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1.
PLoS One ; 19(2): e0297753, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38335229

RESUMO

CO2 blasting has been identified as a potent method for enhancing the permeability of coal seams and improving gas drainage efficiency. This study is focused on elucidating the deformation and fracture mechanisms of coal and rock during CO2 blasting and on identifying the precursor characteristics of these processes. To this end, a CO2 blasting-induced coal rock fracture pressure model and a gas pressure distribution model were developed. The research utilized a self-developed CO2 blasting test platform along with a non-contact full-strain field measurement analysis system. Briquette samples were subjected to CO2 blasting tests under controlled experimental conditions, which included an axial pressure of 1.0 MPa and variable gas pressures of 0.5, 1.0, and 1.5 MPa. This methodology enabled the capture of the principal strain field on the surface of the samples. The Gray Level Co-occurrence Matrix (GLCM) was employed to extract and analyze the grayscale and texture features of the strain cloud maps, facilitating a quantitative assessment of their evolution. The aim was to pinpoint the precursor characteristics associated with coal rock cracking and crack propagation. The results revealed that: (1) During the cracking and subsequent propagation of samples, the strain field's grayscale histogram underwent a transformation from a "broad and low" to a "narrow and high" configuration, with a consistent increase in peak frequency. Specifically, at 3 ms, a primary crack was observed in the sample, evidenced by a grayscale peak frequency of 0.0846. By 9 ms, as the crack propagated, the grayscale peak frequency escalated to 0.1626. (2) The texture feature parameters experienced their initial abrupt change at 3ms. Correlation with the gas pressure distribution model indicated that this was the crack initiation moment in the sample. (3) A secondary abrupt shift in the texture feature parameters occurred at 9ms, in conjunction with experimental phenomena, was identified as the crack propagation phase. Monitoring the grayscale and texture features of the principal strain field on the coal rock surface proved effective in recognizing the precursor characteristics of crack initiation and propagation. This research has the potential to reduce blasting costs in coal mines, optimize blasting effects, and provided theoretical guidance for enhancing gas extraction efficiency from deep and low permeability coal seams.


Assuntos
Dióxido de Carbono , Minas de Carvão , Dióxido de Carbono/análise , Carvão Mineral/análise , Minas de Carvão/métodos , Permeabilidade
2.
Bioorg Med Chem ; 101: 117609, 2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-38364599

RESUMO

In this study, we have designed, synthesized and tested three series of novel dihydropteridone derivatives possessing isoindolin-1-one or isoindoline moieties as potent inhibitors of PLK1/BRD4. Remarkably, most of the compounds showed preferable inhibitory activity against PLK1 and BRD4. Compound SC10 exhibited excellent inhibitory activity with IC50 values of 0.3 nM and 60.8 nM against PLK1 and BRD4, respectively. Meanwhile, it demonstrated significant anti-proliferative activities against three tumor-derived cell lines (MDA-MB-231 IC50 = 17.3 nM, MDA-MB-361 IC50 = 8.4 nM, and MV4-11 IC50 = 5.4 nM). Moreover, SC10 exhibited moderate rat liver microsomal stability (CLint = 21.3 µL·min-1·mg-1), acceptable pharmacokinetic profile (AUC0-t = 657 ng·h·mL-1, oral bioavailability of 21.4 %) in Sprague-Dawley rats, reduced hERG toxicity, acceptable PPB and CYP450 inhibition. Further research indicated that SC10 could induce MV4-11 cell arrest at the S phase and apoptosis in a dose-dependent manner. This investigation provided us with an initial point for developing novel anticancer agents as dual inhibitors of PLK1 and BRD4.

