Abnormal expression of Tau in damaged oligodendrocytes of HLD1 mice

Patients with hypomyelinating leukodystrophies(H LDs),multiple sclerosis(MS),and leukodystrophies including Aicardi-Goutieres syndrome,adrenoleukodystrophy,Alexander disease,Canavan disease,cerebrotendinous xanthomatosis,Krabbe disease/globoid cell leukodystrophy,metachromatic leukodystrophy.

Gut microbial metabolite targets HDAC3-FOXK1-interferon axis in fibroblast-like synoviocytes to ameliorate rheumatoid arthritis

Rheumatoid arthritis(RA)is an autoimmune disease.Early studies hold an opinion that gut microbiota is environmentally acquired and associated with RA susceptibility.However,accumulating evidence demonstrates that genetics also shape the gut microbiota.It is known that some strains of inbred laboratory mice are highly susceptible to collagen-induced arthritis(CIA),while the others are resistant to CIA.Here,we show that transplantation of fecal microbiota of CIA-resistant C57BL/6J mice to CIA-susceptible DBA/1J mice confer CIA resistance in DBA/1J mice.C57BL/6J mice and healthy human individuals have enriched B.fragilis than DBA/1J mice and RA patients.Transplantation of B.fragilis prevents CIA in DBA/1J mice.We identify that B.fragilis mainly produces propionate and C57BL/6J mice and healthy human individuals have higher level of propionate.Fibroblast-like synoviocytes(FLSs)in RA are activated to undergo tumor-like transformation.Propionate disrupts HDAC3-FOXK1 interaction to increase acetylation of FOXK1,resulting in reduced FOXK1 stability,blocked interferon signaling and deactivation of RA-FLSs.We treat CIA mice with propionate and show that propionate attenuates CIA.Moreover,a combination of propionate with anti-TNF etanercept synergistically relieves CIA.These results suggest that B.fragilis or propionate could be an alternative or complementary approach to the current therapies.

Implications of Olig2 silencing in oligodendrocyte precursor cells

Oligodendrocytes(OLs)are the only myelinforming cells in the central nervous system.Their differentiation from OL precursor cells(OPCs)occurs throughout life and is mediated by numerous intrinsic and extrinsic factors.OL transcription factor 2(Olig2),a basic helix-loophelix transcription factor,is one of the intrinsic factors that specify the OL lineage.It is expressed by both OPCs and OLs,and no variant of Olig2 has yet been identified in rodents.Although the function of Olig2 in OL maturation and myelination is still under debate.

Disease-associated oligodendrocyte signatures in neurodegenerative disease:the known and unknown

Oligodendrocytes are one of the most abundant cell types in the central nervous system(CNS)and act in close contact with neurons to assist with their cellular function and health(Kuhn et al.,2019).Oligodendrocytes play particular roles in rapid nerve impulse conduction through the wrapping of their myelinating projections a round a nerve axon,as well as by offering trophic and metabolic support for the high energy expenditure of neurons.Additionally。

血府逐瘀汤对狼疮性肾炎患者胸腺肽β4及Ea-RFC的影响

目的探讨血府逐瘀汤辅助治疗狼疮性肾炎(LN)的效果及对患者胸腺肽β4及Ea花环细胞(Ea-RFC)形成率的影响。方法选取河北北方学院附属第二医院2020年1月至2021年6月收治的60例狼疮性肾炎患者,按随机数字表法分为观察组(行血府逐瘀汤联合泼尼松与环磷酰胺治疗)30例与对照组(行泼尼松与环磷酰胺治疗)30例,治疗18个月。观察组治疗后临床效果、中医症状、胸腺肽β4表达、Ea-RFC形成率、肾功能及不良反应。结果观察组治疗总有效率为96.67%,高于对照组的80.00%,差异有统计学意义(P<0.05)。治疗后,观察组纳少腹胀、腰膝酸软、面色不华、口黏口苦等中医症状积分低于对照组,差异有统计学意义(P<0.05)。治疗后,观察组红细胞沉降率、血清肌酐及胸腺肽β4表达低于对照组,Ea-RFC形成率高于对照组,差异有统计学意义(P<0.05)。治疗后,观察组不良反应发生率与对照组比较差异无统计学意义(P>0.05)。结论血府逐瘀汤辅助治疗LN患者疗效确切,能减少患者体内胸腺肽β4表达,提高Ea-RFC,改善肾功能,安全性较高。

