软骨细胞的老化对软骨蛋白聚糖代谢的影响

目的:探讨体外培养猪耳软骨细胞在老化过程中,软骨蛋白聚糖(aggrecan)的代谢状况与分子结构的变化及其水解酶(aggrecanase)表达水平的改变。由此进一步阐明aggrecan在组织工程软骨构建中起决定性的作用。方法:取体外培养P1-P8各代猪耳软骨细胞及其培养液,爱茜蓝(Alcian Blue)法检测培养液中蛋白聚糖的含量和糖胺聚糖(glycosaminoglycan,GAG)的分子结构。RT-PCR检测aggre-canase-1和-2的mRNA表达水平。结果:在P1细胞的培养液中,蛋白聚糖的含量和长链/高度硫酸化的GAG含量都是最高的。由P4细胞开始,这2项指标均显著减少(P<0.01),且两者的变化趋势有显著的相关性(P<0.01)。Aggrecanase-1 mRNA在前3代细胞基本无表达,P4细胞中有显著上升(P<0.01),随后逐渐减少,P8细胞又不再表达。Aggrecanase-2 mRNA的表达呈随机状态,与细胞代数无显著性相关(P>0.05)。结论:体外培养软骨细胞的老化对aggrecan的代谢有非常大的影响。一方面aggrecan的合成减少、大分子聚合物形成受阻;另一方面胞外基质的水解作用加剧,最终导致老化细胞的基质崩解。     

Cavity cooling of an optically levitated submicron particle

The coupling of a levitated submicron particle and an optical cavity field promises access to a unique parameter regime both for macroscopic quantum experiments and for high-precision force sensing. We report a demonstration of such controlled interactions by cavity cooling the center-of-mass motion of an optically trapped submicron particle. This paves the way for a light–matter interface that can enable room-temperature quantum experiments with mesoscopic mechanical systems.     

儿童复发性腹股沟斜疝的腹腔镜内环结扎术治疗

目的探讨腹腔镜内环结扎术治疗儿童复发性腹股沟斜疝的优势及手术经验。 方法选择2013年1月至2018年1月，广州市妇女儿童医疗中心收治的34例复发性腹股沟斜疝患儿为研究对象。回顾性分析其临床病例资料。根据本次入院采取的手术治疗方式，将其分为腹腔镜组(n＝19，采用腹腔镜内环结扎术)和开放手术组(n＝15，采用疝囊高位结扎术)。采用独立样本t检验及χ²检验，对2组患儿一般临床资料、术中及术后情况等，进行统计学分析。本研究符合2013年修订的《世界医学协会赫尔辛基宣言》要求，所有患儿监护人均于术前签署手术治疗知情同意书。 结果①开放手术组患儿术后，3例出现阴囊血肿，1例出现医源性隐睾。2组患儿术后均未发生伤口感染、睾丸萎缩、阴囊积液及再次复发等其他并发症。②2组患儿中，男性患儿所占比例、月龄及初次手术为腹腔镜手术所占比例比较，差异均无统计学意义(P>0.05)。腹腔镜组患儿的手术时间、术中出血量、住院时间及术后并发症发生率分别为(30.0±10.7) min、(1.0±0.3) mL、(1.2±0.4) d、0，均显著短于或少于开放手术组的(44.7±24.5) min、(2.3±1.3) mL、(3.3±1.0) d、26.7%；其住院费用为(7 547±820)元，则显著高于开放手术组的(5 488±1 218)元，并且差异均有统计学意义(t＝－2.347、P＝0.044，t＝－3.859、P＝0.002，t＝－8.171、P<0.001，P＝0.029，t＝5.580、P<0.001)。 结论腹腔镜内环结扎术治疗儿童复发性腹股沟斜疝，具有安全有效、术中情况良好、术后并发症少等优势，但住院费用相对偏高。     

Activins and activin antagonists in hepatocellular carcinoma

In many parts of the world hepatocellular carcinoma （HCC） is among the leading causes of cancer-related mortality but the underlying molecular pathology is still insufficiently understood. There is increasing evidence that activins, which are members of the transforming growth factor β （TGFβ） superfamily of growth and differentiation factors, could play important roles in liver carcinogenesis. Activins are disulphide-linked homoor heterodimers formed from four different β subunits termed βA, βB, βC, and βE, respectively. Activin A, the dimer of two βA subunits, is critically involved in the regulation of cell growth, apoptosis, and tissue architecture in the liver, while the hepatic function of other activins is largely unexplored so far. Negative regulators of activin signals include antagonists in the extracellular space like the binding proteins follistatin and FLRG, and at the cell membrane antagonistic coreceptors like Cripto or BAMBI. Additionally, in the intracellular space inhibitory Smads can modulate and control activin activity. Accumulating data suggest that deregulation of activin signals contributes to pathologic conditions such as chronic inflammation, fibrosis and development of cancer. The current article reviews the alterations in components of the activin signaling pathway that have been observed in HCC and discusses their potential significance for liver tumorigenesis.     

