Imbalanced optimal feedback motor control system in spinocerebellar ataxia type 3.

BACKGROUND AND PURPOSE: Human motor planning and control depend highly on optimal feedback control systems, such as the neocortex-cerebellum circuit. Here, diffusion tensor imaging was used to verify the disruption of the neocortex-cerebellum circuit in spinocerebellar ataxia type 3 (SCA3), and the circuit's disruption correlation with SCA3 motor dysfunction was investigated. METHODS: This study included 45 patients with familial SCA3, aged 17-67 years, and 49 age- and sex-matched healthy controls, aged 21-64 years. Tract-based spatial statistics and probabilistic tractography was conducted using magnetic resonance images of the patients and controls. The correlation between the local probability of probabilistic tractography traced from the cerebellum and clinical symptoms measured using specified symptom scales was also calculated. RESULTS: The cerebellum-originated probabilistic tractography analysis showed that structural connectivity, mainly in the subcortical cerebellar-thalamo-cortical tract, was significantly reduced and the cortico-ponto-cerebellar tract was significantly stronger in the SCA3 group than in the control group. The enhanced tract was extended to the right lateral parietal region and the right primary motor cortex. The enhanced neocortex-cerebellum connections were highly associated with disease progression, including duration and symptomatic deterioration. Tractography probabilities from the cerebellar to parietal and sensorimotor areas were significantly negatively correlated with motor abilities in patients with SCA3. CONCLUSION: To our knowledge, this study is the first to reveal that disrupting the neocortex-cerebellum loop can cause SCA3-induced motor dysfunctions. The specific interaction between the cerebellar-thalamo-cortical and cortico-ponto-cerebellar pathways in patients with SCA3 and its relationship with ataxia symptoms provides a new direction for future research.

Handwriting Movement Abnormalities in Older Adults with Silent Cerebral Small Vessel Disease-A Preliminary Study.

BACKGROUND: The features of cerebral small vessel disease (CSVD) range from occurrence of asymptomatic radiological markers to symptomatic characteristics that include cognitive deficits and gait decline. The aim of the present study was to examine whether handwriting movement is abnormal in older people with CSVD through handwriting and drawing tasks using digitized handwriting kinematic assessment technology. METHODS: Older subjects (n = 60) were grouped according to Fazekas score, with 16 in the Severe CSVD group, 12 in the Non-severe group and 32 in the Healthy group. Kinematic data were recorded and analyzed during handwriting and drawing tasks: signature; writing of Chinese characters ("" and ""); and Archimedes' spiral drawing. RESULTS: The Severe CSVD group showed lower velocity and higher tortuosity during signature writing, lower velocity of stroke #4 of "" and vertical size of "" than did the Non-severe and Healthy groups. Both Severe CSVD and Non-severe CSVD subjects displayed higher average normalized jerk than did the Healthy group. Partial correlation analysis adjusting for age, gender, education, and mini-mental state evaluation (MMSE) showed that CSVD burden was positively associated with tortuosity of signature and average normalized jerk of Archimedes' spiral, and was negatively associated with velocity of strokes #3 and #4 of "", as well as vertical size of "". CONCLUSIONS: Older adults with CSVD showed abnormal handwriting movement. And the handwriting abnormalities captured by digitized handwriting analysis were correlated with CSVD severity in users of simplified Chinese characters.

Variability, asymmetry and bilateral coordination of gait during single- and dual-task walking of patients with cerebral small vessel disease.

