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1.
Genome Res ; 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39009472

RESUMO

N 6-Methyladenosine (m6A) is a prevalent and highly regulated RNA modification essential for RNA metabolism and normal brain function. It is particularly important in the hippocampus, where m6A is implicated in neurogenesis and learning. Although extensively studied, its presence in specific cell types remains poorly understood. We investigated m6A in the hippocampus at a single-cell resolution, revealing a comprehensive landscape of m6A modifications within individual cells. Through our analysis, we uncovered transcripts exhibiting a dense m6A profile, notably linked to neurological disorders such as Alzheimer's disease. Our findings suggest a pivotal role of m6A-containing transcripts, particularly in the context of CAMK2A neurons. Overall, this work provides new insights into the molecular mechanisms underlying hippocampal physiology and lays the foundation for future studies investigating the dynamic nature of m6A RNA methylation in the healthy and diseased brain.

2.
Heliyon ; 10(6): e28279, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38545172

RESUMO

Background: Breast cancer (BC) is the primary cause of cancer mortality. Herein, we aimed to establish and verify a prognostic model consisting of endoplasmic reticulum stress and apoptosis related genes (ERAGs) to predict patient survival. Methods: The Cancer Genome Atlas (TCGA) database was used to download gene expression and clinical data to identify the differentially expressed genes (DEGs). Using univariate Cox regression analysis and the Least Absolute Shrinkage and Selection Operator (LASSO)-penalized Cox proportional hazards regression analysis, the prognostic ERAGs were screened. The predictive performance was evaluated using Kaplan-Meier (KM) survival and receiver operating characteristic (ROC) curve analysis. Furthermore, a nomogram model incorporating clinical parameters and risk scores was constructed and subsequently evaluated using ROC and KM analysis. The correlation analysis, mutation analysis, functional enrichment analysis, and immune infiltration analysis were employed to investigate the specific mechanism of ERAGs. We also used Quantitative Real-Time PCR (RT-qPCR) to verify the differential expression of DE-ERAGs between the breast cancer cell line and mammary epithelial cell line. Results: We constructed a prognostic signature comprising 16 ERAGs. ROC, KM analysis and the nomogram model demonstrated high effectiveness in accurately predicting the overall survival (OS) of BRCA patients. The results of these analysis could provide reference for further mechanism exploration. Conclusion: We developed and assessed a novel molecular predictive model for breast cancer that focuses on endoplasmic reticulum stress and apoptosis in this study. It is a valuable complement to the existing prognostic prediction models for breast cancer.

3.
Artigo em Inglês | MEDLINE | ID: mdl-38408007

RESUMO

While inertial measurement unit (IMU)-based motion capture (MoCap) systems have been gaining popularity for human movement analysis, they still suffer from long-term positioning errors due to accumulated drift and inefficient data transmission via Wi-Fi or Bluetooth. To address this problem, this study introduces an integrated ultrawideband (UWB)-IMU system, named UI-MoCap, designed for simultaneous 3D positioning as well as wireless IMU data transmission through UWB pulses. The UI-MoCap comprises mobile UWB tags and hardware-synchronized UWB base stations. Each UWB tag, a compact circular PCB with a 3.4cm diameter, houses a nine-axis IMU unit and a UWB transceiver for data transmission. The base stations are equipped with a UWB transceiver and an Ethernet controller, ensuring efficient reception and management of messages from multiple tags. Experiments were conducted to evaluate the system's validity and reliability of 3D positioning and IMU data transmission. The results demonstrate that UI-MoCap achieves centimeter-level 3D positioning accuracy and maintains consistent positioning performance over time. Moreover, UI-MoCap exhibits high update rates and a minimal packet loss rate for IMU data transmission, significantly outperforming Wi-Fi-based transmission techniques. Future work will explore the fusion of UWB and IMU technologies to further enhance positioning performance, with a focus on human movement analysis and rehabilitation applications.


