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1.
Pediatr Blood Cancer ; 71(6): e30970, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38556751

RESUMO

Langerhans cell histiocytosis (LCH) is a rare hematologic neoplasm characterized by the clonal proliferation of Langerhans-like cells. Colony-stimulating factor 1 receptor (CSF1R) is a membrane-bound receptor that is highly expressed in LCH cells and tumor-associated macrophages. In this study, a soluble form of CSF1R protein (sCSF1R) was identified by plasma proteome profiling, and its role in evaluating LCH prognosis was explored. We prospectively measured plasma sCSF1R levels in 104 LCH patients and 10 healthy children using ELISA. Plasma sCSF1R levels were greater in LCH patients than in healthy controls (p < .001) and significantly differed among the three disease extents, with the highest level in MS RO+ LCH patients (p < .001). Accordingly, immunofluorescence showed the highest level of membrane-bound CSF1R in MS RO+ patients. Furthermore, the plasma sCSF1R concentration at diagnosis could efficiently predict the prognosis of LCH patients treated with standard first-line treatment (AUC = 0.782, p < .001). Notably, dynamic monitoring of sCSF1R levels could predict relapse early in patients receiving BRAF inhibitor treatment. In vitro drug sensitivity data showed that sCSF1R increased resistance to Ara-C in THP-1 cells expressing ectopic BRAF-V600E. Overall, the plasma sCSF1R level at diagnosis and during follow-up is of great clinical importance in pediatric LCH patients.


Assuntos
Histiocitose de Células de Langerhans , Receptor de Fator Estimulador de Colônias de Macrófagos , Receptores de Fator Estimulador das Colônias de Granulócitos e Macrófagos , Humanos , Histiocitose de Células de Langerhans/diagnóstico , Histiocitose de Células de Langerhans/patologia , Histiocitose de Células de Langerhans/sangue , Masculino , Feminino , Criança , Prognóstico , Pré-Escolar , Lactente , Receptores de Fator Estimulador das Colônias de Granulócitos e Macrófagos/sangue , Adolescente , Estudos Prospectivos , Seguimentos
2.
J Am Chem Soc ; 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38637324

RESUMO

Chiral nanographenes (NGs) have garnered significant interest as optoelectronic materials in recent years. While helically chiral NGs have been extensively studied, axially chiral NGs have only witnessed limited examples, with no prior reports of axially chiral nonbenzenoid NGs. Herein we report an axially chiral nonbenzenoid nanographene featuring six pentagons and four heptagons. This compound, denoted as 2, was efficiently synthesized via an efficient Pd-catalyzed aryl silane homocoupling reaction. The presence of two bulky 3,5-di-tert-butylphenyl groups around the axis connecting the two nonbenzenoid PAH (AHR) segments endows 2 with atropisomeric chirality and high racemization energy barrier, effectively preventing racemization of both R- and S-enantiomers at room temperature. Optically pure R-2 and S-2 were obtained by chiral HPLC separation, and they exhibit circular dichroism (CD) activity at wavelengths up to 660 nm, one of the longest wavelengths with CD responses reported for the chiral NGs. Interestingly, racemic 2 forms a homoconfiguration π-dimer in the crystal lattice, belonging to the I222 chiral space group. Consequently, this unique structure renders crystals of 2 with a second harmonic generation (SHG) response, distinguishing it from all the reported axially chiral benzenoid NGs. Moreover, R-2 and S-2 also exhibit SHG-CD properties.

3.
J Control Release ; 370: 95-109, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38642859

RESUMO

Sonodynamic therapy (SDT) has emerged as a useful approach for tumor treatment. However, its widespread application is impeded by poor pharmacokinetics of existing sonosensitizers. Here we developed a metal-organic nanoplatform, wherein a small-molecule sonosensitizer (hematoporphyrin monomethyl ether, HMME) was ingeniously coordinated with zirconium, resulting in a multifunctional nanosonosensitizer termed Zr-HMME. Through post-synthetic modifications involving PEGylation and tumor-targeting peptide (F3) linkage, a nanoplatform capable of homing on melanoma was produced, which could elicit robust immune responses to suppress tumor lung metastasis in the host organism. Importantly, after seamless incorporation of positron-emitting 89Zr into this nanosonosensitizer, positron emission tomography (PET) could be used to monitor its in vivo pharmacokinetics. PET imaging studies revealed that this nanoplatform exhibited potent tumor accumulation and strong in vivo stability. Using intrinsic fluorescence from HMME, a dual-modal diagnostic capability (fluorescence and PET) was confirmed for this nanosonosensitizer. In addition, the mechanisms of how this nanoplatform interacted with immune system were also investigated. The collective data proved that the coordination structure between small-molecule drug cargos and metals may enhance the functions of each other while mitigating their weaknesses. This straightforward approach can expand the potential applications of suitable drug molecules.