维持性腹膜透析患者外周血NLR PLR HGB水平变化及其与钙磷代谢异常和全因病死率的关系

目的:探究维持性腹膜透析患者外周血中性粒细胞与淋巴细胞比值(NLR)、血小板与淋巴细胞比值(PLR)、血红蛋白(HGB)水平变化及其与钙磷代谢异常和全因病死率的关系。方法:选取2019年3月至2022年6月收治的维持性腹膜透析患者206例,评估患者是否存在钙磷代谢异常,分为异常组和正常组,比较两组外周血NLR、PLR、HGB水平,分析NLR、PLR、HGB与血钙、血磷水平相关性;随访至2022年12月,以全因病死为终点事件,分为病死组和存活组,比较两组外周血NLR、PLR、HGB水平,并用受试者工作特征(ROC)曲线评价NLR、PLR、HGB对患者全因病死的预测价值。结果:异常组外周血NLR、PLR及血磷水平高于正常组,血钙水平低于正常组(P<0.05);但两组年龄、性别、文化程度、原发疾病、透析时间及外周血HGB水平的比较,差异无统计学意义(P>0.05)。维持性血液透析老年患者外周血NLR、PLR与血钙水平呈负相关,与血磷水平呈正相关(P<0.05);而HGB与血钙、血磷水平无明显相关性(P>0.05)。病死组透析时间长于存活组,外周血NLR、PLR及血磷水平高于存活组,血钙水平低于存活组(P<0.05);但两组年龄、性别、文化程度、原发疾病及外周血HGB水平的比较,差异无统计学意义(P>0.05)。ROC曲线分析结果显示,外周血NLR、PLR预测患者全因病死的曲线下面积(AUC)分别为0.777(95%CI:0.688~0.866)、0.781(95%CI:0.668~0.895)。结论:维持性腹膜透析患者钙磷代谢异常与外周血NLR、PLR水平相关,且上述指标对患者全因病死具有一定的预测价值。

基于RNA-seq分析TBL2基因在心肌细胞缺氧/复氧损伤中的作用机制

目的 采用转录组测序技术探讨转导蛋白β样蛋白2(TBL2)基因在大鼠心肌H9c2细胞缺氧/复氧(hypoxia/reoxygenation,H/R)损伤中的影响及其作用机制。方法 通过H/R诱导H9c2细胞建立心肌细胞损伤模型,体外模拟心肌缺血。采用Western blot检测H/R心肌细胞与正常H9c2细胞中TBL2表达水平。H9c2心肌细胞分为si-TBL2组和si-NC组,分别转染TBL2-siRNA、NC-siRNA后,再进行H/R处理,每组分别取3个样本进行RNA-seq。采用DESeq2软件筛选差异表达基因(differentially expressed genes,DEGs)。采用ClusterProfiler对数据进行差异基因的GO和KEGG功能注释和富集分析。使用STRING数据库联合Cytoscape软件建立DEGs的蛋白-蛋白相互作用(PPI)网络并筛选核心基因。结果 与正常H9c2细胞相比,TBL2在H/R心肌细胞中显著升高(P=0.002 2)。转录组测序分析发现si-TBL2组和si-NC组DEGs共905个,其中566个下调基因,309个上调基因。GO功能富集分析结果显示,DEGs主要富集在细胞黏附、调节全身动脉血压、钾离子运输等生物过程,以及细胞外基质、细胞外间隙、参与细胞黏附的蛋白质复合物等细胞组分,跨膜受体活性、信号受体活性、无机阳离子跨膜转运蛋白活性、G蛋白偶联受体活性等分子功能。KEGG通路富集分析结果显示,DEGs主要分布在40条信号通路中,主要包括:细胞黏附分子、神经活性配体-受体相互作用、ECM受体相互作用、PI3K/Akt信号通路、钙信号通路、蛋白质消化和吸收等。通过构建PPI网络图共筛选出7个核心基因,包括:IL-6、LEP、IL-1α、FGF9、GFAP、CD68、AGT。结论 TBL2在心肌梗死细胞模型中显著高表达,抑制TBL2基因在H/R诱导的H9c2心肌细胞损伤模型中有明显差异表达基因,并且参与多种生物学进程和信号通路调节,影响心肌细胞的增殖、凋亡、炎症反应的过程,可能是心肌梗死潜在的治疗靶点。

