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1.
Adv Sci (Weinh) ; : e2405318, 2024 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-39356034

RESUMO

Chronic obstructive pulmonary disease (COPD) stands as the prevailing chronic airway ailment, characterized by chronic bronchitis and emphysema. Current medications fall short in treatment of these diseases, underscoring the urgent need for effective therapy. Prior research indicated immunoproteasome inhibition alleviated various inflammatory diseases by modulating immune cell functions. However, its therapeutic potential in COPD remains largely unexplored. Here, an elevated expression of immunoproteasome subunits LMP2 and LMP7 in the macrophages isolated from mouse with LPS/Elastase-induced emphysema and polarized macrophages in vitro is observed. Subsequently, intranasal administration of the immunoproteasome-specific inhibitor ONX-0914 significantly mitigated COPD-associated airway inflammation and improved lung function in mice by suppressing macrophage polarization. Additionally, ONX-0914 capsulated in PLGA nanoparticles exhibited more pronounced therapeutic effect on COPD than naked ONX-0914 by targeting immunoproteasome in polarized macrophages. Mechanistically, ONX-0914 activated autophagy and endoplasmic reticulum (ER) stress are not attribute to the ONX-0914 mediated suppression of macrophage polarization. Intriguingly, ONX-0914 inhibited M1 polarization through the nuclear factor erythroid 2-related factor-1 (NRF1) and NRF2-P62 axis, while the suppression of M2 polarization is regulated by inhibiting the transcription of interferon regulatory factor 4 (IRF4). In summary, the findings suggest that targeting immunoproteasome in macrophages holds promise as a therapeutic strategy for COPD.

2.
BMC Med ; 22(1): 376, 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39256772

RESUMO

BACKGROUND: Neurogenic erectile dysfunction, characterized by neurological repair disorders and progressive corpus cavernosum fibrosis (CCF), is an unbearable disease with limited treatment success. IL-17A exhibits a complex role in tissue remodelling. Nevertheless, the precise role and underlying mechanisms of IL-17A in CCF under denervation remain unclear. METHODS: PCR array was employed to identified differentially expressed genes between neurogenic ED and normal rats. IL-17A expression and its main target cells were analyzed using Western blotting, immunofluorescence and immunohistochemistry. The phenotypic regulation of IL-17A on corpus cavernosum smooth muscle cells (CSMCs) was evaluated by cell cycle experiments and SA-ß-Gal staining. The mechanism of IL-17A was elucidated using non-target metabolomics and siRNA technique. Finally, IL-17A antagonist and ABT-263 (an inhibitor of B-cell lymphoma 2/w/xL) were utilized to enhance the therapeutic effect in a rat model of neurogenic ED. RESULTS: IL-17A emerged as the most significantly upregulated gene in the corpus cavernosum of model rats. It augmented the senescence transformation and fibrotic response of CSMCs, and exhibited a strong correlation with CCF. Mechanistically, IL-17A facilitated CCF by activating the mTORC2-ACACA signalling pathway, upregulating of CSMCs lipid synthesis and senescence transition, and increasing the secretion of fibro-matrix proteins. In vivo, the blockade of IL-17A-senescence signalling improved erectile function and alleviated CCF in neurogenic ED. CONCLUSIONS: IL-17A assumes a pivotal role in denervated CCF by activating the mTORC2-ACACA signalling pathway, presenting itself as a potential therapeutic target for effectively overcoming CCF and erection rehabilitation in neurogenic ED.


Assuntos
Disfunção Erétil , Fibrose , Interleucina-17 , Pênis , Transdução de Sinais , Animais , Masculino , Disfunção Erétil/tratamento farmacológico , Interleucina-17/metabolismo , Ratos , Transdução de Sinais/efeitos dos fármacos , Pênis/inervação , Pênis/patologia , Alvo Mecanístico do Complexo 2 de Rapamicina/metabolismo , Ratos Sprague-Dawley , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/efeitos dos fármacos , Senescência Celular/efeitos dos fármacos , Modelos Animais de Doenças
3.
Sci Adv ; 10(33): eadn7771, 2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-39151001

