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Background and objectives: Acute mountain sickness (AMS) is a pathology with different symptoms in which the organism is not adapted to the environment that occurs under the special environment of high altitude. Its main mechanism is the organism's tissue damage caused by acute hypobaric hypoxia. Traditional Chinese medicine (TCM) theory focuses on the holistic concept. TCM has made remarkable achievements in the treatment of many mountain sicknesses. This review outlines the pathogenesis of AMS in modern and traditional medicine, the progress of animal models of AMS, and summarizes the therapeutic effects of TCM on AMS. Methods: Using the keywords "traditional Chinese medicine," "herbal medicine," "acute mountain sickness," "high-altitude pulmonary edema," "high-altitude cerebral edema," "acute hypobaric hypoxia," and "high-altitude," all relevant TCM literature published up to November 2023 were collected from Scopus, Web of Science, PubMed, and China National Knowledge Infrastructure databases, and the key information was analyzed. Results: We systematically summarised the effects of acute hypobaric hypoxia on the tissues of the organism, the study of the methodology for the establishment of an animal model of AMS, and retrieved 18 proprietary Chinese medicines for the clinical treatment of AMS. The therapeutic principle of medicines is mainly invigorating qi, activating blood and removing stasis. The components of botanical drugs mainly include salidroside, ginsenoside Rg1, and tetrahydrocurcumin. The mechanism of action of TCM in the treatment of AMS is mainly through the regulation of HIF-1α/NF-κB signaling pathway, inhibition of inflammatory response and oxidative stress, and enhancement of energy metabolism. Conclusion: The main pathogenesis of AMS is unclear. Still, TCM formulas and components have been used to treat AMS through multifaceted interventions, such as compound danshen drip pills, Huangqi Baihe granules, salidroside, and ginsenoside Rg1. These components generally exert anti-AMS pharmacological effects by inhibiting the expression of VEGF, concentration of MDA and pro-inflammatory factors, down-regulating NF-κB/NLRP3 pathway, and promoting SOD and Na + -K + -ATPase activities, which attenuates acute hypobaric hypoxia-induced tissue injury. This review comprehensively analyses the application of TCM in AMS and makes suggestions for more in-depth studies in the future, aiming to provide some ideas and insights for subsequent studies.
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BACKGROUND: The prognosis of high or markedly low diastolic blood pressure (DBP) with normalized on-treatment systolic blood pressure on major adverse cardiovascular events (MACEs) is uncertain. This study examined whether treated isolated diastolic hypertension (IDH) and treated isolated low DBP (ILDBP) were associated with MACEs in patients with hypertension. METHODS AND RESULTS: A total of 7582 patients with on-treatment systolic blood pressure <130 mm Hg from SPRINT (Systolic Blood Pressure Intervention Trial) were categorized on the basis of average DBP: <60 mm Hg (n=1031; treated ILDBP), 60 to 79 mm Hg (n=5432), ≥80 mm Hg (n=1119; treated IDH). MACE risk was estimated using Cox proportional-hazards models. Among the SPRINT participants, median age was 67.0 years and 64.9% were men. Over a median follow-up of 3.4 years, 512 patients developed a MACE. The incidence of MACEs was 3.9 cases per 100 person-years for treated ILDBP, 1.9 cases for DBP 60 to 79 mm Hg, and 1.8 cases for treated IDH. Comparing with DBP 60 to 79 mm Hg, treated ILDBP was associated with an 1.32-fold MACE risk (hazard ratio [HR], 1.32, 95% CI, 1.05-1.66), whereas treated IDH was not (HR, 1.18 [95% CI, 0.87-1.59]). There was no effect modification by age, sex, atherosclerotic cardiovascular disease risk, or cardiovascular disease history (all P values for interaction >0.05). CONCLUSIONS: In this secondary analysis of SPRINT, among treated patients with normalized systolic blood pressure, excessively low DBP was associated with an increased MACE risk, while treated IDH was not. Further research is required for treated ILDBP management.
