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PURPOSE: In East Asia, the incidence of breast cancer has been increasing rapidly, particularly among premenopausal women. An elevated ratio of estrogen-DNA adducts was linked to a higher risk of breast cancer. The present study explored the influence of the interaction between base excision repair (BER) gene polymorphisms and estrogen-DNA adducts on breast cancer risk. METHODS: We conducted a case-control study comprising healthy volunteers and individuals with benign breast disease (control arm, n = 176) and patients with invasive carcinoma or carcinoma in situ (case arm, n = 177). Genotyping for BER-related genes, including SMUG1, OGG1, ERCC5, and APEX1, was performed. A logistic regression model, incorporating interactions between gene polymorphisms, estrogen-DNA adduct ratio, and clinical variables, was used to identify the risk factors for breast cancer. RESULTS: Univariate analysis indicated marginal associations between breast cancer risk and APEX1 rs1130409 T > G (P = 0.057) and APEX1 rs1760944 T > G (P = 0.065). Multivariate regression analysis revealed significant associations with increased breast cancer risk for APEX1_rs1130409 (GT/GG versus TT) combined with a natural logarithmic value of the estrogen-DNA adduct ratio (estimated OR 1.164, P = 0.023) and premenopausal status with an estrogen-DNA adduct ratio > 2.93 (estimated OR 2.433, P = 0.001). CONCLUSION: APEX1_rs1130409 (GT/GG versus TT) polymorphisms, which are related to decreased BER activity, combined with an increased ratio of estrogen-DNA adducts, increase the risk of breast cancer in East Asian women.
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BACKGROUND: The efficacy and safety of Qingda granule (QDG) in managing blood pressure (BP) among grade 1 hypertensive patients with low-moderate risk remain uncertain. METHODS: In the randomized, double-blind, double dummy, non-inferiority and multicenter trial, 552 patients with grade 1 hypertension at low-moderate risk were assigned at a ratio of 1:1 to receive either QDG or valsartan for 4 weeks, followed up by a subsequent 4 weeks. RESULTS: Post-treatment, clinic systolic/diastolic BPs (SBP/DBP) were reduced by a mean change of 9.18/4.04 mm Hg in the QDG group and 9.85/5.05 mm Hg in the valsartan group (SBP P = 0.47, DBP P = 0.16). Similarly, 24-hour, daytime and nighttime BPs were proportional in both groups (P > 0.05) after 4 weeks treatment. After discontinuing medications for 4 weeks, the mean reduction of clinic SBP/DBP were 0.29/0.57 mm Hg in the QDG group compared to -1.59/-0.48 mm Hg in the valsartan group (SBP P = 0.04, DBP P = 0.04). Simultaneously, the 24-hour SBP/DBP were reduced by 0.9/0.31 mm Hg in the QDG group and -1.66/-1.08 mm Hg in the valsartan group (SBP P = 0.006, DBP P = 0.02). And similar results were observed regarding the outcomes of daytime and nighttime BPs. There was no difference in occurrence of adverse events between two groups (P > 0.05). CONCLUSION: QDG proves to be efficacious for grade 1 hypertension at a low-to-medium risk, even after discontinuation of the medication for 4 weeks. These findings provide a promising option for managing grade 1 hypertension and suggest the potential for maintaining stable BP through intermittent administration of QDG. TRIAL REGISTRATION: ChiCTR2000033890.
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Anti-Hipertensivos , Medicamentos de Ervas Chinesas , Hipertensão , Humanos , Anti-Hipertensivos/efeitos adversos , Pressão Sanguínea , China , Método Duplo-Cego , Tetrazóis/efeitos adversos , Valsartana/efeitos adversosRESUMO
Quercetin is kown for its antihypertensive effects. However, its role on hypertensive renal injury has not been fully eucidated. In this study, hematoxylin and eosin staining, terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL) staining, and Annexin V staining were used to assess the pathological changes and cells apoptosis in the renal tissues of Ang II-infused mice and Ang II- stimulated renal tubular epithelial cell line (NRK-52E). A variety of technologies, including network pharmacology, RNA-sequencing, immunohistochemistry, and Western blotting were performed to investigate its underlying mechanisms. Network pharmacology analysis identified multiple potential candidate targets (including TP53, Bcl-2 and Bax) and enriched signaling pathways (including apoptosis and p53 signaling pathway). Quercetin treatment significantly alleviated the pathological changes in renal tissues of Ang II-infused mice and reversed 464 differentially expressed transcripts (DETs), as well as enriched several signaling pathways, including those related apoptosis and p53 pathway. Furthermore, quercetin treatment significantly inhibited the cell apoptosis in renal tissues of Ang II-infused mice and Ang II-stimulated NRK-52E cells. Additionally, quercetin treatment inhibited the upregulation of p53, Bax, cleaved-caspase-9, and cleaved-caspase-3 protein expression and the downregulation of Bcl-2 protein expression in both renal tissue of Ang II-infused mice and Ang II-stimulated NRK-52E cells. Moreover, the molecular docking results indicated a potential binding interaction between quercetin and TP53. Quercetin treatment significantly attenuated hypertensive renal injury and cell apoptosis in renal tissues of Ang II-infused mice and Ang II-stimulated NRK-52E cells, and by targeting p53 may be one of the potential underlying mechanisms.