3.
Int J Biol Macromol ; 262(Pt 2): 130150, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38365157

RESUMO

Magnesium ions (Mg2+) are essential for the folding, functional expression, and structural stability of RNA molecules. However, predicting Mg2+-binding sites in RNA molecules based solely on RNA structures is still challenging. The molecular surface, characterized by a continuous shape with geometric and chemical properties, is important for RNA modelling and carries essential information for understanding the interactions between RNAs and Mg2+ ions. Here, we propose an approach named RNA-magnesium ion surface interaction fingerprinting (RMSIF), a geometric deep learning-based conceptual framework to predict magnesium ion binding sites in RNA structures. To evaluate the performance of RMSIF, we systematically enumerated decoy Mg2+ ions across a full-space grid within the range of 2 to 10 Å from the RNA molecule and made predictions accordingly. Visualization techniques were used to validate the prediction results and calculate success rates. Comparative assessments against state-of-the-art methods like MetalionRNA, MgNet, and Metal3DRNA revealed that RMSIF achieved superior success rates and accuracy in predicting Mg2+-binding sites. Additionally, in terms of the spatial distribution of Mg2+ ions within the RNA structures, a majority were situated in the deep grooves, while a minority occupied the shallow grooves. Collectively, the conceptual framework developed in this study holds promise for advancing insights into drug design, RNA co-transcriptional folding, and structure prediction.

4.
Photoacoustics ; 36: 100594, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38375332

RESUMO

In this article, a mid-infrared all-fiber light-induced thermoelastic spectroscopy (LITES) sensor based on a hollow-core anti-resonant fiber (HC-ARF) was reported for the first time. The HC-ARF was applied as a light transmission medium and gas chamber. The constructed all-fiber structure has merits of low loss, easy optical alignment, good system stability, reduced sensor size and cost. The mid-infrared transmission structure can be utilized to target the strongest gas absorption lines. The reversely-tapered SM1950 fiber and the HC-ARF were spatially butt-coupled with a V-shaped groove between the two fibers to facilitate gas entry. Carbon monoxide (CO) with an absorption line at 4291.50 cm-1 (2.33 µm) was chosen as the target gas to verify the sensing performance. The experimental results showed that the all-fiber LITES sensor based on HC-ARF had an excellent linear response to CO concentration. Allan deviation analysis indicated that the system had excellent long-term stability. A minimum detection limit (MDL) of 3.85 ppm can be obtained when the average time was 100 s.

5.
Small ; : e2310147, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38377273

RESUMO

Fabricating COFs-based electrocatalysts with high stability and conductivity still remains a great challenge. Herein, 2D polyimide-linked phthalocyanine COF (denoted as NiPc-OH-COF) is constructed via solvothermal reaction between tetraanhydrides of 2,3,9,10,16,17,23,24-octacarboxyphthalocyaninato nickel(II) and 2,5-diamino-1,4-benzenediol (DB) with other two analogous 2D COFs (denoted as NiPc-OMe-COF and NiPc-H-COF) synthesized for reference. In comparison with NiPc-OMe-COF and NiPc-H-COF, NiPc-OH-COF exhibits enhanced stability, particularly in strong NaOH solvent and high conductivity of 1.5 × 10-3  S m-1 due to the incorporation of additional strong interlayer hydrogen bonding interaction between the O-H of DB and the hydroxy "O" atom of DB in adjacent layers. This in turn endows the NiPc-OH-COF electrode with ultrahigh CO2 -to-CO faradaic efficiency (almost 100%) in a wide potential range from -0.7 to -1.1 V versus reversible hydrogen electrode (RHE), a large partial CO current density of -39.2 mA cm-2 at -1.1 V versus RHE, and high turnover number as well as turnover frequency, amounting to 45 000 and 0.76 S-1 at -0.80 V versus RHE during 12 h lasting measurement.

6.
Artigo em Inglês | MEDLINE | ID: mdl-38381128

RESUMO

Imaging-guided photodynamic therapy (PDT) holds great potential for tumor therapy. However, achieving the synergistic enhancement of the reactive oxygen species (ROS) generation efficiency and fluorescence emission of photosensitizers (PSs) remains a challenge, resulting in suboptimal image guidance and theranostic efficacy. The hypoxic tumor microenvironment also hinders the efficacy of PDT. Herein, we propose a "two-stage rocket-propelled" photosensitive system for tumor cell ablation. This system utilizes MitoS, a mitochondria-targeted PS, to ablate tumor cells. Importantly, MitoS can react with HClO to generate a more efficient PS, MitoSO, with a significantly improved fluorescence quantum yield. Both MitoS and MitoSO exhibit less O2-dependent type I ROS generation capability, inducing apoptosis and ferroptosis. In vivo PDT results confirm that this mitochondrial-specific type I-II cascade phototherapeutic strategy is a potent intervention for tumor downstaging. This study not only sheds light on the correlation between the PS structure and the ROS generation pathway but also proposes a novel and effective strategy for tumor downstaging intervention.

