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1.
Am J Physiol Cell Physiol ; 327(1): C193-C204, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38682240

RESUMO

Negative pressure wound therapy (NPWT) is extensively used in clinical settings to enhance the healing of wounds. Despite its widespread use, the molecular mechanisms driving the efficacy of NPWT have not been fully elucidated. In this study, skin wound-healing models were established, with administration of NPWT. Vimentin, collagen I, and MMP9 of skin tissues were detected by immunofluorescence (IF). Gene expression analysis of skin wound tissues was performed by RNA-sequencing (RNA-seq). Protein expression was assayed by a Western blotting or IF assay, and mRNA levels were quantified by quantitative PCR. Chromatin accessibility profiles of fibroblasts following NPWT or IL-17 exposure were analyzed by ATAC-seq. In rat wound-healing models, NPWT promoted wound repair by promoting reepithelialization, extracellular matrix (ECM) synthesis, and proliferation, which mainly occurred in the early stage of wound healing. These differentially expressed genes (DEGs) in NPWT wounds versus control wounds were enriched in the IL-17 signaling pathway. IL-17 was identified as an upregulated factor following NPWT in skin wounds. Moreover, the IL-17 inhibitor secukinumab (SEC) could abolish the promoting effect of NPWT on wound healing. Importantly, chromatin accessibility profiles were altered following NPWT and IL-17 stimulation in skin fibroblasts. Our findings suggest that NPWT upregulates IL-17 to promote wound healing by altering chromatin accessibility, which is a novel mechanism for NPWT's efficacy in wound healing.NEW & NOTEWORTHY To our knowledge, this is the first report of the efficacy of negative pressure wound therapy (NPWT) in promoting wound healing via IL-17. Moreover, NPWT and IL-17 can alter chromatin accessibility. Our study identifies a novel mechanism for NPWT's efficacy in wound healing.


Assuntos
Cromatina , Interleucina-17 , Tratamento de Ferimentos com Pressão Negativa , Ratos Sprague-Dawley , Cicatrização , Animais , Interleucina-17/metabolismo , Interleucina-17/genética , Tratamento de Ferimentos com Pressão Negativa/métodos , Cicatrização/efeitos dos fármacos , Ratos , Cromatina/metabolismo , Cromatina/genética , Masculino , Pele/lesões , Pele/metabolismo , Pele/patologia , Pele/efeitos dos fármacos , Fibroblastos/metabolismo , Fibroblastos/efeitos dos fármacos , Transdução de Sinais
2.
Gastroenterology ; 164(3): 424-438, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36436593

RESUMO

BACKGROUND & AIMS: In eukaryotes, the ubiquitin-proteasome system and the autophagy-lysosome pathway are essential for maintaining cellular proteostasis and associated with cancer progression. Our previous studies have demonstrated that phosphatase and tensin homolog (PTEN), one of the most frequently mutated genes in human cancers, limits proteasome abundance and determines chemosensitivity to proteasome inhibitors in cholangiocarcinoma (CCA). However, whether PTEN regulates the lysosome pathway remains unclear. METHODS: We tested the effects of PTEN on lysosome biogenesis and exosome secretion using loss- and gain-of-function strategies in CCA cell lines. Using in vitro dephosphorylation assays, we explored the regulatory mechanism between PTEN and the key regulator of lysosome biogenesis, transcription factor EB (TFEB). Using the migration assays, invasion assays, and trans-splenic liver metastasis mouse models, we evaluated the function of PTEN deficiency, TFEB-mediated lysosome biogenesis, and exosome secretion on tumor metastasis. Moreover, we investigated the clinical significance of PTEN expression and exosome secretion by retrospective analysis. RESULTS: PTEN facilitated lysosome biogenesis and acidification through its protein phosphatase activity to dephosphorylate TFEB at Ser211. Notably, PTEN deficiency increased exosome secretion by reducing lysosome-mediated degradation of multi-vesicular bodies, which further facilitated the proliferation and invasion of CCA. TFEB agonist curcumin analog C1 restrained the metastatic phenotype caused by PTEN deficiency in mouse models, and we highlighted the correlation between PTEN deficiency and exosome secretion in clinical cohorts. CONCLUSIONS: In CCA, PTEN deficiency impairs lysosome biogenesis to facilitate exosome secretion and cancer metastasis in a TFEB phosphorylation-dependent manner.


