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1.
Nat Chem Biol ; 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38720107

RESUMO

Whether stem-cell-like cancer cells avert ferroptosis to mediate therapy resistance remains unclear. In this study, using a soft fibrin gel culture system, we found that tumor-repopulating cells (TRCs) with stem-cell-like cancer cell characteristics resist chemotherapy and radiotherapy by decreasing ferroptosis sensitivity. Mechanistically, through quantitative mass spectrometry and lipidomic analysis, we determined that mitochondria metabolic kinase PCK2 phosphorylates and activates ACSL4 to drive ferroptosis-associated phospholipid remodeling. TRCs downregulate the PCK2 expression to confer themselves on a structural ferroptosis-resistant state. Notably, in addition to confirming the role of PCK2-pACSL4(T679) in multiple preclinical models, we discovered that higher PCK2 and pACSL4(T679) levels are correlated with better response to chemotherapy and radiotherapy as well as lower distant metastasis in nasopharyngeal carcinoma cohorts.

2.
Proc Natl Acad Sci U S A ; 120(23): e2220927120, 2023 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-37252951

RESUMO

We report analytical and numerical investigations of subion-scale turbulence in low-beta plasmas using a rigorous reduced kinetic model. We show that efficient electron heating occurs and is primarily due to Landau damping of kinetic Alfvén waves, as opposed to Ohmic dissipation. This collisionless damping is facilitated by the local weakening of advective nonlinearities and the ensuing unimpeded phase mixing near intermittent current sheets, where free energy concentrates. The linearly damped energy of electromagnetic fluctuations at each scale explains the steepening of their energy spectrum with respect to a fluid model where such damping is excluded (i.e., a model that imposes an isothermal electron closure). The use of a Hermite polynomial representation to express the velocity-space dependence of the electron distribution function enables us to obtain an analytical, lowest-order solution for the Hermite moments of the distribution, which is borne out by numerical simulations.

3.
J Cell Mol Med ; 28(11): e18442, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38842135

RESUMO

Epithelial-mesenchymal transition (EMT) and its reversal process are important potential mechanisms in the development of HCC. Selaginella doederleinii Hieron is widely used in Traditional Chinese Medicine for the treatment of various tumours and Amentoflavone is its main active ingredient. This study investigates the mechanism of action of Amentoflavone on EMT in hepatocellular carcinoma from the perspective of bioinformatics and network pharmacology. Bioinformatics was used to screen Amentoflavone-regulated EMT genes that are closely related to the prognosis of HCC, and a molecular prediction model was established to assess the prognosis of HCC. The network pharmacology was used to predict the pathway axis regulated by Amentoflavone. Molecular docking of Amentoflavone with corresponding targets was performed. Detection and evaluation of the effects of Amentoflavone on cell proliferation, migration, invasion and apoptosis by CCK-8 kit, wound healing assay, Transwell assay and annexin V-FITC/propidium iodide staining. Eventually three core genes were screened, inculding NR1I2, CDK1 and CHEK1. A total of 590 GO enrichment entries were obtained, and five enrichment results were obtained by KEGG pathway analysis. Genes were mainly enriched in the p53 signalling pathway. The outcomes derived from both the wound healing assay and Transwell assay demonstrated significant inhibition of migration and invasion in HCC cells upon exposure to different concentrations of Amentoflavone. The results of Annexin V-FITC/PI staining assay showed that different concentrations of Amentoflavone induces apoptosis in HCC cells. This study revealed that the mechanism of Amentoflavone reverses EMT in hepatocellular carcinoma, possibly by inhibiting the expression of core genes and blocking the p53 signalling pathway axis to inhibit the migration and invasion of HCC cells.


Assuntos
Apoptose , Biflavonoides , Carcinoma Hepatocelular , Movimento Celular , Proliferação de Células , Transição Epitelial-Mesenquimal , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas , Transdução de Sinais , Proteína Supressora de Tumor p53 , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Biflavonoides/farmacologia , Proteína Supressora de Tumor p53/metabolismo , Proteína Supressora de Tumor p53/genética , Transdução de Sinais/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Linhagem Celular Tumoral , Simulação de Acoplamento Molecular , Biologia Computacional/métodos
4.
Brief Bioinform ; 23(1)2022 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-34889446

