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1.
J Alzheimers Dis ; 71(2): 559-567, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31424402

RESUMO

BACKGROUND: Few studies have investigated the correlation between cerebral microbleeds (CMBs), a hemorrhagic imaging marker of cerebral small vessel disease (CSVD), and brain volume. OBJECTIVE: We investigated the association between the burden and locations of CMBs and brain volume in community-dwelling populations. METHODS: Data were obtained from 1,029 participants who underwent brain magnetic resonance imaging (MRI) and APOE genotyping. Volumes of the whole brain, subcortical white matter (WM), cortical gray matter (GM), and hippocampus were extracted. Linear regression models were used to investigate the relationship between the CMB burden and their location with structural changes. RESULTS: Regarding burden, participants with≥3 CMBs had significantly lower whole brain (ß= -1.124, p = 0.0133), subcortical WM (ß= -1.020, p = 0.0043), and hippocampus (ß= -0.015, p = 0.0088) volumes than those without CMBs. Regarding location and burden, the presence of≥3 strictly lobar CMBs was negatively associated with whole brain volume (ß= -2.838, p = 0.0088). Additionally, higher CMB burdens in strictly lobar locations or deep/mixed locations were associated with lower subcortical WM volume (ß= -1.689, p = 0.0482; ß= -0.872, p = 0.0464, respectively). Finally, the presence of≥3 deep/mixed CMBs was associated with lower hippocampus volume (ß= -0.018, p = 0.0088), and these associations were independent of other ischemic markers of CSVD. However, the CMB burden and distributional pattern did not correlate with cortical GM volumes. CONCLUSION: A higher CMB burden, in specific locations, is associated with decreased brain volumes in community-dwelling populations.

2.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 41(3): 344-350, 2019 Jun 30.
Artigo em Chinês | MEDLINE | ID: mdl-31282328

RESUMO

Objective To explore the clinical characteristics of autoimmune disease with dual seropositive antibodies of leucine-rich glioma inactivated 1(LGI1)and contactin-associated protein 2(Caspr2).Methods The clinical data of seven patients with dual seropositive LGI1 and Caspr2 antibodies who were admitted to the Neurology Department of Peking Union Medical College Hospital from July 2014 to December 2017 were retrospectively analyzed.Results Central,peripheral and autonomic nervous systems were all involved in the seven cases;100%(7/7)presented with insomnia,myokymia,neuropahic pain and hyperhydrosis;71%(5/7)showed memory decline or psychiatric and behavioral symptoms;57%(4/7)had urinary hesitation or constipation;and 43%(3/7)had seizure.Electromyography showed 100%(6/6) of the patients had prolonged afterdischarges following normal M waves and/or abnormal spontaneous firing.Electroencephalography revealed slow waves or basic rhythm slowing in 71%(5/7)of patients.Electrocardiography showed sinus tachycardia,axis deviation,and prolonged QT intervals in 71%(5/7)of patients.One patient died from arrhythmia before immunotherapy.One died from pulmonary infection after immunotherapy.Improvement with immunotherapy was documented in the other five cases.No relapse was noted during the 1-2-year follow-up.Conclusions Autoimmune disease with dual seropositive antibodies of LGI1 and Caspr2 can diffusely affect the central,peripheral,and autonomic nervous systems.The possibility of this disease should be considered in patients with acute and subacute onset of neuropsychiatric symptoms,especially in patients with accompanying insomnia,myokymia,and hyperhydrosis.


Assuntos
Autoanticorpos/sangue , Doenças Autoimunes/imunologia , Proteínas de Membrana/imunologia , Proteínas do Tecido Nervoso/imunologia , Proteínas/imunologia , Humanos , Estudos Retrospectivos
3.
World J Gastrointest Oncol ; 11(4): 335-347, 2019 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-31040898