男性酒依赖患者合并贫血影响因素分析及预测模型构建

目的:探讨男性酒依赖患者合并贫血影响因素,并构建相应预测模型。方法:回顾性收集155例男性酒依赖患者临床资料,包括一般临床特征、饮酒情况以及实验室指标等。根据血红蛋白是否<130g/L(男性)将患者分为贫血组(n=63)与非贫血组(n=92),通过单因素及逐步多因素Logistic回归分析筛选男性酒依赖患者合并贫血的影响因素,并建立预测模型,最后采用ROC曲线评估模型预测能力。结果:155例男性酒依赖患者中有63例合并贫血,发生率为40.65%。逐步多因素Logistic回归分析显示,年龄、饮酒量、低钾血症、低蛋白血症、低淋巴细胞与单核细胞比值(LMR)均是男性酒依赖患者合并贫血的影响因素(P均<0.05)。Logistic回归方程为Logit(p)=-9.421+0.055×年龄+0.046×饮酒量+1.386×低钾血症+1.950×低蛋白血症+1.003×低LMR。联合预测因子曲线下面积为0.815,灵敏度为77.8%,特异度为75.0%%,截断值为0.382。结论:年龄、饮酒量、低钾血症、低蛋白血症、低LMR是男性酒依赖患者合并贫血的影响因素;本研究构建预测模型可为临床早期评估男性酒依赖患者合并贫血提供借鉴。

Using microglia-derived extracellular vesicles to capture diversity of microglial activation phenotypes following neurological injury

Microglia are one of the three glial cell populations in the central nervous system(CNS),along with astrocytes and oligodendrocytes.While microglia are unique among brain cells due to their hematologic origin and perform immune functions similar to peripheral macrophages,they are not simply macrophages of the CNS.

不典型强直性脊柱炎误诊原因分析

目的分析强直性脊柱炎(ankylosing sporidylitis,AS)误诊为腰椎间盘突出症、风湿热(rheumatic fever,RF)的原因及防范措施。方法回顾分析2021至2023年收治的AS误诊腰椎间盘突出症1例、RF 1例的病例资料。结果1例为31岁男性,因腰背部及右下肢疼痛伴晨僵3个月就诊,腰椎间盘CT检查示L_(4~5)椎间盘轻度突出,初诊为腰椎间盘突出症,后出现低热,查红细胞沉降率(erythrocyte sedimentation rate,ESR)、C反应蛋白(C reactive protein,CRP)升高、人白细胞抗原B27阳性,骶髂关节CT示双侧骶髂关节面有虫噬样改变,诊断为AS。1例为16岁青少年,因双踝双膝关节肿痛1年余、加重1月余就诊,因抗链球菌溶血素“O”试验(+),合并有多关节疼痛症状,诊断为RF,予苄星青霉素注射后症状好转停用后再发,后行骶髂关节MRI检查示双侧骶髂关节面局部融合,ESR与CRP升高,综合以上排除RF后诊断AS。误诊时间3个月、14个月。2例确诊后均予柳氮磺胺吡啶、甲氨蝶呤、重组人Ⅱ型肿瘤坏死因子受体抗体融合蛋白等治疗后症状消失,随访1~2年病情平稳。结论部分AS患者初期表现不典型,易误诊;加强对AS及相关疾病的认识、诊断及鉴别诊断能力,仔细采集病史,认真查体,早期行骶髂关节影像学检查及人白细胞抗原B27检测,结合临床表现和其他相关检查结果综合分析病情,可避免本病误诊的发生。

