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BACKGROUND: The purpose of this study was to investigate the association between the mean upper cervical spinal cord cross-sectional area (MUCCA) and the risk and severity of cerebral small vessel disease (CSVD). METHODS: Community-dwelling residents in Lishui City, China, from the cross-sectional survey in the PRECISE cohort study (Polyvascular Evaluation for Cognitive Impairment and Vascular Events) conducted from 2017 to 2019. We included 1644 of 3067 community-dwelling adults in the PRECISE study after excluding those with incorrect, incomplete, insufficient, or missing clinical or imaging data. Total and modified total CSVD scores, as well as magnetic resonance imaging features, including white matter hyperintensity, lacunes, cerebral microbleeds, enlarged perivascular spaces, and brain atrophy, were assessed at the baseline. The Spinal Cord Toolbox was used to measure the upper cervical spinal cord cross-sectional area of the C1 to C3 segments of the spinal cord and its average value was taken as MUCCA. Participants were divided into 4 groups according to quartiles of MUCCA. Associations were analyzed using linear regression models adjusted for age, sex, current smoking and drinking, medical history, intracranial volume, and total cortical volume. RESULTS: The means±SD age of the participants was 61.4±6.5 years, and 635 of 1644 participants (38.6%) were men. The MUCCA was smaller in patients with CSVD than those without CSVD. Using the total CSVD score as a criterion, the MUCCA was 61.78±6.12 cm2 in 504 of 1644 participants with CSVD and 62.74±5.94 cm2 in 1140 of 1644 participants without CSVD. Using the modified total CSVD score, the MUCCA was 61.81±6.04 cm2 in 699 of 1644 participants with CSVD and 62.91±5.94 cm2 in 945 of 1644 without CSVD. There were statistical differences between the 2 groups after adjusting for covariates in 3 models. The MUCCA was negatively associated with the total and modified total CSVD scores (adjusted ß value, -0.009 [95% CI, -0.01 to -0.003] and -0.007 [95% CI, -0.01 to -0.0006]) after adjustment for covariates. Furthermore, the MUCCA was negatively associated with the white matter hyperintensity burden (adjusted ß value, -0.01 [95% CI, -0.02 to -0.003]), enlarged perivascular spaces in the basal ganglia (adjusted ß value, -0.005 [95% CI, -0.009 to -0.001]), lacunes (adjusted ß value, -0.004 [95% CI, -0.007 to -0.0007]), and brain atrophy (adjusted ß value, -0.009 [95% CI, -0.01 to -0.004]). CONCLUSIONS: The MUCCA and CSVD were correlated. Spinal cord atrophy may serve as an imaging marker for CSVD; thus, small vessel disease may involve the spinal cord in addition to being intracranial.
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Enfermedades de los Pequeños Vasos Cerebrales , Médula Cervical , Masculino , Adulto , Humanos , Persona de Mediana Edad , Anciano , Femenino , Estudios de Cohortes , Médula Cervical/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Enfermedades de los Pequeños Vasos Cerebrales/diagnóstico por imagen , Enfermedades de los Pequeños Vasos Cerebrales/epidemiología , Enfermedades de los Pequeños Vasos Cerebrales/complicaciones , Médula Espinal/diagnóstico por imagen , Médula Espinal/patología , Atrofia/patologíaRESUMEN
The network nature of the brain is gradually becoming a consensus in the neuroscience field. A set of highly connected regions in the brain network called "rich-club" are crucial high efficiency communication hubs in the brain. The abnormal rich-club organization can reflect underlying abnormal brain function and metabolism, which receives increasing attention. Diabetes is one of the risk factors for neurological diseases, and most individuals with prediabetes will develop overt diabetes within their lifetime. However, the gradual impact of hyperglycemia on brain structures, including rich-club organization, remains unclear. We hypothesized that the brain follows a special disrupted pattern of rich-club organization in prediabetes and diabetes. We used cross-sectional baseline data from the population-based PolyvasculaR Evaluation for Cognitive Impairment and vaScular Events (PRECISE) study, which included 2218 participants with a mean age of 61.3 ± 6.6 years and 54.1% females comprising 1205 prediabetes, 504 diabetes, and 509 normal control subjects. The rich-club organization and network properties of the structural networks derived from diffusion tensor imaging data were investigated using a graph theory approach. Linear mixed models were used to assess associations between rich-club organization disruptions and the subjects' glucose status. Based on the graphical analysis methods, we observed the disrupted pattern of rich-club organization was from peripheral regions mainly located in frontal areas to rich-club regions mainly located in subcortical areas from prediabetes to diabetes. The rich-club organization disruptions were associated with elevated glucose levels. These findings provided more details of the process by which hyperglycemia affects the brain, contributing to a better understanding of the potential neurological consequences. Furthermore, the disrupted pattern observed in rich-club organization may serve as a potential neuroimaging marker for early detection and monitoring of neurological disorders in individuals with prediabetes or diabetes.