RESUMO

BACKGROUND: Human epidermal growth factor receptor 2 (HER2) is an oncogenic driver, and a well-established therapeutic target in breast and gastric cancers. While the role of HER2 as a prognostic biomarker in colorectal adenocarcinomas (CRCs) remains uncertain, its relevance as a therapeutic target has been established. We undertook the present study to evaluate the frequency of HER2 expression in CRC and to correlate it with various clinicopathological variables. AIM: To correlate HER2 protein expression and HER2 gene amplification with clinicopathological features and survival in surgically resected CRC. METHODS: About 1195 consecutive surgically resected CRCs were analyzed by immunohistochemical staining (IHC) to assess HER2 protein expression, and 141 selected tumors were further evaluated by fluorescence in situ hybridization (FISH) to assess HER2 gene amplification. Follow-up information was available for 1058 patients, and using this information we investigated the prevalence of HER2 protein overexpression and gene amplification in a large series of surgically resected CRCs, and evaluated the relationship between overexpression and clinicopathological parameters and prognosis. RESULTS: HER2 IHC scores of 3+, 2+, 1+, and 0 were seen in 31 (2.6%), 105 (8.8%), 475 (39.7%), and 584 (48.9%) tumors, respectively. HER2 gene amplification was seen in 24/29 tumors with an IHC score of 3+ (82.8%; unreadable in 2/31), 12/102 tumors with an IHC score of 2+ (11.8%; unreadable in 2/104), and 0 tumors with IHC score of 1+ (0/10). HER2 gene amplification was seen in 36/1191 tumors (3.0%; unreadable in 4/1195). Among the tumors with HER2 IHC scores of 3+ and 2+, the mean percentage of tumor cells with positive IHC staining was 90% (median 100%, range 40%-100%) and 67% (median 75%, range 5%-95%), respectively (P < 0.05). Among tumors with IHC scores of 2+, those with HER2 gene amplification had a higher number of tumors cells with positive IHC staining (n = 12, mean 93%, median 95%, range 90%-95%) than those without (n = 90, mean 70%, median 50%, range 5%-95%) (P < 0.05). HER2 gene status was significantly associated with distant tumor metastasis and stage (P = 0.028 and 0.025). HER2 protein overexpression as measured by IHC or HER2 gene amplification as measured by FISH was not associated with overall survival (OS) or disease-specific survival for the overall group of 1058 patients. However, further stratification revealed that among patients with tubular adenocarcinomas who were 65 years old or younger (n = 601), those exhibiting HER2 gene amplification had a shorter OS than those without (mean: 47.9 mo vs 65.1 mo, P = 0.04). Among those patients with moderately to poorly differentiated tubular adenocarcinomas, those with positive HER2 tumor IHC scores (2+, 3+) had a shorter mean OS than those with negative HER2 IHC scores (0, 1+) (47.2 mo vs 64.8 mo, P = 0.033). Moreover, among patients with T2 to T4 stage tumors, those with positive HER2 IHC scores also had a shorter mean OS than those with negative HER2 IHC scores (47.1 mo vs 64.8 mo, P = 0.031). CONCLUSION: HER2 protein levels are correlated with clinical outcomes, and positive HER2 expression as measured by IHC confers a worse prognosis in those patients 65 years old or younger with tubular adenocarcinomas.

4.
BMC Pulm Med ; 19(1): 30, 2019 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-30727998

RESUMO

BACKGROUND: Double lumen intubation and one-lung ventilation should be applied without delay in cases of traumatic main bronchial rupture. In most cases, when the patients' vital signs have been stabilized, the repair can be performed. However, when one-lung ventilation is complicated by traumatic wet lung, the mortality rate is likely to be much higher. CASE PRESENTATION: In this case, the patient experienced a left main bronchial rupture, bilateral traumatic wet lung, and acute respiratory distress syndrome (ARDS) because of severe thoracic trauma. Though the patient was treated with intubation and mechanical ventilation (MV), his oxygenation was still not stable. Thus, veno-venous extracorporeal membrane oxygenation (V-V ECMO) was initiated; upon improvement of oxygenation, the patient received an exploratory thoracotomy. Unfortunately, the rupture proved to be irreparable, resulting in a total left pneumonectomy. As there was severe ARDS caused by trauma, ECMO and ultra-low tidal volume (VT) MV strategy (3 ml/kg) were utilized for lung protection post-op. ECMO was sustained up to the 10th day, and MV until the 20th day, post-operation. With the support of MV, ECMO and other comprehensive measures, the patient made a recovery. CONCLUSION: V-V ECMO and ultra-low VT MV helped this thoracic trauma patient survive the lung edema period and prevented ventilator associated pneumonia (VAP). In extreme situations, with the support of ECMO, the tidal volume may be lowered to 3 ml/kg.


Assuntos
Pneumonectomia/efeitos adversos , Edema Pulmonar/diagnóstico por imagem , Síndrome do Desconforto Respiratório do Adulto/terapia , Traumatismos Torácicos/complicações , Oxigenação por Membrana Extracorpórea , Humanos , Pulmão/diagnóstico por imagem , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Edema Pulmonar/etiologia , Respiração Artificial/efeitos adversos , Síndrome do Desconforto Respiratório do Adulto/etiologia , Traumatismos Torácicos/cirurgia , Volume de Ventilação Pulmonar
5.
Chin Med J (Engl) ; 132(5): 551-561, 2019 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-30807354

RESUMO

BACKGROUND: Classification of the pulmonary neuroendocrine tumor (pNET) categories is a step-wise process identified by the presence of necrosis and number of mitoses per 2 mm. In neuroendocrine tumor pathology, Ki-67 was first described as a prognostic factor in the pancreas and incorporated into the grading system of digestive tract neuroendocrine neoplasms in the 2010 WHO classification. However, the significance of Ki-67 in pNETs was still a controversial issue. This study was to investigate the potentially diagnostic value of Ki-67 in pNETs. METHODS: We retrieved 159 surgical specimens of pNETs, including 35 typical carcinoids (TCs), 2 atypical carcinoid (ACs), 28 large-cell neuroendocrine carcinomas (LCNECs), 94 small-cell lung cancers (SCLCs). Manual conventional method (MCM) and computer-assisted image analysis method (CIAM) were used to calculate the Ki-67 proliferative index. In CIAM, 6 equivalent fields (500 × 500 µm) at 10× magnification were manually annotated for digital image analysis. RESULTS: The Ki-67 index among the 4 groups with ranges of 0.38% to 12.66% for TC, 4.34% to 29.48% for AC, 30.67% to 93.74% for LCNEC, and 40.71% to 96.87% for SCLC. The cutoff value of Ki-67 index to distinguish low grade with high grade was 30.07%. For the univariate survival analyses in pNETs, both the overall survival and progression-free survival correlated with Ki-67 index. In addition, the Ki-67 index performed by CIAM was proved to be of great positive correlation with MCM. CONCLUSIONS: Ki-67 index counted by CIAM is a reliable method and can be a useful adjunct to classify the low- and high-grade NETs.