Assuntos
Captura de Movimento , Movimento , Humanos , Reprodutibilidade dos Testes , Organotiofosfatos
4.
Front Oncol ; 14: 1327319, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38380368

RESUMO

Propose: This meta-analysis aimed to determine whether 3D-printed artificial vertebral bodies (AVBs) have superior clinical efficacy compared to conventional titanium mesh cages (TMCs) for spinal reconstruction after total en bloc spondylectomy (TES) for spinal tumors. Methods: Electronic databases, including PubMed, OVID, ScienceDirect, Embase, CINAHL, Web of Science, Cochrane Library, WANFANG, and CNKI, were searched to identify clinical trials investigating 3D-printed AVB versus conventional TMC from inception to August 2023. Data on the operation time, intraoperative blood loss, preoperative and postoperative visual analogue scale (VAS) scores, preoperative and postoperative Frankel classification of spinal cord injury, vertebral body subsidence, and early complications were collected from eligible studies for a meta-analysis. Data were analyzed using Review Manager 5.4 and Stata 14.0. Results: Nine studies assessing 374 patients were included. The results revealed significant differences between the 3D-printed AVB and conventional TMC groups with regard to operation time (P = 0.04), intraoperative blood loss (P = 0.004), postoperative VAS score (P = 0.02), vertebral body subsidence (P < 0.0001), and early complications (P = 0.02). Conversely, the remaining preoperative VAS score and Frankel classifications (pre-and postoperative) did not differ significantly between the groups. Conclusion: The 3D-printed AVB in spinal reconstruction after TES for spinal tumors has the advantages of a short operative time, little intraoperative blood loss, weak postoperative pain, low occurrence of vertebral body subsidence and early complications, and a significant curative effect. This could provide a strong basis for physicians to make clinical decisions. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023441521, identifier CRD42023441521.

6.
J Arthroplasty ; 39(1): 229-235.e4, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37557968

RESUMO

BACKGROUND: Accurate diagnosis of the periprosthetic joint infection (PJI) remains a challenge for surgeons. The purpose of this study was to assess the value of albumin to globulin ratio (AGR) and globulin (GLB) for diagnosing PJI. METHODS: A total of 182 patients undergoing revision after arthroplasty were included and divided into 2 groups, 61 in knee group (PJI: 38; non-PJI: 23) and 121 in hip group (PJI: 26; non-PJI: 95). We used receiver operating characteristic curves to determine the diagnostic value of AGR, GLB, inflammatory markers (erythrocyte sedimentation rate [ESR] and C-reactive protein [CRP]). RESULTS: The receiver operating characteristic curves showed the areas under the curve of AGR, GLB, ESR, and CRP in the knee group were 0.940, 0.928, 0.867, and 0.848, respectively, and they were 0.855, 0.831, 0.886, and 0.912 in the hip group. The optimal predictive cut-off values for AGR in knee and hip groups were 1.375 and 1.295, respectively. The sensitivity and specificity of AGR, respectively, were 94.7% and 87.0% (knee group) and 84.6% and 75.8% (hip group) for diagnosing PJI. The sensitivity of "AGR or ESR" and specificity of "AGR and GLB" in the knee group were 99.6% and 98.9%, respectively. CONCLUSION: For knee or hip groups, the AGR exhibits good value for the diagnosis of PJI comparable with ESR and CRP. The AGR and GLB, together with CRP and ESR, should be used as the preferred indicators for diagnosing PJI. The "AGR or ESR" and "AGR and GLB" in the knee group have an excellent diagnostic value in sensitivity and specificity, respectively.