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BACKGROUND: The mechanisms underlying the relationship between workplace violence (WPV) and depressive symptoms in nurses have been less studied. This study aims to examine the mediating role of fear of future workplace violence (FFWV) and burnout in the association between WPV and depressive symptoms. METHODS: We conducted a cross-sectional web survey at 12 tertiary hospitals in Shandong province, China, in 2020. The Center for Epidemiologic Studies Depression Scale (CESD-10), the Chinese version of the Maslach Burnout Inventory-General Survey and the Fear of Future Violence at Work Scale were used to collect data. Descriptive statistics, independent sample t-test, one-way analysis of variance, Pearson's correlation coefficient, and ordinary least squares regression with bootstrap resampling were used to analyze the data. RESULTS: The prevalence of depressive symptoms was 45.9% among nurses. The regression model showed that FFWV and burnout mediated the relationship between WPV and depressive symptoms. The total effects of WPV on depressive symptoms (3.109, 95% bootstrap CI:2.324 - 3.713) could be decomposed into direct (2.250, 95% bootstrap CI:1.583 - 2.917) and indirect effects (0.769, 95% bootstrap CI:0.543 - 1.012). Indirect effects mediated by FFWV and burnout were 0.203 (95% bootstrap CI:0.090 - 0.348) and 0.443 (95% bootstrap CI:0.262 - 0.642), respectively. Furthermore, serial multiple mediation analyses indicated that the indirect effect mediated by FFWV and burnout in a sequential manner was 0.123 (95% bootstrap CI:0.070 - 0.189). CONCLUSION: The prevalence of depressive symptoms among Chinese nurses was high. The WPV was an important risk factor for depressive symptoms and its negative effect was mediated by FFWV and burnout. The importance of decreasing WPV exposure and level of FFWV and burnout was emphasized to prevent depressive symptoms among nurses. The findings implied that hospital managers and health policy makers should not only develop targeted interventions to reduce exposure to WPV in daily work among all nurses, but also provide psychological support to nurses with WPV experience to reduce FFWV and burnout.
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Esgotamento Profissional , Depressão , Medo , Violência no Trabalho , Humanos , Violência no Trabalho/psicologia , Esgotamento Profissional/psicologia , Esgotamento Profissional/epidemiologia , China/epidemiologia , Depressão/psicologia , Depressão/epidemiologia , Estudos Transversais , Adulto , Feminino , Masculino , Medo/psicologia , Prevalência , Recursos Humanos de Enfermagem Hospitalar/psicologia , Pessoa de Meia-Idade , Enfermeiras e Enfermeiros/psicologia , Inquéritos e Questionários , Adulto JovemRESUMO
PURPOSE: The transition from medical student to practicing physician affects the complex processes of professional identity formation and professionalism, which have a lasting effect on the physician's career development. This study explored two different transitional processes of medical students in Taiwan, the associated rituals during this transitional period (the 'liminal phase') and their effect on the formation of professional identity. METHOD: Using snowball sampling, we recruited 13 medical students from two training systems: six from the traditional postgraduate year programme and seven from the accelerated postgraduate year (A-PGY) programme. Semi-structured interviews were thematically analysed to identify significant themes that encapsulated trainees' experiences. A consistent and mutually confirmed discussion ensured the identification of robust recurring themes. RESULTS: A comparative analysis of the two training modalities provided critical insights into the relative impact of the training dynamics. The A-PGY cohort, subjected to an altered 'incorporation' ritual, encountered an influx of unexpected symbolic social power, complicating their transformation within the liminal phase. Without a defined internship like in the PGY system, A-PGY trainees exhibited confusion and inconsistencies in professional identity formation marked by conflicting internal and external perceptions. This ambiguity affected their clinical training, social integration and overall development of professionalism. The absence of a structured, sequential liminal phase increased conflict and diminished motivation, culminating in an incomplete self-crafting journey for A-PGY trainees. CONCLUSIONS: This study highlights the impact of the well-sequenced implementation of rituals in liminality on professional identity formation. A good transition training programme for medical students should compass sequential rituals in the liminal phase, including clear starting and ending points, supervision by seniors, guided reflection and plenty of opportunities for observation and imitation in context. Optimal training and pivotal elements in a medical training system warrant delicate design and further research when developing and changing the structure of the training programme.
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BACKGROUND: Triglyceride glucose (TyG) index combined with obesity-related indicators [triglyceride glucose-body mass index (TyG-BMI), triglyceride glucose-waist to height ratio (TyG-WHtR), triglyceride glucose-waist circumference (TyG-WC)], represents emerging methodologies for assessing insulin resistance. The objective of this investigation was to explore the correlation between TyG-related indices and gallstone disease. METHODS: The study included 3740 adults from the 2017-2020 period of the National Health and Nutrition Examination Survey. TyG-BMI, TyG-WC, and TyG-WHtR were integrated as both continuous and categorical variables within the multivariate logistic model, respectively to evaluate the connection between various TyG-related indices and gallstone disease. Additionally, restriction cubic splines and subgroup analysis were employed to deepen our understanding of this relationship. RESULTS: When analyzed as continuous variables, positive correlations were observed between TyG-BMI, TyG-WC, TyG-WHtR and gallstone disease. The OR(95%CI) were 1.063(1.045,1.082) for TyG-BMI (per 10-unit), 1.026(1.018,1.034) for TyG-WC (per 10-unit) and 1.483(1.314,1.676) for TyG-WHtR (per 1-unit), respectively. When categorized into quartiles, these three TyG-related indices still show statistically significant associations with gallstone disease. Descending in order, the diagnostic capability for gallstone disease is demonstrated as follows: TyG-WHtR (AUC = 0.667), TyG-BMI (AUC = 0.647), and TyG-WC (AUC = 0.640). CONCLUSION: There were significantly positive associations between TyG-related indices, including TyG-BMI, TyG-WC, and TyG-WHtR, and gallstone disease. Of these indices, TyG-WHtR demonstrated the most favorable performance in identifying the risk of gallstone disease.
