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1.
Orphanet J Rare Dis ; 19(1): 208, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38773525

RESUMO

BACKGROUND: When using traditional extensible intramedullary rods to treat congenital pseudarthrosis of the tibia (CPT), there were cases of re-fracture and internal fixation fracture. Therefore, the authors propose a research hypothesis that a thicker distal extensible intramedullary rod can better protect the tibia and reduce the incidence of refracture PURPOSE: To investigate the clinical efficacy of new and traditional extensible intramedullary rods in the treatment of CPT in children METHODS: From January 2017 to December 2021, the clinical data of 49 children with CPT who were treated with traditional extensible intramedullary rod combined surgery (group A) and new extensible intramedullary rod combined surgery (group B) in our hospital were collected. Inclusive criteria: ① Crawford type IV CPT children; ② The operation was performed by the same team. EXCLUSION CRITERIA: patients with multiple tibial angulation. During follow-up, the initial healing, proximal tibial valgus, tibial length, ankle valgus, refracture and intramedullary rod displacement of CPT children in the two groups were evaluated RESULTS: It was a retrospective investigation. In group A, 26 cases met the inclusion criteria, 24 cases achieved primary healing, with an primary healing rate of 92%, including 1 case of nonunion due to osteomyelitis complications after surgery, and 1 case of delayed healing, with an average healing time of 4.7 ± 0.8 months. 17 cases (68%) had unequal tibia length, with an average difference of 1.6 ± 0.8 cm. Ankle valgus occurred in 10 cases (40%) with an average of 14.4°±4.8°; Proximal tibial valgus occurred in 6 cases (24%) with an average of 7 °± 1.8 °. 20 cases (80%) had tip of the rod migration.10 cases (40%) had re-fracture; The average follow-up time was 2.4 ± 0.4 years. In group B, 22 patients achieved primary healing, and the primary healing rate was 95%, including 1 case with delayed healing. The average healing time was 4.7 ± 1.7months. 14 cases (61%) had unequal tibia length, with an average difference of 1 ± 0.5 cm. Ankle valgus occurred in 4 cases (17%) with an average of 12.3 °±4.9°; The proximal tibia valgus occurred in 9 cases (39%), with an average of 7.7 °±2.5 °. 14 cases (61%) had new type of intramedullary rod displacement. 3 cases (13%) had re-fracture; The average follow-up time was 2.3 ± 0.6years CONCLUSION: Compared with the traditional extended intramedullary rod combined operation, the new type of extended intramedullary rod combined operation has a lower incidence of re-fracture after CPT, but it still needs to be verified by large sample and multi-center research.


Assuntos
Pseudoartrose , Tíbia , Humanos , Pseudoartrose/cirurgia , Pseudoartrose/congênito , Feminino , Masculino , Estudos Retrospectivos , Tíbia/cirurgia , Pré-Escolar , Fixação Intramedular de Fraturas/métodos , Criança , Fraturas da Tíbia/cirurgia , Resultado do Tratamento
2.
Cell Rep ; 43(5): 114237, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38753484

RESUMO

Cardiac dysfunction, an early complication of endotoxemia, is the major cause of death in intensive care units. No specific therapy is available at present for this cardiac dysfunction. Here, we show that the N-terminal gasdermin D (GSDMD-N) initiates mitochondrial apoptotic pore and cardiac dysfunction by directly interacting with cardiolipin oxidized by complex II-generated reactive oxygen species (ROS) during endotoxemia. Caspase-4/11 initiates GSDMD-N pores that are subsequently amplified by the upregulation and activation of NLRP3 inflammation through further generation of ROS. GSDMD-N pores form prior to BAX and VDAC1 apoptotic pores and further incorporate into BAX and VDAC1 oligomers within mitochondria membranes to exacerbate the apoptotic process. Our findings identify oxidized cardiolipin as the definitive target of GSDMD-N in mitochondria of cardiomyocytes during endotoxin-induced myocardial dysfunction (EIMD), and modulation of cardiolipin oxidation could be a therapeutic target early in the disease process to prevent EIMD.


