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OBJECTIVES: To determine the incidence of UI (urinary incontinence) and its subtypes in hypertensive women and examine the association between hypertension and new-onset UI. STUDY DESIGN: We conducted a cohort study on women aged ≥20 years in six regions of China. This cohort study was carried out from 2014 to 2016 at baseline, with follow-up completed in 2018. Information on sociodemographic characteristics, physiological and health behaviours were collected. We calculated the standardized person-year incidence of UI in hypertensive women, and used logistic regression to evaluate the association between hypertension and UI and its subtypes. RESULTS: The standardized incidence of UI, stress UI (SUI), urgency UI (UUI), and mixed UI (MUI) in hypertensive women was 32.2, 21.9, 4.1, and 6.1 per 1000 person-years. Compared with normotensive women, the unadjusted and adjusted OR (odd ratio) for UI in hypertensive women was 2.62 (95 % confidence interval [CI], 2.16-3.18) and 1.70 (95 % CI, 1.14-2.53), respectively; The unadjusted and adjusted OR for SUI in women with hypertension was 2.44 (95 % CI, 1.92-3.09) and 2.60 (95 % CI, 1.68-4.04), respectively; The unadjusted and adjusted OR for UUI in women with hypertension was 2.80 (95 % CI, 1.79-4.37) and 0.54 (95 % CI, 0.13-3.66), respectively; The unadjusted and adjusted OR for MUI in women with hypertension was 2.49 (95 % CI, 1.92-3.09) and 0.60 (95 % CI, 0.19-1.91), respectively. CONCLUSIONS: The incidence of UI in hypertensive women was 32.2/1000 person-years. Hypertension was an independent risk factor for new-onset UI and SUI in Chinese adult women.
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Efficient delivery of nanoparticles (NPs) to plants is important for agricultural application. However, to date, we still lack knowledge about how NPs' charge matters for its translocation pathway, i.e., symplastic and apoplastic pathways, in plants. In this study, we synthesized and used negatively charged citrate sourced carbon dots (C-CDs, -37.97 ± 1.89 mV), Cy5 coated C-CDs (Cy5-C-CDs, -41.90 ± 2.55 mV), positively charged PEI coated carbon dots (P-CDs, +43.03 ± 1.71 mV), and Cy5 coated P-CDs (Cy5-P-CDs, +48.80 ± 1.21 mV) to investigate the role of surface charges and coatings on the employed translocation pathways (symplastic and apoplastic pathways) of charged NPs in plants. Our results showed that, different from the higher fluorescence intensity of P-CDs and Cy5-P-CDs in extracellular than intracellular space, the fluorescence intensity of C-CDs and Cy5-C-CDs was similar between intracellular and extracellular space in cucumber and cotton roots. It suggests that the negatively charged CDs were translocated via both symplastic and apoplastic pathways, but the positively charged CDs were mainly translocated via the apoplastic pathway. Furthermore, our results showed that root applied negatively charged C-CDs demonstrated higher leaf fluorescence than did positively charged P-CDs in both cucumber (8.09 ± 0.99 vs 3.75 ± 0.23) and cotton (7.27 ± 1.06 vs 3.23 ± 0.22), indicating that negatively charged CDs have a higher translocation efficiency from root to leaf than do positively charged CDs. It should be noted that CDs do not affect root cell activities, ROS level, and photosynthetic performance in cucumber and cotton, showing its good biocompatibility. Overall, this study not only figured out that root applied negatively charged CDs employed both symplastic and apoplastic pathways to do the transportation in roots compared with mainly the employment of apoplastic pathway for positively charge CDs, but also found that negatively charge CDs could be more efficiently translocated from root to leaf than positively charged CDs, indicating that imparting negative charge to NPs, at least CDs, matters for its efficient delivery in crops.
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Carbono , Raízes de Plantas , Pontos Quânticos , Carbono/química , Carbono/metabolismo , Pontos Quânticos/química , Pontos Quânticos/metabolismo , Raízes de Plantas/metabolismo , Raízes de Plantas/química , Cucumis sativus/metabolismo , Carbocianinas/químicaRESUMO
The microbiota in the female genital tract is an intricate assembly of diverse aerobic, anaerobic, and microaerophilic microorganisms, which share the space within the reproductive tract and engage in complex interactions. Microbiome dysbiosis may disrupt the symbiotic relationship between the host and microorganisms and play a pivotal role in the pathogenesis of various diseases, including its involvement in the establishment of human papillomavirus (HPV)-associated cervical cancer (CC). Interventions to restore microbiota homeostasis (e.g., probiotics) and bacterial-vector HPV therapeutic vaccines have been reported to be potentially effective in clearing HPV infection and ameliorating cytological abnormalities. In this review, we place emphasis on elucidating the alterations within the cervical-vaginal microbiota as well as the intratumoral microbiota in the context of high-risk HPV (HR-HPV) infection and its subsequent progression to cervical intraepithelial neoplasia/CC. Furthermore, we explore the mechanisms by which these microbial communities exert potential pathogenic or protective effects, including modulating genital inflammation and immune responses, affecting HR-HPV oncogene expression and oncoprotein production, regulating oxidative stress and deoxyribonucleic acid (DNA) damage, and inducing metabolic rewiring. Lastly, we summarize the latest evidence in human trials regarding the efficacy of probiotics, prebiotics and probiotic-vector HPV therapeutic vaccines. This review aims to foster a deeper understanding of the role of the microbiota in HR-HPV infection-related cervix cancer development, and further provide a theoretical basis for the development of preventive and therapeutic strategies based on microbial modulation.
