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At present, the effects of environmental electromagnetic irradiation on the metabolism of organisms have attracted extensive attention, but the mechanism is still not clear. D-glucose plays an important role in the metabolism of organisms. In this work, the change in the optical rotation of D-glucose solution under an electrostatic field is measured experimentally, so as to explain the mechanism of the electric field-induced biological effect. The experimental results show that the electrostatic field can alter the optical rotation of D-glucose solution at different temperatures. Under the different strengths of electrostatic field, the specific rotation of D-glucose solution increases at different temperatures; the maximum increase can reach 2.07%, but the effect of temperature and electric field strength on the rotation increment is nonlinear and very complex. Further, it turns out that the proportion of α-D-glucose in solution increases by up to 3.25% under the electrostatic field, while the proportion of ß-D-glucose decreases by as much as 1.75%. The experimental study confirms that electrostatic field can change the proportion of two conformation molecules (α and ß-D-glucose) in D-glucose solution, which can provide a novel explanation for the mechanism of the electric field-induced biological effect.
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Glucose , Eletricidade Estática , Glucose/química , Rotação Ocular , Soluções , TemperaturaRESUMO
The nervous system interacts with the immune system through a variety of cellular regulators, signaling pathways, and molecular mechanisms. Disruptions in these interactions lead to the development of multiple neurological diseases. Recent studies have identified that specialized pro-resolving mediators (SPMs) play a regulatory role in the neuroimmune system. This study reviews recent research on the function of SPMs in the inflammatory process and their association with the nervous system. The review aims to provide new perspectives for studying the pathogenesis of neurological diseases and identify novel targets for clinical therapy.
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BACKGROUND: Precocious puberty is an endocrine disease that is diagnosed by sex, age, and Tanner stage of puberty. This study aimed to investigate the association between various dietary patterns and early or precocious puberty, especially Traditional dietary patterns, which have been rarely investigated. METHODS: A total of 4085 primary school students in grades 1-3 (6-9 years) completed individual characteristic surveys, health examinations, and food frequency questionnaires (FFQs). Physical examinations were also conducted to assess obesity and pubertal onset. Traditional, Westernized, and Protein dietary patterns were determined by factor analysis, and their associations with pubertal onset were analyzed by multiple logistic regression analysis. RESULTS: Compared to the other two patterns, children who predominant the Traditional dietary pattern were protectively associated with precocious puberty (OR = 0.72, 95% CI = 0.55, 0.94), even after adjusting the confounders (OR = 0.66, 95% CI = 0.48, 0.89). Neither the Westernized nor Protein dietary pattern demonstrated an association with pubertal onset. The Traditional dietary pattern was negatively associated with children's weight status, classified by body mass index (BMI), and was positively associated with parental education. The maternal education and the Protein dietary pattern were negatively related. CONCLUSIONS: Traditional dietary patterns were protective associated with early and precocious puberty among Chinese children. IMPACT: The Traditional dietary pattern was protective associated with early puberty or precocious puberty in children, as found in large-scale population-based public health research. Current research primarily focuses on Westernized dietary patterns, and we studied Traditional dietary patterns to further explore the influence of food on children's puberty development. We discovered that children's preference for Traditional dietary patterns is protective of pubertal development, which implies that society and parents can benefit from diet guidance to protect children's natural development during adolescence.
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Dieta , Puberdade Precoce , Criança , Feminino , Humanos , Masculino , Índice de Massa Corporal , China , Estudos Transversais , Puberdade Precoce/epidemiologia , Inquéritos e QuestionáriosRESUMO
Purpose: Scoliosis is a complex spine deformity with direct functional and cosmetic impacts on the individual. The reference standard for assessing scoliosis severity is the Cobb angle which is measured on radiographs by human specialists, carrying interobserver variability and inaccuracy of measurements. These limitations may result in lack of timely referral for management at a time the scoliotic deformity progression can be saved from surgery. We aimed to create a machine learning (ML) model for automatic calculation of Cobb angles on 3-foot standing spine radiographs of children and adolescents with clinical suspicion of scoliosis across 2 clinical scenarios (idiopathic, group 1 and congenital scoliosis, group 2). Methods: We retrospectively measured Cobb angles of 130 patients who had a 3-foot spine radiograph for scoliosis within a 10-year period for either idiopathic or congenital anomaly scoliosis. Cobb angles were measured both manually by radiologists and by an ML pipeline (segmentation-based approach-Augmented U-Net model with non-square kernels). Results: Our Augmented U-Net architecture achieved a Symmetric Mean Absolute Percentage Error (SMAPE) of 11.82% amongst a combined idiopathic and congenital scoliosis cohort. When stratifying for idiopathic and congenital scoliosis individually a SMAPE of 13.02% and 11.90% were achieved, respectively. Conclusion: The ML model used in this study is promising at providing automated Cobb angle measurement in both idiopathic scoliosis and congenital scoliosis. Nevertheless, larger studies are needed in the future to confirm the results of this study prior to translation of this ML algorithm into clinical practice.