Assuntos
Cardiolipinas , Endotoxemia , Peptídeos e Proteínas de Sinalização Intracelular , Miócitos Cardíacos , Oxirredução , Proteínas de Ligação a Fosfato , Espécies Reativas de Oxigênio , Cardiolipinas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Animais , Endotoxemia/metabolismo , Endotoxemia/patologia , Proteínas de Ligação a Fosfato/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Camundongos , Humanos , Camundongos Endogâmicos C57BL , Masculino , Apoptose , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Mitocôndrias/metabolismo , Gasderminas
4.
Oncol Lett ; 27(6): 244, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38638849

RESUMO

Sarcoma is derived from mesenchymal neoplasms and has numerous subtypes, accounting for 1% of all adult malignancies and 15% of childhood malignancies. The prognosis of metastatic or recurrent sarcoma remains poor. The current study presents two cases of sarcoma enrolled in a phase I dose escalation trial for solid tumor, who had previously failed all standard therapies. These patients were treated with VG161, an immune-stimulating herpes simplex virus type 1 oncolytic virus with payloads of IL-12, IL-15 and IL-15 receptor α unit, and a programmed cell death 1 (PD-1)/PD-1 ligand 1 blocking peptide. Both cases demonstrated stable disease as the best response, accompanied by a noteworthy prolongation of progression-free survival (11.8 months for chondrosarcoma and 11.9 months for soft tissue sarcoma, respectively) at a dose of 2.5×108 PFU/cycle. In addition, the treatment led to the activation of anti-cancer immunity, as evident from cytokine, lymphocyte subset and related pathway analyses of peripheral blood and/or tumor biopsy samples. These promising results suggest that VG161 monotherapy holds promise as an effective treatment for sarcoma and warrants further investigation through clinical trials. The two reported patients were part of a phase I clinical trial conducted and registered on the Australian New Zealand Clinical Trials Registry in Australia (registration no. ACTRN12620000244909; registration date, 26 February, 2020).

5.
BMC Surg ; 24(1): 119, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38654240

RESUMO

PURPOSE: To investigate the application and effectiveness of tension-reducing suture in the repair of hypertrophic scars. METHODS: A retrospective analysis of clinical data was conducted on 82 patients with hypertrophic scars treated at the Department of Burns and Plastic Surgery of Nanjing Drum Tower Hospital from September 2021 to December 2022. Patients were operated with combination of heart-shaped tension-reducing suturing technique and looped, broad, and deep buried (LBD) suturing technique or conventional suture method. Outcomes of surgical treatment were assessed before and 6 months after surgery using the Patient and Observer Scar Assessment Scale (POSAS) and the Vancouver Scar Scale (VSS). RESULTS: Improvements were achieved on scar quality compared to that preoperatively, with a reduction in scar width (1.7 ± 0.6 cm vs. 0.7 ± 0.2 cm, P < 0.001). Assessment using the POSAS and VSS scales showed significant improvements in each single parameter and total score compared to preoperative values (P < 0.05). The Combination method group achieved better score in total score of VSS scale, in color, stiffness, thickness and overall opinion of PSAS scale, and in vascularity, thickness, pliability and overall opinion of OSAS scale. CONCLUSION: The amalgamation of the heart-shaped tension-reducing suturing technique and the LBD suturing technique has shown promising outcomes, garnering notably high levels of patient satisfaction in the context of hypertrophic scar repair. Patients have exhibited favorable postoperative recoveries, underscoring the clinical merit and the prospective broader applicability of this approach in the realm of hypertrophic scar management.


Assuntos
Cicatriz Hipertrófica , Técnicas de Sutura , Humanos , Cicatriz Hipertrófica/etiologia , Cicatriz Hipertrófica/prevenção & controle , Estudos Retrospectivos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto Jovem , Suturas , Adolescente
6.
Biogerontology ; 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38592565

