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1.
Cancer Med ; 13(9): e7231, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38698697

RESUMO

OBJECTIVE: To create a nomogram for predicting the likelihood of venous thromboembolism (VTE) in colon cancer patients from China. METHODS: The data of colon cancer patients from Chongqing University Cancer Hospital between 2019 and 2022 were analyzed. Patients were divided into training set and internal validation set by random split-sample method in a split ratio of 7:3. The univariable and multivariable logistic analysis gradually identified the independent risk factors for VTE. A nomogram was created using all the variables that had a significance level of p < 0.05 in the multivariable logistic analysis and those with clinical significance. Calibration curves and clinical decision curve analysis (DCA) were used to assess model's fitting performance and clinical value. Harrell's C-index (concordance statistic) and the area under the receiver operating characteristic curves (AUC) were used to evaluate the predictive effectiveness of models. RESULTS: A total of 1996 patients were ultimately included. There were 1398 patients in the training set and 598 patients in the internal validation set. The nomogram included age, chemotherapy, targeted therapy, hypertension, activated partial thromboplastin time, prothrombin time, platelet, absolute lymphocyte count, and D-dimer. The C-index of nomogram and Khorana score were 0.754 (95% CI 0.711-0.798), 0.520 (95% CI 0.477-0.563) in the training cohort and 0.713 (95% CI 0.643-0.784), 0.542 (95% CI 0.473-0.612) in the internal validation cohort. CONCLUSIONS: We have established and validated a nomogram to predict the VTE risk of colon cancer patients in China, which encompasses a diverse age range, a significant population size, and various clinical factors. It facilitates the identification of high-risk groups and may enable the implementation of targeted preventive measures.


Assuntos
Neoplasias do Colo , Nomogramas , Tromboembolia Venosa , Humanos , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/epidemiologia , Masculino , Feminino , Neoplasias do Colo/complicações , Neoplasias do Colo/epidemiologia , China/epidemiologia , Pessoa de Meia-Idade , Fatores de Risco , Idoso , Medição de Risco/métodos , Curva ROC , Estudos Retrospectivos , Adulto
2.
J Immunother Cancer ; 12(5)2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38719544

RESUMO

OBJECTIVE: To evaluate the safety and preliminary efficacy of YSCH-01 (Recombinant L-IFN adenovirus) in subjects with advanced solid tumors. METHODS: In this single-center, open-label, investigator-initiated trial of YSCH-01, 14 patients with advanced solid tumors were enrolled. The study consisted of two distinct phases: (1) the dose escalation phase and (2) the dose expansion phase; with three dose groups in the dose escalation phase based on dose levels (5.0×109 viral particles (VP)/subject, 5.0×1010 VP/subject, and 5.0×1011 VP/subject). Subjects were administered YSCH-01 injection via intratumoral injections. The safety was assessed using National Cancer Institute Common Terminology Criteria for Adverse Events V.5.0, and the efficacy evaluation was performed using Response Evaluation Criteria in Solid Tumor V.1.1. RESULTS: 14 subjects were enrolled in the study, including 9 subjects in the dose escalation phase and 5 subjects in the dose expansion phase. Of the 13 subjects included in the full analysis set, 4 (30.8%) were men and 9 (69.2%) were women. The most common tumor type was lung cancer (38.5%, 5 subjects), followed by breast cancer (23.1%, 3 subjects) and melanoma (23.1%, 3 subjects). During the dose escalation phase, no subject experienced dose-limiting toxicities. The content of recombinant L-IFN adenovirus genome and recombinant L-IFN protein in blood showed no trend of significant intergroup changes. No significant change was observed in interleukin-6 and interferon-gamma. For 11 subjects evaluated for efficacy, the overall response rate with its 95% CI was 27.3% (6.02% to 60.97%) and the disease control rate with its 95% CI was 81.8% (48.22% to 97.72%). The median progression-free survival was 4.97 months, and the median overall survival was 8.62 months. In addition, a tendency of decrease in the sum of the diameters of target lesions was observed. For 13 subjects evaluated for safety, the overall incidence of adverse events (AEs) was 92.3%, the overall incidence of adverse drug reactions (ADRs) was 84.6%, and the overall incidence of >Grade 3 AEs was 7.7%, while no AEs/ADRs leading to death occurred. The most common AEs were fever (69.2%), nausea (30.8%), vomiting (30.8%), and hypophagia (23.1%). CONCLUSIONS: The study shows that YSCH-01 injections were safe and well tolerated and exhibited preliminary efficacy in patients with advanced solid tumors, supporting further investigation to evaluate its efficacy and safety. TRIAL REGISTRATION NUMBER: NCT05180851.


