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BACKGROUND: To analyze the real-world growth pattern of very premature infants (VPI) with small for gestational age (SGA) after birth by using the ΔZ value of weight at discharge. METHODS: The clinical data were collected from 28 hospitals in China from September 2019 to December 2020. They were divided into the EUGR(Extrauterine Growth Restriction) and the non-EUGR group according to the criterion of ΔZ value of weight at discharge < -1.28. RESULTS: This study included 133 eligible VPI with SGA. Following the criterion of ΔZ value, the incidence of EUGR was 36.84% (49/133). The birth weight, the 5-min Apgar score, and the proportion of male infants in the EUGR group were lower (P < 0.05). The average invasive ventilation time, cumulative duration of the administration of antibiotics, blood transfusion time, blood transfusion ratio, and total days of hospitalization were significantly higher in the EUGR group (P < 0.05). In the EUGR group, several factors exhibited higher values (P < 0.05), including the initiation of enteral feeding, the volume of milk supplemented with human milk fortifier (HMF), the duration to achieve complete fortification, the cumulative duration of fasting, the duration to achieve full enteral feeding, the length of parenteral nutrition (PN), the number of days required to attain the desired total calorie intake and oral calorie intake, as well as the age at which birth weight was regained. The average weight growth velocity (GV) was significantly lower in the EUGR group (P < 0.001). The incidences of patent ductus arteriosus with hemodynamic changes (hsPDA), neonatal necrotizing enterocolitis (NEC) stage≥ 2, late-onset sepsis (LOS), and feeding intolerance (FI) in the EUGR group were higher (P < 0.05). Multivariate logistic regression analysis showed that birth weight, male, and GV were the protective factors, while a long time to achieve full-dose fortification, slow recovery of birth weight, and NEC stage ≥2 were the independent risk factors. CONCLUSION: SGA in VPI can reflect the occurrence of EUGR more accurately by using the ΔZ value of weight at discharge. Enhancing enteral nutrition support, achieving prompt and complete fortification of breast milk, promoting greater GV, reducing the duration of birth weight recovery, and minimizing the risk of NEC can contribute to a decreased occurrence of EUGR. TRIAL REGISTRATION: CHICTR, ChiCTR1900023418. Registered 26/05/2019, http://www.chictr.org.cn .
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Doenças do Recém-Nascido , Doenças do Prematuro , Feminino , Lactente , Masculino , Recém-Nascido , Humanos , Peso ao Nascer , Idade Gestacional , China/epidemiologia , Leite Humano , Recém-Nascido PrematuroRESUMO
Alzheimer's disease (AD) and dementia are the most worrying health problems faced by people globally today. Although the pathological features of AD consisting of amyloid-beta (Aß) plaques in the extracellular space (ECS) and intracellular tau tangles are well established, the developed medicines targeting these two proteins have not obtained the expected clinical effects. Photobiomodulation (PBM) describes the therapeutic use of red light (RL) or near-infrared light (NIR) to serve as a noninvasive neuroprotective strategy for brain diseases. The present review discusses the mechanisms of the photoelectric coupling effect (light energy-induced special electronic transition-related alterations in protein structure) of PBM on reducing Aß toxicity. On the one hand, RL or NIR can directly disassemble Aß in vitro and in vivo. On the other hand, formaldehyde (FA)-inhibited catalase (CAT) and H2O2-inactived formaldehyde dehydrogenase (FDH) are formed a vicious circle in AD; however, light energy not only activates FDH to degrade excessive FA (which crosslinks Aß monomer to form Aß oligomers and senile plaques) but also sensitizes CAT to reduce hydrogen peroxide levels (H2O2, which can facilitate Aß aggregation and enhance FA generation). In addition, it also activates mitochondrial cytochrome-c to produce ATP in the neurons. Clinical trials of phototherapeutics or oral coenzyme Q10 have shown positive effects in AD patients. Hence, a promising strategy combined PBM with nanopacked Q10 has been proposed to apply for treating AD.