Assuntos
Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos , Colangiocarcinoma , Exossomos , PTEN Fosfo-Hidrolase , Animais , Humanos , Camundongos , Autofagia , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Colangiocarcinoma/metabolismo , Modelos Animais de Doenças , Exossomos/metabolismo , Lisossomos/fisiologia , Complexo de Endopeptidases do Proteassoma , PTEN Fosfo-Hidrolase/metabolismo , Estudos Retrospectivos
3.
Cancer Immunol Immunother ; 73(4): 62, 2024 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-38430249

RESUMO

How to increase the response of immune checkpoint inhibitors (ICIs) is a challenge. In clinical, we found that Zoledronic acid (ZA) may increase the anti-tumor effect of immunotherapy for hepatocellular carcinoma (HCC). To explore the underlying mechanism, we established a mouse model of HCC by subcutaneously injecting Hepa1-6 cell line. The result showed that the tumor volume in the ZA plus anti-PD-1 monocloning antibody (anti-PD-1 mAb) treatment groups was significantly smaller than that of control group, and the onset time of tumor inhibition was even shorter than that of the anti-PD-1 mAb group. Using flow cytometry (FC) to detect the proportion of major immune cell subsets in tumor tissues of each group of mice, we found that the synergistic anti-tumor effect of ZA and anti-PD-1 mAb may be related to ZA-induced polarization of macrophages toward the M1 phenotype. Next, we performed bulk RNA sequencing on tumor samples from different groups to obtain differentially expressed genes (DEGs), which were then input DEGs into pathway enrichment analysis. Data indicated that ZA participated in the M1-type polarization via ferroptosis-related pathways. Our results revealed how ZA involves in the anti-tumor effect of PD-1 monoclonal antibody and provided a potential therapeutic candidate for patients with HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Animais , Camundongos , Carcinoma Hepatocelular/metabolismo , Ácido Zoledrônico/farmacologia , Ácido Zoledrônico/uso terapêutico , Receptor de Morte Celular Programada 1 , Neoplasias Hepáticas/metabolismo , Linhagem Celular Tumoral , Microambiente Tumoral
4.
Nanotechnology ; 35(15)2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38198735

RESUMO

Electronical properties of top gate amorphous InGaZnO4thin film transistors (TFTs) could be controlled by post-annealing treatment, which has a great impact on the Al2O3insulator. To investigate the effect of post-annealing on Al2O3, Al/Al2O3/p-Si MOS capacitoras with Al2O3films treated under various post-deposition annealing (PDA) temperature were employed to analysis the change of electrical properties, surface morphology, and chemical components by electrical voltage scanning, atomic force microscope (AFM), and x-ray photoelectron spectroscopy (XPS) technologies. After PDA treatment, the top gate TFTs had a mobility about 7 cm2V-1s-1and the minimum subthreshold swing (SS) about 0.11 V/dec, and the threshold voltage (Vth) shifted from positive direction to negative direction as the post-annealing temperature increased. Electrical properties of MOS capacitors revealed the existence of positive fixed charges and the variation of trap state density with increasing PDA temperature, and further explained the change of negative bias stress (NBS) stability in TFT. AFM results clarified the increased leakage current, degraded SS, and NBS stability in MOS capacitors and TFTs, respectively. XPS results not only illuminated the origin of fixed charges and the trap density variation with PDA temperatures of Al2O3films, but also showed the O and H diffusion from Al2O3into IGZO during post-annealing process, which led to the deviation ofVth, the change of current density, and the negativeVthshift after positive bias stress in TFTs.

