destabilizing the α-helix to favor the unfolded form that cannot bind eIF4E. This type of order-disorder regulatory mechanism is likely to be relevant to other intermolecular regulatory phenomena in the cell.     

储精式宫颈帽用于宫颈解剖位置异常人工授精的临床效果观察

目的:观察储精式宫颈帽用于宫颈解剖位置异常人工授精的临床效果。方法:将宫颈解剖位置异常导致不孕的妇女66例随机分成3组,实验组采用储精式宫颈帽夫精人工授精,对照A组采用宫颈管夫精人工授精,对照B组采用宫腔夫精人工授精,比较各组周期妊娠率。结果:周期妊娠率实验组(21.86%,14/65)高于对照A组(8.06%,5/62)(P<0.05),与对照B组(23.21%,13/56)比较无统计学差异(P>0.05)。结论:储精式宫颈帽夫精人工授精治疗宫颈解剖位置异常所致不孕与宫腔夫精人工授精临床效果一致,明显高于宫颈管夫精人工授精,是一种简单、方便和有效的人工授精方法。     

Rigid bronchoscopy for inhaled pen caps in children

Purpose

The aim of this study was to present the clinical findings and treatment of pen cap inhalation with emphasis on the importance of managing aspirated foreign bodies by rigid bronchoscopy.

Methods and Patients

Of 1280 patients with foreign body inhalation treated from 1997 to 2007, 34 (2.65%) were because of pen cap inhalation. Medical records of these 34 patients were retrospectively reviewed and analyzed for age, sex, symptoms, location of pen cap, treatment, complications, and outcomes.

Results

Of the 34 children with pen cap inhalation, 22 (64.7%) were boys and 12 (35.3%) were girls. They ranged in age from 6 to 14 years, pen caps were most frequently found in the right main stem bronchus (26 cases, 76.4%). A history of an episode of foreign body inhalation (34 cases, 100%) and acute cough (28 cases, 82.3%) were the most common presenting findings. All inhaled pen caps were successfully removed by reverse grasping forceps during rigid bronchoscopy. Tracheotomy, thoracotomy, and bronchotomy were not performed in any patients. There were no severe complications or deaths.

Conclusions

Pen cap inhalation mostly occurs in school-aged children. Patients usually can depict a clear history of pen cap inhalation, which is vital to early diagnosis. Inhaled pen caps can be removed safely by rigid bronchoscopy under general anesthesia combined with topical anesthesia. Open surgical techniques such as tracheotomy, thoracotomy, and bronchotomy can be avoided in most cases. More attention to programs of prevention, public and parent education, and awareness is needed to reduce the incidence of pen cap inhalation.     

Role of endothelial shear stress in the natural history of coronary atherosclerosis and vascular remodeling: molecular, cellular, and vascular behavior

Although the entire coronary tree is exposed to the atherogenic effect of the systemic risk factors, atherosclerotic lesions form at specific arterial regions, where low and oscillatory endothelial shear stress (ESS) occur. Low ESS modulates endothelial gene expression through complex mechanoreception and mechanotransduction processes, inducing an atherogenic endothelial phenotype and formation of an early atherosclerotic plaque. Each early plaque exhibits an individual natural history of progression, regression, or stabilization, which is dependent not only on the formation and progression of atherosclerosis but also on the vascular remodeling response. Although the pathophysiologic mechanisms involved in the remodeling of the atherosclerotic wall are incompletely understood, the dynamic interplay between local hemodynamic milieu, low ESS in particular, and the biology of the wall is likely to be important. In this review, we explore the molecular, cellular, and vascular processes supporting the role of low ESS in the natural history of coronary atherosclerosis and vascular remodeling and indicate likely mechanisms concerning the different natural history trajectories of individual coronary lesions. Atherosclerotic plaques associated with excessive expansive remodeling evolve to high-risk plaques, because low ESS conditions persist, thereby promoting continued local lipid accumulation, inflammation, oxidative stress, matrix breakdown, and eventually further plaque progression and excessive expansive remodeling. An enhanced understanding of the pathobiologic processes responsible for atherosclerosis and vascular remodeling might allow for early identification of a high-risk coronary plaque and thereby provide a rationale for innovative diagnostic and/or therapeutic strategies for the management of coronary patients and prevention of acute coronary syndromes.     

PMMA与铜平衡帽对6MV光子线反散射因子和准直器散射因子测量结果影响的比较研究

目的:通过比较聚甲基丙烯酸甲酯(PMMA)与铜平衡帽对6 MV光子线反散射因子(BSF)和准直器散射因子(Sc)测量结果的影响,提出一种简单易行的测量高能光子线BSF和Sc的方法。材料与方法:分别使用PMMA与铜制平衡帽在SAD和SSD两种方式下测量6MV光子线的BSF和Sc,并比较分析测量数据。结果:相同条件下铜制平衡帽的吸收剂量值测量结果明显偏大,而Sc的数值与变化趋势在不同的平衡帽材料和测量方式下基本不发生变化;BSF、Sc在同一平衡帽、两种测量方式下得到的结果变化不大,但使用PMMA平衡帽的结果略优于铜制平衡帽。结论:为了满足精确测量和简化方法的要求,建议采用SAD测量方式并使用PMMA平衡帽测量Sc与BSF。