RESUMO

Kisspeptin receptor (KISS1R), belonging to the class A peptide-GPCR family, plays a key role in the regulation of reproductive physiology after stimulation by kisspeptin and is regarded as an attractive drug target for reproductive diseases. Here, we demonstrated that KISS1R can couple to the Gi/o pathway besides the well-known Gq/11 pathway. We further resolved the cryo-electron microscopy (cryo-EM) structure of KISS1R-Gq and KISS1R-Gi complexes bound to the synthetic agonist TAK448 and structure of KISS1R-Gq complex bound to the endogenous agonist KP54. The high-resolution structures provided clear insights into mechanism of KISS1R recognition by its ligand and can facilitate the design of targeted drugs with high affinity to improve treatment effects. Moreover, the structural and functional analyses indicated that conformational differences in the extracellular loops (ECLs), intracellular loops (ICLs) of the receptor, and the "wavy hook" of the Gα subunit may account for the specificity of G protein coupling for KISS1R signaling.


Assuntos
Microscopia Crioeletrônica , Receptores de Kisspeptina-1 , Humanos , Ligantes , Receptores de Kisspeptina-1/metabolismo , Receptores de Kisspeptina-1/química , Ligação Proteica , Kisspeptinas/metabolismo , Kisspeptinas/química , Modelos Moleculares , Células HEK293 , Conformação Proteica , Transdução de Sinais , Proteínas de Ligação ao GTP/metabolismo , Proteínas de Ligação ao GTP/química , Relação Estrutura-Atividade
4.
Heliyon ; 10(15): e34896, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39165935

RESUMO

The present study aims to explore the mediating role of reading engagement between instructional quality and reading achievement in China (B-S-J-Z) and the UK, and the pedagogical transportation that has been implemented between China and the UK since 2014. Participants in this study were from PISA 2018 where 12,058 students were from China (B-S-J-Z) and 13,818 were from the UK. Structural equation modeling (SEM) was used to explore the relationships among instructional quality, reading engagement, and reading achievement. The effect of classroom management and cognitive activation on reading achievement was significantly mediated by enjoyment of reading in both China (B-S-J-Z) and the UK. Diversity of reading was found to positively mediate the relationships between classroom management and reading achievement, and between cognitive activation and reading achievement in China (B-S-J-Z), in contrast to the mediating role of reading strategy revealed in the UK. The findings have important implications in that educators from China (B-S-J-Z) and the UK should focus on improving students' reading interests, UK teachers may incorporate diverse sources in reading, and Chinese educators may try different reading teaching strategies. Meanwhile, educators and policymakers may give full consideration to implications based on the specific cultural background. Finally, the limitations and future directions are provided.

6.
Int J Nurs Sci ; 11(3): 301-307, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39156678

RESUMO

Objective: This study aimed to investigate the factors influencing nurses' ability to respond to public health emergencies and understand the relationship between nurses' ability to respond to emergencies and workplace resilience. Methods: A cross-sectional study of 361 nurses from military hospitals was conducted from January 18 to September 6, 2022, using an online survey. The Infectious Diseases Emergency Response Capacity (IDERC) questionnaire and the Workplace Resilience Scale (WRS) were utilized, and sociodemographic information was also collected. Data were analyzed using descriptive statistics and frequency analysis. Differences between groups were identified by one-way analysis of variance, and linear regression was used to analyze the main factors influencing the infectious emergency response capacity. Results: The average infectious emergency response capacity score on the IDERC questionnaire and workplace resilience, measured by WRS, were 4.01 (SD = 0.76) and 3.85 (SD = 0.71), respectively, on a scale of 1-5, indicating high performance. Factors such as degree of education, nurses' service years and experience in epidemic prevention participation were found to be the main influencing factors of the score of IDERC. The level of workplace resilience showed a positive correlation with the capacity to respond to infectious disease, the score of WRS and the service year accounted for 63.6% of the variance in emergency response capabilities. Conclusion: The results indicate an urgent need to strengthen the training of nurses with lower degree of education, shorter service years, no prior work, or no experience of epidemic prevention participation, and hospitals should also prioritize improving nurses' workplace resilience through targeted interventions, enhancing their abilities in infectious disease prevention, preparation, first aid, and subsequent critical patient care.