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Glicemia , Índice de Massa Corporal , Cálculos Biliares , Inquéritos Nutricionais , Triglicerídeos , Humanos , Triglicerídeos/sangue , Feminino , Cálculos Biliares/sangue , Cálculos Biliares/epidemiologia , Masculino , Pessoa de Meia-Idade , Adulto , Glicemia/metabolismo , Circunferência da Cintura , Fatores de Risco , Resistência à Insulina , Estados Unidos/epidemiologia , Obesidade/sangue , Obesidade/epidemiologia , IdosoRESUMO
BACKGROUND: Esophageal carcinoma is a type of cancer that occurs in the esophagus. For patients with locally advanced or metastatic esophageal squamous cell carcinoma who have either experienced disease progression following first-line standard chemotherapy or are intolerant to it, the prognosis is typically poor. Additionally, these patients often bear a substantial economic burden during the course of their treatment. Tislelizumab is a selective PD-1 inhibitor with efficacy proven in locally advanced or metastatic esophageal squamous cell carcinoma. The study aims to evaluate the cost-effectiveness of tislelizumab versus camrelizumab as the second-line treatment in locally advanced or metastatic esophageal squamous cell carcinoma (ESCC) patients in China. METHODS: From the perspective of China's healthcare system, the partitioned survival model with three health states was established in a 3-week cycle and a lifetime horizon. Anchored matching adjusted indirect comparison was used for survival analyses based on individual patient data from RATIONALE 302 trial and the published ESCORT study due to the lack of head-to-head clinical trials. Only direct medical costs were included. Costs and utility values were derived from local charges, the published literature, and related databases. Sensitivity analyses and a scenario analysis were also performed to verify the robustness of the model results. RESULTS: Compared with camrelizumab monotherapy, tislelizumab monotherapy incurred a lower lifetime cost ($8,346 vs. $8,851) and yielded higher quality-adjusted life-years (QALYs) (0.87 vs. 0.63), which resulted in an incremental cost-effectiveness ratio (ICER) of -$2,051/QALY. Tislelizumab monotherapy is a dominant option over camrelizumab monotherapy in China. The three primary parameters upon which this result was most sensitive were the unit cost of camrelizumab, the unit cost of tislelizumab, and the duration of reactive cutaneous capillary endothelial proliferation (RCCEP). According to the probabilistic sensitivity analysis (PSA), tislelizumab monotherapy was 100% cost-effective when the WTP was 1-3 times GDP per capita in China($11,207/QALYâ¼$33,621/QALY). Scenario analysis showed that the result was consistent. CONCLUSION: Tislelizumab monotherapy is a dominant option compared with camrelizumab monotherapy as the second-line treatment for locally advanced or metastatic ESCC in China.
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Anticorpos Monoclonais Humanizados , Análise Custo-Benefício , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/economia , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/economia , Neoplasias Esofágicas/tratamento farmacológico , China , Masculino , Feminino , Pessoa de Meia-Idade , Anos de Vida Ajustados por Qualidade de Vida , Análise de Custo-EfetividadeRESUMO
In this study we investigate the role of Zipper-interacting protein kinase (ZIPK) in high glucose-induced vascular injury, focusing on its interaction with STAT5A and its effects on p53 and inducible nitric oxide synthase (NOS2) expression. Human umbilical vein endothelial cells (HUVECs) are cultured under normal (5â mM) and high (25â mM) glucose conditions. Protein and gene expression levels are assessed by western blot analysis and qPCR respectively, while ROS levels are measured via flow cytometry. ZIPK expression is manipulated using overexpression plasmids, siRNAs, and shRNAs. The effects of the ZIPK inhibitor TC-DAPK6 are evaluated in a diabetic rat model. Our results show that high glucose significantly upregulates ZIPK, STAT5A, p53, and NOS2 expressions in HUVECs, thus increasing oxidative stress. Silencing of STAT5A reduces p53 and NOS2 expressions and reactive oxygen species (ROS) accumulation. ZIPK is essential for high glucose-induced p53 expression and ROS accumulation, while silencing of ZIPK reverses these effects. Overexpression of ZIPK combined with STAT5A silencing attenuates glucose-induced alterations in p53 and NOS2 expression, thereby preventing cell damage. Coimmunoprecipitation reveals a direct interaction between ZIPK and STAT5A in the nucleus under high-glucose condition. In diabetic rats, TC-DAPK6 treatment significantly decreases ZIPK, p53, and NOS2 expressions. Our findings suggest that ZIPK plays a critical role in high glucose-induced vascular injury via STAT5A-mediated pathways, proposing that ZIPK is a potential therapeutic target for diabetic vascular complications.