5.
Angew Chem Int Ed Engl ; : e202411029, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38955769

RESUMO

Graphite (Gr)-based lithium-ion batteries with admirable electrochemical performance below -20 °C are desired but are hindered by sluggish interfacial charge transport and desolvation process. Li salt dissociation via Li+-solvent interaction enables mobile Li+ liberation and contributes to bulk ion transport, while is contradictory to fast interfacial desolvation. Designing kinetically-stable solid electrolyte interphase (SEI) without compromising strong Li+-solvent interaction is expected to compatibly improve interfacial charge transport and desolvation kinetics. However, the relationship between physicochemical features and temperature-dependent kinetics properties of SEI remains vague. Herein, we propose four key thermodynamics parameters of SEI potentially influencing low-temperature electrochemistry, including electron work function, Li+ transfer barrier, surface energy, and desolvation energy. Based on the above parameters, we further define a novel descriptor, separation factor of SEI (SSEI), to quantitatively depict charge (Li+/e-) transport and solvent deprivation processes at Gr/electrolyte interface. A Li3PO4-based, inorganics-enriched SEI derived by Li difluorophosphate (LiDFP) additive exhibits the highest SSEI (4.89×103) to enable efficient Li+ conduction, e- blocking and rapid desolvation, and as a result, much suppressed Li-metal precipitation, electrolyte decomposition and Gr sheets exfoliation, thus improving low-temperature battery performances. Overall, our work originally provides visualized guides to improve low-temperature reaction kinetics/thermodynamics by constructing desirable SEI chemistry.

6.
Angew Chem Int Ed Engl ; 63(21): e202318663, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38516922

RESUMO

Graphite has been serving as the key anode material of rechargeable Li-ion batteries, yet is difficultly charged within a quarter hour while maintaining stable electrochemistry. In addition to a defective edge structure that prevents fast Li-ion entry, the high-rate performance of graphite could be hampered by co-intercalation and parasitic reduction of solvent molecules at anode/electrolyte interface. Conventional surface modification by pitch-derived carbon barely isolates the solvent and electrons, and usually lead to inadequate rate capability to meet practical fast-charge requirements. Here we show that, by applying a MoOx-MoNx layer onto graphite surface, the interface allows fast Li-ion diffusion yet blocks solvent access and electron leakage. By regulating interfacial mass and charge transfer, the modified graphite anode delivers a reversible capacity of 340.3 mAh g-1 after 4000 cycles at 6 C, showing promises in building 10-min-rechargeable batteries with a long operation life.

7.
J Am Chem Soc ; 145(31): 17377-17388, 2023 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-37497917

RESUMO

The five-year survival rate of hepatocellular carcinoma (HCC) remains unsatisfactory. This reflects, in part, the paucity of effective methods that allow the target-specific diagnosis and therapy of HCC. Here, we report a strategy based on engineered human serum albumin (HSA) that permits the HCC-targeted delivery of diagnostic and therapeutic agents. Covalent cysteine conjugation combined with the exploitation of host-guest chemistry was used to effect the orthogonal functionalization of HSA with two functionally independent peptides. One of these peptides targets glypican-3 (GPC-3), an HCC-specific biomarker, while the second reduces macrophage phagocytosis through immune-checkpoint stimulation. This orthogonally engineered HSA proved effective for the GPC-3-targeted delivery of near-infrared fluorescent and phototherapeutic agents, thus permitting target-specific optical visualization and photodynamic ablation of HCC in vivo. This study thus offers new insights into specificity-enhanced fluorescence-guided surgery and phototherapy of HCC through the orthogonal engineering of biocompatible proteins.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Neoplasias Hepáticas/metabolismo , Carcinoma Hepatocelular/terapia , Fototerapia/métodos , Albuminas , Albumina Sérica Humana , Macrófagos/metabolismo , Fagocitose
8.
J Craniofac Surg ; 34(7): e638-e641, 2023 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-37254238