Assuntos
Neoplasias , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Neoplasias/tratamento farmacológico , Idoso , Adulto , Adenoviridae/genética , Terapia Viral Oncolítica/métodos , Terapia Viral Oncolítica/efeitos adversos , Resultado do Tratamento
3.
Nat Commun ; 15(1): 3398, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38649382

RESUMO

Plant species like the Venus flytrap possess unique abilities to intelligently respond to various external stimuli, ensuring successful prey capture. Their nerve-devoided structure provides valuable insights for exploring natural intelligence and constructing intelligent systems solely from materials, but limited knowledge is currently available and the engineering realization of such concept remains a significant challenge. Drawing upon the flytrap's action potential resulting from ion diffusion, we propose a signal accumulation/attenuation model and a corresponding liquid metal-based logic module, which operates on the basis of the shape change of liquid metal within a sodium hydroxide buffer solution. The module itself exhibits memory and counting properties without involving any other electronic components, intelligently responding to various stimulus sequences, and reproducing the flytrap's most logical function. We also demonstrate and forecast its potential as a moving window integration-based high-pass filter, artificial synapse in neural networks, and other related applications. This research provides a fresh perspective on comprehending the intelligence inherent in nature and its realization through physical structures, which is expected to inspire logic device development in a broad engineering field.

6.
Opt Express ; 32(6): 8723-8735, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38571123

RESUMO

In this study, a Si defect structure was added into the silica network in order to activate the bismuth and silica structure active center. TD-DFT theoretical simulations show that the Bi and Si ODC(I) models can excite the active center of the E-band at 1408 nm. Additionally, the Bi-doped silica fiber (BDSF) with improved fluorescence was fabricated using atomic layer deposition (ALD) combined with the modified chemical vapor deposition (MCVD) technique. Some tests were used to investigate the structural and optical properties of BDSF. The UV-VIS spectral peak of the BDSF preform is 424 cm-1, and the binding energy of XPS is 439.3 eV, indicating the presence of Bi° atom in BDSF. The Raman peak near 811 cm-1 corresponds to the Bi-O bond. The Si POL defect lacks a Bi-O structure, and the reason for the absence of simulated active center from the E-band is explained. A fluorescence spectrometer was used to analyze the emission peak of a BDSF at 1420 nm. The gain of the BDSF based optical amplifier was measured 28.8 dB at 1420 nm and confirmed the effective stimulation of the bismuth active center in the E-band.

7.
Adv Mater ; : e2402445, 2024 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-38583077

RESUMO

Brain disorders represent a significant challenge in medical science due to the formidable blood-brain barrier (BBB), which severely limits the penetration of conventional therapeutics, hindering effective treatment strategies. This review delves into the innovative realm of biomimetic nanodelivery systems, including stem cell-derived nanoghosts, tumor cell membrane-coated nanoparticles, and erythrocyte membrane-based carriers, highlighting their potential to circumvent the BBB's restrictions. By mimicking native cell properties, these nanocarriers emerge as a promising solution for enhancing drug delivery to the brain, offering a strategic advantage in overcoming the barrier's selective permeability. The unique benefits of leveraging cell membranes from various sources is evaluated and advanced technologies for fabricating cell membrane-encapsulated nanoparticles capable of masquerading as endogenous cells are examined. This enables the targeted delivery of a broad spectrum of therapeutic agents, ranging from small molecule drugs to proteins, thereby providing an innovative approach to neurocare. Further, the review contrasts the capabilities and limitations of these biomimetic nanocarriers with traditional delivery methods, underlining their potential to enable targeted, sustained, and minimally invasive treatment modalities. This review is concluded with a perspective on the clinical translation of these biomimetic systems, underscoring their transformative impact on the therapeutic landscape for intractable brain diseases.