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Disbiose , Microbiota , Infecções por Papillomavirus , Probióticos , Neoplasias do Colo do Útero , Vagina , Humanos , Feminino , Neoplasias do Colo do Útero/virologia , Neoplasias do Colo do Útero/microbiologia , Neoplasias do Colo do Útero/terapia , Infecções por Papillomavirus/virologia , Infecções por Papillomavirus/terapia , Vagina/microbiologia , Vagina/virologia , Probióticos/uso terapêutico , Probióticos/administração & dosagem , Papillomaviridae/patogenicidade , Papillomaviridae/fisiologia , Colo do Útero/microbiologia , Colo do Útero/virologia , Vacinas contra Papillomavirus/administração & dosagem , Displasia do Colo do Útero/virologia , Displasia do Colo do Útero/microbiologia , Displasia do Colo do Útero/terapia , Prebióticos/administração & dosagemRESUMO
BACKGROUND: Research on the co-production of multiple enzymes by Bacillus velezensis as a novel species is still a topic that needs to be studied. This study aimed to investigate the fermentation characteristics of B. velezensis D6 co-producing α-amylase and protease and to explore their enzymatic properties and applications in fermentation. RESULTS: The maximum co-production of α-amylase and protease reached 13.13 ± 0.72 and 2106.63 ± 64.42 U mL-1, respectively, under the optimal fermented conditions (nutrients: 20.0 g L-1 urea, 20.0 g L-1 glucose, 0.7 g L-1 MnCl2; incubation conditions: initial pH 7.0, temperature 41 °C, 8% inoculation size and 30% working volume). Moreover, the genetic co-expression of α-amylase and protease increased from 0 to 24 h and then decreased after 36 h at the transcriptional level, which coincided with the growth trend of B. velezensis D6. The optimal reaction temperature of α-amylase was 55-60 °C, while that of protease was 35-40 °C. The activities of α-amylase and protease were retained by over 80% after thermal treatment (90 °C, 1 h), which indicated that two enzymes co-produced by B. velezensis D6 demonstrated excellent thermal stability. Moreover, the two enzymes were stable over a wide pH range (pH 4.0-8.0 for α-amylase; pH 4.0-9.0 for protease). Finally, the degrees of hydrolysis of corn, rice, sorghum and soybeans by α-amylase from B. velezensis D6 reached 44.95 ± 2.95%, 57.16 ± 2.75%, 52.53 ± 4.01% and 20.53 ± 2.42%, respectively, suggesting an excellent hydrolysis effect on starchy raw materials. The hydrolysis degrees of mackerel heads and soybeans by protease were 43.93 ± 2.19% and 26.38 ± 1.72%, respectively, which suggested that the protease from B. velezensis D6 preferentially hydrolyzed animal-based protein. CONCLUSION: This is a systematic study on the co-production of α-amylase and protease by B. velezensis D6, which is crucial in widening the understanding of this species co-producing multi-enzymes and in exploring its potential application. © 2024 Society of Chemical Industry.
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This study aimed to explore the effects of different disturbances on the fungal communities in the sediments of the Jialing River in order to provide scientific basis for the protection of the river ecosystem. The fungal community in the sediments of the main stream of the Jialing River was taken as the research object, and high-throughput sequencing and bioinformatics techniques were used to analyze the differences in the composition and function of fungal communities in river sediment of different types of disturbance ï¼project disturbance, tributary disturbance, sand mining disturbance, and reclamation disturbanceï¼ and non-disturbance sections. The results showed thatï¼ â The reclamation and project disturbances significantly inhibited the diversity and richness of fungal communities ï¼P<0.05ï¼. The tributary disturbance increased the richness of fungal communities, whereas the impact of sand mining disturbance on sediment fungal communities was not significant. â¡ The diversity and composition of fungal communities tended to be similar at the different sampling sites in the section with low input of exogenous substances ï¼non-disturbance and sand mining disturbanceï¼, whereas there were obvious differences in the diversity of fungal communities at the different sampling sites of high input of external substances ï¼tributary disturbance, project disturbance, and reclamation disturbanceï¼ sections. ⢠Ascomycota, Rozellomycota, and Basidiomycota were the main dominant fungal phyla in the sediments of the Jialing River. The relative abundance of Rozellomycota was the highest in the sand mining interference section, and the relative abundance of Basidiomycota was the highest in the tributary interference section. Project disturbance significantly increased the relative abundance of saprotrophs, animal pathogens, plant pathogens, and dung saprotrophs, whereas other disturbances inhibited the relative abundance of fungal parasitic fungi, plant pathogens, and plant saprophytes. In conclusion, human disturbance has caused changes in fungal diversity, community structure, and function in the sediment of the Jialing River, and xenobiotic input was a key factor contributing to this phenomenon. The results can provide a reference for predicting and evaluating the ecological quality of river sediments.