7.
Updates Surg ; 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-39162930

RESUMO

Large-wound treatment often requires autologous skin grafting or skin flap transfer, causing iatrogenic secondary injuries. Thus, we have developed an automatic wound closure system that consists of a stretch module, microcontroller, and touch screen. Full-thickness wounds (8 × 14 cm) on Bama miniature pigs were manually closed by direct suture in control animals and with three different tension levels performed by the automatic device in the experimental animals. Wound-closure conditions, post-closure healing, and scars were evaluated. Post-operative microscopic changes in collagen fibers, local cell apoptosis, and changes in vascular density were compared between the two wound-closure techniques. In the control group and the first experimental group, which used a traction force of 15 N, primary wound closure could not be achieved. The other two experimental groups used a traction force of 30 N and 60 N and all wounds achieved primary closure. Collagen-fiber stretching was observed histologically in all groups and collagen-fiber breakdown occurred in some wounds when the traction force was 60 N. Scar hyperplasia was significantly reduced in the automatic wound closure system groups. The collagen content decreased, cell apoptosis increased, and vascular density decreased in local tissues in the early post-closure stage, but eventually recovered to normal-skin levels. In summary, we developed an automatic wound closure system that effectively and safely stretches dermal-collagen fibers under an appropriate traction force (30 N) and stretch wound-peripheral skin to cover the wound, achieve primary closure, and reduce scar hyperplasia.

8.
J Chin Med Assoc ; 87(9): 870-877, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38984546

RESUMO

BACKGROUND: This study aimed to investigate the clinical efficacy of intra-articular injections of medical chitosan for treating knee osteoarthritis (KOA) and measure the lipid metabolism profiles of the synovial tissue. METHODS: Sixty patients with KOA undergoing conservative treatment were recruited and randomized into two groups: one without pharmacological intervention (OA group) and the other receiving course-based intra-articular medical chitosan injections (CSI group). Quantitative lipidomic profile of synovial tissue was analyzed. Functional scores, including Kellgren-Lawrence rating (K-L), Visual Analog Scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scoring, and American Knee Society (AKS) scoring were conducted. RESULTS: Survival from the initial conservative treatment to final knee arthroplasty was significantly longer in the CSI group compared to the OA group. Except for the presurgery VAS score, no statistically significant differences were observed in the other scores, including K-L, initial VAS, WOMAC, and AKS. However, the CSI group experienced more reductions in AKS-Knee subscores compared to the OA group. Compared to the CSI group, the OA group exhibited a significant upregulation in most differential lipids, particularly triacylglycerides (TAGs, 77%). The OA group had notably higher levels of long-chain unsaturated fatty acids. CONCLUSION: Intra-articular injection of medical chitosan significantly prolongs the survival period before knee arthroplasty and reduces the deposition of TAGs metabolites.


Assuntos
Quitosana , Osteoartrite do Joelho , Membrana Sinovial , Triglicerídeos , Humanos , Osteoartrite do Joelho/tratamento farmacológico , Quitosana/administração & dosagem , Injeções Intra-Articulares , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Membrana Sinovial/metabolismo
9.
Semin Ophthalmol ; : 1-12, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38949222

RESUMO

OBJECTIVE: To dynamically track the publications on central serous chorioretinopathy (CSC) and depict the research status and hot spots to guide future research. METHODS: Gather all papers published in this area between 2004 and 2024 in the WOSCC databases comprehensively, assess their trends, and characterize the contributions of various nations, authors, institutions, and journals. In addition, VOSviewer, CiteSpace, and R software are used to obtain the most popular keywords for the topic. RESULTS: A total of 2,203 papers were published across 1,863 institutions in 59 countries. Among these, 6,907 authors contributed to publications in 300 journals and generated a total of 35,638 citations. The number of publications continues to grow steadily. Notably, Jay Chhablani's team/Lab stands out as the leading contributor with ownership of 84 publications. Through keyword network analysis and clustering techniques, risk factor-related clustering, imaging-related clustering, pathogenesis-related clustering, and treatment-related clustering were identified. Furthermore, keyword analysis has unveiled emerging frontier areas including pachychoroid disease, choroidal vasculature abnormalities, PDT therapy, and optical coherence tomography that have garnered increasing interest. CONCLUSION: This study presents a comprehensive review of central serous retinopathy research conducted in the past two decades, highlighting key trends and exploring emerging research frontiers within this field. As such, it provides valuable references and suggestions for researchers engaged in studying this topic.