RESUMO

BACKGROUND: The hemifacial congenital giant nevus impacts both physical and mental health of the patients. Excision is typically the most suitable option in these situations, but reconstructing the subsequent surgical defects is always a serious challenge. METHODS: Between February 2012 and January 2021, a retrospective review of 4 patients who suffered from hemifacial congenital giant nevus was conducted, and they were treated by pre-expanded scalp flap and deltopectoral flap simultaneously. All patients receive tissue expansion, nevus resection, expanded skin flap transfer, and pedicle division. RESULTS: Four patients with hemifacial congenital giant nevi were successfully treated with no major complications. One patient with a transferred deltopectoral flap experienced distal necrosis of the flap, and healed after dressing changes. No recurrence of the nevus was found during the follow-up period, and the transferred skin flaps match well with facial skin in contour and color. CONCLUSION: This modified pre-expanded scalp flap combined with a deltopectoral flap provides an easy and reliable way for hemifacial reconstruction in patients with a congenital giant nevus.


Assuntos
Nevo Pigmentado , Procedimentos de Cirurgia Plástica , Neoplasias Cutâneas , Retalhos Cirúrgicos , Humanos , Nevo/cirurgia , Couro Cabeludo/cirurgia , Neoplasias Cutâneas/cirurgia , Neoplasias Cutâneas/congênito , Transplante de Pele , Retalhos Cirúrgicos/cirurgia , Nevo Pigmentado/cirurgia , Resultado do Tratamento
9.
Aesthet Surg J ; 43(9): NP687-NP695, 2023 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-37184121

RESUMO

BACKGROUND: Accessory auricles are common congenital external ear malformations. However, it remains challenging to treat a complicated accessory auricle and reconstruct the involved tragus. OBJECTIVES: In this study the aim was to present a new classification of accessory auricles and the surgical management of each type. METHODS: We retrospectively reviewed the records of 110 patients who underwent accessory auricle surgery. The accessory auricle was classified by 3 types, according to its morphology and relationship with the tragus: Types I, II, and III. The type III accessory auricle was divided into 3 subtypes: IIIa, IIIb, and IIIc. The surgical techniques utilized varied among the different types. RESULTS: The total number of accessory auricles in 110 patients was 149. Type I was the most common type (52.3%), followed by types II (31.5%) and III (16.1%). Among the type III subtypes, type IIIa was observed in 12 (8.1%), type IIIb in 3 (2%), and type IIIc in 9 (6%) ears. None of the patients experienced short-term complications. Three patients (4 ears) showed mild hypertrophic scarring. Three patients (3 ears) showed a smaller tragus than the normal side. The average score for aesthetic outcomes was 3.7 points on a 4-point Likert scale. CONCLUSIONS: Classification of accessory auricles provides guidance for surgery. Different surgical techniques were employed based on the type of accessory auricle. The final incision at the edge of the reconstructed tragus provided an aesthetically pleasing outcome.


Assuntos
Pavilhão Auricular , Procedimentos de Cirurgia Plástica , Humanos , Procedimentos de Cirurgia Plástica/efeitos adversos , Estudos Retrospectivos , Orelha Externa/cirurgia , Orelha Externa/anormalidades , Pavilhão Auricular/cirurgia , Estética
10.
Angew Chem Int Ed Engl ; 62(23): e202301073, 2023 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-37011095

RESUMO

Without excess Li, anode-free Li-metal batteries (AFLMBs) have been proposed as the most likely solution to realizing highly-safe and cost-effective Li-metal batteries. Nevertheless, short cyclic life puzzles conventional AFLMBs due to anodic dead Li accumulation with a local current concentration induced by irreversible electrolyte depletion, insufficient active Li reservoir and slow Li+ transfer at the solid electrolyte interphase (SEI). Herein, SrI2 is introduced into carbon paper (CP) current collector to effectively suppress dead Li through synergistic mechanisms including reversible I- /I3 - redox reaction to reactivate dead Li, dielectric SEI surface with SrF2 and LiF to prevent electrolyte decomposition and highly ionic conductive (3.488 mS cm-1 ) inner layer of SEI with abundant LiI to enable efficient Li+ transfer inside. With the SrI2 -modified current collector, the NCM532/CP cell delivers unprecedented cyclic performances with a capacity of 129.2 mAh g-1 after 200 cycles.