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Doença de Alzheimer , Humanos , Doença de Alzheimer/radioterapia , Doença de Alzheimer/tratamento farmacológico , Peróxido de Hidrogênio , Peptídeos beta-Amiloides/química , Peptídeos beta-Amiloides/metabolismo , Peptídeos beta-Amiloides/uso terapêutico , Catalase , LuzRESUMO
BACKGROUND: Stroke is a leading cause of death and functional impairment in older people. To assess the prospective association between fasting blood glucose-to-glycated hemoglobin ratio and all-cause mortality and poor prognosis in stroke patients. METHODS: A total of 971 Chinese inpatients with acute stroke (mean age of 65.7) were consecutively enrolled in the prospective clinical study and followed up for 12 months after discharge. Stress hyperglycemia was measured using the ratio of fasting blood glucose (FBG, mmol/L)/glycated hemoglobin (HbA1c, %). The primary outcome was all-cause mortality, and secondary outcomes were poor prognosis defined as infectious complications, a National Institutes of Health Stroke Scale (NIHSS) score ≥ 6, a Barthel Index score ≤ 60, or a modified Rankin Scale (mRS) score of 3-6, presented as multivariate-adjusted odds ratios (ORs) with 95% confidence intervals (CIs) across the quartiles of the FBG/HbA1c ratio. RESULTS: There were 35 (4.1%) all-cause deaths at 3 months and 85 (11.4%) at 12 months. The inpatients with the highest quartile of the FBG/HbA1c ratio had a higher risk of all-cause death at 3 months (adjusted OR: 5.16, 95% CI: 1.03-25.74) and at 12 months (adjusted OR: 2.59, 95% CI: 1.14-5.89)) and a higher risk of infectious complications (adjusted OR 2.37, 95% CI 1.27-4.43) and dysfunction (adjusted OR 1.79, 95% CI 1.06-3.01) during hospitalization than inpatients with the lowest quartile. CONCLUSIONS: Stress hyperglycemia, measured by the FBG/HbA1c ratio, was associated with an increased risk of adverse outcomes, including all-cause death, infectious complications, and dysfunction after stroke.
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Hiperglicemia , Acidente Vascular Cerebral , Idoso , Glicemia , China/epidemiologia , Jejum , Seguimentos , Hemoglobinas Glicadas , Hospitais , Humanos , Hiperglicemia/diagnóstico , Pacientes Internados , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/terapiaRESUMO
BACKGROUND: Biallelic mutations in the MYORG gene were first identified as the cause of recessively inherited primary familial brain calcification. Interestingly, some heterozygous carriers also exhibited brain calcifications. OBJECTIVES: To further investigate the role of single heterozygous MYORG mutations in the development of brain calcifications. METHODS: A nation-wide cohort of Chinese primary familial brain calcification probands was enrolled from March 2016 through September 2019. Mutational analysis of MYORG was performed in 435 primary familial brain calcification probands who were negative for mutations in the other four known primary familial brain calcification-causative genes (SLC20A2, PDGFRB, PDGFB, and XPR1). RESULTS: Biallelic MYORG mutations were identified in 14 primary familial brain calcification patients from 10 unrelated families. Interestingly, 12 heterozygous carriers from seven of these families also exhibited mild-to-moderate brain calcifications. Moreover, single heterozygous mutations were detected in an additional 9 probands and in 7 of their family members affected with brain calcifications. In our cohort, clinical and imaging penetrance of individuals with biallelic mutations were 100%, whereas among individuals with heterozygous mutations, penetrance of imaging phenotype was reduced to 73.7% (28 of 38) and clinical penetrance was much lower. Most (34 of 38) remained asymptomatic whereas 4 carriers had symptoms of uncertain clinical significance (nonspecific depression, epilepsy and late-onset parkinsonism). Compared with individuals with biallelic MYORG mutations, individuals with heterozygous mutations had brain calcifications with much lower calcification scores (P < 2e-16). CONCLUSIONS: Presence of brain calcifications in individuals with heterozygous MYORG mutations suggested a semidominant inheritance pattern with incomplete penetrance. This finding further expanded the genotype-phenotype correlations of MYORG-related primary familial brain calcification. © 2020 International Parkinson and Movement Disorder Society.
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Encefalopatias , Glicosídeo Hidrolases/genética , Encéfalo/diagnóstico por imagem , Encefalopatias/diagnóstico por imagem , Encefalopatias/genética , Heterozigoto , Humanos , Mutação/genética , Linhagem , Receptor do Retrovírus Politrópico e XenotrópicoRESUMO
BACKGROUND: Very recently, the MYORG gene was identified as a novel causative gene for autosomal-recessive primary familial brain calcification. OBJECTIVE: To investigate the clinical, genetic, and neuroradiological characteristics of primary familial brain calcification patients with biallelic MYORG mutations in China. METHODS: We collected clinical and neuroradiological data of 169 Chinese patients with primary familial brain calcification, including 151 sporadic patients and 18 patients from 13 families compatible with an autosomal-recessive mode of inheritance. Mutational analysis of MYORG was performed in the cohort. RESULTS: We identified four, including three novel, MYORG mutations segregating in four families with 5 patients: one nonsense mutation (c.1431C>A, p.Y477*), one missense mutation (c.687G>T, p.W229C), and two nonframeshift indels (c.348_349insCTGGCCTTCCGC, p.116_117insLAFR; c. 428_442delTGCACTTCTTCATCC, p.143_147delLHFFI). The 12-base-pair insertion, c.348_349insCTGGCCTTCCGC, was found in either homozygous or heterozygous state in 2 probands of our cohort and another Chinese primary familial brain calcification patient previously reported on in the literature. Haplotype analysis of our patients harboring the insertion indicated a founder effect in the ethnic Han Chinese population. To date, biallelic MYORG mutations have been reported in 17 patients (including our cohort). Most patients were symptomatic (13 of 17; 76.5%), and the most recurrent symptoms were movement disorders (10 of 17; 58.8%), cognitive decline (7 of 17; 41.2%), and cerebellar symptoms (6 of 17; 35.3%). All patients had calcifications on comprehensive cranial CT, most frequently located in the basal ganglia (17 of 17; 100%), cerebellum (17 of 17; 100%), subcortical white matter (14 of 17; 82.4%), and thalamus (13 of 17; 76.5%). CONCLUSIONS: We confirmed MYORG as a novel causative gene for primary familial brain calcification and further expanded the mutational and phenotypic spectrum of MYORG-related primary familial brain calcification. © 2018 International Parkinson and Movement Disorder Society.