RESUMO

In biomedical networks, molecular associations are important to understand biological processes and functions. Many computational methods, such as link prediction methods based on graph neural networks (GNNs), have been successfully applied in discovering molecular relationships with biological significance. However, it remains a challenge to explore a method that relies on representation learning of links for accurately predicting molecular associations. In this paper, we present a novel GNN based on link representation (LR-GNN) to identify potential molecular associations. LR-GNN applies a graph convolutional network (GCN)-encoder to obtain node embedding. To represent associations between molecules, we design a propagation rule that captures the node embedding of each GCN-encoder layer to construct the LR. Furthermore, the LRs of all layers are fused in output by a designed layer-wise fusing rule, which enables LR-GNN to output more accurate results. Experiments on four biomedical network data, including lncRNA-disease association, miRNA-disease association, protein-protein interaction and drug-drug interaction, show that LR-GNN outperforms state-of-the-art methods and achieves robust performance. Case studies are also presented on two datasets to verify the ability to predict unknown associations. Finally, we validate the effectiveness of the LR by visualization.


Assuntos
Biologia Computacional/métodos , Redes Neurais de Computação , Algoritmos , Tecnologia Biomédica/métodos , Comunicação Celular , Aprendizado Profundo , Interações Medicamentosas , Humanos , MicroRNAs , Domínios e Motivos de Interação entre Proteínas , RNA Longo não Codificante , Projetos de Pesquisa
5.
Exp Eye Res ; 241: 109856, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38479725

RESUMO

Rhodopsin-mediated autosomal dominant retinitis pigmentosa (RHO-adRP) causes progressive vision loss and is potentially incurable, accounting for 25% of adRP cases. Studies on RHO-adRP mechanism were at large based on the biochemical and cellular properties, especially class-3. Nonetheless, the absence of an appropriate model for class-3 RHO-adRP has impeded comprehensive exploration. Here, induced pluripotent stem cells (iPSCs) were generated from a healthy control and two sibling RP patients with the same point mutation, c.403C>T (p.R135W). The first three-dimensional (3D) retinal organoid model of a class-3 RHO point mutation from patient-derived iPSCs was generated. Significant defects were observed in rod photoreceptors in terms of localization, morphology, transcriptional profiling and single cell resolution, to better understand the human disease resulting from RHO mutations from a developmental perspective. This first human model of class-3 RHO-adRP provides a representation of patient's retina in vitro and displays features of RHO-adRP retinal organoids relevant for therapeutic development.


Assuntos
Retina , Retinose Pigmentar , Humanos , Retinose Pigmentar/genética , Mutação , Rodopsina/genética , Organoides
6.
Chem Res Toxicol ; 37(6): 957-967, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38771128

RESUMO

Lung cancer is the main cause of cancer deaths around the world. Nitrosamine 4-(methyl nitrosamine)-1-(3-pyridyl)-1-butanone (NNK) is a tobacco-specific carcinogen of lung cancer. Abundant evidence implicates long noncoding RNAs (lncRNAs) in tumorigenesis. Yet, the effects and mechanisms of lncRNAs in NNK-induced carcinogenesis are still unclear. In this study, we discovered that NNK-induced transformed Beas-2B cells (Beas-2B-NNK) showed increased cell migration and proliferation while decreasing rates of apoptosis. RNA sequencing and differentially expressed lncRNAs analyses showed that lncRNA PSMB8-AS1 was obviously upregulated. Interestingly, silencing the lncRNA PSMB8-AS1 in Beas-2B-NNK cells reduced cell proliferation and migration and produced cell cycle arrest in the G2/M phase along with a decrease in CDK1 expression. Conclusively, our results demonstrate that lncRNA PSMB8-AS1 could promote the malignant characteristics of Beas-2B-NNK cells by regulating CDK1 and affecting the cell cycle, suggesting that it may supply a new prospective epigenetic mechanism for lung cancer.


Assuntos
Brônquios , Carcinógenos , Ciclo Celular , Proliferação de Células , Células Epiteliais , Nicotiana , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Brônquios/citologia , Brônquios/patologia , Brônquios/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Nicotiana/efeitos adversos , Ciclo Celular/efeitos dos fármacos , Carcinógenos/toxicidade , Nitrosaminas/toxicidade , Linhagem Celular , Movimento Celular/efeitos dos fármacos
7.
Langmuir ; 40(22): 11491-11503, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38770578

RESUMO

Foam flooding is an important tool for reservoir development. This study aims to further investigate the interaction between stimulus-responsive wormlike micelle (WLM)-CO2 foams and crude oil. We performed micromorphology experiments as our major studies and used molecular dynamics simulations as an auxiliary tool for interfacial analysis. We utilized foam generation, liquid separation, and defoaming as the entry points of experimental research and energy as the quantitative assessment index to investigate the dynamic process of the action of different oil contents and oil phase types in a DOAPA@NaSal-H+ foam system. We also examined the role of NaSal in the generation and development of the foam system. Results indicated that the law of crude oil's effect on foam could be summarized as "low contents are beneficial and high contents are harmful." In addition, although the DOAPA@NaSal-H+ foam system has high compatibility for saturated and aromatic hydrocarbons, it is highly suitable for application in reservoir environments with relatively high asphaltene and resin contents. Through combined experimental and simulation approaches, we clarified the law governing the stability of the DOAPA@NaSal-H+ foam system in different oil-containing environments, identified the key role of NaSal, and provided a reference for the targeted application of the DOAPA@NaSal-H+ foam system in different oil reservoirs.

