Proteomics analysis of lysine crotonylation and 2-hydroxyisobutyrylation reveals significant features of systemic lupus erythematosus

Introduction/objectives

To seek significant features of systemic lupus erythematosus (SLE) by utilizing bioinformatics analysis.

Method

Liquid chromatography-tandem mass spectrometry (LC–MS/MS) was used to quantify lysine crotonylation (Kcr) and lysine 2-hydroxyisobutyrylation (Khib) in peripheral blood mononuclear cells (PBMCs) of systemic lupus erythematosus (SLE) patients and normal controls.

Results

Seventy-six differentially modified proteins (DMPs) dually modified by Kcr and Khib were identified between SLE patients and healthy people. GO enrichment analysis prompted significant enrichment of seventy-six DMPs in MHC class II protein complex binding and leukocyte migration. KEGG pathways were enriched in antigen processing and presentation pathway and leukocyte transendothelial migration pathway. Six DMPs (CLTC, HSPA1B, HSPA8, HSP90AB1, HSPD1, and PDIA3) were identified in antigen processing and presentation pathway, of which HSPA8 was the core protein. Significant changes of Kcr and Khib in HSPA8 may increase ATP hydrolysis and promote antigen binding to MHC II molecule. In leukocyte transendothelial migration pathway, 7 DMPs (ACTN1, ACTN4, EZR, MSN, RAC1, RHOA, and VCL) were identified. MSN was the protein with the most modification sites in this pathway. In amino terminal ferm region of MSN, Kcr and Khib expression change may lead to the adhesion between leukocytes and endothelial cells, which was an important step of leukocyte migration.

Conclusion

Kcr and Khib may promote the antigen presentation and jointly regulate the tissue damage mediated by leukocyte migration in SLE patients, which may play key roles in the pathogenesis of SLE probably.

创伤性脊柱骨折合并脊髓损伤患者血清pNF-H动态变化及其与脊髓损伤程度的相关性

目的 探讨创伤性脊柱骨折合并脊髓损伤患者血清磷酸化高分子量神经微丝蛋白(pNF-H)动态变化与脊髓损伤程度的相关性.方法 回顾性分析2017年1月—2019年1月平煤神马医疗集团总医院脊柱外科收治的创伤性脊柱骨折患者94例,其中合并脊髓损伤48例(脊髓损伤组),男性35例,女性13例;年龄18～60岁,平均50.7岁;致伤原因:道路交通伤20例,摔伤16例,高处坠落伤7例,砸伤5例.单纯脊柱骨折46例(单纯骨折组),男性30例,女性16例;年龄18～60岁,平均50.8岁;致伤原因:道路交通伤18例,摔伤13例,高处坠落伤8例,砸伤7例.选取同期笔者医院进行体检的健康者40例作为健康对照组,男性30例,女性10例;年龄18～60岁,平均50.8岁.比较各组间伤后12h、24h、3d、7d、14d血清pNF-H浓度变化;并分析脊髓损伤组不同美国脊髓损伤协会(ASIA)神经功能分级患者12h、24h、3d、7d、14d时血清pNF-H浓度变化,采用Spearman检验分析血清pNF-H动态变化与ASIA神经功能分级的相关性.结果 伤后12h、24h、3d、7d、14d,脊髓损伤组血清pNF-H浓度高于相应时间点单纯骨折组、健康对照组(P<0.05),单纯骨折组血清pNF-H浓度高于相应时间点健康对照组(P<0.05).不同ASIA分级患者不同时间点血清pNF-H浓度比较差异有统计学意义(P<0.05);在12h、24h、3d、7d、14d时A级患者血清pNF-H浓度高于B、C、D级(P<0.05),B级患者血清pNF-H浓度高于C、D级(P<0.05),C级患者血清pNF-H浓度高于D级(P<0.05);血清pNF-H与A-SIA分级存在负相关(r=-0.951,P<0.05).结论 创伤性脊柱骨折合并脊髓损伤患者血清pNF-H浓度随时间变化,而ASIA分级越严重血清pNF-H浓度越高.     