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Encefalopatias/genética , Calcinose/genética , Glicosídeo Hidrolases/genética , Mutação/genética , Proteínas Cotransportadoras de Sódio-Fosfato Tipo III/genética , Adulto , Gânglios da Base/patologia , China , Estudos de Coortes , Análise Mutacional de DNA/métodos , Feminino , Heterozigoto , Humanos , Masculino , Doenças Neurodegenerativas/genética , LinhagemRESUMO
BACKGROUND: The effect of prior antiplatelet (AP) therapy on the risk of hemorrhagic transformation (HT), and on functional outcomes of acute ischemic stroke (AIS) after intravenous thrombolysis (IVT), is not known. We performed a retrospective analysis to determine whether history of AP therapy is associated with post-thrombolysis HT and poor prognosis in AIS patients. METHODS: Data pertaining to 145 patients with AIS, who underwent IVT between October 2008 and January 2015, were analyzed. The patients were divided into 2 groups based on whether or not they had received prior AP therapy. Neurological outcomes at 24 hours and 3 months after IVT therapy were assessed. Intergroup difference in cost of treatment was also evaluated. A multivariate logistic regression model was used to identify independent predictors of post-thrombolysis HT. RESULTS: Among 145 patients, 23 (15.8%) had received prior AP therapy. On multivariate analyses, older age (odds ratio [OR]: 1.084; confidence interval [CI], 1.028-1.144) and prior AP therapy (OR: 3.318; CI, 1.172-9.398) were found to be independent predictors of HT. CONCLUSION: In this study, prior AP therapy was independently associated with post-thrombolysis HT in AIS.
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Isquemia Encefálica/tratamento farmacológico , Fibrinolíticos/efeitos adversos , Hemorragias Intracranianas/induzido quimicamente , Inibidores da Agregação Plaquetária/efeitos adversos , Acidente Vascular Cerebral/tratamento farmacológico , Terapia Trombolítica/efeitos adversos , Fatores Etários , Idoso , Isquemia Encefálica/diagnóstico , Feminino , Fibrinolíticos/administração & dosagem , Humanos , Infusões Intravenosas , Hemorragias Intracranianas/diagnóstico , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Inibidores da Agregação Plaquetária/administração & dosagem , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Fatores de Tempo , Resultado do TratamentoRESUMO
Background: Allergic rhinitis (AR) is a pervasive global health issue, and currently, there is a scarcity of targeted drug therapies available. This study aims to identify potential druggable target genes for AR using Mendelian randomization (MR) analysis. Methods: MR analysis was conducted to assess the causal effect of expression quantitative trait loci (eQTL) in the blood on AR. Data on AR were collected from 2 datasets: FinnGen(R9) (11,009 cases and 359,149 controls) and UK Biobank (25,486 cases and 87,097 controls). Colocalization analysis was utilized to assess the common causal genetic variations between the identified drug target genes and AR. We also employed available genome-wide association studies (GWAS) data to gauge the impact of druggable genes on AR biomarkers and other allergic diseases. Results: This study employs MR to analyze the relationship between 3410 druggable genes and AR. After Bonferroni correction, 10 genes were found to be significantly associated with AR risk (P < 0.05/3410). Colocalization analysis revealed a significant causal relationship between the expression variation of CFL1 and EFEMP2 genes and AR, sharing direct causal variants (colocalization probability PP.H3 + PP.H4 > 0.8), highlighting their importance as potential therapeutic targets for AR. The CFL1 gene showed a causal link with levels of thymic stromal lymphopoietin (TSLP), eosinophil count, and interleukin-13 (IL-13) (P = 0.016, 7.45E-16, 0.00091, respectively). EFEMP2 was also causally related to eosinophil count, IL-13, and interleukin-17 (IL-17) (P = 0.00012, 0.00091, 0.032, respectively). PheWAS analysis revealed significant associations of CFL1 with asthma, whereas EFEMP2 showed associations with both asthma and eczema. Protein-Protein Interaction (PPI) network analysis further unveiled the direct interactions of EFEMP2 and CFL1 with proteins related to immune regulation and inflammatory responses, with 77.64% of the network consisting of direct bindings, indicating their key roles in modulating AR-related immune and inflammatory responses. Notably, there was an 8.01% significant correlation between immune-related pathways and genes involved in inflammatory responses. Conclusion: These genes present notable associations with AR biomarkers and other autoimmune diseases, offering valuable targets for developing new AR therapies.