8.
Ecotoxicol Environ Saf ; 276: 116259, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38581905

RESUMO

Gestational cadmium exposure increases the risk of preeclampsia. Placenta mitophagy was activated in preeclampsia. The aim of present study was to explore the mechanism of cadmium-induced mitophagy activation and its association with preeclampsia. Mitophagy markers expression levels were detected by quantitative real-time PCR, Western blot, immunofluorescence and immunochemistry in preeclampsia placenta. JEG3 cells were treated with CdCl2, iopanoic acid (IOP), 3-methyladenine and PGC1α SiRNA to verify mechanism of cadmium-induced mitophagy. Mitophagy marker LC3BII/I and P62 expression were increased and mitochondrial membrane receptor protein TOM20 and FUNDC1 expression were decreased in preeclampsia placenta as compared with that in normotension control. Mitophagy marker LC3BII/I and P62 expression were increased and TOM20 and FUNDC1 expression was decreased in CdCl2-treated JEG3 cells. Meanwhile, mitochondrial biogenesis regulator, PGC1α expression was decreased in preeclampsia and CdCl2-treated JEG3 cells. The expressions of LC3B and P62 were increased and the expressions of TOM20, FUNDC1 and PGC1α were decreased in IOP-treated cell. PGC1α SiRNA transfection led to increased expression of LC3BII/I and P62 and decreased expression of TOM20 and FUNDC1. The expression of sFlt1 was increased in preeclampsia placenta, CdCl2-treated cells, in IOP-treated cells and in PGC1α SiRNA transfected cells. 3-methyladenine treatment protected the increased expression of sFlt1 in CdCl2-treated cells, in IOP-treated cells and in PGC1α SiRNA transfected cells. Meanwhile, co-treatment of cadmium and IOP or PGC1αSiRNA led to a reduce expressions of OPA1, MFN1, MFN2 and FUNDC1 as compared to cadmium-treated, IOP-treated and PGC1α SiRNA-treated cells. These results elucidated that maternal cadmium exposure activated placenta mitophagy through downregulation of thyroid hormone receptor signal mediated decreased expression of PGC1α and was associated with the occurrence of preeclampsia.


Assuntos
Mitofagia , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo , Placenta , Pré-Eclâmpsia , Receptores dos Hormônios Tireóideos , Humanos , Pré-Eclâmpsia/induzido quimicamente , Feminino , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Gravidez , Mitofagia/efeitos dos fármacos , Placenta/efeitos dos fármacos , Placenta/metabolismo , Receptores dos Hormônios Tireóideos/genética , Receptores dos Hormônios Tireóideos/metabolismo , Cádmio/toxicidade , Regulação para Baixo/efeitos dos fármacos , Adulto , Transdução de Sinais/efeitos dos fármacos
9.
BMC Surg ; 24(1): 126, 2024 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-38678296