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Doenças Cardiovasculares , Hipertensão , Hipotensão , Idoso , Feminino , Humanos , Masculino , Pressão Sanguínea/fisiologia , Doenças Cardiovasculares/etiologia , Fatores de Risco de Doenças Cardíacas , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Hipertensão/complicações , Fatores de RiscoRESUMO
Methods: Related studies on PD and ferroptosis were searched in Web of Science Core Collection (WOSCC) from inception to 2023. VOSviewer, CiteSpace, RStudio, and Scimago Graphica were employed as bibliometric analysis tools to generate network maps about the collaborations between authors, countries, and institutions and to visualize the co-occurrence and trends of co-cited references and keywords. Results: A total of 160 original articles and reviews related to PD and ferroptosis were retrieved, produced by from 958 authors from 162 institutions. Devos David was the most prolific author, with 9 articles. China and the University of Melbourne had leading positions in publication volume with 84 and 12 publications, respectively. Current hot topics focus on excavating potential new targets for treating PD based on ferroptosis by gaining insight into specific molecular mechanisms, including iron metabolism disorders, lipid peroxidation, and imbalanced antioxidant regulation. Clinical studies aimed at treating PD by targeting ferroptosis remain in their preliminary stages. Conclusion: A continued increase was shown in the literature within the related field over the past decade. The current study suggested active collaborations among authors, countries, and institutions. Research into the pathogenesis and treatment of PD based on ferroptosis has remained a prominent topic in the field in recent years, indicating that ferroptosis-targeted therapy is a potential approach to halting the progression of PD.
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Ferroptose , Doença de Parkinson , Humanos , Doença de Parkinson/tratamento farmacológico , Antioxidantes , China , Peroxidação de LipídeosRESUMO
Peripheral nerve injury (PNI) results in persistent pain, a burning sensation, tingling, or complete loss of sensation. Treating large nerve defects is a major challenge, and the use of autologous nerve grafts (ANGs) cannot overcome this challenge. Hence, substitutes for ANGs that can serve as artificial nerve fibers are urgently needed in the clinical treatment of PNI. To develop such substitutes, we genetically engineered a virus nanofiber (M13 phage) that displays a high density of RGD peptide on its sidewall, producing an RGD-displaying phage (R-phage). In the presence of neural stem cells (NSCs), the resultant negatively charged R-phage nanofibers were electrostatically bound to a complex (with a net positive charge) of negatively charged fibrin and positively charged polyethyleneimine (PEI). The biocompatible injectable fibrin gel (FG) was integrated with R-phage and seeded with NSCs, forming a hydrogel termed R-phage/FG, which is further extruded through a syringe to form a fiber. The developed fiber-shaped hydrogel exhibited the desired excellent physical-chemical properties, and controllable and appropriate mechanical properties (170-240 kPa) similar to native nerve. The R-phage/FG not only promoted NSC adhesion, infiltration, and proliferation, but also induced efficient preferential differentiation of NSCs into neurons in the hydrogels in a non-differentiating medium within only 4 days. After the NSC-seeded R-phage/FG was injected into the long-gap (10 mm) defect of a rat's sciatic nerve, a solid neuron-rich hydrogel fiber was formed as an artificial nerve fiber graft that stimulated neurogenesis in the transplanted area within 60 days for nerve regeneration. These results suggest that the R-phage/FG fiber represents a potential substitute ANG for repairing large nerve injuries. This work demonstrates a new phage-based biomaterial that can be used as a graft for treating PNI through neurogenesis.