8.
World J Urol ; 42(1): 454, 2024 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-39073634

RESUMO

BACKGROUND: The morphology of tumor thrombus varies from person to person and it may affect surgical methods and tumor prognosis. However, studies on the morphology of tumor thrombus are limited. The purpose of our study was to evaluate the impact of tumor thrombus morphology on surgical complexity. METHODS: We retrospectively reviewed the clinical data of 229 patients with renal cell carcinoma combined with inferior vena cava (IVC) tumor thrombus who underwent surgical treatment at Peking University Third Hospital between January 2014 and December 2021. The patients were divided into floating morphology (107 patients) and filled morphology (122 patients) tumor thrombi groups. Chi-square and Mann-Whitney U tests were used for categorical and continuous variables, respectively. Postoperative complications were evaluated using the Clavien-Dindo surgical complication classification method. RESULTS: Patients with filled morphology tumor thrombus required more surgical techniques than those with floating morphology tumor thrombus, which was reflected in more open surgeries (P < 0.001), more IVC interruptions (P <0.001), lesser use of the delayed occlusion of the proximal inferior vena cava (DOPI) technique (P < 0.001), and a greater need for cut-off of the short hepatic vein (P < 0.001) and liver dissociation (P = 0.001). Filled morphology significantly increased the difficulty of surgery in patients with renal cell carcinoma with tumor thrombus, reflected in longer operation time (P < 0.001), more surgical blood loss (P <0.001), more intra-operative blood transfusion (P < 0.001), and longer postoperative hospital stay (P < 0.001). Filled morphology tumor thrombus also led to more postoperative complications (53% vs. 20%; P < 0.001). CONCLUSION: Compared with floating morphology thrombus, filled morphology thrombus significantly increased the difficulty of surgery in patients with renal cell carcinoma with IVC tumor thrombus.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Células Neoplásicas Circulantes , Veia Cava Inferior , Trombose Venosa , Humanos , Carcinoma de Células Renais/cirurgia , Carcinoma de Células Renais/patologia , Neoplasias Renais/cirurgia , Neoplasias Renais/patologia , Veia Cava Inferior/patologia , Veia Cava Inferior/cirurgia , Feminino , Masculino , Estudos Retrospectivos , Pessoa de Meia-Idade , China/epidemiologia , Células Neoplásicas Circulantes/patologia , Trombose Venosa/patologia , Trombose Venosa/cirurgia , Idoso , Nefrectomia/métodos , Complicações Pós-Operatórias/epidemiologia , Adulto
9.
Environ Res ; 252(Pt 1): 118881, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38582430

RESUMO

Nitrate reduction in bio-electrochemical systems (BESs) has attracted wide attention due to its low sludge yields and cost-efficiency advantages. However, the high resistance of traditional electrodes is considered to limit the denitrification performance of BESs. Herein, a new graphene/polypyrrole (rGO/PPy) modified electrode is fabricated via one-step electrodeposition and used as cathode in BES for improving nitrate removal from wastewater. The formation and morphological results support the successful formation of rGO/PPy nanohybrids and confirm the part covalent bonding of Py into GO honeycomb lattices to form a three-dimensional cross-linked spatial structure. The electrochemical tests indicate that the rGO/PPy electrode outperforms the unmodified electrode due to the 3.9-fold increase in electrochemical active surface area and 6.9-fold decrease in the charge transfer resistance (Rct). Batch denitrification activity tests demonstrate that the BES equipped with modified rGO/PPy biocathode could not only achieve the full denitrification efficiency of 100% with energy recovery (15.9 × 10-2 ± 0.14 A/m2), but also favor microbial attach and growth with improved biocompatible surface. This work provides a feasible electrochemical route to fabricate and design a high-performance bioelectrode to enhance denitrification in BESs.