11.
Cancer Sci ; 113(12): 4151-4164, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36114745

RESUMO

Oncogene-derived metabolic reprogramming is important for anabolic growth of cancer cells, which is now considered to be not simply rely on glycolysis. Pentose phosphate pathway and tricarboxylic acid cycle also play pivotal roles in helping cancer cells to meet their anabolic and energy demands. The present work focused on gankyrin, a relatively specific oncogene in hepatocellular carcinoma (HCC), and its impact on glycolysis and mitochondrial homeostasis. Metabolomics, RNA-seq analysis, and subsequent conjoint analysis illustrated that gankyrin regulated the pentose phosphate pathway (PPP), tricarboxylic acid (TCA) cycle, and mitochondrial function and homeostasis, which play pivotal roles in tumor development. Mechanistically, gankyrin was found to modulate HCC metabolic reprogramming via TIGAR. Gankyrin positively regulated the transcription of TIGAR through Nrf2, which bound to the antioxidant response elements (AREs) in the promoter of TIGAR. Interestingly, TIGAR feedback regulated the transcription of Nrf2 and subsequently gankyrin by promoting nuclear importation of PGC1α. The loop between gankyrin, Nrf2, and TIGAR accelerated glucose metabolism toward the PPP and TCA cycle, which provided vital building blocks, such as NADPH, ATP, and ribose of tumor and further facilitated the progression of HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patologia , Ciclo do Ácido Cítrico , Neoplasias Hepáticas/patologia , Glicólise , Glucose/metabolismo
12.
Small ; 18(23): e2107664, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35527335

RESUMO

Incorporation of ceramic materials into separators has been frequently applied in both research and industry to improve the overall high-temperature performances of lithium ion batteries. However, inorganic ceramic particles tend to form aggregation in separators and even fall off in the separator matrix due to the inferior combination between ceramic particles and polymer matrix, giving rise to a decrease in separator porosity and thus the degradation of battery performances. Herein, a single-layer core-shell architecture is designed to reinforce the polymer matrix through encircling Al2 O3 particles by poly(vinylidene fluoride) with strong inter-molecular interaction. The 3D-reinforced microstructure effectively improves pore distribution and thermal stability to resist the dimensional deformation at high temperatures, thus giving rise to a high Coulombic efficiency of 99.16% and 87.5% capacity retention after 500 cycles at 80 °C for LiFePO4 /Li batteries. In particular, the excellent performances of the proposed separator microstructure are confirmed with a thickness value of commercial separators. This work provides a promising strategy to fabricate a core-shell structural composite separator for stable lithium ion batteries at high temperatures.

13.
Proc Natl Acad Sci U S A ; 116(51): 25784-25789, 2019 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-31792185

RESUMO

For individuals who sustain devastating composite tissue loss, vascularized composite allotransplantation (VCA; e.g., hand and face transplantation) has the potential to restore appearance and function of the damaged tissues. As with solid organ transplantation, however, rejection must be controlled by multidrug systemic immunosuppression with substantial side effects. As an alternative therapeutic approach inspired by natural mechanisms the body uses to control inflammation, we developed a system to enrich regulatory T cells (Tregs) in an allograft. Microparticles were engineered to sustainably release TGF-ß1, IL-2, and rapamycin, to induce Treg differentiation from naïve T cells. In a rat hindlimb VCA model, local administration of this Treg-inducing system, referred to as TRI-MP, prolonged allograft survival indefinitely without long-term systemic immunosuppression. TRI-MP treatment reduced expression of inflammatory mediators and enhanced expression of Treg-associated cytokines in allograft tissue. TRI-MP also enriched Treg and reduced inflammatory Th1 populations in allograft draining lymph nodes. This local immunotherapy imparted systemic donor-specific tolerance in otherwise immunocompetent rats, as evidenced by acceptance of secondary skin grafts from the hindlimb donor strain and rejection of skin grafts from a third-party donor strain. Ultimately, this therapeutic approach may reduce, or even eliminate, the need for systemic immunosuppression in VCA or solid organ transplantation.