4.
Zhongguo Dang Dai Er Ke Za Zhi ; 26(4): 420-424, 2024 Apr 15.
Artigo em Chinês | MEDLINE | ID: mdl-38660908

RESUMO

Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder. With the emergence of disease-modifying therapies, the prognosis of SMA has significantly improved, drawing increased attention to the importance of home rehabilitation and nursing management. Long-term, standardized home rehabilitation and nursing can delay the progression of SMA, enhance the psychological well-being, and improve the quality of life of both patients and caregivers. This article provides an overview of the goals of home rehabilitation, basic functional training methods, respiratory management, and nutritional management for SMA patients, as well as psychological health issues, emphasizing the significance of obtaining appropriate home rehabilitation and support during the care process.


Assuntos
Atrofia Muscular Espinal , Humanos , Atrofia Muscular Espinal/reabilitação , Atrofia Muscular Espinal/terapia , Serviços de Assistência Domiciliar , Qualidade de Vida
5.
Aesthet Surg J ; 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38518757

RESUMO

BACKGROUND: Despite increasing demand for breast capsular surgery to treat various benign and malignant implant-related pathologies, high-quality evidence elucidating complication profiles of capsulectomy and capsulotomy is lacking. OBJECTIVES: We provide the largest-scale analysis of associated outcomes and complications using the Tracking Operations and Outcomes for Plastic Surgeons (TOPS) database, and investigate clinical scenarios that may subject patients to increased risks for complications, most notably, extent of capsular surgery (complete vs partial), and index indication of implantation (aesthetic vs reconstructive). METHODS: An analysis of the TOPS database from 2008-2019 was performed. CPT codes were used to identify complete capsulectomy and partial capsulectomy/capsulotomy cases. Breast implant exchange procedures constituted procedural controls. RESULTS: In total, 7,486 patients (10,703 breasts) undergoing capsulectomy or capsulotomy were assessed. Relative to controls, capsulectomy (4.40% vs 5.79%; p = 0.0154), but not capsulotomy (4.40% vs 4.50%; p = 0.8876), demonstrated higher overall complication rates. Both capsulectomies (0.83% vs 0.23%; p < 0.0001) and capsulotomies (0.56% vs 0.23%; p = 0.0307) also had greater rates of seroma relative to controls. Subgroup analyses demonstrated that reconstructive patients, relative to aesthetic patients, experienced greater overall complications (6.76% vs 4.34%; p < 0.0001), and increased risks for seroma (1.06% vs 0.47%; p = 0.0016), dehiscence (0.46% vs 0.14%; p = 0.0059), surgical site infections (1.03% vs 0.23%; p < 0.0001), and implant loss (0.52% vs 0.23%; p = 0.0401). A detailed synthesis of 30-day outcomes, including all patient- and breast-specific complications, for both capsulectomy and capsulotomy, stratified according to all potential confounders, is presented herein. CONCLUSIONS: Surgeries on the breast capsule are overall safe, though complete capsulectomies and reconstructive patients were associated with significantly increased operative risks. Present findings will enhance patient selection, counselling, and informed consent.