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Conectoma , Hiperglucemia , Estado Prediabético , Femenino , Humanos , Persona de Mediana Edad , Anciano , Masculino , Imagen de Difusión Tensora/métodos , Estado Prediabético/diagnóstico por imagen , Estudios Transversales , Encéfalo/diagnóstico por imagen , Glucosa , Vías NerviosasRESUMEN
ALK-rearranged renal cell carcinoma (ALK-RCC) is rare, molecularly defined RCC subtype in the recently published fifth edition of World Health Organization classification of tumors. In this study, we described 9 ALK-RCCs from a clinicopathologic, immunohistochemical, and molecular genetic aspect, supporting and extending upon the observations by previous studies regarding this rare subgroup of RCC. There were 6 male and 3 female patients with ages ranging from 14 to 59 years (mean, 34.4 years). None of the patients had sickle cell trait. The diagnosis was based on radical or partial nephrectomy specimen for 8 patients and on biopsy specimen for 1. Tumor size ranged from 2.5 to 7.2 cm (mean, 2.8 cm). Follow-up was available for 6 of 9 patients (6-36 months); 5 had no tumor recurrence or metastasis and 1 developed lung metastasis at 24 months. The patient was subsequently treated with resection of the metastatic tumor followed by crizotinib-targeted therapy, and he was alive without tumor 12 months later. Histologically, the tumors showed a mixed growth of multiple patterns, including papillary, solid, tubular, tubulocystic, cribriform, and corded, often set in a mucinous background. The neoplastic cells had predominantly eosinophilic cytoplasm. Focally, clear cytoplasm with polarized nuclei and subnuclear vacuoles (n = 1), and pale foamy cytoplasm (n = 1) were observed on the tumor cells. The biopsied tumor showed solid growth of elongated tubules merging with bland spindle cells. Other common and uncommon features included psammomatous microcalcifications (n = 5), rhabdoid cells (n = 4), prominent intracytoplasmic vacuoles (n = 4), prominent chronic inflammatory infiltrate (n = 3), signet ring cell morphology (n = 2), and pleomorphic cells (n = 2). By immunohistochemistry, all 9 tumors were diffusely positive for ALK(5A4) and 4 of 8 tested cases showed reactivity for TFE3 protein. By fluorescence in situ hybridization analysis, ALK rearrangement was identified in all the 9 tumors; none of the tested tumors harbored TFE3 rearrangement (0/4) or gains of chromosomes 7 and 17 (0/3). ALK fusion partners were identified by RNA-sequencing in all 8 cases analyzed, including EML4 (n = 2), STRN (n = 1), TPM3 (n = 1), KIF5B (n = 1), HOOK1 (n = 1), SLIT1 (n = 1), and TPM1(3'UTR) (n = 1). Our study further expands the morphologic and molecular genetic spectrum of ALK-RCC.
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BACKGROUND: Bladder cancer (BC) is a very common urinary tract malignancy that has a high incidence and lethality. In this study, we identified BC biomarkers and described a new noninvasive detection method using serum and urine samples for the early detection of BC. METHODS: Serum and urine samples were retrospectively collected from patients with BC (n = 99) and healthy controls (HC) (n = 50), and the expression levels of 92 inflammation-related proteins were examined via the proximity extension analysis (PEA) technique. Differential protein expression was then evaluated by univariate analysis (p < 0.05). The expression of the selected potential marker was further verified in BC and adjacent tissues by immunohistochemistry (IHC) and single-cell sequencing. A model was constructed to differentiate BC from HC by LASSO regression and compared to the detection capability of FISH. RESULTS: The univariate analysis revealed significant differences in the expression levels of 40 proteins in the serum (p < 0.05) and 17 proteins in the urine (p < 0.05) between BC patients and HC. Six proteins (AREG, RET, WFDC2, FGFBP1, ESM-1, and PVRL4) were selected as potential BC biomarkers, and their expression was evaluated at the protein and transcriptome levels by IHC and single-cell sequencing, respectively. A diagnostic model (a signature) consisting of 14 protein markers (11 in serum and three in urine) was also established using LASSO regression to distinguish between BC patients and HC (area under the curve = 0.91, PPV = 0.91, sensitivity = 0.87, and specificity = 0.82). Our model showed better diagnostic efficacy than FISH, especially for early-stage, small, and low-grade BC. CONCLUSION: Using the PEA method, we identified a panel of potential protein markers in the serum and urine of BC patients. These proteins are associated with the development of BC. A total of 14 of these proteins can be used to detect early-stage, small, low-grade BC. Thus, these markers are promising for clinical translation to improve the prognosis of BC patients.
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Detección Precoz del Cáncer , Neoplasias de la Vejiga Urinaria , Humanos , Estudios Retrospectivos , Curva ROC , Detección Precoz del Cáncer/métodos , Neoplasias de la Vejiga Urinaria/patología , Biomarcadores de TumorRESUMEN
BACKGROUND: We aimed to examine the association between adipose tissue-specific insulin resistance and atherosclerotic burden and plaques in intracranial, extracranial, and coronary arteries in community residents without diabetes. METHODS: Adipose tissue-specific insulin resistance index (Adipo-IR) was calculated by fasting serum insulin and free fatty acids and categorized into 4 groups according to the quartiles. The 3.0 T magnetic resonance imaging scanner was used to assess intracranial and extracranial atherosclerotic plaques, while computed tomography angiography was used to assess coronary atherosclerotic plaques. Intracranial, extracranial, and coronary atherosclerotic burden was assessed by segmental stenosis segment scores of the corresponding arterial segments, respectively. Binary and ordinal logistic regression models were utilized to investigate the relationship of Adipo-IR with the presence of atherosclerotic plaques and atherosclerotic burden. RESULTS: Of 2,719 participants (mean [standard deviation] age, 60.9 [6.6] years; 1,441 [53.0%] women), the prevalence of intracranial atherosclerotic plaques, extracranial atherosclerotic plaques, and coronary plaques were 432 (15.9%), 975 (35.9%), and 1,160 (42.7%), respectively. Compared with individuals with the lowest quartile, participants with the fourth quartile of the Adipo-IR were associated with intracranial atherosclerotic burden (common odds ratio [cOR]: 1.35; 95% confidence interval [CI]: 0.99-1.82), coronary plaque (odds ratio [OR]: 1.45; 95% CI: 1.15-1.83), and segment stenosis score (cOR: 1.44; 95% CI: 1.15-1.81) after adjustment for age, sex, and current smoking. CONCLUSION: Adipose tissue-specific insulin resistance is associated with atherosclerotic burden and plaques in intracranial and coronary arteries in Chinese community nondiabetic residents.
