脂蛋白相关磷脂酶A2、胰岛素样生长因子-1与老年VD患者认知功能的关系及预测价值研究

目的 探讨脂蛋白相关磷脂酶A2（Lp-PLA2）、胰岛素样生长因子-1（IGF-1）与老年血管性痴呆（VD）患者认知功能的关系及预测价值。方法 选择2019 年3～6 月在我院接受治疗的VD 患者60 例为研究对象，同时选取同期在我院接受检查的健康者60 例为对照组，比较两组患者的Lp-PLA2、IGF-1、简易智力状态检查量表评分（MMSE）水平；采用Pearson 相关性分析法对Lp-PLA2、IGF-1 与MMSE 评分的相关性进行分析；采用受试者工作曲线（ROC）下面积（AUC）比较Lp-PLA2、IGF-1 对VD 的预测价值。结果 观察组患者的Lp-PLA2 水平明显高于对照组（P＜0.05），观察组患者的IGF-1、MMSE 评分明显低于对照组（P＜0.05）；Lp-PLA2 与MMSE 评分呈负相关性，IGF-1 与MMSE 评分呈正相关性；Lp-PLA2 与IGF-1 诊断VD 的AUC 值分别为0.940、0.954。结论Lp-PLA2 水平越低，IGF-1 水平越高，患者的认知功能越好，且Lp-PLA2、IGF-1 对老年VD 患者均具有较高的预测价值。     

维生素A营养状况对学龄前支气管哮喘患儿T淋巴细胞亚群、相关炎症介质及预后转归的影响

目的 研究维生素A营养状况对学龄前支气管哮喘患儿T淋巴细胞亚群、相关细胞因子及预后转归的影响,为支气管哮喘防治提供理论依据。方法 收集2017年6月-2019年6月鄂东医疗集团黄石市妇幼保健院收治的学龄前支气管哮喘患儿120例的临床资料(病例组),同期选择本院体检的健康的学龄期儿童80例对照组。将病例组按照住院期间维生素A营养状况分为维生素A正常组、维生素A边缘缺乏组、维生素A缺乏组。比较病例组和对照组维生素A营养状况,并记录不同维生素A状况组干预前后T淋巴细胞亚群、相关炎症介质及预后转归。结果 病例组维生素A水平[(0.73±0.32)μmol/L]显著低于对照组[(1.02±0.23)μmol/L](t=5.957,P＜0.05),且病例组维生素A营养状况显著差于对照组(Z=4.865,P＜0.05),维生素A缺乏组治疗后的CD4+、CD4+/CD8+均低于另外两组,CD8+高于另外两组,差异有统计学意义(P＜0.05)。维生素A缺乏组治疗后的hs-CRP、EOS、IL-6高于另外两组,差异有统计学意义(P＜0.05)。三组治疗临床疗效比较差异有统计学意义(χ²=13.165,P＜0.05),其中以维生素A缺乏组临床疗效最差(52.17%),维生素A正常组最高(94.74%)。结论 维生素A边缘缺乏或缺乏在学龄前支气管哮喘患儿中较为常见,对患儿细胞免疫功能、炎症反应的改善及疾病的预后转归造成不良影响,临床应当加强患儿维生素A的监测,适时酌情补充维生素A制剂以改善患儿预后。     