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Aprendizado de Máquina , Escoliose , Humanos , Escoliose/diagnóstico por imagem , Escoliose/congênito , Adolescente , Estudos Retrospectivos , Feminino , Masculino , Criança , Coluna Vertebral/diagnóstico por imagem , Coluna Vertebral/anormalidades , Radiografia/métodosRESUMO
INTRODUCTION: Ovarian hyperstimulation syndrome (OHSS) is a common complication during assisted conception treatment, mostly seen in patients with ovarian hyperresponsiveness such as polycystic ovary syndrome, especially in post-invitro fertilization and embryo transfer (IVF-ET) pregnancies. Its main symptoms are abdominal distension, abdominal pain, nausea and vomiting with ascites, pleural fluid, leukocytosis, hemoconcentration and hypercoagulation. This disease is a self-limiting disease and can be gradually cured by rehydration, albumin infusion and correction of electrolyte disorders in moderate to severe cases. Luteal rupture is a more common gynecological emergency abdomen. The combination of twin pregnancy, OHSS and ruptured corpus luteum is very rare. We successfully avoided the stimulation of the risk of pregnancy abortion by surgical exploration through dynamic ultrasound monitoring and vital signs observation in the absence of experience in primary care, and the patient hard-won twin pregnancy was successfully treated conservatively. PATIENT CONCERNS: The patient is a 30-year-old post-IVF-ET woman with an established twin pregnancy, OHSS and sudden onset of lower abdominal pain. DIAGNOSIS: Twin pregnancy, OHSS combined with ruptured corpus luteum. INTERVENTIONS: Rehydration, albumin infusion, low molecular heparin for thromboprophylaxis, luteinizing support, ambulatory ultrasound monitoring. OUTCOMES: After more than 10 days of standardized treatment for OHSS, dynamic ultrasound monitoring and close observation of vital signs, the patient was discharged cured of her condition and is continuing her pregnancy. CONCLUSION: Our case shows that the possibility of acute abdominal rupture of the corpus luteum is still present in the case of combined OHSS in pregnancy, and that some patients with corpus luteum rupture can heal spontaneously during close testing to avoid the increased risk of miscarriage with surgical exploration.
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Aborto Espontâneo , Síndrome de Hiperestimulação Ovariana , Tromboembolia Venosa , Humanos , Gravidez , Feminino , Adulto , Síndrome de Hiperestimulação Ovariana/complicações , Gravidez de Gêmeos , Fertilização in vitro/efeitos adversos , Anticoagulantes , Tromboembolia Venosa/etiologia , Corpo Lúteo , Aborto Espontâneo/etiologia , Transferência Embrionária/efeitos adversos , Dor Abdominal/etiologia , Albuminas , Indução da Ovulação/efeitos adversosRESUMO
Purpose: Scoliosis is a deformity of the spine, and as a measure of scoliosis severity, Cobb angle is fundamental to the diagnosis of deformities that require treatment. Conventional Cobb angle measurement and assessment is usually done manually, which is inherently time-consuming, and associated with high inter- and intra-observer variability. While there exist automatic scoliosis measurement methods, they suffer from insufficient accuracy. In this work, we propose a two-step segmentation-based deep learning architecture to automate Cobb angle measurement for scoliosis assessment using X-Ray images. Methods: The proposed architecture involves two steps. In the first step, we utilize a novel Augmented U-Net architecture to generate segmentations of vertebrae. The second step includes a non-learning-based pipeline to extract landmark coordinates from the segmented vertebrae and filter undesirable landmarks. Results: Our proposed Augmented U-Net architecture achieved a Symmetric Mean Absolute Percentage Error of 9.2%, with approximately 90% of estimations having less than 10 degrees difference compared with the AASCE-MICCAI challenge 2019 dataset ground truths. We further validated the model using an internal dataset and achieved almost the same level of performance. Conclusion: The proposed architecture is robust in providing automated spinal vertebrae segmentations and Cobb angle measurement, and is potentially generalizable to real-world clinical settings.