10.
BMC Public Health ; 24(1): 1929, 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39026258

RESUMO

BACKGROUND: Many personnel respond to natural disasters like earthquakes and tsunamis and frequent public health events like Ebola and COVID-19. However, research on emergency assistance personnel remains limited. This study aims to describe the perceived well-being among responders deployed in isolated or emergency international missions while providing practical references to intervene in developing similar missions. METHODS: For this qualitative phenomenological study, purposive sampling was used following the principle of maximum differentiation to select personnel deployed on an emergency mission for over a year. Data collection continued until data saturation. Phenomenologically semi-structured interviews helped explore the physical and psychological status of the participants with Colaizzi's method. RESULTS: Eleven personnel were interviewed after the mission, with four major themes being identified: 'perceived somatic change,' 'perceived emotional change,' 'behavioral change,' and 'coping with perceived change.' CONCLUSIONS: The mental health status of the emergency assistance personnel was affected by multiple factors from external and internal environments. The current study explored the physical and psychological feelings and emotions of emergency assistance personnel during an emergency mission. The study provided a practical reference for health management under similar missions. REGISTRATIONS: Not registered.


Assuntos
COVID-19 , Socorristas , Pesquisa Qualitativa , Humanos , Masculino , Feminino , Adulto , Socorristas/psicologia , Socorristas/estatística & dados numéricos , COVID-19/psicologia , COVID-19/epidemiologia , Adaptação Psicológica , Pessoa de Meia-Idade , Nível de Saúde , Saúde Pública , Saúde Mental , Entrevistas como Assunto
11.
Sci Rep ; 14(1): 13319, 2024 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-38858454

RESUMO

Prevention of subsequent fracture is a major public health challenge in the field of osteoporosis prevention and treatment, and older women are at high risk for osteoporotic fractures. This study aimed to examine factors associated with subsequent fracture in older Chinese women with osteoporosis. We collected data on 9212 older female patients with osteoporotic fractures from 580 medical institutions in 31 provinces of China. Higher odds of subsequent fractures were associated with age of 70-79 years (OR 1.218, 95% CI 1.049-1.414), age ≥ 80 (OR 1.455, 95% CI 1.222-1.732), index fracture site was vertebrae (OR 1.472, 95% CI 1.194-1.815) and hip (OR 1.286, 95% CI 1.041-1.590), index fracture caused by fall (OR 1.822, 95% CI 1.281-2.591), strain (OR 1.587, 95% CI 1.178-2.139), no inducement (OR 1.541, 95% CI 1.043-2.277), and assessed as high risk of fracture (OR 1.865, 95% CI 1.439-2.416), BMD T-score ≤ -2.5 (OR 1.725, 95% CI 1.440-2.067), history of surgery (OR 3.941, 95% CI 3.475-4.471) and trauma (OR 8.075, 95% CI 6.941-9.395). Low risk of fall (OR 0.681, 95% CI 0.513-0.904), use of anti-osteoporosis medication (AOM, OR 0.801, 95% CI 0.693-0.926), and women who had received fall prevention health education (OR 0.583, 95% CI 0.465-0.730) associated with lower risk. The areas under the curve of the prediction model was 0.818. The sensitivity was 67.0% and the specificity was 82.0%. The prediction model showed a good ability to predict the risk of subsequent fracture in older women with osteoporotic fractures and are suitable for early self-measurement which may benefit post-fracture management.