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Accumulation of persistent organic pollutants polycyclic aromatic hydrocarbons (PAHs) in soil has become a global problem. Composting is considered one of the more economical methods of soil remediation and is important for the resourceful use of wastes. Agroforestry waste is produced in huge amounts and is utilized at low rates, hence there is an urgent need to manage it. Here, leaf (LVS) or rice straw (SVS) was co-composting with aged contaminated soil to investigate bacteria interaction to PAHs degradation and humus formation. The degradation rate of high molecular weight PAHs (HMW-PAHs) in LVS and SVS reached 58.9% and 52.5%, and the low molecular weight PAHs (LMW-PAHs) were 77.5% and 65%. Meanwhile, the humus increased by 44.8% and 60.5% in LVS and SVS at the end of co-composting. The topological characteristics and community assembly of the bacterial community showed that LVS had higher complexity and more keystones than SVS, suggesting that LVS might more beneficial for the degradation of PAHs. The stability of the co-occurrence network and stochastic processes (dispersal limitation) dominated community assembly made SVS beneficial for humus formation. Mantel test and structural equation models indicated that the transformation of organic matter was important for PAHs degradation and humus formation. Degradation of HMW-PAHs led to bacterial succession, which affected the formation of precursors and ultimately increased the humus content. This study provided potential technology support for improving the quality of agroforestry organic waste composting and degrading PAHs in aged contaminated soil.
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Compostagem , Hidrocarbonetos Policíclicos Aromáticos , Poluentes do Solo , Biodegradação Ambiental , Poluentes do Solo/análise , Solo/química , Bactérias/metabolismo , Microbiologia do SoloRESUMO
The purpose of this study was to evaluate the economics of Annao Pills combined with antihypertensive drugs in the treatment of primary hypertension in the Chinese medical setting. TreeAge pro 2018 was used for cost-effect analysis and sensitivity analysis of the two treatment regimens. The intervention time of the simulation model was 2 weeks. The cost parameters were derived from Yaozhi.com, and the effect parameters were based on Meta-analysis of randomized controlled trial(RCT) involving Annao Pills. The experimental group was treated with Annao Pills combined with anti-hypertensive drugs(nifedipine controlled-release tablets + losartan potassium tablets), and the control group was treated with anti-hypertensive drugs(nifedipine controlled-release tablets + losartan potassium tablets). The basic analysis showed that the incremental cost-effect ratio(ICER) of the two groups was 2 678.67 yuan, which was less than 7.26% of the per capita disposable income in 2022. That is, compared with anti-hypertensive drugs alone, Annao Pills combined with antihypertensive drugs cost 2 678.67 yuan more for each additional patient with primary hypertension. The results of sensitivity analysis verified the robustness of the basic analysis results. The probability sensitivity results showed that when the patient's personal willingness to pay the price was higher than 2 650 yuan, the probability of the regimen in the experimental group was higher, which was consistent with the results of the basic analysis. In conclusion, when the price was higher than 2 650 yuan, Annao Pills combined with anti-hypertensive drugs was more economical than anti-hypertensive drugs alone in terms of improving the response rate of the patients with primary hypertension.
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Anti-Hipertensivos , Nifedipino , Humanos , Anti-Hipertensivos/uso terapêutico , Análise Custo-Benefício , Árvores de Decisões , Preparações de Ação Retardada , Hipertensão Essencial , Losartan/uso terapêuticoRESUMO
From the perspective of lncRNA MALAT1 regulating cholesterol metabolism in chondrocytes, this paper explores the effect and mechanism of Tougu Xiaotong Capsules(TGXTC) in delaying the degeneration of osteoarthritis. After one week of adaptive feeding, 48(8-week-old) C57BL/6 mice were randomly divided into a blank group(12 mice) and a model group(36 mice) by random number table method. The mice in the model group were anesthetized by inhalation of 5% isoflurane, and the OA model was induced by Hulth method. The experiment randomly divided the mice into a model group(12 mice), a drug-positive group(taururso-deoxycholic acid)(12 mice), and a TGXTC group(12 mice). The drug-positive group was given 500 mg·kg~(-1) taurodeoxycholic acid by intragastric administration. TGXTC group was given TGXTC 368 mg·kg~(-1) by gavage. The blank group and model group were given the same amount of normal saline for four weeks. After the intervention, the mice in each group were killed under anesthesia, and the knee cartilage tissue was separated and collected. The morphologic changes of knee cartilage were observed. The level of lncRNA MALAT1 in the cartilage tissue was detected by real-time PCR. The protein expressions of ABCA1, ApoA1, LXRß, CHOP, and caspase-3 in mouse articular cartilage were detected by Western blot. Lentivirus-coated plasmid was used to transfect mouse chondrocytes with sh-MALAT1. The gene levels of lncRNA MALAT1 in mouse chondrocytes transfected with sh-MALAT1 were detected by real-time PCR. Western blot was used to detect the effect of TGXTC on the protein content of ABCA1, ApoA1, LXRß, CHOP, and caspase-3 in thapsigargin(TG)-induced mouse chondrocytes after lncRNA MALAT1 knockdown. Flow cytometry was used to detect the effect of TGXTC on apoptosis of TG-induced mouse chondrocytes after lncRNA MALAT1 knockdown. The results of HE and saffranine O staining showed that compared with the model group, the structure of the cartilage layer was basically intact; the damage degree of joint structure was significantly improved, and the cartilage matrix was significantly enhanced by saffranine O staining in the TGXTC group and drug-positive group. Compared with the model group, the lncRNA MALAT1 level was significantly decreased in the TGXTC group and drug-positive group. Compared with the model group, the protein content of ABCA1, ApoA1, and LXRß was significantly increased, while that of CHOP and caspase-3 in the TGXTC group and drug-positive group significantly decreased. Compared with the TG group, the lncRNA MALAT1 level in the TG+sh-MALAT1 group was decreased. The lncRNA MALAT1 level in the TG+sh-MA-LAT1+TGXTC group was increased compared with the TG+TGXTC group. Western blot results showed that compared with the model group, protein expressions of ABCA1, ApoA1, LXRß, CHOP, and caspase-3 in the TGXTC group were significantly decreased, after lncRNA MALAT1 knockdown, the regulation and apoptosis of ABCA1, ApoA1, LXRß, CHOP, and caspase-3 in TG-induced mouse chondrocytes were weakened by TGXTC. TGXTC can improve the disorder of cholesterol metabolism in OA chondrocytes and delay OA degeneration, which is closely related to the regulation of lncRNA MALAT1.
