Hypoxia and HIF-1α expression in the epiphyseal cartilage following ischemic injury to the immature femoral head

HIF-1α has been shown to be a central mediator of cellular response to hypoxia. The role it plays after ischemic injury to the immature femoral head is unknown. The purpose of this study was to determine the region of the femoral head affected by hypoxia following ischemic injury to the immature femoral head and to determine the site of HIF-1α activation and revascularization. We hypothesize that the epiphyseal cartilage, rather than the bony epiphysis, is the site of HIF-1α activation following ischemic osteonecrosis and that the epiphyseal cartilage plays an important role in the revascularization process.Materials and methodsFemoral head osteonecrosis was surgically induced in 56 immature pigs. Hypoxyprobe staining, cell viability assay, HIF-1α western blot, RT-qPCR of HIF-1α, VEGF, VEGFR2, and PECAM, and micro-CT assessments of microfil-infused femoral heads were performed.ResultsSevere hypoxia was present in the bony epiphysis and the lower part of the epiphyseal cartilage following ischemia. In the bony epiphysis, extensive cell death and tissue necrosis was observed with degradation of proteins and RNAs which precluded further analysis. In the epiphyseal cartilage, the loss of cell viability was limited to its deep layer with the remainder of the cartilage remaining viable. Furthermore, the cartilage from the ischemic side showed a significant increase in HIF-1α protein level and HIF-1α expression. VEGF expression in the cartilage was dramatically and significantly increased at 24 h, 2 and 4 weeks (p < 0.05 for all) with 5 to 10 fold increase being observed on the ischemic side compared to the normal side. PECAM and VEGFR2 expressions in the cartilage were both significantly decreased at 24 h but returned to the normal levels by 2 and 4 weeks, respectively. Micro-CT showed revascularization of the cartilage on the ischemic side with the vessel volume/total volume equaling the normal side by 4 weeks.ConclusionsAcute ischemic injury to the immature femoral head induced severe hypoxia and cell death in the bony epiphysis and the deep layer of the epiphyseal cartilage. Viable chondrocytes in the superficial layer of the epiphyseal cartilage showed HIF-1α activation and VEGF upregulation with subsequent revascularization occurring in the cartilage.     

Changes of autologous neural stem cells in the hippocampi of aging mice

Although there is possibility of cognitive disturbance in aging people, many of them live for long life and enjoy well-functioning brain during the whole life-span. The biological basis of longevity is unknown. In this study, we investigated the influence of aging on hippocampal neural stem cells (NSCs), and the correlations between hippocampal neurogenesis and cognitive function. The result showed that the protein production and mRNA expression of nestin, and the number of BrdU⁺ cells in dentate gyrus (DG) of the aged non-dementia mice were clearly higher than that in the aged dementia mice and the young adult mice. We also found that the number of NeuN⁺ (neuron-specific nuclear antigen) cells in DG and CA1, choline O-acetyltransferase (ChAT, EC 2.3.1.6) production and mRNA expression in hippocampi of the aged-dementia mice were significantly reduced as compared to that of the young adult mice and the aged non-dementia mice, whereas the number of NeuN⁺ cells, ChAT production and mRNA expression of the aged non-dementia mice has no difference with that of the young adult mice. Glial fibrillary acidic protein (GFAP) expression in the hippocampi of aged dementia mice significantly higher than that of the young adult mice and the aged non-dementia mice. Our results suggest that aging sometimes does not cause changing of the number of neurons and the hippocampal neurogenesis. Increment of DNA replication and neuron replacement, promotion of differentiation of neural stem cells, enhancement of neuronal proliferation, facilitation of synaptic plasticity of neurons may all benefit to the maintenance of the normal cognitive ability in the aged mice.     

Safety but Limited Efficacy of Ensartinib in ROS1-Positive NSCLC: A Single-Arm,Multicenter Phase 2 Study

IntroductionSome ALK inhibitors with good inhibition of ROS1 in preclinical studies have been reported to be possibly beneficial in ROS1-positive NSCLC. In this work, we studied the efficacy and safety of ensartinib in the treatment of patients with ROS1-positive NSCLC.MethodsThe exploratory study was a phase 2, single-arm, multicenter design (NCT03608007). Patients with ROS1-positive NSCLC with a previous chemotherapy line number of less than or equal to 1 who received ensartinib at the dose of 225 mg once daily were enrolled. The primary end point was objective response rate evaluated by an investigator per Response Evaluation Criteria in Solid Tumors version 1.1.ResultsFrom June 2018 to July 2019, a total of 59 patients were enrolled at 23 centers in the People’s Republic of China. At the time of data cutoff, the median follow-up was 19.8 months (range: 0.8–22.5). The median objective response rate was 27.0 % (95 % confidence interval [CI]: 13.8–44.1) with 10 partial responses. Median duration of response was 4.8 months (95 % CI: 1.8–10.8). The median progression-free survival was 4.6 months (95 % CI: 4.0–6.4). The median overall survival was not estimable (95 % CI: 14.9–not estimable). Of four patients with brain metastases, intracranial disease control was reported in three (75.0 %, 95 % CI: 19.4–99.4). The most common treatment-related adverse events (TRAEs) were rash and liver enzyme abnormalities, with good prognosis after adjustment for dosage and concomitant medication. Most of the TRAEs were of grades 1 to 2, and incidence of grade greater than or equal to 3 TRAEs was 25.4 %.ConclusionsEnsartinib had a modest efficacy in patients with ROS1-positive NSCLC with an acceptable safety profile.     