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Background: Despite the increasing availability of therapeutic drugs for autoimmune diseases, many patients still struggle to achieve their treatment goals. Our aim was to identify whether drugs originally used to treat bone density could be applied to the treatment of autoimmune diseases through Mendelian randomization (MR). Methods: Using summary statistics from genome-wide association studies, we used a two-sample MR design to estimate the correlation between autoimmune diseases and BMD-related drug targets. Data from the DrugBank and ChEMBL databases were used to identify the drug targets of anti-osteoporosis medications. The Wald ratio test or inverse-variance weighting method was used to assess the impact of genetic variation in drug target(s) on autoimmune disease therapy. Results: Through our analysis, we discovered a negative correlation between genetic variability in a specific gene (ESR1) in raloxifene/colecalciferol and various autoimmune disorders such as ankylosing spondylitis, endometriosis, IgA nephropathy, rheumatoid arthritis, sarcoidosis, systemic lupus erythematosus, and type 1 diabetes. Conclusion: These results indicate a possible link between genetic differences in the drug targeting ESR1 and susceptibility to autoimmune disorders. Hence, our study offers significant support for the possible use of drugs targeting ESR1 for the management of autoimmune disorders. MR and drug repurposing are utilized to investigate the relationship between autoimmune diseases and bone mineral density, with a focus on ESR1.
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Alzheimer's disease (AD), which is a prevailing type of dementia, presents a significant global health concern. The current therapies do not meet clinical expectations. Amyloid-beta (Aß) has been found to induce endogenous formaldehyde (FA) accumulation by inactivating FA dehydrogenase (FDH); in turn, excessive FA triggers Aß aggregation that eventually leads to AD onset. Hence, scavenging FA by astaxanthin (ATX, a strong exogenous antioxidant) may be pursued as a promising disease-modifying approach. Here, we report that liposomal nanoparticles coupled with PEG (PEG-ATX@NPs) could enhance water-solubility of ATX and alleviate cognitive impairments by scavenging FA and reducing Aß deposition. To enable drug delivery to the brain, liposomes were used to encapsulate ATX and then coupled with PEG, which produced liposomal nanoparticles (PEGATX@NPs) with a diameter of <100 nm. The PEG-ATX@NPs reduced Aß neurotoxicity by both degrading FA and reducing FA-induced Aß assembly in vitro. Intraperitoneal administration of PEG-ATX@NPs in APPswe/PS1dE9 mice (APP/PS1, a familial model of AD), not only decreased the levels of brain FA and malondialdehyde (MDA, a typical product of oxidative stress), but also attenuated both intracellular Aß oligomerization and extracellular Aß-related senile plaque (SP) formation. These pathological changes were accompanied by rescued ability of spatial learning and memory. Collectively, PEG-ATX@NPs improved the water-solubility, bioavailability, and effectiveness of ATX. Thus, it has the potential to be developed as a safe and effective strategy for treating AD.
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Doença de Alzheimer , Peptídeos beta-Amiloides , Xantofilas , Animais , Camundongos , Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide , Lipossomos , Camundongos Transgênicos , Fenótipo , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/química , Água , Xantofilas/administração & dosagem , Xantofilas/químicaRESUMO
Purpose: To explore the predictive value of nutritional risk for all-cause death and functional outcomes among elderly acute stroke patients. Patients and Methods: A total of 479 elderly acute stroke patients were enrolled in this study. The nutritional risk of patients was screened by the GNRI and NRS-2002. The primary outcome was all-cause death, and the secondary outcome was poor prognosis defined as a modified Rankin Scale (mRS) score ≥3. Results: Based on the NRS-2002, patients with nutritional risk had a higher risk of all-cause death at 3 months (adjusted OR: 3.642, 95% CI 1.046~12.689) and at 3 years (adjusted OR: 2.266, 95% CI 1.259~4.076) and a higher risk of adverse functional outcomes at 3 months (adjusted OR: 2.748, 95% CI 1.518~4.972. Based on the GNRI, compared to those without nutritional risk, patients with mild malnutrition also had a higher risk of all-cause death at 3 months (adjusted OR: 7.186, 95% CI 1.550~33.315) and at 3 years (adjusted OR: 2.255, 95% CI 1.211~4.199) and a higher risk of adverse functional outcomes at 3 months (adjusted OR: 1.947, 95% CI 1.030~3.680), so patients with moderate and severe malnutrition had a higher risk of all-cause death at 3 months (adjusted OR: 6.535, 95% CI 1.380~30.945) and at 3 years (adjusted OR: 2.498, 95% CI 1.301~4.799) and a higher risk of adverse functional outcomes at 3 months (adjusted OR: 2.213, 95% CI 1.144~4.279). Conclusion: Nutritional risk increases the risk of poor short-term and long-term outcomes in elderly patients with acute stroke. For elderly stroke patients, we should pay attention to early nutritional risk screening, and effective intervention should be provided to improve the prognosis of such patients.