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Nanofibras , Traumatismos dos Nervos Periféricos , Ratos , Animais , Nanofibras/química , Ratos Sprague-Dawley , Hidrogéis/química , Fibrina , Neurônios , Diferenciação CelularRESUMO
Background and objectives: Autophagy is a cellular process where damaged organelles or unwanted proteins are packaged into a double-membrane structure and transported to lysosomes for degradation. Autophagy plays a regulatory role in various hematologic malignancies, including acute myeloid leukemia (AML). However, there are few bibliometric studies on the role of autophagy in AML. The purpose of this study is to clarify the role of autophagy in acute myeloid leukemia through bibliometric analysis. Methods: The literature on autophagy and AML research from 2003 to 2023 was searched in Web of Science Core Collection, and bibliometric tools such as VOSviewer 1.6.18, Cite Space (6.1.R3), RStudio (R package bibliometrix), and Scimago Graphica were used to understand the current status and hotspots of autophagy and AML research. The study conducted an analysis of various dimensions including the quantity of publications, countries, institutions, journals, authors, co-references, keywords, and to predict future development trends in this field by drawing relevant visualization maps. Results: A total of 343 articles were obtained, published in 169 journals, written by 2,323 authors from 295 institutions in 43 countries. The journals with the most publications were Blood and Oncotarget. China had the most publications, and Chongqing Medical University and Sun Yat-sen University had the most publications. The author with the highest number of publications was Tschan, Mario P. The main types of research included clinical research, in vitro experiments, in vivo experiments, public database information, and reviews, and the forms of therapeutic effects mainly focused on genetic regulation, traditional Chinese medicine combination, autophagy inhibitors, and drug targets. The research hotspots of autophagy and AML in the past 17 years have focused on genetic regulation, autophagy inhibition, and targeted drugs. Chemotherapy resistance and mitochondrial autophagy will be the forefront of research. Conclusion: The gradual increase in the literature on autophagy and AML research and the decline after 2022 could be a result of authors focusing more on the type of research and the quality of the literature. The current research hotspots are mainly genetic regulation, autophagy inhibition, and autophagy-related targeted drugs. In future, autophagy will remain the focus of the AML field, with research trends likely to focus more on AML chemotherapy resistance and mitochondrial autophagy.
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BACKGROUND: An optimal antithrombotic strategy for patients aged 80 years or older with atrial fibrillation (AF) remains elusive. OBJECTIVE: Using a systematic review with traditional and network meta-analysis, we investigated outcomes in AF patients ≥80 years treated with different antithrombotic strategies. METHODS: We searched eligible randomised controlled trials (RCTs) and observational studies from MEDLINE, EMBASE, Cochrane Library and Web of Science databases from inception to 16 December 2021. Research comparing treatment outcomes of novel oral anticoagulants (NOACs), aspirin, vitamin K antagonists (VKAs) or no oral anticoagulant/placebo therapy in patients ≥80 years with AF were included. Outcomes were stroke or systemic embolism (SSE), major bleeding, all-cause mortality, intracranial bleeding (ICH) and gastrointestinal bleeding. Traditional and network meta-analyses were performed. Net clinical benefit integrating SSE and major bleeding was calculated. RESULTS: Fifty-three studies were identified for analysis. In the meta-analysis of RCTs, risk of SSE (risk ratio [RR]: 0.82; 95% confidence interval [CI]: 0.73-0.99) and ICH (RR: 0.38; 95% CI: 0.28-0.52) was significantly reduced when NOACs were compared with VKAs. Network meta-analysis of RCTs demonstrated that edoxaban (P-score: 0.8976) and apixaban (P-score: 0.8528) outperformed other antithrombotic therapies by showing a lower major bleeding risk and better net clinical benefit. Both traditional and network meta-analyses from RCTs combining with observational studies showed consistent results. CONCLUSIONS: In patients aged 80 years or older with AF, NOACs have better outcomes than VKAs regarding efficacy and safety profiles. Edoxaban and apixaban may be preferred treatment options since they are safer than other antithrombotic strategies.