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Escoliose , Humanos , Adolescente , Escoliose/diagnóstico por imagem , Coluna Vertebral , Variações Dependentes do Observador , Reprodutibilidade dos TestesRESUMO
Clinically, the effective treatment for patients with acute ischemic stroke (AIS) is very limited. Therefore, this paper aims to investigate the mechanism how astragalus polysaccharide (APS) exerts protective effect against AIS and provide a new method for the treatment of AIS. Cell surface antigen flow cytometry and immunofluorescence were used to identify M1 and M2 microglia. Western blot was used to evaluate the expression of associated protein. Oxygen-glucose deprivation (OGD) was used to simulate the effect of AIS on rat microglia. The middle cerebral artery occlusion (MCAO) model was established to simulate the effect of AIS in vivo. Evans blue dye (EBD) was used to evaluate the permeability of blood-brain barrier (BBB). Western blot and cell surface antigen flow cytometry results showed that APS promoted the M2 polarization of rat microglia by inhibiting the expression of purinergic receptor (P2X7R). APS reversed the effect of OGD on the polarization of rat microglia M1/ M2 by regulating P2X7R. APS reversed the effect of MCAO on the polarization of rat microglia M1/ M2 in vivo. Furthermore, APS inhibited the expression of P2X7R by promoting the degradation of adenosine triphosphate (ATP) in the cerebral cortex of MCAO rats. In addition, APS contributed to maintain the integrity of BBB. Summarily, APS can reduce brain injury by promoting the degradation of ATP in microglia and inhibiting the expression of P2X7R after AIS.
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Astrágalo , AVC Isquêmico/metabolismo , Microglia , Polissacarídeos , Substâncias Protetoras , Trifosfato de Adenosina/metabolismo , Animais , Barreira Hematoencefálica/efeitos dos fármacos , Linhagem Celular , Infarto da Artéria Cerebral Média/metabolismo , Masculino , Microglia/citologia , Microglia/efeitos dos fármacos , Polissacarídeos/química , Polissacarídeos/farmacologia , Substâncias Protetoras/química , Substâncias Protetoras/farmacologia , Ratos , Ratos Sprague-Dawley , Receptores Purinérgicos P2X7/metabolismoRESUMO
BACKGROUND: Migraine is one of the most common neurological diseases which has been treated by active substances from traditional Chinese medicine (TCM), such as ligustrazine, an extract of the Chinese herb Chuanxiong. However, the pathogenesis of migraine and the curative mechanisms of ligustrazine have remained unclear. The genes P2X3, TRPV1, ERK, and c-fos have been implicated to play a role. In this work, we attempted to elucidate the analgesic mechanism of ligustrazine using a classic migraine-representative rat model. METHODS: The migraine rat model was established by administration of nitroglycerin (NTG). Ligustrazine treatment was administered by intravenous injection. The animal's behavior was continuously recorded, and then trigeminal ganglions (TGs) were isolated. Total RNA was extracted from cells and total protein was extracted from TG. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot analyses were used to detect the levels of P2X3, TRPV1, c-Fos, and ERK in TG. RESULTS: Ligustrazine could reduce the neurological activities of NTG-induced migraine rats. The rats TG nerve showed varying degrees of expression of P2X3, TRPV1, c-Fos and ERK expression element. Ligustrazine could inhibit over-expression of P2X3, TRPV1, c-fos, and ERK in the TG nerve of NTG-induced migraine rats. CONCLUSIONS: Our results demonstrated that ligustrazine had potent activity against NTG-induced migraine rats through inhibition of the c-fos/ERK signaling pathway. This work may provide a comprehensive basis for a better understanding of the pathogenesis of migraine and the curative mechanisms of ligustrazine.