羟基红花黄色素A通过抑制程序性坏死减轻小鼠重症中暑引起的急性肺损伤

目的 研究羟基红花黄色素A（HSYA）是否在重症中暑肺损伤中起保护作用及其可能的作用机制。方法 使用不同浓度（1.125、2.25、4.5 mg/kg）HSYA腹腔注射预处理小鼠，建立重症中暑（sHS）小鼠模型，分为低、中、高剂量HSYA中暑组、单纯中暑组及正常对照组，12只/组。初步观察及比较各组热耐受的情况，以确定HSYA最佳治疗剂量；后使用中剂量HSYA及RIP1活化抑制剂Nec-1预处理小鼠，分组为HSYA+HS组、Nec-1+HS组、HS组及正常对照组，8只/组，观察72 h恢复期核心体温变化特征，比较热耐受情况及生存情况。给予相同处理因素处理小鼠分组为正常对照组，HS组，HSYA+HS组及Nec-1+HS组，正常对照组6只，其余18只/组，分别于重症中暑恢复期不同阶段（0、2、6、12、24 h）处死小鼠，每个时间点处死3只小鼠，收集小鼠的肺组织、肺泡灌洗液及血液样本，取肺组织行HE染色，并进行病理评分，检测肺湿干重比，肺含水量，肺泡灌洗液中白细胞、中性粒细胞、蛋白含量；ELISA法检测肺泡灌洗液中HMGB1水平及血清中TNF-α、IL-6及HMGB1水平；Western blotting检测恢复期（2、6、12 h）肺组织中RIP1、RIP3、MLKL-s358、MLKL表达水平，及经HSYA预处理后MLKL-s358蛋白水平。结果 中剂量及高剂量HSYA预处理可明显改善小鼠热耐受能力，中剂量与高剂量无显著差异，后续药物预处理以中剂量（2.25 mg/kg）作为标准剂量；与HS组相比，HSYA+HS组和Nec-1+HS组小鼠热耐受程度均增加（P<0.05），HSYA+HS组和Nec-1+HS组无明显差异。HSYA及Nec-1预处理组小鼠生存率增加（P<0.05），肺组织病理评分、TNF-α、IL-6及HMGB1水平降低（P<0.05），肺湿干重比，肺含水量，肺泡灌洗液中白细胞、中性粒细胞、蛋白含量及HMGB1水平降低（P<0.05），HS小鼠恢复期肺组织RIP1水平及MLKL-s358磷酸化水平升高（P<0.05），与HS组相比，HSYA+HS组MLKL-s358磷酸化水平降低。结论 重症中暑小鼠肺组织可发生程序性坏死，HSYA可通过抑制程序性坏死发挥肺保护作用。     

Annexin A13 predicts poor prognosis for lung adenocarcinoma patients and accelerates the proliferation and migration of lung adenocarcinoma cells by modulating epithelial–mesenchymal transition

This study aimed to investigate the role of ANXA13 in lung adenocarcinoma (LUAD) growth, migration, and the underlying mechanisms. Firstly, in the TCGA dataset for LUAD, ANXA13 is found to be highly expressed in patients with LUAD and high expression of ANXA13 predicted poor outcomes in LUAD patients. Consistently, the data of qRT-PCR showed that the expression of ANXA13 was higher in LUAD cell lines (Calu-3, LTEP-a-2, and NCI-H1395) than that in normal lung cell line BEAS2B. Then, we performed gain- and loss of function of ANXA13 in NCI-H1395 and Calu-3 cells, respectively. The results displayed that deficiency of ANXA13 suppresses cell proliferation, invasion, and migration in Calu-3 cells and overexpression of ANXA13 augments cell proliferation, invasion, and migration in NCI-H1395 cells. Finally, it was found that silencing of ANXA13 obviously raised the protein expression levels of E-cadherin and reduced the protein levels of N-cadherin, Vimentin, and Snail in Calu-3 cells whereas overexpression of ANXA13 obviously receded the protein expression levels of E-cadherin and enhanced the protein levels of N-cadherin, Vimentin, and Snail in NCI-H1395 cells. This study analyzed the biological effects of ANXA13 in LUAD cells, indicating that ANXA13 could regard as a therapeutic target for LUAD.     

COPD患者相关炎性因子水平与其病情严重程度的相关性研究

探讨慢性阻塞性肺病(COPD)患者的可溶性髓系细胞触发受体-1(sTREM-1)、结缔组织生长因子(CTGF)、亲环素-A(CyPA)水平与其病情严重程度的相关性。ELISA检测COPD患者与健康人血清sTREM-1、CTGF、CyPA水平。结果显示,COPD患者sTREM-1、CTGF、CyPA水平高于健康人。随着肺功能分级的增加,COPD患者血清中sTREM-1、CTGF、CyPA水平也随之增加。sTREM-1、CTGF、CyPA水平与FEV1/FVC呈现显著负相关性(P＜0.05)。Logistic回归分析显示,sTREM-1、CTGF、CyPA水平是严重COPD的影响因素。结果说明,COPD患者血清sTREM-1、CTGF、CyPA水平显著升高,并且与患者肺功能指标显著相关,可用于判断COPD患者的病情严重程度。     