Assuntos
Desnitrificação , Eletrodos , Grafite , Polímeros , Pirróis , Grafite/química , Polímeros/química , Pirróis/química , Técnicas Eletroquímicas/métodos , Fontes de Energia Bioelétrica , Nitratos/química , Carbono/química , Fibra de Carbono/química
10.
J Chem Phys ; 160(17)2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38748014

RESUMO

Fatty acids from cooking fumes and hypochlorous acid (HOCl) released from indoor cleaning adversely affect respiratory health, but the molecular-level mechanism remains unclear. Here, the effect of cooking oil fumes [palmitic acid (PA), oleic acid (OA), and linoleic acid (LA)] on lung model phospholipid (POPG) hydrochlorination mediated by HOCl at the air-water interface of the hanged droplets was investigated. Interfacial hydrochlorination of POPG was impeded by OA and LA, while that of POPG was facilitated by PA. The effect on POPG hydrochlorination increased with the decrease in oil fume concentration. A potential mechanism with respect to the chain length of these oil fumes, regardless of their saturation, was proposed. PA with a short carbon chain looses the POPG packing and leads to the exposure of the C=C double bonds of POPG, whereas OA and LA with a long carbon chain hinder HOCl from reaching the C=C bonds of POPG. These results for short chain and low concentration dependence suggest that the decay of oil fumes or the conversion of short-chain species by indoor interfacial chemistry might be adverse to lung health. These results provide insights into the relationship between indoor multicomponent pollutants and the respiratory system.


Assuntos
Poluição do Ar em Ambientes Fechados , Ácidos Graxos , Ácidos Graxos/química , Ácido Hipocloroso/química , Culinária , Fosfolipídeos/química
11.
J Sep Sci ; 47(13): e2400234, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39005007

RESUMO

In this study, we employed a combination approach for the preparative separation of constituents from Ginkgo biloba L. leaves. It involved multi-stage solvent extractions utilizing two-phase multi-solvent systems and countercurrent chromatography (CCC) separations using three different solvent systems. The n-heptane/ethyl acetate/water (1:1:2, v/v) and n-heptane/ethyl acetate/methanol/water (HepEMWat, 7:3:7:3, v/v) solvent systems were screened out as extraction systems. The polarities of the upper and lower phases in the multi-solvent systems were adjustable, enabling the effectively segmented separation of complex constituents in G. biloba L. The segmented products were subsequently directly utilized as samples and separated using CCC with the solvent systems acetate/n-butanol/water (4:1:5, v/v), HepEMWat (5:5:5:5, v/v), and HepEMWat (9:1:9:1, v/v), respectively. As a result, a total of 11 compounds were successfully isolated and identified from a 2 g methanol extract of G. biloba L through two-stage extraction and three CCC separation processes; among them, nine compounds exhibited high-performance liquid chromatography purity exceeding 85%.


Assuntos
Distribuição Contracorrente , Ginkgo biloba , Extratos Vegetais , Folhas de Planta , Solventes , Ginkgo biloba/química , Solventes/química , Folhas de Planta/química , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Cromatografia Líquida de Alta Pressão , Água/química , Metanol/química , Acetatos/química , Extrato de Ginkgo
12.
BMC Urol ; 24(1): 31, 2024 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-38310214

RESUMO

BACKGROUND: Surgical treatment for renal cell carcinoma (RCC) and inferior vena cava (IVC) tumor thrombus (TT) is difficult, and the postoperative complication rate is high. This study aimed to explore the safety and oncologic outcomes of neoadjuvant stereotactic ablative body radiotherapy (SABR) combined with surgical treatment for RCC and IVC-TT. METHODS: Patients with RCC and IVC-TTs were enrolled in this study. All patients received neoadjuvant SABR focused on the IVC at a dose of 30 Gy in 5 fractions, followed by 2 ~ 4 weeks of rest. Then, radical nephrectomy and IVC tumor thrombectomy were performed for each patient. Adverse effects, perioperative outcomes, and long-term prognoses were recorded. RESULTS: From June 2018 to January 2019, 8 patients were enrolled-4 with Mayo grade II TT and 4 with Mayo grade III TT. Four (50%) patients had complicated IVC wall invasion according to CT/MRI. All patients received neoadjuvant SABR as planned. Short-term local control was observed in all 8 patients. Only Grade 1-2 adverse events were reported. In total, 3 (37.5%) laparoscopic surgeries and 5 (62.5%) open surgeries were performed. The median operation time was 359 (IQR: 279-446) min, with a median intraoperative bleeding volume of 750 (IQR: 275-2175) ml. The median postoperative hospital stay was 7 (5-10) days. With a 26-month (range: 5-41) follow-up period, the estimated mean overall survival was 30.67 ± 5.38 months. CONCLUSIONS: This is the first preoperative radiotherapy study in Asia that focused on patients with TT. This study revealed the considerable safety of neoadjuvant SABR for RCC with IVC-TT. TRIAL REGISTRATION: This study was registered in the Chinese Clinical Trials Registry on 2018-03-08 (ChiCTR1800015118). For more information, please see the direct link ( https://www.chictr.org.cn/showproj.html?proj=25747 ).