Assuntos
Fraturas por Osteoporose , Humanos , Feminino , Idoso , Fraturas por Osteoporose/epidemiologia , Fraturas por Osteoporose/etiologia , Estudos Transversais , China/epidemiologia , Idoso de 80 Anos ou mais , Pessoa de Meia-Idade , Medição de Risco , Fatores de Risco , Densidade Óssea , Acidentes por Quedas/estatística & dados numéricos , Osteoporose/complicações , Osteoporose/epidemiologia , População do Leste Asiático
12.
Int J Antimicrob Agents ; 64(2): 107235, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38851462

RESUMO

BACKGROUND: Nemonoxacin malate is a novel non-fluorinated quinolone for oral and intravenous (IV) administration. This phase 3, multicentre, randomised, double-blind, double-dummy, parallel-controlled clinical trial (NCT02205112) evaluated the efficacy and safety of IV nemonoxacin vs. levofloxacin for the treatment of community-acquired pneumonia (CAP) in adult patients. METHODS: Eligible patients were randomised to receive 500 mg nemonoxacin or levofloxacin via IV infusion, once daily for 7-14 days. The primary endpoint was the clinical cure rate at the test-of-cure (TOC) visit in the modified intent-to-treat (mITT) population. Secondary efficacy and safety were also compared between nemonoxacin and levofloxacin. RESULTS: Overall, 525 patients were randomised and treated with nemonoxacin (n = 349) or levofloxacin (n = 176). The clinical cure rate was 91.8% (279/304) for nemonoxacin and 85.7% (138/161) for levofloxacin in the mITT population (P > 0.05). The clinical efficacy of nemonoxacin was non-inferior to levofloxacin for treatment of CAP. Microbiological success rate with nemonoxacin was 88.8% (95/107) and with levofloxacin was 87.8% (43/49) (P > 0.05) at the TOC visit in the bacteriological mITT population. The incidence of drug-related adverse events (AEs) was 37.1% in the nemonoxacin group and 22.2% in the levofloxacin group. These AEs were mostly local reactions at the infusion site, nausea, elevated alanine aminotransferase/aspartate aminotransferase (ALT/AST), and QT interval prolongation. The nemonoxacin-related AEs were mostly mild and resolved after discontinuation of nemonoxacin. CONCLUSIONS: Nemonoxacin 500 mg IV once daily for 7-14 days is effective and safe and non-inferior to levofloxacin for treating CAP in adult patients.


Assuntos
Antibacterianos , Infecções Comunitárias Adquiridas , Levofloxacino , Quinolonas , Humanos , Infecções Comunitárias Adquiridas/tratamento farmacológico , Masculino , Feminino , Pessoa de Meia-Idade , Levofloxacino/uso terapêutico , Levofloxacino/efeitos adversos , Levofloxacino/administração & dosagem , Método Duplo-Cego , Antibacterianos/uso terapêutico , Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Adulto , Idoso , Resultado do Tratamento , Quinolonas/uso terapêutico , Quinolonas/administração & dosagem , Quinolonas/efeitos adversos , Administração Intravenosa , Infusões Intravenosas , Adulto Jovem , Pneumonia/tratamento farmacológico , Pneumonia Bacteriana/tratamento farmacológico , Pneumonia Bacteriana/microbiologia , Idoso de 80 Anos ou mais
13.
BMC Med Educ ; 24(1): 617, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38834998

RESUMO

BACKGROUND: Medical students frequently face challenges in academic adjustment, necessitating effective support and intervention. This study aimed to investigate the impact of stressful life events on medical students' academic adjustment, focusing on the mediating roles of depression and anxiety. It also differentiated the impacts between at-risk students (those with academic failures) and their peers respectively. METHODS: This case-control study involved 320 at-risk medical students and 800 other students from a university in western China. Participants anonymously completed the scales of stressful life events, depression, anxiety, and academic adjustment. T-tests, ANOVA, Pearson correlation, and structural equation modeling were employed for statistical analysis. RESULTS: Depression and anxiety were significantly more prevalent in at-risk students (46.8% and 46.1%, respectively) than in controls (34.0% and 40.3%, respectively). Notably, at-risk students had poorer academic adjustment (t = 5.43, p < 0.001). The structural equation modeling had good fit indices and the results indicated that depression and anxiety fully mediated the effects of stressful life events on academic adjustment. For at-risk students, stressful life events significantly decreased academic adjustment through increased depression and anxiety (p < 0.001). Conversely, anxiety had a positive effect on academic adjustment in other students. CONCLUSION: Targeted interventions focusing on depression and anxiety could reduce the negative impact of stressful life events on medical students' academic adjustment. However, educators have to distinguish the differences between at-risk students and others.