艳山姜挥发油通过调控巨噬细胞CD36和ABCA1表达抑制泡沫细胞的形成

目的:观察艳山姜挥发油对氧化低密度脂蛋白(ox-LDL)诱导巨噬细胞转化为泡沫细胞的抑制作用,并探索其机制。方法:使用佛波酯(PMA,100μg·L^-1)诱导人白血病单核细胞(THP-1)24 h后形成巨噬细胞,实验分为4组,分别为空白组(无血清RPMI 1640),模型组(80 mg·L^-1ox-LDL),艳山姜挥发油低剂量组(80 mg·L^-1ox-LDL+4μg·L^-1艳山姜挥发油),艳山姜挥发油高剂量组(80 g·L^-1ox-LDL+20μg·L^-1艳山姜挥发油)。噻唑蓝(MTT)比色法检测艳山姜挥发油对巨噬细胞的活性的影响,蛋白免疫印迹法(Western blot)检测巨噬细胞中白细胞分化抗原36(CD36)和三磷酸腺苷结合盒转运体A1(ABCA1)的表达,酶联免疫吸附测定(ELISA)检测巨噬细胞内胆固醇酯含量,油红O染色法检测巨噬细胞中脂质小滴的含量。结果:艳山姜挥发油对巨噬细胞无毒性。与空白组比较,模型组的巨噬细胞内脂滴和胆固醇酯的含量显著增加(P<0.01),CD36蛋白表达显著上升(P<0.01),ABCA1蛋白表达无显著变化;与模型组比较,艳山姜挥发油显著抑制巨噬细胞中脂滴和胆固醇酯的含量(P<0.01),下调CD36的蛋白表达(P<0.01),上调ABCA1蛋白的表达(P<0.01),艳山姜挥发油可抑制巨噬细胞向泡沫细胞的转化。结论:艳山姜挥发油对ox-LDL诱导的巨噬细胞向泡沫细胞的形成具有抑制作用,该药理作用与艳山姜挥发油下调巨噬细胞CD36和上调ABCA1蛋白的表达有关。     

Clinical and molecular spectrum of Wiedemann-Steiner syndrome,an emerging member of the chromatinopathy family

Wiedemann-Steiner syndrome (OMIM #605130) is a rare congenital malformation syndrome characterized by hypertrichosis cubiti associated with short stature; consistent facial features, including long eyelashes, thick or arched eyebrows with a lateral flare, wide nasal bridge, and downslanting and vertically narrow palpebral fissures; mild to moderate intellectual disability; behavioral difficulties; and hypertrichosis on the back. It is caused by heterozygous pathogenic variants in KMT2A. This gene has an established role in histone methylation, which explains the overlap of Wiedemann-Steiner syndrome with other chromatinopathies, a heterogeneous group of syndromic conditions that share a common trigger: The disruption of one of the genes involved in chromatin modification, leading to dysfunction of the epigenetic machinery.     

Psychological Outcome after Hemorrhagic Stroke is Related to Functional Status

BackgroundTo identify opportunities to improve morbidity after hemorrhagic stroke, it is imperative to understand factors that are related to psychological outcome.Design/MethodsWe prospectively identified patients with non-traumatic hemorrhagic stroke (intracerebral or subarachnoid hemorrhage) between January 2015 and February 2021 who were alive 3-months after discharge and telephonically assessed 1) psychological outcome using the Quality of Life in Neurological Disorders anxiety, depression, emotional and behavioral dyscontrol, fatigue and sleep disturbance inventories and 2) functional outcome using the modified Rankin Scale (mRS) and Barthel Index. We also identified discharge destination for all patients. We then evaluated the relationship between abnormal psychological outcomes (T-score >50) and discharge destination other than home, poor 3-month mRS score defined as 3-5 and poor 3-month Barthel Index defined as <100.Results73 patients were included; 41 (56%) had an abnormal psychological outcome on at least one inventory. There were 41 (56%) patients discharged to a destination other than home, 44 (63%) with poor mRS score and 28 (39%) with poor Barthel Index. Anxiety, depression, emotional and behavioral dyscontrol and sleep disturbance were all associated with a destination other than home, poor mRS score, and poor Barthel Index (all p<0.05). Fatigue was related to poor mRS score and poor Barthel Index (p=0.005 and p=0.006, respectively).ConclusionMultiple psychological outcomes 3-months after hemorrhagic stroke are related to functional status. Interventions to improve psychological outcome and reduce morbidity in patients with poor functional status should be explored by the interdisciplinary team.