Progress on Prevention and Treatment of Cerebral Small Vascular Disease Using Integrative Medicine.

Cerebral small vessel disease (CSVD) is a senile brain lesion caused by the abnormal structure and function of arterioles, venules and capillaries in the aging brain. The etiology of CSVD is complex, and disease is often asymptomatic in its early stages. However, as CSVD develops, brain disorders may occur, such as stroke, cognitive dysfunction, dyskinesia and mood disorders, and heart, kidney, eye and systemic disorders. As the population continues to age, the burden of CSVD is increasing. Moreover, there is an urgent need for better screening methods and diagnostic markers for CSVD, in addition to preventive and asymptomatic- and mild-stage treatments. Integrative medicine (IM), which combines the holistic concepts and syndrome differentiations of Chinese medicine with modern medical perspectives, has unique advantages for the prevention and treatment of CSVD. In this review, we summarize the biological markers, ultrasound and imaging features, disease-related genes and risk factors relevant to CSVD diagnosis and screening. Furthermore, we discuss IM-based CSVD prevention and treatment strategies to stimulate further research in this field.

Untargeted Metabolomic Profiling of Liver in a Chronic Intermittent Hypoxia Mouse Model.

Obstructive sleep apnea (OSA) has been demonstrated to be associated with liver injury. Nevertheless, the mechanisms linking the two disorders remain largely unexplored to date. Based on UHPLC/Q-TOF MS platform, the present study aimed to study the hepatic metabolomic profiling in a chronic intermittent hypoxia (CIH) mouse model to identify altered metabolites and related metabolic pathways. C57BL/6 Mice (n = 12 each group) were exposed to intermittent hypoxia or control conditions (room air) for 12 weeks. At the end of the exposure, liver enzymes and histological changes were assessed. Untargeted metabolomics approach by UHPLC/Q-TOF MS and orthogonal partial least squares-discriminant analysis (OPLS-DA) were applied to screen altered metabolites in mice liver. Bioinformatics analyses were applied to identify the related metabolic pathways. CIH treatment caused a remarkable liver injury in mice. A total of 27 differential metabolites in negative ion mode and 44 in positive ion mode were identified between the two groups. These metabolites were correlated to multiple biological and metabolic processes, including various amino acid metabolism, membrane transport, lipid metabolism, carbohydrate metabolism, nucleotide metabolism, ferroptosis, etc. three differential metabolites including glutathione, glutathione disulfide, arachidonic acid (peroxide free) were identified in the ferroptosis pathway. CIH was associated with a significant metabolic profiling change in mice liver. The metabolites in amino acid metabolism, membrane transport, lipid metabolism, carbohydrate metabolism, nucleotide metabolism, and ferroptosis played an important role in CIH-induced liver injury. These findings contribute to a better understanding of the mechanisms linking OSA and liver injury and help identify potential therapeutic targets.

Diffusion kurtosis imaging of microstructural changes in brain tissue affected by acute ischemic stroke in different locations.

The location of an acute ischemic stroke is associated with its prognosis. The widely used Gaussian model-based parameter, apparent diffusion coefficient (ADC), cannot reveal microstructural changes in different locations or the degree of infarction. This prospective observational study was reviewed and approved by the Institutional Review Board of Xiamen Second Hospital, China (approval No. 2014002).Diffusion kurtosis imaging (DKI) was used to detect 199 lesions in 156 patients with acute ischemic stroke (61 males and 95 females), mean age 63.15 ± 12.34 years. A total of 199 lesions were located in the periventricular white matter (n = 52), corpus callosum (n = 14), cerebellum (n = 29), basal ganglia and thalamus (n = 21), brainstem (n = 21) and gray-white matter junctions (n = 62). Percentage changes of apparent diffusion coefficient (ΔADC) and DKI-derived indices (fractional anisotropy [ΔFA], mean diffusivity [ΔMD], axial diffusivity [ΔDa], radial diffusivity ΔDr, mean kurtosis [ΔMK], axial kurtosis [ΔKa], and radial kurtosis [ΔKr]) of each lesion were computed relative to the normal contralateral region. The results showed that (1) there was no significant difference in ΔADC, ΔMD, ΔDa or ΔDr among almost all locations. (2) There was significant difference in ΔMK among almost all locations (except basal ganglia and thalamus vs. brain stem; basal ganglia and thalamus vs. gray-white matter junctions; and brainstem vs. gray-white matter junctions. (3) The degree of change in diffusional kurtosis in descending order was as follows: corpus callosum > periventricular white matter > brainstem > gray-white matter junctions > basal ganglia and thalamus > cerebellum. In conclusion, DKI could reveal the differences in microstructure changes among various locations affected by acute ischemic stroke, and performed better than diffusivity among all groups.