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BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide. Genetic factors play important roles in PD risk. rs653765 and rs514049 of ADAM10 were reported to be associated with Alzheimer's disease (AD) in Caucasian population; however, the association of the two variants with PD in Chinese Han population remains unknown. The present investigation aimed to explore the possible association of ADAM10 variants with PD in Chinese Han population. METHODS: We enrolled 565 PD patients and 518 healthy controls to conduct a case-control study. DNA samples were extracted from peripheral blood leukocytes, and the genotypes were determined by utilization of MassARRAY platform. Plasma levels were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: We found CC genotype of rs514049 was associated with an increased risk of PD (OR (95% CI) = 3.776 (1.127-11.217), p = 0.018). The C allele frequency of rs514049 was significantly higher in PD group (OR (95% CI) = 1.328 (1.031-1.709), p = 0.028), especially in male subgroup (OR (95% CI) = 1.484 (1.053-2.092), p = 0.024). However, there was no significant difference in the genotype or allele frequencies for rs653765 within the groups. Plasma levels were significantly decreased in PD patients compared with controls (p < 0.001). CONCLUSIONS: Our data suggested that C allele of rs514049 in ADAM10 may increase the risk of PD in Chinese Han population, especially in males. The decreased plasma levels are probably involved in PD development.
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Proteína ADAM10/genética , Proteína ADAM10/metabolismo , Secretases da Proteína Precursora do Amiloide/genética , Secretases da Proteína Precursora do Amiloide/metabolismo , Predisposição Genética para Doença , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Doença de Parkinson/genética , Doença de Parkinson/metabolismo , Polimorfismo de Nucleotídeo Único , Idoso , Alelos , Povo Asiático/genética , Estudos de Casos e Controles , China , Feminino , Frequência do Gene , Estudos de Associação Genética , Genótipo , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Three new tryptamine derivatives diaporols T-V (1-3) were isolated by adding tryptamine into the culture of Diaporthe sp., a fungus obtained from the leaves of Rhizophora stylosa. The structures of these compounds were elucidated by NMR spectroscopy and high resolution mass spectroscopic data. Among them, compound 1 showed moderate cytotoxic activity against SW480 cancer cell with IC50 9.84 µM.
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Rhizophoraceae , Biotransformação , Fungos , Estrutura Molecular , Triptaminas/farmacologiaAssuntos
Potenciais Pós-Sinápticos Excitadores , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Giro do Cíngulo/metabolismo , Potenciação de Longa Duração , Terminações Pré-Sinápticas/metabolismo , Dor Aguda/tratamento farmacológico , Animais , Dor Crônica/tratamento farmacológico , Hipocampo/metabolismo , Humanos , Aprendizagem , Sistema de Sinalização das MAP Quinases , Neurônios/metabolismo , Transdução de Sinais , Sinapses/metabolismoRESUMO
The genetic background such as copy number, integration site and chromosome karyotype of exogenous genes of transgenic animals obtained by random integration is still unclear. There may be some problems such as silent integration, invalid integration, toxic integration and unpredictable expression level of exogenous genes. In this study, six primary (F0) and their corresponding offspring (F1) of human lactoferrin (hLF) transgenic goats were selected as the research objects, and blood samples were collected from jugular vein and DNA were extracted. The genetic background and expression level of exogenous genes were studied by chromosome karyotype analysis, real-time quantitative PCR (qPCR), ELISA and Western blotting. The chromosomes of six F0 transgenic goats had no obvious morphological variation, number change and other abnormalities. The relative copy number was different (2-16) and could be steadily inherited to the next generation. The copy number of F0 and F1 hLF gene was the same. The highest expression level of hLF was 1.12 g/L in F1 transgenic goats (L3-1, 8 copies). The results proved that the integrated exogenous genes could steadily inherit the next generation, and did not cause obstacles to the growth and development of transgenic goat individuals. Moreover, there was no obvious correlation between the number of copies and the expression level of hLF. This laid a foundation for the new varieties cultivation of transgenic goats and other transgenic animals, and analysis of genetic background.
