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1.
Heliyon ; 10(14): e34225, 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-39108913

RESUMO

Introduction: Primary Sjögren's syndrome (PSS) is a systemic autoimmune disease that mainly affects exocrine glands. Little is known about PSS associated cervical and intracranial cerebral large-vessel vasculitis outside of individual case reports. Methods: We present 5 cases of ischemic stroke or transient ischemic stroke (TIA) caused by PSS associated cervical and intracranial large-vessel vasculitis. Literature review was performed to summarize and identify the demographic, clinical features, treatment, and prognosis of this condition. Results: The review resulted in 8 included articles with 8 patients, plus our 5 new patients, leading to a total of 13 subjects included in the analysis. The median age was 43 (range, 17-69) years old, among which 69.2 % (9/13) were female, and 92.3 % (12/13) came from Asia. Among them, 84.6 % (11/13) presented with cerebral infarction and 70.0 % (7/10) with watershed infarction. Middle cerebral artery (MCA) (6/13, 46.2 %) and internal carotid artery (ICA) (6/13, 46.2 %) were the most frequently involved arteries. Remarkable vessel wall concentric thickening and enhancement was observed in 57.1 % (4/7) patients and intravascular thrombi was identified in 28.6 % (2/7) patients. Glucocorticoid combined with non-glucocorticoid immunosuppressants (8/12, 66.7 %) were the most often chosen medication therapy and 4 patients received surgical intervention. Conclusion: Asian females are the most vulnerable population to ischemic stroke or TIA due to PSS associated cervical and intracranial large-vessel vasculitis. Cerebral infarctions were characterized by recurrence and watershed pattern. Magnetic resonance vessel wall imaging (MR-VWI) helps to identify the inflammatory pathology of large vessel lesion in PSS.

2.
Acad Radiol ; 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39095262

RESUMO

RATIONALE AND OBJECTIVES: This study aimed to employ deep learning techniques to analyze and validate an automatic prognostic biomarker for predicting outcomes following intracerebral hemorrhage (ICH). MATERIALS AND METHODS: This study included patients with ICH whose onset-to-imaging time (OIT) was less than 6 h. Patients were randomly divided into training and test sets at a 7:3 ratio. Using the Resnet50 deep learning method, we extracted features from the hematoma and perihematomal edema (PHE) areas and constructed a 90-day prognosis prediction model using logistic regression. To evaluate predictive efficacy and clinical significance, we employed logistic regression to train three models: Clinical, Deep Score, and the combined Clinical-Deep Learning (Merge). RESULTS: Our study comprised 1098 patients (652 male, 446 female), with a mean Glasgow Coma Scale (GCS) score of 10. Univariate and multivariate analyses identified age, intraventricular hemorrhage (IVH), hematoma and PHE volume, and admission GCS score as independent prognostic factors. Additionally, 15 deep learning features were retained through LASSO regression. In the training set, the AUC values for the three models were as follows: Clinical model (0.88), Deep Score (0.91), and Merge model (0.94). In the test set, the Merge model exhibited a significantly higher AUC value than the other models. Calibration curves revealed satisfactory calibration of the Merge model nomogram in both training and test sets. CONCLUSION: Our Merge model nomogram is an objective and effective prognostic tool, offering personalized risk assessments for 90-day functional outcomes in patients with ICH.

3.
Stroke Vasc Neurol ; 2024 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-39097332

RESUMO

Mild stroke symptoms are cited as the reason for not using tissue-type plasminogen activator in 29-43% of time-eligible patients. Previous studies suggested that not all of these patients had a good recovery or even survival to hospital discharge. Since then, stroke guidelines worldwide recommended thrombolysis in minor but disabling strokes.Dual antiplatelet treatment with aspirin and clopidogrel was more effective than aspirin alone for reducing subsequent events in patients with minor stroke if started within 24 hours of onset in both CHANCE (Clopidogrel in High-Risk Patients with Acute Non-disabling Cerebrovascular Events) and POINT (Platelet-Oriented Inhibition in New TIA and Minor Ischaemic Stroke) trials. Recently, both PRISMS (The Potential of rtPA for Ischemic Strokes With Mild Symptoms) trial and TEMPO-2(The Potential of rtPA for Ischemic Strokes With Mild Symptoms) trial showed that treatment with thrombolysis versus antiplatelet did not increase the likelihood of favourable functional outcome at 90 days among patients with minor non-disabling acute ischaemic strokes. Therefore, a narrative review on thrombolysis for patients with minor strokes from published studies may help practicing clinicians.