RESUMO

Skin photoaging is mostly caused by ultraviolet A (UVA), although active medications to effectively counteract UVA-induced photoaging have not yet been created. Resveratrol, a naturally occurring polyphenol found in the skin of grapes, has been shown to have various biological functions such as anti-inflammatory and antioxidant characteristics. However, the role of resveratrol in UVA-induced photoaging has not been clarified. We investigated the mechanism of action of resveratrol by UVA irradiation of human skin fibroblasts (HSF) and innovatively modified a mouse model of photoaging. The results demonstrated that resveratrol promoted AMP-activated protein kinase (AMPK) phosphorylation to activate autophagy, reduce reactive oxygen species (ROS) production, inhibit apoptosis, and restore normal cell cycle to alleviate UVA-induced photoaging. In addition, subcutaneous injection of resveratrol not only improved the symptoms of roughness, erythema, and increased wrinkles in the skin of UVA photodamaged mice, but also alleviated epidermal hyperkeratosis and hyperpigmentation, reduced inflammatory responses, and inhibited collagen fiber degradation. In conclusion, our studies proved that resveratrol can treat UVA-induced photoaging and elucidated the possible molecular mechanisms involved, providing a new therapeutic strategy for future anti-aging.

7.
Comput Biol Med ; 173: 108245, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38531253

RESUMO

PURPOSE: This study aimed to evaluate and optimize intraocular lens (IOL) power selection for cataract patients with high axial myopia receiving trifocal IOLs. DESIGN: A multi-center, retrospective observational case series was conducted. Patients having an axial length ≥26 mm and undergoing cataract surgery with trifocal IOL implanted were studied. METHODS: Preoperative biometric and postoperative outcome data from 139 eyes were collected to train and test various machine learning (ML) models (support vector machine, linear regression, and stacking regressor) using five-fold cross-validation. The models' performance was further validated externally using data from 48 eyes enrolled from other hospitals. Performance of seven IOL calculation formulas (BUII, Kane, EVO, K6, DGS, Holladay I, and SRK/T) were examined with and without ML models. RESULTS: The results of cross-validation revealed improvements across all IOL calculation formulas, especially for K6 and Holladay I. The model increased the percentage of eyes with a prediction error (PE) within ±0.50 D from 71.94% to 79.14% for K6, and from 35.25% to 51.80% for Holladay I. In external validation involving 48 patients from other centers, six out of seven formulas demonstrated a reduction in the mean absolute error (MAE). K6's PE within ±0.50 D improved from 62.50% to 77.08%, and Holladay I from 16.67% to 58.33%. CONCLUSIONS: In this study, we conducted a comprehensive evaluation of seven IOL power calculation formulas in high axial myopia cases and explored the effectiveness of the Stacking Regressor model in augmenting their accuracy. Of these formulas, K6 and Holladay I exhibited the most significant improvements, suggesting that integrating ML may have varying levels of effectiveness across different formulas but holds substantial promise in improving the predictability of IOL power calculations in patients with long eyes.


Assuntos
Catarata , Lentes Intraoculares , Miopia , Humanos , Miopia/cirurgia , Óptica e Fotônica , Refração Ocular , Estudos Retrospectivos
9.
J Ethnopharmacol ; 325: 117812, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38301984

