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1.
J Ovarian Res ; 17(1): 126, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38890751

RESUMO

Ovarian cancer is a common malignant tumor in women, with a high mortality rate ranking first among gynecological tumors. Currently, there is insufficient understanding of the causes, pathogenesis, recurrence and metastasis of ovarian cancer, and early diagnosis and treatment still face great challenges. The sensitivity and specificity of existing ovarian cancer screening methods are still unsatisfactory. Centromere protein O (CENP-O) is a recently discovered structural centromere protein that is involved in cell death and is essential for spindle assembly, chromosome separation, and checkpoint signaling during mitosis. The abnormal high expression of CENP-O was detected in various tumors such as bladder cancer and gastric cancer, and it participates in the regulation of tumor cell proliferation. In this study, we detect the expression abundance of CENP-O mRNA in different ovarian cancer cells ( ES-2, A2780, Caov-3, OVCAR-3 and SK-OV-3). The biological function changes of cell proliferation and apoptosis were detected and the role of CENP-O in ovarian cancer cell proliferation and apoptosis was explored by knocking down the expression of CENP-O gene. The results showed that CENP-O gene was significantly expressed in 5 types of ovarian cancer cell lines. After knocking down the CENP-O gene, the proliferation and cloning ability of ovarian cancer cells decreased, and the apoptosis increased. This study indicates that CENP-O has the potential to be a molecular therapeutic target, and downregulating the expression of CENP-O gene can break the unlimited proliferation ability of cancer cells and promote their apoptosis, providing a foundation and new ideas for subsequent molecular mechanism research and targeted therapy.


Assuntos
Apoptose , Proliferação de Células , Proteínas Cromossômicas não Histona , Neoplasias Ovarianas , Feminino , Humanos , Apoptose/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Proteínas Cromossômicas não Histona/genética , Proteínas Cromossômicas não Histona/metabolismo , Regulação Neoplásica da Expressão Gênica , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia
2.
Int J Biol Macromol ; 265(Pt 1): 130724, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38479656

RESUMO

The influence of RG-I domains on high methoxyl pectin (HMP) sugar-acid gel properties has rarely been reported. In our work, HMP was modified by enzymatic de-esterification and degradation of RG-I domains to compare and analyze the relationship between the structure and final sugar-acid gel properties. The results showed that the degree of esterification (DE) of REP (pectin degraded by rhamnosidase) and GEP (pectin debranched by galactosidase) was the same as that of untreated HMP, whereas the DE of PMEP (pectin de-esterified by pectin methyl esterase) decreased from 59.63 % to 54.69 %. The monosaccharide composition suggested no significant changes in the HG and RG-I structural domains of PMEP. In contrast, the percentage of RG-I structural domains of REP and GEP dropped from 37 % to about 28 %, accompanied by a reduction in the proportion of the RG-I backbones and side chains. The rheological characterization of sugar-acid gels demonstrated an enhanced gel grade for PMEP and a weakened one for REP and GEP. Moreover, we constructed a correlation relationship between the fine structure of pectin and the properties of the sugar-acid gels, confirming the critical contribution of the RG-I region (especially the neutral sugar side chains) to the HMP sugar-acid gels.


Assuntos
Pectinas , Açúcares , Pectinas/química , Esterificação , Géis/química
3.
Anal Chem ; 96(8): 3335-3344, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38363654

RESUMO

Metabolomics has emerged as a powerful tool in biomedical research to understand the pathophysiological processes and metabolic biomarkers of diseases. Nevertheless, it is a significant challenge in metabolomics to identify the reliable core metabolites that are closely associated with the occurrence or progression of diseases. Here, we proposed a new research framework by integrating detection-based metabolomics with computational network biology for function-guided and network-based identification of core metabolites, namely, FNICM. The proposed FNICM methodology is successfully utilized to uncover ulcerative colitis (UC)-related core metabolites based on the significantly perturbed metabolic subnetwork. First, seed metabolites were screened out using prior biological knowledge and targeted metabolomics. Second, by leveraging network topology, the perturbations of the detected seed metabolites were propagated to other undetected ones. Ultimately, 35 core metabolites were identified by controllability analysis and were further hierarchized into six levels based on confidence level and their potential significance. The specificity and generalizability of the discovered core metabolites, used as UC's diagnostic markers, were further validated using published data sets of UC patients. More importantly, we demonstrated the broad applicability and practicality of the FNICM framework in different contexts by applying it to multiple clinical data sets, including inflammatory bowel disease, colorectal cancer, and acute coronary syndrome. In addition, FNICM was also demonstrated as a practicality methodology to identify core metabolites correlated with the therapeutic effects of Clematis saponins. Overall, the FNICM methodology is a new framework for identifying reliable core metabolites for disease diagnosis and drug treatment from a systemic and a holistic perspective.