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Patrimônio Genético , Animais , Animais Geneticamente Modificados , Fibroblastos , Cabras , Humanos , LactoferrinaRESUMO
The NLR family pyrin domain containing 3 (NLRP3) inflammasome was reported to be regulated by autophagy and activated during inflammatory procession of Parkinson's disease (PD). Berberine (BBR) is well-studied to play an important role in promoting anti-inflammatory response to mediate the autophagy activity. However, the effect of Berberine on NLRP3 inflammasome in PD and its potential mechanisms remain unclear. Hence, in this study, we investigated the effects of BBR on 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mice, by evaluating their behavioral changes, dopaminergic (DA) neurons loss, neuroinflammation, NLRP3 inflammasome and autophagic activity. BBR was also applied in BV2 cells treated with 1-methyl-4-pehnyl-pyridine (MPP+). The autophagy inhibitor 3-Methyladenine (3-MA) was administrated to block autophagy activity both in vivo and in vitro. In our in vivo studies, compared to MPTP group, mice in MPTP + BBR group showed significant amelioration of behavioral disorders, mitigation of neurotoxicity and NLRP3-associated neuroinflammation, enhancement of the autophagic process in substantia nigra (SN). In vitro, compared to MPP+ group, BBR significantly decreased the level of NLRP3 inflammasome including the expressions of NLRP3, PYD and CARD domain containing (PYCARD), cleaved caspase 1 (CASP1), and mature interleukin 1 beta (IL1B), via enhancing autophagic activity. Furthermore, BBR treatment increased the formation of autophagosomes in MPP+-treated BV2 cells. Taken together, our data indicated that BBR prevents NLRP3 inflammasome activation and restores autophagic activity to protect DA neurons against degeneration in vivo and in vitro, suggesting that BBR may be a potential therapeutic to treat PD.
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Alzheimer's disease (AD) is a common neurodegenerative disease, characterized by cognitive dysfunction; however, the therapeutic strategies are not fully understood. Huang-Lian-Jie-Du-Decoction (HLJDD) is a famous traditional Chinese herbal formula that has been widely used clinically to treat dementia. Recently, according to previous study and our clinical practice, we generate a new modification of HLJDD (named modified-HLJDD). In this study, we indicated that modified-HLJDD attenuated learning and memory deficiencies in Aß 1-42 oligomer-induced AD model, and we confirmed the exact metabolites in modified-HLJDD solution, as compared with HLJDD by UHPLC-Q-TOF-MS. Using GC-Q-TOF/MS-based metabolomics, we identified adenosine as the potential significant metabolite, responsible for modified-HLJDD regulating energy metabolism and synaptic plasticity in AD model. We also revealed that the potential underlying mechanism of modified-HLJDD in AD model may involve NMDA receptor-mediated glutamatergic transmission and adenosine/ATPase/AMPK cascade. Moreover, we also indicated the differential gut microbiota which mainly involved Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria at the phylum level upon modified-HLJDD treatment in AD model. Based on the correlation of metabolomic analysis with microbiome analysis, we clarified that Dorea is the most affected microbiota with adenosine upon modified-HLJDD treatment in AD model. Thus, our study suggests that modified-HLJDD may serve as a potential therapeutic drug in treating AD.
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Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides/metabolismo , Anti-Inflamatórios não Esteroides/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Fragmentos de Peptídeos/metabolismo , Sinapses/química , Sinapses/metabolismo , Transmissão Sináptica/efeitos dos fármacos , Doença de Alzheimer/patologia , Animais , Modelos Animais de Doenças , Humanos , Masculino , Camundongos , Plasticidade Neuronal/efeitos dos fármacos , Sinapses/patologiaRESUMO
OBJECTIVE: To evaluate the safety and efficacy of removing blood stasis (RBS) herbal medicine for the treatment of acute intracerebral haemorrhage (AICH) within a 6-hour time window. STUDY DESIGN: A randomised, multicentre, double-blind, placebo-controlled study performed in 14 hospitals in China. PARTICIPANTS AND INTERVENTIONS: Patients with AICH were randomly assigned to receive a placebo, the ICH-1 (Intracerebral Haemorrhage) formula (eight herbs, including the RBS herbs hirudo and tabanus) or the ICH-2 formula (six herbs without the RBS herbs hirudo and tabanus) within 6 hours of ICH onset. OUTCOMES: The primary safety outcome was the incidence of haematoma enlargement at 24 hours and at 10 days after treatment. The secondary outcome was the incidence of poor prognosis (mortality or modified Rankin Scale score ≥5) assessed at 90 days after symptom onset. RESULTS: A total of 324 subjects were randomised between October 2013 and May 2016: 105 patients received placebo; 108 patients received the ICH-1 formula; and 111 patients received the ICH-2 formula. The incidence of haematoma enlargement at 24 hours was 7.8% in the placebo group, 12.3% in the ICH-1 group and 7.5% in the ICH-2 group; the incidence of haematoma enlargement on day 10 was 1.1% in the placebo group, 1.1% in the ICH-1 group, and 3.1% in the ICH-2 group, with no significant differences among the groups (P>0.05). The mortality rates were 3.8% in the placebo group, 2.8% in the ICH-1 group, and 0.9% in the ICH-2 group; the incidences of poor prognosis were 7.1% in the placebo group, 6.0% in the ICH-1 group and 4.8% in the ICH-2 group at 3 months, with no significant differences among the groups (p>0.05). However, the overall frequency of treatment-emergent adverse events in the ICH-1 group (12.1%) was higher among the three groups (5.8% and 2.8%, respectively, p<0.05). All three cases of serious adverse events were in the ICH-1 group. CONCLUSIONS: Ultra-early administration of ICH-1 formula for AICH patients did not exert significant beneficial effects on clinical outcomes but increased the risk of bleeding, which probably resulted from the inclusion of RBS herbal medicines in ICH-1. TRIALREGISTRATION NUMBER: NCT01918722.
