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Acute lung injury (ALI) is a disease characterized by extensive lung damage and rampant inflammation, with a high mortality rate and no effective treatments available. Morinda officinalis oligosaccharides (MOOs), derived from the root of the traditional Chinese medicinal herb Morinda officinalis, known for its immune-boosting properties, presents a novel therapeutic possibility. To date, the impact of MOOs on ALI has not been explored. Our study aimed to investigate the potential protective effects of MOOs against ALI and to uncover the underlying mechanisms through an integrated approach of network pharmacology, molecular docking, and experimental validation. We discovered that MOOs significantly mitigated the pathological damage and decreased the expression of pro-inflammatory cytokines in LPS-induced ALI in mice. Complementary in vitro studies further demonstrated that MOOs effectively attenuated the M1 polarization induced by LPS. Network pharmacology analysis identified HSP90AA1, HSP90AB1, and NF-κB as key overlapping targets within a protein-protein interaction (PPI) network. Furthermore, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses elucidated the biological processes and signaling pathways implicated in MOOs' therapeutic action on ALI. Subsequently, molecular docking affirmed the binding of MOOs to the active sites of these identified targets. Corroborating these findings, our in vivo and in vitro experiments consistently demonstrated that MOOs significantly inhibited the LPS-induced upregulation of HSP90 and NF-κB. Collectively, these findings suggest that MOOs confer protection against ALI through a multi-target, multi-pathway mechanism, offering a promising new therapeutic strategy to mitigate this severe pulmonary condition.
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Lesão Pulmonar Aguda , Lipopolissacarídeos , Simulação de Acoplamento Molecular , Morinda , Oligossacarídeos , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/metabolismo , Lesão Pulmonar Aguda/patologia , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Animais , Morinda/química , Camundongos , Oligossacarídeos/farmacologia , Oligossacarídeos/química , Oligossacarídeos/isolamento & purificação , Masculino , Células RAW 264.7 , Camundongos Endogâmicos C57BL , Citocinas/metabolismo , NF-kappa B/metabolismoRESUMO
Electronic health (eHealth) is a strategy to improve the physical and mental condition of a human, collecting daily physiological data and information from digital apparatuses. Body weight and blood pressure (BP) are the most popular and important physiological data. The goal of this study is to develop a minimal contact BP measurement method based on a commercial body weight-fat scale, capturing biometrics when users stand on it. The pulse transit time (PTT) is extracted from the ballistocardiogram (BCG) and impedance plethysmogram (IPG), measured by four strain gauges and four footpads of a commercial body weight-fat scale. Cuffless BP measurement using the electrocardiogram (ECG) and photoplethysmogram (PPG) serves as the reference method. The BP measured by a commercial BP monitor is considered the ground truth. Twenty subjects participated in this study. By the proposed model, the root-mean-square errors and correlation coefficients (r2s) of estimated systolic blood pressure and diastolic blood pressure are 7.3 ± 2.1 mmHg and 4.5 ± 1.8 mmHg, and 0.570 ± 0.205 and 0.284 ± 0.166, respectively. This accuracy level achieves the C grade of the corresponding IEEE standard. Thus, the proposed method has the potential benefit for eHealth monitoring in daily application.
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Tecido Adiposo , Determinação da Pressão Arterial , Humanos , Pressão Sanguínea , Impedância Elétrica , Peso CorporalRESUMO
With 252 species, Pseudopoda Jäger, 2000, is the largest genus in the family Sparassidae and is widely distributed in South (49 species in Bhutan, India, Nepal and Pakistan), East (158 species in China and Japan) and Southeast Asia (51 species in Indonesia, Laos, Myanmar, Thailand and Vietnam). Few species have been found in more than one region. In this paper, three new species of Pseudopoda are described from East and Southeast Asia. Among them, one from China: P.fengtongzhaiensis Jäger & Liu, sp. nov. (â); one from Laos: P.baimai Jäger & Liu, sp. nov. (â); and one from Thailand: P.inthanonensis Jäger & Liu, sp. nov. (â). Additionally, the female of P.kavanaughi Zhang, Jäger & Liu, 2023 is described for the first time. Photos of the habitus and genitalia, as well as a distribution map of all four species, are provided.
