Endoplasmic reticulum stress improved chicken tenderness,promoted apoptosis and autophagy during postmortem ageing

In this study,endoplasmic reticulum(ER)stress inducer tunicamycin(TM)and inhibitor 4-phenylbutyric acid(4-PBA)were used to treat postmortem chicken breast muscle to investigate changes in tenderness and effects on apoptosis and autophagy during 5 days ageing.TM-induced ER stress reduced shear force,enhanced myofibril fragmentation index(MFI),disrupted myofibril structure,increased desmin degradation,and activatedμ-calpain and caspase-12.In addition,TM-induced ER stress increased the expression of Bax,Bim,and cytochrome c,and decreased the expression of Bcl-x L.Furthermore,TM-induced ER stress improved the conversion of LC3I to LC3II,raised the expression of Beclin-1,and decreased the expression of p62,PI3K,and m TOR.The opposite results were observed after 4-PBA treatment.These results suggested that ER stress could improve chicken tenderness,promote apoptosis and autophagy during chicken postmortem ageing.

Controlling the dynamic behavior of decentralized cluster through centralized approaches

How to control the dynamic behavior of large-scale artificial active matter is a critical concern in experimental research on soft matter, particularly regarding the emergence of collective behaviors and the formation of group patterns. Centralized systems excel in precise control over individual behavior within a group, ensuring high accuracy and controllability in task execution. Nevertheless, their sensitivity to group size may limit their adaptability to diverse tasks. In contrast, decentralized systems empower individuals with autonomous decision-making, enhancing adaptability and system robustness. Yet, this flexibility comes at the cost of reduced accuracy and efficiency in task execution. In this work, we present a unique method for regulating the centralized dynamic behavior of self-organizing clusters based on environmental interactions. Within this environment-coupled robot system, each robot possesses similar dynamic characteristics, and their internal programs are entirely identical. However, their behaviors can be guided by the centralized control of the environment, facilitating the accomplishment of diverse cluster tasks. This approach aims to balance the accuracy and flexibility of centralized control with the robustness and task adaptability of decentralized control. The proactive regulation of dynamic behavioral characteristics in active matter groups, demonstrated in this work through environmental interactions, holds the potential to introduce a novel technological approach and provide experimental references for studying the dynamic behavior control of large-scale artificial active matter systems.

Analyses of Chicken Tenderness Traits Based on Transcriptome Sequencing

The calpain system is ubiquitous in cells, mainly comprising calpains and calpain inhibitors, and is a widespread calcium-dependent cysteine protease in organisms that is involved in many cellular processes such as muscle degradation in vivo and affects the tenderness of meat after animal slaughter. The study found 128 DEGs that probably regulated tenderness traits were selected from 16 significantly enriched GO terms by transcriptome sequencing analysis, and found that the developmental changes in the expression levels of the CAPN1 gene in the pectoral and leg muscles were significantly positively correlated ( P <0.05) with the cumulative growth values of live weight and comb weight. The developmental changes in the expression levels of the CAST gene in the pectoral and leg muscles were not significantly correlated with the cumulative growth values of live weight and comb weight. Our results helped demonstrate the potential molecular mechanisms of tenderness in chickens and provide valuable information for chicken breeding.

Effects of Different Rearing Modes on the Muscular Histological Traits and Meat Tenderness of Chicken

[ Objective] The aim of this experiment was to explore the effects of different rearing modes on muscle histological traits and muscle ten demess and to provide theoretical basis for regulating chicken meat quality. [ Method] The effects of outdoor rearing, indoor rearing and cage rea ring modes on the muscular histological traits and meat tenderness of Hetian chicken at the age of 8 weeks, 12 weeks and 16 weeks were re searched. [Result] The results showed that the breast and thigh muscle fibre diameter and muscle shear force of outdoor rearing chicken were sig nificently higher than that of cage rearing chicken （ P 〈 0.05）, and muscle fibre density was significantly lower than that of cage rearing chicken （ P 〈 0.05）. With aging, the muscle fibre diameter and shear force increased and muscle fibre density decreased （ P 〈 0.05）. The muscle fibre di ameter and shear force of male were higher than that of female. The correlation analysis showed that the breast muscle shear force had a signifi cantly positive relation with fibre diameter and negative relation with fibre density （ P 〈 0.05）, but thigh muscle shear force had an insignificantly pos itive relation with fibre diameter and fibre density. [ Condusion] Muscular histological traits varied in different rearing modes, and the outdoor rearing promoted the muscular fibre development and increased the muscular shear force.

