Toll-like receptors (TLR2 and TLR4) antagonist mitigates the onset of cerebral small vessel disease through PI3K/Akt/GSK3ß pathway in stroke-prone renovascular hypertensive rats.

To examine the effect and mechanism of Toll-Like Receptors (TLR2, TLR4) antagonist in CSVD. The rat model of stroke-induced renovascular hypertension (RHRSP) was constructed. TLR2 and TLR4 antagonist was administrated by Intracranial injection. Morris water maze was used to observe the behavioral changes of rat models. HE staining, TUNEL staining and Evens Blue staining were performed to evaluate the permeability of the blood-brain barrier (BBB) and examine the CSVD occurrence and neuronal apoptosis. The inflammation and oxidative stress factors were detected by ELISA. Hypoxia-glucose-deficiency (OGD) ischemia model was constructed in cultured neurons. Western blot and ELISA were used to examine the related protein expression in TLR2/TLR4 signaling pathway and PI3K/Akt/GSK3ß signaling pathway. The RHRSP rat model was successfully constructed, and the blood well and BBB permeability were altered. The RHRSP rats showed cogitative impairment and excessive immune response. After TLR2/TLR4 antagonist administration, the behavior of model rats were improved, cerebral white matter injury was reduced, and the expression of several key inflammatory factors including TLR4, TLR2, Myd88 and NF-kB were decreased, as well as the ICAM-1, VCAM-1, inflammation and oxidative stress factors. In vitro experiments showed that TLR4 and TLR2 antagonist increased the cell viability, inhibited the apoptosis, and decreased p-Akt and p-GSK3ß expression. Moreover, the PI3K inhibitors resulted in decreased anti-apoptotic and anti-inflammatory effects of TLR4 and TLR2 antagonist. These results suggested that TLR4 and TLR2 antagonist achieved protective effect on the RHRSP through the PI3K/Akt/GSK3ß pathway.

Analysis of Psychological Trends and Policy Recommendations of Medical Staff in Northern China in the Latter Stages of the COVID-19 Pandemic.

Aim: Since the 2019 coronavirus disease (COVID-19) outbreak, medical staff have faced greater psychological stress and are prone to psychological problems such as anxiety and depression, as confirmed by several studies. This study further clarifies the psychological status of Chinese medical staff during the stable phase of the pandemic through a cross-sectional investigation in a large population sample in northern China. Methods: Subjects: Clinical frontline medical staff from seven hospitals in Liaoning Province were recruited from November 2020 to February 2021. Research Tools: The research tools used were the Self-Rating Anxiety Scale (SAS), Self-Rating Depression Scale (SDS), Simplified Coping Style Questionnaire (SCSQ), and General Status Questionnaire. Statistical Analysis: SPSS 22.0, ANOVA variance analysis, and multiple logistics regression were used for statistical analysis. P-values of <0.05 indicated significant statistical differences. Results: A total of 3,144 medical staff completed the survey (599 men [19.1%] and 2,545 women [80.9%]; 1,020 doctors [32.4%] and 2,124 nurses [67.6%]). Among all subjects, the rates of anxiety and depression were 21.1% (663/3, 144) and 43.9% (1,381/3,144), respectively. Multiple logistic comparative analysis revealed that age (OR = 1.272, 95% CI = 1.036-1.561, P = 0.022), the need for psychological counseling (OR = 1.566, 95% CI = 1.339-1.830, P < 0.001), and the coexistence of depression (OR = 0.050, 95% CI = 0.038-0.066, P < 0.001) were significantly associated with anxiety. Coexisting anxiety was also associated with the occurrence of depression (OR = 0.050, 95% CI = 0.038-0.065, P < 0.001). Conclusions: In the later stages of the pandemic in China, the occurrence rates of anxiety and depression among medical staff remain high. In addition to age, there is little correlation between anxiety or depression and general factors such as gender and profession. As a special group, medical staff show different psychological changes at various times during a stressful event. Concerning for the psychological needs of medical staff and different psychologically oriented policy implementation are needed.

Evaluation of hemodynamic characteristics in posterior circulation infarction patients with vertebral artery dominance by color doppler flow imaging and transcranial doppler sonography.

PURPOSE: The aim of this study was to investigate the hemodynamic characteristics of posterior circulation infarction (PCI) patients with the vertebral artery dominance (VAD) using Color Doppler flow imaging (CDFI) and Transcranial Doppler sonography (TCD) and to explore the pathogenesis of PCI caused by VAD. MATERIALS AND METHODS: A total of 186 consecutive PCI patients were enrolled. All the patients underwent magnetic resonance (MR) examination and the clinical data were collected. According to the brain magnetic resonance angiography (MRA), the patients were divided into VAD and non-VAD groups. CDFI and TCD were performed to identify the hemodynamic parameters of the vertebral artery (VA) and basilar artery (BA). RESULTS: The male population was significantly more frequent in the VAD group (71.3%) as compared to the non-VAD group (53.1%). The significant difference in hemodynamic parameters was observed between VAD and non-VAD groups. Resistance index (RI) of extracranial and intracranial VA was different as well. There were also differences in the VA side-to-side diameter difference-value, peak velocity (Vp), mean velocity (Vm) and pulsatility index (PI) with varying degrees of BA curvature. CONCLUSIONS: VA and BA hemodynamic changes caused by VAD may be an important risk factor in the process of occurrence of PCI. The combination of CDFI and TCD can help to detect the hemodynamic changes in the intracranial and extracranial segments of VA and BA. This can have important clinical value in understanding the pathogenesis of PCI.

