Phloretin, a flavonoid present in various plants, has been reported to exert anticarcinogenic effects. However, the mechanism of its chemo-preventive effect on human glioblastoma cells is not fully understood. This study aimed to investigate the molecular mechanism of phloretin and its associated chemo-preventive effect in human glioblastoma cells. The results indicate that phloretin inhibited cell proliferation by inducing cell cycle arrest at the G0-G1 phase and induced apoptosis of human glioblastoma cells. Phloretin-induced cell cycle arrest was associated with increased expression of p27 and decreased expression of cdk2, cdk4, cdk6, cyclinD and cyclinE. Moreover, the PI3K/AKT/mTOR signaling cascades were suppressed by phloretin in a dose-dependent manner. In addition, phloretin triggered the mitochondrial apoptosis pathway and generated reactive oxygen species (ROS). This was accompanied by the up-regulation of Bax, Bak and c-PARP and the down-regulation of Bcl-2. The antioxidant agents N-acetyl-L-cysteine and glutathione weakened the effect of phloretin on glioblastoma cells. In conclusion, these results demonstrate that phloretin exerts potent chemo-preventive activity in human glioblastoma cells through the generation of ROS.

Ethnic disparity of cerebral small vessel disease (CSVD) has been reported previously but understanding of its clinical-anatomical is sparse. Two cohorts of CSVD patients from Peking University First Hospital, China and University Hospital of Ulm, Germany were retrospectively collected between 2013 and 2017. Visual rating scales and semiautomatic computer-assisted quantitative analysis were used to describe the neuroimaging features of CSVD, including lacunes, enlarged perivascular spaces, white matter changes and microbleeds. After exclusion of confounding neurological disorders, 165 out of 220 Chinese and 86 out of 98 German patients’ data were analyzed. Mean age of patients was 64.0 ± 11.9 years in China and 73.9 ± 10.3 years in Germany. Cognitive deficits were more prominent in the German group, mainly in the cognitive domains of language and delayed recall. Neuroimaging comparison showed that lacunes were more common and white matter lesion load was more severe in German than Chinese patients. Spatial distribution analysis suggested that Chinese patients showed more deep and infratentorial lesions (microbleeds and lacunes), while lesions in German patients were more frequently located in the lobes or subcortical white matter. In conclusion, different age of onset and anatomical distribution of lesions exist between Chinese and German CSVD patients in the observed population.

Vascular endothelial cell (EC) and blood–brain barrier (BBB) dysfunction is the core pathogenesis of cerebral small vessel disease (CSVD). Moreover, animal experiments have shown the importance of connexin (Cx)-43 in EC and BBB function. In this study, we recruited 200 patients diagnosed with sporadic CSVD. Initially, we examined imaging scores of white matter hyperintensities (WMH), lacunar infarction (LI), and cerebral microbleeds (CMB). Additionally, we performed next-generation sequencing of the GJA1 gene (Cx43 coding gene) to examine correlation between these single-nucleotide polymorphisms and the burden and distribution of CSVD. Fourteen target loci were chosen. Of these, 13 loci (92.9%) contributed toward risk for cerebellar LI, one locus (7.1%) was shown to be a protective factor for lobar CMB after FDR adjustment. In conclusion, single-nucleotide polymorphisms in the GJA1 gene appear to affect the distribution but not severity of CSVD.

Background and Purpose: Studies on the regional differences in hospital costs of acute ischemic stroke (AIS) are scarce in China. We aimed to explore the regional differences in hospital costs and identify the determinants of hospital costs in each region.Methods: Data were collected from the Chinese Acute Ischemic Stroke Treatment Outcome Registry (CASTOR), a multicenter prospective study on patients diagnosed with AIS and hospitalized from 2015 to 2017. Univariate and multivariate analyses were undertaken to identify the determinants of hospital costs of AIS.Results: A total of 8,547 patients were included in the study, of whom 3,700 were from the eastern area, 2,534 were from the northeastern area, 1,819 were from the central area, and 494 were from the western area. The median hospital costs presented a significant difference among each region, which were 2175.9, 2175.1, 2477.7, and 2282.4 dollars in each area, respectively. Each region showed a similar hospital cost proportion size order of cost components, which was Western medicine costs, other costs, diagnostic costs, and traditional medicine costs, in descending order. Male sex, diabetes mellitus, severe stroke symptoms, longer length of stay, admission to the intensive care unit, in-hospital complications of hemorrhage, and thrombectomy were independently associated with hospital costs in most regions.Conclusion: Hospital costs in different regions showed a similar proportion size order of components in China. Each region had different determinants of hospital costs, which reflected its current medical conditions and provided potential determinants for increasing medical efficiency according to each region's situation.

Background and Purpose: There is limited information on symptomatic intracranial hemorrhage (sICH) in stroke patients without thrombolysis. This study aimed to evaluate the risk factors of sICH and the association between sICH and the prognosis at 3 and 12 months in acute ischemic stroke patients without thrombolysis.Methods: Data originated from the Chinese Acute Ischemic Stroke Treatment Outcome Registry. Univariate analysis and multivariate logistic regression were used to screen the risk factors of sICH. Multivariable logistic regression models were used to assess the association of sICH with poor outcome and all-cause mortality.Results: Totally, 9,484 patients were included, of which 69 (0.73%) had sICH. Atrial fibrillation (odds ratio [OR], 3.682; 95% confidence interval [CI], 1.945–6.971; p < 0.001), history of tumors (OR, 2.956; 95% CI, 1.115–7.593; p = 0.024), and the National Institutes of Health Stroke Scale (NIHSS) score on admission ([6–15: OR, 2.344; 95% CI, 1.365–4.024; p = 0.002] [>15: OR, 4.731; 95% CI, 1.648–13.583; p = 0.004]) were independently associated with sICH. After adjustment of the confounders, patients with sICH had a higher risk of poor outcome (OR, 1.983; 95% CI, 1.117–3.521; p = 0.018) at 3 months and that of all-cause mortality at 3 (OR, 6.135; 95% CI, 2.328–16.169; p < 0.001) and 12 months (OR, 3.720; 95% CI, 1.513–9.148; p = 0.004).Conclusion: sICH occurred in 0.73% of acute ischemic stroke patients without thrombolysis and was associated with a worse prognosis at 3 and 12 months. Atrial fibrillation, history of tumors, and NIHSS score at admission were independent risk factors of sICH.