7.
Nano Lett ; 24(7): 2181-2187, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38340079

RESUMO

Recently discovered as an intrinsic antiferromagnetic topological insulator, MnBi2Te4 has attracted tremendous research interest, as it provides an ideal platform to explore the interplay between topological and magnetic orders. MnBi2Te4 displays distinct exotic topological phases that are inextricably linked to the different magnetic structures of the material. In this study, we conducted electrical transport measurements and systematically investigated the anomalous Hall response of epitaxial MnBi2Te4 films when subjected to an external magnetic field sweep, revealing the different magnetic structures stemming from the interplay of applied fields and the material's intrinsic antiferromagnetic (AFM) ordering. Our results demonstrate that the nonsquare anomalous Hall loop is a consequence of the distinct reversal processes within individual septuple layers. These findings shed light on the intricate magnetic structures in MnBi2Te4 and related materials, offering insights into understanding their transport properties and facilitating the implementation of AFM topological electronics.

8.
Anal Chem ; 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38330436

RESUMO

Normally, small-molecule fluorescent probes dependent on the mitochondrial membrane potential (MMP) are invalid for fixed cells and tissues, which limits their clinical applications when the fixation of pathological specimens is imperative. Given that mitochondrial morphology is closely associated with disease, we developed a long-chain mitochondrial probe for fixed cells and tissues, DMPQ-12, by installing a C12-alkyl chain into the quinoline moiety. In fixed cells stained with DMPQ-12, filament mitochondria and folded cristae were observed with confocal and structural illumination microscopy, respectively. In titration test with three major phospholipids, DMPQ-12 exhibited a stronger binding force to mitochondria-exclusive cardiolipin, revealing its targeting mechanism. Moreover, mitochondrial morphological changes in the three lesion models were clearly visualized in fixed cells. Finally, by DMPQ-12, three kinds of mitochondria with different morphologies were observed in situ in fixed muscle tissues. This work breaks the conventional concept that organic fluorescent probes only stain mitochondria with normal membrane potentials and opens new avenues for comprehensive mitochondrial investigations in research and clinical settings.

9.
Integr Cancer Ther ; 23: 15347354231226127, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38317410

RESUMO

BACKGROUND: People living with a cancer diagnosis often experience cancer-related fatigue (CRF). Between 9% and 45% of people report CRF as moderate to severe, negatively impacting their quality-of-life (QOL). The evidence-base for managing CRF recommends exercise-related therapies over pharmaceutical interventions. One such exercise-like therapy is Baduanjin mind-body exercise (MBE), which has additional benefits. A remotely delivered program may further benefit people with CRF. The primary objective of this pilot will test study feasibility of a remotely delivered Baduanjin MBE exercise program for people living with CRF. METHODS: This is a randomized wait-list controlled pilot study and will take place in Sydney, Australia. Subject to informed consent, 40 adults with moderate CRF levels and receiving or previously received adjuvant chemotherapy, will undertake a home-based 8-week Baduanjin MBE program supported by online resources and instructors. The primary feasibility outcomes are recruitment, enrollment, retention, and adherence rates; and safety as measured by tolerance and adverse-event frequency. Clinical outcomes (eg, changes in CRF, QOL, and participant perceptions) are assessed at pre-intervention, week 1, week 4, week 8, and post-intervention. Analyses follows the Intent-to-Treat (all participants as per randomization) and per-protocol (participants adhering to the protocol). Missing data will be imputed from previous data entries and regression models may be tested to predict missing outcomes. DISCUSSION: To our knowledge, this is the first study evaluating the feasibility and effects of Baduanjin MBE on CRF using a remote delivery method. These feasibility data will inform a fully powered future trial investigating evidence of effect on CRF and QOL.Trial registration: Australian and New Zealand Clinical Trials Registry (ANZCTR 12623000177651).Ringgold ID: 651498 Chinese Medicine Centre.


