Polydendrocytes in development and myelin repair

Polydendrocytes (NG2 cells) are a distinct type of glia that populate the developing and adult central nervous systems (CNS). In the adult CNS, they retain mitotic activity and represent the largest proliferating cell population. Genetic and epigenetic mechanisms regulate the fate of polydendrocytes, which give rise to both oligodendrocytes and astrocytes. In addition, polydendrocytes actively differentiate into myelin-forming oligodendrocytes in response to demyelination. This review summarizes the current knowledge regarding polydendrocyte development, which provides an important basis for understanding the mechanisms that lead to the remyelination of demyelinated lesions.     

心复康丸对压力超负荷大鼠心肌肥厚的影响

目的观察心复康丸对压力超负荷性心肌肥厚大鼠超声心动指标及心肌肥厚程度的影响。方法 Wistar雄性大鼠采用腹主动脉缩窄的方法复制心肌肥厚和心室重构的模型。造模4周后,随机分为假手术组(S组)、模型组(M组)、依那普利组(E组)、心复康丸低剂量组(L组)、心复康丸高剂量组(H组)。分别于术后8周、12周采用超声心动评价心功能,并观察心脏肥大指数变化。结果术后8周,M组大鼠出现压力超负荷介导的向心性肥厚,术后12周,M组大鼠心功能进入失代偿期,E组和H组大鼠上述病理性改变均能被抑制;此两组还具有降低心脏肥大指数的作用(P0.01)。结论心复康丸具有改善超声心动指标,延缓心肌肥厚的作用,并存在一定量效关系。     

用于老年基础医学研究与临床辅助诊断的神经肽Y及其受体Y1-6检测方法的初步设想

神经肽Y（NPY）作为机体内一种主要的神经递质和能量调控因子，广泛参与机体各种生理功能的调节，是维持机体内环境稳态的重要物质之一。随着对其研究的不断深入，人们发现它可通过与特定靶细胞膜上不同NPY受体Y1-6的特异性结合而启动并激活相应细胞信号传导通路，从而参与对机体生理功能和靶细胞增殖分化的调控，且NPY及其受体在体内的表达水平又可影响机体的正常生理功能、细胞代谢活动、以及这种改变所诱导或促进或参与的某些老年性疾病的发生、发展及转归，并对相关药物的防治带来明显影响。因此，对NPY及其受体含量的检测项目已成为相关老年性疾病与合并症的发病机制分析、疾病进程观察、治疗效果评价、疾病痊愈判断及预后跟踪随访的重要辅助诊断指标之一。为此，本文通过对可用于老年基础医学研究与临床辅助诊断的NPY及其受体检测的酶联免疫吸附法、放射免疫测定法、荧光免疫检测法、化学发光免疫分析法、免疫组织化学法、压电石英晶片免疫传感器法、免疫印迹法、斑点免疫层析及胶体金法、受体放射配基结合分析法、放射自显影法、液体芯片技术、微粒子酶免分析法等进行NPY及其受体检测方法的综述，并提出前瞻性设想和设计，希望这些用于检测NPY及其受体指标的方法能为未来老年医学的研究和临床应用奠定基础。     

cAbl tyrosine kinase mediates reactive oxygen species- and caveolin-dependent AT1 receptor signaling in vascular smooth muscle: role in vascular hypertrophy

Important output signals of the angiotensin subtype 1 receptor (AT1R) in vascular smooth muscle cells (VSMCs) are mediated by angiotensin II (Ang II)-stimulated transactivation of the epidermal growth factor receptor (EGF-R), which is critical for vascular hypertrophy. Ang II-induced EGF-R transactivation is mediated through cSrc, a proximal target of reactive oxygen species (ROS) derived from NAD(P)H oxidase (NOX) and is dependent on AT(1)R trafficking through caveolin1 (Cav1)-enriched lipid rafts. Underlying molecular mechanisms are incompletely understood. The nonreceptor tyrosine kinase, proto-oncogene cAbl is a substrate of Src and is a major mediator for ROS-dependent tyrosine phosphorylation of Cav1. We thus hypothesized that cAbl is important for ROS-, cSrc-, and Cav1-dependent growth-related AT1R signal transduction. Here we show that Ang II induces tyrosine phosphorylation of cAbl in rat VSMCs and mouse aorta, and that Ang II promotes association of cAbl with AT(1)R, both of which are Src-dependent. Pretreatment of rat VSMCs with the NOX inhibitor diphenylene iodonium or the antioxidants N-acetylcysteine or ebselen significantly inhibited Ang II-induced cAbl phosphorylation. Cell fractionation shows that both EGF-Rs and cAbl are found basally in Cav1-enriched membrane fractions. Knockdown of cAbl protein using small interference RNA inhibits Ang II-stimulated: (1) trafficking of AT1R into, and EGF-R out of, Cav1-enriched lipid rafts; (2) EGF-R transactivation; (3) appearance of the transactivated EGF-R and phospho-Cav1 at focal adhesions; and (4) vascular hypertrophy. These studies provide a novel role of cAbl in the spatial and temporal organization of growth-related AT1R signaling in VSMCs and suggest that cAbl may be generally important in signaling of G-protein coupled receptors.     