4.
Alzheimers Dement ; 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39023044

RESUMO

INTRODUCTION: Alzheimer's disease (AD) is a devastating neurological disease with complex genetic etiology. Yet most known loci have only identified from the late-onset type AD in populations of European ancestry. METHODS: We performed a two-stage genome-wide association study (GWAS) of AD totaling 6878 Chinese and 63,926 European individuals. RESULTS: In addition to the apolipoprotein E (APOE) locus, our GWAS of two independent Chinese samples uncovered three novel AD susceptibility loci (KIAA2013, SLC52A3, and TCN2) and a novel ancestry-specific variant within EGFR (rs1815157). More replicated variants were observed in the Chinese (31%) than in the European samples (15%). In combining genome-wide associations and functional annotations, EGFR and TCN2 were prioritized as two of the most biologically significant genes. Phenome-wide Mendelian randomization suggests that high mean corpuscular hemoglobin concentration might protect against AD. DISCUSSION: The current study reveals novel AD susceptibility loci, emphasizes the importance of diverse populations in AD genetic research, and advances our understanding of disease etiology. HIGHLIGHTS: Loci KIAA2013, SLC52A3, and TCN2 were associated with Alzheimer's disease (AD) in Chinese populations. rs1815157 within the EGFR locus was associated with AD in Chinese populations. The genetic architecture of AD varied between Chinese and European populations. EGFR and TCN2 were prioritized as two of the most biologically significant genes. High mean corpuscular hemoglobin concentrations might have protective effects against AD.

5.
CNS Neurosci Ther ; 30(7): e14857, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39014454

RESUMO

AIMS: Apply established cerebrospinal fluid (CSF) and serum biomarkers and novel combined indicators based on the amyloid/tau/neurodegeneration (ATN) framework to improve diagnostic and prognostic power in patients with rapidly progressive dementias (RPDs). METHODS: CSF and serum biomarkers of Alzheimer's disease (AD) common neuropathology including Aß42, Aß40, p-Tau, and t-Tau were measured in cognitively normal (CN) controls (n = 33) and three RPD groups with rapidly progressive AD (rpAD, n = 23), autoimmune encephalitis (AE, n = 25), and Creutzfeldt-Jakob disease (CJD, n = 28). Logistic regression and multiple linear regression were used for producing combined indicators and prognostic assessment, respectively, including A&T, A&N, T&N, A&T&N, etc. RESULTS: Combined diagnostic indicator with A&T&N had the potential for differentiating AE from other types of RPDs, identifying 62.51% and 75% of AE subjects based on CSF and serum samples, respectively, compared to 39.13% and 37.5% when using autoantibodies. CSF t-Tau was associated with survival in the CJD group (adjusted R-Square = 0.16, p = 0.02), and its prognosis value improved when using combined predictors based on the ATN framework (adjusted R-Square = 0.273, p = 0.014). CONCLUSION: Combined indicators based on the ATN framework provide a novel perspective for establishing biomarkers for early recognition of RPDs due to treatment-responsive causes.