Assuntos
Neoplasias , Qualidade de Vida , Adulto , Humanos , Estudos de Viabilidade , Austrália , Terapia por Exercício/métodos , Neoplasias/complicações , Fadiga/etiologia , Fadiga/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto
10.
J Cancer ; 15(5): 1299-1313, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38356701

RESUMO

Colorectal cancer (CRC) is the second leading cause of cancer-related deaths worldwide. Early diagnosis of the disease can greatly improve the clinical prognosis for patients with CRC. Unfortunately, there are no current simple and effective early diagnostic markers available. The transfer RNA (tRNA)-derived RNA fragments (tRFs) are a class of small non-coding RNAs (sncRNAs), which have been shown to play an important role in the development and prognosis of CRC. However, only a few studies on tRFs as early diagnostic markers in CRC have been conducted. In this study, previously ignored tRFs expression data were extracted from six paired small RNA sequencing data in the Sequence Read Archive (SRA) database using MINTmap. Three i-tRFs, derived from the tRNA that transports glutamate (i-tRF-Glu), were identified and used to construct a random forest diagnostic model. The model performance was evaluated using the receiver operating characteristic (ROC) curve and precision-recall (PR) curve. The area under the curves (AUC) for the ROC and PR was 0.941 and 0.944, respectively. We further verified the differences in expression of the these i-tRF-Glu in the tissue and plasma of both CRC patients and healthy subjects using quantitative real-time PCR (qRT-PCR). We found that the ROC-AUC of the three was greater than traditional plasma tumor markers such as CEA and CA199. Our bioinformatics analysis suggested that the these i-tRF-Glu are associated with cancer development and glutamate (Glu)-glutamine (Gln) metabolism. Overall, our study uncovered these i-tRF-Glu that have early diagnostic significance and therapeutic potential for CRC, this warrants further investigation into the diagnostic and therapeutic potential of these i-tRF-Glu in CRC.

11.
Artigo em Inglês | MEDLINE | ID: mdl-38349972

RESUMO

Fluorescent polyelectrolytes have attracted tremendous attention due to their unique properties and wide applications. However, current research objects of fluorescent polyelectrolytes mainly focus on side-chain charged polyelectrolytes, and the applications of polyelectrolytes in plant cytomembrane imaging with long time and high specificity still remain challenging. Herein, long-time and targeted fluorescence imaging of plant cytomembranes was achieved for the first time using main-chain charged polyelectrolytes (MCCPs) with aggregation-induced emission (AIE). A series of MCCPs were designed and synthesized, among which the red-emissive and AIE-active MCCP with a triphenylamine linker and a cyano group around the cationic ring-fused heterocyclic core showed the best fluorescence imaging performance of plant cells. Unlike other MCCPs and its neutral form of polymer, this cyano-substituted conjugated polyelectrolyte can specifically target the cytomembrane of plant cells within a short staining time with many advantages, including wash-free staining, high photostability and imaging integrity, excellent durability (at least 12 h), and low biotoxicity. In addition to onion epidermal cells, this AIE fluorescence probe also shows good imaging capabilities for other kinds of plant cells such as Glycine max and Vigna radiata. Such an AIE-active MCCP-based imaging system provides an effective design strategy to develop fluorescence probes with high specificity and long-term imaging ability toward plant plasma membranes.

12.
J Am Chem Soc ; 146(6): 4260-4269, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38305175

RESUMO

Quantum tunneling, a phenomenon that allows particles to pass through potential barriers, can play a critical role in energy transfer processes. Here, we demonstrate that the proper design of organic-inorganic interfaces in two-dimensional (2D) hybrid perovskites allows for efficient triplet energy transfer (TET), where quantum tunneling of the excitons is the key driving force. By employing temperature-dependent and time-resolved photoluminescence and pump-probe spectroscopy techniques, we establish that triplet excitons can transfer from the inorganic lead-iodide sublattices to the pyrene ligands with rapid and weakly temperature-dependent characteristic times of approximately 50 ps. The energy transfer rates obtained based on the Marcus theory and first-principles calculations show good agreement with the experiments, indicating that the efficient tunneling of triplet excitons within the Marcus-inverted regime is facilitated by high-frequency molecular vibrations. These findings offer valuable insights into how one can effectively manipulate the energy landscape in 2D hybrid perovskites for energy transfer and the creation of diverse excitonic states.

