ABSTRACT
Bone defects remain a significant challenge in clinical orthopedics, but no targeted medication can solve these problems. Inspired by inflammatory targeting properties of macrophages, inflammatory microenvironment of bone defects was exploited to develop a multifunctional nanocarrier capable of targeting bone defects and promoting bone regeneration. The avidin-modified black phosphorus nanosheets (BP-Avidin, BPAvi) were combined with biotin-modified Icaritin (ICT-Biotin, ICTBio) to synthesize Icaritin (ICT)-loaded black phosphorus nanosheets (BPICT). BPICT was then coated with macrophage membranes (MMs) to obtain MMs-camouflaged BPICT (M@BPICT). Herein, MMs allowed BPICT to target bone defects area, and BPICT accelerated the release of phosphate ions (PO43-) and ICT when exposed to NIR irradiation. PO43- recruited calcium ions (Ca2+) from the microenvironment to produce Ca3(PO4)2, and ICT increased the expression of osteogenesis-related proteins. Additionally, M@BPICT can decrease M1 polarization of macrophage and expression of pro-inflammatory factors to promote osteogenesis. According to the results, M@BPICT provided bone growth factor and bone repair material, modulated inflammatory microenvironment, and activated osteogenesis-related signaling pathways to promote bone regeneration. PTT could significantly enhance these effects. This strategy not only offers a solution to the challenging problem of drug-targeted delivery in bone defects but also expands the biomedical applications of MMs-camouflaged nanocarriers.
Subject(s)
Avidin , Osteogenesis , Avidin/metabolism , Avidin/pharmacology , Biotin , Phototherapy , Macrophages/metabolism , Bone Regeneration , Phosphorus/pharmacology , PhosphatesABSTRACT
In this paper, a water-based metasurface with adjustable reflection amplitude is proposed. The overall structure uses a transparent substrate as a water-based container, and the upper surface is loaded with a double-ring-shaped resistive film. As the height of the water in the container gradually increases from 0 mm to 0.5 mm, within a broadband range from 0.1 GHz to 30 GHz, the maximum adjustable range of the reflection amplitude is -2 dB to -12 dB. The water-based metasurface switches from a state of strong reflection to a state of absorption. The test results are in good agreement with the simulation results. Because the tunable metasurface is transparent to visible light, it can be used for electromagnetic shielding of windows of airplanes.
ABSTRACT
BACKGROUND: Although hematopoietic stem cell transplantation provides the chances of survival for aplastic anemia patients, it is also related to many treatment-related physical and psychological side effects that severely influence the quality of life. Exercise interventions have shown positive results in mixed hematology populations. The study aims to determine the effectiveness of exercise rehabilitation in improving the quality of life, fatigue, and physical function in these patients. METHODS: The study will enroll a total of 82 aplastic anemia patients receiving hematopoietic stem cell transplantation. They will be randomly divided into two groups in a 1:1 ratio. The intervention group will participate in structured exercise rehabilitation (plus usual care), while control group participants will receive usual care. The exercise rehabilitation program will be performed from neutrophil and platelet engraftment until 100 days after transplantation. All outcomes will be measured at the following time points: the neutrophil and platelet engraftment (± 1day, T0), discharge from the transplantation module (± 1 day, T1), hospital discharge (± 1 day, T2), and 100 days post-transplantation (± 5 days, T3). DISCUSSION: This study aims to assess the effectiveness of exercise rehabilitation for aplastic anemia patients receiving hematopoietic stem cell transplantation in a Chinese single center. It is particularly vital to conduct the studies in this population. Moreover, the evidence obtained from the study will provide evidence for future research and clinical practice to exercise in aplastic anemia patients. TRIAL REGISTRATION: ChiCTR2200060762. Registered on May 2022, www.trialregister.nl/trial/7702.
Subject(s)
Anemia, Aplastic , Exercise Therapy , Hematopoietic Stem Cell Transplantation , Quality of Life , Randomized Controlled Trials as Topic , Humans , Anemia, Aplastic/rehabilitation , Anemia, Aplastic/therapy , Exercise Therapy/methods , Treatment Outcome , Adult , Male , Adolescent , Female , Young Adult , Fatigue/etiology , Middle Aged , Time Factors , China , Recovery of FunctionABSTRACT
The effective repair of bone defects has long been a major challenge in clinical practice. Currently, research efforts mostly focus on achieving sufficiently good bone repair, with little attention paid to achieving both good and fast repair. However, achieving highly efficient (H-efficient) bone repair, which is both good and fast, can shorten the treatment cycle and facilitate rapid patient recovery. Therefore, the development of a H-efficient bone repair material is of significant importance. This study incorporated the previously developed osteoinductive photothermal agent (PTA) BPICT into printing paste to prepare a near-infrared (NIR)-responsive BPICT scaffold. Subsequently, the effects of photothermal therapy (PTT) on bone repair and drug release were assessed in vitro. To further validate the H-efficient bone repair properties of the BPICT scaffold, the scaffold was implanted into bone defects and its ability to promote bone repair in vivo was evaluated through radiology and histopathological analysis. The results indicated that compared to scaffolds containing only Icaritin (ICT), the BPICT scaffold can achieve PTT to promote bone repair through NIR irradiation, while also enabling the controlled release of ICT from the scaffold to enhance bone repair. Within the same observation period, the BPICT scaffold achieves more efficient bone repair than the ICT scaffold, significantly shortening the bone repair cycle while ensuring the effectiveness of bone repair. Therefore, the NIR-responsive scaffold based on PTT-mediated controlled release of bone growth factors represents a feasible solution for promoting H-efficient bone repair in the area of bone defects.