滞动针干预“激痛点”对肌筋膜疼痛综合征模型大鼠中枢镇痛的作用机制

背景:滞动针治疗肌筋膜疼痛综合征的镇痛效果显著,但镇痛机制尚不明确。目的:探索滞动针干预激痛点缓解肌筋膜疼痛综合征疼痛的作用机制。方法:按照随机数字表法将54只SD大鼠随机分为空白组(n=16)和造模组(n=38),造模组采用“打击结合离心运动”方式制备左侧股内侧肌筋膜疼痛综合征模型,造模12周后随机挑选6只验证造模成功,将剩余32只造模大鼠随机分为模型组(n=16)与滞动针组(n=16),使用滞动针对滞动针组大鼠左侧股内侧肌局部激痛点进行干预治疗,2次/周,治疗4周。造模前后及治疗后进行左足机械缩足阈值测定;治疗后第4周,苏木精-伊红染色观察大鼠左侧股内侧肌肌肉组织形态学变化,ELISA法检测血清和中脑导水管周围灰质中P物质、β-内啡肽水平,免疫组化检测中脑导水管周围灰质中小胶质细胞标志物(Iba-1)和c-fos阳性表达,Western Blot检测中脑导水管周围灰质脑源性神经营养因子蛋白表达。结果与结论:①与空白组比较,造模后模型组、滞动针组大鼠机械缩足阈值降低(P<0.05);治疗4周后,滞动针组大鼠机械缩足阈值高于模型组(P<0.05);②苏木精-伊红染色结果显示,模型组肌纤维排列紊乱、粗细不等,肌细胞增大并出现核内移现象,细胞内出现圆形挛缩结节以及紧张带;滞动针组肌纤维排列整齐,肌细胞多呈角状,细胞内偶见挛缩结节;③与空白组比较,模型组血清中P物质水平升高(P<0.05),血清中β-内啡肽及脑中P物质、β-内啡肽水平均降低(P<0.05);与模型组比较,滞动针组血清中P物质水平降低(P<0.05),血清中β-内啡肽及脑中P物质、β-内啡肽水平均升高(P<0.05);④与空白组比较,模型组c-fos、Iba-1阳性表达及脑源性神经营养因子蛋白均升高(P<0.05);与模型组比较,滞动针组c-fos阳性表达升高(P<0.05),Iba-1阳性表达及脑源性神经营养因子蛋白均降低(P<0.05);(5)结果表明,滞动针可能通过抑制中脑导水管周围灰质小胶质细胞的活性、下调脑源性神经营养因子蛋白表达间接促进小胶质细胞向M2表型极化释放β-内啡肽、增加c-fos神经元兴奋性,从而降低中枢致敏程度,有效缓解肌筋膜疼痛综合征疼痛的症状。

Muscular Histological Traits and Meat Tenderness of Different Local Broilers

Objective＇ To study the muscular histological traits and their relationship with meat tenderness in local broilers and provide a theoretical basis for promoting meat quality of broiler. [Methed] The diameter and density of muscle fiber of three local varieties of chicken （Beijing Fatty broil- er, Fujian Hetian broiler and Taining Black broiler） were detected at the age of 8 weeks, 12 weeks and 16 weeks. And the differences in the diame- ter and density of muscle fiber as well as their relationship with meat tenderness were respectively analyzed with SAS software. [ Resultl Fatty broil- er had the smallest muscle fiber diameter while Hetian broiler the largest; Fatty broiler had the highest muscle fiber density while Hetian broiler the lowest Hetian broiler had the highest muscle shear force of leg muscle while Black broiler the lowest （ P 〈0.05） ; Black broiler had the highest mus- cle shear force of breast muscle while Fatty broiler the lowest （P〈0.05）. The correlation analysis showed that the shear force of breast muscle and leg muscle had significantly positive relation with fiber diameter and significantly negative relation with fiber density （ P 〈 0.05）. [ Conclusion] Muscu- lar histological traits varied in different local broilers, and the muscular shear force had significantly relation with fiber diameter and density.