Assuntos
Peptídeos beta-Amiloides , Biomarcadores , Demência , Progressão da Doença , Proteínas tau , Humanos , Proteínas tau/sangue , Proteínas tau/líquido cefalorraquidiano , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Peptídeos beta-Amiloides/sangue , Prognóstico , Demência/diagnóstico , Demência/sangue , Demência/líquido cefalorraquidiano , Biomarcadores/sangue , Biomarcadores/líquido cefalorraquidiano , Síndrome de Creutzfeldt-Jakob/diagnóstico , Síndrome de Creutzfeldt-Jakob/sangue , Síndrome de Creutzfeldt-Jakob/líquido cefalorraquidiano , Fragmentos de Peptídeos/líquido cefalorraquidiano , Fragmentos de Peptídeos/sangue , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/sangue , Doença de Alzheimer/líquido cefalorraquidiano , Idoso de 80 Anos ou mais
6.
J Chromatogr A ; 1730: 465121, 2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-38959659

RESUMO

Mechanistic models are powerful tools for chromatographic process development and optimization. However, hydrophobic interaction chromatography (HIC) mechanistic models lack an effective and logical parameter estimation method, especially for multi-component system. In this study, a parameter-by-parameter method for multi-component system (called as mPbP-HIC) was derived based on the retention mechanism to estimate the six parameters of the Mollerup isotherm for HIC. The linear parameters (ks,i and keq,i) and nonlinear parameters (ni and qmax,i) of the isotherm can be estimated by the linear regression (LR) and the linear approximation (LA) steps, respectively. The remaining two parameters (kp,i and kkin,i) are obtained by the inverse method (IM). The proposed method was verified with a two-component model system. The results showed that the model could accurately predict the protein elution at a loading of 10 g/L. However, the elution curve fitting was unsatisfactory for high loadings (12 g/L and 14 g/L), which is mainly attributed to the demanding experimental conditions of the LA step and the potential large estimation error of the parameter qmax. Therefore, the inverse method was introduced to further calibrate the parameter qmax, thereby reducing the estimation error and improving the curve fitting. Moreover, the simplified linear approximation (SLA) was proposed by reasonable assumption, which provides the initial guess of qmax without solving any complex matrix and avoids the problem of matrix unsolvable. In the improved mPbP-HIC method, qmax would be initialized by the SLA and finally determined by the inverse method, and this strategy was named as SLA+IM. The experimental validation showed that the improved mPbP-HIC method has a better curve fitting, and the use of SLA+IM reduces the error accumulation effect. In process optimization, the parameters estimated by the improved mPbP-HIC method provided the model with excellent predictive ability and reasonable extrapolation. In conclusion, the SLA+IM strategy makes the improved mPbP-HIC method more rational and can be easily applied to the practical separation of protein mixture, which would accelerate the process development for HIC in downstream of biopharmaceuticals.


Assuntos
Interações Hidrofóbicas e Hidrofílicas , Cromatografia Líquida/métodos , Modelos Lineares , Proteínas/isolamento & purificação , Proteínas/química , Proteínas/análise , Modelos Químicos
7.
Sci Total Environ ; 948: 174896, 2024 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-39047832

RESUMO

Acute ischemic stroke (AIS) is one of the most predominant causes of mortality and disability in China. Significant uncertainties in stroke diagnosis and time of onset have resulted in inconsistent evidence on the association between ambient air pollution and the risk of AIS. The present study aimed to evaluate the impact of air pollution on AIS onset based on high time-resolution air pollution data and a stroke-specific registry across the past five years. Hourly concentrations of PM2.5, PM10, O3, SO2, CO, NO2 and nitrous acid (HONO) were monitored from 2017 to 2021, with which a distributed lag non-linear model and conditional logistic regression models coupled with a time-stratified case-crossover design were applied to 106,623 AIS cases recorded in the Shanghai Stroke Service (4S) database during the study period. Results from the conditional logistic regression models indicate that acute exposure to PM2.5, PM10, SO2, NO2 and HONO was found to be associated with AIS onset, respectively. The corresponding cumulative excessive risks of AIS onset were 0.8 %, 1 %, 2.4 %, 2.1 % and 1.8 % for each interquartile range increase in the respective concentration. The longest lag-effect (up to 13 h) was observed for reactive nitrogen species (RNS), such as NO2 and HONO, which remained robust in two-pollutant models. Similar important role of RNS in AIS onset were confirmed by the distributed lag non-linear model. By demonstrating the transient effect of ambient air pollution on AIS, especially the relationships between RNS and AIS for the first time, our study provides stringent evidence for future mitigation strategies for pollution emission and public health.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , AVC Isquêmico , Espécies Reativas de Nitrogênio , China/epidemiologia , Poluentes Atmosféricos/análise , Poluição do Ar/estatística & dados numéricos , Humanos , AVC Isquêmico/epidemiologia , Material Particulado/análise , Exposição Ambiental/estatística & dados numéricos , Masculino , Feminino , Idoso
8.
J Hazard Mater ; 477: 135321, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-39068886