Subject(s)
Bone Regeneration , Infrared Rays , Tissue Scaffolds , Tissue Scaffolds/chemistry , Animals , Bone Regeneration/drug effects , Photothermal Therapy , Mice , Osteogenesis/drug effects , HumansABSTRACT
Porous poly (lactic-co-glycolic acid)/ß-tricalcium phosphate/Icaritin (PLGA/ß-TCP/ICT, PTI) scaffold is a tissue engineering scaffold based on PLGA/ß-TCP containing Icaritin, the main active ingredient of the Chinese medicine Epimedium. Due to its excellent mechanical properties and osteogenic effect, PTI scaffold has the potential to promote bone defect repair. However, the release of ICT from the scaffolds is difficult to control. In this study, we constructed Ti3C2Tx@PLGA/ICT microspheres (TIM) and evaluated their characterization as well as ICT release under near-infrared (NIR) irradiation. We utilized TIM to modify the PT scaffold and performed biological experiments. First, we cultured rat bone marrow mesenchymal stem cells on the scaffold to assess biocompatibility and osteogenic potential under on-demand NIR irradiation. Subsequently, to evaluate the osteogenic properties of TIM-modified scaffold in vivo, the scaffold was implanted into a femoral condyle defect model. TIM have excellent drug-loading capacity and encapsulation efficiency for ICT, and the incorporation of Ti3C2Tx endows TIM with photothermal conversion capability. Under 0.90 W cm-2 NIR irradiation, the temperature of TIM maintained at 42.0 ± 0.5°C and the release of ICT was accelerated. Furthermore, while retaining its original properties, the TIM-modified scaffold was biocompatible and could promote cell proliferation, osteogenic differentiation, and biomineralization in vitro, as well as the osteogenesis and osseointegration in vivo, and its effect was further enhanced through the modulation of ICT release under NIR irradiation. In summary, TIM-modified scaffold has the potential to be applied in bone defects repairing.
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Background: Aplastic anemia is characterized by anemia, hemorrhage and infection, and is accompanied by a variety of complications and psychological burden. Therefore, the quality of life of AA patients is not optimistic. Our team is committed to developing an assessment tool for the quality of life of AA patients, and adopting an iterative strategy of cognitive interview and expert consultation to solve the challenges encountered in item revision. Purpose: We aim to use the strategy of cognitive interview and expert consultation to inform revision of the QLS-AA into a user-friendly tool with unambiguous items and improve the content validity of the scale. Methods: We used an iterative strategy of cognitive interview and expert consultation. Two rounds of cognitive interview were conducted to identify problems with item comprehension, recall and other cognitive processes. As well as, a multi-disciplinary group of expert consultation was consulted to review the rationality of item revisions. Results: In the first round of cognitive interview, 16 participants responded to 107 items. Among them, the most common problems were "clarification" and "item duplication". Based on the results of the first round of interview, an expert consultation was organized. A total of 16 amendments were put forward by the expert and 14 were adopted. In the second round of cognitive interviews, A total of 5 participants were included and 64 items were evaluated. Two items were suggested to be revised, and the remaining items were accurately understood and recognized by all participants. Couclusion: This study highlights the key issues to consider when incorporating patient perspectives into quality measurement. The revision of QLS-AA through the strategy of cognitive interview and expert consultation may provide valuable insights into the measurement of quality of life in aplastic patients. Trial Registration Number: ChiCTR2100047575.
