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1.
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.

2.
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
3.
Acta Biomater ; 179: 313-324, 2024 Apr 15.
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.


Assuntos
Doxorrubicina , Tomografia por Emissão de Pósitrons , Radioisótopos , Neoplasias de Mama Triplo Negativas , Zircônio , Neoplasias de Mama Triplo Negativas/diagnóstico por imagem , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Zircônio/química , Animais , Tomografia por Emissão de Pósitrons/métodos , Humanos , Linhagem Celular Tumoral , Feminino , Doxorrubicina/farmacologia , Doxorrubicina/química , Polímeros/química , Camundongos , Sistemas de Liberação de Medicamentos , Polietilenoglicóis/química , Camundongos Nus
4.
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.

5.
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.

6.
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.

7.
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.

8.
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.

9.
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
10.
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
11.
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
12.
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
13.
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.

14.
Cells ; 12(21)2023 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-37947603

RESUMO

Cannabis is now one of the most commonly used illicit substances among pregnant women. This is particularly concerning since developmental exposure to cannabinoids can elicit enduring neurofunctional and cognitive alterations. This study investigates the mechanisms of learning and memory deficits resulting from prenatal cannabinoid exposure (PCE) in adolescent offspring. The synthetic cannabinoid agonist WIN55,212-2 was administered to pregnant rats, and a series of behavioral, electrophysiological, and immunochemical studies were performed to identify potential mechanisms of memory deficits in the adolescent offspring. Hippocampal-dependent memory deficits in adolescent PCE animals were associated with decreased long-term potentiation (LTP) and enhanced long-term depression (LTD) at hippocampal Schaffer collateral-CA1 synapses, as well as an imbalance between GluN2A- and GluN2B-mediated signaling. Moreover, PCE reduced gene and protein expression of neural cell adhesion molecule (NCAM) and polysialylated-NCAM (PSA-NCAM), which are critical for GluN2A and GluN2B signaling balance. Administration of exogenous PSA abrogated the LTP deficits observed in PCE animals, suggesting PSA mediated alterations in GluN2A- and GluN2B- signaling pathways may be responsible for the impaired hippocampal synaptic plasticity resulting from PCE. These findings enhance our current understanding of how PCE affects memory and how this process can be manipulated for future therapeutic purposes.


Assuntos
Canabinoides , Moléculas de Adesão de Célula Nervosa , Humanos , Ratos , Feminino , Animais , Gravidez , Adolescente , Moléculas de Adesão de Célula Nervosa/metabolismo , Canabinoides/farmacologia , Canabinoides/metabolismo , Plasticidade Neuronal/fisiologia , Hipocampo/metabolismo , Transtornos da Memória/metabolismo
16.
J Orthop Surg Res ; 18(1): 801, 2023 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-37884925

RESUMO

BACKGROUND: The unilaterally extrapedicular approach is adopted increasingly to perform balloon kyphoplasty in treating osteoporotic lumbar fractures, which is intended to improve radiological and clinical efficacy. We compared the efficacy and safety of this method with a unilaterally transpedicular approach. METHODS: We conducted a single-center, randomized controlled trial enrolling participants with a one-level osteoporotic lumbar fracture in less than 1 month. Patients were randomly assigned to undergo kyphoplasty via either a unilaterally extrapedicular approach (treatment group) or a unilaterally transpedicular approach (control group). The primary outcome was the difference in change from baseline to 1 month in visual analog scale (VAS) scores between the two groups. Secondary outcome measures included vertebral height ratio, operation time, fluoroscopic times, hemoglobin loss, and cement leakage between groups. Data were analyzed by intention to treat principle. RESULTS: A total of 80 participants were assigned to the treatment group (n = 40) and control group (n = 40), with three and two patients lost to follow-up during 12 months in the two groups, respectively. At 1 month postoperatively, the treatment group showed a greater reduction in VAS score from baseline, compared with the control group (mean difference between groups = 0.63, 95%CI 0.19-1.06). There were no significant between-group differences in restoration in anterior, middle, and posterior vertebral body (P > 0.05). No significant differences were found in the rate of cement leakage and perioperative hemoglobin loss (P > 0.05). CONCLUSION: Compared with balloon kyphoplasty via the unilaterally transpedicular approach in treating lumbar OVCFs, the unilaterally extrapedicular approach appears to be promising in achieving effective pain relief, adequate cement infusion, short operation time, less fluoroscopy exposure, and comparable risk of cement leakage and vessel injury. It is an alternative approach for lumbar OVCFs treated with kyphoplasty.