基于肌肉激活的斜方肌平衡训练对偏瘫肩痛患者上肢运功功能及神经电生理的影响

目的:本研究探讨斜方肌平衡训练对卒中偏瘫后肩痛患者上肢运动功能及神经电生理的影响。方法:选取2021年10月~202 3年11月在广东省第二中医院康复科住院且符合纳入标准的卒中偏瘫后肩痛患者144例,随机分为对照组和观察组各72例。两组患者均采用常规用药及神经发育学治疗,对照组在此基础上采用肩胛带的稳定性训练,观察组在对照组的基础上采用斜方肌平衡训练(侧卧位肩外旋、侧卧位外旋、俯卧位水平外展、俯卧位水平后伸),两组患者训练均30min/次,1次/d,5次/周,连续训练6周;分别在治疗前和治疗6周后,对两组患者分别进行Fugl-Meycr上肢运动功能评分和VAS视觉模拟评分,以及上肢静息运动阈值(rMT)、中枢运动传导时间(CMCT)检测。结果:观察组9例及对照组7例患者因提前出院中途退出被剔除,最终观察组63例,对照组65例。治疗后,两组患者的VAS评分均较治疗前降低(P<0.05),FMA-UE评分均较治疗前升高(P<0.05),且观察组治疗后的VAS评分低于对照组(P<0.05),FMA-UE评分高于对照组(P<0.05)。治疗后,两组患者的rMT和CMCT均较治疗前降低(P<0.05),且观察组治疗后的rMT和CMCT均低于对照组(P<0.05)。结论:在肩胛带的稳定性训练基础上,斜方肌平衡训练能更好的改善偏瘫后肩痛患者的疼痛、运动功能及神经电生理。

Study on the Cutting Rooting of Syriga Microphylla with Tender Branches

[Objective] The study was carried out in order to find out the best method of rapid cutting rooting of Syriga microphylla with tender branches.[Method] Effect of rooting reagent with different concentrations on the rapid cutting rooting of Syriga microphylla with tender branches was studied in our paper.[Result] There was great difference between cuttings with auxin and without auxin.[Conclusion] Tender branches treated by 90 mg/L indole butyric acid（IBA）had the best cutting rooting.

Variation Law of Pericarp Tenderness of Super Sweet Corn Kernel

To investigate the variation law of pericarp tenderness in growth progress of super sweet corn kernel, the values of pericarp tenderness of 10 super sweet corn inbreeds were measured during kernel growth, and the variations under differ- ent conditions were analyzed. The results showed that there existed gradient differ- ences in pericarp tenderness among the 10 materials, of which PE10 had the best pericarp tenderness, T105 took medial place, and $33205 performed worst in peri- carp tenderness. Pericarp tenderness values of these 3 inbreeds increased curvedly from 12 to 24 days after pollination, in the spring （Wuhan, Hubei） and winter （Ling- shui, Hainan） of 2014. Moreover, the average pericarp tenderness at different time points presented the same decreasing order of $33205, T105, PE10, which was not altered by enviroment. With the growth of kernel, for one material, the difference of pericarp tenderness under different environments presented a law of increment, re- duction, uniformity. As for optimum-picking time, there was four days difference be- tween the spring in Wuhan and winter in Lingshui. However, there was no obvious difference in pericarp tenderness on the optimum picking time, which indicated that growing environment could affect the variation ratio of pericarp tenderness, but it still depended on the nature of materials.

Multilevel analysis of the central-peripheral-target organ pathway:contributing to recovery after peripheral nerve injury

Peripheral nerve injury is a common neurological condition that often leads to severe functional limitations and disabilities.Research on the pathogenesis of peripheral nerve injury has focused on pathological changes at individual injury sites,neglecting multilevel pathological analysis of the overall nervous system and target organs.This has led to restrictions on current therapeutic approaches.In this paper,we first summarize the potential mechanisms of peripheral nerve injury from a holistic perspective,covering the central nervous system,peripheral nervous system,and target organs.After peripheral nerve injury,the cortical plasticity of the brain is altered due to damage to and regeneration of peripheral nerves;changes such as neuronal apoptosis and axonal demyelination occur in the spinal cord.The nerve will undergo axonal regeneration,activation of Schwann cells,inflammatory response,and vascular system regeneration at the injury site.Corresponding damage to target organs can occur,including skeletal muscle atrophy and sensory receptor disruption.We then provide a brief review of the research advances in therapeutic approaches to peripheral nerve injury.The main current treatments are conducted passively and include physical factor rehabilitation,pharmacological treatments,cell-based therapies,and physical exercise.However,most treatments only partially address the problem and cannot complete the systematic recovery of the entire central nervous system-peripheral nervous system-target organ pathway.Therefore,we should further explore multilevel treatment options that produce effective,long-lasting results,perhaps requiring a combination of passive(traditional)and active(novel)treatment methods to stimulate rehabilitation at the central-peripheral-target organ levels to achieve better functional recovery.