RESUMO

BACKGROUND: The primary duodenal gastrointestinal stromal tumor (GIST) is a rare type of gastrointestinal tract tumor. Limited resection (LR) has been increasingly performed for duodenal GIST. However, only a few studies reported minimally invasive limited resection (MI-LR) for primary duodenal GIST. METHODS: The clinical data of 33 patients with primary duodenal GIST from December 2014 to February 2024 were retrospectively analyzed including 23 who received MI-LR and 10 who received laparoscopic or robotic pancreaticoduodenectomy (LPD/RPD). RESULTS: A total of 33 patients with primary duodenal GIST were enrolled and retrospectively reviewed. Patients received MI-LR exhibited less OT (280 vs. 388.5min, P=0.004), EBL (100 vs. 450ml, P<0.001), and lower morbidity of postoperative complications (52.2% vs. 100%, P=0.013) than LPD/RPD. Patients received LPD/RPD burdened more aggressive tumors with larger size (P=0.047), higher classification (P<0.001), and more mitotic count/50 HPF(P=0.005) compared with patients received MI-LR. The oncological outcomes were similar in MI-LR group and LPD/RPD group. All the patients underwent MI-LR with no conversion, including 12 cases of LLR and 11 cases of RLR. All of the clinicopathological data of the patients were similar in both groups. The median OT was 280(210-480) min and 257(180-450) min, and the median EBL was 100(20-1000) mL and 100(20-200) mL in the LLR and the RLR group separately. The postoperative complications mainly included DGE (LLR 4 cases, 33.4% and RLR 4 cases, 36.4%), intestinal fistula (LLR 2 cases, 16.7%, and RLR 0 case), gastrointestinal hemorrhage (LLR 0 case and RLR 1 case, 9.1%), and intra-abdominal infection (LLR 3 cases, 25.0% and RLR 1 case, 9.1%). The median postoperative length of hospitalization was 19.5(7-46) days in the LLR group and 19(9-38) days in the RLR group. No anastomotic stenosis, local recurrence or distant metastasis was observed during the follow-up period in the two groups. CONCLUSIONS: Minimally invasive limited resection is an optional treatment for primary duodenal GIST with satisfactory short-term and long-term oncological outcomes.


Assuntos
Neoplasias Duodenais , Estudos de Viabilidade , Tumores do Estroma Gastrointestinal , Laparoscopia , Humanos , Tumores do Estroma Gastrointestinal/cirurgia , Tumores do Estroma Gastrointestinal/patologia , Estudos Retrospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Neoplasias Duodenais/cirurgia , Neoplasias Duodenais/patologia , Resultado do Tratamento , Idoso , Laparoscopia/métodos , Procedimentos Cirúrgicos Robóticos/métodos , Pancreaticoduodenectomia/métodos , Adulto , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Procedimentos Cirúrgicos Minimamente Invasivos/métodos
10.
J Mater Chem B ; 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38683028

RESUMO

The prosperity of chemodynamic therapy provides a new strategy for tumor treatment. However, the lack of reactive oxygen species and the specific reductive tumor microenvironment have limited the further development of chemodynamic therapy. Herein, we reported a Fe-based cyclically catalyzing double free radical system for tumor therapy by catalyzing exogenous potassium persulfate (K2S2O8) and endogenous hydrogen peroxide (H2O2). Sufficient amounts of Fe3+ and S2O82- were delivered to tumor sites via tumor-targeted hyaluronic acid (HA) encapsulated mesoporous silica nanoparticles (MSNs) and released under the dual stimulation of acid and hyaluronidase (HAase) in the tumor microenvironment. Fe3+ was reduced to Fe2+ by the reducing agents of loaded tannic acid (TA) and intracellular glutathione (GSH), and Fe2+ was subsequently reacted with S2O82- and endogenous H2O2 to produce two types of ROS (˙OH and SO4-˙), showing an excellent anti-tumor effect. This process not only supplied Fe2+ for the catalysis of active substances, but also reduced the concentration of reduced substances in cells, which was conducive to the existence of free radicals for the efficient killing of tumor cells. Therefore, this iron-based catalysis of exogenous and exogenous active substances to realize a dual-radical oncotherapy nanosystem would provide a new perspective for chemodynamic therapy.

11.
Pharmaceutics ; 16(4)2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38675217

RESUMO

Immunotherapy is a clinically effective method for treating tumors. Manganese can activate the cGAS-STING signaling pathway and induce an anti-tumor immune response. However, its efficacy is hindered by non-specific distribution and low uptake rates. In this study, we employed microfluidic technology to design and develop an innovative preparation process, resulting in the creation of a novel manganese lipid nanoparticle (LNM). The lipid manganese nanoparticle produced in this process boasts a high manganese payload, excellent stability, the capacity for large-scale production, and high batch repeatability. LNM has effectively demonstrated the ability to activate the cGAS-STING signaling pathway, induce the production of pro-inflammatory cytokines, and inhibit tumor development. Notably, LNM does not require combination chemotherapy drugs or other immune activators. Therefore, LNM presents a safe, straightforward, and efficient strategy for anti-tumor immune activation, with the potential for scalable production.