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PRRX1-fused mesenchymal neoplasm is a recently identified, rare subcutaneous soft tissue neoplasm that is characterized by fusion of PRRX1 (exon 1) with NCOA1 (exon 13) in the majority of reported cases. Although initially considered to be fibroblastic, a possibility of neural or neuroectodermal differentiation has been suggested in a subset of cases. We report a 26-year-old female with a 4.0 cm painless mass located in the subcutis of the left thigh. Microscopically, the tumor was well-circumscribed and multinodular and was composed of relatively monomorphic ovoid to spindle cells arranged in loose fascicles, trabeculae, and cords within alternating myxoid and fibrous matrix, and vascularized stroma. Mitotic figures were scarce and necrosis was not observed. By immunohistochemistry, the neoplastic cells demonstrated focal co-expression of S100 protein and SOX10 and were negative for epithelial membrane antigen, smooth muscle actin, desmin, CD34, STAT6, HMB45, Melan-A, and MUC4. The expression of Rb1 was retained. Targeted RNA-sequencing identified a novel transcript fusion of PRRX1 (exon 1)::NCOA1 (exon 15), which was further confirmed by reverse transcription polymerase chain reaction and Sanger sequencing. The tumor was narrowly excised and no tumor recurrence or metastasis was identified after 13 months of follow-up. In summary, we report a new case of PRRX1-fused mesenchymal neoplasm, expanding the molecular genetic spectrum and providing further support for possible neural or neuroectodermal differentiation of this emerging soft tissue tumor entity.
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BACKGROUND: 10-year atherosclerotic cardiovascular disease (ASCVD) risk scores were useful for predicting large vessel disease, but the relationships between them and cerebral small vessel disease (CSVD) were unclear. Our study aimed to evaluate associations of 10-year ASCVD risk scores with CSVD and its magnetic resonance imaging (MRI) markers. METHODS: Community-dwelling residents from the PolyvasculaR Evaluation for Cognitive Impairment and vaScular Events study were included in this cross-sectional study. At baseline, we collected data related to the Framingham Risk Score (FRS), pooled cohort equation (PCE), prediction for ASCVD risk in China (China-PAR) and Systematic COronary Risk Evaluation model 2 (SCORE2), and classified participants into low, moderate and high groups. Participants underwent brain MRI scans. We evaluated white matter hyperintensity (WMH), lacunes, cerebral microbleeds (CMBs) and enlarged perivascular spaces in basal ganglia (BG-EPVS) according to criteria of Wardlaw and Rothwell, and calculated total CSVD score and modified total CSVD score. RESULTS: A total of 3063 participants were included, and 53.5% of them were female. A higher FRS was associated with higher total CSVD score (moderate vs. low: cOR 1.89, 95% CI 1.53-2.34; high vs. low: cOR 3.23, 95%CI 2.62-3.97), and the PCE, China-PAR or SCORE2 score was positively related to total CSVD score (P < 0.05). Moreover, higher 10-year ASCVD scores were associated with higher odds of WMH (P < 0.05), lacunes (P < 0.05), CMBs (P < 0.05) and BG-EPVS (P < 0.05). CONCLUSIONS: The 10-year ASCVD scores were positively associated with CSVD and its MRI markers. These scores provided a method of risk stratification in the population with CSVD.
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Enfermedades de los Pequeños Vasos Cerebrales , Imagen por Resonancia Magnética , Humanos , Femenino , Masculino , Enfermedades de los Pequeños Vasos Cerebrales/diagnóstico por imagen , Enfermedades de los Pequeños Vasos Cerebrales/epidemiología , Anciano , Estudios Transversales , Medición de Riesgo , Persona de Mediana Edad , China/epidemiología , Factores de Riesgo , Aterosclerosis/epidemiología , Aterosclerosis/diagnóstico por imagen , Aterosclerosis/diagnóstico , Disfunción Cognitiva/epidemiología , Disfunción Cognitiva/diagnóstico , Valor Predictivo de las PruebasRESUMEN
BACKGROUND: Life's Essential 8 (LE8), the recently updated construct for quantifying cardiovascular health, is related to the risks of cardiovascular events. The present study aimed to evaluate associations of LE8 score with the multi-territorial extent of atherosclerosis in a community-dwelling population. METHODS: Data were derived from the baseline cross-sectional survey of the PolyvasculaR Evaluation for Cognitive Impairment and vaScular Events (PRECISE) study in Lishui City. The LE8 included overall, medical and behavior LE8 scores, and were categorized as low (< 60), moderate (60-<80), and high (≥ 80) groups. Vascular magnetic resonance imaging was used to evaluate intracranial and extracranial arteries; thoracoabdominal computed tomography angiography to evaluate coronary, subclavian, aorta, renal, ilio-femoral arteries; and ankle-brachial index to evaluate peripheral arteries. The presence of atherosclerotic plaque or stenosis in any territory was defined as plaque or vascular stenosis with 1 territory affected or more in these arteries. The extent of atherosclerotic plaques or stenosis was assessed according to the number of these 8 vascular sites affected, and graded as four grades (none, single territory, 2-3 territories, 4-8 territories). RESULTS: Of 3065 included participants, the average age was 61.2 ± 6.7 years, and 53.5% were women (n = 1639). The moderate and high overall LE8 groups were associated with lower extent of multi-territorial plaques [common odds ratio (cOR) 0.44, 95% confidence interval (CI), 0.35-0.55; cOR 0.16, 95%CI, 0.12-0.21; respectively] and stenosis (cOR 0.51, 95%CI, 0.42-0.62; cOR 0.16, 95%CI, 0.12-0.21; respectively) after adjustment for potential covariates. Similar results were observed for medical LE8 score with the extent of multi-territorial plaques and stenosis (P < 0.05). We also found the association between behavior LE8 score and the extent of multi-territorial stenosis (P < 0.05). CONCLUSIONS: The higher LE8 scores, indicating healthier lifestyle, were associated with lower presence and extent of atherosclerotic plaque and stenosis in southern Chinese adults. Prospective studies are needed to further validate these findings.