Episodic Migraine With and Without Aura: Key Differences and Implications for Pathophysiology,Management, and Assessing Risks

Purpose of Review

To review the pathophysiologic, epidemiologic, and clinical evidence for similarities and differences between migraine with and without aura.

Recent Findings

The ICHD-3 has recently refined the diagnostic criteria for aura to include positive symptomatology, which better differentiates aura from TIA. Although substantial evidence supports cortical spreading depression as the cause of visual aura, the role (if any) of CSD in headache pain is not well understood. Recent imaging evidence suggests a possible hypothalamic origin for a headache attack, but further research is needed. Migraine with aura is associated with a modest increase in the risk of ischemic stroke. The etiology for this association remains unclear. There is a paucity of evidence regarding treatments specifically aimed at the migraine with aura subtype, or whether migraine with vs without aura responds to treatment differently. Migraine with typical aura is therefore often treated similarly to migraine without aura. Lamotrigine, daily aspirin, and flunarizine have evidence for efficacy in prevention of migraine with aura, and magnesium, ketamine, furosemide, and single-pulse transcranial magnetic stimulation have evidence for use as acute treatments. Although triptans have traditionally been contraindicated in hemiplegic migraine and migraine with brainstem aura, this prohibition is being reconsidered in the face of evidence suggesting that use may be safe.

Summary

The debate as to whether migraine with and without aura are different entities is ongoing. In an era of sophisticated imaging, genetic advancement, and ongoing clinical trials, efforts to answer this question are likely to yield important and clinically meaningful results.

     

Sleep Disorders and Migraine: Review of Literature and Potential Pathophysiology Mechanisms

Migraine shares a complex and poorly understood relationship with sleep. Patients consistently report poor sleep prior to migraine attacks and during them, identifying poor sleep as a migraine trigger. However, anecdotally, sleep is reported to serve a therapeutic role in terminating headache. Are the associations between migraine and sleep simply the result of various bidirectional relationships? A growing body of evidence suggests there may be a common underlying etiology as well. Our objective was to review studies of sleep and migraine from the last 2 decades utilizing validated subjective and objective measures of sleep and to explore potential mechanisms underlying this complex relationship by incorporating recent advances in neuroscience. We specifically focus on insomnia, obstructive sleep apnea, parasomnias, sleep related movement disorders, and REM sleep related disorders and their relationship to migraine. Parts of brainstem‐cortical networks involved in sleep physiology are unintentionally being identified as important factors in the common migraine pathway. Recent discoveries on anatomic localization (the hypothalamus as a key and early mediator in the pathophysiology of migraine), common mediating signaling molecules (such as serotonin and dopamine), and the discovery of a new CNS waste removal system, the glymphatic system, all point to a common pathophysiology manifesting in migraine and sleep problems.     

Non-linear renal function decline is frequent in patients with type 2 diabetes who progress fast to end-stage renal disease and is associated with African-Caribbean ethnicity and HbA1c variability

To our knowledge, there are no studies examining eGFR trajectories in an ethnically diverse cohort of T2DM patients with established DKD and long follow-up. We conducted a retrospective analysis of medical records of T2DM patients attending a specialist diabetes renal clinic in order to identify risk factors and specific eGFR trajectories associated with ESRD. There is limited information and long term follow-up on eGFR trajectories in ethnically diverse cohorts of T2DM patients with established diabetic kidney disease. We conducted a retrospective analysis of medical records of 398 T2DM patients (46.5% African-Carribean ethnicity) to identify risk factors and specific eGFR trajectories associated with end-stage renal disease (ESRD). A non-linear eGFR trajectory was observed in 59% of the 71 patients who reached ESRD. African-Caribbean ethnicity and glycaemic variability are independently associated with distinct non-linear eGFR trajectories that result in fast progression to ESRD. Clinicians should be aware that non-linear eGFR decline is frequent in patients with T2DM who have fast progression to ESRD. Predicting renal function decline based on patterns and early changes in eGFR trajectories and associated risk factors, may better enable individualized risk stratification and care for those at highest risk of rapid progression to ESRD.