RESUMO

Rice consumption is a major pathway for human cadmium (Cd) exposure. Understanding Cd behavior in the soil-rice system, especially under field conditions, is pivotal for controlling Cd accumulation. This study analyzed Cd concentrations and isotope compositions (δ114/110Cd) in rice plants and surface soil sampled at different times, along with urinary Cd of residents from typical Cd-contaminated paddy fields in Youxian, Hunan, China. Soil water-soluble Cd concentrations varied across sampling times, with δ114/110Cdwater lighter under drained than flooded conditions, suggesting supplementation of water-soluble Cd by isotopically lighter Cd pools, increasing Cd phytoavailability. Both water-soluble Cd and atmospheric deposition contributed to rice Cd accumulation. Water-soluble Cd's contribution increased from 28-52% under flooded to 58-87% under drained conditions due to increased soil Cd phytoavailability. Atmospheric deposition's contribution (12-72%) increased with potential atmospheric deposition flux among sampling areas. The enrichment of heavy Cd isotopes occurred from root-stem-grain to prevent rice Cd accumulation. The different extent of enrichment of heavy isotopes in urine indicated different Cd exposure sources. These findings provide valuable insights into the speciation and phytoavailability changes of Cd in the soil-rice system and highlight the potential application of Cd isotopic fingerprinting in understanding the environmental fate of Cd.


Assuntos
Cádmio , Oryza , Poluentes do Solo , Oryza/metabolismo , Oryza/química , Cádmio/análise , Cádmio/metabolismo , Poluentes do Solo/metabolismo , Poluentes do Solo/análise , China , Solo/química , Humanos , Isótopos , Raízes de Plantas/metabolismo , Raízes de Plantas/química , Monitoramento Ambiental , Fracionamento Químico
9.
Nat Commun ; 15(1): 5924, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39009607

RESUMO

The genetic contribution of protein-coding variants to immune-mediated diseases (IMDs) remains underexplored. Through whole exome sequencing of 40 IMDs in 350,770 UK Biobank participants, we identified 162 unique genes in 35 IMDs, among which 124 were novel genes. Several genes, including FLG which is associated with atopic dermatitis and asthma, showed converging evidence from both rare and common variants. 91 genes exerted significant effects on longitudinal outcomes (interquartile range of Hazard Ratio: 1.12-5.89). Mendelian randomization identified five causal genes, of which four were approved drug targets (CDSN, DDR1, LTA, and IL18BP). Proteomic analysis indicated that mutations associated with specific IMDs might also affect protein expression in other IMDs. For example, DXO (celiac disease-related gene) and PSMB9 (alopecia areata-related gene) could modulate CDSN (autoimmune hypothyroidism-, psoriasis-, asthma-, and Graves' disease-related gene) expression. Identified genes predominantly impact immune and biochemical processes, and can be clustered into pathways of immune-related, urate metabolism, and antigen processing. Our findings identified protein-coding variants which are the key to IMDs pathogenesis and provided new insights into tailored innovative therapies.