Assuntos
Micropartículas Derivadas de Células/metabolismo , Terapia de Imunossupressão/métodos , Linfócitos T Reguladores/citologia , Tolerância ao Transplante/fisiologia , Alotransplante de Tecidos Compostos Vascularizados/métodos , Animais , Citocinas/metabolismo , Sistemas de Liberação de Medicamentos , Imunossupressores/metabolismo , Ratos
14.
Hepatology ; 71(6): 2005-2022, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31541481

RESUMO

BACKGROUND AND AIMS: Cancer cell survival depends on the balance between reactive oxygen species production and scavenging, which is regulated primarily by NRF2 during tumorigenesis. Here, we demonstrate that deletion of RBP5-mediating protein (RMP) in an autonomous mouse model of intrahepatic cholangiocarcinoma (ICC) delays tumor progression. APPROACH AND RESULTS: RMP-overexpressing tumor cells exhibited enhanced tolerance to oxidative stress and apoptosis. Mechanistically, RMP competes with NRF2 for binding to the Kelch domain of KEAP1 (Kelch-like ECH-associated protein 1) through the E**E motif, leading to decreased NRF2 degradation via ubiquitination, thus increasing NRF2 nuclear translocation and downstream transactivation of antioxidant genes. This RMP-KEAP1-NRF2 axis promotes ICC tumorigenesis, metastasis, and drug resistance. Consistent with these findings, the RMP level in human ICC is positively correlated with the protein level of NRF2 and is associated with poor prognosis. CONCLUSION: These findings reveal that RMP is involved in the oxidative stress defense program and could be exploited for targeted cancer therapies.


Assuntos
Carcinogênese , Colangiocarcinoma/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Proteínas Repressoras/metabolismo , Animais , Apoptose , Carcinogênese/efeitos dos fármacos , Carcinogênese/metabolismo , Linhagem Celular , Transformação Celular Neoplásica/metabolismo , Colangiocarcinoma/patologia , Resistencia a Medicamentos Antineoplásicos , Humanos , Camundongos , Estresse Oxidativo
15.
Anal Bioanal Chem ; 413(12): 3153-3165, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33796932

RESUMO

Comprehensive prognostic risk prediction of hepatocellular carcinoma (HCC) after surgical treatment is particularly important for guiding clinical decision-making and improving postoperative survival. Hence, we aimed to build prognostic models based on serum metabolomics data, and assess the prognostic risk of HCC within 5 years after surgical resection. A pseudotargeted gas chromatography-mass spectrometry (GC-MS)-based metabolomics method was applied to analyze serum profiling of 78 HCC patients. Important metabolic features with discriminant ability were identified by a novel network-based metabolic feature selection method based on combinational significance index (N-CSI). Subsequently, phenylalanine and galactose were further identified to be relevant with mortality by the Cox regression analysis, while galactose and tyrosine were associated with recurrence and metastasis. Two models to predict risk of mortality (risk score of overall survival, RSOS) and risk of recurrence and metastasis (risk score of disease-free survival, RSDFS) were generated based on two panels of metabolites, respectively, which present favorable ability to predict prognosis of HCC, especially when combined with clinical staging system. The performance of models was further validated in an external independent cohort from 91 HCC patients. This study demonstrated that metabolomics is a powerful tool for risk screening of HCC prognosis.