OBJECTIVE: We investigated coefficient of variation (CV), gait asymmetry (GA) and phase coordination index (PCI) in cerebral small vessel disease (CSVD) patients during single-task walking (STW) and dual-task walking (DTW) and explored the relationship between above parameters with disease severity and cognitive function. METHODS: This cross-sectional study collected cognitive function indices and gait parameters from 23 healthy controls and 94 patients with CSVD during STW and DTW. According to the Fazekas scales, the severity of CSVD valued by white matter hyperintensity (WMH) were divided into control, mild, moderate, severe and control group. MRIs were analyzed for WMHs, CMB, lacunes, etc. RESULTS: The control group showed lower PCI than CSVD patients during STW; no differences were detected among the disease severity groups. During DTW, all four groups exhibited significant differences in PCI and CV. For the moderate and severe groups, coordination and variation significantly differed between the two walking methods. There were correlations between the PCI and GA in the moderate and severe groups (R = 0.376, R = 0.573 during DTW; R = 0.414, R = 0.643 during STW) and no correlations in the control group and mild CSVD group. CONCLUSION: PCI and CV may be vital for detecting the symptoms in the early stage of CSVD disease. We also verified that the PCI could become the bridge across the cognition and motor disorder in CSVD, which was helpful for evaluating clinical symptoms comprehensively.

EEG complexity correlates with residual consciousness level of disorders of consciousness.

BACKGROUND AND OBJECTIVE: Electroencephalography (EEG) and neuroimaging measurements have been highly encouraged to be applied in clinics of disorders of consciousness (DOC) to improve consciousness detection. We tested the relationships between neural complexity measured on EEG and residual consciousness levels in DOC patients. METHODS: Resting-state EEG was recorded from twenty-five patients with DOC. Lempel-Ziv complexity (LZC) and permutation Lempel-Ziv complexity (PLZC) were measured on the EEG, and their relationships were analyzed with the consciousness levels of the patients. RESULTS: PLZC and LZC values significantly distinguished patients with a minimally conscious state (MCS), vegetative state/unresponsive wakefulness syndrome (VS/UWS), and healthy controls. PLZC was significantly correlated with the Coma Recovery Scale-Revised (CRS-R) scores of DOC patients in the global brain, particularly in electrodes locating in the anterior and posterior brain regions. Patients with higher CRS-R scores showed higher PLZC values. The significant difference in PLZC values between MCS and VS/UWS was mainly located in the bilateral frontal and right hemisphere regions. CONCLUSION: Neural complexity measured on EEG correlates with residual consciousness levels of DOC patients. PLZC showed higher sensitivity than LZC in the classification of consciousness levels.

[Droplet freeze-thawing system based on solid surface vitrification and laser rewarming].

Ultra-rapid cooling and rewarming rate is a critical technical approach to achieve ice-free cells during the freezing and melting process. A set of ultra-rapid solid surface freeze-thaw visualization system was developed based on a sapphire flim, and experiments on droplet freeze-thaw were carried out under different cryoprotectant components, volumes and laser energies. The results showed that the cooling rate of 1 µL mixed cryoprotectant [1.5 mol/L propylene glycol (PG) + 1.5 mol/L ethylene glycol (EG) + 0.5 mol/L trehalose (TRE)] could be 9.2×10 3 °C/min. The volume range of 1-8 µL droplets could be vitrified. After comparing the proportions of multiple cryoprotectants, the combination of equal proportion mixed permeability protectant and trehalose had the best vitrification freezing effect and more uniform crystallization characteristics. During the rewarming operation, the heating curve of glassy droplets containing gold nanoparticles was measured for the first time under the action of 400-1 200 W laser power, and the rewarming rate was up to the order of 10 6 °C/min. According to the droplet images of different power rewarming processes, the laser power range for ice-free rewarming with micron-level resolution was clarified to be 1 400-1 600 W. The work of this paper simultaneously realizes the ultra-high-speed temperature ramp-up, transient visual observation and temperature measurement of droplets, providing technical means for judging the ice free droplets during the freeze-thaw process. It is conducive to promoting the development of ultra-rapid freeze-thaw technology for biological cells and tissues.

Cerebral small vessel disease alters neurovascular unit regulation of microcirculation integrity involved in vascular cognitive impairment.

