Awake craniotomy for gliomas involving motor-related areas: classification and function recovery

Journal of Neuro-Oncology - Glioblastoma (GBM) remains one of the most lethal primary brain tumors in children and adults. Targeting tumor metabolism has emerged as a promising-targeted therapeutic...     

MicroRNAs and target genes in epileptogenesis

Epilepsy is a chronic brain dysfunction. Current antiepileptic medicines cannot prevent epileptogenesis. Increasing data have shown that microRNAs (miRNAs) are selectively altered within the epileptic hippocampi of experimental models and human tissues, and these alterations affect the genes that control epileptogenesis. Furthermore, manipulation of miRNAs in animal models can modify epileptogenesis. As a result, miRNAs have been proposed as promising targets for treating epilepsy. We searched PubMed using the terms “microRNAs/miRNAs AND epilepsy”, “microRNAs/miRNAs AND epileptogenesis”, and “microRNAs/miRNAs AND seizure”. We selected the articles in which the relationship between miRNAs and target gene(s) was validated and manipulation of miRNAs in in vivo epilepsy models modified epileptogenesis during the chronic phase via gene regulation. A total of 13 miRNAs were found in the present review. Based on the current analysis of miRNAs and their target gene(s), each miRNA has limitations as a potential epilepsy target. Importantly, miR-211 or miR-128 transgenic mice displayed seizures. These findings highlight new developments for epileptogenesis prevention. Developing novel strategies to modify epileptogenesis will be effective in curing epilepsy patients. This article provides an overview of the clinical application of miRNAs as novel targets for epilepsy.     

丹参川芎联合骨瓜或骨肽对糖尿病骨质疏松患者糖代谢和骨代谢的影响

目的:探讨在丹参川芎治疗基础上,结合骨瓜或骨肽应用于糖尿病骨质疏松症对糖代谢、骨代谢作用价值。方法:选取2016年3月至2017年9月湖北省黄石市第二医院受诊的糖尿病骨质疏松症患者253例作为研究对象。将应用丹参川芎结合骨瓜治疗的128例归为骨瓜组,将予以丹参川芎结合骨肽治疗的125例归为骨肽组,分析2组糖化血红蛋白(Hb A1c)、空腹血糖(FBG) N-端中段骨钙素(N-MID-OT)、骨特异性碱性磷酸酶(BAP),骨形态发生蛋白-2(BMP-2),骨钙素(BBGP)。骨密度(BMD),甲状旁腺素(PTH)、碱性磷酸酶(ALP),β-胶原特殊序列(β-CTx),并比较药物安全性。结果:1)骨瓜组糖代谢Hb A1c(7. 41±0. 64)%、钙离子(2. 21±0. 28) mmol/L、FBG(6. 12±0. 59) mmol/L、血磷(1. 42±0. 25)mmol/L在治疗后与骨肽组Hb A1c(7. 79±0. 51)%、钙离子(2. 27±0. 33) mmol/L、FBG(6. 37±0. 83) mmol/L、血磷(1. 35±0. 31) mmol/L差异无统计学意义(P 0. 05); 2)骨肽组N-MID-OT(16. 37±2. 83) ng/m L和骨瓜组差异无统计学意义(P0. 05),BAP(142. 26±10. 66)μg/L、BGP(5. 07±1. 32)μg/L显著低于骨瓜组,BMP-2 (86. 35±6. 24) ng/L显著高于骨瓜组,差异有统计学意义(P 0. 05); 3)骨肽组BMD(0. 57±0. 13) g/cm3显著高于骨瓜组,PTH(32. 26±2. 15) pg/m L、ALP(72. 35±5. 19) U/L显著低于骨瓜组,差异有统计学意义(P 0. 05),β-CTx(0. 39±0. 02) ng/m L和骨瓜组(0. 42±0. 04)ng/m L差异无统计学意义著(P 0. 05); 4)骨瓜组不良反应率(3. 13%)显著低于骨肽组(9. 60%),差异有统计学意义(P 0. 05)。结论:对于糖尿病骨质疏松症的治疗,基于丹参川芎,增加注射用骨肽比较注射用骨瓜提取物,更能促进患者多项骨代谢指标、血清生化指标及BMD的恢复,二者具有相似的调节糖代谢的作用,但骨肽不良反应相对较高,临床上应结合患者实际情况进行药物的选择。     