6.
Neuron ; 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38518778

RESUMO

Although bile acids play a notable role in depression, the pathological significance of the bile acid TGR5 membrane-type receptor in this disorder remains elusive. Using depression models of chronic social defeat stress and chronic restraint stress in male mice, we found that TGR5 in the lateral hypothalamic area (LHA) predominantly decreased in GABAergic neurons, the excitability of which increased in depressive-like mice. Upregulation of TGR5 or inhibition of GABAergic excitability in LHA markedly alleviated depressive-like behavior, whereas down-regulation of TGR5 or enhancement of GABAergic excitability facilitated stress-induced depressive-like behavior. TGR5 also bidirectionally regulated excitability of LHA GABAergic neurons via extracellular regulated protein kinases-dependent Kv4.2 channels. Notably, LHA GABAergic neurons specifically innervated dorsal CA3 (dCA3) CaMKIIα neurons for mediation of depressive-like behavior. LHA GABAergic TGR5 exerted antidepressant-like effects by disinhibiting dCA3 CaMKIIα neurons projecting to the dorsolateral septum (DLS). These findings advance our understanding of TGR5 and the LHAGABA→dCA3CaMKIIα→DLSGABA circuit for the development of potential therapeutic strategies in depression.

7.
Acta Biomater ; 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38490483

RESUMO

Nanoscale coordination polymer (NCP) is a class of hybrid materials formed by self-assembly of metal ions and organic ligands through coordination. The applications of NCP in biomedicine are quite extensive due to the diversity choice of metal ions and organic ligands. Here we designed Zr-P1 NCP based on Zr4+ selected as metal ion nodes and tetrakis(4-carboxyphenyl) ethylene as bridging ligands. Zr-P1 NCP was modified with functionalized pyrene derived polyethylene glycol (Py-PAA-PEG-Mal) on the surface and further conjugated with cRGD for active targeting of integrin αvß3 overexpressed in triple-negative breast cancer. Doxorubicin was loaded on Zr-P1 NCP with encapsulation efficiency up to 22 % for the treatment of triple negative breast cancer. 89Zr-P1 NCP can be used for in vivo tumor imaging due to the fluorescence properties resulting from the enhanced aggregation-induced Emission (AIE) behavior of P1 ligands and its positron emission tomography (PET) capability. Cellular evaluation indicated that the functionalized Zr-P1@PEG-RGD presented a good function for tumor cell targeting imaging and doxorubicin could be targeted to triple negative breast cancer when it was loaded onto Zr-P1@PEG-RGD, which corroborated with the in vivo results. In summary, 89Zr-P1@PEG-RGD can serve as a biocompatible nanoplatform for fluorescence and PET image-guided cargo delivery. STATEMENT OF SIGNIFICANCE: Nanoscale coordination polymer (NCP) is a class of hybrid materials formed by self-assembly of metal ions and organic ligands through coordination. The diversity of available metals and ligand structures upon NCP synthesis plays an advantage in establishing multimodal imaging platforms. Here we designed 89Zr-P1@PEG-RGD NCP based on Zr4+ selected as metal ion nodes and tetrakis(4-carboxyphenyl) ethylene as bridging ligands. 89Zr-P1@PEG-RGD nanomaterials have positron emission tomography (PET) capability due to the incorporation of zirconium-89, which can be used for in vivo tumor imaging with high sensitivity. The chemotherapeutic drug DOX was loaded on Zr-P1 NCP for the treatment of triple-negative breast cancer, and dual modality imaging can provide visual guidance for drug delivery.

8.
Cancer Gene Ther ; 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38480975

RESUMO

Esophageal squamous cell carcinoma (ESCC) is one of the most common human malignancies worldwide and is associated with high morbidity and mortality. Current treatment options are limited, highlighting the need for development of novel effective agents. Here, a high-throughput drug screening (HTS) was performed using ESCC cell lines in both two- and three-dimensional culture systems to screen compounds that have anti-ESCC activity. Our screen identified romidepsin, a histone deactylase inhibitor, as a potential anti-ESCC agent. Romidepsin treatment decreased cell viability, induced apoptosis and cell cycle arrest in ESCC cell lines, and these findings were confirmed in ESCC cell line-derived xenografted (CDX) mouse models. Mechanically, romidepsin induced transcriptional upregulation of DNA damage-inducible transcript 4 (DDIT4) gene by histone hyperacetylation at its promoter region, leading to the inhibition of mammalian target of rapamycin complex 1 (mTORC1) pathway. Furthermore, romidepsin exhibited better efficacy and safety compared to the conventional therapeutic drugs in ESCC patient-derived xenografted (PDX) mouse models. These data indicate that romidepsin may be a novel option for anti-ESCC therapy.