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Fungos , Sedimentos Geológicos , Rios , Rios/microbiologia , Sedimentos Geológicos/microbiologia , Sedimentos Geológicos/química , Fungos/classificação , China , Ecossistema , Biodiversidade , Monitoramento AmbientalRESUMO
BACKGROUND: Long-term immunosuppressive maintenance therapy is necessary to prevent the rejection of xenografts. However, it is still unclear which oral immunosuppressant is most suitable for pig-to-human xenotransplantation . METHODS: A xenogeneic mixed lymphocyte reaction (MLR) system was established using peripheral blood mononuclear cells (PBMCs) isolated from wildtype (WT) or GTKO/CMAHKO/ß4GalNT2KO (TKO) pigs as stimulator cells and human PBMCs as responder cells. Various concentrations of tacrolimus (Tac), cyclosporine (CsA), or rapamycin (Rapa) were added to the MLR system as interventions. The inhibitory effects of the three immunosuppressants on the proliferation and cytokine production of human T cells were studied and compared. The inhibitory effect of anti-CD154 mAb alone or in combination with Tac/CsA/Rapa on xenoreactive MLR was also investigated. RESULTS: PBMCs from both WT and TKO pigs stimulated significant proliferation of human T cells. Tac had a strong inhibitory effect on human T-cell proliferation stimulated by pig PBMCs. CsA inhibited human T-cell proliferation in a typical dose-dependent manner. When Tac and CsA concentrations reached 5 and 200 ng/mL, respectively, the proliferation rates of CD3+/CD4+/CD8+ T cells were reduced almost to a negative level. Even at high concentrations, Rapa had only a moderate inhibitory effect on xenogeneic MLR. The inhibitory effects of these three immunosuppressants on xenogeneic T-cell responses were further confirmed by the detection of CD25 expression and supernatant cytokines (IL-2, IL-6, IFN-γ, TNF-α, IL-4, IL-10, and IL-17). Although anti-CD154 mAb monotherapy showed only moderate inhibitory effects on xenoreactive T-cell proliferation, low-dose anti-CD154 mAb combined with low-dose Tac, CSA, or Rapa could produce significant synergistic inhibitory effects. CONCLUSION: Tac is more efficient than CsA or Rapa in inhibiting xenogeneic T-cell responses in vitro. If used in combination with anti-CD154 mAb, all the three immunosuppressants can achieve satisfactory synergistic inhibitory effects.
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Proliferação de Células , Ciclosporina , Imunossupressores , Teste de Cultura Mista de Linfócitos , Sirolimo , Tacrolimo , Transplante Heterólogo , Animais , Sirolimo/farmacologia , Humanos , Tacrolimo/farmacologia , Imunossupressores/farmacologia , Ciclosporina/farmacologia , Transplante Heterólogo/métodos , Suínos , Proliferação de Células/efeitos dos fármacos , Linfócitos T/imunologia , Linfócitos T/efeitos dos fármacos , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Citocinas/metabolismo , Citocinas/imunologia , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/efeitos dos fármacos , Animais Geneticamente ModificadosRESUMO
OBJECTIVES: To develop an innovative magnetic resonance imaging (MRI)-based PUMCH (Peking Union Medical College Hospital) classification system aimed at standardising the diagnosis of congenital cervical malformations (CCMs) by identifying their distinctive MRI features. METHODS: Seventy-nine consecutive patients with CCM underwent pre-treatment pelvic MRI; three experienced gynaecological radiologists retrospectively analysed these images. Qualitative assessments included Rock et al's classification; PUMCH classification; haematometra; cervical signal features; ovarian endometriosis; haematosalpinx; and uterine, vaginal, urinary, and musculoskeletal malformations. Quantitative assessments involved the uterine volume, sagittal cervical length, and maximum ovarian cross-sectional area. The surgical treatment types were also recorded. Statistical methods were used to incorporate differences in clinical features and surgical methods into our classification. RESULTS: Morphologically, CCMs were categorised into three types: type I (53%) was characterised by the presence of a cervix with visible cervical canals; type II (23%) featured an existing cervix with concealed cervical canals; and type III (24%) indicated cervical aplasia, which involves a blind end in the lower part of the uterine corpus. Haematometra was significantly more prevalent in patients with type I CCM than in those with type II (p < 0.001). There were three cervical signal patterns: no signal (27%), no evident layer differentiation (21%), and multi-layer differentiation with haematocele (52%). Most patients (94%) had complete vaginal atresia. Type I CCM patients had a higher likelihood of regaining normal uterovaginal anatomy compared to types II and III. CONCLUSIONS: Our proposed PUMCH classification system has a high potential for enhancing the efficiency of clinical diagnosis among patients with CCM. CRITICAL RELEVANCE STATEMENT: The proposed new PUMCH classification promised to elevate the conventional diagnostic trajectory for congenital cervical malformations, offering a valuable framework to refine the selection and planning of surgical interventions, thereby enhancing overall clinical efficacy. KEY POINTS: Effective classification of congenital cervical malformations is desirable to optimise the diagnostic process. We presented a PUMCH classification of congenital cervical malformations using pelvic MRI. The new classification significantly aids clinical triage for congenital cervical malformations.