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Leaf color mutants are ideal materials for studying chlorophyll metabolism, chloroplast development, and photosynthesis in plants. We discovered a novel eggplant (Solanum melongena L.) mutant yl20 (yellow leaf 20) that exhibits yellow leaves. In this study, we compared the leaves of the mutant yl20 and wild type (WT) plants for cytological, physiological, and transcriptomic analyses. The results showed that the mutant yl20 exhibits abnormal chloroplast ultrastructure, reduced chlorophyll and carotenoid contents, and lower photosynthetic efficiency compared to the WT. Transcriptome data indicated 3267 and 478 differentially expressed genes (DEGs) between WT and yl20 lines in the cotyledon and euphylla stages, respectively, where most DEGs were downregulated in the yl20. Gene Ontology (GO) analysis revealed the "plastid-encoded plastid RNA polymerase complex" and the "chloroplast-related" terms were significantly enriched. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis demonstrated that the significantly enriched DEGs were involved in flavone and flavonol biosynthesis, porphyrin and chlorophyll metabolism, etc. We speculated that these DEGs involved in significant terms were closely related to the leaf color development of the mutant yl20. Our results provide a possible explanation for the altered phenotype of leaf color mutants in eggplant and lay a theoretical foundation for plant breeding.
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The study aims to explore the relationship among metacognition (MC), fear of disease of progression (FoP), psychological distress (PD), and quality of life (QoL), and verify whether FoP and PD have a chain mediating effect between MC and QoL. 231 hematologic tumor patients in a large tertiary hospital were investigated by using Meta-Cognitions Questionnaire-30, Fear of Progression Questionnaire-Short Form, Hospital Anxiety and Depression Scale, and Functional Assessment of Cancer Therapy scale. Data analyses were performed using IBM SPSS (version 25.0) and the PROCESS macro (version 4.1). The results showed that the direct impact of MC on QoL was not statistically significant. However, the indirect influence of MC on QoL manifest through the independent influences of PD and FoP, as well as the chain mediating effect of "PD â FoP." In addition, all four dimensions of QoL (physical, social and family, emotional, and functional) satisfy the chain mediation model, except for the social and family domain. These insights advance our comprehension of the intricate interplay between MC and QoL, underscoring the importance of improving MC to alleviate patients' PD, mitigate FoP, and ultimately improve the QoL of hematologic tumor patients.
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Neoplasias Hematológicas , Metacognição , Qualidade de Vida , Humanos , Neoplasias Hematológicas/psicologia , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Metacognição/fisiologia , Idoso , Inquéritos e Questionários , Medo/psicologia , Progressão da Doença , Angústia PsicológicaRESUMO
We report the design of a self-assembled aptamer-micelle nanostructure that achieves selective and strong binding of otherwise low-affinity aptamers at physiological conditions. Specific recognition ability is directly built into the nanostructures. The attachment of a lipid tail onto the end of nucleic acid aptamers provides these unique nanostructures with an internalization pathway. Other merits include: extremely low off rate once bound with target cells, rapid recognition ability with enhanced sensitivity, low critical micelle concentration values, and dual-drug delivery pathways. To prove the potential detection/delivery application of this aptamer-micelle in biological living systems, we mimicked a tumor site in the blood stream by immobilizing tumor cells onto the surface of a flow channel device. Flushing the aptamer-micelles through the channel demonstrated their selective recognition ability under flow circulation in human whole-blood sample. The aptamer-micelles show great dynamic specificity in flow channel systems that mimic drug delivery in the blood system. Therefore, our DNA aptamer-micelle assembly has shown high potential for cancer cell recognition and for in vivo drug delivery applications.
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Aptâmeros de Nucleotídeos , Sistemas de Liberação de Medicamentos , Micelas , Nanoestruturas/química , Neoplasias/tratamento farmacológico , Aptâmeros de Nucleotídeos/química , Aptâmeros de Nucleotídeos/metabolismo , Aptâmeros de Nucleotídeos/uso terapêutico , Linhagem Celular Tumoral , Portadores de Fármacos/química , Portadores de Fármacos/metabolismo , Endocitose , Citometria de Fluxo/métodos , Corantes Fluorescentes/metabolismo , HumanosRESUMO
Acute lung injury (ALI) is a severe clinical disorder characterized by dysregulated inflammatory responses, leading to high rates of morbidity and mortality. Cinobufagin, a primary component isolated from cinobufotalin, exerts strong anticancer effects. However, there are few reports on its role in ALI, and it is unclear whether cinobufagin affects lipopolysaccharide (LPS)-induced ALI. Therefore, the present study aimed to investigate the effect of cinobufagin on LPS-induced ALI and to assess its potential mechanism of action. The results showed that cinobufagin alleviated lung histopathological changes and protected the permeability of lung tissues in LPS-induced ALI. In addition, cinobufagin effectively suppressed inflammatory responses through the induction of autophagy in LPS-induced ALI cells and in a mouse model. Moreover, cinobufagin enhanced autophagy through the p53/mTOR pathway in LPS-induced ALI. Herein, it was reported for the first time that cinobufagin inhibited the inflammatory response of LPS-induced ALI, which laid the foundation for further understanding and development of cinobufagin as a potential new drug for ALI.