Assuntos
Artrite Infecciosa , Artroplastia de Quadril , Artroplastia do Joelho , Globulinas , Infecções Relacionadas à Prótese , Humanos , Estudos Retrospectivos , Biomarcadores , Infecções Relacionadas à Prótese/diagnóstico , Infecções Relacionadas à Prótese/cirurgia , Artroplastia de Quadril/efeitos adversos , Artroplastia do Joelho/efeitos adversos , Proteína C-Reativa/análise , Artrite Infecciosa/cirurgia , Sensibilidade e Especificidade , Sedimentação Sanguínea
7.
Anal Chem ; 95(30): 11236-11242, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37467354

RESUMO

Controllable self-assembly of the DNA-linked gold nanoparticle (AuNP) architecture for in vivo biomedical applications remains a key challenge. Here, we describe the use of the programmed DNA tetrahedral structure to control the assembly of three different types of AuNPs (∼20, 10, and 5 nm) by organizing them into defined positioning and arrangement. A DNA-assembled "core-satellite" architecture is built by DNA sequencing where satellite AuNPs (10 and 5 nm) surround a central core AuNP (20 nm). The density and arrangement of the AuNP satellites around the core AuNP were controlled by tuning the size and amount of the DNA tetrahedron functionalized on the core AuNPs, resulting in strong electromagnetic field enhancement derived from hybridized plasmonic coupling effects. By conjugating with the Raman molecule, strong surface-enhanced Raman scattering photoacoustic imaging signals could be generated, which were able to image microRNA-21 and tumor tissues in vivo. These results provided an efficient strategy to build precision plasmonic superstructures in plasmonic-based bioanalysis and imaging.


Assuntos
Nanopartículas Metálicas , MicroRNAs , Nanoestruturas , Neoplasias , Técnicas Fotoacústicas , Humanos , Ouro/química , Nanopartículas Metálicas/química , Análise Espectral Raman/métodos , DNA/química , Neoplasias/diagnóstico por imagem
8.
Gait Posture ; 104: 58-69, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37321113

RESUMO

PURPOSE: This meta-analysis was performed to compare the spatiotemporal, kinematic, and kinetic gait characteristics during level walking between total knee arthroplasty (TKA) and unicompartmental knee arthroplasty (UKA). METHODS: An electronic database literature search was performed to screen clinical trials which were included the studies evaluating not only spatiotemporal, kinematic, and kinetic gait parameters, but also knee range of motion and knee score (Knee Society Score and Oxford Knee Score, i.e., KSS and OKS). The data analysis was performed using statistical software Stata 14.0 and Review Manager 5.4. RESULTS: Thirteen studies (369 knees) that met the criteria were eventually included in this meta-analysis. The results revealed significant differences between UKA and TKA with regard to walking speed (P = 0.04), stride length (P = 0.02), maximum knee flexion at loading (P = 0.001), the 1st peak of vert-GRF (P = 0.006), the 1st valley of vert-GRF (P = 0.007), knee internal rotational moment (P = 0.04), knee extension (P < 0.00001), and KSS Function score (P = 0.05). In contrast, there were no statistical differences in the remaining spatiotemporal, kinematic, and kinetic gait parameters. CONCLUSION: Medial UKA design is superior to TKA design with regard to walking speed, stride length, maximum knee flexion at loading, the 1st peak and the 1st valley of vert-GRF, knee internal rotational moment, knee extension, and KSS Function score. And it could provide a stronger basis for physicians to make clinical decisions.


Assuntos
Artroplastia do Joelho , Osteoartrite do Joelho , Humanos , Artroplastia do Joelho/métodos , Fenômenos Biomecânicos , Marcha , Caminhada , Articulação do Joelho , Amplitude de Movimento Articular , Osteoartrite do Joelho/cirurgia , Resultado do Tratamento
9.
Biol Pharm Bull ; 46(6): 864-868, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37258152