12.
Biosens Bioelectron ; 257: 116330, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38677022

RESUMO

Perfluorooctanoic acid (PFOA) poses a threat to the environment and human health due to its persistence, bioaccumulation, and reproductive toxicity. Herein, a lanthanide metal-organic framework (Ln-MOF)-based surface molecularly imprinted polymers (SMIPs) ratiometric fluorescence probe (Eu/Tb-MOF@MIPs) and a smartphone-assisted portable device were developed for the detection of PFOA with high selectivity in real water samples. The integration of Eu/Tb MOFs as carriers not only had highly stable multiple emission signals but also prevented deformation of the imprinting cavity of MIPs. Meanwhile, the MIPs layer preserved the fluorescence of Ln-MOF and provided selective cavities for improved specificity. Molecular dynamics (MD) was employed to simulate the polymerization process of MIPs, revealing that the formation of multiple recognition sites was attributed to the establishment of hydrogen bonds between functional monomers and templates. The probe showed a good linear relationship with PFOA concentration in the range of 0.02-2.8 µM, by giving the limit of detection (LOD) of 0.98 nM. Additionally, The red-green-blue (RGB) values analysis based on the smartphone-assisted portable device demonstrated a linear relationship of 0.1-2.8 µM PFOA with the LOD of 3.26 nM. The developed probe and portable device sensing platform exhibit substantial potential for on-site detecting PFOA in practical applications and provide a reliable strategy for the intelligent identification of important targets in water environmental samples.


Assuntos
Técnicas Biossensoriais , Caprilatos , Corantes Fluorescentes , Fluorocarbonos , Estruturas Metalorgânicas , Polímeros Molecularmente Impressos , Smartphone , Poluentes Químicos da Água , Estruturas Metalorgânicas/química , Caprilatos/análise , Caprilatos/química , Corantes Fluorescentes/química , Técnicas Biossensoriais/instrumentação , Fluorocarbonos/química , Fluorocarbonos/análise , Polímeros Molecularmente Impressos/química , Poluentes Químicos da Água/análise , Limite de Detecção , Elementos da Série dos Lantanídeos/química , Espectrometria de Fluorescência/métodos , Humanos
13.
BMC Cancer ; 24(1): 321, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38454345

RESUMO

BACKGROUND: Definitive concurrent chemoradiotherapy (dCCRT) is the gold standard for the treatment of locally advanced esophageal squamous cell carcinoma (ESCC). However, the potential benefits of consolidation chemotherapy after dCCRT in patients with esophageal cancer remain debatable. Prospective randomized controlled trials comparing the outcomes of dCCRT with or without consolidation chemotherapy in patients with ESCC are lacking. In this study, we aim to generate evidence regarding consolidation chemotherapy efficacy in patients with locally advanced, inoperable ESCC. METHODS: This is a multicenter, prospective, open-label, phase-III randomized controlled trial comparing non-inferiority of dCCRT alone to consolidation chemotherapy following dCCRT. In total, 600 patients will be enrolled and randomly assigned in a 1:1 ratio to receive either consolidation chemotherapy after dCCRT (Arm A) or dCCRT alone (Arm B). Overall survival will be the primary endpoint, whereas progression-free survival, locoregional progression-free survival, distant metastasis-free survival, and treatment-related toxicity will be the secondary endpoints. DISCUSSION: This study aid in further understanding the effects of consolidation chemotherapy after dCCRT in patients with locally advanced, inoperable ESCC. TRIAL REGISTRATION: ChiCTR1800017646.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimiorradioterapia , Quimioterapia de Consolidação , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/radioterapia , Carcinoma de Células Escamosas do Esôfago/terapia , Carcinoma de Células Escamosas do Esôfago/patologia , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como Assunto , Ensaios Clínicos Fase III como Assunto , Estudos de Equivalência como Asunto
14.
J Am Chem Soc ; 146(11): 7734-7742, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38447042