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Fruit color is an important commercial characteristic of eggplant (Solanum melongena L.), which affects both the profits of growers and consumer choice. Two eggplant inbred lines were discovered: "Z," which is a light purple color under the fruit calyx, with purple on the fruit apex; and "L," fruits of which are green under the calyx and at the apex. To determine the molecular mechanisms underlying the effect of fruit peel color under the calyx on that at the fruit apex, we conducted a combined transcriptomic and metabolomic analyses of the Z and L inbred eggplant lines. Transcriptome analysis of peel samples from three fruit regions (under the calyx, the apex, and the middle surface) of each line was conducted by RNA sequencing, and generated a total of 791,512,404 clean reads from 18 samples (three biological replicates). Differentially expressed genes (DEGs; n = 424) were identified in comparisons of peel samples from the three sites of L line fruits. Gene ontology analysis showed that "catalytic activity" was extremely significantly enriched. Further, DEGs (n = 8) were enriched in the Kyoto Encyclopedia of Genes and Genomes pathway "flavonoid biosynthesis." Levels of CHI, LDOX, F3'5'H, and dihydroflavonol reductase were higher in the Z line than the L line. In addition, metabolome analysis showed that, 10 differentially accumulated metabolites were detected between peel samples from the apex of L and Z line fruit. The most significant DAM was delphinidin-3-O-rutinoside (Z line content, 34.89 µg/g vs. L line content 0.01 µg/g). Combined transcriptomic and metabolomic analyses indicated that DFR and F3'5'H were closely related to content of the metabolites, cyanidin and delphinidin, and that some downstream metabolites differed significantly between the L and Z lines. Content levels of delphinidin-3-O-rutinoside, delphinidin-3-O-glucoside, cyanidin-3-O-glucoside, and cyanidin-3-O-rutinoside were markedly down-regulated in the L line. Altogether, increased CHI levels could up-regulate the downstream genes, LDOX, F3'5'H, and DFR, which further lead to increasing the content of delphindin. Thus, the uniform purple color was presented at the apex of fruits in Z plants. These findings not only identify key candidate genes, but will also improve understanding of the genetics and the efficiency of breeding for eggplant fruit color.
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Diabetic retinopathy (DR) is a common microvascular complication in patients with diabetes mellitus. DR is caused by chronic hyperglycemia and is characterized by progressive loss of vision because of damage to the retinal microvasculature. In this study, we investigated the regulatory role and clinical significance of the vascular endothelial growth factor (VEGF)/protein kinase C (PKC)/endothelin (ET)/nuclear factor-κB (NF-κB)/intercellular adhesion molecule 1 (ICAM-1) signaling pathway in DR using a rat model. Intraperitoneal injections of the VEGF agonist, streptozotocin (STZ) were used to generate the DR model rats. DR rats treated with the VEGF inhibitor (DR+VEGF inhibitor) were used to study the specific effects of VEGF on DR pathology and the underlying mechanisms. DR and DR+VEGF agonist rats were injected with the PKCß2 inhibitor, GF109203X to determine the therapeutic potential of blocking the VEGF/PKC/ET/NF-κB/ICAM-1 signaling pathway. The body weights and blood glucose levels of the rats in all groups were evaluated at 16 weeks. DR-related retinal histopathology was analyzed by hematoxylin and eosin staining. ELISA assay was used to estimate the PKC activity in the retinal tissues. Western blotting and RT-qPCR assays were used to analyze the expression levels of PKC-ß2, VEGF, ETs, NF-κB, and ICAM-1 in the retinal tissues. Immunohistochemistry was used to analyze VEGF and ICAM-1 expression in the rat retinal tissues. Our results showed that VEGF, ICAM-1, PKCß2, ET, and NF-κB expression levels as well as PKC activity were significantly increased in the retinal tissues of the DR and DR+VEGF agonist rat groups compared to the control and DR+VEGF inhibitor rat groups. DR and DR+VEGF agonist rats showed significantly lower body weight and significantly higher retinal histopathology scores and blood glucose levels compared to the control and DR+VEGF inhibitor group rats. However, treatment of DR and DR+VEGF agonist rats with GF109203X partially alleviated DR pathology by inhibiting the VEGF/ PKC/ET/NF-κB/ICAM-1 signaling pathway. In summary, our data demonstrated that inhibition of the VEGF/ PKC/ET/NF-κB/ICAM-1 signaling pathway significantly alleviated DR-related pathology in the rat model. Therefore, VEGF/PKC/ET/NF-κB/ICAM-1 signaling axis is a promising therapeutic target for DR.