Determination of oxygen extraction fraction using magnetic resonance imaging in canine models with internal carotid artery occlusion.

Perfusion of the penumbra tissue below the flow threshold for functional disturbance but above that for the maintenance of morphological integrity is the target for therapy in acute ischaemic stroke. The measurement of the oxygen extraction fraction (OEF) may provide a direct assessment of tissue viability, so that irreversible tissue damage and penumbra can be reliably identified. By using an asymmetric spin echo single-shot echo planar imaging (ASE-SSEPI) sequence, the quantitative OEF was obtained in the ischaemic brain tissues of canine models with internal carotid artery occlusion. TTC staining, which delineated the regions of infarct and penumbra, was used for defining the corresponding regions on OEF maps. The threshold of the OEF to discriminate the infarct cores and penumbral tissues was then determined according to the OEF values at different times. With repeated-measures ANOVA, the OEF of the infarcted regions was found to be time dependent. An OEF greater than 0.48 best predicted cortical infarction at 1.5 hr, with an area under the receiving operating characteristic curve of 0.968, a sensitivity of 97.5%, and a specificity of 92.5%. Our results may be helpful in the evaluation of tissue viability during stroke events.

Parameters of diffusional kurtosis imaging for the diagnosis of acute cerebral infarction in different brain regions.

Diffusional kurtosis imaging (DKI) is a new type diffusion-weighted sequence which measures the non-Gaussianity of water diffusion. The present study aimed to investigate whether the parameters of DKI could distinguish between differences in water molecule diffusion in various brain regions under the conditions of acute infarction and to identify the optimal DKI parameter for locating ischemic lesions in each brain region. A total of 28 patients with acute ischemic stroke in different brain regions were recruited for the present study. The relative values of DKI parameters were selected as major assessment indices, and the homogeneity of background image and contrast of adjacent structures were used as minor assessment indices. According to the brain region involved in three DKI parametric maps, including mean kurtosis (MK), axial kurtosis (Ka) and radial kurtosis (Kr), 112 groups of regions of interest were outlined in the following regions: Corpus callosum (n=17); corona radiata (n=26); thalamus (n=21); subcortical white matter (n=24); and cerebral cortex (n=24). For ischemic lesions in the corpus callosum and corona radiata, significant increases in relative Ka were detected, as compared with the other parameters (P<0.05). For ischemic lesions in the thalamus, subcortical white matter and cerebral cortices, an increase in the three parameters was detected, however this difference was not significant. Minor assessment indices demonstrated that Ka lacked tissue contrast and the background of Kr was heterogeneous; thus, MK was the superior assessment parameter for ischemic lesions in these regions. In conclusion, Ka is better suited for the diagnosis of acute ischemic lesions in highly anisotropic brain regions, such as the corpus callosum and corona radiate. MK may be appropriate for the lesions in low anisotropic or isotropic brain regions, such as the thalamus, subcortical white matter and cerebral cortices.

Evaluation of mean diffusion and kurtosis MRI mismatch in subacute ischemic stroke: Comparison with NIHSS score.

Neurological deterioration (ND) is a devastating complication following ischemic stroke. This study aimed to identify the differences in lesion characteristics in subacute ischemic stroke patients with and without ND using diffusional kurtosis imaging (DKI), as well as to confirm the responsible lesions that may lead to ND, as assessed by the National Institutes of Health Stroke Scale (NIHSS) score. Seventy-nine patients with subacute cerebral infarction were allocated to the ND (-) and ND (+) groups according to the NIHSS score and lesion number. The mean diffusion (MD) lesions were significantly larger than the mean kurtosis (MK) deficits in the ND (+) group (P<0.05); however, there was no significant difference in the ND (-) group (P>0.05). The MD and MK in the lesion recovered to normal levels over time; however, the recovery trends in the ND (+) group were substantially slower than the ND (-) group. The differences between the two groups were only significant regarding the MK (p<0.05). Furthermore, multiple infarction lesions exhibited good consistency in the ND (-) group, but were non-homogeneous in the ND (+) group. To the best of our knowledge, this is the first study to demonstrate that a significant MD/MK mismatch and heterogeneity of multiple ischemic lesions on MK in subacute ischemic stroke may represent a new expansion of an ischemic lesion or acute reinfarction, which is closely related to ND.