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OBJECTIVES: To evaluate the robustness of radiomics features among photon-counting detector CT (PCD-CT) and dual-energy CT (DECT) systems. METHODS: A texture phantom consisting of twenty-eight materials was scanned with one PCD-CT and four DECT systems (dual-source, rapid kV-switching, dual-layer, and sequential scanning) at three dose levels twice. Thirty sets of virtual monochromatic images at 70 keV were reconstructed. Regions of interest were delineated for each material with a rigid registration. Ninety-three radiomics were extracted per PyRadiomics. The test-retest repeatability between repeated scans was assessed by Bland-Altman analysis. The intra-system reproducibility between dose levels, and inter-system reproducibility within the same dose level, were evaluated by intraclass correlation coefficient (ICC) and concordance correlation coefficient (CCC). Inter-system variability among five scanners was assessed by coefficient of variation (CV) and quartile coefficient of dispersion (QCD). RESULTS: The test-retest repeatability analysis presented that 97.1% of features were repeatable between scan-rescans. The mean ± standard deviation ICC and CCC were 0.945 ± 0.079 and 0.945 ± 0.079 for intra-system reproducibility, respectively, and 86.0% and 85.7% of features were with ICC > 0.90 and CCC > 0.90, respectively, between different dose levels. The mean ± standard deviation ICC and CCC were 0.157 ± 0.174 and 0.157 ± 0.174 for inter-system reproducibility, respectively, and none of the features were with ICC > 0.90 or CCC > 0.90 within the same dose level. The inter-system variability suggested that 6.5% and 12.8% of features were with CV < 10% and QCD < 10%, respectively, among five CT systems. CONCLUSION: The radiomics features were non-reproducible with significant variability in values among different CT techniques. CLINICAL RELEVANCE STATEMENT: Radiomics features are non-reproducible with significant variability in values among photon-counting detector CT and dual-energy CT systems, necessitating careful attention to improve the cross-system generalizability of radiomic features before implementation of radiomics analysis in clinical routine. KEY POINTS: CT radiomics stability should be guaranteed before the implementation in the clinical routine. Radiomics robustness was on a low level among photon-counting detectors and dual-energy CT techniques. Limited inter-system robustness of radiomic features may impact the generalizability of models.
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Intergroup trust is a crucial psychological foundation for promoting ethnic unity and maintaining social stability. This study explored the dynamic relationship between intergroup contact and trust among adolescents in ethnic regions of China and sought to uncover the mechanisms behind this relationship. Through a two-wave longitudinal survey of 679 adolescents, employing the Intergroup Contact Experience Scale, the Intergroup Trust Scale, and the UCLA Loneliness Scale, the study yielded several findings: (1) Over the year, a significant increase in intergroup contact was observed among the adolescents. Notably, junior high students demonstrated a marked rise in intergroup trust, whereas no significant change was discernible in high school students. (2) Cross-lagged analysis indicated that early intergroup contact significantly predicted subsequent intergroup trust and loneliness. Initial loneliness also forecasted future intergroup trust, yet early intergroup trust did not predict later intergroup contact or loneliness. (3) Loneliness served as a partial mediator in the longitudinal link between intergroup contact and trust among these adolescents. These findings reinforce the premise that in China's ethnic regions, intergroup contact is a precursor to intergroup trust, both directly enhancing trust among adolescents and indirectly by reducing loneliness.
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Etnicidade , Solidão , Confiança , Humanos , Adolescente , Confiança/psicologia , China , Masculino , Feminino , Solidão/psicologia , Estudos Longitudinais , Etnicidade/psicologia , Relações Interpessoais , Estudantes/psicologiaRESUMO
The non-neural cholinergic system plays a critical role in regulating immune equilibrium and tissue homeostasis. While the expression of choline acetyltransferase (ChAT), the enzyme catalyzing acetylcholine biosynthesis, has been well documented in lymphocytes, its role in the myeloid compartment is less understood. Here, we identify a significant population of macrophages (MÏs) expressing ChAT and synthesizing acetylcholine in the resolution phase of acute peritonitis. Using Chat-GFP reporter mice, we observed marked upregulation of ChAT in monocyte-derived small peritoneal MÏs (SmPMs) in response to Toll-like receptor agonists and bacterial infections. These SmPMs, phenotypically and transcriptionally distinct from tissue-resident large peritoneal macrophages, up-regulated ChAT expression through a MyD88-dependent pathway involving MAPK signaling. Notably, this process was attenuated by the TRIF-dependent TLR signaling pathway, and our tests with a range of neurotransmitters and cytokines failed to induce a similar response. Functionally, Chat deficiency in MÏs led to significantly decreased peritoneal acetylcholine levels, reduced efferocytosis of apoptotic neutrophils, and a delayed resolution of peritonitis, which were reversible with exogenous ACh supplementation. Intriguingly, despite B lymphocytes being a notable ChAT-expressing population within the peritoneal cavity, Chat deletion in B cells did not significantly alter the resolution process. Collectively, these findings underscore the crucial role of MÏ-derived acetylcholine in the resolution of inflammation and highlight the importance of the non-neuronal cholinergic system in immune regulation.