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Diabetes Mellitus Experimental , Retinopatia Diabética , Ratos , Animais , Retinopatia Diabética/tratamento farmacológico , Retinopatia Diabética/metabolismo , Retinopatia Diabética/patologia , NF-kappa B/metabolismo , Molécula 1 de Adesão Intercelular/metabolismo , Molécula 1 de Adesão Intercelular/uso terapêutico , Fator A de Crescimento do Endotélio Vascular/metabolismo , Proteína Quinase C beta/metabolismo , Glicemia , Diabetes Mellitus Experimental/metabolismo , Ratos Sprague-Dawley , Transdução de Sinais/fisiologiaRESUMO
BACKGROUND: Although numerous studies have described the application of artificial intelligence (AI) in diabetic retinopathy (DR) screening among diabetic populations, studies among populations in rural areas are rare. The purpose of this study was to evaluate the application value of an AI-based diagnostic system for DR screening in rural areas of midwest China. METHODS: In this diagnostic accuracy study, diabetes mellitus (DM) patients in the National Basic Public Health Information Systems of Licheng County and Lucheng County of Changzhi city from July to December 2020 were selected as the target population. A total of 7824 eyes of 3933 DM patients were enrolled in this screening; the patients included 1395 males and 2401 females, with an average age of 19-87 years (63±8.735 years). All fundus photographs were collected by a professional ophthalmologist under natural pupil conditions in a darkroom using the Zhiyuan Huitu fundus image AI analysis software EyeWisdom. The AI-based diagnostic system and ophthalmologists were tasked with diagnosing the photos independently, and the consistency rate, sensitivity and specificity of the two methods in diagnosing DR were calculated and compared. RESULTS: The prevalence rates of DR according to the ophthalmologist and AI diagnoses were 22.7% and 22.5%, respectively; the consistency rate was 81.6%. The sensitivity and specificity of the AI system relative to the ophthalmologists' grades were 81.2% (95% confidence interval [CI]: 80.3% 82.1%) and 94.3% (95% CI: 93.7% 94.8%), respectively. There was no significant difference in diagnostic outcomes between the methods (χ2 = 0.329, P = 0.566, P>0.05), and the AI-based diagnostic system had high consistency with the ophthalmologists' diagnostic results (κ = 0.752). CONCLUSION: Our research demonstrated that DR patients in rural area hospitals can be screened feasibly. Compared with that of the ophthalmologists, however, the accuracy of the AI system must be improved. The results of this study might lend support to the large-scale application of AI in DR screening among different populations.