13.
J Imaging Inform Med ; 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38319438

RESUMO

This study aims to develop a semiautomated pipeline and user interface (LiVaS) for rapid segmentation and labeling of MRI liver vasculature and evaluate its time efficiency and accuracy against manual reference standard. Retrospective feasibility pilot study. Liver MR images from different scanners from 36 patients were included, and 4/36 patients were randomly selected for manual segmentation as referenced standard. The liver was segmented in each contrast phase and masks registered to the pre-contrast segmentation. Voxel-wise signal trajectories were clustered using the k-means algorithm. Voxel clusters that best segment the liver vessels were selected and labeled by three independent radiologists and a research scientist using LiVaS. Segmentation times were compared using a paired-sample t-test on log-transformed data. The agreement was analyzed qualitatively and quantitatively using DSC for hepatic and portal vein segmentations. The mean segmentation time among four readers was significantly shorter than manual (3.6 ± 1.4 vs. 70.0 ± 29.2 min; p < 0.001), even when using a higher number of clusters to enhance accuracy. The DSC for portal and hepatic veins reached up to 0.69 and 0.70, respectively. LiVaS segmentations were overall of good quality, with variations in performance related to the presence/severity of liver disease, acquisition timing, and image quality. Our semi-automated pipeline was robust to different MRI vendors in producing segmentation and labeling of liver vasculature in agreement with expert manual annotations, with significantly higher time efficiency. LiVaS could facilitate the creation of large, annotated datasets for training and validation of neural networks for automated MRI liver vascularity segmentation. HIGHLIGHTS: Key Finding: In this pilot feasibility study, our semiautomated pipeline for segmentation of liver vascularity (LiVaS) on MR images produced segmentations with simultaneous labeling of portal and hepatic veins in good agreement with the manual reference standard but at significantly shorter times (mean LiVaS 3.6 ± 1.4 vs. mean manual 70.0 ± 29.2 min; p < 0.001). Importance: LiVaS was robust in producing liver MRI vascular segmentations across images from different scanners in agreement with expert manual annotations, with significant ly higher time efficiency, and therefore potential scalability.

14.
World J Diabetes ; 15(1): 43-52, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38313855

RESUMO

BACKGROUND: Among older adults, type 2 diabetes mellitus (T2DM) is widely recognized as one of the most prevalent diseases. Diabetic nephropathy (DN) is a frequent complication of DM, mainly characterized by renal microvascular damage. Early detection, aggressive prevention, and cure of DN are key to improving prognosis. Establishing a diagnostic and predictive model for DN is crucial in auxiliary diagnosis. AIM: To investigate the factors that impact T2DM complicated with DN and utilize this information to develop a predictive model. METHODS: The clinical data of 210 patients diagnosed with T2DM and admitted to the First People's Hospital of Wenling between August 2019 and August 2022 were retrospectively analyzed. According to whether the patients had DN, they were divided into the DN group (complicated with DN) and the non-DN group (without DN). Multivariate logistic regression analysis was used to explore factors affecting DN in patients with T2DM. The data were randomly split into a training set (n = 147) and a test set (n = 63) in a 7:3 ratio using a random function. The training set was used to construct the nomogram, decision tree, and random forest models, and the test set was used to evaluate the prediction performance of the model by comparing the sensitivity, specificity, accuracy, recall, precision, and area under the receiver operating characteristic curve. RESULTS: Among the 210 patients with T2DM, 74 (35.34%) had DN. The validation dataset showed that the accuracies of the nomogram, decision tree, and random forest models in predicting DN in patients with T2DM were 0.746, 0.714, and 0.730, respectively. The sensitivities were 0.710, 0.710, and 0.806, respectively; the specificities were 0.844, 0.875, and 0.844, respectively; the area under the receiver operating characteristic curve (AUC) of the patients were 0.811, 0.735, and 0.850, respectively. The Delong test results revealed that the AUC values of the decision tree model were lower than those of the random forest and nomogram models (P < 0.05), whereas the difference in AUC values of the random forest and column-line graph models was not statistically significant (P > 0.05). CONCLUSION: Among the three prediction models, random forest performs best and can help identify patients with T2DM at high risk of DN.

15.
Sci Adv ; 10(5): eadj3808, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38306424

RESUMO

G protein-coupled receptor 39 (GPR39) senses the change of extracellular divalent zinc ion and signals through multiple G proteins to a broad spectrum of downstream effectors. Here, we found that GPR39 was prevalent at inhibitory synapses of spinal cord somatostatin-positive (SOM+) interneurons, a mechanosensitive subpopulation that is critical for the conveyance of mechanical pain. GPR39 complexed specifically with inhibitory glycine receptors (GlyRs) and helped maintain glycinergic transmission in a manner independent of G protein signalings. Targeted knockdown of GPR39 in SOM+ interneurons reduced the glycinergic inhibition and facilitated the excitatory output from SOM+ interneurons to spinoparabrachial neurons that engaged superspinal neural circuits encoding both the sensory discriminative and affective motivational domains of pain experience. Our data showed that pharmacological activation of GPR39 or augmenting GPR39 interaction with GlyRs at the spinal level effectively alleviated the sensory and affective pain induced by complete Freund's adjuvant and implicated GPR39 as a promising therapeutic target for the treatment of inflammatory mechanical pain.