Assuntos
Carcinoma Neuroendócrino/metabolismo , Antígeno Ki-67/metabolismo , Tumores Neuroendócrinos/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Neuroendócrino/patologia , Feminino , Humanos , Imuno-Histoquímica , Leucemia Linfocítica Crônica de Células B/metabolismo , Leucemia Linfocítica Crônica de Células B/patologia , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/patologia , Prognóstico , Organização Mundial da Saúde
6.
Front Neurol ; 9: 813, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30319537

RESUMO

Objectives: The lesion topography of medullary infarction (MI) is heterogeneous and its correlation with stroke etiology remains elusive. We aim to clarify the lesion pattern of MI and to assess its correlation with stroke etiology. Material and Methods: Of 1129 subjects with available DWI in SMART study (a multi-center trial concerning secondary stroke prevention in China) between April 2008 and December 2010, 43 patients with DWI confirmed MI (3.8%) were retrospectively evaluated. Lesions were categorized as lateral and medial medullary infarction (LMI and MMI, 33 and 10 subjects respectively) at 3 levels rostro-caudally and correlated with the stroke etiology. Clinical profiles and long-term prognosis were analyzed. Results: Large artery atherosclerosis, small vessel occlusion, cardiogenic embolism and artery dissection accounted for 29, 11, 1, and 2 infarcts, respectively. Large artery disease was the most common cause in LMI (24 of 33, 72.7%) whereas small vessel occlusion was not uncommon in MMI (5 of 10, 50.0%). Though the difference of infarct pattern between large artery atherosclerosis and small vessel occlusion was insignificant, two distinct lesion patterns were considered to be relevant: (1) Rostral MMI with continuous medial pontine infarctions were more likely attributed to small vessel occlusion than large artery atherosclerosis. Kameda et al. (2) MMI with ventral to dorsal extension were more often caused by large artery disease than small vessel occlusion. Median NIHSS at admission was 4. During a median follow-up of 17 months, 2 patients died and 2 experienced recurrent ischemic events, 39 of 41 subjects (95.1%) were functional independent (mRS 0-2). Conclusions: This multi-center study demonstrates that MI has distinct lesion pattern depending on various stroke etiologies and mechanisms. Future investigations with larger sample size should establish the lesion pattern of MI and validate its correlation with the stroke etiology and mechanisms, which might improve stroke management.

7.
Front Neurol ; 9: 723, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30210443

RESUMO

Background and Objective: Studies on relations between arterial stiffness and full spectrum of radiological features of cerebral small vessel disease (CSVD) are scarce. We aim to investigate the association of arterial stiffness with lacunes, white matter hyperintensities (WMH), microbleeds (CMBs), dilated perivascular spaces (PVS), and brain atrophy in a community-based sample. Methods: A total of 953 participants (55.7 ± 9.4 years) who underwent brachial-ankle pulse wave velocity (baPWV) and brain magnetic resonance imaging were included. Lacunes, CMBs, and PVS were visually rated. Brain structure and WMH were automatically segmented. Brain parenchyma fraction (BPF), a surrogate index of brain atrophy, was calculated as a ratio of brain parenchyma volume to total intracranial volume. Multivariable logistic and linear regressions were used to investigate the associations between baPWV and CSVD. Subsequently, we explored these associations in strata of age. Results: Increased baPWV was associated with severe PVS in white matter (OR, 1.09; 95%CI, 1.01-1.17; p = 0.022), larger WMH volume (ß, 0.08; 95%CI, 0.04-0.12; p < 0.001), lower BPF (ß, -0.09; 95%CI, -0.15- -0.03; p = 0.007), and marginally associated with strictly lobar CMBs (OR, 1.11; 95%CI, 1.00-1.23; p = 0.055), but not with lacunes. WMH volume mediated the relation between baPWV and BPF. In age subgroup analysis, the association of baPWV with PVS in white matter was stronger among those aged <55 years, whereas the association with brain atrophy was more prominent among those aged ≥55 years. Increased baPWV was associated with larger WMH volume in both younger and older individuals. Conclusions: Increased arterial stiffness was associated with most of imaging markers of CSVD, including PVS in white matter, larger WMH volume, strictly lobar CMBs, and brain atrophy, but not lacunes. The mechanisms underlying these associations and their potential clinical significances warrant further investigations.