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Acetilcolina , Colina O-Acetiltransferase , Macrófagos Peritoneais , Peritonite , Animais , Colina O-Acetiltransferase/metabolismo , Colina O-Acetiltransferase/genética , Peritonite/imunologia , Peritonite/metabolismo , Camundongos , Macrófagos Peritoneais/metabolismo , Macrófagos Peritoneais/imunologia , Acetilcolina/metabolismo , Fator 88 de Diferenciação Mieloide/metabolismo , Fator 88 de Diferenciação Mieloide/genética , Camundongos Endogâmicos C57BL , Transdução de Sinais , Inflamação/metabolismo , Inflamação/patologia , Linfócitos B/imunologia , Linfócitos B/metabolismo , Receptores Toll-Like/metabolismo , Fagocitose , Macrófagos/metabolismo , Macrófagos/imunologia , Camundongos KnockoutRESUMO
Manipulating single electrons at the atomic scale is vital for mastering complex surface processes governed by the transfer of individual electrons. Polarons, composed of electrons stabilized by electron-phonon coupling, offer a pivotal medium for such manipulation. Here, using scanning tunneling microscopy and spectroscopy (STM/STS) and density functional theory (DFT) calculations, we report the identification and manipulation of a new type of polaron, dubbed van der Waals (vdW) polaron, within mono- to trilayer ultrathin films composed of Sb2O3 molecules that are bonded via vdW attractions. The Sb2O3 films were grown on a graphene-covered SiC(0001) substrate via molecular beam epitaxy. Unlike prior molecular polarons, STM imaging observed polarons at the interstitial sites of the molecular film, presenting unique electronic states and localized band bending. DFT calculations revealed the lowest conduction band as an intermolecular bonding state, capable of ensnaring an extra electron through locally diminished intermolecular distances, thereby forming an intermolecular vdW polaron. We also demonstrated the ability to generate, move, and erase such vdW polarons using an STM tip. Our work uncovers a new type of polaron stabilized by coupling with intermolecular vibrations where vdW interactions dominate, paving the way for designing atomic-scale electron transfer processes and enabling precise tailoring of electron-related properties and functionalities.
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Introduction: It remains unclear whether depressive symptoms are associated with increased all-cause mortality and to what extent depressive symptoms are associated with chronic disease and all-cause mortality. The study aims to explore the relationship between depressive symptoms and all-cause mortality, and how depressive symptoms may, in turn, affect all-cause mortality among Chinese middle-aged and older people through chronic diseases. Methods: Data were collected from the China Health and Retirement Longitudinal Study (CHARLS). This cohort study involved 13,855 individuals from Wave 1 (2011) to Wave 6 (2020) of the CHARLS, which is a nationally representative survey that collects information from Chinese residents ages 45 and older to explore intrinsic mechanisms between depressive symptoms and all-cause mortality. The Center for Epidemiological Studies Depression Scale (CES-D-10) was validated through the CHARLS. Covariates included socioeconomic variables, living habits, and self-reported history of chronic diseases. Kaplan-Meier curves depicted mortality rates by depressive symptom levels, with Cox proportional hazards regression models estimating the hazard ratios (HRs) of all-cause mortality. Results: Out of the total 13,855 participants included, the median (Q1, Q3) age was 58.00 (51.00, 63.00) years. Adjusted for all covariates, middle-aged and older adults with depressive symptoms had a higher all-cause mortality rate (HR = 1.20 [95% CI, 1.09-1.33]). An increased rate was observed for 55-64 years old (HR = 1.23 [95% CI, 1.03-1.47]) and more than 65 years old (HR = 1.32 [95% CI, 1.18-1.49]), agricultural Hukou (HR = 1.44, [95% CI, 1.30-1.59]), and nonagricultural workload (HR = 1.81 [95% CI, 1.61-2.03]). Depressive symptoms increased the risks of all-cause mortality among patients with hypertension (HR = 1.19 [95% CI, 1.00-1.40]), diabetes (HR = 1.41[95% CI, 1.02-1.95]), and arthritis (HR = 1.29 [95% CI, 1.09-1.51]). Conclusion: Depressive symptoms raise all-cause mortality risk, particularly in those aged 55 and above, rural household registration (agricultural Hukou), nonagricultural workers, and middle-aged and older people with hypertension, diabetes, and arthritis. Our findings through the longitudinal data collected in this study offer valuable insights for interventions targeting depression, such as early detection, integrated chronic disease care management, and healthy lifestyles; and community support for depressive symptoms may help to reduce mortality in middle-aged and older people.