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Placa Aterosclerótica , Humanos , Estudios Transversales , Masculino , Femenino , Placa Aterosclerótica/diagnóstico por imagen , Anciano , Persona de Mediana Edad , Constricción Patológica , Vida Independiente/tendenciasRESUMEN
SMARCB1/INI1-deficient soft tissue tumors with epithelioid and myxoid features are diverse and mainly include soft tissue myoepithelial tumor, extraskeletal myxoid chondrosarcoma, and the recently described myoepithelioma-like tumor of the vulvar region and myxoepithelioid tumor with chordoid features. Because of their overlapping features, the accurate diagnosis and classification of these tumors are often challenging. Herein, we report two unique cases of SMARCB1/INI1-deficient soft tissue neoplasm with epithelioid and myxoid features occurring in male paratesticular region. The first case was a 52-year-old man presented with an intermittent painful left paratesticular mass for 1 year. The second case was a 41-year-old man presented with a painless paratesticular mass on the right side for 3 months. Both patients underwent an orchiectomy. After 6 and 26 months of follow-up, both were alive with no evidence of recurrence or metastasis. In both cases, the tumor was relatively well-demarcated and showed monomorphic round to epithelioid cells arranged in a nested, trabecular, reticular, and corded pattern, setting in a myxohyalinized and vascularized matrix. The tumor cells showed relatively uniform round nuclei with vesicular chromatin and variably prominent nucleoli. No rhabdoid cells were identified. Mitoses numbered 3 and 2 per 10 high-power fields. Tumor necrosis or lymphovascular invasion was absent. Immunohistochemically, both tumors expressed epithelial membrane antigen (focal), calponin (focal), and CD99. SMARCB1/INI1 expression was deficient in both cases. In addition, case 1 diffusely expressed pan-cytokeratin, and case 2 diffusely expressed CD34 and synaptophysin. Molecular genetically, case 1 showed SMARCB1 homozygous deletion as detected by fluorescence in-situ hybridization (FISH), and case 2 demonstrated SMARCB1 copy number deletions by next-generation sequencing and SMARCB1 monoallelic deletion by FISH. Both cases lacked EWSR1 rearrangements by FISH. The overall clinicopathologic profiles of the two cases made it difficult to classify them as one of the established categories of SMARCB1/INI1-deficient mesenchymal tumors. Our study further expands the clinicopathologic and molecular spectrum of SMARCB1/INI1-deficient epithelioid and myxoid neoplasms and highlights the challenges to diagnose these tumors.
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Condrosarcoma , Neoplasias de los Tejidos Conjuntivo y Blando , Neoplasias de los Tejidos Blandos , Humanos , Masculino , Persona de Mediana Edad , Adulto , Homocigoto , Eliminación de Secuencia , Proteína SMARCB1/genética , Condrosarcoma/patología , Neoplasias de los Tejidos Conjuntivo y Blando/diagnóstico , Neoplasias de los Tejidos Conjuntivo y Blando/genética , Neoplasias de los Tejidos Blandos/diagnóstico , Neoplasias de los Tejidos Blandos/genética , Neoplasias de los Tejidos Blandos/patología , Biomarcadores de TumorRESUMEN
AIMS: Few population-based studies have investigated the association between insulin resistance and atherosclerotic burden in intra- and extra-cranial arteries. The purpose of this study is to explore the relationship between insulin resistance and intra- and extra-cranial atherosclerotic burden in community-based nondiabetic participants. METHODS: This is a cross-sectional analysis from a population-based prospective cohort-PolyvasculaR Evaluation for Cognitive Impairment and vaScular Events (PRECISE) study in China. The homeostasis model assessment of insulin resistance (HOMA-IR) and insulin sensitivity indices (ISI0-120) were stratified by the quartiles, respectively. The atherosclerotic presence of plaques and burden was evaluated by high-resolution MRI. Binary or ordinal logistic regression was performed to assess the association between HOMA-IR or ISI0-120 and the presence and burden of atherosclerosis. RESULTS: Among the 2754 participants, the mean age was 60.9 ± 6.6 years, and 1296 (47.1%) were males. Compared with the lowest quartile of HOMR-IR, the highest quartile of HOMA-IR (indicating a higher level of insulin resistance) was associated with an increased presence of plaques (OR:1.54, 95% CI:1.14-2.08), and atherosclerotic burden (OR:1.53, 95%CI:1.14-2.07) in intracranial arteries. Meanwhile, we observed a similar relationship between HOMA-IR and the presence or burden in extracranial atherosclerosis. The first (indicating a higher level of insulin resistance) quartiles of ISI0-120 were associated with the intracranial plaques (Q1, OR:1.56, 95%CI:1.16-2.11) and atherosclerotic burden (Q1, OR:1.57, 95%CI:1.17-2.12), but not extracranial plaques or atherosclerotic burden, compared with the fourth quartile of ISI0-120. CONCLUSIONS: Insulin resistance was associated with an increased intra-and extra-cranial atherosclerotic burden in the nondiabetic elderly Chinese population.