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Fibrilação Atrial , Acidente Vascular Cerebral , Humanos , Fibrilação Atrial/complicações , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/tratamento farmacológico , Metanálise em Rede , Fibrinolíticos/efeitos adversos , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Anticoagulantes/efeitos adversos , Hemorragia/induzido quimicamente , Administração OralRESUMO
The occurrence of microorganisms has been confirmed in the tumor microenvironment (TME) of many different organs. Microorganisms (e.g., phage, virus, bacteria, fungi, and protozoa) present in TME modulate TME to inhibit or promote tumor growth in species-dependent manners due to the special physiological and pathological features of each microorganism. Such microorganism-TME interactions have recently been emulated to turn microorganisms into powerful cancer theranostic agents. To facilitate scientists to explore microorganisms-TME interactions further to develop improved cancer theranostics, here we critically review the characteristics of different microorganisms that can be found in TME, their interactions with TME, and their current applications in cancer diagnosis and therapy. Clinical trials of using microorganisms for cancer theranostics are also summarized and discussed. Moreover, the emerging technology of whole-metagenome sequencing that can be employed to precisely determine microbiota spectra is described. Such technology enables scientists to gain an in-depth understanding of the species and distributions of microorganisms in TME. Therefore, scientists now have new tools to identify microorganisms (either naturally present in or introduced into TME) that can be used as effective probes, monitors, vaccines, or drugs for potentially advancing cancer theranostics to clinical applications.
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Neoplasias , Microambiente Tumoral , Humanos , Neoplasias/tratamento farmacológico , Medicina de PrecisãoRESUMO
BanXia-YiYiRen (Pinellia Ternata and Coix Seed, BX-YYR) has been clinically proven to be an effective Chinese medicine compatible with the treatment of insomnia. However, the underlying mechanism of BX-YYR against insomnia remains unclear. This study aimed to explore the pharmacological mechanisms of BX-YYR in treating insomnia based on network pharmacology and experimental validation. The drug-disease targets were obtained using publicly available databases. The analysis revealed 21 active compounds and 101 potential targets of BX-YYR from the pharmacological database of Chinese medicine system and analysis platform (TCMSP) and 1020 related targets of insomnia from the GeneCards and Online Mendelian Inheritance in Man (OMIM) databases. Furthermore, 38 common targets of BX-YYR against insomnia were identified, and these common targets were used to construct a protein-protein interaction (PPI) network. The visual PPI network was constructed by Cytoscape software. The top three genes from PPI according to degree value are FOS, AKT1, and CASP3. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were applied to reveal the potential targets and signaling pathways involved in BX-YYR against insomnia, especially the serotonergic pathway. In addition, molecular docking revealed that baicalein, beta-sitosterol, and stigmasterol displayed strong binding to AKT1, FOS, PRKCA, and VEGFA. Experimental study found that BX-YYR against insomnia might play a role in improving sleep by modulating the serotonergic pathway. In summary, our findings revealed the underlying mechanism of BX-YYR against insomnia and provided an objective basis for further experimental study and clinical application.
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Medicamentos de Ervas Chinesas , Simulação de Acoplamento Molecular , Farmacologia em Rede , Mapas de Interação de Proteínas/efeitos dos fármacos , Distúrbios do Início e da Manutenção do Sono , Animais , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Masculino , Ratos , Ratos Wistar , Distúrbios do Início e da Manutenção do Sono/tratamento farmacológico , Distúrbios do Início e da Manutenção do Sono/metabolismoRESUMO
Tetracycline antibiotics as the emerging pollutants had been drawn abroad increasing concerns. An agricultural waste, the lignocellulosic hazelnut shell, was used as the carbon source to prepare the nanocomposites of zero-valent iron@biochar by pyrolytic reduction method at 1123 K for 2 h in N2 atmosphere. The adsorptive removal of tetracycline, oxytetracycline and chlortetracycline by the zero-valent iron@biochar from aqueous solution was investigated by batch method. The optimal experimental conditions were found to be at pH 6-7 with a contact time of 40 min. The adsorbed amounts of oxytetracycline, chlortetracycline and tetracycline at 298 K were 52.7, 42.5 and 39.1 mg g-1, respectively. Adsorption process of three antibiotics by the nanocomposite pursued Langmuir and pseudo-second-order equations. Thermodynamic parameters illustrated that the adsorption was spontaneous and endothermic intrinsically. The high removal efficiencies up to 95% of the zero-valent iron@biochar for oxytetracycline and chlortetracycline from the culture wastewaters had opened the potential applications for the removal of the antibiotics.