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Coagulação Sanguínea/efeitos dos fármacos , Hemorragia Cerebral , Medicamentos de Ervas Chinesas , Hematoma , Hemorragia , Fitoterapia , Hemorragia Cerebral/complicações , Hemorragia Cerebral/diagnóstico , Hemorragia Cerebral/tratamento farmacológico , Hemorragia Cerebral/mortalidade , China , Método Duplo-Cego , Monitoramento de Medicamentos/métodos , Monitoramento de Medicamentos/estatística & dados numéricos , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/efeitos adversos , Medicamentos de Ervas Chinesas/classificação , Feminino , Hematoma/diagnóstico , Hematoma/etiologia , Hematoma/prevenção & controle , Hemorragia/induzido quimicamente , Hemorragia/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Mortalidade , Fitoterapia/efeitos adversos , Fitoterapia/métodos , Tempo para o Tratamento , Resultado do TratamentoRESUMO
Grouted splice sleeve (GSS) connectors are mainly used in precast concrete structures. However, errors in manual operation during construction cause grouted defects in the GSS connector, which can lead to a negative effect on the overall mechanical properties of the structures. Owing to the complex structure of precast concrete members with a GSS connector, it is difficult to detect grouted defects effectively using traditional ultrasonic parameters. In this paper, a wavelet packet analysis algorithm was developed to effectively detect grouted defects using the ultrasonic method, and a verified experiment was carried out. Laboratory detection was performed on the concrete specimens with a GSS connector before grouting, in which the grouted defects were mimicked with five sizes in five GSS connectors of each specimen group. A simple and convenient ultrasonic detection system was developed, and the specimens were detected. According to the proposed grouted defect index, the results demonstrated that when the grouted defects reached certain sizes, the proposed method could detect the grouted defects effectively. The proposed method is effective and easy to implement at a construction site with simple instruments, and so provides an innovative method for grouted defects detection of precast concrete members.
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Genetic factors play significant roles in the causes of Parkinson's disease (PD). Recently, a meta-analysis of genome-wide association study (GWAS) has identified 17 loci associated with PD. The objective of our study was to investigate the association of 17 single-nucleotide polymorphisms with the risk of PD in Chinese population. We performed a case-control association study, and 1189 subjects comprising 652 PD patients and 537 controls were genotyped by using a Mass ARRAY System or a TaqMan assay. We found that rs601999 (OR (95% CI) = 3.378 (2.273-5.051), p < 0.001), rs11343 (OR (95% CI) = 0.426 (0.210-0.862), p = 0.018), rs353116 (OR (95% CI) = 0.738 (0.577-0.943), p = 0.015), and rs2280104 (OR (95% CI) = 1.371 (1.078-1.743), p = 0.010) were significantly associated with PD in Chinese population. However, no significant association was found in the remaining 13 single-nucleotide polymorphisms between both groups.