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Diabetic ulcers represent a chronic condition characterized by prolonged hyperglycemia and delayed wound healing, accompanied by endocrine disorders, inflammatory responses, and microvascular damage in the epidermal tissue, demanding effective clinical treatment approaches. For thousands of years, ancient Chinese ethnopharmacological studies have documented the use of Poria cocos (Schw.) Wolf in treating diabetic ulcers. Recent research has substantiated the diverse pharmacological effects of Poria cocos (Schw.) Wolf, including its potential to alleviate hyperglycemia and exhibit anti-inflammatory, antioxidant, and immune regulatory properties, which could effectively mitigate diabetic ulcer symptoms. Furthermore, being a natural medicine, Poria cocos (Schw.) Wolf has demonstrated promising therapeutic effects and safety in the management of diabetic ulcers, holding significant clinical value. Despite its potential clinical efficacy and applications in diabetic ulcer treatment, the primary active components and underlying pharmacological mechanisms of Poria cocos (Schw.) Wolf remains unclear. Further investigations are imperative to establish a solid foundation for drug development in this domain. AIM OF THE STUDY AND MATERIALS AND METHODS: In this study, we aimed to identify the active compounds and potential targets of Poria cocos (Schw.) Wolf using UHPLC-Q-TOF-MS and TCMSP databases. Additionally, we attempt to identify targets related to diabetic ulcers. Following enrichment analysis, a network of protein-protein interactions was constructed to identify hub genes based on the common elements between the two datasets. To gain insights into the binding activities of the hub genes and active ingredients, molecular docking analysis was employed. Furthermore, to further validate the therapeutic effect of Poria cocos (Schw.) Wolf, we exerted in vitro experiments using human umbilical vein vascular endothelial cells and human myeloid leukemia monocytes (THP-1). The active ingredient of Poria cocos (Schw.) Wolf was applied in these experiments. Our investigations included various assays, such as CCK-8, scratch test, immunofluorescence, western blotting, RT-PCR, and flow cytometry, to explore the potential of Poria cocos (Schw.) Wolf triterpenoid extract (PTE) in treating diabetic ulcers. RESULTS: The findings here highlighted PTE as the primary active ingredient in Poria cocos (Schw.) Wolf. Utilizing network pharmacology, we identified 74 potential targets associated with diabetic ulcer treatment for Poria cocos (Schw.) Wolf, with five hub genes (JUN, MAPK1, STAT3, AKT1, and CTNNB1). Enrichment analysis revealed the involvement of multiple pathways in the therapeutic process, with the PI3K-AKT signaling pathway showing significant enrichment. Through molecular docking, we discovered that relevant targets within this pathway exhibited strong binding with the active components of Poria cocos (Schw.) Wolf. In vitro experiments unveiled that PTE (10 mg/L) facilitated the migration of human umbilical vein vascular endothelial cells (P < 0.05). PTE also increased the expression of CD31 and VEGF mRNA (P < 0.05) while activating the expressions of p-PI3K and p-AKT (P < 0.05). Moreover, PTE demonstrated its potential by reducing the expression of IL-1ß, IL-6, TNF-α, and NF-κB mRNA in THP-1 (P < 0.05) and fostering M2 macrophage polarization. These results signify the potential therapeutic effects of PTE in treating diabetic ulcers, with its beneficial actions mediated through the PI3K-AKT signaling pathway. CONCLUSIONS: PTE is the main active ingredient in Poria cocos (Schw.) Wolf that exerts therapeutic effects. Through PI3K-AKT signaling pathway activation and inflammatory response reduction, PTE promotes angiogenesis, thereby healing diabetic ulcers.


Assuntos
Antineoplásicos , Diabetes Mellitus , Medicamentos de Ervas Chinesas , Hiperglicemia , Triterpenos , Wolfiporia , Lobos , Animais , Humanos , Proteínas Proto-Oncogênicas c-akt , Wolfiporia/química , Fosfatidilinositol 3-Quinases , Úlcera , Simulação de Acoplamento Molecular , Células Endoteliais , Transdução de Sinais , Antineoplásicos/farmacologia , Triterpenos/farmacologia , Triterpenos/uso terapêutico , Triterpenos/análise , RNA Mensageiro , Diabetes Mellitus/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico
10.
Protein Sci ; 33(3): e4904, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38358126

RESUMO

UBE2T is an attractive target for drug development due to its linkage with several types of cancers. However, the druggability of ubiquitin-conjugating E2 (UBE2T) is low because of the lack of a deep and hydrophobic pocket capable of forming strong binding interactions with drug-like small molecules. Here, we performed fragment screening using 19 F-nuclear magnetic resonance (NMR) and validated the hits with 1 H-15 N-heteronuclear single quantum coherence (HSQC) experiment and X-ray crystallographic studies. The cocrystal structures obtained revealed the binding modes of the hit fragments and allowed for the characterization of the fragment-binding sites. Further screening of structural analogues resulted in the identification of a compound series with inhibitory effect on UBE2T activity. Our current study has identified two new binding pockets in UBE2T, which will be useful for the development of small molecules to regulate the function of this protein. In addition, the compounds identified in this study can serve as chemical starting points for the development of UBE2T modulators.