Assuntos
Sequenciamento do Exoma , Proteínas Filagrinas , Humanos , Masculino , Feminino , Adulto , Predisposição Genética para Doença/genética , Pessoa de Meia-Idade , Doenças do Sistema Imunitário/genética , Análise da Randomização Mendeliana , Mutação , Proteômica , Variação Genética , Asma/genética , Asma/imunologia , Idoso , Dermatite Atópica/genética , Dermatite Atópica/imunologia
11.
Nat Hum Behav ; 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38987357

RESUMO

Recent expansion of proteomic coverage opens unparalleled avenues to unveil new biomarkers of Alzheimer's disease (AD). Among 6,361 cerebrospinal fluid (CSF) proteins analysed from the ADNI database, YWHAG performed best in diagnosing both biologically (AUC = 0.969) and clinically (AUC = 0.857) defined AD. Four- (YWHAG, SMOC1, PIGR and TMOD2) and five- (ACHE, YWHAG, PCSK1, MMP10 and IRF1) protein panels greatly improved the accuracy to 0.987 and 0.975, respectively. Their superior performance was validated in an independent external cohort and in discriminating autopsy-confirmed AD versus non-AD, rivalling even canonical CSF ATN biomarkers. Moreover, they effectively predicted the clinical progression to AD dementia and were strongly associated with AD core biomarkers and cognitive decline. Synaptic, neurogenic and infectious pathways were enriched in distinct AD stages. Mendelian randomization did not support the significant genetic link between CSF proteins and AD. Our findings revealed promising high-performance biomarkers for AD diagnosis and prediction, with implications for clinical trials targeting different pathomechanisms.

12.
Nat Commun ; 15(1): 5540, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956042

RESUMO

Iron plays a fundamental role in multiple brain disorders. However, the genetic underpinnings of brain iron and its implications for these disorders are still lacking. Here, we conduct an exome-wide association analysis of brain iron, measured by quantitative susceptibility mapping technique, across 26 brain regions among 26,789 UK Biobank participants. We find 36 genes linked to brain iron, with 29 not being previously reported, and 16 of them can be replicated in an independent dataset with 3,039 subjects. Many of these genes are involved in iron transport and homeostasis, such as FTH1 and MLX. Several genes, while not previously connected to brain iron, are associated with iron-related brain disorders like Parkinson's (STAB1, KCNA10), Alzheimer's (SHANK1), and depression (GFAP). Mendelian randomization analysis reveals six causal relationships from regional brain iron to brain disorders, such as from the hippocampus to depression and from the substantia nigra to Parkinson's. These insights advance our understanding of the genetic architecture of brain iron and offer potential therapeutic targets for brain disorders.


Assuntos
Encéfalo , Sequenciamento do Exoma , Ferro , Humanos , Ferro/metabolismo , Encéfalo/metabolismo , Masculino , Feminino , Análise da Randomização Mendeliana , Estudo de Associação Genômica Ampla , Doença de Parkinson/genética , Doença de Parkinson/metabolismo , Pessoa de Meia-Idade , Predisposição Genética para Doença/genética , Idoso , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Adulto , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo
13.
World J Clin Cases ; 12(19): 3800-3806, 2024 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-38994310

RESUMO

BACKGROUND: Hypocalcemia is highly common in hospitalized patients, especially in those with trauma, On the other hand, abnormal calcium metabolism is an important metabolic challenge; however, it is often neglected and untreated, and certain factors may induce serious neurological and cardiovascular complications. AIM: To retrospectively analyze the impact of hypocalcemia on the prognosis of patients with multiple traumas. METHODS: The study was conducted from January 2020 to December 2021. Ninety-nine patients with multiple injuries were treated at the critical care medicine department of Fuyang People's Hospital. The selected indicators included sex, age, and blood calcium and hematocrit levels. Many indicators were observed, including within 24 h of hospitalization, and the prognosis was collected after 28 d. Based on the blood calcium levels, the patients were divided into the following two groups: Normocalcemia and hypocalcemia. Of the 99 patients included, 81 had normocalcemia, and 18 had hypocalcemia. Separate experiments were conducted for these two groups. RESULTS: There was an association between serum calcium levels and the prognosis of patients with polytrauma. CONCLUSION: Clinically, the prognosis of patients with multiple traumas can be preliminarily evaluated based on serum calcium levels.