血浆NT-proBNP检测在稳定期无肺动脉高压COPD患者中的意义

目的 探讨血浆NT-proBNP检测在彩超检查无肺动脉高压或肺心病稳定期慢性阻塞性肺疾病(COPD)中的意义.方法 选60例COPD患者和30例健康对照者,并进行血浆BNP检测、超声心动图检查、动脉血气分析和肺功能测定.对血浆BNP水平高的COPD患者和血浆BNP水平低的COPD患者进行2年的急性加重期情况的随访比较.结果 稳定期COPD患者血浆NT-ProBNP(680.6±54.78) pg/ml显著高于健康对照组[(120.4± 15.65) pg/ml] (P＜0.05).血浆NT-ProBNP水平和射血分数之间呈显著负相关(r=-0.56,P＜0.05)和肺动脉收缩压呈显著正相关(r=0.68,P＜0.05).在2年的急性加重情况随访期间,以NT-proBNP≥500 pg/n1为截点值,血浆NT-ProBNP水平高的COPD患者从开始随访到初次的COPD急性加重的时间[(6.25±1.23)月]较血浆NT-ProBNP水平低的患者加重的时间[(10.13±2.08)月]显著缩短(P＜0.05),且急性加重的次数(3.35±0.25)显著增加(P＜0.05).结论 血浆BNP是一种非侵入性生物标志物,可以作为COPD潜在肺动脉高压及左室功能障碍的一个筛选参数,并可作为稳定期患者急性加重的预测因素.     

Low back pain: Influence of early MR imaging or CT on treatment and outcome - a randomized controlled study protocol

Objective:To establish whether early use of magnetic resonance imaging (MRI) or computed tomography (CT) influences treatment and outcome of patients with low back pain.Methods:This study will be implemented from March 2021 to March 2022 at Huzhou Traditional Chinese Medicine Hospital Affiliated to Zhejiang Chinese Medical University. The experiment was granted through the Research Ethics Committee of Huzhou Traditional Chinese Medicine Hospital Affiliated to Zhejiang Chinese Medical University (R609320987). Patients who have symptomatic lumbar spine disorders at presentation are eligible for the trial if there is clinical uncertainty about the need for imaging (MRI or CT). Patients are excluded who required immediate referral for imaging (those who had signs suggestive of serious abnormalities or disease or who required surgical intervention), who have undergone MR imaging or CT of the spine within 1 year, who do not need imaging, and who have pain of a nonspinal origin. The primary outcome measure is the Aberdeen Low Back Pain (ALBP) score. Other principal outcome measure is the Short Form 36.Results:Table 1 will show the quality of life outcome measures between groups.Conclusion:This study may guide the policy makers to develop an evidence-based protocol to assess the effect of early use of MRI or CT in the treatment of patients with low back pain.     

Plasma dilution improves cognition and attenuates neuroinflammation in old mice

Our recent study has established that young blood factors are not causal, nor necessary, for the systemic rejuvenation of mammalian tissues. Instead, a procedure referred to as neutral blood exchange (NBE) that resets signaling milieu to a pro-regenerative state through dilution of old plasma, enhanced the health and repair of the muscle and liver, and promoted better hippocampal neurogenesis in 2-year-old mice (Mehdipour et al., Aging 12:8790–8819, 2020). Here we expand the rejuvenative phenotypes of NBE, focusing on the brain. Namely, our results demonstrate that old mice perform much better in novel object and novel texture (whisker discrimination) tests after a single NBE, which is accompanied by reduced neuroinflammation (less-activated CD68⁺ microglia). Evidence against attenuation/dilution of peripheral senescence-associated secretory phenotype (SASP) as the main mechanism behind NBE was that the senolytic ABT 263 had limited effects on neuroinflammation and did not enhance hippocampal neurogenesis in the old mice. Interestingly, peripherally acting ABT 263 and NBE both diminished SA-βGal signal in the old brain, demonstrating that peripheral senescence propagates to the brain, but NBE was more robustly rejuvenative than ABT 263, suggesting that rejuvenation was not simply by reducing senescence. Explaining the mechanism of the positive effects of NBE on the brain, our comparative proteomics analysis demonstrated that dilution of old blood plasma yields an increase in the determinants of brain maintenance and repair in mice and in people. These findings confirm the paradigm of rejuvenation through dilution of age-elevated systemic factors and extrapolate it to brain health and function.

     

Long-term renal outcomes of mesangial proliferative lupus nephritis in Chinese patients

Clinical Rheumatology - This study aimed to explore the long-term outcomes of mesangial proliferative lupus nephritis (LN class II) and the factors associated with its relapse and histological...     

Evaluation of adalimumab biosimilar candidate (HS016) in Chinese patients with active ankylosing spondylitis based on a health survey: sub-analysis of a phase 3 study

Clinical Rheumatology - The equivalence of the biosimilar HS016 to adalimumab (Humira) for the treatment of active ankylosing spondylitis (AS) patients has been previously validated. The aim was to...