A cross-sectional study on diabetes epidemiology among people aged 40 years and above in Shenyang, China.

This study aimed at understanding the diabetic prevalence, awareness, treatment and control rates and their influencing factors among people aged ≥ 40 years in Shenyang, China. A face-to-face cross-sectional epidemiological survey was conducted on the respondents using the national unified questionnaire. A total of 3922 respondents were enrolled, including 609 cases of diabetes. The diabetic prevalence rate was 15.5%, and was higher in rural areas than that in urban areas (17.7% vs. 14.2%, p = 0.004), while no difference was observed between men and women (14.8% vs. 16.1%, p = 0.242). Advanced age, hypertension and dyslipidemia were the diabetes influencing factors. Among the 609 respondents with diabetes, the diabetic awareness and treatment rates, and the control rate of fasting plasma glucose were 82.3%, 36.6% and 17.1%, respectively. In different age groups, the diabetic awareness rate was higher in men than that in women, and the treatment rate was higher in women than that in men. The diabetic patients, who consumed fruit for ≥ 5 days a week, accounted for 16.3%, and their diabetic treatment (28.1%) and control rates (44.1%) were lower. Shenyang people aged ≥ 40 years have higher diabetic prevalence and awareness rates, and lower diabetic treatment and control rates. Finally, it is necessary to enhance awareness and education about diabetes, to improve its treatment and control rates.

TLK2 enhances aggressive phenotypes of glioblastoma cells through the activation of SRC signaling pathway.

Glioblastoma are among the most common forms of cancer affecting the central nervous system, and yet there is currently no effective means of treating them. In the current study, we reported that tousled-like kinase 2 (TLK2) is a key factor in glioblastoma that modulates SRC signaling, thereby driving tumor malignancy. TLK2 is commonly upregulated in glioblastoma, and such upregulation was associated with poor patient outcomes. TLK2 overexpression induced cell growth, migration, invasion, and epithelial-mesenchymal transition, and cell cycle arrest, while TLK2 knockdown had the opposite effect. SRC pathway inhibition by Saracatinib resulted in reduced TLK2-mediated glioblastoma migration, invasion, confirming a key role for SRC signaling in regulating the functions of TLK2. Together, our findings demonstrate that glioblastoma TLK2 overexpression acts as a key driver of tumor malignancy via SRC signaling pathway.

Significance of Magnetic Resonance Imaging (MRI) T2 Hyperintense Endo-Vessels Sign in Progressive Posterior Circulation Infarction.

BACKGROUND MRI FLAIR hyperintense vessels sign (FHVs) is a special imaging marker that plays a key role in acute infarction imaging and diagnosis. However, FHVs have not been studied in the context of progressive posterior circulation infarction (PPCI), and little is known about the association of hyperintense endo-vessels sign (HEVs) on transverse section MRI with infarction. Thus, our objective here was to investigate the clinical significance of transverse MRI T2 HEVs in patients with PPCI. MATERIAL AND METHODS In this retrospective, case-control study, we enrolled 100 consecutive posterior circulation infarction patients. All the patients underwent head MRI examinations on the onset day and the seventh day after admission. Neurologic deficits of the patients were assessed by the National Institutes of Health Stroke Scale (NIHSS) scores upon admission and after 7 days. Infarction volume on DWI was compared. RESULTS HEVs were detected in 25 of 37 patients in the PPCI group (67.6%) and 22 of 63 patients in the NPPCI group (34.9%). Logistic regression analysis showed that the proportion of HEVs in the PPCI group was higher than in the NPPCI group (P=0.007). Among all the patients, HEVs were detected in 15 of 18 patients (83.3%) with occlusion of the vertebral artery or basilar artery, and 17 of 23 (73.9%) showed severe stenosis. The proportion of vertebrobasilar artery occlusions in the PPCI group was higher than in the NPPCI group (P<0.05). MRI DWI showed that 20 patients had cerebellum infarction among 23 vertebral artery HEVs patients, and 14 patients had brainstem infarction among 15 basilar artery HEVs patients. All of the 9 vertebral and basilar artery HEVs patients had brainstem infarction. The increase in NIHSS scores from baseline to 7 days was significantly greater in patients with HEVs than in patients without HEVs in the PPCI group (P=0.002). The expansion of the infarction size from baseline to 7 days was significantly larger in patients with HEVs than in patients without HEVs in the PPCI group (P=0.037). CONCLUSIONS HEVs are frequently detected in patients with vertebrobasilar artery territory infarction, and they can be considered as a special imaging marker for vertebral artery and basilar artery occlusion and severe stenosis. HEVs can indicate whether or not posterior circulation infarction progresses and they may be an independent risk factor of PPCI.