NLR、Aβ、IGF-1对老年结直肠癌根治术患者术后早期认知功能的预测价值

目的 探讨血清中性粒细胞与淋巴细胞比值(NLR)、β-淀粉样蛋白(Aβ)、胰岛素样生长因子-1(IGF-1)对老年结直肠癌根治术患者术后认知功能障碍(POCD)的预测价值。方法 分析2019年1月至2022年12月合肥市第八人民医院收治的122例行腹腔镜结直肠癌根治术患者的临床资料,术后使用简易精神状态检查表(MMSE)对患者认知功能进行评估,将患者分为POCD组及非POCD组。对两组术后24 h内血清NLR、Aβ、IGF-1水平进行比较,二元Logistic回归分析患者术后发生POCD的影响因素,受试者工作曲线(ROC)分析血清NLR、Aβ、IGF-1水平对老年结直肠癌根治术患者发生POCD的预测价值。结果 术后7 d共有54例患者出现POCD。POCD组NLR及Aβ水平高于非POCD组,IGF-1水平低于非POCD组,差异均有统计学意义(t=5.894、6.108、6.481,P<0.05);多元Logistic回归分析显示,手术时间长、NLR及Aβ上升、IGF-1下降是患者术后发生POCD的危险因素(P<0.05),受教育年限高是患者术后发生POCD的保护因素(P<0.05);ROC曲线结果显示,血清NLR、Aβ、IGF-1单独及联合检测预测老年结直肠癌根治术患者发生POCD的曲线下面积分别为0.774、0.779、0.794、0.910,联合检测优于单一检测(P<0.05)。结论 血清NLR、Aβ、IGF-1水平异常可能与老年结直肠癌根治术患者发生POCD有关,通过三者联合检测对预测POCD发生具有较好的应用价值。

Molecular mechanosensors in osteocytes

Osteocytes, the most abundant and long-lived cells in bone, are the master regulators of bone remodeling. In addition to their functions in endocrine regulation and calcium and phosphate metabolism, osteocytes are the major responsive cells in force adaptation due to mechanical stimulation. Mechanically induced bone formation and adaptation, disuse-induced bone loss and skeletal fragility are mediated by osteocytes, which sense local mechanical cues and respond to these cues in both direct and indirect ways. The mechanotransduction process in osteocytes is a complex but exquisite regulatory process between cells and their environment, between neighboring cells, and between different functional mechanosensors in individual cells. Over the past two decades, great efforts have focused on finding various mechanosensors in osteocytes that transmit extracellular mechanical signals into osteocytes and regulate responsive gene expression. The osteocyte cytoskeleton, dendritic processes, Integrin-based focal adhesions, connexin-based intercellular junctions, primary cilium, ion channels, and extracellular matrix are the major mechanosensors in osteocytes reported so far with evidence from both in vitro and in vitro studies. This review aims to give a systematic introduction to osteocyte mechanobiology, provide details of osteocyte mechanosensors, and discuss the roles of osteocyte mechanosensitive signaling pathways in the regulation of bone homeostasis.

Not only myelination: the immune-inflammatory functions of oligodendrocytes

Oligodendrocytes(OLs)are highly specialized cells of the central nervous system(CNS).Their primary and most investigated role is to form myelin,a multilamellar fatty membrane that enwraps axons ensuring their insulation and the saltatory conduction of nerve impulses.The formation of myelin is a complex process during which the OL precursor cells(OPCs,also known as NG2-glia)become mature OLs through a highly regulated program of differentiation.In addition,OPCs persist in the adult grey and white matter parenchyma,representing approximately 6%of the total number of CNS cells.Beyond their role in myelin generation and turn-over,it is now clear that OPCs have the capability to control tissue homeostasis and to sense and react to inflammation which characterizes many neurological diseases.