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Nanocompostos , Poluentes Químicos da Água , Adsorção , Antibacterianos , Carvão Vegetal , Ferro , Cinética , Tetraciclinas , Poluentes Químicos da Água/análiseRESUMO
3-Nitro-4-hydroxy-phenylarsonic acid (3-NHPAA), an organic-arsenic compound, as one of widely used antibacterial veterinary drug, has greatly attracted the attention due to its potential threats on ecological environment. A series of the nanocomposites of zirconia nanoparticles with crystal phases (pure monoclinic, pure tetragonal and mixed phase (monoclinic + tetragonal)) anchored on reduced graphene oxide were produced through managing the concentration of triethanolamine solution and the reaction time. The effects of the crystal phases of the zirconia in the structure of the nanocomposites were played a key role in the adsorption performances of the 3-NHPAA. Experiment data identified the nanocomposites with monoclinic phase of zirconia excelled at the adsorption of the 3-NHPAA with a higher adsorption capacity up to 207.2 mg g-1. The uptake of the 3-NHPAA by the three nanocomposites was implemented within 60 min and highly pH-dependent which illustrated electrostatic attraction between them as a main mechanism during the adsorption process. A wider pH range (3.8-8.8) for the uptake of the 3-NHPAA by the nanocomposites with the monoclinic phase of zirconia was obtained compared with the nanocomposites containing tetragonal phase (3.8-5.9) or the mixed phase (3.8-7.1) of zirconia. The adsorption of the 3-NHPAA was well described by the pseudo-second order kinetic and Langmuir equations. The thermodynamic parameters suggested that the adsorption of the 3-NHPAA over the three nanocomposites was endothermic and spontaneous in nature. In summary, the nanocomposites of reduced graphene oxide and monoclinic phase of zirconia nanoparticles as an adsorbent were better to the adsorption of the 3-NHPAA.
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Arsênio , Grafite , Nanocompostos , Preparações Farmacêuticas , Poluentes Químicos da Água , Adsorção , Arsênio/análise , Concentração de Íons de Hidrogênio , Cinética , Poluentes Químicos da Água/análise , ZircônioRESUMO
Acute lung injury (ALI) is a complex clinical syndrome with high morbidity and mortality rates. Autophagy is an adaptive process that plays a complex role in ALI. The aim of this study was to investigate the effects of autophagy on lipopolysaccharide (LPS)-induced lung injury by establishing a rat ALI model and to further explore the possible mechanisms involved. Rats were pretreated with the autophagy inhibitor 3-methyladenine (3-MA) or the autophagy activator rapamycin before they were challenged with the intratracheal instillation of LPS (5â¯mg/kg). The level of autophagy in the lung tissue was detected. Lung injury and vascular permeability were assessed. The role of the mechanistic target of rapamycin (mTOR)-mediated Unc-51-like kinase 1 (ULK1) and the class III PI3 kinase VPS34 in autophagy regulation was examined. LPS challenge induced autophagy and rapamycin pretreatment enhanced autophagy activity in LPS-induced ALI rats. LPS caused severe lung injury and high pulmonary vascular permeability, which could be alleviated by enhancing autophagy. In addition, the inhibition of mTOR upregulated the expression of ULK1 and VPS34 and thus increased LPS-induced autophagy. Autophagy plays a protective role in LPS-induced ALI, and enhancing autophagy via the inhibition of mTOR alleviates lung injury and pulmonary barrier function. Moreover, mTOR negatively mediates ULK1 and VPS34 to regulate LPS-induced autophagy in rats.