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Trombose Venosa , Humanos , Carcinoma de Células Renais/radioterapia , Carcinoma de Células Renais/cirurgia , Carcinoma de Células Renais/complicações , Neoplasias Renais/patologia , Terapia Neoadjuvante/efeitos adversos , Nefrectomia/efeitos adversos , Projetos Piloto , Estudos Prospectivos , Estudos Retrospectivos , Trombectomia , Veia Cava Inferior/cirurgia , Veia Cava Inferior/patologia , Trombose Venosa/complicações
13.
Appl Opt ; 63(13): 3399-3405, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38856524

RESUMO

Weakly coupled mode-division multiplexing (MDM) transmission over legacy laid multimode fiber (MMF) has great economic efficiency and can enormously enhance the capacity of short-reach optical interconnections. In order to be compatible with cost-efficient intensity-modulation/direct-detection (IM/DD) transceivers, weakly coupled mode-group demultiplexers that can simultaneously receive each mode group of MMFs are highly desired. In this paper, we propose a scalable low-modal-crosstalk mode-group demultiplexer over MMF based on multiplane light conversion (MPLC). Multiple input Hermite-Gaussian (HG) modes of MMF are first converted to bridging modes that are composed of H G 00 modes distributed as a right-angle triangle in Cartesian coordinates, and then each H G 00 mode belonging to a degenerate mode group is mapped to different overlapped H G n0 modes with vertical orientation for simultaneous detection. With the help of bridging modes, the MPLC-based mode-group demultiplexer can efficiently demultiplex all mode groups in standard MMFs with less than 20 phase masks. A nine-mode-group demultiplexer is further designed for demonstration, and simulation results show that the MPLC-based demultiplexer achieves low modal crosstalk of lower than -22.3d B at 1550 nm and lower than -17.9d B over the C-band for all the nine mode groups with only 16 phase masks.

14.
Nucleic Acids Res ; 50(13): 7529-7544, 2022 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-35766425

RESUMO

Prokaryotic Argonaute proteins (pAgos) widely participate in hosts to defend against the invasion of nucleic acids. Compared with the CRISPR-Cas system, which requires a specific motif on the target and can only use RNA as guide, pAgos exhibit precise endonuclease activity on any arbitrary target sequence and can use both RNA and DNA as guide, thus rendering great potential for genome editing applications. Hitherto, most in-depth studies on the structure-function relationship of pAgos were conducted on thermophilic ones, functioning at ∼60 to 100°C, whose structures were, however, determined experimentally at much lower temperatures (20-33°C). It remains unclear whether these low-temperature structures can represent the true conformations of the thermophilic pAgos under their physiological conditions. The present work studied three pAgos, PfAgo, TtAgo and CbAgo, whose physiological temperatures differ significantly (95, 75 and 37°C). By conducting thorough experimental and simulation studies, we found that thermophilic pAgos (PfAgo and TtAgo) adopt a loosely-packed structure with a partially-melted surface at the physiological temperatures, largely different from the compact crystalline structures determined at moderate temperatures. In contrast, the mesophilic pAgo (CbAgo) assumes a compact crystalline structure at its optimal function temperature. Such a partially-disrupted structure endows thermophilic pAgos with great flexibility both globally and locally at the catalytic sites, which is crucial for them to achieve high DNA-cleavage activity. To further prove this, we incubated thermophilic pAgos with urea to purposely disrupt their structures, and the resulting cleavage activity was significantly enhanced below the physiological temperature, even at human body temperature. Further testing of many thermophilic Agos present in various thermophilic prokaryotes demonstrated that their structures are generally disrupted under physiological conditions. Therefore, our findings suggest that the highly dynamical structure with a partially-melted surface, distinct from the low-temperature crystalline structure, could be a general strategy assumed by thermophilic pAgos to achieve the high DNA-cleavage activity.