9.
Signal Transduct Target Ther ; 9(1): 37, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38360862

RESUMO

The human gastrointestinal tract is populated with a diverse microbial community. The vast genetic and metabolic potential of the gut microbiome underpins its ubiquity in nearly every aspect of human biology, including health maintenance, development, aging, and disease. The advent of new sequencing technologies and culture-independent methods has allowed researchers to move beyond correlative studies toward mechanistic explorations to shed light on microbiome-host interactions. Evidence has unveiled the bidirectional communication between the gut microbiome and the central nervous system, referred to as the "microbiota-gut-brain axis". The microbiota-gut-brain axis represents an important regulator of glial functions, making it an actionable target to ameliorate the development and progression of neurodegenerative diseases. In this review, we discuss the mechanisms of the microbiota-gut-brain axis in neurodegenerative diseases. As the gut microbiome provides essential cues to microglia, astrocytes, and oligodendrocytes, we examine the communications between gut microbiota and these glial cells during healthy states and neurodegenerative diseases. Subsequently, we discuss the mechanisms of the microbiota-gut-brain axis in neurodegenerative diseases using a metabolite-centric approach, while also examining the role of gut microbiota-related neurotransmitters and gut hormones. Next, we examine the potential of targeting the intestinal barrier, blood-brain barrier, meninges, and peripheral immune system to counteract glial dysfunction in neurodegeneration. Finally, we conclude by assessing the pre-clinical and clinical evidence of probiotics, prebiotics, and fecal microbiota transplantation in neurodegenerative diseases. A thorough comprehension of the microbiota-gut-brain axis will foster the development of effective therapeutic interventions for the management of neurodegenerative diseases.


Assuntos
Doenças Neurodegenerativas , Probióticos , Humanos , Encéfalo/metabolismo , Doenças Neurodegenerativas/terapia , Doenças Neurodegenerativas/metabolismo , Eixo Encéfalo-Intestino , Probióticos/uso terapêutico , Prebióticos
10.
Aesthet Surg J ; 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38366026

RESUMO

BACKGROUND: Social media platforms have come to represent integral components of the professional marketing and advertising strategy for plastic surgeons. Effective and consistent content development, however, remains technically demanding and time consuming, prompting most to employ, at non-negligible costs, social media marketing specialists for content planning and development. OBJECTIVES: The present study aims to investigate the ability of presently available artificial intelligence (AI) models to assist plastic surgeons in their social media content development and sharing plans. METHODS: An AI Large Language Model was prompted on the study's objectives through a series of standardized user interactions; social media platforms of interest, on which the AI model was prompted, included Instagram, TikTok, and X (formerly Twitter). RESULTS: A one-year, entirely AI-generated social media plan, comprising a total of 1091 posts for the three aforementioned social media platforms, is presented herein. Themes of the AI-generated content proposed for each platform were classified into 6 categories, including patient-related, practice-related, educational, "uplifting", interactive, and promotional posts. Overall, 91 publicly recognized holidays, observant, and awareness days were incorporated into the content calendars. The AI model demonstrated an ability to differentiate between the distinct formats of each of the three social media platforms investigated, generating unique ideas for each, and providing detailed content development and posting instructions, scripts, and post captions, leveraging features specific to each platform. CONCLUSIONS: By providing detailed and actionable social media content creation and posting plans to plastic surgeons, presently available AI models can be readily leveraged to assist in and significantly alleviate the burden associated with social media account management, content generation, and potentially patient conversion.

11.
Acta Pharm Sin B ; 14(2): 667-681, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38322327

RESUMO

Studies have suggested that the nucleus accumbens (NAc) is implicated in the pathophysiology of major depression; however, the regulatory strategy that targets the NAc to achieve an exclusive and outstanding anti-depression benefit has not been elucidated. Here, we identified a specific reduction of cyclic adenosine monophosphate (cAMP) in the subset of dopamine D1 receptor medium spiny neurons (D1-MSNs) in the NAc that promoted stress susceptibility, while the stimulation of cAMP production in NAc D1-MSNs efficiently rescued depression-like behaviors. Ketamine treatment enhanced cAMP both in D1-MSNs and dopamine D2 receptor medium spiny neurons (D2-MSNs) of depressed mice, however, the rapid antidepressant effect of ketamine solely depended on elevating cAMP in NAc D1-MSNs. We discovered that a higher dose of crocin markedly increased cAMP in the NAc and consistently relieved depression 24 h after oral administration, but not a lower dose. The fast onset property of crocin was verified through multicenter studies. Moreover, crocin specifically targeted at D1-MSN cAMP signaling in the NAc to relieve depression and had no effect on D2-MSN. These findings characterize a new strategy to achieve an exclusive and outstanding anti-depression benefit by elevating cAMP in D1-MSNs in the NAc, and provide a potential rapid antidepressant drug candidate, crocin.