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Estudos de Associação Genética , Doença de Parkinson/genética , Polimorfismo de Nucleotídeo Único/genética , Idoso , Povo Asiático/genética , Estudos de Casos e Controles , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , RiscoRESUMO
Many publications reported that genetic dysfunction mediates abnormal immune responses in the brain, which is important for the development of neurodegenerative diseases, especially for Parkinson's disease (PD). This immune disorder results in subsequent inflammatory reaction, which stimulates microglia or other immune cells to secrete cytokines and chemokines and disturbs the proportion of peripheral blood lymphocyte subsets contributing to dopaminergic (DA) neuron apoptosis. Furthermore, the abnormal immune related signal pathways caused by genetic variants promote chronic inflammation destroying the blood-brain barrier, which allows infiltration of different molecules and blood cells into the central nervous system (CNS) exerting toxicity on DA neurons. As a result, the inflammatory reaction in the CNS accelerates the progression of Parkinson's disease and promotes α-synuclein aggregation and diffusion among DA neurons in the procession of Parkinson's disease. Thus, for disease evaluation, the genetic mediated abnormal immune response in PD may be assessed based on the multiple immune molecules and inflammatory factors, as well as the ratio of lymphocyte subsets from PD patient's peripheral blood as potential biomarkers.
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Neurônios Dopaminérgicos/imunologia , Imunidade Celular/genética , Imunidade Celular/imunologia , Doença de Parkinson/genética , Doença de Parkinson/imunologia , Animais , Neurônios Dopaminérgicos/patologia , Humanos , Inflamação/genética , Inflamação/imunologia , Inflamação/patologia , Mediadores da Inflamação/imunologia , Degeneração Neural/genética , Degeneração Neural/imunologia , Degeneração Neural/patologia , Doença de Parkinson/patologiaRESUMO
BACKGROUND: Abnormal expression of major histocompatibility complex class I (MHC-I) is increased in dopaminergic (DA) neurons in the substantia nigra (SN) in Parkinson's disease (PD). Low-molecular-mass protein 7 (ß5i) is a proteolytic subunit of the immunoproteasome that regulates protein degradation and the MHC pathway in immune cells. METHODS: In this study, we investigated the role of ß5i in DA neurons using a 6-hydroxydopamine (6-OHDA) model in vitro and vivo. RESULTS: We showed that 6-OHDA upregulated ß5i expression in DA neurons in a concentration- and time-dependent manner. Inhibition and downregulation of ß5i induced the expression of glucose-regulated protein (Bip) and exacerbated 6-OHDA neurotoxicity in DA neurons. The inhibition of ß5i further promoted the activation of Caspase 3-related pathways induced by 6-OHDA. ß5i also activated transporter associated with antigen processing 1 (TAP1) and promoted MHC-I expression on DA neurons. CONCLUSION: Taken together, our data suggest that ß5i is activated in DA neurons under 6-OHDA treatment and may play a neuroprotective role in PD.
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Objective: To investigate the effect of acupuncture on Parkinson's disease (PD) patients with tremor and its potential neuromechanism by functional magnetic resonance imaging (fMRI). Methods: Forty-one PD patients with tremor were randomly assigned to true acupuncture group (TAG, n = 14), sham acupuncture group (SAG, n = 14) and waiting group (WG, n = 13). All patients received levodopa for 12 weeks. Patients in TAG were acupunctured on DU20, GB20, and the Chorea-Tremor Controlled Zone, and patients in SAG accepted sham acupuncture, while patients in WG received no acupuncture treatment until 12 weeks after the course was ended. The UPDRS II and III subscales, and fMRI scans of the patients' brains were obtained before and after the treatment course. UPDRS II and III scores were analyzed by SPSS, while the degree centrality (DC), regional homogeneity (ReHo) and amplitude low-frequency fluctuation (ALFF) were determined by REST. Results: Acupuncture improved the UPDRS II and III scores in PD patients with tremor without placebo effect, only in tremor score. Acupuncture had specific effects on the cerebrocerebellar pathways as shown by the decreased DC and ReHo and increased ALFF values, and nonspecific effects on the spinocerebellar pathways as shown by the increased ReHo and ALFF values (P < 0.05, AlphaSim corrected). Increased ReHo values were observed within the thalamus and motor cortex of the PD patients (P < 0.05, AlphaSim corrected). In addition, the default mode network (DMN), visual areas and insula were activated by the acupuncture with increased DC, ReHo and/or ALFF, while the prefrontal cortex (PFC) presented a significant decrease in ReHo and ALFF values after acupuncture (P < 0.05, AlphaSim corrected). Conclusions: The cerebellum, thalamus and motor cortex, which are connected to the cerebello-thalamo-cortical (CTC) circuit, were modulated by the acupuncture stimulation to alleviate the PD tremor. The regulation of neural activity within the cognitive brain regions (the DMN, visual areas, insula and PFC) together with CTC circuit may contributes to enhancing movement and improving patients' daily life activities.