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Colesterol , Condrócitos , Medicamentos de Ervas Chinesas , Camundongos Endogâmicos C57BL , Osteoartrite , RNA Longo não Codificante , Animais , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Condrócitos/metabolismo , Condrócitos/efeitos dos fármacos , Camundongos , Osteoartrite/metabolismo , Osteoartrite/genética , Osteoartrite/tratamento farmacológico , Colesterol/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/administração & dosagem , Masculino , Humanos , CápsulasRESUMO
Based on UHPLC-Q-Exactive Orbitrap HRMS coupled with the network pharmacology and molecular docking, the common material basis and molecular mechanisms of Bletillae Rhizoma for melasma, gastrointestinal hemorrhage, lung cancer and bronchoplumonary inflammation as "homotherapy for heteropathy" were explored. The fingerprint of 17 batches of Bletillae Rhizoma from different areas was established using HPLC, and the similarity analysis was carried out. The common chemical components of the 17 batches of Bletillae Rhizoma were identified using UHPLC-Q-Exactive Orbitrap HRMS. Depending on the bioavailability and drug-like properties of the common components, the active chemical components were screened, and then their protein targets were collected using the Traditional Chinese Medicine Database and Analysis Platform(TCMSP) and SwissTargetPrediction database. The protein targets related to diseases were retrieved from the databases DrugBank, TTD and GeneCards to produce a Venn diagram. The shared targets were obtained between drugs and diseases as "homotherapy for heteropathy" targets. The protein-protein interaction(PPI) was analyzed with the STRING database, and KEGG and GO analyses of the "homotherapy for heteropathy" targets were performed using the Bioconductor database. Cytoscape 3.7.2 software was employed to construct the "chemical components of Bletillae Rhizoma-homotherapy for heteropathy targets" network and PPI network, and topological analysis was conducted to screen out the key active chemical components and core targets. Finally, the affinity between the active components and core targets was evaluated using the molecular docking by AutoDock Vina 4.2.6, which verified the interaction between them. Thirteen common peaks were identified by fingerprint chromatography, and the similarity between different batches was 0.941-0.998. Fifty-three chemical components were identified by mass spectrometry in Bletillae Rhizoma, and 18 common chemical constituents were obtained in the 17 batches of Bletillae Rhizoma. Network pharmacologic screening showed that the pharmacodynamic substances of Bletillae Rhizoma for melasma, gastrointestinal hemo-rrhage, lung cancer and bronchoplumonary inflammation with "homotherapy for heteropathy" were 11 compounds, such as polysaccharides, biphenanthrenes, dihydrophenanthrenes and bibenzyls. There were 42 common targets identified for the treatment of different diseases. These targets were involved in biological processes such as cell response to chemical stress, reactive oxygen species and positive regulation of protein kinase B signal transduction. They were also involved in 121 signaling pathways, encompassing vital pathways such as PI3K-Akt, ErbB, Rap1, FoxO, MAPK and estrogen. Molecular docking results showed a strong affinity between the key active components and the core targets. This study provides a preliminary explanation of how Bletillae Rhizoma exerts its therapeutic effect on chloasma, gastrointestinal hemorrhage, lung cancer, and bronchopneumonic lesions as "homotherapy for heteropathy" through a combined action involving multiple components, targets, and pathways. These findings offer a certain theoretical basis for the further deve-lopment and application of Bletillae Rhizoma.