RESUMO

Precisely controlling the architecture and spatial arrangement of plasmonic heterostructures offers unique opportunities to tailor the catalytic property, whereas the lack of a wet-chemistry synthetic approach to fabricating nanostructures with high-index facets limits their practical applications. Herein, we describe a universal synthetic strategy to construct Au/Rh freestanding superstructures (SSs) through the selective growth of ordered Rh nanoarrays on high-index-faceted Au nanobipyramids (NBPs). This synthetic strategy works on various metal nanocrystal substrates and can yield diverse Au/Rh and Pd/Rh SSs. Especially, the obtained Au NBP/Rh SSs exhibit high photocatalytic activity toward N2 fixation as a result of the spatially separated architecture, local electric field enhancement, and the antenna-reactor mechanism. Both theoretical and experimental results reveal that the Au NBPs can function as nanoantennas for light-harvesting to generate hot charge carriers for driving N2 fixation, while the Rh nanoarrays can serve as the active sites for N2 adsorption and activation to synergistically promote the overall catalytic activity in the Au NBP/Rh SSs. This work offers new avenues to rationally designing and constructing spatially separated plasmonic photocatalysts for high-efficiency catalytic applications.

15.
Front Plant Sci ; 15: 1362287, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38455733

RESUMO

Rose black spot disease caused by Marssonina rosae is among the most destructive diseases that affects the outdoor cultivation and production of roses; however, the molecular mechanisms underlying the defensive response of roses to M. rosae have not been clarified. To investigate the diversity of response to M. rosae in resistant and susceptible rose varieties, we performed transcriptome and metabolome analyses of resistant (KT) and susceptible (FG) rose varieties and identified differentially expressed genes (DEGs) and differentially accumulated metabolites (DAMs) in response to M. rosae at different time points. In response to M. rosae, DEGs and DAMs were mainly upregulated compared to the control and transcription factors were concentrated in the WRKY and AP2/ERF families. Gene Ontology analysis showed that the DEGs of FG were mainly enriched in biological processes, such as the abscisic acid-activated signaling pathway, cell wall, and defense response, whereas the DEGs of KT were mainly enriched in Golgi-mediated vesicle transport processes. Kyoto Encyclopedia of Genes and Genomes analysis showed that the DEGs of both varieties were concentrated in plant-pathogen interactions, plant hormone signal transduction, and mitogen-activated protein kinase signaling pathways, with the greatest number of DEGs associated with brassinosteroid (BR) in the plant hormone signal transduction pathway. The reliability of the transcriptome results was verified by qRT-PCR. DAMs of KT were significantly enriched in the butanoate metabolism pathway, whereas DAMs of FG were significantly enriched in BR biosynthesis, glucosinolate biosynthesis, and tryptophan metabolism. Moreover, the DAMs in these pathways were significantly positively correlated with the DEGs. Disease symptoms were aggravated when FG leaves were inoculated with M. rosae after 24-epibrassinolide treatment, indicating that the response of FG to M. rosae involves the BR signaling pathway. Our results provide new insights into the molecular mechanisms underlying rose response to M. rosae and lay a theoretical foundation for formulating rose black spot prevention and control strategies and cultivating resistant varieties.