8.
Front Neurol ; 9: 498, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29997570

RESUMO

Background: Recent studies have shown that renal disease is associated with magnetic resonance imaging (MRI) markers of cerebral small vessel disease (CSVD), independent of traditional vascular risk factors. Although large artery lesions might be involved in the cerebrorenal association, evidence has been lacking. Methods: A total of 928 participants from a population-based cohort study were included. Kidney injury measurements included urinary albumin-to-creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR). CSVD was assessed on MRI by white matter hyperintensity volume (WMHV), lacunes, brain parenchymal fraction (BPF), cerebral microbleeds (CMBs), and perivascular space. Carotid plaques and brachial-ankle pulse wave velocity (baPWV) were used to assess large artery atherosclerosis and stiffness. Multivariable linear and logistic regression and additional interaction models were used for statistical analysis. Results: Individuals with elevated ACR had higher prevalence of lacunes and more WMHV (p = 0.001 and 0.000, respectively), those with decreased eGFR had smaller brain volume, higher prevalence of lacunes and deep CMBs (p = 0.009, p = 0.017) and p = 0.010 respectively). Interaction analysis revealed that carotid plaque and baPWV significantly enhanced the association between eGFR and BPF (p = 0.001 and p = 0.002, respectively), that is, the association of eGFR with BPF was only significant among participants with carotid plaque and higher baPWV. In addition, carotid plaque enhanced the association between ACR and WMHV (p = 0.034) and baPWV enhanced the association between ACR and the presence of lacunes (p = 0.027). Modifying effect of large vessel disease markers on the association between kidney injury measurements and CMBs was not significant. Conclusion: Evaluation of subclinical CVSD in individuals with kidney injury is warranted, especially in those with combined large artery disease.

9.
J Stroke ; 20(2): 239-246, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29886722

RESUMO

BACKGROUND AND PURPOSE: Epidemiological data of cerebral small vessel disease (CSVD) in the general population of China are lacking. We report on the prevalence of lacunes, white matter hyperintensity (WMH), and cerebral microbleeds (CMBs) in a community-based sample in China and compare the results with those of other studies. METHODS: This was a cross-sectional analysis of the population-based Shunyi Study in China. A total of 1,211 stroke-free participants (mean age, 55.6±9.3 years; 37.4% men) with available 3 Tesla (3T) magnetic resonance images were included in this analysis. Demographic information and risk factor data were assessed. The overall and age-specific prevalence of lacunes, WMH, and CMBs was evaluated. Associations between cardiovascular risk factors and the presence of these lesions were analyzed by multiple logistic regression. RESULTS: Our study showed a prevalence of 14.5% for lacunes, 72.1% for periventricular hyperintensity (PVH), 65.4% for deep white matter hyperintensity (DWMH), and 10.6% for CMBs. When compared with other community-based samples, individuals in the same age group showed a higher burden of lacunes and a relatively lower prevalence of CMBs. Advanced age was independently associated with the prevalence of these CSVD markers, while the presence of hypertension increased the risk of lacunes, PVH/DWMH, and CMBs in deep or infratentorial locations. CONCLUSIONS: A higher burden of lacunes but a relatively lower prevalence of CMBs was observed in this Chinese population. This notable result highlights the challenge of CSVD prevention in China. Chinese have a risk factor profile for CSVD similar to those in other populations.

10.
Hum Brain Mapp ; 39(11): 4452-4461, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29956412

RESUMO

In the elderly, brain structural deficits and gait disturbances due to cerebral small vessel disease (CSVD) have been well demonstrated. The relationships among CSVD, brain atrophy, and motor impairment, however, are far from conclusive. Particularly, the effect of CSVD on subcortical nuclear atrophy, motor performance of upper extremities, and associating patterns between brain atrophy and motor impairment remains largely unknown. To address these gaps, this study recruited 770 community-dwelling subjects (35-82 years of age), including both CSVD and non-CSVD individuals. For each subject, four motor tests involving upper and lower extremities were completed. High-resolution structural MRI was applied to extract gray matter (GM) volume, white matter volume, cortical thickness, surface area, and subcortical nuclear (caudate, putamen, pallidum, and thalamus) volumes. The results showed worse motor performance of lower extremities but relatively preserved performance of upper extremities in the CSVD group. Intriguingly, there was a significant association between the worse performance of upper extremities and atrophy of whole-brain GM and pallidum in the CSVD group but not in the non-CSVD group. In addition, mediation analysis confirmed a functional CSVD-to-"brain atrophy"-to-"motor impairment" pathway, that is, a mediating role of thalamic atrophy in the CSVD effect on walking speed in the elderly, indicating that CSVD impairs walking performance through damaging the integrity of the thalamus in aging populations. These findings provide important insight into the functional consequences of CSVD and highlight the importance of evaluating upper extremities functions and exploring their brain mechanisms in CSVD populations during aging.