Assuntos
Proteínas Argonautas , Clivagem do DNA , Proteínas Argonautas/metabolismo , DNA/genética , DNA/metabolismo , Humanos , Células Procarióticas/metabolismo , RNA/metabolismo
15.
BMC Public Health ; 24(1): 2488, 2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39266983

RESUMO

BACKGROUND: There are significant sex differences in the incidence of stroke or diabetes mellitus. However, little is known about sex differences in stroke rehospitalization among diabetic patients. OBJECT: To explore the sex differences in short-term and long-term rehospitalization of ischemic stroke patients with Type 2 diabetes mellitus. METHODS: A retrospective cohort study was conducted from 2017 to 2021. The rehospitalization events of ischemic stroke patients with diabetes mellitus were identified by the national unified Electronic Health Record. Propensity score matching was applied to adjust for multiple covariates, and LASSO regression was used to screen for independent variables. Cox proportional hazards model was utilized to analyze the different sex in short-term (90 days, 1 year) and long-term (5 years) rehospitalization in ischemic stroke patients with type 2 diabetes mellitus. RESULT: A total of 10,724 ischemic stroke patients were included in this study, of whom 5,952 (55.5%) were males. After a 1:1 propensity score matching, there were 3,460 males and 2,772 females. After adjusting for confounding factors, female patients with type 2 diabetes had an increased risk of ischemic stroke rehospitalization at 90 days (HR: 1.94, 95%CI: 1.13-3.33, P < 0.05), 1 year (HR: 1.65, 95%CI:1.22-2.23, P = 0.001), and 5 years (HR: 1.58, 95%CI: 1.26-1.97, P < 0.001). However, there was no significant relationship between male patients with type 2 diabetes and the risk of ischemic stroke rehospitalization, either in the short or long term. CONCLUSION: Females with type 2 diabetes mellitus have a higher risk of ischemic stroke rehospitalization in both the short-term and long-term.


Assuntos
Diabetes Mellitus Tipo 2 , AVC Isquêmico , Readmissão do Paciente , Humanos , Feminino , Masculino , Estudos Retrospectivos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Readmissão do Paciente/estatística & dados numéricos , Pessoa de Meia-Idade , Idoso , AVC Isquêmico/epidemiologia , Fatores Sexuais , Fatores de Risco , Pontuação de Propensão , Modelos de Riscos Proporcionais
16.
Neurosurg Rev ; 47(1): 549, 2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39237692

RESUMO

This study aims to discuss the identification of the C1 nerve root as an effective surgical approach to successfully locate the shunting point of craniocervical junction spinal dural arteriovenous fistula (CCJ-SDAVF) intraoperatively. This study included all patients with CCJ-SDAVF who underwent surgical treatment using the far-lateral transcondylar approach at a single institution from January 2017 to June 2023. Data on patient demographics, clinical and angiographic characteristics of CCJ-SDAVF, surgical details, and treatment outcomes were collected. Follow-up assessments were conducted for all patients until December 31, 2023. The study included a total of 7 patients, comprising 5 men(71.4%) and 2 women (28.6%), with an average age of 57.6 years. Among them, 4 patients (57.1%) developed diffuse subarachnoid hemorrhage(SAH), while 2 patients (28.6%) experienced progressive cervical myelopathy. The shunting points of all CCJ-SDAVFs, which exhibited engorged veins, were identified next to the C1 root. Complete obliteration of CCJ-SDAVFs was successfully achieved in all patients, as confirmed by postoperative angiography one month later. No recurrent CCJ-SDAVFs were observed two years after the operation. Among the patients, 5 (71.4%) experienced good functional recovery, as indicated by an mRS score ranging from 0 to 1, while the remaining 2 patients (28.6%) showed incomplete functional recovery. The surgical interruption of CCJ-SDAVFs is the preferred treatment option, given its high obliteration rate and favorable functional recovery outcomes. We advocate the identification of C1 spinal nerve root as a crucial surgical step to identify the shunting points of CCJ- SDAVFs.


Assuntos
Malformações Vasculares do Sistema Nervoso Central , Raízes Nervosas Espinhais , Humanos , Pessoa de Meia-Idade , Masculino , Feminino , Malformações Vasculares do Sistema Nervoso Central/cirurgia , Raízes Nervosas Espinhais/cirurgia , Idoso , Estudos Retrospectivos , Adulto , Resultado do Tratamento , Procedimentos Neurocirúrgicos/métodos , Vértebras Cervicais/cirurgia , Hemorragia Subaracnóidea/cirurgia , Doenças da Medula Espinal/cirurgia
17.
J Med Internet Res ; 2024 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-39219230