苦参素联合胸腺肽治疗慢性乙型肝炎

目的探讨苦参素联合胸腺肽治疗慢性乙型肝炎的疗效，寻找治疗慢性乙型肝炎的有效方法。方法治疗组用苦参素葡萄糖注射液600mg，胸腺肽100mg，静脉注射，每日1次，使用12周后口服12周。对照组使用α干扰素500万U，皮下注射，隔日1次，胸腺肽100mg，肌肉注射，每周2次，用24周。两组患者均为乙型肝炎病毒单纯感染者。HB-sAg、HBeAg、HBcAb阳性，HBVDNA≥10^5拷贝／L。丙氨酸氨基转移酶（ALT）≥150U／L。结果治疗24周，苦参素组52例中39例（75．0％）ALT正常，干扰素组48例中38例（79．2％）ALT正常，差异无统计学意义（P〉0．05）。苦参素组HBeAg、HBVDNAM例（59．6％）转阴。干扰素组HBsAg转阴1例（2．1％），HBeAg27例转阴（56．2％），HBVDNA29例转阴，占60．4％。两组病原学比较，差异无统计学意义（P〉0．05）。停药随访12—24周，苦参素组31例近期治愈者18例（58．1％）复发，ALT升高，HBeAg和HBVDNA转阳。而干扰素组近期治愈的29例中10例（34．5％）ALT升高，HBeAg和HBVDNA转阳，X^2=1．09，P〉0．05。远期疗效比较，差异无统计学意义（P〉0．05）。结论苦参素与干扰素治疗慢性乙型肝炎，不论是近期还是远期疗效，差异均无统计学意义。在乙型肝炎的治疗中可以使用苦参素，但要延长疗程，和其他免疫调节剂联合使用，可能有增加疗效的作用。     

中性粒细胞明胶酶相关载脂蛋白与冠状动脉临界病变患者FFR的相关性

目的 探讨血清中性粒细胞明胶酶相关载脂蛋白（NGAL）水平与冠状动脉临界病变患者血流储备分数(FFR) 的相关性及其临床意义。 方法 回顾性分析海南医学院第二附属医院2019年1月～2021年1月经冠状动脉造影检查为冠状动脉临界病变(冠状动脉狭窄程度为50%～70%) 并行FFR检查的244例患者临床资料,根据冠状动脉FFR测得值分为FFR＜0.8组(83例)和FFR≥0.8组(161例)。入选患者均于冠状动脉造影检查前检测血清NGAL、总胆固醇、甘油三酯、肌酐、血糖等指标。采用相关分析、多因素Logistic回归分析和受试者工作特征曲线（ROC）探讨NGAL与FFR的相关性。 结果 FFR＜0.8组患者血清NGAL水平明显高于FFR≥0.8组［71.93（50.12,150.45）μg/L vs34.99（24.47,50.58）μg/L,P＜0.001］,NGAL水平与FFR值呈负相关(r=0.505,P＜0.001);经多因素Logistic回归分析,NGAL是冠状动脉临界病变患者心肌缺血的独立预测因子（OR=1.029,95%CI：1.017～1.041,P＜0.001）;ROC曲线分析显示,最佳的截断点为52.51μg/L,应用FFR值=0.8作为判断冠状动脉临界病变患者有无心肌缺血的灵敏度为79.50%,特异度为73.49%。 结论 血清NGAL水平升高是冠状动脉临界病变患者FFR降低的独立危险因素,其有望成为诊断冠状动脉临界病变患者心肌有无功能性缺血的潜力生物学指标。     