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Desnutrição , Pirimidinas , Acidente Vascular Cerebral , Estirenos , Tiofenos , Idoso , Humanos , Seguimentos , ChinaRESUMO
Yang-deficiency constitution (YADC) is linked to a higher vulnerability to various diseases, such as cold coagulation and blood stasis (CCBS) syndrome and infertility. Endometrial hyperplastic processes (EHPs) are a leading cause of infertility in women and are characterized by CCBS. However, it remains unclear whether YADC is related to the development of EHPs. METHODS: We recruited 202 EHPs patients including 147 with YADC (YEH group) and 55 with non-YADC (NYEH group). Fecal samples were collected from 8 YEH patients and 3 NYEH patients and analyzed using 16S rRNA V3-V4 sequencing for gut microbiota analysis. We obtained constitution survey data and a differential gut microbiota dataset from the literature for further analysis. Bioinformatics analysis was conducted using gut microbiota-related genes from public databases. RESULTS: YADC was significantly more prevalent in EHPs than non-YADC (P < 0.001), suggesting it as a potential risk factor for EHPs occurrence (ORpopulation survey = 13.471; ORhealthy women = 5.173). The YEH group had higher levels of inflammation, estrogen, and tamoxifen-related flora compared to NYEH and healthy YADC groups. There was an interaction between inflammation, estrogen, differential flora, and EHPs-related genes, particularly the TNF gene (related to inflammation) and the EGFR gene (related to estrogen), which may play a crucial role in EHPs development. CONCLUSION: YEH individuals exhibit significant changes in their gut microbiota compared to NYEH and healthy YADC. The interaction between specific microbiota and host genes is believed to play a critical role in the progression of EHPs.
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BACKGROUND: Aspirin is recommended for secondary stroke prevention in patients with moderate-to-severe ischaemic stroke but can lead to gastrointestinal intolerance and bleeding. Indobufen is used as an alternative antiplatelet agent in some countries, despite an absence of large-scale clinical trials for this indication. We tested the hypothesis that indobufen is non-inferior to aspirin in reducing the risk of new stroke at 90 days in patients with moderate-to-severe ischaemic stroke. METHODS: We conducted a randomised, double-blind, double-dummy, active control, non-inferiority trial at 163 tertiary and district general hospitals in China. Eligible participants were aged 18-80 years with acute moderate-to-severe ischaemic stroke (National Institutes of Health Stroke Scale score 4-18). We randomly assigned (1:1) participants within 72 h of the onset of symptoms to receive either indobufen (100 mg tablet twice per day) or aspirin (100 mg tablet once per day) for 90 days. The randomisation sequence was computer generated centrally and stratified by local participating centres. Masked local investigators assigned the random code to patients in ascending order and provided a treatment kit corresponding to the random code. The primary efficacy outcome was new stroke and the primary safety outcome was severe or moderate bleeding, both within 90 days. This primary efficacy outcome was assessed in all randomly assigned and consenting patients and in a per-protocol group (ie, all patients finishing the treatment without major violation of the trial protocol). Safety analyses were done in the safety-analysis population (ie, all patients who received at least one dose of the study drug and had a safety assessment available). We assessed the non-inferiority of indobufen versus aspirin using the one-sided upper limit of the 95% CI of the hazard ratio (HR) with a prespecified non-inferiority margin of 1·25. This trial is registered with ClinicalTrials.gov (NCT03871517). FINDINGS: This trial took place between June 2, 2019, and Nov 28, 2021. Of 84 093 patients screened, 5438 patients were randomly assigned to receive either indobufen (n=2715) or aspirin (n=2723), all of whom were included in the primary analyses. Median age was 64·2 years (IQR 56·1-70·6); 1921 (35·3%) were women and 3517 (64·7%) were men. Stroke occurred within 90 days in 213 (7·9%) patients in the indobufen group versus 175 (6·4%) in the aspirin group (HR 1·23, 95% CI 1·01-1·50; pnon-inferiority=0·44). Moderate or severe bleeding occurred in 18 (0·7%) patients in the indobufen group and in 28 (1·0%) in the aspirin group (0·63, 95% CI 0·35 to 1·15; p=0·13). Adverse events within 90 days occurred in 666 (24·5%) patients in the indobufen group and 679 (24·9%) patients in the aspirin group (p=0·73). INTERPRETATION: In patients with acute moderate-to-severe ischaemic stroke, indobufen was not non-inferior to aspirin because the upper limit of the 95% CI was greater than 1·25. Furthermore, indobufen seemed to be inferior to aspirin in reducing the risk of recurrent stroke at 90 days because the lower limit of the 95% CI was greater than 1·00. Although moderate or severe bleeding did not differ between groups, these findings do not support the use of indobufen for secondary stroke prevention in patients with moderate-to-severe ischaemic stroke. FUNDING: Hangzhou Zhongmei Huadong Pharmaceutical and Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.