Assuntos
Enzimas de Conjugação de Ubiquitina , Ubiquitina , Enzimas de Conjugação de Ubiquitina/metabolismo , Sítios de Ligação
11.
J Environ Manage ; 354: 120153, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38394868

RESUMO

Aggravated metal pollution in wetland and riparian zones has become a global environmental issue, necessitating the identification of sustainable remediation approaches. Salix exhibits great potential as a viable candidate for metal(loid) remediation. However, the underlying mechanisms for its effectiveness in different flooding regimes with Pb pollution have not been extensively studied. In this study, fast-growing Salix×jiangsuensis 'J172' was selected and planted in different Pb polluted soils (control, 400 and 800 mg ∙ kg-1) under non-flooded and flooded (CF: continuous flooding and IF: intermittent flooding) conditions for 60 days. This study aimed to explore the effects of flooding on Salix growth performance, physiological traits, and the relationship between Pb uptake/translocation and root Fe plaques. Salix×jiangsuensis 'J172' exhibited excellent tolerance and adaptation to Pb pollution with a tolerance index (TI) exceeding 0.6, even at the highest Pb levels. Moreover, the TIs under flooded conditions were higher than that under non-flooded conditions, suggesting that flooding could alleviate Pb toxicity under co-exposure to Pb and flooding. Leaf malondialdehyde (MDA) exhibited a dose-dependent response to Pb exposure; however, CF or IF mitigated the oxidative damage induced by Pb toxicity with decreased MDA content (2.2-11.9%). The superoxide dismutase and peroxidase activities were generally enhanced by flooding, but combined stress (flooding and Pb) significantly decreased catalase activity. Pb was predominantly accumulated in Salix roots, and flooding markedly increased root Pb accumulation by 19.2-173.0% compared to non-flooded condition. Additionally, a significant positive correlation was observed between the iron (Fe) content of the root plaque and root Pb accumulation, indicating that the formation of Fe plaque on the root surface could enhance the phytostabilization of Pb in Salix. The current findings highlight that fast-growing woody plants are suitable for phyto-management of metal-polluted wetlands and can potentially minimize the risk of metal mobility in soils.


Assuntos
Salix , Poluentes do Solo , Ferro , Chumbo/toxicidade , Biodegradação Ambiental , Antioxidantes/farmacologia , Plantas , Solo , Poluentes do Solo/análise , Raízes de Plantas/química
13.
Front Pediatr ; 11: 1157192, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37915984

RESUMO

Background: Physeal bar resection has been used for partial growth arrest treatment for a decade while removing the bony bar minimally invasively and accurately is challenging. This research aims to illustrate a modified arthroscopically assisted surgery, by which all the procedure was under all-inside visualization, without the constant exchange between burring under fluoroscopy, followed by irrigation, suction, and arthroscopy of the canal. Methods: We retrospectively reviewed the patients who sustained physeal bar resection under direct all-inside visualization of the arthroscope during 2016-2021. Patients who underwent physeal bar resection with the aid of an arthroscope for identifying the physeal cartilage but not resecting and visualizing the physeal bar simultaneously were excluded from this study. Results: In total, nine patients with ten related joints were included in this study. All the patients were followed up for at least two years. The average following time was 28.5 ± 6.7 months. Eight patients with nine related joints had an improvement of angular deformity, averaging 8.3 ± 6.9 degrees, and one had a worsening of the angular deformity. All the patients had a leg length discrepancy improvement, while four patients still had LLD >1 cm. The surgery time was 3.1 ± 0.7 h. There were no postoperative fractures, infections, or intraoperative complications such as neurovascular injury. Conclusions: Using clamps to form a closed osteocavity could make physeal bar resection under all-inside arthroscopic visualization feasible, which is minimally invasive, accurate, and safe.

14.
Biochem Biophys Res Commun ; 689: 149238, 2023 12 31.
Artigo em Inglês | MEDLINE | ID: mdl-37979329

RESUMO

UBE2T is an E2 ubiquitin ligase critical for ubiquitination of substrate and plays important roles in many diseases. Despite the important function, UBE2T is considered as an undruggable target due to lack of a pocket for binding to small molecules with satisfied properties for clinical applications. To develop potent and specific UBE2T inhibitors, we adopted a high-throughput screening assay and two compounds-ETC-6152 and ETC-9004 containing a sulfone tetrazole scaffold were identified. Solution NMR study demonstrated the direct interactions between UBE2T and compounds in solution. Further co-crystal structures reveal the binding modes of these compounds. Both compound hydrolysation and formation of a hydrogen bond with the thiol group of the catalytic cysteine were observed. The formation of covalent complex was confirmed with mass spectrometry. As these two compounds inhibit ubiquitin transfer, our study provides a strategy to develop potent inhibitors of UBE2T.