Assuntos
Ansiedade , Depressão , Estresse Psicológico , Estudantes de Medicina , Humanos , Estudantes de Medicina/psicologia , Feminino , Masculino , China/epidemiologia , Depressão/epidemiologia , Estudos de Casos e Controles , Ansiedade/epidemiologia , Estresse Psicológico/epidemiologia , Adulto Jovem , Acontecimentos que Mudam a Vida , Adaptação Psicológica , Adulto
14.
Psychol Res Behav Manag ; 17: 2377-2389, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38912160

RESUMO

Purpose: Resilience is considered as a protective factor that can assist individuals to reduce post-traumatic stress reactions. In recent years, armies in many countries have widely implemented resilience training programs before deployment to prevent or reduce post-deployment combat stress reactions. Therefore, this study aims to review what is known about resilience interventions for military personnel in pre deployment. Methods: Based on Arskey and O'Malley's framework, a scoping review was completed. This review was performed through searching databases including PubMed, Embase, Web of Science, Medline and the Cochrane Library, and screening literature to extract data, finally summarizing the findings. Results: A total of 25 studies focusing on resilience interventions for military personnel in pre deployment were involved and analyzed using intervention approaches, outcome measures, intervention effects, and so on. Conclusion: Based on the existing evidence in this review, it is cautiously believed that the resilience intervention program for military personnel before deployment is effective. However, there is no single effective best method even the same type intervention can make different effects in different situations and populations. Therefore, the population differences and context should be fully considered in constructing and implementing program to build military personnel resilience.

15.
Clin Transl Oncol ; 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38877363

RESUMO

PURPOSE: This study aimed to further evaluate the potential value of Pan-Immune-Inflammation Value (PIV) as a prognostic marker in patients with laryngeal and pharyngeal tumors. METHODS: A total of 545 patients with laryngeal and pharyngeal tumors who underwent surgery at Qilu Hospital of Shandong University were included. We determined the optimal cutoff of PIV and divided the patients into two groups. The relationship between PIV and clinicopathological features was explored by the chi-square test and the Mann-Whitney U test. Survival analysis and Cox regression analysis were used to evaluate the relationship between PIV and overall survival (OS) and disease-free survival (DFS). We also compared the prognostic predictive value of PIV with other inflammation-related markers. Finally, we developed a simple scoring prediction model based on several independent prognostic parameters. RESULTS: We found that PIV was statistically associated with clinicopathological features such as tumor stage (p < 0.001), node stage (p = 0.001), postoperative chemotherapy (p = 0.026), and vascular thrombosis (p = 0.027). Survival analysis demonstrated a significant correlation between elevated PIV and reduced OS and DFS (p < 0.0001). Multivariate Cox regression analysis further confirmed PIV as a prognostic indicator (HR 2.507; 95% CI 1.343-4.681; p = 0.004), which is superior to SII, NLR, MLR and PLR. Three of the independent prognostic factors screened by multivariate Cox regression analysis were selected to be used to create a scoring system with a concordance index of 0.756. CONCLUSIONS: Elevated PIV is associated with poor prognosis in patients with laryngeal and pharyngeal tumors, suggesting that PIV may be an important adjunctive indicator for assessing patient prognosis. REGISTRATION INFORMATION: Registration number: KYLL-202307-001, date: July 2023.