12.
Aesthet Surg J ; 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38318684

RESUMO

BACKGROUND: Large Language Models (LLMs) have revolutionized the way plastic surgeons and their patients may access and leverage artificial Intelligence (AI). OBJECTIVES: The present study aims to comparatively assess the performance of two current publically-available and patient-accessible LLMs in the potential application of AI as postoperative medical support chatbots in an aesthetic surgeon's practice. METHODS: Twenty-two simulated postoperative patient presentations following aesthetic breast plastic surgery were devised and expert-validated. Complications varied in their latency within the postoperative period, as well as urgency of required medical attention. In response to each patient-reported presentation, Open AI's ChatGPT and Google's Bard, in their unmodified and freely available versions, were objectively assessed for their comparative accuracy in generating an appropriate differential diagnosis, most likely diagnosis, suggested medical disposition, treatments or interventions to begin from home, and/or red flag signs/symptoms indicating deterioration. RESULTS: ChatGPT cumulatively and significantly outperformed Bard across all objective assessement metrics examined (66% vs. 55%, respectively; p < 0.05). Accuracy in generating an appropriate differential diagnosis were 61% for ChatGPT, and 57% for Bard (p = 0.45). ChatGPT asked an average of 9.2 questions on history, relative to 6.8 questions by Bard (p < 0.001), following which, accuracies of 91% vs. 68% at arriving at the most-likely diagnosis were noted, respectively (p < 0.01). Appropriate medical dispositions were suggested with an accuracy of 50% by ChatGPT, and 41% by Bard (p = 0.40); relevant home interventions/treatments with an accuracy of 59% and 55% (p = 0.94), and red flag signs/symptoms with accuracies of 79% and 54% (p < 0.01), respectively. Detailed and comparative performance breakdowns according to complication latency and urgency are presented herein. CONCLUSIONS: ChatGPT represents the superior LLM for the potential application of AI technology in postoperative medical support chatbots. Imperfect performance and limitations identified herein may guide the necessary refinement to facilitate adoption.

13.
J Am Chem Soc ; 146(9): 6377-6387, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38385755

RESUMO

We present comprehensive computational and experimental studies on the mechanism of an asymmetric photoredox/Pd dual-catalytic reductive C(sp3)-C(sp3) homocoupling of allylic electrophiles. In stark contrast to the canonical assumption that photoredox promotes bond formation via facile reductive elimination from high-valent metal-organic species, our computational analysis revealed an intriguing low-valent allylpalladium pathway that features tandem operation of Pd(0/II/I)-Pd(0/II/I/II) cycles. Specifically, we propose that (i) the photoredox/Pd system enables the in situ generation of allyl radicals from low-valent Pd(I)-allyl species, and (ii) effective interception of the fleeting allyl radical by the chiral Pd(I)-allyl species results in the formation of an enantioenriched product. Notably, the cooperation of the two pathways highlights the bifunctional role of Pd(I)-allyl species in the generation and interception of transient allyl radicals. Moreover, the mechanism implies divergent substrate-activation modes in this homocoupling reaction, suggesting a theoretical possibility for cross-coupling. Combined, the current study offers a novel mechanistic hypothesis for photoredox/Pd dual catalysis and highlights the use of low-valent allylpalladium as a means to efficiently intercept radicals for selective asymmetric bond constructions.