Assuntos
Carcinoma Hepatocelular/sangue , Cromatografia Gasosa-Espectrometria de Massas/métodos , Neoplasias Hepáticas/sangue , Metabolômica/métodos , Adulto , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Feminino , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Prognóstico , Reprodutibilidade dos Testes , Análise de Sobrevida
16.
J Craniofac Surg ; 32(2): 726-729, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33705020

RESUMO

BACKGROUND: Ear reconstruction is one of the most challenging procedures for plastic surgeons. The costal cartilage is the most accepted material, and the framework fabrication methods also vary with the different ear reconstruction methods. This study aimed to present our clinical experience using a novel method for costal cartilage framework fabrication with the "fully expansion technique" ear reconstruction without a skin graft. From January 2017 to June 2018, 107 patients with unilateral microtia underwent ear reconstruction with the fully expansion technique. Costal cartilage was designed into different components and stacked up to form the multilayer structure and adequate projection. Preexpansion provided larger skin flap for fully cover the anterior and posterior parts of the framework. Then the anterior ear structures and the posterior sulcus, as well as the ideal bilateral symmetry, were established simultaneously without a skin graft. A total of 107 patients in this group were followed up for 8 to 24 month, and altogether 98 patients (91.6%) were satisfied with the reconstruction. The cartilage "stack-up" framework fabrication and fully expansion technique provided a well-defined, well-projected, and bilateral symmetrical reconstructed ear.


Assuntos
Microtia Congênita , Cartilagem Costal , Procedimentos de Cirurgia Plástica , Microtia Congênita/cirurgia , Cartilagem da Orelha/cirurgia , Orelha Externa/cirurgia , Humanos , Transplante de Pele , Retalhos Cirúrgicos
17.
J Proteome Res ; 19(8): 3533-3541, 2020 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-32618195

RESUMO

Assessment and prediction of prognostic risk in patients with hepatocellular carcinoma (HCC) would greatly benefit the optimal treatment selection. Here, we aimed to identify the critical metabolites associated with the outcomes and develop a risk score to assess the prognosis of HCC patients after curative resection. A total of 78 serum samples of HCC patients were analyzed by liquid chromatography-mass spectrometry to characterize the metabolic profiling. A novel network-based feature selection method (NFSM) was developed to define the critical metabolites with the most discriminant capacity to outcomes. The metabolites defined by NFSM was further reduced by Cox regression analysis to generate a prognostic metabolite panel-phenylalanine and choline. Furthermore, univariate and multivariate Cox regression analyses were applied to combine the metabolite panel with the presence of satellite nodes to generate a global prognostic index (GPI) score for overall survival assessment. Compared with the current clinical classification systems, including the Barcelona-clinic liver cancer stage, tumor-node-metastasis stage, and albumin-bilirubin grade, the GPI score presented comparable performance, according to the time-dependent receiver operating characteristic curves and was validated in an independent cohort, which suggested that metabolomics could serve as a helpful tool to stratify the HCC prognostic risk after operation.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/cirurgia , Cromatografia Líquida , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/cirurgia , Espectrometria de Massas , Metabolômica , Prognóstico
18.
Pharm Res ; 37(11): 222, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33067715

RESUMO

AIM: The high doses of oral tacrolimus (TAC) (1,2) necessary to prevent acute rejection (AR) after vascularized composite allotransplantation (VCA) are associated with systemic adverse effects. The skin is the most antigenic tissue in VCA and the primary target of AR. However, the short-term use of topical TAC (Protopic®), as an off-label adjunct to oral TAC, to treat AR episodes pro re nata (PRN), has yielded inconsistent results. There is lack of data on the pharmacokinetics and tissue distribution of topical TAC in VCA, that hampers our understanding of the reasons for unreliable efficacy. Toward this goal, we evaluated the ability of topical TAC to achieve high local tissue concentrations at the site of application with low systemic concentrations. MATERIALS AND METHODS: We assessed the pharmacokinetics and tissue distribution of topical TAC (Protopic®, 0.03%) after single or repeated topical application in comparison to those after systemic delivery in rats. Animals received a single topical application of TAC ointment (Group 1) or an intravenous (IV) injection of TAC (Group 2) at a dose of 0.5 mg/kg. In another experiment, animals received daily topical application of TAC ointment (Group 3), or daily intraperitoneal (IP) injection of TAC (Group 4) at a dose of 0.5 mg/kg for 7 days. TAC concentrations in blood and tissues were analyzed by Liquid Chromatography-Mass Spectrometry (LC/MS-MS). RESULTS: Following single topical administration, TAC was absorbed slowly with a Tmax of 4 h and an absolute bioavailability of 11%. The concentrations of TAC in skin and muscle were several folds higher than whole blood concentrations. Systemic levels remained subtherapeutic (< 3 ng/ml) with repeated once daily applications. CONCLUSION: Topical application of TAC ointment (Protopic®, 0.03%) at a dose of 0.5 mg/kg/day provided high concentrations in the local tissues with low systemic exposure. Repeated topical administration of TAC is well tolerated with no local or systemic adverse effects. This study confirms the feasibility of topical application of TAC for site specific graft immunosuppression and enables future applications in VCA.