16.
bioRxiv ; 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38915480

RESUMO

PUF RNA-binding proteins are broadly conserved stem cell regulators. Nematode PUF proteins maintain germline stem cells (GSCs) and, with key partner proteins, repress differentiation mRNAs, including gld-1. Here we report that PUF protein FBF-2 and its partner LST-1 form a ternary complex that represses gld-1 via a pair of adjacent FBF-2 binding elements (FBEs) in its 3ÚTR. One LST-1 molecule links two FBF-2 molecules via motifs in the LST-1 intrinsically-disordered region; the gld-1 FBE pair includes a well-established 'canonical' FBE and a newly-identified noncanonical FBE. Remarkably, this FBE pair drives both full RNA repression in GSCs and full RNA activation upon differentiation. Discovery of the LST-1-FBF-2 ternary complex, the gld-1 adjacent FBEs, and their in vivo significance predicts an expanded regulatory repertoire of different assemblies of PUF-partner complexes in nematode germline stem cells. It also suggests analogous PUF controls may await discovery in other biological contexts and organisms.

17.
J Affect Disord ; 361: 256-267, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-38862077

RESUMO

BACKGROUND: Research into the shared and distinct brain dysfunctions in patients with schizophrenia (SCZ) and major depressive disorder (MDD) has been increasing. However, few studies have explored the application of functional near-infrared spectroscopy (fNIRS) in investigating brain dysfunction and enhancing diagnostic methodologies in these two conditions. METHODS: A general linear model was used for analysis of brain activation following task-state fNIRS from 131 patients with SCZ, 132 patients with MDD and 130 healthy controls (HCs). Subsequently, seventy-seven time-frequency analysis methods were used to construct new features of fNIRS, followed by the implementation of five machine learning algorithms to develop a differential diagnosis model for the three groups. This model was evaluated by comparing it to both a diagnostic model relying on traditional fNIRS features and assessments made by two psychiatrists. RESULTS: Brain activation analysis revealed significantly lower activation in Broca's area, the dorsolateral prefrontal cortex, and the middle temporal gyrus for both the SCZ and MDD groups compared to HCs. Additionally, the SCZ group exhibited notably lower activation in the superior temporal gyrus and the subcentral gyrus compared to the MDD group. When distinguishing among the three groups using independent validation datasets, the models utilizing new fNIRS features achieved an accuracy of 85.90 % (AUC = 0.95). In contrast, models based on traditional fNIRS features reached an accuracy of 52.56 % (AUC = 0.66). The accuracies of the two psychiatrists were 42.00 % (AUC = 0.60) and 38.00 % (AUC = 0.50), respectively. CONCLUSION: This investigation brings to light the shared and distinct neurobiological abnormalities present in SCZ and MDD, offering potential enhancements for extant diagnostic systems.


Assuntos
Transtorno Depressivo Maior , Esquizofrenia , Espectroscopia de Luz Próxima ao Infravermelho , Humanos , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/fisiopatologia , Esquizofrenia/fisiopatologia , Esquizofrenia/diagnóstico , Esquizofrenia/diagnóstico por imagem , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Feminino , Masculino , Adulto , Aprendizado de Máquina , Diagnóstico Diferencial , Pessoa de Meia-Idade , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Neuroimagem Funcional/métodos , Estudos de Casos e Controles , Lobo Temporal/diagnóstico por imagem , Lobo Temporal/fisiopatologia , Adulto Jovem
18.
Int J Nurs Stud ; 157: 104829, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38901123