RESUMO

Dysfunction of lung microvascular endothelium is a major feature in the pathobiology of pulmonary edema and hypoxic respiratory failure. Histamine induces lung microvascular endothelial barrier disruption and hyperpermeability upon evoking intracellular Ca2+ ([Ca2+]i) dynamics via binding to its receptors. Transient receptor potential canonical (TRPC) channels are Ca2+-permeable channel and stimulated by the agonists of G-protein-coupled receptors (GPCR). Here, we assessed histamine induced [Ca2+]i increases in human lung microvascular endothelial cells (HLMVEC) by using live cell Ca2+ imaging. We found that histamine increased [Ca2+]i was maintained at a static elevated level after a transient peak. The elevated Ca2+ plateau was vanished when extracellular Ca2+ was removed, indicating Ca2+ influx from extracellular mediated the histamine-induced Ca2+ plateau. TRPC4/5 channels antagonists, ML204 (10 µM) and HC070 (1 µM), significantly inhibited the Ca2+ plateaus, which was not influenced by Pyr3 or larixyl, the antagonists of TRPC3/6. Furthermore, ML204 or HC070 effectively suppressed the permeability response to histamine in HLMVEC. Our results indicated that histamine-induced Ca2+ influx may be mediated by TRPC4/5 channels and the antagonist of the channel significantly improved histamine-induced HLMVEC dysfunction.


Assuntos
Células Endoteliais , Canais de Potencial de Receptor Transitório , Humanos , Células Endoteliais/metabolismo , Histamina/farmacologia , Histamina/metabolismo , Canais de Cátion TRPC , Canais de Potencial de Receptor Transitório/metabolismo , Pulmão , Cálcio/metabolismo
10.
ACS Appl Mater Interfaces ; 15(19): 22977-22984, 2023 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-37145038

RESUMO

The principal hallmark of Alzheimer's disease (AD) is neuron mitochondrial dysfunction, whereas mitochondrial miRNAs potentially play important roles. Nevertheless, efficacious mitochondria organelle therapeutic agents for treatment and management of AD are highly advisable. Herein, we report a multifunctional DNA tetrahedron-based mitochondria-targeted therapeutic platform, termed tetrahedral DNA framework-based nanoparticles (TDFNs), which was modified with triphenylphosphine (TPP) for mitochondria-targeting, cholesterol (Chol) for crossing the central nervous system, and functional antisense oligonucleotide (ASO) for both AD diagnosis and gene silencing therapy. After injecting intravenously through the tail vein of 3 × Tg-AD model mice, TDFNs can both easily cross the blood brain barrier and accurately arrive at the mitochondria. The functional ASO could not only be detected via the fluorescence signal for diagnosis but also mediate the apoptosis pathway through knocking miRNA-34a down, leading to recovery of the neuron cells. The superior performance of TDFNs suggests the great potential in mitochondria organelle therapeutics.


Assuntos
Doença de Alzheimer , MicroRNAs , Camundongos , Animais , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Mitocôndrias/metabolismo , Neurônios/metabolismo , DNA Mitocondrial/metabolismo
11.
Adv Healthc Mater ; 12(20): e2202986, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-36943933

RESUMO

Mitochondria-targeted therapeutics are an attractive approach against energy-dependent cancer. However, effective mitochondria organelle therapeutics agents are still highly desirable. Herein, a mitochondria-targeted therapeutics platform, termed CDM@MUiO-DP@MCHM, consisting of macrophages-cancer hybrid membrane (MCHM) encapsulated MUiO-66 metal-organic frameworks (MOFs) is reported, which is loaded with microRNA (miRNA) biomarker detection probe (DP) for cancer diagnosis and copper-depleting moiety (CDM) for mitochondrial copper depletion to suppress cancer growth. Using nude mice bearing MCF-7 as model, after injecting intravenously via the caudal vein of mice, the encapsulation of MCHM can not only greatly enhance the cancer homing-targeting ability of the nanoparticles (NPs) but also endows the NPs the immune escape capacity to extend the circulation time. The miRNA-21 biomarker can be detected by the fluorescence signal for diagnosis, while the CDM induced energy deficiency and compromised mitochondria membrane potential, leading to apoptosis of the cancer cell. The good performance of CDM@MUiO-DP@MCHM suggest the great potential mitochondria organelle therapeutics.