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Lesão Pulmonar Aguda/imunologia , Autofagia , Serina-Treonina Quinases TOR/imunologia , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/patologia , Animais , Proteína Homóloga à Proteína-1 Relacionada à Autofagia/imunologia , Líquido da Lavagem Broncoalveolar/imunologia , Classe III de Fosfatidilinositol 3-Quinases/imunologia , Interleucina-1beta/imunologia , Lipopolissacarídeos , Pulmão/imunologia , Pulmão/patologia , Masculino , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/imunologiaRESUMO
We report a paper-based surface-enhanced Raman spectroscopy (SERS) biosensor integrating the enrichment capability, namely enPSERS biosensor, for the sensitive, label-free detection of free bilirubin in blood serum for the accurate diagnosis of jaundice and its related diseases. This biosensor comprises multifunctional graphene oxide-plasmonic gold nanostar (GO-GNS) hybrids decorated on the filter paper, which integrates the high sensitivity of SERS detection, enrichment for serum bilirubin and fluorescence superquenching capability of GO-GNS hybrids for sensitive detection of serum bilirubin. The study of adsorption kinetics reveals that both electrostatic and π-π interactions between the GO-GNS hybrids and targets are responsible for the enrichment of bilirubin, and the adsorption process follows the pseudo-second-order kinetic model. The results of SERS detection of bilirubin in blood serum show two differential linear response ranges from 5.0 to 150⯵M and 150-500⯵M with the detection limit as low as 0.436⯵M. The comparison of the results obtained from our present enPSERS biosensor with the commercial diazo reaction method for determination of free bilirubin in blood serum reveals the clinical effectiveness and suitability of the developed paper-based SERS biosensor. We believe that this sensitive and label-free SERS biosensor holds considerable promise for clinical translation in accurate diagnosis of jaundice.
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Bilirrubina/isolamento & purificação , Técnicas Biossensoriais , Icterícia/sangue , Análise Espectral Raman/métodos , Bilirrubina/sangue , Ouro/química , Grafite/química , Humanos , Nanopartículas Metálicas/química , Papel , Propriedades de SuperfícieRESUMO
We report a ratiometric strategy for detection of different types of breast cancer cells by surface-enhanced Raman spectroscopy (SERS), which simultaneously quantifies the levels of dual biomarkers distinctly expressed on cancer cells to consequently achieve their expression ratio. Two SERS nanoprobes that are encoded with distinct SERS signatures are conjugated with urokinase plasminogen activation receptor (uPAR)- and epidermal growth factor receptor (EGFR)-targeting peptides. The SERS imaging of single live cells can accurately quantify the cellular biomarker expression difference from the SERS intensity ratio and is further employed for cancer cell screening. The results show that MDA-MB-231 and MCF-7 exhibit distinct expression of the uPAR and EGFR and they can be respectively discriminated by the intensity ratio of SERS signals from uPAR- and EGFR-targeting SERS nanoprobes. The ratiometric strategy permits background-free SERS detection of cancer cells and dramatically improves the signal-to-noise ratio of targeted cellular SERS imaging, thus enabling accurate cancer cell screening without the need for additional references. It is believed that the present ratiometric method should be a promising avenue for breast cancer diagnostics and screening, which can be easily extended for detection of other cancer cell types.
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Nanopartículas Metálicas/química , Neoplasias/diagnóstico , Análise Espectral Raman/métodos , Neoplasias da Mama/diagnóstico , Linhagem Celular Tumoral , Receptores ErbB/química , Receptores ErbB/uso terapêutico , Humanos , Receptores de Ativador de Plasminogênio Tipo Uroquinase/química , Receptores de Ativador de Plasminogênio Tipo Uroquinase/uso terapêuticoRESUMO
BACKGROUND: Primary dysmenorrhea (PD) is one of the most common health complaints all over the world, specifically among young females. Acupuncture has been employed to relieve the pain-based symptoms and to avoid the side effects of conventional medication, and wrist-ankle acupuncture (WAA) has confirmed analgesic efficacy for various types of pain. The aim of this study is to evaluate the immediate analgesia effect of WAA on PD of young females. METHODS/DESIGN: This study will carry out a randomized parallel controlled single-blind trial to observe the immediate analgesia effect of WAA in PD of young females. Sixty participants who meet inclusion criteria will be recruited from September 2016 to September 2017 in Changhai hospital of China. They are randomly assigned to WAA therapy or sham acupuncture groups (30 patients for each group), and then receive real or sham acupuncture treatment, respectively. In this trial, the primary outcome measure is simple form of McGill pain questionnaire (SF-MPQ), while expectation and treatment credibility scale (ETCS), safety assessment, the COX menstrual symptom scale (CMSS), questionnaire about the feeling of being punctured are included in the secondary outcomes. DISCUSSION: This trial will be the first study protocol designed to evaluate the immediate analgesia effect of WAA in PD of young females. The strengths in methodology, including rigorous randomized, sham-controlled, participants-blinded and assessors-blinded, will guarantee the quality of this study. WAA doesn't require any needling sensation, so non-penetrating sham acupuncture can serve as an effective placebo intervention in this trial. TRIALS REGISTRATION: Chinese Clinical Trial Registry (identifier: ChiCTR-IOR-16008546 ; registration date: 27 May 2016).