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Depressão , Humanos , Masculino , Feminino , China/epidemiologia , Depressão/epidemiologia , Depressão/mortalidade , Pessoa de Meia-Idade , Doença Crônica/mortalidade , Estudos Longitudinais , Idoso , Causas de Morte , Fatores de Risco , Mortalidade/tendências , Modelos de Riscos ProporcionaisRESUMO
Ovarian cancer (OV) poses a significant challenge in clinical settings due to its difficulty in early diagnosis and treatment resistance. FOXP4, belonging to the FOXP subfamily, plays a pivotal role in various biological processes including cancer, cell cycle regulation, and embryonic development. However, the specific role and importance of FOXP4 in OV have remained unclear. Our research showed that FOXP4 is highly expressed in OV tissues, with its elevated levels correlating with poor prognosis. We further explored FOXP4's function through RNA sequencing and functional analysis in FOXP4-deficient cells, revealing its critical role in activating the Wnt signaling pathway. This activation exacerbates the malignant phenotype in OV. Mechanistically, FOXP4 directly induces the expression of protein tyrosine kinase 7 (PTK7), a Wnt-binding receptor tyrosine pseudokinase, which causes abnormal activation of the Wnt signaling pathway. Disrupting the FOXP4-Wnt feedback loop by inactivating the Wnt signaling pathway or reducing FOXP4 expression resulted in the reduction of the malignant phenotype of OV cells, while restoring PTK7 expression reversed this effect. In conclusion, our findings underscore the significance of the FOXP4-induced Wnt pathway activation in OV, suggesting the therapeutic potential of targeting this pathway in OV treatment.
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Fatores de Transcrição Forkhead , Neoplasias Ovarianas , Receptores Proteína Tirosina Quinases , Via de Sinalização Wnt , Animais , Feminino , Humanos , Camundongos , beta Catenina/metabolismo , Moléculas de Adesão Celular/metabolismo , Moléculas de Adesão Celular/genética , Linhagem Celular Tumoral , Proliferação de Células , Fatores de Transcrição Forkhead/metabolismo , Fatores de Transcrição Forkhead/genética , Regulação Neoplásica da Expressão Gênica , Camundongos Nus , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/genética , Receptores Proteína Tirosina Quinases/metabolismo , Receptores Proteína Tirosina Quinases/genéticaRESUMO
⢠Endometrial hyperplasia can be classified as either hyperplasia without atypia or atypical hyperplasia. ⢠Abnormal uterine bleeding is the most common symptom of endometrial hyperplasia. Transvaginal ultrasound is recommended for initial imaging to evaluate endometrial hyperplasia (evidence level 2+), while transrectal ultrasound is recommended for virgo patients (evidence level 3). ⢠Endometrial biopsy should be used to confirm diagnosis in patients where endometrial lesions are suspected. Effective histological approaches to make definite diagnoses include diagnostic curettage (evidence level 2++), hysteroscopic-guided biopsy (evidence level 2+) and endometrial aspiration biopsy (evidence level 2-). ⢠Progesterone is the preferred medication for the treatment of endometrial hyperplasia without atypia. Compared to oral progestins, placement of a levonorgestrel-releasing intrauterine system (LNG-IUS) has been associated with higher regression rates, lower recurrence rates and fewer adverse events which can be the initial treatment method. (Meta evidence level 1-, RCT evidence level 2+). Ultrasound and endometrial biopsies should be performed every 6 months during treatment to evaluate its effect and treatment should continue until no pathological changes are observed in two consecutive endometrial biopsies. Hysterectomy is not the preferred choice of treatment for patients with endometrial hyperplasia without atypia. ⢠Minimally invasive hysterectomy is indicated for patients with endometrial atypical hyperplasia (evidence level 1+), bilateral fallopian tubes should also be removed (evidence level 2+). In cases where surgery cannot be tolerated, fertility is desired or the patient is younger than 45 years old, medical therapy is recommended (evidence level 3). LNG-IUS is the preferred medical therapy method (evidence level 2+). Endometrial pathologic evaluation should be performed every 3 months during conservative treatments, with adjustments made to dosages or approaches based on observed response to medication. Treatment should continue until no pathological changes are detected in two consecutive endometrial biopsies (evidence level 2++). There is no indication of sentinel lymph nodes biopsy and/or lymphadenectomy for hyperplasia with or without atypia. ⢠Total hysterectomy is recommended to treat patients with recurrent endometrial atypical hyperplasia (evidence level 3); however, medical conservative therapy may be considered for patients hoping to become pregnant in the future. ⢠Patients with fully regressed disease who would like to become pregnant should be advised to seek assistance through assisted reproductive technologies (evidence level 3). ⢠Long-term follow-up is suggested for patients after endometrial hyperplasia treatment (evidence level 2+). Patient education is imperative for improving medication adherence, increasing regression rates and lowering recurrence rates (evidence level 3).