Assuntos
Colite Ulcerativa , Metabolômica , Humanos , Metabolômica/métodos , Biologia Computacional/métodos , Colite Ulcerativa/diagnóstico
4.
Curr Med Sci ; 43(5): 1051-1060, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37806993

RESUMO

OBJECTIVE: Osteogenesis is vitally important for bone defect repair, and Zuo Gui Wan (ZGW) is a classic prescription in traditional Chinese medicine (TCM) for strengthening bones. However, the specific mechanism by which ZGW regulates osteogenesis is still unclear. The current study is based on a network pharmacology analysis to explore the potential mechanism of ZGW in promoting osteogenesis. METHODS: A network pharmacology analysis followed by experimental validation was applied to explore the potential mechanisms of ZGW in promoting the osteogenesis of bone marrow mesenchymal stem cells (BMSCs). RESULTS: In total, 487 no-repeat targets corresponding to the bioactive components of ZGW were screened, and 175 target genes in the intersection of ZGW and osteogenesis were obtained. And 28 core target genes were then obtained from a PPI network analysis. A GO functional enrichment analysis showed that the relevant biological processes mainly involve the cellular response to chemical stress, metal ions, and lipopolysaccharide. Additionally, KEGG pathway enrichment analysis revealed that multiple signaling pathways, including the phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) signaling pathway, were associated with ZGW-promoted osteogensis. Further experimental validation showed that ZGW could increase alkaline phosphatase (ALP) activity as well as the mRNA and protein levels of ALP, osteocalcin (OCN), and runt related transcription factor 2 (Runx 2). What's more, Western blot analysis results showed that ZGW significantly increased the protein levels of p-PI3K and p-AKT, and the increases of these protein levels significantly receded after the addition of the PI3K inhibitor LY294002. Finally, the upregulated osteogenic-related indicators were also suppressed by the addition of LY294002. CONCLUSION: ZGW promotes the osteogenesis of BMSCs via PI3K/AKT signaling pathway.


Assuntos
Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Osteogênese , Farmacologia em Rede , Diferenciação Celular , Transdução de Sinais
5.
BMJ Open Qual ; 12(2)2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37130695

RESUMO

Hypocalcaemia following thyroid surgery can occur in up to 38% of patients. With over 7100 thyroid surgeries performed in 2018 in the UK, this is a common postoperative complication. Undertreated hypocalcaemia can result in cardiac arrhythmias and death. Preventing adverse events from hypocalcaemia requires preoperative identification and treatment of at-risk patients with vitamin D deficiency, timely recognition of postoperative hypocalcaemia and prompt appropriate treatment with calcium supplementation. This project aimed to design and implement a perioperative protocol for prevention, detection and management of post-thyroidectomy hypocalcaemia. A retrospective audit of thyroid surgeries (n=67; October 2017 to June 2018) was undertaken to establish baseline practice of (1) preoperative vitamin D levels assessment, (2) postoperative calcium checks and incidence of postoperative hypocalcaemia and (3) management of postoperative hypocalcaemia. A multidisciplinary team approach following quality improvement principles was then used to design a perioperative management protocol with all relevant stakeholders involved. After dissemination and implementation, the above measures were reassessed prospectively (n=23; April-July 2019). The percentage of patients having their preoperative vitamin D measured increased from 40.3% to 65.2%. Postoperative day-of-surgery calcium checks increased from 76.1% to 87.0%. Hypocalcaemia was detected in 26.8% of patients before and 30.43% of patients after protocol implementation. The postoperative component of the protocol was followed in 78.3% of patients. Limitations include low number of patients which precluded from analysis of the impact of the protocol on length of stay. Our protocol provides a foundation for preoperative risk stratification and prevention, early detection and subsequent management of hypocalcaemia in thyroidectomy patients. This aligns with enhanced recovery protocols. Moreover, we offer suggestions for others to build on this quality improvement project with the aim to further advance the perioperative care of thyroidectomy patients.