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Medicamentos de Ervas Chinesas , Neoplasias Pulmonares , Simulação de Acoplamento Molecular , Farmacologia em Rede , Rizoma , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Cromatografia Líquida de Alta Pressão , Rizoma/química , Neoplasias Pulmonares/tratamento farmacológico , Hemorragia Gastrointestinal/tratamento farmacológico , Melanose/tratamento farmacológico , Orchidaceae/química , Inflamação/tratamento farmacológico , Espectrometria de MassasRESUMO
Hepatic fibrosis is the pathological repair response of the liver to chronic injury; hepatic stellate cell (HSC) activation is the central link in the pathogenesis of hepatic fibrosis. Previously, we showed that kinetin, a plant cytokinin hormone, has a protective effect on CCl4-induced liver injury in mice. However, the role of kinetin in liver fibrosis remains unclear. We aimed to study these protective effects and to determine the mechanisms by which kinetin mediates HSC activation and apoptosis. For this purpose, the human HSC line LX-2 was treated with 10 ng/ml transforming growth factor-ß1 (TGF-ß1) for 24 h to stimulate activation. We found that treatment with kinetin at the sub-cytotoxic dose of 40 µg/ml for 48 h reduced the expression of the HSC activation marker α-SMA and inhibited the secretion of extracellular matrix proteins. In addition, kinetin was found to inhibit the proliferation and migration of LX-2 cells. We found that kinetin induced apoptosis in LX-2 cells by increasing the level of cleaved-caspase 3 and the Bax-to-Bcl-2 ratio. Interestingly, these effect were not observed in quiescent HSCs, suggesting that they are activation-dependent. Further study showed that kinetin attenuates activation and promotes apoptosis of LX-2 cells in vitro in part by suppressing the TGF-ß1/Smad signaling pathway.
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Células Estreladas do Fígado , Fator de Crescimento Transformador beta1 , Humanos , Camundongos , Animais , Fator de Crescimento Transformador beta1/metabolismo , Cinetina/metabolismo , Cinetina/farmacologia , Cinetina/uso terapêutico , Cirrose Hepática/metabolismo , Transdução de Sinais , ApoptoseRESUMO
The detection of sleep apnea is critical for assessing sleep quality. It is also a proven biometric in diagnosing cardiovascular and other diseases. Recent studies have shown that radar-based non-contact vital sign monitoring system can effectively detect sleep apnea. However, the detection accuracy in the current study still needs to be improved. In this paper, we propose a sleep apnea detection framework based on FMCW radar. First, the radar system is employed to record the sleep data throughout the night with polysomnography (PSG) comparison. Then, in order to extract more accurate respiratory signal from the raw radar data, the signal processing methods are investigated to solve the observed discontinuity phenomenon. Finally, machine learning methods are adopted. The apneic and not-apneic events are classified accurately by selecting effective features of respiratory signal. As shown in the experimental results, the proposed system could achieve a good classification performance with an accuracy of 95.53%, a sensitivity of 72.60%, a specificity of 97.32%, a Kappa of 0.68, and an F-score of 0.84.
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Aprendizado de Máquina , Processamento de Sinais Assistido por Computador , Síndromes da Apneia do Sono , Humanos , Polissonografia/métodos , Síndromes da Apneia do Sono/diagnósticoRESUMO
OBJECTIVE: Patients with Graves' disease who remain hyperthyroid under the treatment of antithyroid drugs (ATD) or cannot tolerate ATD usually receive radioactive iodine (RAI) to control disease activity. This pilot study aimed to identify predictors of prolonged euthyroidism > 12 months after receiving RAI. METHODS: Demographic, clinical, and laboratory data from 117 patients receiving RAI were retrospectively collected, including age, gender, body surface area, smoking status, free thyroxine, thyrotropin, thyrotropin binding inhibiting immunoglobulin, microsomal antibody, thyroglobulin antibody, medication history, and thyroid volume. Only 85 patients without missing values were included in statistical analysis. The calculated RAI dose was the estimated thyroid volume × 0.4. The difference and ratio between the actual and calculated RAI doses were examined. A stepwise logistic regression analysis was conducted to identify important predictors of prolonged euthyroidism > 12 months. The cut-off values for discretizing continuous covariates were estimated by fitting generalized additive models. RESULTS: Among the 85 patients on RAI, 18 (21.2%) achieved prolonged euthyroidism > 12 months, 38 (44.7%) remained hyperthyroid with decreased ATD doses, but 29 (34.1%) suffered permanent hypothyroidism and needed long-term levothyroxine. Logistic regression analysis revealed that patients with age > 66 years, 33 < age ≤ 66 years, quitting smoking vs nonsmoking or current smoking, 600 < micorsomal antibody ≤ 1729 IU/mL, 47% < thyrotropin binding inhibiting immunoglobulin ≤ 81%, 7 < thyroglobulin antibody ≤ 162 IU/mL, 0.63 < ratio between actual and calculated RAI doses ≤ 1.96, or taking hydroxychloroquine would have a higher chance of reaching prolonged euthyroidism > 12 months after receiving RAI. Its area under the Receiver Operating Characteristic (ROC) curve was 0.932. CONCLUSION: Patients with Graves' disease who received an actual RAI dose close to the calculated RAI dose achieved prolonged euthyroidism > 12 months if they also took hydroxychloroquine during RAI treatment.