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Hiperplasia Endometrial , Humanos , Feminino , Hiperplasia Endometrial/terapia , Hiperplasia Endometrial/patologia , Hiperplasia Endometrial/diagnóstico , Levanogestrel/uso terapêutico , Levanogestrel/administração & dosagem , Progestinas/uso terapêutico , Dispositivos Intrauterinos Medicados , Histeroscopia/métodos , China , Ultrassonografia , Biópsia , Histerectomia , Endométrio/patologia , Curetagem , Progesterona/uso terapêutico , Progesterona/administração & dosagemRESUMO
BACKGROUND: Myofascial pelvic pain (MFPP), which is identified by tender points in the pelvic floor musculature, is a prevalent source of chronic pelvic pain in women. It may lead to physical and mental exhaustion, reproductive concerns, and coping difficulties in daily life and work than the disease itself. Pain-related cognitive processes can affect pain relief and quality of life. Kinesiophobia, self-efficacy and pain catastrophizing are frequently treated as mediators between pain and its related consequences. Greater kinesiophobia and pain catastrophizing have been shown to be associated with adverse functional outcomes, while higher self-efficacy has been related with improved quality of life. Regarding MFPP in females of childbearing age, it remains unclear whether the effects of kinesiophobia, self-efficacy and pain catastrophizing on daily interference are direct or indirect; the influence on each variable is, therefore, not entirely evident. AIM: The present study aimed to evaluate the relationship between pain and daily interference in reproductive-age women with MFPP through kinesiophobia, self-efficacy and pain catastrophizing, as well as to identify areas for future investigation and intervention based on the data collected from this population. METHODS: This is a multi-center cross-sectional study. The study was conducted from November 15, 2022 to November 10, 2023, 202 reproductive-age women with MFPP were recruited from 14 hospitals in ten provinces of China. The demographic variables, Brief Pain Inventory, Tampa Scale of Kinesiophobia, Pain Self-Efficacy Questionnaire, and Pain Catastrophizing Scale were used to measure the participants' related information. The data was described and analyzed using Descriptive analyses, Pearson correlation analysis, and Serial mediation modeling. RESULTS: Pain not only had a direct positive impact (B = 0.575; SE = 0.081; 95%CI: LL = 0.415, UL = 0.735) on daily interference, but also had an indirect impact on daily interference through the independent mediating role of pain catastrophizing (B = 0.088; SE = 0.028; 95%CI: LL = 0.038, UL = 0.148), the chain mediating of kinesiophobia and catastrophizing (B = 0.057; SE = 0.019; 95%CI: LL = 0.024, UL = 0.098), and the four-stage serial mediating of kinesiophobia, self-efficacy and catastrophizing (B = 0.013; SE = 0.006; 95%CI: LL = 0.003, UL = 0.027). The proposed serial mediation model showed a good fit with the collected data. CONCLUSION: The findings illustrate the significance of addressing pain catastrophizing and kinesiophobia (especially catastrophizing), and increasing self-efficacy in pain therapy, and suggest that functional recovery be integrated into pain therapy for reproductive-age women suffering from MFPP.
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Catastrofização , Dor Pélvica , Autoeficácia , Humanos , Feminino , Catastrofização/psicologia , Adulto , Dor Pélvica/psicologia , Adulto Jovem , Qualidade de Vida/psicologia , Medição da Dor , Síndromes da Dor Miofascial/psicologia , Estudos Transversais , Pessoa de Meia-Idade , Medo/psicologia , Transtornos Fóbicos/psicologia , Inquéritos e Questionários , Adolescente , CinesiofobiaRESUMO
Background: Colpocleisis is one of traditional surgical procedures for elderly and frail women with advanced pelvic organ prolapse. The occurrence of de novo urinary incontinence following colpocleisis was considered to impair the postoperative quality of life. The incidence of de novo urinary incontinence after colpocleisis has been reported to be ranging from 6.6 % to 27 %. There was an absence of prospective large-sample study to investigate the accurate incidence of de novo urinary incontinence following colpocleisis and the impact on the quality of life till now. Purpose: s The primary objective was to report the incidence of de novo urinary incontinence after colpocleisis. The second objectives were to evaluate the long-term quality of life in patients with de novo urinary incontinence, and to conduct detailed pre- and post-operative evaluations of lower urinary tract symptoms. Methods: This prospective study included 253 patients with symptomatic pelvic organ prolapse who underwent colpocleisis between 2009 and 2021. De novo urinary incontinence was defined as the occurrence of urinary incontinence 3 months postoperatively. All patients were required to complete the Urinary Distress Inventory questionnaire and the Urinary Impact Questionnaire for the evaluation of patients' quality of life, and the Patient Global Impression of Improvement questionnaire for the evaluation of patients' satisfaction. Results: 245 patients (245/253, 96·8 %) completed the 3-month follow-up, and were included in the final analysis. The incidence of de novo urinary incontinence was 5.4 % (10/185). There was no significant difference in the Urinary Distress Inventory -6 scores (22.50 vs. 10.30, P = 0.276) or the subjective satisfaction rate (100 % vs. 98.9 %, P = 0.250) between the patients with or without de novo urinary incontinence at the long-term follow-up. The incidence of voiding difficulty was significantly reduced after colpocleisis (27.8 % vs. 0.0 %, P < 0.001). The patients' quality of life indicated by Urinary Distress Inventory-6 and Urinary Impact Questionnaire-7 scores were significantly improved postoperatively (26.27 vs. 13.39, and 19.13 vs. 6.05, P < 0.05). Conclusion: The incidence of de novo urinary incontinence after colpocleisis was very low. Patients' quality of life, and low urinary tract symptoms were significantly improved after colpocleisis.