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Diabetes Mellitus , Retinopatia Diabética , Adulto , Idoso , Idoso de 80 Anos ou mais , Inteligência Artificial , China/epidemiologia , Retinopatia Diabética/diagnóstico , Retinopatia Diabética/epidemiologia , Feminino , Fundo de Olho , Humanos , Masculino , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Adulto JovemRESUMO
OBJECTIVE: To compare the efficacy between acupuncture-moxibustion treatment by stages and femoston for premature ovarian insufficiency (POI). METHODS: A total of 66 patients with POI were randomly divided into an observation group (33 cases, 3 cases dropped off) and a control group (33 cases, 2 cases dropped off). The patients in the observation group, based on the theory of "transformation of yin and yang", were treated with acupuncture-moxibustion by stages in the postmenstrual period, ovulatory period, premenstrual period and menstrual period, once every other day, 3 times a week. The patients in the control group were treated with oral administration of femoston (estradiol tablets/estradiol and dydrogesterone tablets, 1 tablet per day). Both groups were treated for 3 menstrual cycles. The ovarian function (serum follicle-stimulating hormone [FSH], luteinizing hormone [LH], estradiol [E2], anti-mullerian hormone [AMH] and antral follicle count [AFC]) and perimenopausal symptoms [modified Kupperman index (KI) scale score] were observed before and after treatment, and the menstrual improvement of the two groups was compared. RESULTS: Compared before treatment, the serum levels of FSH and LH were decreased (P<0.01), the levels of E2 were increased (P<0.01) in the two groups after treatment; the serum level of AMH and AFC in the observation group were increased after treatment (P<0.01). After treatment, the serum level of AMH and AFC in the observation group were higher than those in the control group (P<0.05). After treatment, there was no significant difference in the menstrual return rate and menstrual regularity rate between the amenorrhea patients of the two groups (P>0.05). After treatment, the modified KI scale scores in the two groups were reduced (P<0.01), and the modified KI scale score in the observation group was lower than that in the control group (P<0.05). CONCLUSION: Acupuncture- moxibustion treatment by stages based on the theory of "transformation of yin and yang" has similar efficacy with femoston in improving serum sex hormone level and menstrual symptoms in patients with POI, and has advantages in improving serum AMH level, AFC and perimenopausal symptoms.
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Terapia por Acupuntura , Moxibustão , Insuficiência Ovariana Primária , Pontos de Acupuntura , Feminino , Hormônio Foliculoestimulante , Humanos , Insuficiência Ovariana Primária/terapiaRESUMO
Abnormal glucose and lipid metabolism in COVID-19 patients were recently reported with unclear mechanism. In this study, we retrospectively investigated a cohort of COVID-19 patients without pre-existing metabolic-related diseases, and found new-onset insulin resistance, hyperglycemia, and decreased HDL-C in these patients. Mechanistically, SARS-CoV-2 infection increased the expression of RE1-silencing transcription factor (REST), which modulated the expression of secreted metabolic factors including myeloperoxidase, apelin, and myostatin at the transcriptional level, resulting in the perturbation of glucose and lipid metabolism. Furthermore, several lipids, including (±)5-HETE, (±)12-HETE, propionic acid, and isobutyric acid were identified as the potential biomarkers of COVID-19-induced metabolic dysregulation, especially in insulin resistance. Taken together, our study revealed insulin resistance as the direct cause of hyperglycemia upon COVID-19, and further illustrated the underlying mechanisms, providing potential therapeutic targets for COVID-19-induced metabolic complications.
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COVID-19/sangue , Hiperglicemia/sangue , Resistência à Insulina , Metabolismo dos Lipídeos , Lipídeos/sangue , SARS-CoV-2/metabolismo , Adulto , Idoso , Biomarcadores/sangue , COVID-19/complicações , Feminino , Humanos , Hiperglicemia/etiologia , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Functional nanomaterials based on molecular self-assembly hold great promise for applications in biomedicine and biotechnology. However, their efficacy could be a problem and can be improved by precisely controlling the size, structure, and functions. This would require a molecular engineering design capable of producing monodispersed functional materials characterized by beneficial changes in size, shape, and chemical structure. To address this challenge, we have designed and constructed a series of amphiphilic oligonucleotide molecules. In aqueous solutions, the amphiphilic oligonucleotide molecules, consisting of a hydrophilic oligonucleotide covalently linked to hydrophobic diacyllipid tails, spontaneously self-assemble into monodispersed, three-dimensional micellar nanostructures with a lipid core and a DNA corona. These hierarchical architectures are results of intermolecular hydrophobic interactions. Experimental testing further showed that these types of micelles have excellent thermal stability and their size can be fine-tuned by changing the length of the DNA sequence. Moreover, in the micelle system, the molecular recognition properties of DNA are intact, thus, our DNA micelles can hybridize with complimentary sequences while retaining their structural integrity. Importantly, when interacting with cell membranes, the highly charged DNA micelles are able to disintegrate themselves and insert into the cell membrane, completing the process of internalization by endocytosis. Interestingly, the fluorescence was found accumulated in confined regions of cytosole. Finally, we show that the kinetics of this internalization process is size-dependent. Therefore, cell permeability, combined with small sizes and natural nontoxicity are all excellent features that make our DNA-micelles highly suitable for a variety of applications in nanobiotechnology, cell biology, and drug delivery systems.