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Aterosclerosis , Resistencia a la Insulina , Anciano , Masculino , Humanos , Persona de Mediana Edad , Femenino , Estudios Transversales , Estudios Prospectivos , Aterosclerosis/epidemiología , Cráneo , Placa AmiloideRESUMEN
BACKGROUND: Data are limited on the association of metabolic dysfunction-associated fatty liver disease (MAFLD) with systemic atherosclerosis. This study aimed to examine the relationship between MAFLD and the extent of atherosclerotic plaques and stenosis, and presence of polyvascular disease (PolyVD). METHODS: In this cross-sectional study, MAFLD was diagnosed based on the presence of metabolic dysfunction (MD) and fatty liver disease (FLD). MAFLD was divided into three subtypes: MAFLD with diabetes mellitus (DM), MAFLD with overweight or obesity (OW), as well as MAFLD with lean/normal weight and at least two metabolic abnormalities. Atherosclerosis was evaluated, with vascular magnetic resonance imaging for intracranial and extracranial arteries, thoracoabdominal computed tomography angiography for coronary, subclavian, aorta, renal, iliofemoral arteries, and ankle-brachial index for peripheral arteries. The extent of plaques and stenosis was defined according to the number of these eight vascular sites affected. PolyVD was defined as the presence of stenosis in at least two vascular sites. RESULTS: This study included 3047 participants, with the mean age of 61.2 ± 6.7 years and 46.6% of male (n = 1420). After adjusting for potential confounders, MAFLD was associated with higher extent of plaques (cOR, 2.14, 95% CI 1.85-2.48) and stenosis (cOR, 1.47, 95% CI 1.26-1.71), and higher odds of presence of PolyVD (OR, 1.55, 95% CI 1.24-1.94) as compared with Non-MAFLD. In addition, DM-MAFLD and OW-MAFLD were associated with the extent of atherosclerotic plaques and stenosis, and presence of PolyVD (All P < 0.05). However, lean-MAFLD was only associated with the extent of atherosclerotic plaques (cOR, 1.63, 95% CI 1.14-2.34). As one component of MAFLD, FLD per se was associated with the extent of plaques and stenosis in participants with MAFLD. Furthermore, FLD interacted with MD to increase the odds of presence of systemic atherosclerosis (P for interaction ≤ 0.055). CONCLUSIONS: MAFLD and its subtypes of DM-MAFLD and OW-MAFLD were associated with the extent of atherosclerotic plaques and stenosis, and presence of PolyVD. This study implicated that FLD might be a potential target of intervention for reducing the deleterious effects of MAFLD on systemic atherosclerosis.
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Aterosclerosis , Enfermedad del Hígado Graso no Alcohólico , Placa Aterosclerótica , Masculino , Humanos , Persona de Mediana Edad , Anciano , Estudios Transversales , Constricción Patológica , Aterosclerosis/diagnóstico por imagen , Aterosclerosis/epidemiologíaRESUMEN
INTRODUCTION: Cerebral small vessel disease (CSVD) is a significant burden of morbidity and mortality among elderly people around the world. Epidemiological data with complete CSVD evaluations and a large sample size in the general population are still limited. METHODS: Community-dwelling residents in Lishui city in China from the cross-sectional survey of the Polyvascular Evaluation for Cognitive Impairment and Vascular Events (PRECISE) study were included in this study from 2017 to 2019. All participants underwent 3 Tesla brain magnetic resonance images to assess CSVD imaging markers. Demographic and risk factor data were collected. The general and age-specific prevalence of lacune, confluent white matter hyperintensity (WMH), moderate-severe enlarged perivascular spaces (EPVS), cerebral microbleed (CMB), and total CSVD score (an ordinal scale from 0 to 4, counting the presence of four imaging markers of CSVD) was evaluated. Associations between vascular risk factors and these markers were analyzed by multivariable logistic regression. RESULTS: A total of 3,063 participants were enrolled. The mean age was 61.2 years and 46.5% were men. The most prevalent CSVD marker was confluent WMH (16.7%), followed by CMB (10.2%), moderate-severe EPVS in the basal ganglia (BG-EPVS) (9.8%), and lacune (5.6%). 30.5% of the participants have at least one of the four markers (total CSVD score ≥1 points). The prevalence of CSVD markers increases as age increases. Age and hypertension were independent risk factors for four CSVD markers and the total CSVD score. CONCLUSIONS: In this Chinese cohort with community-based adults aged 50-75 years, our findings showed a prevalence of 30.5% for CSVD. The most prevalent CSVD marker was confluent WMH, followed by CMB, moderate-severe BG-EPVS, and lacune. The risk factors for CSVD must be strictly screened and controlled in adults living in the community.