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Doença de Graves , Hipertireoidismo , Iodo , Neoplasias da Glândula Tireoide , Humanos , Pré-Escolar , Radioisótopos do Iodo/uso terapêutico , Projetos Piloto , Tireoglobulina , Estudos Retrospectivos , Hidroxicloroquina/uso terapêutico , Doença de Graves/tratamento farmacológico , Doença de Graves/radioterapia , Hipertireoidismo/tratamento farmacológico , Antitireóideos/uso terapêutico , TireotropinaRESUMO
BACKGROUND: Older adults with different living arrangements may have different mental health statuses and different factors that influence their mental health. The aim of the present study is to investigate the prevalence and determinants of depressive symptoms among community-dwelling older adults in China based on differences in their living arrangements. METHODS: Participants were 6,055 older adults from the 2015 China Health and Retirement Longitudinal Study. Depressive symptoms and their determinants were evaluated using the 10-item Center for Epidemiologic Studies Depression Scale and multivariate logistic regression analysis, respectively. RESULTS: The prevalence of depressive symptoms among older adults living alone, as a couple, and with children was 47.8%, 33.2%, and 39.5%, respectively. The common risk factors for depressive symptoms were shorter sleep duration, poorer activities of daily living, and poorer self-rated health. Women, those with lower educational levels, and those suffering from chronic diseases had a higher risk of depressive symptoms among older adults living as a couple and those living with children. Smoking and participation in economic activities were also risk factors of depressive symptoms among older adults living with children and those living alone, respectively. CONCLUSIONS: The findings suggest that older adults living as couples had the lowest prevalence of depressive symptoms, while those living alone had the highest prevalence of depressive symptoms. The determinants of depressive symptoms differed by living arrangement; hence, they should be considered in future interventions.
Assuntos
Depressão , Vida Independente , Humanos , Feminino , Idoso , Depressão/diagnóstico , Depressão/epidemiologia , Estudos Transversais , Atividades Cotidianas , Prevalência , Estudos Longitudinais , China/epidemiologiaRESUMO
BACKGROUND: This study aimed to investigate the proportion of prehypertension cases progressing to hypertension among Chinese middle-aged and elderly populations over a 2-year period and related influencing factors. METHODS: Data were obtained from the China Health and Retirement Longitudinal Study, and 2,845 individuals who were ≥ 45 years old and prehypertensive at baseline were followed from 2013-2015. Structured questionnaires were administered, and blood pressure (BP) and anthropometric measurements were performed by trained personnel. Multiple logistic regression analysis was done to investigate factors associated with prehypertension progressing to hypertension. RESULTS: Over the 2-year follow-up, 28.5% experienced progression of prehypertension to hypertension; this occurred more frequently in men than women (29.7% vs. 27.1%). Among men, older age (55-64 years: adjusted odds ratio [aOR] = 1.414, 95% confidence interval [CI]:1.032-1.938; 65-74 years: aOR = 1.633, 95%CI: 1.132-2.355; ≥ 75 years: aOR = 2.974, 95%CI: 1.748-5.060), obesity (aOR = 1.634, 95%CI: 1.022-2.611), and number of chronic diseases (1: aOR = 1.366, 95%CI: 1.004-1.859; ≥ 2: aOR = 1.568, 95%CI: 1.134-2.169) were risk factors for progression to hypertension whereas being married/cohabiting (aOR = 0.642, 95% CI: 0.418-0.985) was a protective factor. Among women, risk factors included older age (55-64 years: aOR = 1.755, 95%CI: 1.256-2.450; 65-74 years: aOR = 2.430, 95%CI: 1.605-3.678; ≥ 75 years: aOR = 2.037, 95% CI: 1.038-3.995), married/cohabiting (aOR = 1.662, 95%CI: 1.052-2.626), obesity (aOR = 1.874, 95%CI: 1.229-2.857), and longer naps (≥ 30 and < 60 min: aOR = 1.682, 95%CI: 1.072-2.637; ≥ 60 min: aOR = 1.387, 95%CI: 1.019-1.889). CONCLUSIONS: Chinese middle-aged and elderly individuals experienced a risk of prehypertension progressing to hypertension over a 2-year period, although the influencing factors differed by sex; this should be considered in interventions.
Assuntos
Hipertensão , Pré-Hipertensão , Masculino , Idoso , Pessoa de Meia-Idade , Humanos , Feminino , Pré-Hipertensão/epidemiologia , Estudos Longitudinais , População do Leste Asiático , Hipertensão/etiologia , Fatores de Risco , Obesidade/epidemiologia , Obesidade/complicações , PrevalênciaRESUMO
BACKGROUND: Fear of future workplace violence (FFWV) has a negative impact on individuals' health. However, no study has investigated the association between FFWV and depressive symptoms. Nurses with different experiences of workplace violence may have different levels of FFWV and differences in mental health. This study explored the association between FFWV and depressive symptoms among Chinese nurses with different experiences of workplace violence. METHODS: A cross-sectional study was conducted involving 1888 Chinese nurses from 12 tertiary hospitals in Shandong Province. The Fear of Future Violence at Work scale was used to measure FFWV. Depressive symptoms were assessed using the 10-item Center for Epidemiologic Studies Depression scale. Multiple logistic regression analysis was used to examine the association between FFWV and depressive symptoms. RESULTS: The prevalence of depressive symptoms was 45.9% (no aggression group: 24.3%; non-physical violence group: 46.1%; physical violence group: 63.7%), and 72.8% of nurses had high levels of fear of future workplace violence (no aggression group: 60.2%; non-physical violence group: 75.6%; physical violence group: 70.8%). Compared with low levels of FFWV, high levels of FFWV were associated with more depressive symptoms among nurses in the no aggression group (odds ratio [OR] = 3.269, 95% confidence interval [CI]: 1.102-9.695) and in the non-physical violence group (OR = 2.338, 95% CI: 1.385-3.945). CONCLUSION: Nurses who had experienced physical violence had the most depressive symptoms and nurses with experience of non-physical violence had the greatest FFWV. Our findings suggested that there was a significant association between FFWV and depressive symptoms among Chinese nurses in the no aggression and non-physical violence groups. Hospital administrators need to address FFWV needs when developing strategies to reduce depressive symptoms among nurses.