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DNA/química , Micelas , Linhagem Celular , Permeabilidade da Membrana Celular , Humanos , Microscopia de Fluorescência , Nanoestruturas/química , Tamanho da PartículaRESUMO
Over the past few years, single-walled carbon nanotubes (SWNTs) have been the focus of intense research motivated by their unique physical and chemical properties. This review specifically summarizes recent progress in the development of fluorescence biosensors that integrate the quenching property of SWNTs and the recognition property of functional nucleic acids. SWNTs are substantially different from organic quenchers, showing superior quenching efficiency for a variety of fluorophores, with low background and high signal-to-noise ratio, as well as other advantages derived from the nanomaterial itself. As the second key component of biosensors, functional nucleic acids can bind to either their complementary DNA or a target molecule with the ability to recognize a broad range of targets from metal ions to organic molecules, proteins, and even live cells. By taking advantage of the strengths and properties of both SWNTs and nucleic acid based aptamers, a series of fluorescence biosensors have been designed and fabricated for the detection of a broad range of analytes with high selectivity and sensitivity.
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Técnicas Biossensoriais/tendências , Corantes Fluorescentes/química , Nanotubos de Carbono/química , Técnicas Biossensoriais/instrumentação , DNA/química , Concentração de Íons de HidrogênioRESUMO
OBJECTIVE: To compare the clinical therapeutic effect of electroacupuncture (EA) combined with penetrating moxibustion and biofeedback electrical stimulation on postpartum pelvic organ prolapsed (POP). METHODS: A total of 60 patients with POP who had delivery 6 weeks ago were randomized into an observation group and a control group, 30 cases in each one. In the observation group, EA was applied at Zigong (EX-CA 1), Ciliao (BL 32), Huiyang (BL 35), etc. while penetrating moxibustion was performed at acupoints of abdomen and lumbosacral region alternately every other day. In the control group, biofeedback electrical stimulation was provided. The treatment for 6 weeks was given once every other day, 3 times a week in both groups. Before treatment, after treatment and 6 months after delivery, pelvic floor muscle strength, pelvic organ prolapse quantification (POP-Q) evaluation and pelvic floor impact questionnaire short form-7 (PFIQ-7) were observed to assess the therapeutic effect. RESULTS: Compared before treatment, the sustained contraction and rapid contraction force of pelvic floor muscle after treatment and 6 months after delivery were increased in both of the two groups (P<0.05), and the changes in the observation group were larger than those in the control group (P<0.05). After treatment and 6 months after delivery, the POP degree in the observation group was alleviated to the control group (P<0.05). Compared before treatment, the scores of PFIQ-7 after treatment and 6 months after delivery were reduced in the two groups (P<0.05), and the changes in the observation group were larger than those in the control group (P<0.05). CONCLUSION: Electroacupuncture combined with penetrating moxibustion can strengthen the pelvic floor muscle contractility of patients with postpartum pelvic organ prolapse, and are superior to biofeedback electrical stimulation in improving the pelvic organ prolapse status and life quality.
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Eletroacupuntura , Moxibustão , Prolapso de Órgão Pélvico/terapia , Período Pós-Parto , Feminino , Humanos , Diafragma da Pelve , Qualidade de Vida , Inquéritos e Questionários , Resultado do TratamentoRESUMO
We report temporal patterns of viral shedding in 94 patients with laboratory-confirmed COVID-19 and modeled COVID-19 infectiousness profiles from a separate sample of 77 infector-infectee transmission pairs. We observed the highest viral load in throat swabs at the time of symptom onset, and inferred that infectiousness peaked on or before symptom onset. We estimated that 44% (95% confidence interval, 25-69%) of secondary cases were infected during the index cases' presymptomatic stage, in settings with substantial household clustering, active case finding and quarantine outside the home. Disease control measures should be adjusted to account for probable substantial presymptomatic transmission.