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Enfermedades de los Pequeños Vasos Cerebrales , Masculino , Anciano , Adulto , Humanos , Persona de Mediana Edad , Femenino , Prevalencia , Estudios Transversales , Enfermedades de los Pequeños Vasos Cerebrales/diagnóstico por imagen , Enfermedades de los Pequeños Vasos Cerebrales/epidemiología , Encéfalo , Imagen por Resonancia Magnética , Factores de RiesgoRESUMEN
BACKGROUND: The purpose of this study is to examine the associations of Life's Simple 7 (LS7) with risks of cerebral small vessel disease (CSVD) and its magnetic resonance imaging markers. METHODS: Community-dwelling residents in Lishui city in China from the cross-sectional survey of the PRECISE study (Polyvascular Evaluation for Cognitive Impairment and Vascular Events) were included in this study from 2017 to 2019. LS7 was analyzed as the total score, medical score (derived from the 3 metrics based on medical history and testing), and behavioral score (based on 4 metrics based on behaviors), and categorized as poor, intermediate, or ideal. A CSVD score or a modified CSVD score was derived from 4 magnetic resonance imaging markers (lacunes, microbleeds, perivascular spaces, and white matter hyperintensity) at baseline. Binary logistic regression or ordinal logistic regression model was used to estimate the relationship of LS7 scores with CSVD and magnetic resonance imaging markers. RESULTS: A total of 3061 participants were included in this study. Compared with poor total LS7 score, ideal LS7 total score was associated with reduced adjusted odds of higher CSVD score (common odds ratio [cOR], 0.73 [95% CI, 0.58-0.90]) and higher modified CSVD score (cOR, 0.78 [95% CI, 0.64-0.95]). Compared with poor LS7 medical score, ideal LS7 medical score was associated with reduced adjusted odds of higher CSVD score (cOR, 0.65 [95% CI, 0.53-0.80]) and higher modified CSVD score (cOR, 0.67 [95% CI, 0.56-0.81]). Higher total LS7 score and LS7 medical score were associated with a lower risk of white matter hyperintensities and lacunes. Higher LS7 behavioral score was associated with lower risk of lacunes. CONCLUSIONS: Ideal LS7 score, indicating excellent cardiovascular health, was associated with lower total CSVD burden. Optimizing the risk factors captured by LS7 may reduce the progression of CSVD.
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Enfermedades de los Pequeños Vasos Cerebrales , Biomarcadores , Enfermedades de los Pequeños Vasos Cerebrales/complicaciones , Enfermedades de los Pequeños Vasos Cerebrales/diagnóstico por imagen , Estudios Transversales , Humanos , Imagen por Resonancia Magnética , Factores de RiesgoRESUMEN
BACKGROUND: The aim of this study was to investigate the relationship between serum cystatin C levels and the presence and severity of cerebral small vessel disease (CSVD). METHODS: Community-dwelling residents in the Lishui city in China from the cross-sectional survey of the PRECISE (Poly-Vascular Evaluation for Cognitive Impairment and Vascular Events) cohort study were included in present study from 2017 to 2019. Total CSVD burden and modified total CSVD burden score, as well as the markers of CSVD on magnetic resonance imaging, including white matter hyperintensity, lacunes, cerebral microbleeds, and perivascular spaces, were assessed at baseline survey. Participants were divided into 4 groups according to the quartiles of cystatin C. The association of serum cystatin C with total CSVD burden and imaging markers was analyzed using ordinal or binary logistic regression models. Furthermore, 2-sample Mendelian randomization analysis was performed to investigate the genetically predicted effect of cystatin C on CSVD. RESULTS: A total of 3061 participants were included in this study. The mean age of the participants was 61.2±6.7 years, and 1637 (53.5%) were women. Higher level of cystatin C was associated with an increased total CSVD burden and modified total CSVD burden (Q4 versus Q1: common odds ratio [OR], 1.30 [95% CI, 1.03-1.64] and 1.32 [95% CI, 1.01-1.73]) after adjustment for covariates. Further, compared with the first quartile of cystatin C, subjects in the last quartile had higher risk of lacunes (OR, 1.99 [95% CI, 1.05-3.76]), modified white matter hyperintensity burden (common OR, 1.42 [95% CI, 1.07-1.90]), and moderate-to-severe perivascular spaces (OR, 2.15 [95% CI, 1.29-3.59]) but not cerebral microbleeds. The Mendelian randomization analysis showed that a genetically predicted higher cystatin C level was associated with increased risk of lacunar stroke (OR, 1.16 [95% CI, 1.06-1.27]). CONCLUSIONS: In this community-based study, we found a possible association between cystatin C and CSVD, especially for lacunes, that was independent of estimated glomerular filtration rate.