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Background: There are many problems of psychological burden in patients with tumor implanted in port of intravenous infusion. However, more attention is paid to its complications in the literature, and psychological problems are seldom concerned. The purpose of this study was to explore the psychological state and needs of tumor patients after implantation of an intravenous infusion port and provide valuable references for psychological interventions. Method: A semi-structured interview was conducted with 11 patients with intravenous infusion ports. Colaizzi's 7-step analysis was used to analyze the interview data. Results: According to the primary information, four themes and nine sub-themes were extracted: (1) lack of self-worth, (2) multiple emotional experiences (guilt, doubt, worry, and gain). (3) Poor self-management and self-maintenance awareness (over-reliance on medical staff, unchanged family roles, lack of related knowledge). (4) Expectations and suggestions for the future (inner expectations, suggestions for infusion ports). Conclusion: The patient's psychological state should be carefully monitored during tube implantation, to relieve the patient's tension and anxiety and improve nursing satisfaction and patient outcomes.
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There are complex and diverse substances in traditional vinegars, some of which have been identified as biologically active factors, but the variety of functional compounds is currently restricted. In this study, it was aimed to determine the bioactive compounds in 10 typical functional vinegars. The findings shown that total flavonoids (0.21-7.19 mg rutin equivalent/mL), total phenolics (0.36-3.20 mg gallic acid equivalent/mL), and antioxidant activities (DPPH: 3.17-47.63 mmol trolox equivalent/L, ABTS: 6.85-178.29 mmol trolox equivalent/L) varied among different functional vinegars. In addition, the concentrations of the polysaccharides (1.17-44.87 mg glucose equivalent/mL) and total saponins (0.67-12.46 mg oleanic acid equivalent/mL) were determined, which might play key role for the function of tested vinegars. A total of 8 organic acids, 7 polyphenol compounds and 124 volatile compounds were measured and tentatively identified. The protocatechuic acid (4.81-485.72 mg/L), chlorogenic acid (2.69-7.52 mg/L), and epicatechin (1.18-97.42 mg/L) were important polyphenol compounds in the functional vinegars. Redundancy analysis indicated that tartaric acid, oxalic acid and chlorogenic acid were significantly positively correlated with antioxidant capacity. Various physiologically active ingredients including cyclo (Pro-Leu), cyclo (Phe-Pro), cyclo (Phe-Val), cyclo (Pro-Val), 1-monopalmitin and 1-eicosanol were firstly detected in functional vinegars. Principle component analysis revealed that volatiles profile of bergamot Monascus aromatic vinegar and Hengshun honey vinegar exhibited distinctive differences from other eight vinegar samples. Moreover, the partial least squares regression analysis demonstrated that 11 volatile compounds were positively correlated with the antioxidant activity of vinegars, which suggested these compounds might be important functional substances in tested vinegars. This study explored several new functionally active compounds in different functional vinegars, which could widen the knowledge of bioactive factor in vinegars and provide new ideas for further development of functional vinegar beverages.
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Ácido Acético , Antioxidantes , Ácido Clorogênico , Ácido Gálico , PolifenóisRESUMO
Purpose: This study aimed to develop a novel and feasible modification strategy to improve the solubility and antitumor activity of resiquimod (R848) by utilizing the supramolecular effect of 2-hydroxypropyl-beta-cyclodextrin (2-HP-ß-CD). Methods: R848-loaded PLGA nanoparticles modified with 2-HP-ß-CD (CD@R848@NPs) were synthesized using an enhanced emulsification solvent-evaporation technique. The nanoparticles were then characterized in vitro by several methods, such as scanning electron microscopy (SEM), differential scanning calorimetry (DSC), Fourier transform infrared (FTIR) spectroscopy, particle size analysis, and zeta potential analysis. Then, the nanoparticles were loaded with IR-780 dye and imaged using an in vivo imaging device to evaluate their biodistribution. Additionally, the antitumor efficacy and underlying mechanism of CD@R848@NPs in combination with an anti-TNFR2 antibody were investigated using an MC-38 colon adenocarcinoma model in vivo. Results: The average size of the CD@R848@NPs was 376 ± 30 nm, and the surface charge was 21 ± 1 mV. Through this design, the targeting ability of 2-HP-ß-CD can be leveraged and R848 is delivered to tumor-supporting M2-like macrophages in an efficient and specific manner. Moreover, we used an anti-TNFR2 antibody to reduce the proportion of Tregs. Compared with plain PLGA nanoparticles or R848, CD@R848@NPs increased penetration in tumor tissues, dramatically reprogrammed M1-like macrophages, removed tumors and prolonged patient survival. Conclusion: The new nanocapsule system is a promising strategy for targeting tumor, reprogramming tumor -associated macrophages, and enhancement immunotherapy.