电针对慢性炎性疼痛大鼠Wnt/β-catenin以及ERK/MAPK信号通路相关蛋白表达的影响＊

目的 探究电针（EA）对慢性炎性疼痛大鼠Wnt/β-catenin信号通路和ERK/MAPK信号通路的调控作用。方法 通过完全弗氏佐剂建立慢性炎性疼痛大鼠（CFA）模型。实验分为4组：对照组（NS组）、模型组（CFA组）、模型组+电针组（CFA+EA组）和模型组+假电针组（CFA+Sham EA组），每组6只大鼠。模型建立8天后进行EA治疗，每天1次，每次30 min。用Up-down法评价机械痛阈值，用丙酮刺激大鼠致炎足底观察冷刺激诱发痛的反应评分，用ELISA检测血清和左后足组织中前列腺素E2（Urinary prostaglandin E2，PGE2）、白介素-6（Interleukin-6，IL-6）、肿瘤坏死因子-α（Tumor necrosis factor-α，TNF-α）、白介素-1β（Interleukin-1β，IL-1β）和脑源性神经营养因子（Brain-derived neurotrophic factor，BDNF）的表达水平，用Western blot检测左后足组织中Wnt家族成员1蛋白（Wnt family member 1，Wnt-1）、β连环蛋白（catenin beta 1，β-catenin）和糖原合酶激酶-3（Glycogen synthase kinase-3 beta，GSK-3β）的表达水平以及cAMP反应元件结合蛋白（cAMP response element binding protein，CREB）和细胞外信号调节激酶（Extracellular signal-regulated kinase，ERK）蛋白的磷酸化水平。结果 与CFA模型组相比，治疗后第5天及第7天，EA显著提高了CFA大鼠的机械痛阈值（P < 0.05），并显著降低了CFA大鼠的冷刺激评分（P < 0.05）。此外，EA显著降低了CFA大鼠血清和左后足组织中PGE2、IL-6、TNF-α、IL-1β和BDNF的表达水平和左后足组织中Wnt-1和β-catenin的蛋白表达水平以及CREB和ERK蛋白的磷酸化水平（均P < 0.05），并显著升高了左后足组织中GSK-3β的蛋白表达水平（P < 0.05）。结论 EA显著改善了大鼠慢性炎性疼痛，其机制可能与抑制Wnt/β-catenin信号通路和ERK/MAPK信号通路有关。     

Müller Glia Are a Major Cellular Source of Survival Signals for Retinal Neurons in Diabetes

To dissect the role of vascular endothelial growth factor receptor-2 (VEGFR2) in Müller cells and its effect on neuroprotection in diabetic retinopathy (DR), we disrupted VEGFR2 in mouse Müller glia and determined its effect on Müller cell survival, neuronal integrity, and trophic factor production in diabetic retinas. Diabetes was induced with streptozotocin. Retinal function was measured with electroretinography. Müller cell and neuronal densities were assessed with morphometric and immunohistochemical analyses. Loss of VEGFR2 caused a gradual reduction in Müller glial density, which reached to a significant level 10 months after the onset of diabetes. This observation was accompanied by an age-dependent decrease of scotopic and photopic electroretinography amplitudes and accelerated loss of rod and cone photoreceptors, ganglion cell layer cells, and inner nuclear layer neurons and by a significant reduction of retinal glial cell line–derived neurotrophic factor and brain-derived neurotrophic factor. Our results suggest that VEGFR2-mediated Müller cell survival is required for the viability of retinal neurons in diabetes. The genetically altered mice established in this study can be used as a diabetic animal model of nontoxin-induced Müller cell ablation, which will be useful for exploring the cellular mechanisms of neuronal alteration in DR.     

两种不同缝线方法治疗原发性翼状胬肉的疗效比较

目的：观察2种不同缝线方法治疗原发性翼状胬肉的临床疗效。方法：前瞻性研究。选取2015年4月 至2018年4月于解放军乌鲁木齐市第474医院住院并手术的翼状胬肉患者128例(128眼)，采用随机数字表法随机分成观察组和对照组，每组64例（64眼）。观察组采用翼状胬肉切除联合连续缝合自体结膜瓣移植治疗，对照组采用翼状胬肉切除联合间断缝合自体结膜瓣移植治疗。观察2组术后1、3、 7 d的疼痛、角膜刺激症状程度；角膜荧光染色确定2组角膜上皮完全愈合时间；6个月随访中记录结膜完全愈合、瘢痕纤维增生及胬肉复发情况。2组间各指标的比较采用独立样本t检验；2组间率的比 较采用卡方检验（必要时辅以Fisher精确概率法直接计算P值）。结果：疼痛和刺激症状评分方面，观察组术后1 d和3 d均低于对照组（疼痛评分：t=-40.477，P<0.001；t=-23.376，P<0.001。刺激症状评分： t=-18.431，P<0.001；t=-7.894，P<0.001)，术前和术后7 d，2组间差异无统计学意义。角膜荧光染色 显示角膜上皮完全愈合率方面，观察组术后3 d和5 d均高于对照组（χ2 =4.354，P=0.037；χ2 =13.333， P<0.001），术后7 d组间差异无统计学意义。观察组的痊愈率高于对照组（χ2 =8.848，P=0.003），观察 组的瘢痕痊愈率低于对照组（χ2 =8.214，P=0.004），2组胬肉复发率差异无统计学意义。观察组拆线 时间早于对照组（t=-32.686，P<0.001），拆线耗时短于对照组（t=-20.236，P<0.001），拆线疼痛评分低于对照组（t=-26.580，P<0.001），差异均有统计学意义。结论：翼状胬肉切除联合连续缝合自体结膜瓣移植治疗原发性翼状胬肉，术后眼部疼痛、刺激、炎症反应轻，角膜上皮愈合更快，可明显减少瘢痕的形成，术后拆线更早，拆线耗时短且疼痛感较轻。     