14.
J Affect Disord ; 362: 323-333, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-38971194

RESUMO

BACKGROUND: Shift work is associated with susceptibility to several neuropsychiatric disorders. This study aims to investigate the effect of shift work on the incidence of neuropsychiatric disorders, and highlighting how individual variability may influence the association. METHODS: UK Biobank participants with employment information were included. Cox survival was conducted in main and subgroup analyses. Correlation analyses explored the impact of shift work on brain structures, and mediation analyses were performed to elucidate the shared underlying mechanisms. Shift work tolerance was evaluated through survival analyses contrasting the risks associated with five neuropsychiatric disorders in shift versus non-shift workers across different demographic or occupational strata. RESULTS: The analysis encompassed 254,646 participants. Shift work was associated with higher risk of dementia (HR 1.29, 95 % CI 1.10-1.52), anxiety (1.08, 1.01-1.15), depression (1.29, 1.22-1.36), and sleep disorders (1.18, 1.09-1.28), but not stroke (p = 0.20). Shift work was correlated with decreasing volume of various brain regions, particularly in thalamus, lateral orbitofrontal, and middle temporal. Mediation analysis revealed that increased immune response and glucose levels are common pathways linking shift work to these disorders. We observed diversity in shift work tolerance across different individual characteristics, among which socioeconomic status and length of working hours were the most essential. LIMITATIONS: Self-reported employment information may cause misclassification and recall bias. And since we focused on the middle-aged population, the conclusions may not be representative of younger or older populations. CONCLUSIONS: Our findings indicated the need to monitor shift worker health and provide personalized management to help adapt to shift work.


Assuntos
Jornada de Trabalho em Turnos , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Jornada de Trabalho em Turnos/efeitos adversos , Reino Unido/epidemiologia , Adulto , Incidência , Idoso , Demência/epidemiologia , Tolerância ao Trabalho Programado/fisiologia , Ansiedade/epidemiologia , Transtornos do Sono-Vigília/epidemiologia , Encéfalo/fisiopatologia , Transtornos Mentais/epidemiologia , Depressão/epidemiologia
15.
J Chromatogr A ; 1731: 465156, 2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-39047442

RESUMO

The single-component Mollerup model, with over 40 direct applications and 442 citations, is the most widely used activity model for chromatographic mechanistic modeling. Many researchers have extended this formula to multi-component systems by directly adding subscripts, a modification deemed thermodynamically inconsistent (referred to as the reference model). In this work, we rederived the asymmetric activity model for multi-component systems, using the van der Waals equation of state, and termed it the multi-component Mollerup model. In contrast to the reference model, our proposed model accounts for the contributions of all components to the activity. Three numerical experiments were performed to investigate the impact of the three different activity models on the chromatographic modeling. The results indicate that our proposed model represents a thermodynamically consistent generalization of the single-component Mollerup model to multi-component systems. This communication advocates adopting of the multi-component Mollerup model for activity modeling in multi-component chromatographic separation to enhance thermodynamic consistency.


Assuntos
Termodinâmica , Modelos Químicos , Cromatografia/métodos , Modelos Teóricos
16.
Chin Med J (Engl) ; 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-39048312