Assuntos
Encéfalo/diagnóstico por imagem , Doenças de Pequenos Vasos Cerebrais/diagnóstico por imagem , Transtornos dos Movimentos/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Atrofia , Encéfalo/patologia , Doenças de Pequenos Vasos Cerebrais/complicações , Doenças de Pequenos Vasos Cerebrais/patologia , Estudos de Coortes , Feminino , Substância Cinzenta/patologia , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Transtornos dos Movimentos/etiologia , Transtornos dos Movimentos/patologia , Tamanho do Órgão , Substância Branca/patologia
11.
Int J Hematol ; 108(3): 254-266, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29748856

RESUMO

To investigate the prognostic value of tumor-infiltrating T-cell density and programmed cell death ligand-1 (PD-L1) expression in diffuse large B cell lymphoma (DLBCL). One-hundred-twenty-five Chinese DLBCL patients were enrolled in our study and provided samples; 76 of all cases were treated with rituximab (R). Tumor tissues were immunostained and analyzed for CD3+ and CD8+ tumor-infiltrating T-cell density, tumoral PD-L1, and microenvironmental PD-L1 (mPD-L1). The density of CD3 was rated as high in 33.6% cases, while 64.0% of DLBCLs were classified as high CD8 density. Of all cases, 16.8% were PD-L1+. Of the remaining PD-L1-DLBCLs, 29.8% positively expressed mPD-L1. Both CD3 high density and CD8 high density were associated with mPD-L1 positivity (P = 0.001 and P = 0.0001). In multivariate analysis, independently, high CD3 density predicted better OS (P = 0.023), while CD8 high density and PD-L1 positivity were both associated with prolonged PFS (P = 0.013 and P = 0.036, respectively). Even in the subgroup treated with R, univariate analyses indicated that high CD3 density and PD-L1 positivity were associated with better OS (P = 0.041) and PFS (P = 0.033), respectively. The infiltrating densities of CD3+ T-cells, CD8+ T-cells, and PD-L1 expression are predictive of survival in DLBCLs, irrespective of R usage.


Assuntos
Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Complexo CD3 , Linfócitos T CD8-Positivos/patologia , Expressão Gênica , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/patologia , Rituximab/uso terapêutico , Linfócitos T/patologia , Microambiente Tumoral/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Grupo com Ancestrais do Continente Asiático , Feminino , Previsões , Humanos , Imuno-Histoquímica , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Sobrevida , Adulto Jovem
12.
Stroke ; 49(5): 1135-1140, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29581240

RESUMO

BACKGROUND AND PURPOSE: Intracranial arterial dolichoectasia (IADE) is a poorly understood arteriopathy compared with intracranial atherosclerotic stenosis (ICAS). We aimed to investigate the risk factors of IADE and ICAS and their relationship with neuroimaging markers of cerebral small vessel disease in a population-based study. METHODS: This study comprised 1237 participants (aged 57.2±9.4 years, 37.6% men) who underwent brain magnetic resonance imaging and magnetic resonance angiography. IADE was assessed based on basilar artery dolichoectasia (diameter, height of bifurcation, and laterality of basilar artery) and dilation of basilar artery and internal carotid artery (intracranial volume-adjusted diameter ≥2 SD). ICAS was defined as any degree of stenosis in at least 1 intracranial artery. The neuroimaging markers of cerebral small vessel disease, including lacunes, white matter hyperintensities, microbleeds, dilated perivascular spaces, and brain atrophy, were evaluated. RESULTS: Basilar arterial dolichoectasia was observed in 3.6% (45/1237); intracranial arterial dilation in 5.9% (67/1142); and ICAS in 15.7% (194/1237). Older age, higher systolic blood pressure, diabetes mellitus, higher LDL-C (low-density lipoprotein cholesterol) and lower HDL-C (high-density lipoprotein cholesterol) were associated with the presence of ICAS (all P<0.001), whereas only older age was associated with IADE. ICAS was associated with lacunes (odds ratio, 2.91; 95% confidence interval, 1.96-4.34; P<0.001), increased white matter hyperintensities volume (ß±SE, 0.54±0.13; P<0.001), and brain atrophy (ß±SE, -1.16±0.21; P<0.001), whereas basilar arterial dolichoectasia was mainly associated with dilated perivascular spaces in basal ganglia (odds ratio, 2.20; 95% confidence interval, 1.20-4.02; P=0.01) and, to a lesser extent, associated with lacunes and microbleeds. CONCLUSIONS: IADE and ICAS had different risk factor profiles and associated with different imaging phenotypes of cerebral small vessel disease, suggesting different underlying mechanisms.