Assuntos
Dor , Receptores Acoplados a Proteínas G , Humanos , Neurônios/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Receptores de Glicina/metabolismo , Transdução de Sinais , Medula Espinal/metabolismo
16.
Angew Chem Int Ed Engl ; : e202401014, 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38334002

RESUMO

Developing high connectivity (>8) three-dimensional (3D) covalent organic frameworks (COFs) towards new topologies and functions remains a great challenge owing to the difficulty in getting high connectivity organic building blocks. This however represents the most important step towards promoting the diversity of COFs due to the still limited dynamic covalent bonds available for constructing COFs at this stage. Herein, highly connected phthalocyanine-based (Pc-based) 3D COFs MPc-THHI-COFs (M=H2 , Ni) were afforded from the reaction between 2,3,9,10,16,17,23,24-octacarboxyphthalocyanine M(TAPc) (M=H2 , Ni) and 5,5',5'',5''',5'''',5'''''-(triphenylene-2,3,6,7,10,11-hexayl)hexa(isophthalohydrazide) (THHI) with 12 connecting sites. Powder X-ray diffraction analysis together with theoretical simulations and transmission electron microscopy reveals their crystalline nature with an unprecedented non-interpenetrated shp topology. Experimental and theoretical investigations disclose the broadened visible light absorption range and narrow optical band gap of MPc-THHI-COFs. This in combination with their 3D nanochannels endows them with efficient photocatalysis performance for H2 O2 generation from O2 and H2 O via 2e- oxygen reduction reaction and 2e- water oxidation reaction under visible-light irradiation (λ >400 nm). This work provides valuable result for the development of high connectivity functional COFs towards diverse application potentials.

17.
Nat Med ; 2024 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-38242982

RESUMO

Hepatocellular carcinoma (HCC), particularly when accompanied by microvascular invasion (MVI), has a markedly high risk of recurrence after liver resection. Adjuvant immunotherapy is considered a promising avenue. This multicenter, open-label, randomized, controlled, phase 2 trial was conducted at six hospitals in China to assess the efficacy and safety of adjuvant sintilimab, a programmed cell death protein 1 inhibitor, in these patients. Eligible patients with HCC with MVI were randomized (1:1) into the sintilimab or active surveillance group. The sintilimab group received intravenous injections every 3 weeks for a total of eight cycles. The primary endpoint was recurrence-free survival (RFS) in the intention-to-treat population. Key secondary endpoints included overall survival (OS) and safety. From September 1, 2020, to April 23, 2022, a total of 198 eligible patients were randomly allocated to receive adjuvant sintilimab (n = 99) or undergo active surveillance (n = 99). After a median follow-up of 23.3 months, the trial met the prespecified endpoints. Sintilimab significantly prolonged RFS compared to active surveillance (median RFS, 27.7 versus 15.5 months; hazard ratio 0.534, 95% confidence interval 0.360-0.792; P = 0.002). Further follow-up is needed to confirm the difference in OS. In the sintilimab group, 12.4% of patients experienced grade 3 or 4 treatment-related adverse events, the most common of which were elevated alanine aminotransferase levels (5.2%) and anemia (4.1%). These findings support the potential of immune checkpoint inhibitors as effective adjuvant therapy for these high-risk patients. Chinese Clinical Trial Registry identifier: ChiCTR2000037655 .