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Terapia por Acupuntura/métodos , Tornozelo/fisiologia , Dismenorreia/terapia , Punho/fisiologia , Adolescente , Adulto , Feminino , Humanos , Projetos de Pesquisa , Adulto JovemRESUMO
A new type of carbene-based ruthenium sensitizer, CB104, with a highly conjugated ancillary ligand, diphenylvinylthiophene-substituted benzimidazolepyridine, was designed and developed for dye-sensitized solar cell applications. The influence of the thiophene antenna on the performance of the cell anchored with CB104 was investigated. Compared with the dye CBTR, the conjugated thiophene in the ancillary ligand of CB104 enhanced the molar extinction coefficient of the intraligand π-π* transition and the intensity of the lower energy metal-to-ligand charge-transfer band. However, the incident photon-to-current conversion efficiency spectrum of the cell anchored with CB104 (0.15â mM) showed a maximum of 63 % at 420â nm. The cell sensitized with the dye CB104 attained a power conversion efficiency of 7.30 %, which was lower than that of the cell with nonconjugated sensitizer CBTR (8.92 %) under the same fabrication conditions. The variation in the performance of these two dyes demonstrated that elongating the conjugated light-harvesting antenna resulted in the reduction of short-circuit photocurrent density, which might have been due to the aggregation of dye molecules. In the presence of a coabsorbate, chenodeoxycholic acid, the CB104-sensitized cell exhibited an enhanced photocurrent density and achieved a photovoltaic efficiency of 8.36 %.
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OBJECTIVE: To observe the effect of electroacupuncture (EA) stimulation of "Fenglong" (ST 40) on blood lipid contents and inflammatory factor levels in hyperlipemia rats so as to elucidate its mechanism underlying improvement of hyperlipemia. METHODS: Fifty male SD rats were randomized into 5 groups: normal, model, diet -control, EA intervention (EA), diet-control + EA groups, with 10 rats in each group. Hyperlipemia model was established by feeding the animals with high-fat diet for 30 days. After modeling, rats in the diet-control group were fed with routine fodder. EA was applied to bilateral "Fenglong" (ST 40) for 30 min, once daily for 30 days. Following intraperitoneal injection of 1640 culture fluid, the peritoneal fluid was collected and centrifuged for extracting macrophages. Flow cytometry (FCM) was employed to determine the levels of tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) after adding fluoresce-labeled antibodies. RESULTS: The contents of serum TC and LDL-C were remarkably higher and HDL-C level was significantly lower in the model group than in the normal group (P < 0.01). After EA intervention, serum TC and LDL-C showed an apparent decrease (P < 0.01). Compared with the normal group, percentages of CD11 b, TNF-alpha and IL-6 were significantly increased in the model group (P < 0.01), while in comparison with the model group, percentages of CD11 b in both EA and diet-control + EA groups, TNF-alpha and IL-6 percentages of macrophages in the diet-control, EA and diet-control + EA groups were notably decreased (P < 0.05, P < 0.01). The effects of the diet-control + EA group were considerably superior to those of the diet-control group in lowering CD11 b, TNF-alpha and IL-6 percentages (P < 0.05, P < 0.01). No significant differences were found between the diet-control and EA groups in the aforementioned indexes (P > 0.05). CD11 b level indicates changes of macrophage level due to its specific marker character. CONCLUSION: EA stimulation of "Fenglong" (ST 40) is effective in lowering serum TC, LDL-C, and macrophage TNF-alpha and IL-6 levels in hyperlipemia rats.