Cerebral small vessel disease (CSVD) is a generic term used for intracranial vascular disorders caused by the structural changes of cerebral microvessels, including the small arteries, arterioles, capillaries and venules. CSVD exhibits various neuroimaging features and is associated clinical characteristics. Although CSVD is recognized as the leading cause of vascular cognitive impairment (VCI), the underlying mechanism(s) remains elusive. Growing evidence indicates a significant association between altered neurovascular unit (NVU) functioning and the pathophysiology of evolving CSVD-induced VCI. Therefore, research is required to understand how NVU dysregulation contributes to cognitive impairment due to CSVD. In this review, we describe the link between the neuroimaging focal lesions and cognitive alterations. We also discuss the potential pathological role of NVU dysregulation in the entry of pathogens from the blood into the parenchyma by altering the blood-brain barrier (BBB), affecting the cerebral microvascular and consequently cause VCI. Next, we review the coupling of neural activity with cerebral blood flow to control the microvascular perfusion; and the disrupted clearance of metabolic byproducts with CSF-ISF exchange via perivascular pathways and glymphatic system. Finally, we discussed the possible therapeutic interventions in CSVD.

Imaging features of lipoma arborescens.

BACKGROUND: Lipoma arborescens is characterized by the villous proliferation of the synovium and diffuse hyperplasia of fatty tissue in the subsynovial layer, almost always with a periarticular lesion. According to past articles, fewer cases have depicted the imaging features of lipoma arborescens. PURPOSE: To evaluate the computed tomography (CT) and magnetic resonance imaging (MRI) features of lipoma arborescens. MATERIAL AND METHODS: The imaging features of 15 patients with pathologically proven lipoma arborescens were retrospectively analyzed including lesion number, shape, location, size, margins, attenuation on CT, and signal intensity and enhancement patterns on MR images. RESULTS: All cases (n=15) showed joint or bursa effusion. The primary lesion attached to the bursa wall adjacent to the bone in 13 cases and to the lateral wall in two cases. CT shows a mass with fatty tissue attenuation values in the suprapatellar pouch (n=3) or subdeltoid bursa with an erosion of the humeral head (n=2), among them two cases showed branched slightly high density in the center of the fat density tissue. Fifteen cases on routine MRI display mass-like subsynovial mass with fatty tissue signal on all of the sequences and suppression of the signal on fat-suppression sequences. Among them, five lesions showed branched slightly low T1-weighted imaging, high proton density-weighted imaging, and T2-weighted imaging signals in the center. It showed the enhancement of the linear surface and the bursa wall in contrast-enhanced MRI (n=3). CONCLUSION: Lipoma arborescens have specific CT and MRI features that enable them to make a conclusive diagnosis of this rare condition, which helps the diagnosis before treatment.

Mechanism of total glucosides of paeony in hypoxia/reoxygenation-induced cardiomyocyte pyroptosis.

Inflammasome-mediated pyroptosis can aggravate myocardial ischemia/reperfusion injury. Total glucosides of paeony (TGP) is widely used in anti-inflammation. This study investigated the effect of TGP on pyroptosis of hypoxia/reoxygenation (H/R)-induced cardiomyocytes. HL-1 cells were subjected to H/R treatment. H/R-induced cardiomyocytes were treated with TGP at different concentrations (50, 100, and 200 mg/kg). The viability of H/R-induced cardiomyocytes was measured. The levels of lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD), and reactive oxygen species (ROS) were determined. The activity of caspase-1, the expressions of NLRP3 and GSDMD-N, and the concentrations of IL-1ß and IL-18 were examined. miR-181a-5p expression in H/R cardiomyocytes was determined. The targeting relationship between miR-181a-5p and adenylate cyclase 1 (ADCY1) was verified. Functional rescue experiments were performed to verify the effect of miR-181a-5p or ADCY1 on the pyroptosis of H/R cardiomyocytes. TGP enhanced H/R-induced cardiomyocyte viability in a dose-dependent manner, reduced LDH, MDA, and ROS levels, increased SOD level, decreased caspase-1 activity, reduced NLRP3 and GSDMD-N expressions, and inhibited IL-1ß and IL-18 concentrations. TGP suppressed miR-181a-5p expression in H/R cardiomyocytes. miR-181a-5p targeted ADCY1. miR-181a-5p overexpression or ADCY1 inhibition reversed the inhibitory effect of TGP on the pyroptosis of H/R cardiomyocytes. Collectively, TGP alleviated the pyroptosis of H/R cardiomyocytes via the miR-181a-5p/ADCY1 axis.