Assuntos
Hipocalcemia , Humanos , Hipocalcemia/etiologia , Hipocalcemia/prevenção & controle , Hipocalcemia/diagnóstico , Cálcio , Glândula Tireoide , Estudos Retrospectivos , Melhoria de Qualidade , Medicina Estatal , Vitamina D , Tireoidectomia/efeitos adversos , Tireoidectomia/métodos
6.
Phytochem Anal ; 34(7): 830-841, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36843182

RESUMO

BACKGROUND: Semen Aesculi, a traditional Chinese herbal medicine, has a long history of use for treating chest and abdominal pain with distension. In addition, the horse chestnut (Aesculus hippocastanum L.) is another species of Aesculus in Europe and has notable clinical significance in alleviating chronic venous insufficiency, hemorrhoids, and postoperative edema. Thus, highlighting the comparative study of Semen Aesculi and horse chestnut may broaden clinical applications. OBJECTIVES: To conduct a comprehensive comparative analysis on the chemical profiling of these two varieties and determine whether they have equivalent clinical efficacy by integrating plant metabolomics and multivariate statistical methods. METHODS: Initially, a comprehensive characterisation was performed using ultra-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry (UPLC-QTOF-MS/MS) platform, and in total 44 active ingredients were identified. Then, untargeted metabolomics combined with principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) was applied for the discrimination of a German species and three official Chinese species. Next, 24 marker compounds responsible for the discrimination of different species were screened out and used to predict the species of unknown samples by genetic algorithm-optimised support vector machine (GA-SVM) with a high prediction accuracy. Finally, a heatmap visualisation was employed for clarifying the distribution of the identified active ingredients. RESULTS: The three species of Chinese Semen Aesculi showed distinct separation from each other, while European horse chestnut and Aesculus chinensis Bunge were similar in chemical composition. CONCLUSIONS: This work provided experimental evidence for further expanding the clinical application of Chinese Semen Aesculi and promoted the species identification and quality control of Semen Aesculi.


Assuntos
Aesculus , Espectrometria de Massas em Tandem/métodos , Quimiometria , Sementes , Metabolômica/métodos , Cromatografia Líquida de Alta Pressão/métodos
7.
Zhongguo Zhong Yao Za Zhi ; 48(24): 6765-6777, 2023 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-38212036

RESUMO

In this study, ultra-performance liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS~E) was used to analyze the plasma components of Danzhi Xiaoyao Formula after oral administration. Forty-nine plasma components were found in the serum of rats by comparing the compound extract, drug-containing serum, and blank serum. Components, such as 6-hydroxycoumarin, poricoic acid F, deoxoglabrolide, 30-norhederagenin, kanzonol R, 3',6'-di-O-galloylpaeoniflorin, 16α-hydroxytrametenolic acid, 16-deoxyporicoic acid B, 3-O-acetyl-16α-hydroxytrametenolic acid, and 16α,25-dihydroxydehydroeburiconic acid, were first found in rat serum. Behavioral tests, including the tail suspension test, novel object recognition test, and novelty-suppressed feeding test, were conducted for behavioral analysis. It was confirmed that this formula had therapeutic effects on perimenopausal depression. Furthermore, in combination with the network pharmacology method, 53 core targets including MAPK1, HRAS, AKT1, EGFR, and ESR1 were screened, and these targets participated in 165 signaling pathways, including PI3K-AKT, AMPK, VEGFA, MAPK, and HIF-1. In summary, the potential effects of Danzhi Xiaoyao Formula in treating perimenopausal depression are associated with mechanisms in accelerating inflammation repair, improving neuroplasticity, affecting neurotransmitters, regulating estrogen levels, and promoting new blood vessel formation.