Assuntos
Estruturas Metalorgânicas , MicroRNAs , Nanopartículas , Neoplasias , Animais , Camundongos , Cobre/farmacologia , Camundongos Nus , Neoplasias/tratamento farmacológico , Mitocôndrias , MicroRNAs/farmacologia
12.
Comput Biol Med ; 158: 106813, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36966553

RESUMO

The correction accuracy of an external fixator is crucial to the treatment outcome of deformity correction and patient safety. In this study, the mapping model is established between the pose error and kinematic parameter error of the motor-driven parallel external fixator (MD-PEF). Subsequently, the kinematic parameter identification and error compensation algorithm of the external fixator is established based on the least squares method. An experimental platform based on the developed MD-PEF and Vicon motion capture system is constructed for kinematic calibration experiments. Experimental results show that the correction accuracy of the MD-PEF after calibration is as follows: translation accuracy dE1 = 0.36 mm, axial translation accuracy dE2 = 0.25 mm, angulation accuracy dE3 = 0.27°, and rotation accuracy dE4 = 0.2°. The accuracy detection experiment verifies the kinematic calibration results, which further validates the feasibility and reliability of the error identification and compensation algorithm constructed by the least squares method. The calibration approach used in this work also provides an effective way to improve the accuracy of other medical robots.


Assuntos
Fixadores Externos , Tíbia , Humanos , Fenômenos Biomecânicos , Reprodutibilidade dos Testes , Tíbia/cirurgia , Resultado do Tratamento
13.
Int J Med Robot ; 19(3): e2502, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36705096

RESUMO

BACKGROUND: The use of external fixators to treat foot and ankle deformities remains a challenge in orthopedic surgery due to their diversity. We hope to improve the automation and accuracy of the correction process. METHODS: A three-degree-of-freedom (3-DOF) electromotor-driven external fixator for uniplanar foot and ankle deformities was proposed. Computer-assisted correction software was developed to help surgeons use digital technology to measure the required parameters from patients' X-ray radiographs. The correction trajectory and the prescriptions were generated in the software based on the proposed correction strategy. RESULTS: Two clinical cases were simulated to verify the correction ability of the developed external fixator. The results showed that the angular and displacement deformities were well corrected. CONCLUSIONS: The developed external fixator can accurately and automatically correct foot and ankle deformities with the help of computer-assisted correction software, which significantly reduces the burden on surgeons and patients.


Assuntos
Tornozelo , Procedimentos Ortopédicos , Humanos , Tornozelo/diagnóstico por imagem , Tornozelo/cirurgia , Raios X , Articulação do Tornozelo/cirurgia , Fixadores Externos , Procedimentos Ortopédicos/métodos
14.
Chin J Cancer Res ; 35(6): 675-685, 2023 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-38204443