Vitrification with microinjection of single seminiferous tubules: an efficient cryopreservation approach for limited testicular tissue.

RESEARCH QUESTION: Is vitrification with microinjection of single seminiferous tubules an efficient cryopreservation approach for limited testicular tissue? DESIGN: Testicular tissue from 10 patients with normal spermatogenesis were assigned to a fresh control group or one of the following cryopreservation procedures: uncontrolled slow freezing (USF) using either 1.5 or 2.1 M DMSO combined with sucrose and vitrification with or without single seminiferous tubules microinjection. RESULTS: Single seminiferous tubules microinjected with cryoprotective agents (CPA) enhanced the penetration of CPA compared with CPA-treated testicular tissue fragments. Microinjection of seminiferous tubules (VLP) maintained tubule structural integrity and germ cell numbers, and reduced spermatogonial apoptosis after cryopreservation compared with vitrification without microinjection (apoptosis rate: VLP versus vitrification without microinjection, P = 0.047; VLP versus USF, P= 0.049). Freezing of single seminiferous tubules using 0.25-ml straws and traditional sperm freezing methods protected sperm retrieval and recovery rates, and the progressive motility index. CONCLUSIONS: Vitrification of single seminiferous tubule with microinjection of low CPA concentration is an effective approach to testicular cryopreservation.

Risk of mother-to-child transmission of hepatitis B virus after fetal blood sampling: a report of six cases.

BACKGROUND: Hepatitis B virus (HBV) remains a major global public health problem worldwide; in endemic areas, mother-to-child transmission (MTCT) of HBV is the most common transmission route. Previous studies have shown that amniocentesis for prenatal diagnosis increases the risk of MTCT of HBV among highly viraemic mothers. However, no data is available on MTCT related fetal blood sampling (FBS) because of the paucity of cases or lack of attention. We present a case series of HBV-infected women who underwent FBS with or without antiviral therapy during pregnancy and discuss the risk of MTCT after FBS. CASE PRESENTATION: Six hepatitis B surface antigen (HBsAg)-positive pregnant women who underwent FBS for prenatal diagnosis were retrospectively reviewed. Their infants were followed up with HBV serology parameters until at least 12 months of age. Among 6 cases, two hepatitis B e-antigen (HBeAg)-positive mothers had high viral loads > 7.0 log10 IU/mL, and one of them received antiviral therapy at 26+ 3 gestational weeks and achieved an anticipated level of 4.52 log10 IU/mL before FBS, while the other one did not receive any antiviral treatment. The other 4 cases were HBeAg-negative with low viral loads. Only a child born to the HBeAg-positive mother, who had no antiviral therapy with a viral load of 7.48 log10 IU/mL before FBS, was found to have MTCT with HBsAg persistently positive from birth to 12 months of age. The other 5 children were both HBsAg-negative and HBsAb-positive at the end of follow-up. CONCLUSIONS: FBS may increase the risk of MTCT of HBV in women with HBeAg-positive and high viral loads; therefore, FBS should be avoided in this high-risk population. Maternal HBV serologic testing and awareness of the potential risk of MTCT should be recommended before FBS. Antiviral therapy may be effective to decrease the risk of MTCT after FBS in highly viraemic women.

Neuroprotective effects of troxerutin and cerebroprotein hydrolysate injection on the neurovascular unit in a rat model of Middle cerebral artery occlusion.