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Betacoronavirus/fisiologia , Infecções por Coronavirus/transmissão , Pneumonia Viral/transmissão , Eliminação de Partículas Virais , COVID-19 , Infecções por Coronavirus/epidemiologia , Humanos , Pandemias , Pneumonia Viral/epidemiologia , SARS-CoV-2RESUMO
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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BACKGROUND: The clinical manifestations and factors associated with the severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections outside of Wuhan are not clearly understood. METHODS: All laboratory-confirmed cases with SARS-Cov-2 infection who were hospitalized and monitored in Guangzhou Eighth People's Hospital were recruited from January 20 to February 10. RESULTS: A total of 275 patients were included in this study. The median patient age was 49 years, and 63.6% had exposure to Wuhan. The median virus incubation period was 6 days. Fever (70.5%) and dry cough (56.0%) were the most common symptoms. A decreased albumin level was found in 51.3% of patients, lymphopenia in 33.5%, and pneumonia based on chest computed tomography in 86%. Approximately 16% of patients (nâ =â 45) had severe disease, and there were no deaths. Compared with patients with nonsevere disease, those with severe disease were older, had a higher frequency of coexisting conditions and pneumonia, and had a shorter incubation period (all Pâ <â .05). There were no differences between patients who likely contacted the virus in Wuhan and those who had no exposure to Wuhan. Multivariate logistic regression analysis indicated that older age, male sex, and decreased albumin level were independently associated with disease severity. CONCLUSIONS: Most of the patients infected with SARS-CoV-2 in Guangzhou, China are not severe cases and patients with older age, male, and decreased albumin level were more likely to develop into severe ones.
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DNA sensors and microarrays permit fast, simple, and real-time detection of nucleic acids through the design and use of increasingly sensitive, selective, and robust molecular probes. Specifically, molecular beacons (MBs) have been employed for this purpose; however, their potential in the development of solid-surface-based biosensors has not been fully realized. This is mainly a consequence of the beacon's poor stability because of the hairpin structure once immobilized onto a solid surface, commonly resulting in a low signal enhancement. Here, we report the design of a new MB that overcomes some of the limitations of MBs for surface immobilization. Essentially, this new design adds locked nucleic acid bases (LNAs) to the beacon structure, resulting in a LNA molecular beacon (LMB) with robust stability after surface immobilization. To test the efficacy of LMBs against that of regular molecular beacons (RMBs), the properties of selectivity, sensitivity, thermal stability, hybridization kinetics, and robustness for the detection of target sequences were compared and evaluated. A 25-fold enhancement was achieved for the LMB on surface with detection limits reaching the low nanomolar range. In addition, the LMB-based biosensor was shown to possess better stability, reproducibility, selectivity, and robustness when compared to the RMB. Therefore, as an alternative to conventional DNA and as a prospective tool for use in both DNA microarrays and biosensors, these results demonstrate the potential of the locked nucleic acid bases for nucleic acid design for surface immobilization.
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Técnicas Biossensoriais/métodos , Sondas de Ácido Nucleico/síntese química , Oligonucleotídeos/química , Animais , Sequência de Bases , Biotecnologia , Bovinos , Extratos Celulares , Cinética , Hibridização de Ácido Nucleico , Sondas de Ácido Nucleico/química , Sondas de Ácido Nucleico/genética , Análise de Sequência com Séries de Oligonucleotídeos , Sensibilidade e Especificidade , Propriedades de Superfície , TemperaturaRESUMO
To take full advantage of locked nucleic acid (LNA) based molecular beacons (LNA-MBs) for a variety of applications including analysis of complex samples and intracellular monitoring, we have systematically synthesized a series of DNA/LNA chimeric MBs and studied the effect of DNA/LNA ratio in MBs on their thermodynamics, hybridization kinetics, protein binding affinity and enzymatic resistance. It was found that the LNA bases in a MB stem sequence had a significant effect on the stability of the hair-pin structure. The hybridization rates of LNA-MBs were significantly improved by lowering the DNA/LNA ratio in the probe, and most significantly, by having a shared-stem design for the LNA-MB to prevent sticky-end pairing. It was found that only MB sequences with DNA/LNA alternating bases or all LNA bases were able to resist nonspecific protein binding and DNase I digestion. Additional results showed that a sequence consisting of a DNA stretch less than three bases between LNA bases was able to block RNase H function. This study suggested that a shared-stem MB with a 4 base-pair stem and alternating DNA/LNA bases is desirable for intracellular applications as it ensures reasonable hybridization rates, reduces protein binding and resists nuclease degradation for both target and probes. These findings have implications on the design of LNA molecular probes for intracellular monitoring application, disease diagnosis and basic biological studies.