16.
Heliyon ; 10(5): e27576, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38463838

RESUMO

Objectives: Recently, there has been extensive research on dual immunotherapy for advanced or metastatic non-small cell lung cancer (NSCLC), yet a comprehensive evaluation is lacking. This study aimed to rank the available treatment options and assess the efficacy and safety of dual immunotherapy regimens through the implementation of a Bayesian network meta-analysis (NMA). Materials and methods: A thorough search was conducted to recognize eligible randomized controlled trials (RCTs) on March 20, 2023. Overall survival (OS), progression-free survival (PFS), treatment-related adverse events (TRAEs) and grade ≥3 TRAEs were evaluated to identify the efficacy and safety of dual immunotherapy regimens. The surface under the cumulative ranking curve (SUCRA) and P score were employed to rank the treatments. Results: Eleven clinical trials involving six different regimens were included in this study. The combination of anti-programmed cell death protein 1/programmed cell death ligand 1 (PD-1/PD-L1) antibodies with anti-T-cell immunoglobulin and ITIM domain (TIGIT) antibodies emerged as the most promising regimen for improving OS and PFS, followed by anti-PD-1/PD-L1 + anti-cytotoxic T lymphocyte antigen 4 (CTLA-4) + chemotherapy treatment and anti-PD-1/PD-L1 + anti-CTLA-4 treatment. The forest plots demonstrated that these three regimens were all superior to chemotherapy. The above results were observed in both unselected treatment line and first-line settings. The least likely to be associated with TRAEs and grade ≥3 TRAEs were respectively anti-CTLA-4 treatment and anti-PD-1/PD-L1 + anti-TIGIT treatment, with anti-PD-1/PD-L1 + anti-CTLA-4 + chemotherapy treatment to be the worst. Conclusions: This NMA validated the promising efficacy and safety of dual immunotherapy in advanced or metastatic NSCLC. Among them, anti-PD-1/PD-L1 + anti-TIGIT regimen emerges as a highly potential therapeutic approach. Ongoing research efforts should focus on improving treatment regimens, identifying biomarkers, and managing TRAEs to optimize the patient benefits of dual immunotherapy.

17.
Int J Mol Sci ; 25(5)2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38473803

RESUMO

Mevalonate kinase (MevK) is an important enzyme in the mevalonate pathway that catalyzes the phosphorylation of mevalonate into phosphomevalonate and is involved in juvenile hormone biosynthesis. Herein, we present a structure model of MevK from the red flour beetle Tribolium castaneum (TcMevK), which adopts a compact α/ß conformation that can be divided into two parts: an N-terminal domain and a C-terminal domain. A narrow, deep cavity accommodating the substrate and cofactor was observed at the junction between the two domains of TcMevK. Computational simulation combined with site-directed mutagenesis and biochemical analyses allowed us to define the binding mode of TcMevK to cofactors and substrates. Moreover, TcMevK showed optimal enzyme activity at pH 8.0 and an optimal temperature of 40 °C for mevalonate as the substrate. The expression profiles and RNA interference of TcMevK indicated its critical role in controlling juvenile hormone biosynthesis, as well as its participation in the production of other terpenoids in T. castaneum. These findings improve our understanding of the structural and biochemical features of insect Mevk and provide a structural basis for the design of MevK inhibitors.


Assuntos
Besouros , Fosfotransferases (Aceptor do Grupo Álcool) , Tribolium , Animais , Tribolium/genética , Besouros/metabolismo , Ácido Mevalônico/metabolismo , Hormônios Juvenis/metabolismo
18.
BMC Oral Health ; 24(1): 301, 2024 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-38431628

RESUMO

BACKGROUND: This study aimed to investigate the potential associations between alveolar bone thickness, bucco-palatal inclination of maxillary lateral incisors, and lateral incisor root resorption in patients with unilateral maxillary impacted canines (UMICs). METHODS: A total of three hundred and five subjects (120 males, 185 females; mean age, 16.39 years; standard deviation, 4.04) with UMICs were included. Canine position and root resorption were assessed using CBCT. UMICs were divided into palatal, buccal and mid-alveolus groups (PICs, BICs and MAICs), with 117, 137 and 51 subjects, respectively. Alveolar bone thickness and bucco-palatal inclination of lateral incisors were measured using the Dolphin software. RESULTS: The prevalence of lateral incisor root resorption was significantly lower in the BICs (13.9%) than MAICs (29.4%) and PICs (29.1%). Alveolar bone thickness of the apical area was smaller in UMICs with lateral incisor root resorption than no resorption in both PICs (8.33 ± 1.64 vs 10.53 ± 2.55 mm) and BICs (8.94 ± 1.85 vs 10.76 ± 2.28 mm). Furthermore, lateral incisors on the impacted side were more buccally inclined in PICs with lateral incisor root resorption than no resorption, while in both BICs and MAICs, there was no statistical difference between lateral incisor root resorption than no resorption. Moreover, alveolar bone thickness of the apical area, rather than bucco-palatal inclination of lateral incisors, was significantly correlated with lateral incisor root resorption both in PICs and BICs. CONCLUSIONS: Lateral incisor root resorption is less common in BICs. Thinner alveolar bone thickness at the apical area of lateral incisors can be considered as a potential risk factor for lateral incisor root resorption in UMICs.