Purpose: Cerebral ischemic stroke, caused by obstruction of the blood flow to the brain, initiates a complex cascade of pathophysiological changes. The aim of the present study was to assess the protective role and the underlying mechanism of troxerutin and cerebroprotein hydrolysate (TCH) injections for five days in rats subjected to middle cerebral artery occlusion (MCAO).Materials and Methods: Male Sprague-Dawley rats treated with either TCH or a vehicle (0.9% saline) via intraperitoneal injection were examined one or three days after MCAO.Results: TCH alleviated neurological deficits and reduced infarct volume, innate immune response, blood-brain barrier destruction, and suppressed cell apoptosis. The therapeutic effects of TCH were achieved by diminished neuronal nitric oxide synthase (nNOS) and inducible nitric oxide synthase (iNOS), and increased endothelial nitric oxide synthase (eNOS). Furthermore, L-NAME showed an inhibitory effect against TCH after MCAO on eNOS expression, NO and peroxynitrite production, neurobehavioral score, and infarct volume.Conclusions: The results indicate that injection of TCH has multifaceted neuroprotective effects against MCAO via regulation of the various NOS isoforms.

Preoperative MRI-Based Radiomic Machine-Learning Nomogram May Accurately Distinguish Between Benign and Malignant Soft-Tissue Lesions: A Two-Center Study.

BACKGROUND: Preoperative differentiation between malignant and benign soft-tissue masses is important for treatment decisions. PURPOSE/HYPOTHESIS: To construct/validate a radiomics-based machine method for differentiation between malignant and benign soft-tissue masses. STUDY TYPE: Retrospective. POPULATION: In all, 206 cases. FIELD STRENGTH/SEQUENCE: The T1 sequence was acquired with the following range of parameters: relaxation time / echo time (TR/TE), 352-550/2.75-19 msec. The T2 sequence was acquired with the following parameters: TR/TE, 700-6370/40-120 msec. The data were divided into a 3.0T training cohort, a 1.5T MR validation cohort, and a 3.0T external validationcohort. ASSESSMENT: Twelve machine-learning methods were trained to establish classification models to predict the likelihood of malignancy of each lesion. The data of 206 cases were separated into a training set (n = 69) and two validation sets (n = 64, 73, respectively). STATISTICAL TESTS: 1) Demographic characteristics: a one-way analysis of variance (ANOVA) test was performed for continuous variables as appropriate. The χ2 test or Fisher's exact test was performed for comparing categorical variables as appropriate. 2) The performance of four feature selection methods (least absolute shrinkage and selection operator [LASSO], Boruta, Recursive feature elimination [RFE, and minimum redundancy maximum relevance [mRMR]) and three classifiers (support vector machine [SVM], generalized linear models [GLM], and random forest [RF]) were compared for selecting the likelihood of malignancy of each lesion. The performance of the radiomics model was assessed using area under the receiver-operating characteristic curve (AUC) and accuracy (ACC) values. RESULTS: The LASSO feature method + RF classifier achieved the highest AUC of 0.86 and 0.82 in the two validation cohorts. The nomogram achieved AUCs of 0.96 and 0.88, respectively, in the two validation sets, which was higher than that of the radiomic algorithm in the two validation sets and clinical model of the validation 1 set (0.92, 0.88 respectively). The accuracy, sensitivity, and specificity of the radiomics nomogram were 90.5%, 100%, and 80.6%, respectively, for validation set 1; and 80.8%, 75.8%, and 85.0% for validation set 2. DATA CONCLUSION: A machine-learning nomogram based on radiomics was accurate for distinguishing between malignant and benign soft-tissue masses. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2 J. Magn. Reson. Imaging 2020;52:873-882.

Efficacy and safety of cinepazide maleate injection in patients with acute ischemic stroke: a multicenter, randomized, double-blind, placebo-controlled trial.