Assuntos
Depressão , Medicamentos de Ervas Chinesas , Animais , Ratos , Cromatografia Líquida de Alta Pressão , Depressão/tratamento farmacológico , Farmacologia em Rede , Perimenopausa , Fosfatidilinositol 3-Quinases , Medicamentos de Ervas Chinesas/farmacologia , Simulação de Acoplamento Molecular
8.
Front Psychol ; 13: 1104073, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36733856

RESUMO

To address the fierce competition for corporate innovation in the digital economy, this study introduces knowledge integration capability as a mediating variable in light of social information processing theory, and explores the mechanism of team learning climate on innovation performance. Data were collected from a sample of 184 team members for statistical analysis, and Statistical methods such as descriptive statistical analysis, correlation analysis, and regression analysis were used to verify the study hypotheses through SPSS and Amos software, and the results showed that: (1) Team learning climate has a significant positive effect on knowledge integration capability. (2) Team learning climate has a significant positive effect on innovation performance. (3) Knowledge integration capability has a significant positive effect on innovation performance. (4) Knowledge integration capability partially mediates the role between team learning climate and innovation performance. The results proved the perspective of knowledge integration capability for the mechanism of team learning climate on innovation performance from the perspective of knowledge integration capability, and provided theoretical references for creating a learning climate in companies to promote members' knowledge learning and enhance innovation performance.

9.
Bioresour Bioprocess ; 9(1): 70, 2022 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38647553

RESUMO

Indirubin is a bisindole compound for the treatment of chronic myelocytic leukemia. Here, we presented a structure-guided method to improve the activity of a flavin-containing monooxygenase (bFMO) for the efficient production of indirubin in Escherichia coli. A flexible loop interlocked with the active pocket through a helix and the substrate tunnel rather than the active pocket in bFMO were identified to be two reconfigurable structures to improve its activity, resulting in K223R and N291T mutants with enhanced catalytic activity by 2.5- and 2.0-fold, respectively. A combined modification at the two regions (K223R/D317S) achieved a 6.6-fold improvement in catalytic efficiency (kcat/Km) due to enhancing π-π stacking interactions stabilization. Finally, an engineered E. coli strain was constructed by metabolic engineering, which could produce 860.7 mg/L (18 mg/L/h) indirubin, the highest yield ever reported. This work provides new insight into the redesign of FMOs to boost their activities and an efficient approach to produce indirubin.

10.
PLoS Negl Trop Dis ; 14(7): e0008453, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32730341

RESUMO

BACKGROUND: Severe fever with thrombocytopenia syndrome virus (SFTSV) is a novel tick-borne phlebovirus, which is listed in the most dangerous pathogens by the World Health Organization, and has 12-30% fatality rates. SFTSV antibodies were reported in minks that experienced abortion or reproductive failure. The aim of this study was to determine whether SFTSV infection causes an adverse pregnancy outcome in the fetus using a pregnant mouse model. METHODOLOGY/PRINCIPAL FINDINGS: We found SFTSV in the fetus after infection in pregnant mice, and some dams showed adverse pregnancy outcomes after infection with SFTSV including placental damage, fetal reabsorption, and fetal intrauterine growth restriction (IUGR). SFTSV had obvious tropism characteristics in the placenta, especially in the labyrinth. In early-gestation, pregnant mice infected with SFTSV had fetal IUGR and a high viral load in the fetus. The virus widely spread in infected fetuses, including the hindbrain, thymus, heart, spinal cord, and liver. CONCLUSIONS: Our study demonstrated that SFTSV was vertically transmitted to the fetus through the placental barrier of immunocompetent mice, and resulted in adverse pregnancy outcomes.


Assuntos
Infecções por Bunyaviridae/patologia , Feto/anormalidades , Feto/virologia , Phlebovirus , Alquilantes/toxicidade , Animais , Feminino , Hospedeiro Imunocomprometido , Camundongos , Camundongos Endogâmicos C57BL , Mitomicina/toxicidade , Gravidez
11.
Soc Sci Med ; 259: 113113, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32646627