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Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Aspirina/uso terapêutico , Acidente Vascular Cerebral/prevenção & controle , Isquemia Encefálica/complicações , Resultado do Tratamento , AVC Isquêmico/tratamento farmacológico , AVC Isquêmico/complicações , Método Duplo-CegoRESUMO
Alzheimer's disease (AD) is characterized by the presence of senile plaques in the brain. However, medicines targeting amyloid-beta (Aß) have not achieved the expected clinical effects. This review focuses on the formation mechanism of the Aß dimer (the basic unit of oligomers and fibrils) and its tremendous potential as a drug target. Recently, age-associated formaldehyde and Aß-derived formaldehyde have been found to crosslink the nontoxic Aß monomer to form the toxic dimers, oligomers and fibrils. Particularly, Aß-induced formaldehyde accumulation and formaldehyde-promoted Aß aggregation form a vicious cycle. Subsequently, formaldehyde initiates Aß toxicity in both the early-and late-onset AD. These facts also explain why AD drugs targeting only Aß do not have the desired therapeutic effects. Development of the nanoparticle-based medicines targeting both formaldehyde and Aß dimer is a promising strategy for improving the drug efficacy by penetrating blood-brain barrier and extracellular space into the cortical neurons in AD patients.
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Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides/antagonistas & inibidores , Formaldeído/farmacologia , Fármacos Neuroprotetores/farmacologia , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/metabolismo , Formaldeído/química , Humanos , Fármacos Neuroprotetores/química , Agregados Proteicos/efeitos dos fármacosRESUMO
A 37-year old man presented a slight delay in early developmental milestones, cognitive decline, difficulty walking, cerebellar signs and extrapyramidal signs. Brain magnetic resonance imaging (MRI) showed a thin corpus callosum, cerebral atrophy, non-specific white-matter hyperintensity, and cerebellar atrophy. The genetic test revealed a putative homozygous deletion in SPG21 from exon 3 through exon 7, which was further validated by long-range primer-walking PCR. This is the first report of Chinese patient with Mast syndrome carrying a large homozygous SPG21 deletion.
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Proteínas Adaptadoras de Transdução de Sinal/genética , Demência/genética , Paraplegia Espástica Hereditária/genética , Adulto , Povo Asiático , Deleção de Genes , Humanos , Masculino , Linhagem , Deleção de Sequência , Sequenciamento do ExomaRESUMO
BACKGROUND: The red cell index (RCI) was described as a biomarker for evaluating respiratory function in previous studies, but the relationship between RCI and stroke, remained a mystery. The present study aimed to probe the association between RCI at 24-hr and 3-month mortality and functional outcomes among acute ischemic stroke (AIS) patients treated with recombinant tissue plasminogen activator (r-tPA). METHODS: A total of 217 AIS patients between January 2016 and January 2019 were recruited in this retrospective study. AIS patients were grouped in terms of RCI tertiles. Predictive factors were confirmed via multivariate logistic regression analysis. The receiver operating characteristic (ROC) was used to assess the ability of RCI in predicting mortality. In addition, the risk of 3-month all-cause mortality was evaluated by Cox proportional hazard model. RESULTS: We grouped AIS patients into tertiles with the purpose of comparing clinical factors and RCI levels. Multivariate logistic regression analysis presented that RCI (odds ratio [OR] = 1.443, 95% confidence interval [CI] [1.167-1.786], p = 0.001) was an independent biomarker for 3-month all-cause mortality. The best cutoff value of RCI was 2.41 (area under the curve [AUC] = 0.639, 95% CI [0.501-0.778], p = .032), with a sensitivity of 40.9% and a specificity of 89.7%. Cox survival analysis demonstrated a positive significant correlation between RCI (hazard ratio [HR] = 1.332, 95% CI [1.148-1.545], p < .001) and mortality risk. CONCLUSION: RCI, a potential predictor, was significantly associated with 3-month mortality in AIS patients with r-tPA.