RESUMO

BACKGROUND: One of the significant changes in intensive care medicine over the past two decades is the acknowledgement that improper mechanical ventilation settings substantially contribute to pulmonary injury in critically ill patients. Artificial intelligence (AI) solutions can be used to optimize mechanical ventilation settings in intensive care units (ICUs) and to improve patient outcomes. Specifically, machine learning algorithms can be trained on large datasets of patient information and mechanical ventilation settings. These algorithms can then predict patient responses to different ventilation strategies and suggest personalized ventilation settings for individual patients. OBJECTIVE: In this study, we aimed to design and evaluate an AI solution that could tailor an optimal ventilator strategy for each critically ill patient who requires mechanical ventilation. METHODS: We proposed a reinforcement learning-based AI solution using observational data from multiple ICUs in the US. The primary outcome was hospital mortality. Secondary outcomes were the proportion of optimal oxygen saturation and the proportion of optimal mean arterial blood pressure. We trained our AI agent to recommend low/medium/high levels of three ventilator settings - positive end-expiratory pressure (PEEP), fraction of inspired oxygen (FiO2) and ideal body weight-adjusted tidal volume - according to patients' health conditions. We defined a policy as a set of rules guiding ventilator setting changes given specific clinical scenarios. Off-policy evaluation metrics were applied to evaluate the AI policy. RESULTS: We studied 21,595 and 5,105 patients' ICU stays from the eICU Collaborative Research (eICU) and Medical Information Mart for Intensive Care IV (MIMIC-IV) databases respectively. Using the learnt AI policy, we estimated the hospital mortality rate (eICU 12.1±3.1%; MIMIC-IV 29.1±0.9%), proportion of optimal oxygen saturation (eICU 58.7±4.7%; MIMIC-IV 49.0±1.0%), and proportion of optimal mean arterial blood pressure (eICU 31.1±4.5%; MIMIC-IV 41.2±1.0%). Based on multiple quantitative and qualitative evaluation metrics, our proposed AI solution outperformed observed clinical practice.We studied 21,595 5105 and 5,105 21595 patients' ' ICU stays from the Medical Information Mart for Intensive Care -IV (MIMIC-IV)(1) and eICU Collaborative Research (eICU) and Medical Information Mart for Intensive Care IV (MIMIC-IV) databases respectively. Observed hospital mortality rates were 18.2% (eICU) and 31.1% (MIMIC-IV). UsingFor the learnt AI policy, we estimated the hospital mortality rate (eICU 14.7±0.7%; MIMIC-IV 29.1±0.9%), proportion of optimal oxygen saturation (eICU 57.8±1.0%; MIMIC-IV 49.0±1.0%), and proportion of optimal mean arterial blood pressure (eICU 34.7 ± 1.0%; MIMIC-IV 41.2±1.0%). Based on multiple quantitative and qualitative evaluation metrics, our proposed AI solution has potential to outperformed observed clinical practice. CONCLUSIONS: Our study found that customizing ventilation settings for individual patients led to lower estimated hospital mortality rates compared to actual rates. This highlights the potential effectiveness of using RL methodology to develop AI models that analyze complex clinical data for optimizing treatment parameters. Additionally, our findings suggest the integration of this model into a clinical decision support system for refining ventilation settings, supporting the need for prospective validation trials.

18.
Luminescence ; 39(8): e4867, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39152781

RESUMO

Heteroatom doping has become an important method to enhance the performance of traditional carbon dots in modern times. Selenium (Se) is a nonmetallic trace element with excellent redox properties and is therefore essential for health. Previous studies have mainly used pure chemicals as selenium sources to prepare selenium-doped carbon dots (Se-CDs), but the precursor pure chemicals have the disadvantages of being expensive, difficult to obtain, toxic, and having low fluorescence yields of the synthesised Se-CDs. Fortunately, our team achieved successful synthesis of selenium carbon dots, exhibiting excellent luminescence and biocompatibility through a one-step hydrothermal method using selenium-enriched natural plant Cardamine, as an alternative to selenium chemicals. This approach aims to address the limitations and high costs associated with Se-CDs precursors. Electron spin resonance spectroscopy (ESR) and cellular antioxidant tests have confirmed the protective ability of Se-CDs against oxidative damage induced by excessive reactive oxygen species (ROS). A new concept and method for synthesizing selenium carbon dots on the basis of biomass, a rationale for the antioxidant effects on human health, and a wide range of development and application possibilities were offered in this work.