Assuntos
Inibidores de Calcineurina/farmacocinética , Aloenxertos Compostos/transplante , Imunossupressores/farmacocinética , Tacrolimo/farmacocinética , Alotransplante de Tecidos Compostos Vascularizados , Administração Tópica , Animais , Inibidores de Calcineurina/administração & dosagem , Inibidores de Calcineurina/sangue , Aloenxertos Compostos/imunologia , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto/efeitos dos fármacos , Imunossupressores/administração & dosagem , Imunossupressores/sangue , Injeções Intravenosas , Masculino , Músculo Esquelético/metabolismo , Estudo de Prova de Conceito , Ratos Endogâmicos Lew , Pele/metabolismo , Tacrolimo/administração & dosagem , Tacrolimo/sangue , Distribuição Tecidual , Alotransplante de Tecidos Compostos Vascularizados/efeitos adversos
19.
J Craniofac Surg ; 31(2): 351-354, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31764551

RESUMO

Titanium mesh was widely used for cranium defect repair but associated with high complication rates. In this study, the authors describe a method using latissimus dorsi-myocutaneous flap in the repair of titanium mesh exposure and scalp defect after cranioplasty, and the plate retaining is also achieved. Fifteen patients from April 2012 to May 2016 underwent this procedure, the age ranged from 32 to 62 years and 47 years old on average, and all the patient had plate exposure combined with surgical site infection and variation of scalp defect. All the patients had fully flap survive, and follow up ranged from 6 months to 24 months, 1 patient had titanium mesh re-expose and received additional operation to remove the plate. The free latissimus dorsi musculocutaneous flap could supply large size of bulky tissue coverage with good blood supply and strong anti-infection ability. This method was an option for retaining the titanium mesh and repairing the exposure for the mild infection with small size scalp defect patient.


Assuntos
Retalho Miocutâneo/cirurgia , Couro Cabeludo/cirurgia , Músculos Superficiais do Dorso/cirurgia , Telas Cirúrgicas , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Crânio/cirurgia , Titânio , Resultado do Tratamento
20.
Sensors (Basel) ; 20(6)2020 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-32235755

RESUMO

The fast estimation of blue-green laser transmission characteristics through the fluctuating sea surface, such as refraction angles and transmittance, is very important to correct operating parameters, detection depth and anti-detection warning in airborne Light Detection and Ranging (LiDAR) applications. However, the geometry of the sea surface is changed by complex environment factors, such as wind and wave, which significantly affect the rapid acquisition of the blue-green laser transmission characteristics. To address this problem, a fast analysis method is provided to rapidly compute the blue-green laser transmittance and refraction angles through the fluctuating sea surface driven by different wind directions and speeds. In the method, a three-dimensional wave model driven by the wind was built to describe the wave spatial distribution varying with time. Using the wave model, the propagation path of the scanning laser footprint was analyzed using the proposed meshing method, thus the transmittance and refraction angles of the optical path can be fast obtained by using parallel computing. The simulation results imply that the proposed method can reduce the time consumption by 70% compared with the traditional analytical method with sequential computing. This paper provides some statistical laws of refraction angles and transmittance through the fluctuating sea surface under different wind conditions, which may serve as a basic for fast computation of airborne LiDAR transmission characteristics in complex environments.

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