RESUMO

Across the world, people living with schizophrenia (PLS) are often cared for by family caregivers. This is especially true in China where community-based systems of care for PLS are underdeveloped. Thus, family caregivers of PLS may experience emotional distress and burden in the absence of community-based services. Pearlin (1990) proposed a highly influential model for understanding the stress process and its relationship to health and wellbeing. Although the model has been examined worldwide, it has yet to be studied in China for caregivers of PLS. In the present study, we use Pearlin's stress process model to examine the mediating effect of perceived caregiver burden, family functioning, and caregivers' positive feelings about caregiving on PLS global functioning and caregiver depressive symptoms. We also examine whether the model differs for parent and spouse caregivers. A total of 327 primary family caregivers of PLS in Hunan province, China, were assessed cross-sectionally using culturally-validated measures. Bootstrap methods with Hayes's PROCESS Macro were used to test multiple mediation models of global functioning scores of PLS and caregiver depressive symptoms. In this first study of the stress process model of family caregivers of PLS in China, the results generally support the model. Caregiver perceived burden, family functioning, and positive caregiver feelings about caregiving all mediate the relationship between PLS global functioning and caregiver depression, with perceived caregiver burden having the strongest indirect effect. Analyses also show that the stress process differs between parent and spouse caregivers, with perceived caregiver burden a mediator for both groups but family functioning only a mediator for parent depressive symptoms. We discuss implications of these findings for extending the stress process model cross-culturally; suggest hypotheses for future research to examine parent and spouse differences; and discuss fruitful directions for intervention.


Assuntos
Cuidadores , Esquizofrenia , Estresse Psicológico , Adaptação Psicológica , Cuidadores/psicologia , China , Efeitos Psicossociais da Doença , Estudos Transversais , Família , Humanos , Pais , Esquizofrenia/enfermagem , Cônjuges
12.
Health Qual Life Outcomes ; 18(1): 94, 2020 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-32252766

RESUMO

PURPOSE: The Family Burden Interview Schedule (FBIS-24) and the Zarit Caregiver Burden Interview (ZBI-22) are among the most widely used measures for assessing caregiving burden, but their psychometric performances have not been compared in the same study of caregivers of people living with schizophrenia (PLS). This is important because the measures assess overlapping constructs- the FBIS-24 assesses objective burden (e.g., completion of manual tasks) and the ZBI-22 assesses subjective burden (e.g., perceived distress, stigma). This study seeks to fill this gap by comparing the reliability and validity of the FBIS-24 and the ZBI-22 in a Chinese community sample of caregivers of PLS. METHODS: A Cross-sectional stud was conducted in a community-based mental health service program in Central South part of China. A total of 327 primary family caregivers of PLS completed face-to-face interviews of the FBIS-24, the ZBI-22, the Patient Health Questionnaire (PHQ-9), the Generalized Anxiety Disorder Scale (GAD-7), and the Family Adaptation, Partnership, Growth, Affection and Resolve Index scale (APGAR), and PLS were assessed using the Global Assessment of Function scale (GAF). RESULTS: Our findings show that both the FBIS-24 and ZBI-22 have comparable psychometric performance in terms of the internal consistency, convergent validity and known group's validity. CONCLUSION: Both the FBIS-24 and the ZBI-22 are psychometrically sound measures of caregiving burden but the choice of which measure to use will depend on the research question.


Assuntos
Cuidadores/psicologia , Questionário de Saúde do Paciente/normas , Esquizofrenia/terapia , Adulto , Idoso , China , Estudos Transversais , Família/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Psicometria/normas , Qualidade de Vida/psicologia , Reprodutibilidade dos Testes
13.
J Vis Exp ; (157)2020 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-32202532

RESUMO

Sexual behavior is highly species-specific. Although rodents have slightly different sexual behaviors, mice and rats have a similar sexual behavioral pattern. The purpose of this article is to describe the hormone-induced estrus ovariectomized female model and the experimental procedure for the assessment of sexual behavior of male mice. The most important sexual behavioral elements are demonstrated in the video and illustrations. The critical steps, advantages, and limitations of the sexual behavior test are explained as well. Finally, the behavior parameters are presented, and mounting, intromission, and ejaculation processes in mating are distinguished. Behavioral parameters are assessed in terms of the occurred duration and counts during the test period.