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Pontos de Acupuntura , Eletroacupuntura , Hiperlipidemias/terapia , Interleucina-6/sangue , Lipídeos/sangue , Macrófagos/imunologia , Fator de Necrose Tumoral alfa/sangue , Animais , Humanos , Hiperlipidemias/sangue , Hiperlipidemias/imunologia , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
EBV infects more than 90% of the human population and persists in most individuals as a latent infection where the viral genome is silenced by host-driven methylation. The lytic cycle is initiated when the viral protein Zta binds to methylated BRLF1 and BRRF1 promoters. Although studies reveal the role of Zta and methylation changes in the viral genome upon EBV infection to reactivation, whether Zta plays any role in alteration of methylation in the host genome remains unknown. Using an inducible model, we demonstrate that global DNA methylation, based on whole-genome 5-methylcytosine content, and regional DNA methylation in repetitive elements, imprinting genes and the X chromosome, remains unchanged in response to Zta expression. Expression of DNA methyltransferases was also unaffected by ectopically expressed Zta. Our data imply that alteration of host gene expression following EBV reactivation may reflect methylation-independent Zta-mediated gene activation and not epigenetic modification of the host genome.
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Metilação de DNA/genética , Infecções por Vírus Epstein-Barr/genética , Infecções por Vírus Epstein-Barr/virologia , Herpesvirus Humano 4/metabolismo , Transativadores/metabolismo , 5-Metilcitosina/metabolismo , Sequência de Bases , Linhagem Celular Tumoral , Proteína 1 de Resposta de Crescimento Precoce/genética , Proteína 1 de Resposta de Crescimento Precoce/metabolismo , Genoma Viral/genética , Impressão Genômica , Herpesvirus Humano 4/genética , Humanos , Proteínas Imediatamente Precoces/genética , Proteínas Imediatamente Precoces/metabolismo , Fator de Crescimento Insulin-Like II/genética , Fator de Crescimento Insulin-Like II/metabolismo , Dados de Sequência Molecular , Regiões Promotoras Genéticas , Análise de Sequência de DNA , Transativadores/genética , Inativação do Cromossomo X/genéticaRESUMO
The low-copy repeat (LCR) is a new class of repetitive DNA element and has been implicated in many human disorders, including DiGeorge/velocardiofacial syndrome (DGS/VCFS). It is now recognized that nonallelic homologous recombination (NAHR) through LCRs flanking the chromosome 22q11.2 region leads to genome rearrangements and results in the DGS/VCFS. To refine the structure and content of chromosome 22q11.2 LCRs, we applied computational analysis to dissect region-specific LCRs using publicly available sequences. Nine distinct duplicons between 1.6 and 65 kb long and sharing >95% sequence identity were identified. The presence of these sequence motifs supports the NAHR mechanism. Further sequence analysis suggested that the previously defined 3-Mb deletion may actually comprise two deletion intervals of similar size close to each other and thus indistinguishable when using fluorescence in situ hybridization (FISH) analysis. The differentially deleted regions contain several hypothetical proteins and UniGene clusters and may partially explain the clinical heterogeneity observed in DGS/VCFS patients with the 3-Mb common deletion. To implement further sequence information in molecular medicine, we designed a real-time quantitative PCR assay and validated the method in 122 patients with suspected DGS/VCFS. The assay detected 28 patients with chromosome 22q11.2 deletion later confirmed using FISH. Our results indicated that the developed assay is reliable as well as time and cost effective for clinical diagnosis of chromosome 22q11.2 deletion. They also suggest that this methodology can be applied to develop a molecular approach for clinical detection and diagnosis of other genomic disorders.