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Enfermedades de los Pequeños Vasos Cerebrales , Cistatina C , Anciano , Hemorragia Cerebral/complicaciones , Enfermedades de los Pequeños Vasos Cerebrales/diagnóstico por imagen , Enfermedades de los Pequeños Vasos Cerebrales/epidemiología , Estudios de Cohortes , Estudios Transversales , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Insulin resistance is an important cause of cardiovascular events and cerebral infarction development. We aimed to investigate the association of the triglyceride glucose (TyG) index with atherosclerotic burden and plaques in coronary, intra- and extracranial arteries in participants with non-diabetes, and compared the results with that of the homeostasis model assessment of insulin resistance (HOMA-IR). METHODS: Participants without diabetes in the PolyvasculaR Evaluation for Cognitive Impairment and vaScular Events (PRECISE) study were included. We categorized participants by tertiles of the TyG index and the concordance/discordance of the TyG index and HOMA-IR. Discordance was defined as a TyG index equal to or greater than the median and HOMA-IR less than the median, or vice versa. The atherosclerosis plaques and burden in coronary, intra- and extracranial arteries were evaluated. The association of HOMA-IR and TyG index with the presence of atherosclerotic plaques and atherosclerotic burden was assessed by binary and ordinal logistic regression models, respectively. RESULTS: Among 2,719 included participants, the average age was 60.9 (± 6.6) years, and 53.0% were female. Both TyG index and HOMA-IR were associated with increased odds of coronary/intra- and extracranial atherosclerotic plaques and burden after adjustment for age, sex, currenting smoking and drinking (all P < 0.05). However, the association between HOMA-IR and intracranial atherosclerosis was not statistically significant after adjustment for all potential confounders. Discordantly high TyG index with HOMA-IR had a higher odd of extracranial plaque (odds ratio [OR]: 1.34, 95% confidence interval [CI]: 1.04-1.71), extracranial atherosclerotic burden (common odds ratio [cOR]: 1.35, 95% CI 1.06-1.71), coronary plaque (OR: 1.30, 95% CI 1.01-1.68) and segment stenosis score (cOR: 1.39, 95% CI 1.09-1.78) as compared with concordantly low TyG index with HOMA-IR. The TyG index had a better net reclassification improvement ability than HOMA-IR for atherosclerotic plaques when adding to baseline model. CONCLUSION: Elevated TyG index was associated with increased odds of atherosclerosis in coronary/intra- and extracranial arteries. Compared with HOMA-IR, the TyG index was more strongly associated with intracranial atherosclerosis. Moreover, discordantly high TyG index with HOMA-IR was also important for atherosclerosis identification.
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Aterosclerosis , Resistencia a la Insulina , Placa Aterosclerótica , Aterosclerosis/diagnóstico , Aterosclerosis/epidemiología , Biomarcadores , Glucemia , Femenino , Glucosa , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , TriglicéridosRESUMEN
Tanshinone IIa is a key ingredient extracted from the traditional Chinese medicine Salvia miltiorrhiza (Danshen), and is widely used to treat various cardiovascular diseases. Vascular calcification is a common pathological change of cardiovascular tissues in patients with chronic kidney disease, diabetes, hypertension and atherosclerosis. However, whether Tanshinone IIa inhibits vascular calcification and the underlying mechanisms remain largely unknown. This study aims to investigate whether Tanshinone IIa can inhibit vascular calcification using high phosphate-induced vascular smooth muscle cell and aortic ring calcification model, and high dose vitamin D3 (vD3)-induced mouse models of vascular calcification. Alizarin red staining and calcium quantitative assay showed that Tanshinone IIa significantly inhibited high phosphate-induced vascular smooth muscle cell and aortic ring calcification. qPCR and Western blot showed that Tanshinone IIa attenuated the osteogenic transition of vascular smooth muscle cells. In addition, Tanshinone IIa also significantly inhibited high dose vD3-induced mouse aortic calcification and aortic osteogenic transition. Mechanistically, Tanshinone IIa inhibited the activation of NF-κB and ß-catenin signaling in normal vascular smooth muscle cells. Similar to Tanshinone IIa, inhibition of NF-κB and ß-catenin signaling using the chemical inhibitors SC75741 and LF3 attenuated high phosphate-induced vascular smooth muscle cell calcification. These results suggest that Tanshinone IIa attenuates vascular calcification at least in part through inhibition of NF-κB and ß-catenin signaling, and Tanshinone IIa may be a potential drug for the treatment of vascular calcification.
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FN-kappa B , Calcificación Vascular , Animales , Ratones , FN-kappa B/genética , FN-kappa B/metabolismo , beta Catenina/genética , beta Catenina/metabolismo , Transducción de Señal , Miocitos del Músculo Liso/metabolismo , Calcificación Vascular/tratamiento farmacológico , Calcificación Vascular/metabolismo , Fosfatos/metabolismoRESUMEN
KEY MESSAGE: Using a fixed RIL population derived from a widely used foxtail millet backbone breeding line and an elite cultivar, we constructed a high-density bin map and identified six novel multi-environment effect QTLs and seven candidate genes for dwarf phenotype. Plant height is an important trait that determines tradeoffs between competition and resource allocation, which is crucial for yield potential. To improve the C4 model plant foxtail millet (Setaria italica) productivity, it is necessary to isolate plant height-related genes that contribute to ideal plant architecture in breeding. In the present study, we generated a foxtail millet population of 333 recombinant inbred lines (RILs) derived from a cross between a backbone line Ai 88 and an elite cultivar Liaogu 1. We evaluated plant height in 13 environmental conditions across 4 years, the mean plant height of the RIL population ranged from 89.5 to 149.9 cm. Using deep re-sequencing data, we constructed a high-density bin map with 3744 marker bins. Quantitative trait locus (QTL) mapping identified 26 QTLs significantly associated with plant height. Of these, 13 QTLs were repeatedly detected under multiple environments, including six novel QTLs that have not been reported before. Seita.1G242300, a gene encodes gibberellin 2-oxidase-8, which was detected in nine environments in a 1.54-Mb interval of qPH1.3, was considered as an important candidate gene. Moreover, other six genes involved in GA biosynthesis or signaling pathways, and fifteen genes encode F-box domain proteins which might function as E3 ligases, were also considered as candidate genes in different QTLs. These QTLs and candidate genes identified in this study will help to elucidate the genetic basis of foxtail millet plant height, and the linked markers will be useful for marker-assistant selection of varieties with ideal plant architecture and high yield potential.