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Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Biomarcadores , Isquemia Encefálica/tratamento farmacológico , Índices de Eritrócitos , Fibrinolíticos/uso terapêutico , Humanos , Prognóstico , Estudos Retrospectivos , Acidente Vascular Cerebral/tratamento farmacológico , Terapia Trombolítica , Ativador de Plasminogênio Tecidual/uso terapêutico , Resultado do TratamentoRESUMO
AIM: The main purpose of this study was to investigate the dynamic changes of neutrophils-lymphocytes ratios (NLRs) in patients with acute ischemic stroke (AIS) and their relationships with 3-month prognostic outcomes. METHODS: Two hundred ninety-one patients with AIS were included in this study, followed up for 3 months. At admission, 1 and 7 days after recombinant tissue plasminogen activator (r-tPA) injection, blood samples were obtained. Outcome events included excellent outcome, good outcome, and death defined as modified Rankin Scale (mRS) scores of 0-1, 0-2, and 6 respectively. RESULTS: NLRs measured in admission and 7 days after r-tPA treatment were associated with prognosis outcome after 3 months. Twenty-four-hour NLR is an excellent indicator in forecasting (excellent outcome's the areas under the curve (AUC) = 0.725; good outcome AUC = 0.742; death AUC = 0.759). In addition, we were surprised to find that dynamic increase in NLR within 24 h is significantly related to excellent and good outcomes. CONCLUSIONS: Twenty-four-hour NLR is related to the severity of AIS and poor prognosis, which can help early risk stratification. SIGNIFICANCE: We can predict the prognosis of AIS more accurately. Compared with previous studies, our study has shown the dynamic changes of NLR and its relationship with NIHSS and multiple prognostic.
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Isquemia Encefálica/sangue , AVC Isquêmico/sangue , Linfócitos/metabolismo , Neutrófilos/metabolismo , Terapia Trombolítica/tendências , Idoso , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/terapia , Feminino , Fibrinolíticos/administração & dosagem , Seguimentos , Humanos , AVC Isquêmico/diagnóstico , AVC Isquêmico/terapia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Terapia Trombolítica/métodos , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND AND AIMS: Malnutrition is prevalent among individuals with acute ischaemic stroke (AIS) and may worsen clinical outcomes. There is no consensus on the best tool for nutritional screening in this population. The present study compared four screening tools and one diagnostic tool in terms of their prognostic significance in predicting short-term and long-term outcomes in AIS patients. METHODS: We included patients admitted to five major hospitals in Wenzhou and diagnosed with a primary diagnosis of AIS from October 1 to December 31, 2018. The Controlling Nutritional Status (CONUT) score, the Geriatric Nutritional Risk Index (GNRI), the Malnutrition Universal Screening Tool (MUST), the Nutritional Risk Screening Tool 2002 (NRS-2002) and the European Society for Clinical Nutrition and Metabolism diagnostic criteria for malnutrition (ESPEN-DCM) were assessed at admission. The clinical outcomes were evaluated by the modified Rankin Scale (mRS) and mortality at 3 months and 12 months after discharge. RESULTS: Five hundred and ninety-three patients were included in our prospective study. The mean age was 67.3 ± 12.0 years. Based on the mRS score, 125 patients exhibited poor functional recovery (an mRS ≥3) at 3 months after discharge. Seventeen patients died during the 3-month follow-up period, and the other 25 did not survive 12 months. Multivariate binary logistic regression revealed that inadequate nutritional status at admission, as determined by the CONUT, GNRI, MUST, NRS-2002 and ESPEN-DCM, were independently associated with poor outcomes in AIS patients 3 months after discharge. Both MUST ≥2 and NRS-2002 ≥ 3 showed significant associations with poor outcomes at 12-month post-discharge. Further analysis with the receiver operator characteristic (ROC) curve showed similar results, where all the tools predicted the poor outcomes at 3 months while only the NRS-2002 and MUST scores were significantly associated with the mRS at 12 months post-discharge. Moreover, the area under the curve (AUC) of MUST and NRS-2002 were significantly larger than those for the other tools. The optimal cut-off values of the MUST and NRS-2002 to predict poor outcomes were scores of ≥2 and ≥ 3 points, respectively. CONCLUSIONS: Our data supported a deleterious effect of inadequate nutrition, as evidenced by the nutrition screening tools or ESPEN-DCM, on clinical outcomes during and beyond the acute phase of AIS. We recommended the use of the MUST and NRS-2002 in guiding nutritional support in AIS patients, as they have higher predictive power and can predict both short-term and long-term outcomes.