Assuntos
Cisteína , Ubiquitina , Ubiquitina/metabolismo , Cisteína/metabolismo , Enzimas de Conjugação de Ubiquitina/metabolismo , Ubiquitinação , Ensaios de Triagem em Larga Escala
15.
Pharm Biol ; 61(1): 1462-1473, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37691404

RESUMO

CONTEXT: Diabetic wounds (DW) are a complication of diabetes and slow wound healing is the main manifestation. Methylene blue (MB) has been shown to exhibit therapeutic effects on diabetes-related diseases. OBJECTIVE: To investigate the mechanisms of action of MB-nanoemulsion (NE) in the treatment of DW. MATERIALS AND METHODS: The concentration of MB-NE used in the in vivo and in vitro experiments was 0.1 mg/mL. Streptozocin-induced diabetic mice were used as models. The mice were separated into nondiabetic, diabetic, MB-NE treated, and NE-treated groups. Intervention of high glucose-induced human umbilical vein endothelial cells using MB-NE. The mechanism by which MB-NE promotes DW healing is investigated by combining histological analysis, immunofluorescence analysis, TUNEL and ROS assays and western blotting. RESULTS: In diabetic mice, the MB-NE accelerated DW healing (p < 0.05), promoted the expression of endothelial cell markers (α-SMA, CD31 and VEGF) (p < 0.05), and reduced TUNEL levels. In vitro, MB accelerated the migration rate of cells (p < 0.05); promoted the expression of CD31, VEGF, anti-apoptotic protein Bcl2 (p < 0.05) and decreased the expression of the pro-apoptotic proteins cleaved caspase-3 and Bax (p < 0.05). MB upregulated the expression of Nrf2, catalase, HO-1 and SOD2 (p < 0.05). In addition, MB reduced the immunofluorescence intensity of TUNEL and ROS in cells and reduced apoptosis. The therapeutic effect of MB was attenuated after treatment with an Nrf2 inhibitor (ML385). DISCUSSION AND CONCLUSION: This study provides a foundation for the application of MB-NE in the treatment of DW.


Assuntos
Diabetes Mellitus Experimental , Humanos , Animais , Camundongos , Diabetes Mellitus Experimental/tratamento farmacológico , Azul de Metileno/farmacologia , Fator 2 Relacionado a NF-E2 , Espécies Reativas de Oxigênio , Fator A de Crescimento do Endotélio Vascular , Células Endoteliais da Veia Umbilical Humana
16.
BMC Geriatr ; 23(1): 591, 2023 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-37743469

RESUMO

BACKGROUND: A third of older people take five or more regular medications (polypharmacy). Conducting medication reviews in primary care is key to identify and reduce/ stop inappropriate medications (deprescribing). Recent recommendations for effective deprescribing include shared-decision making and a multidisciplinary approach. Our aim was to understand when, why, and how interventions for medication review and deprescribing in primary care involving multidisciplinary teams (MDTs) work (or do not work) for older people. METHODS: A realist synthesis following the Realist And Meta-narrative Evidence Syntheses: Evolving Standards guidelines was completed. A scoping literature review informed the generation of an initial programme theory. Systematic searches of different databases were conducted, and documents screened for eligibility, with data extracted based on a Context, Mechanisms, Outcome (CMO) configuration to develop further our programme theory. Documents were appraised based on assessments of relevance and rigour. A Stakeholder consultation with 26 primary care health care professionals (HCPs), 10 patients and three informal carers was conducted to test and refine the programme theory. Data synthesis was underpinned by Normalisation Process Theory to identify key mechanisms to enhance the implementation of MDT medication review and deprescribing in primary care. FINDINGS: A total of 2821 abstracts and 175 full-text documents were assessed for eligibility, with 28 included. Analysis of documents alongside stakeholder consultation outlined 33 CMO configurations categorised under four themes: 1) HCPs roles, responsibilities and relationships; 2) HCPs training and education; 3) the format and process of the medication review 4) involvement and education of patients and informal carers. A number of key mechanisms were identified including clearly defined roles and good communication between MDT members, integration of pharmacists in the team, simulation-based training or team building training, targeting high-risk patients, using deprescribing tools and drawing on expertise of other HCPs (e.g., nurses and frailty practitioners), involving patents and carers in the process, starting with 'quick wins', offering deprescribing as 'drug holidays', and ensuring appropriate and tailored follow-up plans that allow continuity of care and management. CONCLUSION: We identified key mechanisms that could inform the design of future interventions and services that successfully embed deprescribing in primary care.