Assuntos
Comportamento Sexual Animal/fisiologia , Animais , Bioensaio , Ejaculação/fisiologia , Estro/efeitos dos fármacos , Feminino , Habituação Psicofisiológica , Hormônios/farmacologia , Masculino , Camundongos , Ovariectomia , Ratos
14.
J Sleep Res ; 29(2): e12960, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31860161

RESUMO

Obstructive sleep apnea (OSA) is a common chronic condition that has a significant impact on the biopsychosocial aspects of the patient's life. There is currently no psychometrically validated patient-reported outcome measure to assess the impact of this condition on the health-related quality of life. We designed a novel instrument based on common patient statements, prioritized by patient preference. Sixty-three patients with OSA and 33 participants with no symptoms of sleep-disordered breathing were asked to complete a 20-item initial questionnaire. The acceptability, reliability and validity of the instrument were assessed using known psychometric techniques. The instrument had strong acceptability and was completed within 180 s with no missing data. Five items were removed as they had a high ceiling factor. A further three items were removed as they did not represent the central construct uniquely. The final 12-item instrument had high internal consistency (Cronbach's alpha 0.91), strong test-retest reliability (p = .83) and high discriminant validity when comparing mean total scores of controls (6.88; 95% confidence interval [CI], 4.67-9.08) and those with OSA (31.39; 95% CI, 27.94-34.84) (p < .001). Further studies are planned to help validate this instrument for clinical use.


Assuntos
Afeto/fisiologia , Medidas de Resultados Relatados pelo Paciente , Psicologia/métodos , Psicometria/métodos , Qualidade de Vida/psicologia , Apneia Obstrutiva do Sono/diagnóstico , Feminino , Humanos , Masculino , Reprodutibilidade dos Testes , Inquéritos e Questionários
15.
Viruses ; 12(1)2019 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-31861844

RESUMO

BACKGROUND: Enterovirus 71 (EV71) is the main pathogen that causes severe hand, foot, and mouth disease with fatal neurological complications. However, its neurovirulence mechanism is still unclear. Candidate virulence sites were screened out at structural protein VP1, but the function of these candidate virulence sites remains unclear. Several studies have shown that autophagy is associated with viral replication. However, the relationship between VP1 and autophagy in human neurons has not been studied. METHODS: A recombinant virus-SDLY107-VP1, obtained by replacing the VP1 full-length gene of the SDLY107 strain with the VP1 full-length gene of the attenuated strain SDJN2015-01-was constructed and tested for replication and virulence. We then tested the effect of the recombinant virus on autophagy in nerve cells. The effect of autophagy on virus replication was detected by western blot and plaque test. Finally, the changes of mTOR signaling molecules during EV71 infection and the effect of mTOR on virus replication at the RNA level were detected. RESULTS: Viral recombination triggered virulence attenuation. The replication ability of recombinant virus SDLY107-VP1 was significantly weaker than that of the parent strain SDLY107. The SDLY107 strain could inhibit autophagic flux and led to accumulation of autophagosomes, while the SDLY107-VP1 strain could not cause autophagosome accumulation. The synthesis of EV71 RNA was inhibited by inhibiting mTOR. CONCLUSIONS: Replacement of VP1 weakened the replication ability of virulent strains and reduced the level of autophagy in nerve cells. This autophagy facilitates the replication of virulent strains in nerve cells. VP1 is an important neurovirulence determinant of EV71, which affects virus replication by regulating cell autophagy. mTOR is a key molecule in this type of autophagy.


Assuntos
Proteínas do Capsídeo/metabolismo , Enterovirus Humano A/fisiologia , Infecções por Enterovirus/metabolismo , Infecções por Enterovirus/virologia , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Replicação Viral , Sequência de Aminoácidos , Autofagossomos , Autofagia , Biomarcadores , Proteínas do Capsídeo/química , Linhagem Celular Tumoral , Interações Hospedeiro-Patógeno , Humanos , Recombinação Genética
16.
PLoS One ; 14(11): e0225314, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31756228