Assuntos
Avaliação Nutricional , Estado Nutricional/fisiologia , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/mortalidade , Idoso , Idoso de 80 Anos ou mais , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/epidemiologia , Isquemia Encefálica/mortalidade , Isquemia Encefálica/terapia , Feminino , Humanos , Masculino , Desnutrição , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/terapia , Resultado do TratamentoRESUMO
Enhanced and selective photocatalytic oxidation of nonylphenol (NP), a typical hydrophobic endocrine disrupting chemicals (EDCs), was realized on hydrophobic titanium dioxide nanotubes (H-TiO2NTs), which was fabricated by an electrochemical anodization method, followed by grafting of perfluorooctyl groups. The water contact angle of catalyst surface changed from 21.1° to 128.4° after hydrophobic modification. H-TiO2NTs showed excellent photocatalytic oxidation performance for NP, that it was completely converted in 40â¯min under irradiation, which was improved for about 17% compared with the hydrophilic TiO2NTs. The enhanced photocatalytic performance of H-TiO2NTs was attributed to the stronger adsorption ability toward NP identified by ATR-FTIR, with an initial adsorption rate of 4 times as higher as that of bare TiO2NTs. Meanwhile, the hydrophobic surface of H-TiO2NTs was beneficial for generation of more hydroxyl radicals. The apparent rate constant of hydroxyl radicals' generation on H-TiO2NTs, which was the main oxidizing species, could reach 1.83 times that of the hydrophilic TiO2NTs. Both the two factors contributed to the successful competition of NP against the coexistent hydrophilic contaminates in the adsorption and oxidation on the catalyst surface, leading to the selective removal of NP in mixed systems finally.
RESUMO
A novel cathodic photoelectrochemical (PEC) sensing method was developed for fast and convenient detection of PCB101 taking advantages of the excellent PEC reducibility of Pd quantum dots (QDs) modified molecularly imprinted TiO2 nanorods (NRs). Attributed to the efficient PEC reduction of PCB101 on the cathode surface, sensitive cathodic photocurrent would be produced with increasing PCB101 concentration under a negative bias potential, giving a low PCB101 detection limit of 5×10-14molL-1. Meanwhile, molecular imprinting (MI) technique was integrated by in situ introduction of MI sites on the surface of TiO2 NRs, so that highly specific adsorption and reduction of PCB101 congener could be obtained. The results indicated that the PEC sensor presented excellent selectivity toward PCB101 with the coexistance of 100-fold excess of other pollutants including the PCBs congeners, other aromatic pollutants, and heavy metal ions. The cathodic PEC sensor was sucessfully applied in determination of PCB101 in real water and soil samples, and the results had good consistency with that obtained by the traditional GC-MS. This work provides a new concept and research basis for fabricating cathodic PEC sensor for the environmental pollutants with specific structures that were easily reduced.
RESUMO
OBJECTIVE: To investigate whether propranolol application as collyrium or intraperitoneal (IP) injection can promote the recovery of oxygen-induced retinopathy (OIR). METHOD: Thirty-six 7-day-old mice were divided into the following 6 groups: normal control, propranolol eye drops, propranolol IP injection, eye drops negative control, IP injection negative control, and pathological model with 6 mice in each. In a typical model of OIR, litters of mice pups with their nursing mothers were exposed to an infant incubator to high oxygen concentration (75 ± 5)% between postnatal day (PD) 7 and PD12, prior to returning to room air. Two routes of propranolol treatment were assessed from PD12 to PD17: IP injection and eye drop, with doses 2 mg/(kg·time), three times a day. Another three groups were given citric acid buffer eye drops, IP injection of citric acid buffer, and negative control were not treated with any drug. Neonatal mice fed in normal conditions served as normal control. Mice were sacrificed at PD17 to evaluate the morphological changes of retinal vessels by fluorescein isothiocyanate-dextran perfusion and retinal whole mount. The retinal neovascularization was evaluated by counting the number of nuclei of the endothelial cell breaking through the internal limiting membrane (ILM). RESULT: Compared with the oxygen-exposed group, the branches of retinal vessels went normal with a less un-perfused area in the propranolol eye drops and propranolol IP injection groups [(38.9 ± 9.9)% and (5.6 ± 2.3)% vs. (16.2 ± 10.0)% and (2.2 ± 0.8)%, (25.9 ± 5.0)% and (2.1 ± 2.7)%, F=36.12 and 14.55, P both<0.001]. The number of nuclei of endothelial cells breaking through the ILM on the retinal cross-section in the propranolol eye drops group decreased (14.2 ± 5.1) per slide, which was less than that in the oxygen-exposed group (49.1 ± 8.9) per slide and the propranolol IP injection group (18.0 ± 5.9) per slide; it was also less than that in the eye drops negative control group (47.4 ± 8.1) per slide (F=187.60, P<0.05). Moreover, the number of nuclei of endothelial cells breaking through the ILM on the retinal cross-section in the propranolol IP injection group was less than that in the IP injection negative control group (49.9 ± 7.1) per slide (P<0.05). CONCLUSION: Propranolol could effectively inhibit the formation of retinal neovascularization in mice; the eye drops was more effective than the IP injection.