18.
Artigo em Inglês | MEDLINE | ID: mdl-38175448

RESUMO

BACKGROUND: Thymidine kinase 1 (TK1) plays a pivotal role in DNA synthesis and cellular proliferation. TK1 has been studied as a prognostic marker and as an early indicator of treatment response in human epidermal growth factor 2 (HER2)-negative early and metastatic breast cancer (BC). However, the prognostic and predictive value of serial TK1 activity in HER2-positive BC remains unknown. METHODS: In the PREDIX HER2 trial, 197 HER2-positive BC patients were randomized to neoadjuvant trastuzumab, pertuzumab, and docetaxel (DPH) or trastuzumab emtansine (T-DM1), followed by surgery and adjuvant epirubicin and cyclophosphamide. Serum samples were prospectively collected from all participants at multiple timepoints: at baseline, after cycle 1, 2, 4, and 6, at end of adjuvant therapy, annually for a total period of 5 years and/or at the time of recurrence. The associations of sTK1 activity with baseline characteristics, pathologic complete response (pCR), event-free survival (EFS), and disease-free survival (DFS) were evaluated. RESULTS: No association was detected between baseline sTK1 levels and all the baseline clinicopathologic characteristics. An increase of TK1 activity from baseline to cycle 2 was seen in all cases. sTK1 level at baseline, after 2 and 4 cycles was not associated with pCR status. After a median follow-up of 58 months, 23 patients had EFS events. There was no significant effect between baseline or cycle 2 sTK1 activity and time to event. A non-significant trend was noted among patents with residual disease (non-pCR) and high sTK1 activity at the end of treatment visit, indicating a potentially worse long-term prognosis. CONCLUSION: sTK1 activity increased following neoadjuvant therapy for HER2-positive BC but was not associated with patient outcomes or treatment benefit. However, the post-surgery prognostic value in patients that have not attained pCR warrants further investigation. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02568839. Registered on 6 October 2015.

19.
J Robot Surg ; 18(1): 8, 2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-38206493

RESUMO

To investigate the effectiveness of continuity of care after robot-assisted adrenal tumor resection under ambulatory mode. Patients who underwent robot-assisted laparoscopic adrenalectomy (RALA) in the ambulatory surgery department and urology department of our hospital from January 2022 to January 2023 were selected as study subjects. Among them, 50 patients in the Department of Urology as the control group were given routine care. The 50 patients in the ambulatory surgery department as the observation group were given continuity of care on the basis of routine care. Observation indexes include: wound healing, blood pressure, blood potassium, renal function impairment, self-care ability in daily life, medication compliance, follow-up rate, and patient satisfaction. There were no remarkable discrepancies between the two groups in terms of demographic data and basic preoperative conditions of the patients. Compared with the control group, the observation group significantly improved the patients' wound healing, postoperative blood pressure and blood potassium and kidney function (P value all < 0.05). Compared with the control group, the observation group significantly improved postoperative patients' ADL scores, follow-up rates within three months after surgery, and patient satisfaction scores (P value all < 0.05). For patients receiving ambulatory mode robot-assisted laparoscopic adrenalectomy, continuity of care can effectively reduce postoperative complications, improve patients' postoperative self-care ability in daily life, medication compliance and follow-up rate, and improve patient satisfaction, which is worthy of promotion and application by nursing workers.


Assuntos
Laparoscopia , Procedimentos Cirúrgicos Robóticos , Robótica , Humanos , Adrenalectomia , Procedimentos Cirúrgicos Robóticos/métodos , Continuidade da Assistência ao Paciente , Potássio
20.
Langmuir ; 2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-38237145

RESUMO

The magnetorheological effect is a critically important mechanical property of magnetic fluids. Accurately capturing the macroscopic properties of magnetorheological fluids with elongated particle forms, such as nanosphere chains, remains a challenging task, particularly due to the complexities arising from particle asymmetry. Traditional particle dynamics primarily utilize spherical particles as computational units, but this approach can lead to significant inaccuracies, especially when analyzing nonspherical magnetorheological fluids, due to the neglect of particle asymmetry. In this work, an advanced particle dynamics model has been developed by integrating the rotation and collision of these asymmetric particles, specifically tailored for the configuration of nanosphere chains. This model exhibits a significant reduction in error by a factor of 3.883, compared to conventional particle models. The results demonstrate that alterations in the geometric characteristics of magnetic nanosphere chains can cause changes in mesoscopic structures and magnetic potential energy, thereby influencing the mechanical properties at the macroscopic level. This work has developed an accurate mesoscopic simulation method for calculating chain-type magnetorheological fluids, establishing a connection between mesoscopic structures and macroscopic properties, and unveiling the tremendous potential for accelerating the design of next-generation magnetic fluids using this approach.

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