脑小血管病:犹如“风暴”过后的全脑灾难

脑小血管病（cerebral small vessel d isease,CSVD）是一种临床及影像综合征,病变累及脑的穿通小动脉、毛细血管及小静脉,临床表现为卒中、痴呆、情感障碍及步态异常,影像学表现为近期皮层下梗死及微梗死灶、腔隙灶、白质高信号（white matter hyperintensitie,WMH）、微出血及出血灶、血管周围间隙扩大及脑萎缩。

Aberrant LETM1 elevation dysregulates mitochondrial functions and energy metabolism and promotes lung metastasis in osteosarcoma

Osteosarcoma is a differentiation-deficient disease,and despite the unique advan-tages and great potential of differentiation therapy,there are only a few known differentia-tion inducers,and little research has been done on their targets.Cell differentiation is associated with an increase in mitochondrial content and activity.The metabolism of some tu-mor cells is characterized by impaired oxidative phosphorylation,as well as up-regulation of aerobic glycolysis and pentose phosphate pathways.Leucine-containing zipper and EF-hand transmembrane protein 1(LETM1)is involved in the maintenance of mitochondrial morphology and is closely associated with tumorigenesis and progression,as well as cancer cell stemness.We found that MG63 and 143B osteosarcoma cells overexpress LETM1 and exhibit abnormalities in mitochondrial structure and function.Knockdown of LETM1 partially restored the mitochon-drial structure and function,inhibited the pentose phosphate pathway,promoted oxidative phosphorylation,and led to osteogenic differentiation.It also inhibited spheroid cell forma-tion,proliferation,migration,and invasion in an in vitro model.When LETM1 was knocked down in vivo,there was reduced tumor formation and lung metastasis.These data suggest that mitochondria are aberrant in LETM1-overexpressing osteosarcoma cells,and knockdown of LETM1 partially restores the mitochondrial structure and function,inhibits the pentose phosphate pathway,promotes oxidative phosphorylation,and increases osteogenic differentiation,thereby reducing malignant biological behavior of the cells.

DeepWMH:无需人工标注训练的脑白质高信号病灶分割工具

White matter hyperintensities(WMHs)on fluid-attenuated inversion recovery(FLAIR)images are imaging features in various neurological diseases and essential markers for clinical impairment and disease progression.WMHs are associated with brain aging and pathological changes in the human brain,such as in Alzheimer’s disease(AD)[1],Parkinson’s disease(PD)[2],cerebral small vessel disease(SVD)[3],multiple sclerosis(MS)[4].

Update on cerebral small vessel disease: a dynamic whole-brain disease

Cerebral small vessel disease(CSVD)is a very common neurological disease in older people.It causes stroke and dementia,mood disturbance and gait problems.Since it is difficult to visualise CSVD pathologies in vivo,the diagnosis of CSVD has relied on imaging findings including white matter hyperintensities,lacunar ischaemic stroke,lacunes,microbleeds,visible perivascular spaces and many haemorrhagic strokes.However,variations in the use of definition and terms of these features have probably caused confusion and difficulties in interpreting results of previous studies.A standardised use of terms should be encouraged in CSVD research.These CSVD features have long been regarded as different lesions,but emerging evidence has indicated that they might share some common intrinsic microvascular pathologies and therefore,owing to its diffuse nature,CSVD should be regarded as a‘whole-brain disease’.Single antiplatelet(for acute lacunar ischaemic stroke)and management of traditional risk factors still remain the most important therapeutic and preventive approach,due to limited understanding of pathophysiology in CSVD.Increasing evidence suggests that new studies should consider drugs that target endothelium and blood–brain barrier to prevent and treat CSVD.Epidemiology of CSVD might differ in Asian compared with Western populations(where most results and guidelines about CSVD and stroke originate),but more community-based data and clear stratification of stroke types are required to address this.