BACKGROUND: Ischemic stroke is a leading cause of morbidity and mortality. Thrombolytic therapy improves disability and survival rates; however, to be effective, it must be given within 4.5 h of onset. Moreover, thrombolytic therapy is frequently contraindicated. Therefore, alternative therapeutic options are required. In China, cinepazide maleate injection has been shown to improve the cerebral collateral circulation and further reduce disability in stroke patients; however, very few studies investigating this therapy have been conducted to date. Therefore, this study aimed to further confirm the efficacy and safety of cinepazide maleate injection in patients with acute ischemic stroke. METHODS: Patients with acute ischemic stroke were administered an intravenous infusion of 320 mg cinepazide maleate or placebo once daily for 14 days. All patients were also administered basic therapy (citicoline sodium). The primary efficacy endpoint was the proportion of patients with a modified Rankin scale (mRS) ≤2 on day 90. Secondary efficacy endpoints included Barthel Index ≥95. Safety was evaluated by recording all adverse events (AEs), monitoring laboratory parameters and vital signs, and electrocardiogram. RESULTS: In total, 937 patients with an acute ischemic stroke were included, with a mean (standard deviation, SD) National Institutes of Health Stroke Scale score of 8.8 (2.4) and a mean (SD) stroke onset of 30.9 (11.4) hours prior. Following treatment for 90 days, the proportion of patients with an mRS score ≤ 2 was significantly higher in the cinepazide maleate group than in the control group (60.9% vs. 50.1%; p = 0.0004). Moreover, the proportion of patients with a Barthel Index of ≥95 on day 90 was also significantly higher in the cinepazide maleate group than in the control group (53.4% vs. 46.7%; p = 0.0230). There were no statistically significant differences in safety parameters between the cinepazide maleate and control groups. CONCLUSIONS: The results of this study show that cinepazide maleate injection is superior to placebo in improving neurological function and activities of daily living, reducing disability, and promoting functional recovery in patients with acute ischemic stroke. Cinepazide maleate injection was safe and well tolerated with no unexpected AEs reported. TRIAL REGISTRATION: Chinese Clinical Trial Registry CTR20160292 and ChiCTR1900023827 . Retrospectively registered June 13, 2019.

Identifying occult maternal malignancies from 1.93 million pregnant women undergoing noninvasive prenatal screening tests.

PURPOSE: Multiple chromosomal aneuploidies may be associated with maternal malignancies and can cause failure of noninvasive prenatal screening (NIPS) tests. However, multiple chromosomal aneuploidies show poor specificity and selectivity for diagnosing maternal malignancies. METHODS: This multicenter retrospective analysis evaluated 639 pregnant women who tested positive for multiple chromosomal aneuploidies on initial NIPS test between January 2016 and December 2017. Women were assessed using genome profiling of copy-number variations, which was translated to cancer risk using a novel bioinformatics algorithm called the cancer detection pipeline (CDP). Sensitivity, specificity, and positive predictive value (PPV) of diagnosing maternal malignancies were compared for multiple chromosomal aneuploidies, the CDP model, and the combination of CDP and plasma tumor markers. RESULTS: Of the 639 subjects, 41 maternal malignant cancer cases were diagnosed. Multiple chromosomal aneuploidies predicted maternal malignancies with a PPV of 7.6%. Application of the CDP algorithm to women with multiple chromosomal aneuploidies allowed 34 of the 41 (83%) cancer cases to be identified, while excluding 422 of 501 (84.2%) of the false positive cases. Combining the CDP with plasma tumor marker testing gave PPV of 75.0%. CONCLUSION: The CDP algorithm can diagnose occult maternal malignancies with a reasonable PPV in multiple chromosomal aneuploidies-positive pregnant women in NIPS tests. This performance can be further improved by incorporating findings for plasma tumor markers.

WITHDRAWN: Whole genome sequencing identifies novel NOTCH3 mutations for leukoaraiosis.