RESUMO
Ultra-high performance liquid chromatography-quadrupole-Exactive Orbitrap high resolution mass spectrometry(UHPLC-Q-Exactive Orbitrap HRMS) was employed to systematically analyze the chemical constituents in Lysionoti Herba, and high perfor-mance liquid chromatography-ultraviolet(HPLC-UV) to determine the content of main compounds. A Synergi~(TM) Hydro-RP 100 Å colu-mn(2 mm×100 mm, 2.5 µm) was used for gradient elution with acetonitrile-0.1% aqueous formic acid as the mobile phase at a flow rate of 0.2 mL·min~(-1) and a column temperature of 40 â. MS and MS/MS were conducted with electrospray ionization(ESI) in both positive and negative modes. The chemical components in Lysionoti Herba were identified by comparison with the retention time and mass spectra of reference compounds and the relevant mass spectral data reported in MS databases and relevant literature. Furthermore, the content of five constituents(neochlorogenic acid, chlorogenic acid, forsythoside B, acteoside, and nevadensin) in different Lysiono-ti Herba samples was simultaneously determined by HPLC-UV at the wavelength of 330 nm. A total of 84 compounds were identified in Lysionoti Herba, including 27 flavonoids, 20 phenylethanoid glycosides, 5 amino acids, 18 organic acids, 1 alkaloid, 6 nucleosides, and 7 others. The content of neochlorogenic acid, chlorogenic acid, forsythoside B, acteoside, and nevadensin showed good linear relationship(r>0.999) with the peak area within certain concentration ranges, which were 3.22-102.90, 12.84-410.82, 31.63-1 012.01, 25.00-800.11, and 4.08-130.51 µg·mL~(-1), respectively. The instrument precision, method repeatability, and solution stability all met requirement, and the average recovery rate was 97.31%-100.2%, with RSD ranging from 0.95% to 2.4%. The content of the five components varied among different Lysionoti Herba samples collected from different regions of Guizhou, and the average content of forsythoside B was the highest. The established qualitative method can rapidly and efficiently identify the chemical components of Lysionoti Herba, and the developed HPLC-UV method can simultaneously determine the content of five components in a simple, ra-pid, and accurate manner, providing a scientific basis for the quality evaluation of Lysionoti Herba.
Assuntos
Medicamentos de Ervas Chinesas , Espectrometria de Massas em Tandem , Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Massas em Tandem/métodos , Ácido Clorogênico , Medicamentos de Ervas Chinesas/químicaRESUMO
BACKGROUND AND PURPOSE: Multiple system atrophy (MSA) has no definitive genetic or environmental (G-E) risk factors, and the integrated effect of these factors on MSA etiology remains unknown. This study was undertaken to investigate the integrated effect of G-E factors associated with MSA and its subtypes, MSA-P and MSA-C. METHODS: A consecutive case-control study was conducted at two medical centers, and the interactions between genotypes of five previously reported susceptible single nucleotide polymorphisms (SNPs; SNCA_rs3857059, SNCA_rs11931074, COQ2_rs148156462, EDN1_rs16872704, MAPT_rs9303521) and graded exposure (never, ever, current) of four environmental factors (smoking, alcohol, drinking well water, pesticide exposure) were analyzed by a stepwise logistic regression model. RESULTS: A total of 207 MSA patients and 136 healthy controls were enrolled. In addition to SNP COQ2_rs148156462 (TT), MSA risk was correlated with G-E interactions, including COQ2_rs148156462 (Tc) × pesticide nonexposure, COQ2_rs148156462 (TT) × current smokers, SNCA_rs11931074 (tt) × alcohol nonusers, and SNCA_rs11931074 (GG) × well water nondrinkers (all p < 0.01), with an area under the receiver operating characteristic curve (AUC) of 0.804 (95% confidence interval [CI] = 0.671-0.847). Modulated risk of MSA-C, with MSA-P as a control, correlated with COQ2_rs148156462 (TT) × alcohol nondrinkers, SNCA_rs11931074 (GG) × well water ever drinkers, SNCA_rs11931074 (Gt) × well water never drinkers, and SNCA_rs3857059 (gg) × pesticide nonexposure (all p < 0.05), with an AUC of 0.749 (95% CI = 0.683-0.815). CONCLUSIONS: Certain COQ2 and SNCA SNPs interact with common environmental factors to modulate MSA etiology and subtype disposition. The mechanisms underlying the observed correlation between G-E interactions and MSA etiopathogenesis warrant further investigation.