GNAS gene mutations affecting XLαs and bone health: A long neglected relationship

The GNAS locus is an imprinted site. The α-subunit of the stimulatory G protein (Gsα) and extralarge variant (XLαs) are the two important products of the GNAS locus. The abnormal expression of Gsα is associated with pseudohypoparathyroidism (PHP) and related disorders, including Albright hereditary osteodystrophy (AHO), pseudopseudohypoparathyroidism (PPHP), and progressive osseous heteroplasia (POH). XLαs protein can mimic the catalytic intracellular synthesis of cyclic adenosine monophosphate (cAMP) by Gsα in response to parathyroid hormone (PTH) stimulation, which may be involved in the pathogenesis of PPHP and POH in patients with paternal GNAS defects. A paternally inherited nonsense variant in the first exon of XLαs in an adult patient may be associated with fractures and osteopetrosis. The relationship between the XLαs product of the GNAS locus and bone remodeling may have been overlooked. Here, we summarize the phenotypes of genetic mouse models and clinical cases of XLαs variations and suggest that the abnormal paternal expression of XLαs may be associated with the development of POH and affect osteoblast and osteoclast differentiation.     

Simultaneous Construct Surface Microstructural and Internal Network-Like Conductive Pathways of Poly(l-lactic acid)/Carbon Nanomaterials Composite Foams

The poly(l -lactic acid) (PLLA)/carbon nanomaterials composite foams with hierarchical surface microstructural and internal conductive pathways are successfully prepared by a simple crystallization-assisted rapid phase separation (CARPS). The dimension and morphology of carbon nanomaterials can induce different crystallization forms to construct the hierarchical surface microstructure, and they are distributed on the phase interface of solvent and non-solvent to form conductive pathways. It is found that the heterogeneous nucleation of nanomaterials promotes a significant increase in crystallinity, and a stacked granular structure formed on the surface promotes the increase of the water contact angle to 148.7°. Foams with interconnecting pore structures contribute to the formation of 85.3% porosity and 12.33 g g⁻¹ oil absorption. Carbon nanomaterials are distributed on the pore walls of the porous foam, which converts the foam from an insulating material to a conducting polymer. Furthermore, the uniform distribution of nanomaterials significantly affects the thermal stability of the PLLA. In belief, the multifunctional biodegradable foam, prepared by a CARPS method, makes it promising for industrial production and has potential applications in electrical conductivity, oil-water separation, and many other fields.     

中药材“地区习惯用药”渐趋分化论

论述了中药材“地区习惯用药”的由来与含义,近现代和历史上的“地区习惯用药”的实例以及产生“地区习惯用药”的原因,随品种性质判明而渐趋分化等。最后提出应该积极研究,促其分化,按其本质分类处理的建议。     

深圳市一孩先天性残疾家庭的二孩同类病研究

本文对深圳市1990～1997年因独生子女先天残疾通过病残儿鉴定再生育二孩的家庭进行调查,并以同期通过鉴定的后天性残疾家庭为内对照,以农村地区一孩先天残疾未经病残儿鉴定生育二孩的家庭为外对照,了解其二孩先天残疾再发情况,尤其是同类病的再发情况,拟对独生子女病残儿医学鉴定和二胎生育指标的审批工作效果进行评价,为优生工作提供依据。研究结果表明,鉴定组一孩先天残疾家庭二孩先天残疾的患病率为5.81％,与广州市1986～1991年情况类似(5.9％),高于外省(辽宁1990～1992年为1.35％)。鉴定组二胎同类病发生率为2.8％,非鉴定组为4.55％,两组比较虽无统计学差异,但病种上却有不同,鉴定组为再发风险低的血友病、先天性共转性内斜视、脑萎缩,而非鉴定组为再发风险高的先天聋哑、进行性肌萎缩。提示病残儿鉴定工作颇有成效,避免了相当一部分遗传病家庭再次生育残疾儿,但某些环节有待进一步完善;对农村一胎先天残疾家庭生育二胎也必须纳入管理范围。     

Ⅱ型糖尿病并发心脏病危险因素的logistic回归分析

探讨Ⅱ型糖尿病并发心脏病的危险因素,用ｌｏｇｉｓｔｉｃ回归模型对糖尿病并发心脏病的危险因素进行分析,结果显示患者体重指数较大、心理评分较高、舒张压高及血脂高,其发生心脏病的风险增加;饮食评分较高,较好的控制饮食,其并发心脏病的风险较低。故较好的控制患者血压、血脂和饮食可以减少并发症的发生、延长患者的寿命 。     

腹腔镜下全子宫切除术的临床评估

目的：对腹腔腔镜下全宫切除的临床价值进行评估。方法：对４３ 例因诊断为子宫肌瘤（３３ 例） 、子宫腺肌症（６例） 及子宫内膜增殖症（４ 例） 的患者行腹腔镜下全子宫切除术,对同时期１２１ 例具有同样适应症的患者行腹式全子宫切除手术。比较两组病人术中术后情况。结果：两组病人的手术时间、术中出血量无显著性差异,腹腔镜下全子宫切除术的手术时间与子宫增大有关,术中出血量与手术时间及子宫大小无关;行腹腔镜下全子宫切除术的病人手术损伤及术后阴道残端出血发生率无增高,术后疼痛的发生率明显减少,术后使用抗菌素时间、术后住院时间及术后恢复正常活动的时间缩短。结论：腹腔镜下全子宫切除术虽不能完全代替腹式全宫切除术,却是一种安全、可靠,适于临床广泛开展的手术方式。     