Role of copper in central nervous system physiology and pathology

Copper is a transition metal and an essential element for the organism,as alterations in its homeostasis leading to metal accumulation or deficiency have pathological effects in several organs,including the central nervous system.Central copper dysregulations have been evidenced in two genetic disorders characterized by mutations in the copper-ATPases ATP7A and ATP7B,Menkes disease and Wilson’s disease,respectively,and also in multifactorial neurological disorders such as Alzheimer’s disease,Parkinson’s disease,amyotrophic lateral sclerosis,and multiple sclerosis.This review summarizes current knowledge about the role of copper in central nervous system physiology and pathology,reports about unbalances in copper levels and/or distribution under disease,describes relevant animal models for human disorders where copper metabolism genes are dysregulated,and discusses relevant therapeutic approaches modulating copper availability.Overall,alterations in copper metabolism may contribute to the etiology of central nervous system disorders and represent relevant therapeutic targets to restore tissue homeostasis.

Meningeal lymphatic vessel crosstalk with central nervous system immune cells in aging and neurodegenerative diseases

Meningeal lymphatic vessels form a relationship between the nervous system and periphery, which is relevant in both health and disease. Meningeal lymphatic vessels not only play a key role in the drainage of brain metabolites but also contribute to antigen delivery and immune cell activation. The advent of novel genomic technologies has enabled rapid progress in the characterization of myeloid and lymphoid cells and their interactions with meningeal lymphatic vessels within the central nervous system. In this review, we provide an overview of the multifaceted roles of meningeal lymphatic vessels within the context of the central nervous system immune network, highlighting recent discoveries on the immunological niche provided by meningeal lymphatic vessels. Furthermore, we delve into the mechanisms of crosstalk between meningeal lymphatic vessels and immune cells in the central nervous system under both homeostatic conditions and neurodegenerative diseases, discussing how these interactions shape the pathological outcomes. Regulation of meningeal lymphatic vessel function and structure can influence lymphatic drainage, cerebrospinal fluid-borne immune modulators, and immune cell populations in aging and neurodegenerative disorders, thereby playing a key role in shaping meningeal and brain parenchyma immunity.

Microglia lactylation in relation to central nervous system diseases

The development of neurodegenerative diseases is closely related to the disruption of central nervous system homeostasis.Microglia,as innate immune cells,play important roles in the maintenance of central nervous system homeostasis,injury response,and neurodegenerative diseases.Lactate has been considered a metabolic waste product,but recent studies are revealing ever more of the physiological functions of lactate.Lactylation is an important pathway in lactate function and is involved in glycolysis-related functions,macrophage polarization,neuromodulation,and angiogenesis and has also been implicated in the development of various diseases.This review provides an overview of the lactate metabolic and homeostatic regulatory processes involved in microglia lactylation,histone versus non-histone lactylation,and therapeutic approaches targeting lactate.Finally,we summarize the current research on microglia lactylation in central nervous system diseases.A deeper understanding of the metabolic regulatory mechanisms of microglia lactylation will provide more options for the treatment of central nervous system diseases.

Potassium and calcium channels in different nerve cells act as therapeutic targets in neurological disorders