Assuntos
Fraturas por Compressão , Cifoplastia , Fraturas por Osteoporose , Fraturas da Coluna Vertebral , Humanos , Cimentos Ósseos/efeitos adversos , Fraturas por Compressão/cirurgia , Hemoglobinas , Cifoplastia/métodos , Fraturas por Osteoporose/diagnóstico por imagem , Fraturas por Osteoporose/cirurgia , Fraturas por Osteoporose/tratamento farmacológico , Fraturas da Coluna Vertebral/diagnóstico por imagem , Fraturas da Coluna Vertebral/cirurgia , Fraturas da Coluna Vertebral/tratamento farmacológico , Resultado do Tratamento
17.
Sci Rep ; 13(1): 16447, 2023 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-37777594

RESUMO

This study aimed to assess the accuracy of cortical bone trajectory (CBT) screws placement guided by a spinous process clamp (SPC) guide. A total of 32 patients who received single-level midline lumbar fusion (MIDLF) surgery between June 2019 and January 2020 were retrospectively analyzed and divided into free-hand (FH) and SPC-guided groups according to the surgical approach. In the FH group, CBT screws was implanted with the assistance of fluoroscopy, while in the SPC group, CBT screws was implanted using the SPC navigator hardwire. A total of 128 screws were assessed in this study, with higher rates of clinically acceptable screw placement (grades A and B) and grade A screws in the SPC group than in the FH guide group (92.2% vs. 79.7%, P = 0.042 and 54.7% vs. 35.9%, P = 0.033, respectively). Misplacement screws (grades C, D, and E) occurred more often in the FH group than in the SPC guide group (20.3% vs. 7.8%, P = 0.042). The incidence of proximal facet joint violation (FJV) was higher in the FH group than in the SPC group (15.6% vs. 3.1%, P = 0.030). The radiation dose and time in the SPC guide group were comparable to those in the FH group (P = 0.063 and P = 0.078). The average operative time was significantly longer in the SPC guide group than in the FH group (267.8 ± 45.5 min vs. 210.9 ± 44.5 min, P = 0.001). Other clinical parameters, such as the average bone mineral density (BMD), intraoperative blood loss, and postoperative hospital stay, were not significantly different. Oswestry disability index (ODI) and back pain visual analogue scale (VAS) scores were significantly improved in both groups compared with preoperatively. SPC guided screw placement was more accurate than the fluoroscopy-assisted FH technique for single-level MIDLF at L4/5. Patients undergoing SPC-guided screw placement can achieve similar clinical outcomes as the fluoroscopy-assisted FH technique.


Assuntos
Parafusos Pediculares , Procedimentos Cirúrgicos Robóticos , Fusão Vertebral , Cirurgia Assistida por Computador , Humanos , Procedimentos Cirúrgicos Robóticos/métodos , Estudos Retrospectivos , Cirurgia Assistida por Computador/métodos , Osso Cortical/diagnóstico por imagem , Osso Cortical/cirurgia , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Fusão Vertebral/métodos
18.
Infect Dis Poverty ; 12(1): 86, 2023 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-37735709

RESUMO

The human papillomavirus (HPV) vaccine is the first vaccine developed specifically targeting the prevention of cervical cancer. For more than 15 years, China has expedited a series of efforts on research and development of the domestically manufactured HPV vaccines, producing local population-based evidence, promoting free HPV vaccination from pilots, and launching action plans to tackle barriers in the scale-up of HPV vaccination. To further roll out the HPV vaccination program in China, several challenges should be addressed to support the steps forward. The availability of more locally manufactured HPV vaccines, pricing negotiation and local evidence supporting the efficacy of one-dose schedule would greatly alleviate the continued supply and financial constraints in China. Meanwhile, more attention should be paid to girls living in low-resource areas and males to ensure equal access to the HPV vaccination. Furthermore, linkage to secondary prevention and further real-world monitoring and evaluation are warranted to inform effective cervical cancer prevention strategies in the post-vaccine era.


Assuntos
Infecções por Papillomavirus , Vacinas contra Papillomavirus , Neoplasias do Colo do Útero , Feminino , Masculino , Humanos , Papillomavirus Humano , Infecções por Papillomavirus/prevenção & controle , Neoplasias do Colo do Útero/prevenção & controle , Vacinação , China
20.
Genes Dis ; 10(3): 771-785, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37396555

RESUMO

Vascular remodeling and angiogenesis are two key processes in the maintenance of vascular homeostasis and involved in a wide array of vascular pathologies. Following these processes, extracellular matrix (ECM) provides the mechanical foundation for vascular walls. Lysyl oxidase (LOX), the key matrix-modifying enzyme, has been demonstrated to significantly affect structural abnormality and dysfunction in the blood vessels. The role of LOX in vascular remodeling and angiogenesis has always been the subject in the current medical research. Therefore, we presently make a summarization of the biosynthesis of LOX and the mechanisms involved in vascular remodeling and angiogenesis, as well as the role of LOX in diseases associated with vascular abnormalities and the therapeutic potential via targeting LOX. In particular, we give a proposal that LOX likely reshapes matrisome-associated genes expressions in the regulation of vascular remodeling and angiogenesis, which serves as a mechanistic insight into the critical role of LOX in these two aspects. Additionally, LOX has also dual effects on the vascular dysfunction, namely, inhibition of LOX for improving hypertension, restenosis and malignant tumor while activation of LOX for curing arterial aneurysm and dissection. LOX-targeted therapy may provide a promising therapeutic strategy for the treatment of various vascular pathologies associated with vascular remodeling and angiogenesis.

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