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Stiff person syndrome with elevated titers of antibodies against cardiolipin and ß2 glycoprotein 1: a case report and literature review.

We reported a Stiff person syndrome (SPS) patient with elevated autoantibodies against cardiolipin and ß2 glycoprotein 1 but without glutamic acid decarboxylase (GAD) antibodies. A 40-year male was admitted due to limited mouth opening for 1 week. His blood routine, biochemical, infectious diseases, tumor markers, radiographic examinations were all normal. At day 3 (D3) after admission, he developed paroxysmal systemic muscle rigidity. At D6, the on-duty physician occasionally gave oral clonazepam, which effectively relieved the symptom. At D13, the titers of cardiolipin and ß2 glycoprotein 1 autoantibodies elevated but the remaining autoantibodies were all in normal ranges. After clonazepam treatment for 1 week, the symptoms were basically relieved, and the titers of these two antibodies returned to normal range with the relief of symptoms. During the 3 years of follow-up, the symptoms did not present again, and the titers of both antibodies were stable in the normal ranges. He had no tumor and other immune system diseases. In summary, we reported a SPS case with elevated cardiolipin and ß2 glycoprotein 1 autoantibodies. The patient was highly responsive to clonazepam therapy, and had favorable outcome in the 3 years follow-up. Our report is helpful for better understand the heterogeneous feature of SPS.

Troxerutin cerebroprotein hydrolysate injection ameliorates neurovascular injury induced by traumatic brain injury - via endothelial nitric oxide synthase pathway regulation.

BACKGROUND: Neurovascular dysfunction caused by traumatic brain injury (TBI) is characterized by cerebralvascular damage, blood-brain barrier (BBB) breakdown, brain edema, etc. This study was designed to assess the protective role of 5 days troxerutin cerebroprotein hydrolysate (TCH) injection treatment against TBI, as well as the potential mechanism. METHODS: The weight-drop model of TBI in male Sprague-Dawley rats was chosen to induce TBI model, rats either with TCH or a vehicle via intraperitoneal injection were examined 3 days after TBI. RESULTS: TCH resulted in alleviation of neurological deficits, reduction of infarct volume, improvement of regional cerebral blood flow (rCBF), amelioration of neuronal death, astrocyte proliferation, endothelial cell loss, and BBB dysintegrity. These effects of TCH treatment against TBI were through endothelial nitric oxide synthase (eNOS) coupling/decoupling status adjustment, which not only increased nitric oxide (NO) level, but also decreased peroxynitrate level expression. CONCLUSIONS: All the results indicated that TCH injection has multifaceted protective effects of neurovascular unit (NVU) against TBI via eNOS pathway regulation.

Lipopolysaccharide Induces Subacute Cerebral Microhemorrhages with Involvement of Nitric Oxide Synthase in Rats.

BACKGROUND: Cerebral microhemorrhage (CMH) is a neuropathological term that could be easily found in cerebral amyloid angiopathy, intracerebral hemorrhages, etc. CMHs could be detected clearly in vivo by magnetic resonance imaging (MRI)-susceptibility-weighted imaging or MRI T2* scan. This terminology is now accepted in the area of neuroimaging. CMHs are quite common in elderly patients and are associated with several other neuropsychiatric disorders. The causes of CMHs are complicated, and neuroinflammation is considered as one of the well-accepted mechanical factors. This study investigated whether lipopolysaccharide (LPS)-induced CMHs occur through the regulation of nitric oxide synthase (NOS) isoforms and reveals the exact underlying mechanism of LPS-induced CMHs. METHODS: Our work successfully developed a subacute model of CMHs in rats. LPS was intraperitoneally injected into rats at 0, 6, and 24 hours, which induced typical CMH features 7 days after the injection. These could be detected on the brain surface or parenchyma by hematoxylin and eosin staining and MRI. RESULTS: LPS-treated rats showed significant activation of astrocytes and microglia, as well as loss of pericytes and disruption of blood-brain barrier. Meanwhile, both astrocytes and microglia were positively correlated with CMH numbers. Furthermore, the expressions of NOS isoforms were also examined, and the levels of neuronal NOS and endothelial NOS were found to be elevated. CONCLUSIONS: These results implied that the NOS isoforms might be involved in the subacute model of CMHs in rats induced by LPS.