14.
J Cell Physiol ; 2024 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-38308641

RESUMO

Recent studies have shown that nucleophagy can mitigate DNA damage by selectively degrading nuclear components protruding from the nucleus. However, little is known about the role of nucleophagy in neurons after spinal cord injury (SCI). Western blot analysis and immunofluorescence were performed to evaluate the nucleophagy after nuclear DNA damage and leakage in SCI neurons in vivo and NSC34 expression in primary neurons cultured with oxygen-glucose deprivation (OGD) in vitro, as well as the interaction and colocalization of autophagy protein LC3 with nuclear lamina protein Lamin B1. The effect of UBC9, a Small ubiquitin-related modifier (SUMO) E2 ligase, on Lamin B1 SUMOylation and nucleophagy was examined by siRNA transfection or 2-D08 (a small-molecule inhibitor of UBC9), immunoprecipitation, and immunofluorescence. In SCI and OGD injured NSC34 or primary cultured neurons, neuronal nuclear DNA damage induced the SUMOylation of Lamin B1, which was required by the nuclear Lamina accumulation of UBC9. Furthermore, LC3/Atg8, an autophagy-related protein, directly bound to SUMOylated Lamin B1, and delivered Lamin B1 to the lysosome. Knockdown or suppression of UBC9 with siRNA or 2-D08 inhibited SUMOylation of Lamin B1 and subsequent nucleophagy and protected against neuronal death. Upon neuronal DNA damage and leakage after SCI, SUMOylation of Lamin B1 is induced by nuclear Lamina accumulation of UBC9. Furthermore, it promotes LC3-Lamin B1 interaction to trigger nucleophagy that protects against neuronal DNA damage.

15.
Retina ; 44(5): 782-790, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38237083

RESUMO

PURPOSE: To evaluate the incidence, associated factors, and outcome of persistent subretinal fluid (SRF) after vitrectomy for macular hole-associated retinal detachment (MHRD). METHODS: A total of 158 eyes from 156 patients with MHRD who achieved macular hole closure after primary vitrectomy were included in the analysis; persistent SRF was defined as the presence of SRF for more than 1 month after first surgery. Preoperative and postoperative parameters were analyzed for their relationship with SRF development. RESULTS: Persistent SRF was observed in 19 eyes (12.0% of 158) postoperatively. Seven eyes (36.8% of 19) with persistent SRF eventually displayed complete absorption during follow-up. Univariate analysis revealed that eyes with persistent SRF were statistically associated with internal limiting membrane inverted flap, duration of symptoms, tamponade (perfluoropropane/silicone oil: 14/5 vs. 35/104, P < 0.001), and MHRD subtype (Type 1/Type 2/Type 3: 15/4/0 vs. 60/40/39, P = 0.003). In multivariate analysis, only internal limiting membrane inverted flap (odds ratio, 15.778, 95% confidence interval, 3.170-78.523; P = 0.001) was positively associated with persistent SRF. There were no significant differences in best-corrected visual acuity improvement ( P = 0.425) between the SRF involved foveal and without involved foveal groups and no significant differences between the SRF complete absorption and incomplete absorption groups. CONCLUSION: Absorption of persistent SRF may be more difficult in MHRD eyes than in ordinary rhegmatogenous retinal detachment eyes. The internal limiting membrane inverted flap in MHRD was associated with a greater likelihood of persistent SRF. The location and incomplete absorption of persistent SRF did not seem to be associated with the final visual outcome.


Assuntos
Tamponamento Interno , Descolamento Retiniano , Perfurações Retinianas , Líquido Sub-Retiniano , Tomografia de Coerência Óptica , Acuidade Visual , Vitrectomia , Humanos , Vitrectomia/métodos , Descolamento Retiniano/cirurgia , Descolamento Retiniano/diagnóstico , Descolamento Retiniano/etiologia , Masculino , Feminino , Perfurações Retinianas/cirurgia , Perfurações Retinianas/diagnóstico , Perfurações Retinianas/etiologia , Estudos Retrospectivos , Idoso , Pessoa de Meia-Idade , Tamponamento Interno/métodos , Tomografia de Coerência Óptica/métodos , Complicações Pós-Operatórias , Seguimentos , Fluorocarbonos/administração & dosagem , Incidência
16.
Angew Chem Int Ed Engl ; 63(3): e202311053, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-37917574

RESUMO

With the rapid development of asymmetric catalysis, the demand for the enantioselective synthesis of complex and diverse molecules with different chiral elements is increasing. Owing to the unique features of atropisomerism, the catalytic asymmetric synthesis of atropisomers has attracted a considerable interest from the chemical science community. In particular, introducing additional chiral elements, such as carbon centered chirality, heteroatomic chirality, planar chirality, and helical chirality, into atropisomers provides an opportunity to incorporate new properties into axially chiral compounds, thus expanding the potential applications of atropisomers. Thus, it is important to perform catalytic asymmetric transformations to synthesize atropisomers bearing multiple chiral elements. In spite of challenges in such transformations, in recent years, chemists have devised powerful strategies under asymmetric organocatalysis or metal catalysis, synthesizing a wide range of enantioenriched atropisomers bearing multiple chiral elements. Therefore, the catalytic asymmetric synthesis of atropisomers bearing multiple chiral elements has become an emerging field. This review summarizes the rapid progress in this field and indicates challenges, thereby promoting this field to a new horizon.