Assuntos
Artéria Basilar/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Doenças de Pequenos Vasos Cerebrais/epidemiologia , Arteriosclerose Intracraniana/epidemiologia , Insuficiência Vertebrobasilar/epidemiologia , Fatores Etários , Idoso , Atrofia , Pressão Sanguínea , Doenças de Pequenos Vasos Cerebrais/diagnóstico por imagem , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Constrição Patológica , Diabetes Mellitus/epidemiologia , Dilatação Patológica , Feminino , Humanos , Arteriosclerose Intracraniana/diagnóstico por imagem , Leucoaraiose/diagnóstico por imagem , Leucoaraiose/epidemiologia , Angiografia por Ressonância Magnética , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neuroimagem , Fenótipo , Fatores de Risco , Insuficiência Vertebrobasilar/diagnóstico por imagem , Substância Branca/diagnóstico por imagem
13.
Exp Mol Med ; 50(1): e433, 2018 01 26.
Artigo em Inglês | MEDLINE | ID: mdl-29371696

RESUMO

Although radiation therapy is a cornerstone of modern management of malignancies, various side effects are inevitably linked to abdominal and pelvic cancer after radiotherapy. Radiation-mediated gastrointestinal (GI) toxicity impairs the life quality of cancer survivors and even shortens their lifespan. Hydrogen has been shown to protect against tissue injuries caused by oxidative stress and excessive inflammation, but its effect on radiation-induced intestinal injury was previously unknown. In the present study, we found that oral gavage with hydrogen-water increased the survival rate and body weight of mice exposed to total abdominal irradiation (TAI); oral gavage with hydrogen-water was also associated with an improvement in GI tract function and the epithelial integrity of the small intestine. Mechanistically, microarray analysis revealed that hydrogen-water administration upregulated miR-1968-5p levels, thus resulting in parallel downregulation of MyD88 expression in the small intestine after TAI exposure. Additionally, high-throughput sequencing showed that hydrogen-water oral gavage resulted in retention of the TAI-shifted intestinal bacterial composition in mice. Collectively, our findings suggested that hydrogen-water might be used as a potential therapeutic to alleviate intestinal injury induced by radiotherapy for abdominal and pelvic cancer in preclinical settings.


Assuntos
Gastroenteropatias/tratamento farmacológico , Gastroenteropatias/etiologia , Microbioma Gastrointestinal/efeitos da radiação , Hidrogênio/farmacologia , Lesões por Radiação/tratamento farmacológico , Regiões 3' não Traduzidas , Administração Oral , Animais , Gastroenteropatias/mortalidade , Microbioma Gastrointestinal/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos da radiação , Hidrogênio/administração & dosagem , Intestino Delgado/efeitos dos fármacos , Intestino Delgado/microbiologia , Intestino Delgado/efeitos da radiação , Masculino , Camundongos Endogâmicos C57BL , MicroRNAs/genética , Fator 88 de Diferenciação Mieloide/genética , Fator 88 de Diferenciação Mieloide/metabolismo , Lesões por Radiação/microbiologia , Lesões por Radiação/mortalidade , Protetores contra Radiação/farmacologia , Soluções
14.
Front Neurol ; 8: 648, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29250028

RESUMO

Background: Few studies have investigated structural imaging findings of cerebral venous thrombosis (CVT) in China. The structural imaging [head computed tomography (CT) and routine brain magnetic resonance imaging (MRI)] can assess any parenchymal lesion secondary to the venous thrombosis and reveal direct signs of intraluminal thrombus. In recent years, many patients can be diagnosed with CVT more rapidly and directly by structural imaging. The aim of the present study is to determine the performance of structural imaging in the diagnosis and outcome of CVT in a large cohort single center of Chinese patients. Methods: We evaluated consecutive patients admitted to our hospital with CVT receiving structural imaging from 1991 to 2015. A neuroradiologist, blinded to clinical data, independently reviewed the structural imaging, including head CT and routine MRI for parenchymal lesions and signs of dural venous sinus thrombosis, as well as the MRV/DSA findings. The Clinical and laboratory data were reviewed and recorded for further analysis. Results: 117 patients were included in this study, 68 (58.1%) were females. Parenchymal lesions were identified in 56.4% (66/117) of the patients on structural imaging, including focal edema in 30.8%, hemorrhage in 19.7%, and brain swelling in 4.3% of the patients. Patients with parenchymal lesions presented with more often seizures (P < 0.001) and less often headache (P = 0.049). Intraluminal thrombus within the sinuses or veins on structural imaging was found in 28.2% (33/117) of the patients. Patients with both intraluminal thrombus and parenchymal lesions on structural imaging had more acute onset (P = 0.01) and present more consciousness disturbance (P = 0.007). Conclusion: Intracranial lesions on structural imaging are frequently found in patients with CVT. Patients with parenchymal lesions on structural imaging, especially with intraluminal thrombus simultaneously, tend to have a severe clinical picture and might lead to a devastating or fatal outcome. Structural imaging may help on early diagnosis and predict the poor outcome of CVT.