急诊眩晕症实施不同药物治疗疗效及安全性

目的针对急诊眩晕症患者通过实施不同药物进行治疗,观察及分析临床疗效。方法选取本院收治的急诊眩晕症患者108例,经随机分为对照组、氯丙嗪组、阿托品组、异丙嗪组,分别给不同药治疗后观察4组患者药物在治疗前后阶段的临床效果。结果与对照组相比,其他3组患者其总有效率均出现明显升高,组间差异存在统计学意义(P<0.05)。经治疗后,其他3组发生眩晕的次数改善效果均较好且安全性程度较高。结论对不同药物用于眩晕症稳定型眩晕治疗效果较为明显,不良反应大大降低,安全度高,不仅增强患者生活质量水平,且在急诊科中具有重要参考价值及意义。     

Spontaneous regression of stage Ⅲ neuroblastoma: A case report

BACKGROUND Neuroblastoma(NB) is the most common type of extracranial solid tumour in children. The overall prognosis of NB is poor, but at the same time, NB shows significant clinical diversity. NB can demonstrate spontaneous regression or can differentiate into benign ganglioneuroma.CASE SUMMARY This study retrospectively analyzed the clinical data of a patient with spontaneous regression of stage Ⅲ NB who was admitted in May 2015. Studies of the spontaneous regression of NB published from October 1946 to September 2019 were retrieved through Pub Med. The clinical manifestations, diagnosis,treatment, and follow-up results were analysed.CONCLUSION Spontaneous regression of stage Ⅲ NB is rare in the clinic. The report of this case is an important supplement to the study of the spontaneous regression of NB.     

基于超声影像组学的乳腺癌预测模型的诊断性能研究

目的评估并比较基于不同机器学习算法建立的乳腺癌超声影像组学预测模型的诊断性能。 方法回顾性收集2017年1月至2019年4月就诊皖南医学院第一附属医院、有明确病理结果的乳腺肿块病例828例，以2018年8月31日为节点将其分为训练集（526例）和验证集（302例），提取肿块的超声影像组学特征并进行特征筛选，运用k最近邻（kNN）、逻辑回归（LR）、朴素贝叶斯（NB）、随机森林（RF）和支持向量机（SVM）5种机器学习算法分别建立预测模型，使用重复交叉验证方法做内部验证，计算比较各模型的敏感度、特异度、阳性预测值（PPV）和阴性预测值（NPV），并实施外部验证，绘制ROC曲线并比较ROC曲线下面积（AUC）以评价模型的鉴别诊断性能，绘制校准曲线评价模型校准度。 结果从提取的109个影像组学特征中筛选出19个特征建立了5种机器学习算法模型。在内部验证中，5种模型的敏感度、特异度、PPV、NPV比较，总体差异均有统计学意义（P均＜0.001）。LR模型的特异度、PPV、NPV中位数分别为0.769、0.816、0.778，3项指标均高于其他4种模型；敏感度中位数为0.824，高于kNN、RF和SVM模型。此外，SVM模型的特异度、PPV、NPV中位数分别为0.706、0.774、0.759，虽均低于LR模型，但均高于其他3种模型。在外部验证中，LR、SVM、RF、kNN和NB的AUC依次为0.890、0.832、0.821、0.746和0.703，其中LR与SVM的AUC差异有统计学意义（P=0.012）；此外，各模型在校准性能上表现并不一致，LR和SVM模型的校准曲线显示乳腺癌实际概率与预测概率之间的一致性较好。 结论以超声影像组学特征为基础，运用不同机器学习算法建立的乳腺癌超声预测模型，均表现出较高的诊断性能，其中LR模型表现最为突出；选择合适的机器学习算法有助于进一步提高预测模型的诊断性能，提供更加准确的量化预测结果。