17.
Aesthet Surg J ; 44(3): 329-343, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-37562022

RESUMO

BACKGROUND: The rapidly evolving field of artificial intelligence (AI) holds great potential for plastic surgeons. ChatGPT, a recently released AI large language model (LLM), promises applications across many disciplines, including healthcare. OBJECTIVES: The aim of this article was to provide a primer for plastic surgeons on AI, LLM, and ChatGPT, including an analysis of current demonstrated and proposed clinical applications. METHODS: A systematic review was performed identifying medical and surgical literature on ChatGPT's proposed clinical applications. Variables assessed included applications investigated, command tasks provided, user input information, AI-emulated human skills, output validation, and reported limitations. RESULTS: The analysis included 175 articles reporting on 13 plastic surgery applications and 116 additional clinical applications, categorized by field and purpose. Thirty-four applications within plastic surgery are thus proposed, with relevance to different target audiences, including attending plastic surgeons (n = 17, 50%), trainees/educators (n = 8, 24.0%), researchers/scholars (n = 7, 21%), and patients (n = 2, 6%). The 15 identified limitations of ChatGPT were categorized by training data, algorithm, and ethical considerations. CONCLUSIONS: Widespread use of ChatGPT in plastic surgery will depend on rigorous research of proposed applications to validate performance and address limitations. This systemic review aims to guide research, development, and regulation to safely adopt AI in plastic surgery.


Assuntos
Procedimentos de Cirurgia Plástica , Cirurgiões , Humanos , Inteligência Artificial , Algoritmos , Idioma
18.
Acta Biomater ; 174: 372-385, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38072226

RESUMO

Targeted delivery of therapeutic drugs to fibrosis-promoting macrophages (FPMs) holds promise as a challenging yet effective approach for the treatment of idiopathic pulmonary fibrosis (IPF). Here, nanocarriers composed of Mn-curcumin metal-organic frameworks (MOFs) were utilized to deliver the immune inhibitor BLZ-945 to the lungs, with the goal of depleting fibrosis-promoting macrophages (FPMs) from fibrotic lung tissues. FPM targeting was achieved by functionalizing the nanocarrier surface with an M2-like FPM binding peptide (M2pep). As a result, significant therapeutic benefits were observed through the successful depletion of approximately 80 % of the M2-like macrophages (FPMs) in a bleomycin-induced fibrosis mouse model treated with the designed M2-like FPM-targeting nanoparticle (referred to as M2NP-BLZ@Mn-Cur). Importantly, the released Mn2+ and curcumin after the degradation of M2NP-BLZ@Mn-Cur accumulated in the fibrotic lung tissue, which can alleviate inflammation and oxidative stress reactions, thereby further improving IPF therapy. This study presents a novel strategy with promising prospects for molecular-targeted fibrosis therapy. STATEMENT OF SIGNIFICANCE: Metal-organic frameworks (MOFs)- based nanocarriers equipped with both fibrosis-promoting macrophage (FPM)-specific targeting ability and therapeutic drugs are appealing for pulmonary fibrosis treatment. Here, we prepared M2pep (an M2-like FPM binding peptide)-modified and BLZ945 (a small molecule inhibitor of CSF1/CSF-1R axis)-loaded Mn-curcumin MOF nanoparticles (M2NP-BLZ@Mn-Cur) for pulmonary fibrosis therapy. The functionalized M2NP-BLZ@Mn-Cur nanoparticles can be preferentially taken up by FPMs, resulting in their depletion from fibrotic lung tissues. In addition, Mn2+and curcumin released from the nanocarriers have anti-inflammation and immune regulation effects, which further enhance the antifibrotic effect of the nanoparticles.