15.
Front Aging Neurosci ; 9: 313, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29021757

RESUMO

Objective: To investigate the correlation between cerebral small vessel disease (CSVD) burden and motor performance of lower and upper extremities in community-dwelling populations. Methods: We performed a cross-sectional analysis on 770 participants enrolled in the Shunyi study, which is a population-based cohort study. CSVD burden, including white matter hyperintensities (WMH), lacunes, cerebral microbleeds (CMBs), perivascular spaces (PVS), and brain atrophy were measured using 3T magnetic resonance imaging. All participants underwent quantitative motor assessment of lower and upper extremities, which included 3-m walking speed, 5-repeat chair-stand time, 10-repeat pronation-supination time, and 10-repeat finger-tapping time. Data on demographic characteristics, vascular risk factors, and cognitive functions were collected. General linear model analysis was performed to identify potential correlations between motor performance measures and imaging markers of CSVD after controlling for confounding factors. Results: For motor performance of the lower extremities, WMH was negatively associated with gait speed (standardized ß = -0.092, p = 0.022) and positively associated with chair-stand time (standardized ß = 0.153, p < 0.0001, surviving FDR correction). For motor performance of the upper extremities, pronation-supination time was positively associated with WMH (standardized ß = 0.155, p < 0.0001, surviving FDR correction) and negatively with brain parenchymal fraction (BPF; standardized ß = -0.125, p = 0.011, surviving FDR correction). Only BPF was found to be negatively associated with finger-tapping time (standardized ß = -0.123, p = 0.012). However, lacunes, CMBs, or PVS were not found to be associated with motor performance of lower or upper extremities in multivariable analysis. Conclusion: Our findings suggest that cerebral microstructural changes related to CSVD may affect motor performance of both lower and upper extremities. WMH and brain atrophy are most strongly associated with motor function deterioration in community-dwelling populations.

16.
Am J Hypertens ; 30(12): 1189-1195, 2017 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-28992193

RESUMO

BACKGROUND: Pulse pressure (PP) is a surrogate marker of arterial stiffness. Studies on baseline PP and long-term outcomes in patients with stroke are limited. We aimed to evaluate whether PP within 3 months after ischemic stroke was associated with long-term stroke outcomes. METHODS: A total of 4,195 patients (61.2 ± 11.6 years, 68.4% men) with first-ever ischemic stroke in 3 months had baseline blood pressure (BP) measured. Study end-points were the combined end-points (recurrent vascular events and all-cause mortality) and recurrent stroke. RESULTS: In the group <60 years of age, the BP components of systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), or PP did not significantly correlate with long-term stroke outcomes. In the group ≥60 years of age, PP was significantly associated with combined end-points (hazards ratio [HR] = 1.35; 95% confidence interval [CI], 1.18-1.54) and recurrent stroke (HR = 1.46; 95% CI, 1.24-1.72). Combination of SBP and PP, DBP and PP, or MAP and PP, respectively, showed no incremental value of SBP, DBP, or MAP in predicting long-term stroke outcomes. CONCLUSIONS: PP was significantly associated with long-term stroke outcomes, and this association was prominent in patients with stroke older than 60 years of age.


Assuntos
Pressão Sanguínea , Isquemia Encefálica/fisiopatologia , Acidente Vascular Cerebral/fisiopatologia , Adulto , Fatores Etários , Idoso , Pressão Arterial , Isquemia Encefálica/mortalidade , Estudos de Coortes , Determinação de Ponto Final , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Acidente Vascular Cerebral/mortalidade , Resultado do Tratamento , Rigidez Vascular
17.
Crit Care Med ; 45(12): e1218-e1225, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28902121

RESUMO

OBJECTIVES: Data about the critical care resources in China remain scarce. The purpose of this study was to investigate the variation and distribution of critical care resources in Guangdong province from 2005 to 2015. DESIGN: Data in regard to critical care resources were collected through questionnaires and visits every 5 years from 2005. SETTING: All hospitals in Guangdong province were screened and hospitals that provide critical care services were enrolled. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: One hundred eleven, 158, and 284 hospitals that provide critical care services were enrolled in the three consecutive surveys respectively. The number of ICUs, ICU beds, intensivists, and nurses increased to 324, 3,956, 2,470, and 7,695, respectively, by 2015. Adjusted by population, the number of ICU beds per 100,000 (100,000) population increased by 147.7% from 2005 to 2015, and the number of intensivists and nurses per 100,000 population increased by 35.3% and 55.1% from 2011 to 2015. However, the numbers in the Pearl River Delta, a richer area, were higher than those in the non-Pearl River Delta area (ICU beds: 4.64 vs 2.58; intensivists: 2.90 vs 1.61; nurses: 9.30 vs 4.71 in 2015). In terms of staff training, only 17.85% of intensivists and 14.29% of nurses have completed a formal accredited critical care training program by 2015. CONCLUSIONS: Our study was the first one to investigate the trend and distribution of critical care resources in China. The quantity of ICU beds and staff has been increasing rapidly, but professional training for staff was inadequate. The distribution of critical care resources was unbalanced. Our study can be beneficial for healthcare policymaking and the allocation of critical care resources in Guangdong province and other provinces in China.