Assuntos
Antioxidantes , Carbono , Luminescência , Pontos Quânticos , Selênio , Selênio/química , Carbono/química , Pontos Quânticos/química , Antioxidantes/química , Antioxidantes/farmacologia , Humanos , Espécies Reativas de Oxigênio/metabolismo , Plantas/química , Plantas/metabolismo
19.
Knee Surg Sports Traumatol Arthrosc ; 32(6): 1622-1630, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38586974

RESUMO

PURPOSE: Both the arthroscopic Broström-Gould and Lasso-loop stitch techniques are commonly used to treat chronic lateral ankle instability (CLAI). The purpose of this study is to introduce an arthroscopic one-step outside-in Broström-Gould (AOBG) technique and compare the mid-term outcomes of the AOBG technique and Lasso-loop stitch technique. METHODS: All CLAI patients who underwent arthroscopic lateral ankle stabilization surgery in our department from 2018 to 2019 were retrospectively enrolled. The patients were divided into two groups according to the surgical methods employed: the AOBG technique (Group A) and the Lasso-loop technique (Group B). The visual analogue scale pain score, American Orthopaedic Foot and Ankle Society ankle hindfoot score, Tegner activity score and Karlsson-Peterson score were evaluated preoperatively and during the follow-up from June to December 2022. The surgical duration, return to sports, sprain recurrence and surgical complications were also recorded and compared. RESULTS: A total of 74 patients (Group A, n = 42; Group B, n = 32) were included in this study with a mean follow-up of 39 months. No statistically significant differences were observed in demographic parameters or follow-up time between the two groups. Postoperative clinical scores indicated a significant improvement (all with p < 0.001) with no significant difference between the two groups (not significant [n.s.]). There was no significant difference in the surgical duration (46.1 vs. 49.7 min, n.s.), return to sports (92.9% vs. 93.8%, n.s.), or sprain recurrence (4.8% vs. 6.3%, n.s.). Only two cases in Group A reported knot irritation (4.8% vs. 0, n.s.), and one case in Group A experienced local skin numbness (0 vs. 3.1%, n.s.), with no significant difference. CONCLUSION: Both the AOBG and Lasso-loop stitch techniques yielded comparable favourable mid-term outcomes and return to sports with a low rate of surgical complications. Both procedures could be feasible strategies for CLAI patients. LEVEL OF EVIDENCE: Level III.


Assuntos
Artroscopia , Instabilidade Articular , Técnicas de Sutura , Humanos , Instabilidade Articular/cirurgia , Artroscopia/métodos , Masculino , Feminino , Estudos Retrospectivos , Adulto , Doença Crônica , Resultado do Tratamento , Recidiva , Ligamentos Laterais do Tornozelo/cirurgia , Volta ao Esporte , Articulação do Tornozelo/cirurgia , Duração da Cirurgia , Medição da Dor , Adulto Jovem
20.
J Craniofac Surg ; 35(4): 1057-1061, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38363290

RESUMO

BACKGROUND: Occipital artery (OA) acts as a vital donor vessel in intra-cranialand extra-cranial bypass. Ultrasonography and digital subtracted angiography (DSA) are becoming increasingly important in the assessment of vascular morphology and hemodynamically; however, quantitative analysis of occipital artery bypass donor vessels by Ultrasonography and DSA are seldom discussed. METHODS: A retrospective study involving 62 cases accepted occipital artery bypass to treat posterior circulation aneurysms or artery occlusion/stenosis. The characteristics of OA are collected and analyzed. RESULTS: Occipital artery bypasses were performed to treat posterior circulation aneurysms in 34 patients and to treat posterior circulation artery occlusion or stenosis in 28 patients. Compared with the ultrasonography group, the DSA group had a greater diameter of OA, and Bland Altman analysis indicated that the discrepancy between the 2 groups was about 0.555 mm. Ultrasonography showed the characteristics of OA: the mean Peak Systolic Velocity (PSV) was 42.98 cm/s, the mean End Diastolic Velocity (EDV) was 8.811 cm/s, and the mean Resistance Index (RI) was 1.46. There were no statistical differences in the diameter of OA, PSV, EDV, and RI between the male group and female group, the elderly group and younger adult group or the left occipital artery group and right occipital artery group. However, compared with patients with posterior circulation aneurysms, patients with artery occlusion or stenosis were older and had higher PSV, RI, and greater diameter in occipital arteries. The mean diameter of occipital arteries was increased in the first postoperative years but reduced in 3 patients during 1 year follow-up. CONCLUSIONS: Both ultrasonography and DSA were effective assessment methods of occipital artery bypasses, and the DSA group had a greater diameter of OA. Age, gender, and left or right sides had little effect on the diameter of OA, PSV, EDV, and RI. Posterior circulation occlusion or stenosis had higher PSV, RI, and greater diameter of the occipital artery when compared with posterior circulation aneurysms. Occipital artery bypasses could increase the diameter of OA in most cases.


Assuntos
Angiografia Digital , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto , Idoso , Aneurisma Intracraniano/cirurgia , Aneurisma Intracraniano/diagnóstico por imagem , Revascularização Cerebral/métodos , Ultrassonografia/métodos , Resultado do Tratamento
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