The central nervous system, information integration center of the body, is mainly composed of neurons and glial cells. The neuron is one of the most basic and important structural and functional units of the central nervous system, with sensory stimulation and excitation conduction functions. Astrocytes and microglia belong to the glial cell family, which is the main source of cytokines and represents the main defense system of the central nervous system. Nerve cells undergo neurotransmission or gliotransmission, which regulates neuronal activity via the ion channels, receptors, or transporters expressed on nerve cell membranes. Ion channels, composed of large transmembrane proteins, play crucial roles in maintaining nerve cell homeostasis. These channels are also important for control of the membrane potential and in the secretion of neurotransmitters. A variety of cellular functions and life activities, including functional regulation of the central nervous system, the generation and conduction of nerve excitation, the occurrence of receptor potential, heart pulsation, smooth muscle peristalsis, skeletal muscle contraction, and hormone secretion, are closely related to ion channels associated with passive transmembrane transport. Two types of ion channels in the central nervous system, potassium channels and calcium channels, are closely related to various neurological disorders, including Alzheimer's disease, Parkinson's disease, and epilepsy. Accordingly, various drugs that can affect these ion channels have been explored deeply to provide new directions for the treatment of these neurological disorders. In this review, we focus on the functions of potassium and calcium ion channels in different nerve cells and their involvement in neurological disorders such as Parkinson's disease, Alzheimer's disease, depression, epilepsy, autism, and rare disorders. We also describe several clinical drugs that target potassium or calcium channels in nerve cells and could be used to treat these disorders. We concluded that there are few clinical drugs that can improve the pathology these diseases by acting on potassium or calcium ions. Although a few novel ion-channelspecific modulators have been discovered, meaningful therapies have largely not yet been realized. The lack of target-specific drugs, their requirement to cross the blood–brain barrier, and their exact underlying mechanisms all need further attention. This review aims to explain the urgent problems that need research progress and provide comprehensive information aiming to arouse the research community's interest in the development of ion channel-targeting drugs and the identification of new therapeutic targets for that can increase the cure rate of nervous system diseases and reduce the occurrence of adverse reactions in other systems.

The complex roles of m^(6)A modifications in neural stem cell proliferation, differentiation, and self-renewal and implications for memory and neurodegenerative diseases

N6-methyladenosine(m^(6)A), the most prevalent and conserved RNA modification in eukaryotic cells, profoundly influences virtually all aspects of mRNA metabolism. mRNA plays crucial roles in neural stem cell genesis and neural regeneration, where it is highly concentrated and actively involved in these processes. Changes in m^(6)A modification levels and the expression levels of related enzymatic proteins can lead to neurological dysfunction and contribute to the development of neurological diseases. Furthermore, the proliferation and differentiation of neural stem cells, as well as nerve regeneration, are intimately linked to memory function and neurodegenerative diseases. This paper presents a comprehensive review of the roles of m^(6)A in neural stem cell proliferation, differentiation, and self-renewal, as well as its implications in memory and neurodegenerative diseases. m^(6)A has demonstrated divergent effects on the proliferation and differentiation of neural stem cells. These observed contradictions may arise from the time-specific nature of m^(6)A and its differential impact on neural stem cells across various stages of development. Similarly, the diverse effects of m^(6)A on distinct types of memory could be attributed to the involvement of specific brain regions in memory formation and recall. Inconsistencies in m^(6)A levels across different models of neurodegenerative disease, particularly Alzheimer's disease and Parkinson's disease, suggest that these disparities are linked to variations in the affected brain regions. Notably, the opposing changes in m^(6)A levels observed in Parkinson's disease models exposed to manganese compared to normal Parkinson's disease models further underscore the complexity of m^(6)A's role in neurodegenerative processes. The roles of m^(6)A in neural stem cell proliferation, differentiation, and self-renewal, and its implications in memory and neurodegenerative diseases, appear contradictory. These inconsistencies may be attributed to the timespecific nature of m^(6)A and its varying effects on distinct brain regions and in different environments.

Heterogeneity of mature oligodendrocytes in the central nervous system

Mature oligodendrocytes form myelin sheaths that are crucial for the insulation of axons and efficient signal transmission in the central nervous system.Recent evidence has challenged the classical view of the functionally static mature oligodendrocyte and revealed a gamut of dynamic functions such as the ability to modulate neuronal circuitry and provide metabolic support to axons.Despite the recognition of potential heterogeneity in mature oligodendrocyte function,a comprehensive summary of mature oligodendrocyte diversity is lacking.We delve into early 20th-century studies by Robertson and Río-Hortega that laid the foundation for the modern identification of regional and morphological heterogeneity in mature oligodendrocytes.Indeed,recent morphologic and functional studies call into question the long-assumed homogeneity of mature oligodendrocyte function through the identification of distinct subtypes with varying myelination preferences.Furthermore,modern molecular investigations,employing techniques such as single cell/nucleus RNA sequencing,consistently unveil at least six mature oligodendrocyte subpopulations in the human central nervous system that are highly transcriptomically diverse and vary with central nervous system region.Age and disease related mature oligodendrocyte variation denotes the impact of pathological conditions such as multiple sclerosis,Alzheimer's disease,and psychiatric disorders.Nevertheless,caution is warranted when subclassifying mature oligodendrocytes because of the simplification needed to make conclusions about cell identity from temporally confined investigations.Future studies leveraging advanced techniques like spatial transcriptomics and single-cell proteomics promise a more nuanced understanding of mature oligodendrocyte heterogeneity.Such research avenues that precisely evaluate mature oligodendrocyte heterogeneity with care to understand the mitigating influence of species,sex,central nervous system region,age,and disease,hold promise for the development of therapeutic interventions targeting varied central nervous system pathology.