Assuntos
Desprescrições , Idoso , Humanos , Cuidadores , Pessoal de Saúde , Revisão de Medicamentos , Atenção Primária à Saúde
17.
Cancer Med ; 12(18): 18479-18490, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37592896

RESUMO

BACKGROUND AND OBJECTIVES: Surgery is an essential treatment for non-distant metastatic cutaneous melanoma (NMCM). We aim to construct and validate prognostic nomograms based on surgical approaches and the clinicopathological characteristics of NMCM patients. METHODS: Data of patients diagnosed with cutaneous melanoma from 2004 to 2015 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Two online nomograms were constructed to predict the 3, 5-year melanoma-specific survival (MSS) for NMCM patients based on the surgical approaches. These nomograms were evaluated by the dynamic Harrell's concordance index (C-index), decision curve analysis and clinical impact curve. Both internal and external data verification were conducted. RESULTS: A total of 14,091 NMCM cases were included in this study. The C-index of the nomograms for the excisional surgery group and amputation group were 0.818 and 0.806, respectively, and 0.763 and 0.731, respectively, in our hospital data validation. After internal and bootstrap verification, our two nomograms showed good accuracy and practicality. CONCLUSION: NMCM patients exhibited equal survival rates independent of resection margin size, while those who needed amputation had worse survival rates. We generated two online nomograms distinguished by surgical approach to predict NMCM patient survival based on clinicopathological characteristics.


Assuntos
Melanoma , Segunda Neoplasia Primária , Neoplasias Cutâneas , Humanos , Nomogramas , Estadiamento de Neoplasias , Melanoma/cirurgia , Neoplasias Cutâneas/cirurgia , Prognóstico , Programa de SEER , Melanoma Maligno Cutâneo
18.
Int Ophthalmol ; 43(11): 3989-3997, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37458945

RESUMO

PURPOSE: To evaluate the tolerance for refractive errors and visual outcomes of extended depth of focus intraocular lens (EDOF IOLs) in patients with previous corneal refractive surgery for myopia. METHODS: Patients from Aier Eye Hospital of Wuhan University with previous myopia excimer laser correction underwent cataract surgery and implantation of an EDOF IOL. The follow-up period was three months. The uncorrected distance, intermediate, and near visual acuities (UDVA, UIVA, UNVA), corrected distance visual acuity (CDVA), spherical equivalent (SE), defocus curve, optical quality, including modulation transfer functions (MTF) and Strehl ratio (SR), National Eye Institute Visual Functioning Questionnaire-14 for Chinese people (VF-14-CN), spectacle independence, and dysphotopsia were assessed. RESULTS: At the final visit, UDVA, CDVA, UIVA, and UNVA (LogMAR) were 0.06 ± 0.09, 0.01 ± 0.06, 0.11 ± 0.08, 0.20 ± 0.10, respectively. The mean spherical equivalent (SE) was - 0.57 ± 0.58D, sphere and cylinder were - 0.24 ± 0.60D, - 0.70 ± 0.58D respectively. No statistical difference in UDVA between eyes with SE in ± 0.50 D and in ± 1.0 D (p > 0.05). Corneal astigmatism > 1.00D has no significant effect on postoperative visual acuity (p > 0.05). The defocus curve showed that visual acuity could reach 0.2 in the refractive range of + 0.50D ~ - 1.50D. SR and MTF values were all higher than before the surgery. In bilateral implantation patients, the VF-14-CN questionnaire score and visual quality were quite excellent. CONCLUSION: The EDOF IOL have a certain tolerance for refractive errors and corneal astigmatism, and it's recommended for patients with prior myopia excimer laser surgery to achieve satisfactory visual performance.