RESUMO

Studies on the willingness to receive institutional eldercare among the rural elderly are scarce. This study aims to explore factors associated with the willingness to receive institutional eldercare and community-based eldercare among the rural elderly. A cross-sectional study was conducted in three rural villages of Changde City, Hunan Province, China. A total of 517 elderly were recruited through multistage sampling from these villages. The dependent variable is the willingness to receive eldercare from family (as reference), institution, and community. The independent variables includes sociodemographic characteristics: having physical disease, depression, anxiety, and daily living activities, and concerns toward home-based, institutional, and community-based care, respectively. Results show that 78.3% of the elderly are willing to receive home-based eldercare, 10.8% institutional eldercare, and 8.5% community-based eldercare. The factors associated with the willingness to receive institutional eldercare are having concerns toward home-based (OR = 4.85, P<0.001) and institutional eldercare (OR = 5.51, P<0.001). The factors associated with community-based care is living alone (OR = 2.18, P = 0.034). Finally, the major concerns toward home-based eldercare are lack of care ability and separation of family members, whereas those toward institutional eldercare are unaffordable services and fear of being abandoned by the children. The major concerns toward community-based eldercare includes affordability and lack of necessary services. In summary, elderly having concerns toward home-based care and having no concerns about institutional care are willing to accept institutional eldercare. Elderly who are living alone is tend to accept community-based care. Unaffordable services and loss of contact with family members are the major concerns of institutional eldercare. Aside from the cost, the lack of necessary care services is also a serious concern of community-based eldercare.


Assuntos
Atividades Cotidianas/psicologia , Ansiedade/epidemiologia , Depressão/epidemiologia , Serviços de Saúde para Idosos/classificação , Serviços de Saúde Rural/classificação , Idoso , China , Estudos Transversais , Feminino , Serviços de Assistência Domiciliar , Cuidados Paliativos na Terminalidade da Vida , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Inquéritos e Questionários
17.
Qual Life Res ; 28(9): 2525-2533, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31089989

RESUMO

BACKGROUND: The purpose of the present study was to determine a statistically valid cutoff score for the Zarit Burden Interview (ZBI) in order to identify family caregivers at risk for depression and anxiety to guide for further assessment and future intervention. METHODS: The ZBI, the Patient Health Questionnaire (PHQ), and the Generalized Anxiety Disorder Scale (GAD) were administered to a representative community sample of 327 family caregivers of schizophrenia individuals. A ZBI cutoff score was determined using three different statistical methods: tree-based modeling, K-means clustering technique and linear regression, followed by contingency analysis and receiver operating characteristic (ROC) curve to compare between depression and anxiety scale scores with the ZBI cutoff. RESULTS: Findings suggest that a cutoff score of 48 in ZBI has significant predictive validity for identifying caregivers at risk for both depression and anxiety. A ZBI cutoff of 48 showed sensitivity of 73% for PHQ and 70% for GAD, specificity of 80% for PHQ and 79% for GAD, PPV (positive predictive value) of 75% for PHQ and 73% for GAD, NPV (negative predictive value) of 78% for PHQ and 76% for GAD. CONCLUSIONS: This cutoff score would enable health care providers to assess family caregivers at risk and provide necessary interventions to improve their quality of life in this important role.


Assuntos
Ansiedade/diagnóstico , Cuidadores/psicologia , Depressão/diagnóstico , Psicometria/métodos , Qualidade de Vida/psicologia , Adulto , Transtornos de Ansiedade/prevenção & controle , Transtorno Depressivo/prevenção & controle , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Esquizofrenia/terapia , Inquéritos e Questionários
18.
BMC Med Res Methodol ; 19(1): 93, 2019 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-31068131

RESUMO

BACKGROUND: While it is widely acknowledged that family burden can be ameliorated with effective psycho-social interventions, how to measure family burden and define a valid cutoff to identify family caregivers in need of such interventions remains a key question. The purpose of the present study was to determine a statistically valid cutoff score for the Family Burden Interview Schedule (FBIS), using the cutoff scores of the Patient Health Questionnaire (PHQ-9) and the Generalized Anxiety Disorder Scale (GAD-7) as the reference. METHODS: The FBIS, PHQ-9, and GAD-7 were administered to a representative community sample of 327 family caregivers of schizophrenia patients. A FBIS cutoff score was determined using three different statistical methods: tree-based modeling, K-means clustering technique and linear regression. Contingency analysis was conducted to compare the FBIS cutoff with depression and anxiety scale scores. RESULTS: Findings proposed a cutoff score of 23 for the FBIS, with sensitivity being 76% for PHQ-9 and 74% for GAD-7, specificity being 68% for PHQ-9 and 67% for GAD-7. CONCLUSION: This cutoff score would enable health care providers to assess family caregivers at risk and provide necessary interventions to improve their quality of life.