RESUMO

Objective: Cervical squamous intraepithelial lesion (SIL) and cervical cancer are major threats to females' health and life in China, and we aimed to estimate the economic burden associated with their diagnosis and treatment. Methods: A nationwide multicenter, cross-sectional, hospital-based survey was conducted in 26 qualified hospitals across seven administrative regions of China. We investigated females who had been pathologically diagnosed with SIL and cervical cancer, and included five disease courses ("diagnosis", "initial treatment", "chemoradiotherapy", "follow-up" and "recurrence/progression/metastasis") to estimate the total costs. The median and interquartile range (IQR) of total costs (including direct medical, direct non-medical, and indirect costs), reimbursement rate by medical insurance, and catastrophic health expenditures in every clinical stage were calculated. Results: A total of 3,471 patients in different clinical stages were analyzed, including low-grade SIL (LSIL) (n=549), high-grade SIL (HSIL) (n=803), cervical cancer stage IA (n=226), IB (n=610), IIA (n=487), IIB (n=282), III (n=452) and IV (n=62). In urban areas, the estimated total costs of LSIL and HSIL were [Formula: see text]1,637.7 (IQR: [Formula: see text]956.4-[Formula: see text]2,669.2) and [Formula: see text]2,467.1 (IQR: [Formula: see text]1,579.1-[Formula: see text]3,762.3), while in rural areas the costs were [Formula: see text]459.0 (IQR: [Formula: see text]167.7-[Formula: see text]1,330.3) and [Formula: see text]1,230.5 (IQR: [Formula: see text]560.6-[Formula: see text]2,104.5), respectively. For patients with cervical cancer stage IA, IB, IIA, IIB, and III-IV, the total costs were [Formula: see text]15,034.9 (IQR: [Formula: see text]11,083.4-[Formula: see text]21,632.4), [Formula: see text]19,438.6 (IQR: [Formula: see text]14,060.0-[Formula: see text]26,505.9), [Formula: see text]22,968.8 (IQR: [Formula: see text]16,068.8-[Formula: see text]34,615.9), [Formula: see text]26,936.0 (IQR: [Formula: see text]18,176.6-[Formula: see text]41,386.0) and [Formula: see text]27,332.6 (IQR: [Formula: see text]17,538.7-[Formula: see text]44,897.0), respectively. Medical insurance covered 43%-55% of direct medical costs for cervical cancer patients, while the coverage for SIL patients was 19%-43%. For most cervical cancer patients, the expense was catastrophic, and the extent of catastrophic health expenditure was about twice large for rural patients than that for urban patients in each stage. Conclusions: The economic burden of SIL and cervical cancer in China is substantial, with a significant proportion of the costs being avoidable for patients with LSIL. Even for those with medical insurance, catastrophic health expenditures are also a major concern for patients with cervical cancer, particularly for those living in rural areas.

15.
J Healthc Eng ; 2022: 4125606, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36337379

RESUMO

End-effector type upper limb rehabilitation robots (ULRRs) are connected to patients at one distal point, making them have simple structures and less complex control algorithms, and they can avoid abnormal motion and posture of the target anatomical joints and specific muscles. Given that the end-effector type ULRR focuses more on the rehabilitation of the combined motion of upper limb chain, assisting the patient to perform collaborative tasks, and its intervention has some advantages than the exoskeleton type ULRR, we developed a novel three-degree-of-freedom (DOF) end-effector type ULRR. The advantage of the mechanical design is that the designed end-effector type ULRR can achieve three DOFs by using a four-bar mechanism and a lifting mechanism; we also developed the patient-specific exercises including patient-passive exercise and patient-cooperative exercise, and the advantage of the developed patient-cooperative exercise is that we simplified the human-robot coupling system model into a single spring system instead of the mass-spring-damp system, which efficiently improved the response speed of the control system. In terms of the organization structure of the work, we introduced the end-effector type ULRR's mechanical design, control system, inverse solution of positions, patient-passive exercise based on the inverse solution of positions and the linear position interpolation of servo drives, and patient-cooperative exercise based on the spring model, in sequence. Experiments with three healthy subjects have been conducted, with results showing good trajectory tracking performance in patient-passive exercise and showing effective, flexible, and good real-time interactive performance in patient-cooperative exercise.


Assuntos
Exoesqueleto Energizado , Robótica , Reabilitação do Acidente Vascular Cerebral , Humanos , Robótica/métodos , Extremidade Superior/fisiologia , Terapia por Exercício/métodos , Postura , Reabilitação do Acidente Vascular Cerebral/métodos
16.
Front Med (Lausanne) ; 9: 951115, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35957855

RESUMO

Coronavirus disease 2019 (COVID-19) caused by coronavirus-2 (SARS-CoV-2) infection has rapidly spread throughout the world and become a major threat to human beings. Cytokine storm is a major cause of death in severe patients. Abatacept can suppress cytokines used as antirheumatic drugs in clinical applications. This study analyzed the molecular mechanisms of abatacept treatment for COVID-19. Differentially expressed genes (DEGs) were identified by analyzing expression profiling of abatacept treatment for rheumatoid arthritis (RA) patients and SARS-CoV-2 infection patients. We found that 59 DEGs were upregulated in COVID-19 patients and downregulated following abatacept treatment. Gene set enrichment analysis (GSEA) and Gene Ontology (GO) analysis showed that immune and inflammatory responses were potential regulatory mechanisms. Moreover, we verified 8 targeting genes and identified 15 potential drug candidates for the treatment of COVID-19. Our study illustrated that abatacept could be a promising property for preventing severe COVID-19, and we predicted alternative potential drugs for the treatment of SARS-CoV-2 infection.