RESUMO

ABSTRACT: Vascular cognitive impairment (VCI) encompasses a wide spectrum of cognitive disorders, ranging from mild cognitive impairment to vascular dementia. Its diagnosis relies on thorough clinical evaluations and neuroimaging. VCI predominately arises from vascular risk factors (VRFs) and cerebrovascular disease, either independently or in conjunction with neurodegeneration. Growing evidence underscores the prevalence of VRFs, highlighting their potential for early prediction of cognitive impairment and dementia in later life. The precise mechanisms linking vascular pathologies to cognitive deficits remain elusive. Chronic cerebrovascular pathology is the most common neuropathological feature of VCI, often interacting synergistically with neurodegenerative processes. Current research efforts are focused on developing and validating reliable biomarkers to unravel the etiology of vascular brain changes in VCI. The collaborative integration of these biomarkers into clinical practice, alongside routine incorporation into neuropathological assessments, presents a promising strategy for predicting and stratifying VCI. The cornerstone of VCI prevention remains the control of VRFs, which includes multi-domain lifestyle modifications. Identifying appropriate pharmacological approaches is also of paramount importance. In this review, we synthesize recent advancements in the field of VCI, including its definition, determinants of vascular risk, pathophysiology, neuroimaging and fluid-correlated biomarkers, predictive methodologies, and current intervention strategies. Increasingly evident is the notion that more rigorous research for VCI, which arises from a complex interplay of physiological events, is still needed to pave the way for better clinical outcomes and enhanced quality of life for affected individuals.

17.
J Cereb Blood Flow Metab ; : 271678X241242911, 2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-39054948

RESUMO

After stroke onset, ischemic brain tissue will progress to infarction unless blood flow is restored. Core growth rate measures the infarction speed from stroke onset. This multicenter cohort study aimed to explore whether core growth rate influences benefit from the reperfusion treatment of endovascular thrombectomy in large ischemic core stroke patients. It identified 134 patients with large core volume >70 mL assessed on brain perfusion image within 9 hours of stroke onset. Of 134 patients, 71 received endovascular thrombectomy and 63 did not receive the treatment. Overall, poor outcomes were frequent, with 3-month severed disability or death rate at 56% in treatment group and 68% in no treatment group (p = 0.156). Patients were then stratified by core growth rate. For patients with 'ultrafast core growth' of >70 mL/hour, rates of poor outcome were especially high in patients without endovascular thrombectomy (n = 13/14, 93%) and relatively lower in patients received the treatment (n = 12/20, 60%, p = 0.033). In contrast, for patients with core growth rate <70 mL/hour, there was not a large difference in poor outcomes between patients with and without the treatment (55% vs. 61%, p = 0.522). Therefore, patients with 'ultrafast core growth' might stand to benefit the most from endovascular treatment.

18.
BMC Neurol ; 24(1): 258, 2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-39054468

RESUMO

OBJECTIVE: Cerebral artery dissection (CeAD) is a rare but serious disease. Genetic risk assessment for CeAD is lacking in Chinese population. We performed genome-wide association study (GWAS) and computed polygenic risk score (PRS) to explore genetic susceptibility factors and prediction model of CeAD based on patients in Huashan Hospital. METHODS: A total of 210 CeAD patients and 280 controls were enrolled from June 2017 to September 2022 in Department of Neurology, Huashan Hospital, Fudan University. We performed GWAS to identify genetic variants associated with CeAD in 140 CeAD patients and 210 control individuals according to a case and control 1:1.5 design rule in the training dataset, while the other 70 patients with CeAD and 70 controls were used as validation. Then Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) enrichment analyses were utilized to identify the significant pathways. We constructed a PRS by capturing all independent GWAS SNPs in the analysis and explored the predictivity of PRS, age, and sex for CeAD. RESULTS: Through GWAS analysis of the 140 cases and 210 controls in the training dataset, we identified 13 leading SNPs associated with CeAD at a genome-wide significance level of P < 5 × 10- 8. Among them, 10 SNPs were annotated in or near (in the upstream and downstream regions of ± 500Kb) 10 functional genes. rs34508376 (OR2L13) played a suggestive role in CeAD pathophysiology which was in line with previous observations in aortic aneurysms. The other nine genes were first-time associations in CeAD cases. GO enrichment analyses showed that these 10 genes have known roles in 20 important GO terms clustered into two groups: (1) cellular biological processes (BP); (2) molecular function (MF). We used genome-wide association data to compute PRS including 32 independent SNPs and constructed predictive model for CeAD by using age, sex and PRS as predictors both in training and validation test. The area under curve (AUC) of PRS predictive model for CeAD reached 99% and 95% in the training test and validation test respectively, which were significantly larger than the age and sex models of 83% and 86%. CONCLUSIONS: Our study showed that ten risk loci were associated with CeAD susceptibility, and annotated functional genes had roles in 20 important GO terms clustered into biological process and molecular function. The PRS derived from risk variants was associated with CeAD incidence after adjusting for age and sex both in training test and validation.