Assuntos
Cuidados Críticos/estatística & dados numéricos , Unidades de Terapia Intensiva/provisão & distribução , China , Equipamentos e Provisões/provisão & distribução , Produto Interno Bruto , Número de Leitos em Hospital/estatística & dados numéricos , Humanos , Recursos Humanos em Hospital/provisão & distribução
18.
Food Chem ; 235: 227-233, 2017 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-28554631

RESUMO

YingDe black tea is produced from crude tea prepared from leaves of Camellia sinensis var. assamica. In this work, we isolated and identified five novel flavanones, namely, amelliaone A-E (1-5), along with seven known compounds 6-12 from the ethanol extract of YingDe black tea. The structures of these five novel phenolic compounds were determined using extensive 1D and 2D nuclear magnetic resonance spectroscopy experiments. The compounds were further evaluated for antioxidant, α-glucosidase inhibitory, and cytotoxic activities. Compound 1 exhibited higher α-glucosidase inhibitory activity with a half-maximum inhibitory concentration value (IC50) of 10.2µM compared with acarbose (18.2µM).


Assuntos
Camellia sinensis/química , Flavanonas/análise , Inibidores de Glicosídeo Hidrolases/análise , Antioxidantes , Chá/química , alfa-Glucosidases/análise
19.
Acta Pharmacol Sin ; 37(12): 1597-1605, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27665846

RESUMO

AIM: Deacetylisovaltratum (DI) is isolated from the traditional Chinese herbal medicine Patrinia heterophylla Bunge, which exhibits anti-cancer activity. Here, we investigated the effects of DI on human gastric carcinoma cell lines in vitro and elucidated its anti-cancer mechanisms. METHODS: Human gastric carcinoma AGS and HGC-27 cell lines were treated with DI, and cell viability was detected with MTT assay. Cell cycle stages, apoptosis and mitochondrial membrane potential were measured using flow cytometry. Protein levels were analyzed by Western blotting. Tubulin polymerization assays and immunofluorescence were used to characterize the tubulin polymerization process. RESULTS: DI inhibited the cell viability of AGS and HGC-27 cells in a dose- and time-dependent manner with IC50 values of 12.0 and 28.8 µmol/L, respectively, at 24 h of treatment. Treatment with DI (10-100 µmol/L) dose-dependently promoted tubulin polymerization, and induced significant G2/M cell cycle arrest in AGS and HGC-27 cells. Moreover, DI treatment disrupted mitochondrial membrane potential and induced caspase-dependent apoptosis in AGS and HGC-27 cells. CONCLUSION: DI induces G2/M-phase arrest by disrupting tubulin polymerization in human gastric cancer cells, which highlights its potent anti-cancer activity and potential application in gastric cancer therapy.


Assuntos
Antineoplásicos/farmacologia , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Neoplasias Gástricas/tratamento farmacológico , Moduladores de Tubulina/farmacologia , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Potenciais da Membrana/efeitos dos fármacos , Tubulina (Proteína)/química , Moduladores de Tubulina/química
20.
Biomed Res Int ; 2016: 9508493, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27340674

RESUMO

Objective. To systematically review the efficacy and potential immunomodulatory effect of ulinastatin combined with thymosin α1 (UTI) for sepsis. Design. A systematic review and meta-analysis of randomized controlled trials (RCTs). Data Sources. The following databases: PubMed, Embase, and Cochrane Central were searched to identify related clinical trials. The search terms were "ulinastatin", "thymosin", and "sepsis". Results. Six RCTs, 944 septic patients in total, were included in this meta-analysis. The result shows UTI increased the 28-day survival rate of septic patients, odds ratio (OR) = 2.01, 95% CI [1.53, 2.64]. After the treatment with UTI, the APACHE II score (four studies) dropped 4.72 further, mean = -4.72, 95% CI [-6.54, -2.91] (p < 0.00001). The mean time of ICU stay (four studies) in UTI group decreased 3.03 days further, mean = -3.03 [-6.99, 0.95] (p = 0.14), and mechanical ventilation time (four studies) decreased 2.05 days, mean = -1.81 [-2.96, -0.66] (p = 0.002). With the treatment of UTI, CD4+T cells raised 5.13%, mean = 5.13, 95% CI [2.75, 7.50] (p < 0.0001); there was no significant change in CD8+T cells, mean = -0.74 [-2.93, 1.45] (p = 0.51). Conclusion. According to this meta-analysis, with the treatment of UTI, the short-term survival rate of septic patients was increased and the illness severity was alleviated. ICU stay and mechanical ventilation time were effectively shortened. The beneficial effect of UTI might be due to the potential immunomodulatory effects of these two drugs.


Assuntos
Glicoproteínas/administração & dosagem , Fatores Imunológicos/administração & dosagem , Insuficiência Respiratória/mortalidade , Sepse/tratamento farmacológico , Sepse/mortalidade , Timosina/análogos & derivados , Adulto , Idoso , Idoso de 80 Anos ou mais , Causalidade , Comorbidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Ensaios Clínicos Controlados Aleatórios como Assunto , Respiração Artificial/mortalidade , Insuficiência Respiratória/prevenção & controle , Fatores de Risco , Sepse/diagnóstico , Taxa de Sobrevida , Timalfasina , Timosina/administração & dosagem , Resultado do Tratamento
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