Assuntos
Astigmatismo , Lentes Intraoculares , Miopia , Facoemulsificação , Erros de Refração , Humanos , Astigmatismo/etiologia , Astigmatismo/cirurgia , Implante de Lente Intraocular/efeitos adversos , Facoemulsificação/efeitos adversos , Estudos Prospectivos , Lentes Intraoculares/efeitos adversos , Refração Ocular , Desenho de Prótese , Satisfação do Paciente
19.
Microbiol Spectr ; 11(4): e0108323, 2023 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-37378525

RESUMO

Verticillium dahliae is a soilborne fungal pathogen that causes disease on many economically important crops. Based on the resistance or susceptibility of differential cultivars in tomato, isolates of V. dahliae are divided into three races. Avirulence (avr) genes within the genomes of the three races have also been identified. However, the functional role of the avr gene in race 3 isolates of V. dahliae has not been characterized. In this study, bioinformatics analysis showed that VdR3e, a cysteine-rich secreted protein encoded by the gene characterizing race 3 in V. dahliae, was likely obtained by horizontal gene transfer from the fungal genus Bipolaris. We demonstrate that VdR3e causes cell death by triggering multiple defense responses. In addition, VdR3e localized at the periphery of the plant cell and triggered immunity depending on its subcellular localization and the cell membrane receptor BAK1. Furthermore, VdR3e is a virulence factor and shows differential pathogenicity in race 3-resistant and -susceptible hosts. These results suggest that VdR3e is a virulence factor that can also interact with BAK1 as a pathogen-associated molecular pattern (PAMP) to trigger immune responses. IMPORTANCE Based on the gene-for-gene model, research on the function of avirulence genes and resistance genes has had an unparalleled impact on breeding for resistance in most crops against individual pathogens. The soilborne fungal pathogen, Verticillium dahliae, is a major pathogen on many economically important crops. Currently, avr genes of the three races in V. dahliae have been identified, but the function of avr gene representing race 3 has not been described. We investigated the characteristics of VdR3e-mediated immunity and demonstrated that VdR3e acts as a PAMP to activate a variety of plant defense responses and induce plant cell death. We also demonstrated that the role of VdR3e in pathogenicity was host dependent. This is the first study to describe the immune and virulence functions of the avr gene from race 3 in V. dahliae, and we provide support for the identification of genes mediating resistance against race 3.


Assuntos
Ascomicetos , Verticillium , Virulência/genética , Verticillium/genética , Imunidade Vegetal , Fatores de Virulência/genética , Fatores de Virulência/metabolismo , Doenças das Plantas/microbiologia
20.
BMC Musculoskelet Disord ; 24(1): 482, 2023 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-37312176

RESUMO

OBJECTIVES: To investigate the clinical efficacy and safety of open reduction through anterior minimally invasive approach in the treatment of children with developmental dysplasia of the hip. METHOD: A total of 23 patients (25 hips) less than 2 years with developmental dysplasia of the hip treated by open reduction through anterior minimally invasive approach were treated in our hospital from August 2016 to March 2019. Through the anterior minimally invasive approach, we enter from the gap between sartorius muscle and tensor fasciae lata without cutting off rectus femoris muscle, which can effectively expose the joint capsule and reduce the damage to medial blood vessels and nerves. The operation time, incision length, intraoperative bleeding, hospital stay and surgical complications were observed. The progression of developmental dysplasia of the hip and avascular necrosis of the femoral head were evaluated by imaging examination. RESULT: All patients were performed with follow-up visit for an average of 22 months. The average incision length was 2.5 cm, the average operation time was 26 min, the average intraoperative bleeding was 12ml, and the average hospital stay was 4.9 days. All patients received concentric reduction immediately after operation, and no re-dislocation occurred. At the last follow-up visit, the acetabular index was (25.8 ± 6.4°). During the follow-up visit, X-ray showed avascular necrosis of the femoral head in 4 hips (16%). CONCLUSION: open reduction through anterior minimally invasive approach can achieve good clinical effect in the treatment of infantile developmental dysplasia of the hip.


Assuntos
Displasia do Desenvolvimento do Quadril , Necrose da Cabeça do Fêmur , Humanos , Criança , Necrose da Cabeça do Fêmur/diagnóstico por imagem , Necrose da Cabeça do Fêmur/etiologia , Necrose da Cabeça do Fêmur/cirurgia , Acetábulo , Cabeça do Fêmur , Hospitais , Hiperplasia
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