Comparative Evaluation of Soluble and Insoluble-Bound Phenolics and Antioxidant Activity of Two Chinese Mistletoes.

Mistletoes are used medicinally in order to treat various human illnesses. Few studies have reported on the phenolic content and antioxidant properties of Chinese mistletoes (CMs). In this work, the total phenolic content (TPC), total flavonoid content (TFC), and antioxidant activities of soluble and insoluble-bound phenolic extracts from CMs hosted by Camellia assamica (Mast.) Chang (CMC) and Pyrus, i, f. (CMP) were compared. Phenolic compounds in CMC and CMP were identified and quantified using high-performance liquid chromatography (HPLC). The results indicated that the TPC of soluble phenolic extracts was higher than insoluble-bound phenolic counterparts in both CMC and CMP. In addition, the TPC of soluble, insoluble-bound and total phenolic fractions (9.91 ± 0.23, 4.59 ± 0.27 and 14.50 ± 0.35 µmol ferulic acid equivalents per gram (FAE/g) dry sample) extracted from CMP were higher than those extracted from CMC. The soluble phenolic extracts in CMP showed higher antioxidant activities than those in CMC. Eighteen phenolic compounds from soluble and insoluble-bound phenolic extracts from the CMs were identified and quantified by HPLC. This study indicates that CMC and CMP, especially the latter, could be sources of antioxidants in human health care.

Risk Factors for Silent Lacunar Infarction in Patients with Transient Ischemic Attack.

BACKGROUND Lacunar infarctions represent 25% of ischemic strokes. Lacunar stroke and transient ischemic attack (TIA) share a number of symptoms. This study aimed to assess the potential risk factors for lacunar infarction in patients with TIA. MATERIAL AND METHODS This was a retrospective study performed at the Beijing Military General Hospital in patients with TIA admitted between March 2010 and December 2011. Patients were grouped according to lacunar vs. no lacunar infarction. All patients were diagnosed using diffusion-weighted imaging (DWI) on brain magnetic resonance imaging (MRI). Brain angiography (computed tomography and MRI) was used to measure intracranial stenosis. Carotid artery stenosis was measured by ultrasound. RESULTS Patients with TIA and lacunar infarction (n=298) were older than those without lacunar infarction (n=157) (69.4±10.0 vs. 58.9±9.0 years, P<0.001) and showed a higher frequency of males (51.7% vs. 41.4%, P=0.037), hypertension (75.3% vs. 45.9%, P<0.001), diabetes (32.6% vs. 21.0%, P=0.010), hyperlipidemia (53.4% vs. 29.3%, P<0.001), carotid stenosis (73.2% vs. 40.1%, P<0.001), and intracranial stenosis (55.6% vs. 31.9%, P<0.001), but a lower frequency of alcohol drinking (8.1% vs. 14.0%, P=0.045). Lacunar infarction mostly involved the anterior circulation (62.8%). Multivariate analysis showed that age (odds ratio (OR)=1.085, 95% confidence interval (95%CI): 1.054-1.117, P<0.001), hypertension (OR=1.738, 95%CI: 1.041-2.903, P=0.035), hyperlipidemia (OR=2.169, 95%CI: 1.307-3.601, P=0.003), and carotid stenosis (OR=1.878, 95%CI: 1.099-3.206, P=0.021) were independently associated with lacunar infarction. CONCLUSIONS Age, hypertension, hyperlipidemia, and carotid stenosis were independently associated with silent lacunar infarction in patients with TIA.