Oligodendrocytes in a dish for the drug discovery pipeline:the risk of oversimplification

Myelination,remyelination and demyelination:modeling the in vitro drug discovery pipeline:Demyelination is a multifactorial event occurring in diseases primarily involving myelin forming cells(oligodendrocytes,OLs)and their precursors(oligodendrocyte precursor cells,OPCs)such as multiple sclerosis,but is also involved in the pathology of other central nervous system(CNS)injuries and diseases,such as neonatal encephalopathy。

Overexpression of Lrp5 enhanced the anti-breast cancer effects of osteocytes in bone

Osteocytes are the most abundant cells in bone,which is a frequent site of breast cancer metastasis.Here,we focused on Wnt signaling and evaluated tumor-osteocyte interactions.In animal experiments,mammary tumor cells were inoculated into the mammary fat pad and tibia.The role of Lrp5-mediated Wnt signaling was examined by overexpressing and silencing Lrp5 in osteocytes and establishing a conditional knockout mouse model.The results revealed that administration of osteocytes or their conditioned medium(CM)inhibited tumor progression and osteolysis.Osteocytes overexpressing Lrp5 or β-catenin displayed strikingly elevated tumor-suppressive activity,accompanied by downregulation of tumor-promoting chemokines and upregulation of apoptosis-inducing and tumor-suppressing proteins such as p53.The antitumor effect was also observed with osteocyte-derived CM that was pretreated with a Wnt-activating compound.Notably,silencing Lrp5 in tumors inhibited tumor progression,while silencing Lrp5 in osteocytes in conditional knockout mice promoted tumor progression.Osteocytes exhibited elevated Lrp5 expression in response to tumor cells,implying that osteocytes protect bone through canonical Wnt signaling.Thus,our results suggest that the Lrp5/β-catenin axis activates tumor-promoting signaling in tumor cells but tumor-suppressive signaling in osteocytes.We envision that osteocytes with Wnt activation potentially offer a novel cell-based therapy for breast cancer and osteolytic bone metastasis.

Light of the stars:calcium signals light up astrocytes in the presence of autoreactive CD4+T cells

Introduction:Astrocytes play important roles in the central nervous system(CNS)to support and regulate CNS function.They are abundant type of glia that form a meshwork of interconnected cells almost completely tiling the CNS.Each astrocyte extends densely ramified processes that establish close contacts and interaction with other astrocytes,neurons and blood vessels,placing these cells in an ideal position to control extracellular milieu and to exert global effects on CNS physiology.

CHROMOSOME ABERRATION IN LYMPHOCYTES OF INHABITANTS IN HIGH BACKGROUND RADIATION AREA IN YANGJIANG

Inhabitants living in high background radiationarea (HBRA) in Yangjiang county,Guangdong provincebordering on the South China Sea,expose to 330 mR/afrom environmental gamma radiation,which is threetimes as high as that in control area (CA).

STUDY ON THE EFFECT OF DNA REPAIR IN PERIPHERAL LYMPHOCYTES OF DIABETES MELLITUS

The purpose of this study is to check the effect ofDiabetes mellitus on DNA repair of peripheral lympho-cytes.With liquid scintillation counting,the valueof lymphocytes unscheduled ~3H-TdR incorporation in-dex in the aged patients with diabetes mellitus grou-

Reducing sympathetic nervous tone in aged rats bettered cardiomyocyte contraction by improving the response of β_2-adrenoceptor

The study was to investigate the effect of reducing central sympathetic nervous tone with clonidine on cardiomyocyte contraction,and further to analyze the influence of reducing the central sympathetic nervous tone on response of β1 and β2-AR in aged ventricular myocytes.Sprague-Dawley rats were randomly divided into three groups:adult group,aged group and aged group with clonidine.

CHROMOSOMAL ABERRATIONS OF PERIPHERAL BLOOD LYMPHOCYTES OF WORKERS AT A SULPHURIC ACID FACTORY

The frequencies of chromosomal aberrationsof the peripheral blood lymphocytes from 40workers chronically exposed to sulphurdioxide (SO2) at a sulphuric acid factory inTaiyuan city,North China,were studied.It was shown that the mean frequencies ofchromosomal aberrations or lymphocytes