Human induced pluripotent stem cell-derived therapies for regeneration after central nervous system injury

In recent years,the progression of stem cell therapies has shown great promise in advancing the nascent field of regenerative medicine.Considering the non-regenerative nature of the mature central nervous system,the concept that“blank”cells could be reprogrammed and functionally integrated into host neural networks remained intriguing.Previous work has also demonstrated the ability of such cells to stimulate intrinsic growth programs in post-mitotic cells,such as neurons.While embryonic stem cells demonstrated great potential in treating central nervous system pathologies,ethical and technical concerns remained.These barriers,along with the clear necessity for this type of treatment,ultimately prompted the advent of induced pluripotent stem cells.The advantage of pluripotent cells in central nervous system regeneration is multifaceted,permitting differentiation into neural stem cells,neural progenitor cells,glia,and various neuronal subpopulations.The precise spatiotemporal application of extrinsic growth factors in vitro,in addition to microenvironmental signaling in vivo,influences the efficiency of this directed differentiation.While the pluri-or multipotency of these cells is appealing,it also poses the risk of unregulated differentiation and teratoma formation.Cells of the neuroectodermal lineage,such as neuronal subpopulations and glia,have been explored with varying degrees of success.Although the risk of cancer or teratoma formation is greatly reduced,each subpopulation varies in effectiveness and is influenced by a myriad of factors,such as the timing of the transplant,pathology type,and the ratio of accompanying progenitor cells.Furthermore,successful transplantation requires innovative approaches to develop delivery vectors that can mitigate cell death and support integration.Lastly,host immune responses to allogeneic grafts must be thoroughly characterized and further developed to reduce the need for immunosuppression.Translation to a clinical setting will involve careful consideration when assessing both physiologic and functional outcomes.This review will highlight both successes and challenges faced when using human induced pluripotent stem cell-derived cell transplantation therapies to promote endogenous regeneration.

脑衰老与外泌体研究进程及现状的文献计量学分析

背景:近年来随着生物医学的快速发展,脑衰老和外泌体的研究受到越来越多的关注,但目前还没有文献对该领域进行文献计量学分析。目的:客观分析近15年国内外关于脑衰老和外泌体的相关文献,总结梳理该领域的研究现状、热点和发展趋势。方法:以Web of Science的核心数据库为检索平台,下载了从建库至2022-12-28发表的有关脑衰老和外泌体的文献,使用CiteSpace 6.1.R6可视化软件从国家、机构、作者、关键词、共被引文献等方面对数据进行分析。结果与结论:共纳入1045篇研究文献,国内外关于脑衰老和外泌体研究的发文量呈逐年增长趋势,美国以发文量429篇居于首位,中国以发文量277篇位居第二。美国路易斯安那州立大学以发文量16篇位居第一。路易斯安那州立大学的Lukiw,Walter J教授是发文量最大的作者,麻省理工学院Bartel DP教授是被引用最多的作者。产量最高的期刊是《International Journal of Molecular Sciences》。阿尔茨海默病、microRNA、基因表达、细胞外囊泡、外泌体、氧化应激和生物标志物等是最相关的术语。根据对热门话题的研究,生物标志物已成为一个新的研究热点。以上结果表明,近15年来脑衰老和外泌体的研究呈逐渐上升趋势,研究方向由最初探究与脑衰老相关的中枢神经系统疾病miRNA的表达,已逐渐转向为寻找能成为识别和诊断神经退行性疾病的生物标志物,基于外泌体miRNA的方法已经成为中枢神经系统疾病有希望的治疗策略。