Assuntos
Cuidadores/psicologia , Indicadores Básicos de Saúde , Nível de Saúde , Psicometria/métodos , Transtornos de Ansiedade/diagnóstico , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida/psicologia , Esquizofrenia/terapia
19.
Eur J Radiol ; 113: 251-257, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30927956

RESUMO

BACKGROUND: A key challenge in thyroid carcinoma is preoperatively diagnosing malignant thyroid nodules. The purpose of this study was to compare the classification performance of linear and nonlinear machine-learning algorithms for the evaluation of thyroid nodules using pathological reports as reference standard. METHODS: Ethical approval was obtained for this retrospective analysis, and the informed consent requirement was waived. A total of 1179 thyroid nodules (training cohort, n = 700; validation cohort, n = 479) were confirmed by pathological reports or fine-needle aspiration (FNA) biopsy. The following ultrasonography (US) featu res were measured for each nodule: size (maximum diameter), margins, shape, aspect ratio, capsule, hypoechoic halo, composition, echogenicity, calcification pattern, vascularity, and cervical lymph node status. We analyzed five nonlinear and three linear machine-learning algorithms. The diagnostic performance of each algorithm was compared by using the area under the curve (AUC) of the receiver operating characteristic curve. We repeated this process 1000 times to obtain the mean AUC and 95% confidence interval (CI). RESULTS: Overall, nonlinear machine-learning algorithms demonstrated similar AUCs compared with linear algorithms. The Random Forest and Kernel Support Vector Machines algorithms achieved slightly greater AUCs in the validation cohort (0.954, 95% CI: 0.939-0.969; 0.954 95%CI: 0.939-0.969, respectively) than other algorithms. CONCLUSIONS: Overall, nonlinear machine-learning algorithms share similar performance compared with linear algorithms for the evaluation the malignancy risk of thyroid nodules.


Assuntos
Neoplasias da Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Biópsia por Agulha Fina/métodos , Calcinose/patologia , Métodos Epidemiológicos , Feminino , Humanos , Linfonodos/patologia , Aprendizado de Máquina , Masculino , Pessoa de Meia-Idade , Pescoço/patologia , Neoplasias da Glândula Tireoide/classificação , Nódulo da Glândula Tireoide/classificação , Ultrassonografia , Adulto Jovem
20.
Front Behav Neurosci ; 13: 21, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30873013

RESUMO

Objective: No study has comprehensively evaluated the effect of postweaning isolation on the social and sexual behaviors of a certain strain of rodents in ethology. The present study aims to explore how and to what extent isolation rearing after postweaning affects the social and sexual behaviors of male CD-1 mice in adulthood systematically. Methods: Male CD-1 mice were randomly assigned to two groups: isolation reared (IS, one mouse per cage, n = 30) and group housed (GH, five mice per cage, n = 15). The mice underwent isolation rearing from postnatal day 23 to day 93. Then, social affiliation, recognition and memory were measured through selection task experiments. Social interaction under a home cage and novel environment were measured via resident-intruder and social interaction test, respectively. Furthermore, sexual preference, homosexual and heterosexual behaviors were measured. Results: Our study found that postweaning isolation increased the social affiliation for conspecifics (p = 0.001), reduced social recognition (p = 0.042) and impaired social memory. As for social interaction, isolated mice showed a remarkably increased aggression toward the intruder male in a home cage or novelty environment. For instance, isolated mice presented a short attack latency (p < 0.001), high attack frequency (p < 0.001) and long attack duration (p < 0.001). In addition, isolated mice exhibited further social avoidance. Contrastingly, isolated mice displayed a reduced sexual preference for female (IS: 61.47 ± 13.80%, GH: 70.33 ± 10.06%, p = 0.038). As for heterosexual behavior, isolated mice have a short mating duration (p = 0.002), long mounting latency (p = 0.002), and long intromission latency (p = 0.015). However, no association was observed between postweaning isolation and homosexual behavior in male CD-1 mouse. Conclusion: Postweaning isolation increased the social affiliation, impaired the social cognition and considerably increased the aggression in social interaction of adult male CD-1 mice. Postweaning isolation induced a decreased sexual preference for female in adulthood. Postweaning isolation extended the latency to mate, thereby reducing mating behavior. No association was observed between isolation and homosexual behavior.

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