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Mapeo Cromosómico/métodos , Cromosomas de las Plantas/genética , Regulación de la Expresión Génica de las Plantas , Fitomejoramiento , Proteínas de Plantas/metabolismo , Sitios de Carácter Cuantitativo , Setaria (Planta)/genética , Genoma de Planta , Secuenciación de Nucleótidos de Alto Rendimiento , Proteínas de Plantas/genética , Polimorfismo de Nucleótido Simple , Setaria (Planta)/anatomía & histología , Setaria (Planta)/crecimiento & desarrolloRESUMEN
KEY MESSAGE: Multi-environment QTL mapping identified 23 stable loci and 34 co-located QTL clusters for panicle architecture and grain yield-related traits, which provide a genetic basis for foxtail millet yield improvement. Panicle architecture and grain weight, both of which are influenced by genetic and environmental factors, have significant effects on grain yield potential. Here, we used a recombinant inbred line (RIL) population of 333 lines of foxtail millet, which were grown in 13 trials with varying environmental conditions, to identify quantitative trait loci (QTL) controlling nine agronomic traits related to panicle architecture and grain yield. We found that panicle weight, grain weight per panicle, panicle length, panicle diameter, and panicle exsertion length varied across different geographical locations. QTL mapping revealed 159 QTL for nine traits. Of the 159 QTL, 34 were identified in 2 to 12 environments, suggesting that the genetic control of panicle architecture in foxtail millet is sensitive to photoperiod and/or other environmental factors. Eighty-eight QTL controlling different traits formed 34 co-located QTL clusters, including the triple QTL cluster qPD9.2/qPL9.5/qPEL9.3, which was detected 23 times in 13 environments. Several candidate genes, including Seita.2G388700, Seita.3G136000, Seita.4G185300, Seita.5G241500, Seita.5G243100, Seita.9G281300, and Seita.9G342700, were identified in the genomic intervals of multi-environmental QTL or co-located QTL clusters. Using available phenotypic and genotype data, we conducted haplotype analysis for Seita.2G002300 and Seita.9G064000,which showed high correlations with panicle weight and panicle exsertion length, respectively. These results not only provided a basis for further fine mapping, functional studies and marker-assisted selection of traits related to panicle architecture in foxtail millet, but also provide information for comparative genomics analyses of cereal crops.
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Cromosomas de las Plantas/genética , Grano Comestible/fisiología , Regulación de la Expresión Génica de las Plantas , Fenotipo , Proteínas de Plantas/metabolismo , Sitios de Carácter Cuantitativo , Setaria (Planta)/fisiología , Mapeo Cromosómico/métodos , Grano Comestible/genética , Genoma de Planta , Secuenciación de Nucleótidos de Alto Rendimiento , Proteínas de Plantas/genética , Polimorfismo de Nucleótido Simple , Setaria (Planta)/genéticaRESUMEN
Astragaloside IV (AS#IV) has previously demonstrated antitumoractivity. We investigated the effect and mechanisms of AS#IV in relation to epithelial-mesenchymal transition (EMT), viainterference with the Wnt/ß-catenin signaling pathway in gliomaU251 cells. Induction of glioma U251 cells by transforming growthfactor (TGF)#ß1 activated EMT, including switching E#cadherin toN-cadherin and altering the expression of Wnt/ß-catenin signalingpathway components such as vimentin, ß-catenin, and cyclin-D1.AS-IV inhibited the viability, invasion, and migration of TGF-ß1-induced glioma U251 cells. AS-IV also interfered with the TGF#ß1-induced Wnt/ß-catenin signaling pathway in glioma U251 cells.These findings indicate that AS#IV prohibits TGF#ß1-induced EMTby disrupting the Wnt/ß-catenin pathway in glioma U251 cells. AS#IV may thus be a potential candidate agent for treating glioma andother central nervous system tumors.
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Neoplasias Encefálicas/metabolismo , Transición Epitelial-Mesenquimal/efectos de los fármacos , Glioma/metabolismo , Saponinas/farmacología , Factor de Crecimiento Transformador beta1/farmacología , Triterpenos/farmacología , Vía de Señalización Wnt/efectos de los fármacos , beta Catenina/metabolismo , Antígenos CD/metabolismo , Apoptosis/efectos de los fármacos , Neoplasias Encefálicas/patología , Cadherinas/metabolismo , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Glioma/patología , Humanos , beta Catenina/antagonistas & inhibidoresRESUMEN
Epithelioid hemangioendothelioma (EHE) is a rare malignant angiocentric vascular neoplasm. Around 90% of classic EHE has a t(1;3)(p36;q25) that results in a WWTR1-CAMTA1 fusion gene, a histologically distinctive subset of EHE has been recently shown to have a t(10;14)(p13;q42)that results in a different fusion gene, YAP1-TFE3. Twenty-one cases of TFE3 Rearranged Epithelioid Hemangioendothelioma have been reported in the literature, and only two cases occurred in bone. In the report, we report additional two cases occurred in the femur and skull and review the related literature.