黄体生成素/促卵泡生成素比值对快进展型中枢性性早熟的预测价值研究

背景 中枢性性早熟(CPP)是儿童内分泌常见疾病,近年来呈逐年增加趋势,依据青春期发育进程可分为快进展型中枢性性早熟(RP-CPP)和缓慢进展型中枢性性早熟(SP-CPP)。RP-CPP具有极大危害,其与SPCPP在早期临床鉴别中存在困难,主要依靠随访中青春期发育进程及骨龄进展情况进行判断,目前缺乏有效的实验室检查指标来预测RP-CPP。目的 探讨促黄体生成素(LH)/促卵泡生成素(FSH)比值对RP-CPP的预测价值。方法回顾性选取2020年1月—2022年5月郑州大学附属儿童医院收治的4~10岁CPP女童(n=380),依据青春期发育进程等指标分为RP-CPP组(n=130)及SP-CPP组(n=250),对两组间的临床特征进行对比分析,进行RP-CPP影响因素的单因素和多因素Logistic回归分析,并绘制LH/FSH比值对RP-CPP预测价值的受试者工作特征(ROC)曲线。结果 RP-CPP组女童的身高、体质量、BMI、胰岛素样生长因子1(IGF-1)、骨龄与实际年龄差值、双侧卵巢体积、LH基础值、雌二醇水平、LH基础值/FSH基础值、LH峰值/FSH峰值均高于SP-CPP组(P<0.05)。多因素Logistic回归分析,结果显示,LH基础值(OR=0.882,95%CI=0.686~0.986,P=0.035)及LH峰值/FSH峰值(OR=0.492,95%CI=0.336~0.723,P<0.001)是CPP患者进展为RP-CPP的影响因素。LH基础值/FSH基础值、LH峰值/FSH峰值均与身高、IGF-1、LH基础值、雌二醇水平、LH峰值、卵巢容积及骨龄呈正相关(P<0.05)。ROC曲线显示LH基础值/FSH基础值、LH峰值/FSH峰值较其他指标对RP-CPP的预测价值更高,LH基础值/FSH基础值为0.63时,约登指数最大为0.258[灵敏度为43.1%,特异度为82.7%,ROC曲线下面积(AUC)=0.644],LH峰值/FSH峰值为1.39时,约登指数最大为0.276(灵敏度为74.6%,特异度53.0%,AUC=0.655),二者联合的预测模型优于单一指标预测模型(AUC=0.668)。对未进行临床干预患儿随访6个月后的基础促性腺激素水平进行分析,随访6个月后RP-CPP组的身高增长、ΔLH、ΔFSH、骨龄增长及卵巢容积增长均多于SP-CPP组(P<0.05)。结论 LH基础值/FSH基础值及LH峰值/FSH峰值是RP-CPP的早期预测指标,当LH/FSH基础值≥0.63或LH峰值/FSH峰值≥1.39时,需考虑RP-CPP的可能性,并且二者联合的预测价值优于单一指标,可作为临床应用促性腺激素释放激素类似物治疗的辅助参考指标。

Transforming growth factor-beta 1 enhances discharge activity of cortical neurons

Transforming growth factor-beta 1(TGF-β1)has been extensively studied for its pleiotropic effects on central nervous system diseases.The neuroprotective or neurotoxic effects of TGF-β1 in specific brain areas may depend on the pathological process and cell types involved.Voltage-gated sodium channels(VGSCs)are essential ion channels for the generation of action potentials in neurons,and are involved in various neuroexcitation-related diseases.However,the effects of TGF-β1 on the functional properties of VGSCs and firing properties in cortical neurons remain unclear.In this study,we investigated the effects of TGF-β1 on VGSC function and firing properties in primary cortical neurons from mice.We found that TGF-β1 increased VGSC current density in a dose-and time-dependent manner,which was attributable to the upregulation of Nav1.3 expression.Increased VGSC current density and Nav1.3 expression were significantly abolished by preincubation with inhibitors of mitogen-activated protein kinase kinase(PD98059),p38 mitogen-activated protein kinase(SB203580),and Jun NH2-terminal kinase 1/2 inhibitor(SP600125).Interestingly,TGF-β1 significantly increased the firing threshold of action potentials but did not change their firing rate in cortical neurons.These findings suggest that TGF-β1 can increase Nav1.3 expression through activation of the ERK1/2-JNK-MAPK pathway,which leads to a decrease in the firing threshold of action potentials in cortical neurons under pathological conditions.Thus,this contributes to the occurrence and progression of neuroexcitatory-related diseases of the central nervous system.