Assuntos
Povo Asiático , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Herança Multifatorial , Polimorfismo de Nucleotídeo Único , Humanos , Estudo de Associação Genômica Ampla/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Herança Multifatorial/genética , Predisposição Genética para Doença/genética , Polimorfismo de Nucleotídeo Único/genética , Povo Asiático/genética , China/epidemiologia , Aneurisma Intracraniano/genética , Aneurisma Intracraniano/epidemiologia , Dissecção Aórtica/genética , Dissecção Aórtica/epidemiologia , Dissecção Aórtica/diagnóstico , Estudos de Casos e Controles , Medição de Risco/métodos , População do Leste Asiático
19.
Small ; : e2404129, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38940500

RESUMO

The synthesis, crystal structure and room-temperature phosphorescence (RTP) of a 2D metal-free inorganic covalent framework ((H2en) [B5O8(OH)], named as CityU-12, and en represents for ethylenediamine) are reported. The precise structure information of CityU-12 has been disclosed through both single-crystal X-ray diffraction (SCXRD) analysis and low-dose high-resolution transmission electron microscopy (LD-HRTEM) study. The SCXRD results show that CityU-12 composes of 2D anionic B─O-based covalent inorganic frameworks with protonated ethylenediamine locating in the pore sites of 2D B─O layers while LD-HRTEM suggests that CityU-12 has an interplanar distance of 0.60 nm for (00 2 ¯ $\bar{2}$ ) crystal plane and 0.60 nm for (10 1 ¯ $\bar{1}$ ) crystal plane. The optical studies show that CityU-12 is an excellent nonconventional RTP material with the emission peak at 530 nm and a lifetime of 1.5 s. The quantum yield is 84.6% and the afterglow time is as long as 2.5 s. This work demonstrates that metal-free B─O frameworks can be promising nonconventional phosphors for RTP.

20.
Artigo em Inglês | MEDLINE | ID: mdl-38861323

RESUMO

PURPOSE: To investigate the factors affecting footplate position and its influence on vault characteristics following implantable collamer lens (ICL) implantation. SETTING: Hunan Provincial People's Hospital, Changsha, China. DESIGN: Retrospective case series. METHODS: This study included 124 patients (124 eyes). Ultrasound biomicroscopy (UBM) was performed to assess the iris and ciliary body morphologies and observe the footplate position. Using multiple linear regression, the relationship between various ocular and ICL parameters and the vault as well as the factors affecting the footplate distance (FD) were analyzed. Based on the FD, three groups were formed: group 1 (<500 µm), group 2 (500-1000 µm), and group 3 (>1000 µm). The distribution of the vault range after surgery was observed for the three groups. RESULTS: Ciliary sulcus angle and FD significantly impacted the vault (adjusted R2=0.190, F=6.763, P<0.001), with FD being the most important factor influencing the vault (Beta=-0.383, P<0.001). Postoperative UBM revealed that the footplate was located at different positions in the posterior chamber, with the majority (52%) being located on the ciliary body. The average size of the four footplate orientations was 0.88±0.24 mm. Multiple linear regression analysis revealed that ciliary body thickness (CBT), iris curvature (IC), and ICL iris contact length (IRCL) significantly influenced the FD (adjusted R2=0.373, F=11.432, P<0.001). The vault range differed significantly among the three groups (X2=32.33, P<0.001). CONCLUSIONS: Different postoperative ICL footplate positions significantly affect the vault. CBT, IC, and IRCL can alter the position of the footplate from the expected position. This study provides reference for ICL size selection and vault prediction.

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