Intravoxel incoherent motion MRI: emerging applications for nasopharyngeal carcinoma at the primary site.

OBJECTIVES: We compared pure molecular diffusion (D), perfusion-related diffusion (D*), perfusion fraction (f) and apparent diffusion coefficient (ADC) based on intravoxel incoherent motion (IVIM) theory in patients with nasopharyngeal carcinoma (NPC). METHODS: Sixty-five consecutive patients (48 men) with suspected NPC were examined using a 3.0-T MR system. Diffusion-weighted imaging (DWI) was performed with 13 b values (range, 0-800 s/mm(2)). We regarded the result of endoscopy and biopsy as the gold standard for detection. D, D* and f were compared between patients with primary NPC and enlarged adenoids. RESULTS: IVIM DWI was successful in 37 of 40 NPC and 23 of 25 enlarged adenoids cases. D (P = 0.001) and f (P < 0.0001) were significantly lower in patients with NPC than in patients with enlarged adenoids, whereas D* was significantly higher (P < 0.0001). However, the ADC was not significantly different between the two groups (P > 0.05). The area under the ROC curve (AUC) for D was 0.849 and was significantly larger than that for ADC (P < 0.05). CONCLUSIONS: IVIM DWI is a feasible technique for investigating primary NPC. D was significantly decreased in primary NPC, and increased D* reflected increased blood vessel generation and parenchymal perfusion in primary NPC. KEY POINTS: • Intravoxel incoherent motion (IVIM) analysis permits separate quantification of diffusion and perfusion. • IVIM DWI is a feasible technique for investigating primary NPC. • IVIM suggests that primary NPC tissue voxels exhibit both perfusion and diffusion.

Experimental quasi-single-photon transmission from satellite to earth.

Free-space quantum communication with satellites opens a promising avenue for global secure quantum network and large-scale test of quantum foundations. Recently, numerous experimental efforts have been carried out towards this ambitious goal. However, one essential step--transmitting single photons from the satellite to the ground with high signal-to-noise ratio (SNR) at realistic environments--remains experimental challenging. Here, we report a direct experimental demonstration of the satellite-ground transmission of a quasi-single-photon source. In the experiment, single photons (~0.85 photon per pulse) are generated by reflecting weak laser pulses back to earth with a cube-corner retro-reflector on the satellite CHAMP, collected by a 600-mm diameter telescope at the ground station, and finally detected by single-photon counting modules after 400-km free-space link transmission. With the help of high accuracy time synchronization, narrow receiver field-of-view and high-repetition-rate pulses (76 MHz), a SNR of better than 16:1 is obtained, which is sufficient for a secure quantum key distribution. Our experimental results represent an important step towards satellite-ground quantum communication.

[Effects of mechanical stress on the proliferation kinetics of the human periodontal fibroblast cells in vitro].

OBJECTIVE: The purpose of this study was to explore the possible principles for remodeling of periodontal tissues under mechanical stretching by investigating the effects of intermittent mechanical stretching delivered by a new invented type of cell stress machine on the proliferation kinetics of the human periodontal fibroblast cells (hPDLFs) in vitro. METHODS: hPDLFs were cultured in vitro. The 4 - 7th generation of hPDLFs were undergone mechanical stretching. All cells were grouped as strained and unstrained (controls). Strained groups cells were gathered after 2, 4 and 6 hours with the stress 1 000, 2 000 and 3 000 mustrain. Flow cytometry (FCM) was used to examine the ratio of DNA (S%) and the index of proliferation(PI). RESULTS: Mechanical force would lead to the change of hPDLFs proliferation. Within the experiment, both 1 000 mustrain and 2 000 mustrain could increase the proliferation index (PI) (P < 0.05). While under 3 000 mustrain, DNA synthesis was significantly decreased( P < 0.05). CONCLUSION: Some range of mechanical stretching accelerates hPDLFs proliferation. This research discusses the remodeling process of periodontal tissues undergoing the mechanical stretching on cytological view, and it makes a basement for further revealing the mechanical strain induced periodontal biological principles. Also it provides a useful direction for clinical orthodontic therapy.