Assuntos
Reabsorção da Raiz , Dente Impactado , Masculino , Feminino , Humanos , Adolescente , Reabsorção da Raiz/diagnóstico por imagem , Reabsorção da Raiz/etiologia , Incisivo/diagnóstico por imagem , Tomografia Computadorizada de Feixe Cônico , Maxila/diagnóstico por imagem , Palato/diagnóstico por imagem , Dente Impactado/complicações , Dente Impactado/diagnóstico por imagem , Dente Canino/diagnóstico por imagem
19.
Langenbecks Arch Surg ; 409(1): 81, 2024 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-38430305

RESUMO

PURPOSE: This study aims to compare the efficiency and clinical outcomes between the suctioning ureteral access sheath (UAS) group and the traditional UAS group during retrograde intrarenal surgery (RIRS) for kidney stones and explore the impact of suctioning UAS on postoperative infectious complications. METHODS: We retrospectively reviewed the clinical data of 162 patients with kidney stones who underwent RIRS with a traditional UAS (n = 74) or a suctioning UAS (n = 71) between March 2021 and May 2023. RESULTS: The mean operative time in suctioning UAS group (39.03 ± 18.01 s) was significantly shorter than that (49.73 ± 20.77 s) in the traditional UAS group (P = 0.037). The mean postoperative hospital stay was significantly shorter in the suctioning UAS group (1.57 ± 0.82d) compared with the traditional UAS group (2.30 ± 1.6 2 d) (P = 0.032). The instant SFRs were significantly higher in the suctioning UAS group (88.73%) than in the traditional UAS group (75.68%) (P = 0.040). The overall SFR in suctioning UAS group (92.96%) was slightly higher than the traditional UAS group (85.14%). The incidence of overall complications was significantly higher in the traditional UAS group (35.14%) than in the suctioning UAS group (16.90%) (P = 0.013). In multivariate analysis, female patients (OR 0.053, P = 0.018), positive urine WBC (OR 10.382, P = 0.034), operative time > 60 min (OR 20.231, P = 0.032), and the application of traditional UAS (OR 0.042, P = 0.017) were independent risk factors associated with infectious complications. CONCLUSION: We demonstrated that suctioning UAS provided a higher instant SFR and fewer postoperative infectious complications during RIRS, and patients with predictable risk factors for infectious complications could potentially benefit from the use of the suctioning UAS.


Assuntos
Cálculos Renais , Ureter , Humanos , Feminino , Estudos Retrospectivos , Cálculos Renais/cirurgia , Tempo de Internação , Análise Multivariada , Complicações Pós-Operatórias/epidemiologia
20.
ACS Appl Mater Interfaces ; 16(12): 14467-14473, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38491944

RESUMO

Surface-enhanced Raman scattering (SERS) has great potential in biological analysis due to its specificity, sensitivity, and non-invasive nature. However, effectively extracting Raman information and avoiding spectral overlapping from biological background interference remain major challenges. In this study, we developed a background-free SERS nanosensor consisting of gold nanobipyramids (Au NBPs) core-Prussian blue (PB) shell (Au NBPs@PB), for endogenous H2S detection. The PB shell degraded quickly upon contact with endogenous H2S, generating a unique Raman signal response in the Raman silent region (1800-2800 cm-1). By taking advantage of the high SERS-activity of Au NBPs and H2S-triggered spectral changes of PB, these SERS nanosensors effectively minimize potential biological interferences. The nanosensor exhibits a detection range of 2.0 µM to 250 µM and a limit of detection (LOD) of 0.34 µM, with good reproducibility and minimal interference. We successfully applied this background-free SERS platform to monitor endogenous H2S concentrations in human serum samples with satisfied results.


Assuntos
Ferrocianetos , Sulfeto de Hidrogênio , Nanopartículas Metálicas , Humanos , Sulfeto de Hidrogênio/análise , Ouro , Reprodutibilidade dos Testes , Análise Espectral Raman/métodos
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