Characteristics of the macula in amblyopic eyes by optical coherence tomography

AIM: To test the hypothesis that amblyopic neuroretina may have an altered thickness when compared to the normal. METHODS: Twenty-five amblyopic, young patients between the ages of 7 and 11 years old were studied. The interested neuroretina areas are defined into 10 sub-regions according to superior-inferior, nasal-temoral, and peri-para axis, which cross the fovela structure. The thicknesses of ten, defined macular regions were separately measured by optical coherence tomography (OCT) and analyzed by t-test. RESULTS: The average thickness of neuroretina in the exact foveola of the amblyopic eyes is larger than that of normal eyes (P<0.05), but the other nine regions have no significant difference. Interestingly, in both the normal and amblyopic eyes, the temporal area looks thinner than other quadrants (P<0.05). CONCLUSION: Thickness alteration may be associated with amblyopic disorders in young patients. Studying a larger volume of subjects of similar age is required to confirm this observation.     

OGDHL silencing promotes hepatocellular carcinoma by reprogramming glutamine metabolism

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转化生长因子β在器官移植排斥反应中的研究进展

转化生长因子β(TGF-β)家族是一个有着多效性的细胞因子,具有调节细胞的增殖、分化、迁移、生存等功能。近年来具有免疫抑制功能的TGF-β被广泛承认和研究,在抑制心脏、肾脏、肝脏等器官移植排斥反应方面有较多报道。该文对TGF-β在心脏、肾脏、肝脏等器官移植中的免疫抑制机制进行综述,认为TGF-β是一种诱导和调节移植耐受的细胞因子并介导抗炎作用在免疫反应中起到重要作用。     

尼可地尔对冠脉多支病变血运重建不完全患者疗效观察

目的观察尼可地尔对冠脉多支病变血运重建不完全患者的疗效。方法选择冠脉多支病变血运重建不完全的58例冠心病患者,随机分为观察组（n=28）和对照组（n=30）,对豫组患者PCI术后常规行冠心病二级预防治疗,观察组在此基础上加用尼可地尔。对比二组患者6min步行实验（6MWD）、超声心动图、观察患者心绞痛缓解、心功能改善情况及发生主要心血管不良事件情况。结果二组患者在治疗期间及随访期间均未发生死亡、心肌梗死、脑卒中事件,而尼可地尔组患者心绞痛发作持续时间及次数明显减少、6min步行距离提高、心功能有明显改善,与对照组相比差异有统计学意义。结论在常规治疗的基础上加用尼可地尔对冠脉多支病变血运重建不完全患者可显著提高运动耐量水平,同时改善心脏功能。     

关节镜下胫骨Inlay技术重建后十字韧带的近期疗效

 目的 探讨关节镜下胫骨Inlay技术双束重建后十字韧带（posterior cruciate ligament,PCL）的近期疗效。方法 2007年3月至2009年9月,采 用关节镜下胫骨Inlay技术行双束PCL重建且随访超过1年的PCL损伤患者17例,男16例,女1例;年龄19~54岁,平均25岁。术前Lysholm膝关节评分（53.4±2.1） 分;国际膝关节评分委员会（International Knee Documentation Committee,IKDC）分级C级7例,D级10例;后抽屉试验阳性17例。术中采用自行设计的胫骨 后方倒打隧道钻具系统制作限深骨隧道。随访时行膝关节X线摄片和螺旋CT检查,观察嵌入骨栓的位置和愈合情况。末次随访时评估Lysholm膝关节评分、IKDC分 级及后抽屉试验,比较与术前的稳定性差异。结果 17例患者均获得随访,随访时间12~28个月,平均17.8个月。末次随访时Lysholm膝关节评分（93.5±1.7）分 ,与术前比较差异有统计学意义（P=0.016）;IKDC分级A级15例、B级2例,与术前比较差异有统计学意义（P=0.021）;后抽屉试验阴性15例,弱阳性2例。术后 12周X线片和螺旋CT示嵌入骨栓的位置满意,愈合良好。结论 胫骨后方倒打隧道钻具系统可以准确制作限深骨隧道,创伤小,使用这种钻具系统的PCL重建术近 期疗效好。