17.
ACS Appl Mater Interfaces ; 14(26): 29599-29612, 2022 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-35737456

RESUMO

Aggregation-induced emission (AIE)-active luminogens (AIEgens) have demonstrated exciting potential for the application in cancer phototheranostics. However, simultaneously achieving tumor-activated bright emission, enhanced reactive oxygen species (ROS) generation, high tumor accumulation, and minimized ROS depletion remains challenging. Here, a metal-organic framework (MOF) hybrid AIEgen theranostic platform is designed, termed A-NUiO@DCDA@ZIF-Cu, composed of an AIEgen-loaded hydrophobic UiO-66 (A-NUiO@DCDA) core and a Cu-doped hydrophilic ZIF-8 (ZIF-Cu) shell. The fluorescence emission and therapeutic ROS activity of AIEgens are restrained during delivery. After uptake by tumor tissues, ZIF-Cu decomposition occurs in response to an acidic tumor microenvironment (TME), and the hydrophobic A-NUiO@DCDA cores self-assemble into large particles, extremely increasing the tumor accumulation of AIEgens. This results in enhanced fluorescence imaging (FLI) and highly improved 1O2 generation ability during photodynamic therapy (PDT). Meanwhile, the released Cu2+ reacts to glutathione (GSH) to generate Cu+, which provides an extra chemodynamic therapy (CDT) function through Fenton-like reactions with overexpressed H2O2, resulting in the GSH depletion-enhanced ROS therapy. As a result of these characteristics, the MOF hybrid AIEgens can selectively kill tumors with excellent efficacy.


Assuntos
Estruturas Metalorgânicas , Neoplasias , Fotoquimioterapia , Linhagem Celular Tumoral , Glutationa , Humanos , Peróxido de Hidrogênio , Estruturas Metalorgânicas/farmacologia , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/química , Ácidos Ftálicos , Espécies Reativas de Oxigênio , Microambiente Tumoral
18.
J Orthop Surg Res ; 17(1): 152, 2022 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-35264236

RESUMO

BACKGROUND: To compare the gait patterns between posterior cruciate retention and substitution in total knee arthroplasty (TKA). METHODS: Electronic databases including the PubMed, Embase, CINAHL, Web of Science, and Cochrane databases were searched to identify clinical trials investigating posterior cruciate retention versus substitution in TKA. The outcome measurements were the kinematic gait parameters (flexion at heel strike, maximum flexion during loading response, flexion range during loading, minimal flexion at terminal stance, maximal flexion at the swing, and total flexion during the gait cycle), Knee Society Score (KSS), knee flexion, knee extension, and walking speed. Statistical software Review Manager 5.4 and Stata 14.0 were used for data analysis. RESULTS: There were finally 9 studies included in this meta-analysis. The results did not reveal differences between posterior cruciate retention (CR) and posterior cruciate substitution (PS) groups in TKA, in terms of kinematic gait parameters, knee extension, walking speed, and KSS. However, the PS group had a significantly larger knee flexion angle than that in the CR group [weighted mean difference = - 3.20, 95% CI - 6.13 to - 0.28, P = 0.03]. CONCLUSION: Both the posterior cruciate retention and posterior cruciate substitution lead to obvious improvements in patient function and have their advantages in getting a good cup position. The PS design is significantly better on the knee flexion, while there are no statistical differences in kinematic gait parameters and outcome scores between them. This might indicate that surgeons do not necessarily need a PS design to substitute the posterior cruciate ligament during TKA.