三子颗粒下调miR-205-5p抑制小鼠脾虚型肠道腺瘤生长研究

目的 探讨三子颗粒通过降低微小核糖核酸-205-5p（miR-205-5p）水平抑制小鼠脾虚型肠道腺瘤生长的作用。方法 取70只4周龄的雄性C57BL/6J小鼠,采用对氧化偶氮甲烷（AOM）/葡聚糖硫酸钠（DSS）诱导小鼠结直肠腺瘤模型,将建模小鼠随机分为模型组、阿司匹林（200 mg·kg^-1）组、miR inhibitor-NC （2 mg·kg^-1）组、miR-205-5p inhibitor （2 mg·kg^-1）组和三子颗粒低、中、高剂量（1.7、3.4、6.8 g·kg^-1）组,造模期间ig给药,每天1次。比较各组小鼠肠道腺瘤的数量并测量腺瘤体积;苏木素-伊红（HE）染色观察小鼠肠道腺瘤的病理情况;CCK-8法检测各组小鼠肠道腺瘤细胞增殖活力;原位末端标记（TUNEL）法检测小鼠肠道腺瘤细胞凋亡;实时荧光定量PCR（qRT-PCR）法检测肠道腺瘤miR-205-5p表达量及磷酸酯酶与张力蛋白同源物（PTEN）、B淋巴细胞瘤-2（Bcl-2）、Bcl-2相关X蛋白（Bax）、Ki67 mRNA表达量;Western blotting法检测PTEN、Bcl-2、Bax、Ki67蛋白表达水平;荧光素酶活性实验验证miR-205-5p和PTEN的靶向关系。结果 与模型组比较,阿司匹林组和三子颗粒低、中、高剂量组小鼠肠道腺瘤数量、体积及细胞增殖活性均显著降低,凋亡率显著升高（P＜0.05）,miR-205-5p表达量、Bcl-2、Ki67 mRNA及蛋白表达量显著降低,PTEN、Bax mRNA及蛋白表达量显著升高（P＜0.05）,其中三子颗粒作用呈剂量相关性;与miR inhibitor-NC组比较,miR-205-5p inhibitor组小鼠肠道腺瘤数量、体积及细胞增殖活性均显著降低,凋亡率显著升高（P＜0.05）,miR-205-5p表达量、Bcl-2、Ki67 mRNA及蛋白表达量显著降低,PTEN、Bax mRNA及蛋白表达量显著升高（P＜0.05）;荧光素酶活性实验证实miR-205-5p可靶向调控PTEN。结论 三子颗粒可抑制小鼠脾虚型肠道腺瘤生长,可能是通过下调miR-205-5p,上调PTEN、Bax表达,下调Bcl-2、Ki67表达发挥作用的。     

CTLA-4 blockade enhances polyfunctional NY-ESO-1 specific T cell responses in metastatic melanoma patients with clinical benefit

Blockade of inhibitory signals mediated by cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) has been shown to enhance T cell responses and induce durable clinical responses in patients with metastatic melanoma. The functional impact of anti-CTLA-4 therapy on human immune responses is still unclear. To explore this, we analyzed immune-related adverse events and immune responses in metastatic melanoma patients treated with ipilimumab, a fully human anti-CTLA-4 monoclonal antibody. Fifteen patients were selected on the basis of availability of suitable specimens for immunologic monitoring, and eight of these showed evidence of clinical benefit. Five of the eight patients with evidence of clinical benefit had NY-ESO-1 antibody, whereas none of seven clinical non-responders was seropositive for NY-ESO-1. All five NY-ESO-1 seropositive patients had clearly detectable CD4⁺ and CD8⁺ T cells against NY-ESO-1 following treatment with ipilimumab. One NY-ESO-1 seronegative clinical responder also had a NY-ESO-1 CD4⁺ and CD8⁺ T cell response, possibly related to prior vaccination with NY-ESO-1. Among five clinical non-responders analyzed, only one had a NY-ESO-1 CD4⁺ T cell response and this patient did not have detectable anti-NY-ESO-1 antibody. Overall, NY-ESO-1-specific T cell responses increased in frequency and functionality during anti-CTLA-4 treatment, revealing a polyfunctional response pattern of IFN-γ, MIP-1β and TNF-α. We therefore suggest that CTLA-4 blockade enhanced NY-ESO-1 antigen-specific B cell and T cell immune responses in patients with durable objective clinical responses and stable disease. These data provide an immunologic rationale for the efficacy of anti-CTLA-4 therapy and call for immunotherapeutic designs that combine NY-ESO-1 vaccination with CTLA-4 blockade.