Assuntos
Curcumina , Fibrose Pulmonar Idiopática , Estruturas Metalorgânicas , Camundongos , Animais , Estruturas Metalorgânicas/farmacologia , Curcumina/farmacologia , Curcumina/uso terapêutico , Curcumina/química , Macrófagos/metabolismo , Fibrose Pulmonar Idiopática/tratamento farmacológico , Fibrose Pulmonar Idiopática/metabolismo , Peptídeos/farmacologia
19.
J Orthop Surg Res ; 18(1): 931, 2023 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-38057793

RESUMO

BACKGROUND: It has been controversial that whether hardware removal will increase the risk of osteonecrosis of femoral head (ONFH) in fracture-healed patients who underwent internal fixation for femoral neck fractures (FNFs). This meta-analysis aimed to clarify the association of hardware removal with secondary hardware removal-induced ONFH (HR-ONFH). METHODS: Four electronic databases (PubMed, Embase, Web of Science, Cochrane Library) were searched for eligible studies published up to March 10, 2023. Studies reporting the relative risk of hardware status (i.e., risk rate, odds ratio [OR], or hazard ratio [HR]) were included. Newcastle-Ottawa scale (NOS) was used to assess risk of bias of included observational studies. Review Manager software was used to pool ORs and adjusted ORs. RESULTS: Five studies were included into quantitative synthesis. Hardware removal was associated with a reduced risk of HR-ONFH in the synthesis of crude odds ratios (OR, 0.62, 95% CI 0.39-0.96). In the synthesis of adjusted odds ratios, hardware removal was associated with an increased risk of HR-ONFH (OR, 1.76, 95% CI 1.23-2.51). CONCLUSION: This study demonstrates that hardware removal was associated with an increased incidence of HR-ONFH in fracture-healed patients who underwent internal fixation due to FNFs.


Assuntos
Fraturas do Colo Femoral , Necrose da Cabeça do Fêmur , Humanos , Fraturas do Colo Femoral/cirurgia , Fraturas do Colo Femoral/complicações , Necrose da Cabeça do Fêmur/etiologia , Necrose da Cabeça do Fêmur/cirurgia , Necrose da Cabeça do Fêmur/epidemiologia , Fixação Interna de Fraturas/efeitos adversos , Incidência , Cabeça do Fêmur
20.
Biomedicines ; 11(12)2023 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-38137354

RESUMO

BACKGROUND: Lung cancer is still the most lethal malignancy in the world, according to the report of Cancer Statistics in 2021. Platinum-based chemotherapy combined with immunotherapy is the first-line treatment in lung cancer patients. However, the 5-year survival rate is always affected by the adverse reactions and drug resistance caused by platinum-based chemotherapy. DNA damage and repair system is one of the important mechanisms that can affect the response to chemotherapy and clinical outcomes in lung cancer patients. OBJECTIVE: The objective of this study is to find the relationship between the polymorphisms of DNA repair genes with the prognosis of platinum-based chemotherapy in lung cancer patients. PATIENTS AND METHODS: We performed genotyping in 17 single nucleotide polymorphisms (SNPs) of Excision Repair Cross-Complementation group (ERCC) genes and X-ray Repair Cross-Complementing (XRCC) genes of 345 lung cancer patients via Sequenom MassARRAY. We used Cox proportional hazard models, state, and plink to analyze the associations between SNPs and the prognosis of lung cancer patients. RESULTS: We found that the ERCC5 rs873601 was associated with the overall survival time in lung cancer patients treated with platinum-based chemotherapy (p = 0.031). There were some polymorphisms that were related to the prognosis in specific subgroups of lung cancer. Rs873601 showed a great influence on the prognosis of patients more than 55 years, Small Cell Lung Cancer (SCLC), and smoking patients. Rs2444933 was associated with prognosis in age less than 55 years, SCLC, metastasis, and stage III/IV/ED patients. Rs3740051 played an important role in the prognosis of SCLC and metastasis patients. Rs1869641 was involved in the prognosis of SCLC patients. Rs1051685 was related to the prognosis in non-metastasis patients. CONCLUSION: The ERCC5 rs873601 (G>A) was a valuable biomarker for predicting the prognosis in lung cancer patients treated with platinum-based chemotherapy.

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