RESUMO

BACKGROUND: The contemporary model for managing heart failure has been extended to a patient-family caregiver dyadic context. However, the key characteristics of the model that can optimise health outcomes for both patients and caregivers remain to be investigated. OBJECTIVES: This study aimed to identify the effects of dyadic care interventions on the behavioural, health, and health-service utilisation outcomes of patients with heart failure and their family caregivers and to explore how the intervention design characteristics influence these outcomes. DESIGN: This study involved systematic review, meta-analysis, and meta-regression techniques. METHODS: We performed a systematic review and meta-analysis, using 12 databases to identify randomised controlled trials or quasi-experimental studies published in English or Chinese between database inception and 31 December 2022. The considered interventions included those targeting patients with heart failure and their family caregivers to enhance disease management. Data synthesis was performed on various patient- and caregiver-related outcomes. The identified interventions were categorised according to their design characteristics for subgroup analysis. Meta-regression was performed to explore the relationship between care delivery methods and their effectiveness. RESULTS: We identified 48 studies representing 9171 patient-caregiver dyads. Meta-analyses suggested the positive effects of dyadic care interventions on patients' health outcomes [Hedges' g (95 % confidence interval {CI}): heart failure knowledge = 1.0 (0.26, 1.75), p = 0.008; self-care confidence = 0.45 (0.08, 0.83), p = 0.02; self-care maintenance = 1.12 (0.55, 1.70), p < 0.001; self-care management = 1.01 (0.54, 1.49), p < 0.001; anxiety = -0.18 (-0.34, -0.02), p = 0.03; health-related quality of life = 0.30 (0.08, 0.51), p < 0.001; hospital admission (risk ratio {95 % CI}: hospital admission = 0.79 (0.65, 0.97), p = 0.007; and mortality = 0.58 (0.36, 0.93), p = 0.02)]. Dyadic care interventions also improved the caregivers' outcomes [Hedges' g (95 % CI): social support = 0.67 (0.01, 1.32), p = 0.05; perceived burden = -1.43 (-2.27, -0.59), p < 0.001]. Although the design of the identified care interventions was heterogeneous, the core care components included enabling and motivational strategies to improve self-care, measures to promote collaborative coping within the care dyads, and nurse-caregiver collaborative practice. Incorporating the first two core components appeared to enhance the behavioural and health outcomes of the patients, and the addition of the last component reduced readmission. Interventions that engaged both patients and caregivers in care provision, offered access to nurses, and optimised continuity of care led to better patient outcomes. CONCLUSIONS: These findings demonstrate that dyadic care interventions can effectively improve disease management in a family context, resulting in better health outcomes for both patients and caregivers. Additionally, this study provides important insights into the more-effective design characteristics of these interventions. REGISTRATION NUMBER: The review protocol was registered in the PROSPERO International Prospective Register of Systematic Reviews (CRD42022322492).


Assuntos
Cuidadores , Insuficiência Cardíaca , Insuficiência Cardíaca/terapia , Insuficiência Cardíaca/enfermagem , Insuficiência Cardíaca/psicologia , Humanos , Cuidadores/psicologia
19.
Photodiagnosis Photodyn Ther ; 48: 104230, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38821236

RESUMO

BACKGROUND: Primary membranous nephropathy (PMN) patients may experience retinal microvascular changes. However, current diagnostic methods for PMN are not accurate in analyzing these modifications. In the present study, optical coherence tomography angiography (OCTA) was used for quantitative measurement of microvascular changes in the eyes of PMN patients. METHODS: A total of 26 patients with PMN and 26 healthy control (HC) were evaluated in this cross-sectional study. Optical coherence tomography (OCT) and OCTA were used to collect retinal thickness (RT) and microvascular parameters in the macula and optic disk in the superficial capillary plexus (SCP) of all subjects. Clinical data were collected from the PMN group. The OCT and OCTA data for PMN and HC group were compared, and the correlation between the OCTA and clinical data in the PMN group was determined. RESULTS: Vascular density (VD) and perfusion density (PD) in the macular area of the PMN group were significantly lower than those of the HC group, especially in the temporal quadrant. No significant difference in the foveal avascular zone (FAZ), optic disc microvascular parameters, RT, and retinal nerve fiber layer (RNFL) thickness was observed between the two groups. Correlation was noted between VD and PD in the macular area and clinical indicators, such as serum creatinine, serum urea nitrogen, 24 h urine volume and urinary protein concentration. CONCLUSION: Microvascular alterations in PMN patients occurred before ocular symptoms. The present quantitative study proposed a measurement method for detecting early retinal vascular injury in PMN patients.


Assuntos
Glomerulonefrite Membranosa , Microcirculação , Vasos Retinianos , Tomografia de Coerência Óptica , Humanos , Tomografia de Coerência Óptica/métodos , Glomerulonefrite Membranosa/fisiopatologia , Glomerulonefrite Membranosa/diagnóstico por imagem , Masculino , Feminino , Estudos Transversais , Pessoa de Meia-Idade , Vasos Retinianos/diagnóstico por imagem , Vasos Retinianos/fisiopatologia , Adulto , Angiofluoresceinografia/métodos , Estudos de Casos e Controles
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