Assuntos
Artroplastia do Joelho/métodos , Marcha/fisiologia , Osteoartrite do Joelho/cirurgia , Reconstrução do Ligamento Cruzado Posterior/métodos , Ligamento Cruzado Posterior , Fenômenos Biomecânicos , Humanos , Articulação do Joelho/fisiopatologia , Articulação do Joelho/cirurgia , Prótese do Joelho , Amplitude de Movimento Articular/fisiologia
19.
J Biomech Eng ; 144(7)2022 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-35079773

RESUMO

Pre-operative correction trajectory planning is one of the important aspects of deformity correction. Avoidance of limb-frame interference is essential to verify the implementability of the preplanned correction trajectory, as well as to maintain the continuity and security of the correction strategy. In this study, a novel interference inspection algorithm is developed to investigate the interaction of the limb and hexapod frame in the treatment of lower limb deformities. The algorithm is built on a minimum distance model of the cone frustum busbar and cylindrical axis using vector analysis. A predefined trajectory is generated by Cartesian coordinate path control. Subsequently, an interference case is performed through numerical simulation and motion simulation. The results show that the conclusion of numerical simulation and motion simulation is consistent, which prove the feasibility of the algorithm. The results also show that it is possible to identify the riskiest struts, which are prone to interfere with the limb, and the riskiest positions. The proposed algorithm can support the clinician in selecting the suitable frame configuration to avoid interference. The algorithm solves the problem that the interference can only be judged by clinical observation in the clinic.


Assuntos
Algoritmos , Fixadores Externos , Simulação por Computador , Extremidade Inferior , Cone de Plantas
20.
Medicine (Baltimore) ; 100(28): e26632, 2021 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-34260555

RESUMO

ABSTRACT: BCL7B plays a potential role in the progression of various cancers, while its role in sarcomas is unknown. We aimed to evaluate BCL7B's diagnostic and prognostic value, and potential BCL7B-related mechanisms in sarcomas based on The Cancer Genome Atlas (TCGA) database. We collected patients with sarcoma from TCGA. Wilcoxon rank sum test was used to compare the expression of BCL7B in sarcoma samples with different clinical-pathologic features. Univariate Cox regression analysis and multivariate Cox regression analysis were used to evaluate prognosis factors for sarcoma. Gene set enrichment analysis (GSEA) was conducted to elucidate the significant functions and pathways associated with BCL7B. BCL7B was a potential biomarker for distinguishing normal and tumor tissues with the analysis of ROC curve (AUC = 0.588). Low BCL7B expression was significantly correlated with tumor multifocal (OR = 0.39 for yes vs no), larger residual tumor (OR = 0.40 for R1,R2 vs RO), male gender (OR = 0.48 for male vs female) and White race (OR = 0.29 for White vs Asian, Black or African American). High BCL7B expression was correlated with leiomyosarcoma histological type (OR = 6.08 for leiomyosarcoma vs dedifferentiated liposarcoma, pleomorphic sarcoma). Univariate and multivariate Cox regression analysis showed that low BCL7B expression was independently associated with poor overall survival (P = .008). GSEA showed that GPCR (G protein-coupled receptors) ligand binding, secreted factors, class A1 rhodopsin-like receptors, extracellular matrix organization, core matrisome, Fc epsilon receptor I mediated NF-κB activation, and WNT signaling pathway were differentially enriched in BCL7B low expression phenotype (|NES| > 1, adjusted P value <.05, and FDR value <0.25). BCL7B may play an important role in sarcoma progression and may be a potential biomarker for prognosis and diagnosis in sarcomas.


Assuntos
Proteínas/genética , Sarcoma/genética , Sarcoma/patologia , Idoso , Biomarcadores Tumorais , Biologia Computacional , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Grupos Raciais , Análise de Regressão , Sarcoma/diagnóstico , Fatores Sexuais
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