眶上神经的走行层次及其临床意义

目的探讨眉区和额部不同手术层面眶上神经的保护方法。方法在１５例成人头部标本上,对眶上神经在眉区和额部的行程、走行层次和入肌点的位置进行解剖观测。结果眶上神经出眶上孔后,以５２．８±７．４°角向外上经额肌筋膜附着处入帽状腱膜下隙,达发际附近穿帽状腱膜和额肌至皮下。眶上神经起始部直径１．４±０．３ｍｍ,本干入肌点至眶上孔的直线距离为４０．２±９．１ｍｍ,水平距离和垂直距离分别为３０．５±８．８ｍｍ和３３．８±８．４ｍｍ。结论根据手术层面的不同,额眉区的深层面手术应注意保护眶上神经     

罗库溴铵、阿曲库铵和琥珀酰胆碱三药肌松作用的对照研究

全麻下组Ⅰ以罗库溴铵０ ．６ ｍｇ／ｋｇ 静注,组Ⅱ以阿曲库铵０ ．５ ｍｇ／ｋｇ 静注,组Ⅲ以琥珀酰胆碱１ ．５ ｍｇ／ｋｇ 静注。结果：气管插管条件,以琥珀酰胆碱组肌松作用最好,而罗库溴铵和阿曲库铵肌松作用相似;罗库溴铵组肌松起效时间、临床恢复时间和无反应时间分别为８６ ．２５ ±２７ ．１３ｓ 、２９ ．９０ ±６ ．２５ ｍｉｎ 和２０ ．８４ ±７ ．９５ ｍｉｎ ,介于其它两药之间。说明,罗库溴铵可为临床提供较好的气管插管条件,且无琥珀酰胆碱的诸多副作用。     

Effects of cerebrospinal fluid from patients with Parkinson disease on dopaminergic cells

BACKGROUND: The pathogenesis of substantia nigra pars compacta neuronal injury in Parkinson disease (PD) remains unknown. Cerebrospinal fluid (CSF) has been reported to contain factors toxic to dopaminergic neurons. OBJECTIVES: To determine whether the cytotoxic effects of CSF of PD patients are specific for dopaminergic neurons, dependent on prior levodopa therapy, and mediated by the cytokine tumor necrosis factor alpha (TNF-alpha). DESIGN: Specimens of CSF were evaluated in dopaminergic (MES 23.5) and nondopaminergic (N18TG2) cell lines for cytotoxicity by viability assay and by the inhibition of tyrosine hydroxylase. After specificity and time and dose response were established, CSF specimens were assayed in a blinded manner. The TNF-alpha levels in CSF were determined by enzyme-linked immunosorbent assay. The toxicity of TNF-alpha in MES 23.5 cells was determined. SETTING: A university-based research facility. SUBJECTS: There were 4 groups of subjects: normal control subjects (n = 10), control subjects with neurologic disease (n = 8), PD patients treated with levodopa (n = 10), and untreated subjects with PD (n= 20). RESULTS: Specimens of CSF from 15 (50%) of 30 PD patients and 2 (11%) of 18 control subjects were cytotoxic to dopaminergic MES 23.5 cells and were nontoxic to the parental cell line N18TG2. There was no correlation between the degree of PD CSF cytotoxicity, levodopa therapy, or the severity and duration of PD. Terminal deoxynucleotidyl transferase-mediated biotin-deoxyuridine triphosphate nick-end labeling (TUNEL) for DNA fragmentation suggested the involvement of apoptotic mechanisms. The inhibition of tyrosine hydroxylase was an early effect of cell injury by PD CSF and correlated with the viability assay. The mean TNF-alpha level was 2.6-fold higher in CSF specimens from PD patients than in those of controls. The addition of recombinant human TNF-alpha equivalent to the highest level determined in PD CSF was not cytotoxic to MES 23.5 cultures. CONCLUSIONS: Blinded CSF specimens from PD patients, regardless of therapy, contain factors that cause specific dopaminergic neuronal cell injury. These factors are present in a substantial proportion of CSF specimens from patients with early PD, before the institution of medical therapy. Levels of TNF-alpha are elevated in the CSF of PD patients, but TNF-alpha is not responsible for the cytotoxicity.     

Protection against amyloid beta peptide toxicity by zinc

Zinc (Zn) is an essential element in normal development and biology, although it is toxic at high concentrations. Recent studies show that Zn at high concentrations accelerates aggregation of amyloid beta peptide (Abeta), the major component of senile plaques in Alzheimer's disease (AD). This study reports the effect of varying Zn concentrations on Abeta toxicity and the mechanism by which low concentrations function in a protective role. At Abeta/Zn molar ratios of 1:0.1 and 1:0.01, Zn produces significant protection against Abeta toxicity in cultured primary hippocampal neurons. At higher concentrations (1:1 molar ratio), Zn offers no protection or enhances Abeta toxicity. The protective effect of Zn against Abeta toxicity is due in part to the enhancement of Na+/K+ ATPase activity which prevents the disruption of calcium homeostasis and cell death associated with Abeta toxicity. Analysis of Na+/K+ ATPase activity in cultured rat cortical cells indicated that Zn exposure alone afforded a 20% increase in enzyme activity, although the differences were statistically insignificant. However, in cortical cultures exposed to a toxic dose of Abeta (50 microM), Zn at concentrations of 5 and 0.5 microM led to significant increases in Na+/K+ ATPase activity compared with levels in cells treated with Abeta alone. Zn at a 1:1 molar ratio (50 microM) led to a significant decrease in enzyme activity. Together, these data suggest that Zn functions as a double-edged sword, affording protection against Abeta at low concentrations and enhancing toxicity at high concentrations.