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INTRODUCTION: The organisational silence of nursing teams has received increasing attention from managers. Chinese nurses have a relatively high score for organisational silence, and male nurses score higher than female nurses. Lack of professional empathy, high pressure in the work environment, and traditional Chinese cultural factors suggest that Chinese male nurses' experiences of and reasons for organisational silence are complex and unique. Taking male nurses in the emergency department as an example, this study explores the experience and meaning of male nurses' organisational silence and provides ideas for nursing managers to understand the silence of male nurses. METHODS AND ANALYSIS: An interpretative phenomenological approach underpins the study design. In this study, the purposive sampling method will be used to select male nurses who meet the inclusion criteria with maximum differentiation as a strategy. Face-to-face semistructured interviews and Van Manen analysis methods will be used for data collection and analysis. ETHICS AND DISSEMINATION: The study was approved by the Ethics Committee of the First Affiliated Hospital of Zhejiang Chinese Medical University (ethical approval ID: 2019-KL-036-01). Participants will provide informed consent, will be able to withdraw at any time and will have their contributions kept confidential. The findings of the study will be shared with relevant stakeholders and disseminated in conference presentations and journal publications. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry (ChiCTR2100047057).
Subject(s)
Emergency Service, Hospital , Nurses, Male , Nursing, Team , China , Humans , Male , Nurses, Male/psychology , Nursing, Team/organization & administrationABSTRACT
BACKGROUND: Demethoxycurcumin (DMC), a natural derivative of curcumin, has anti-inflammatory activities. However, the mechanism has not been fully elucidated. OBJECTIVE: The aim of the current study was to investigate the role of DMC on NLRP3 inflammasome priming. METHODS: Protein expression was quantified by western blotting. Inflammatory cytokines were measured by ELISA. Autophagosomes were evaluated by transmission electron microscopy. RESULTS: DMC inhibited LPS-stimulated NLRP3, pro-caspase-1, and pro-IL-1ß expression. Meanwhile, DMC diminished NLRP3-dependent IL-1ß maturation, caspase-1 activation, IL-1ß, and IL-18 production caused by LPS plus ATP. Moreover, DMC induced autophagy and autophagy inhibitor 3-MA abrogated the role of DMC on NLRP3 inflammasome priming and subsequent activation. DMC also inhibited LPS-stimulated phosphorylation and nuclear translocation of p65 NF-κB. Additionally, DMC significantly increased the PPARγ expression, and the effects of DMC in NF- κB inhibition, autophagy, and NLRP3 inflammasome priming were abrogated by specific PPARγ antagonist T0070907. CONCLUSION: The evidence presented here has confirmed that DMC increases PPARγ expression, resulting in autophagy and NF-κB inhibition, and subsequently inhibits LPS-induced NLRP3 inflammasome priming and subsequent activation.
Subject(s)
Inflammasomes , NF-kappa B , Autophagy , Diarylheptanoids , Inflammasomes/metabolism , NF-kappa B/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , PPAR gamma/metabolism , Signal TransductionABSTRACT
Background: In the perioperative management of Total Knee Arthroplasty (TKA), postoperative fever has always been a concern. Current research focuses on infectious fever, and there is no relevant research on the occurrence of non-infectious fever (NIF) and its risk factors. Hence, the aim of this study was to clarify the risk factors for NIF after TKA, and construct an easy-to-use nomogram. Methods: A retrospective cohort study was conducted. Consecutive patients undergoing primary unilateral TKA were divided into the non-infectious fever group and the control group. Clinicopathological characters were collected from electronic medical records. Univariate Logistic regression was used to analyze the related independent risk factors. The optimal threshold for each selected factor and combined index was determined when the Youden index achieved the highest value. And the predictive nomogram was developed by these independent factors. Results: Ultimately, 146 patients were included in this study. Of them, 57 (39.04%) patients experienced NIF. Results of the univariable logistic regression analysis indicated that intraoperative blood loss (OR, 1.002; 95% CI, 1.000-1.0004), postoperative drainage fluid volume (OR, 1.003; 95% CI, 1.001-1.006) and frequency of blood transfusion (n = 1; OR, 0.227; 95% CI, 0.068-0.757) were independent risk factors of NIF occurrence. The predictive nomogram that incorporated the above independent risk factors was developed, and it yielded an areas under the curves (AUC) of 0.731 (95% CI: 0.651-0.801; P < 0.0001) with 54.39% sensitivity and 82.02% specificity. Conclusions: Non-infectious fever after TKA prolongs the time of antibiotic use and hospital stay. Our results demonstrated that the nomogram may facilitate to predict the individualized risk of NIF occurrence within 7-day by intraoperative blood loss, postoperative drainage fluid volume and frequency of blood transfusion.
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A coumarin-based turn on probe, named 3-((E)-3-(1H-indol-3-yl)acryloyl)-2H-chromen-2-one(IAC) was designed and synthesized for the detection of H2S in aqueous medium. IAC showed no obvious red fluorescence in Tris-HCl(pHâ¯=â¯7.2, 60% DMF), a 28.2-fold fluorescence enhancement was found when 40 equiv. H2S was added. Other analytes such as anions, metal ions and GSH, Cys, Gly did no significant fluorescence enhancement at 580â¯nm to IAC. The red fluorescence enhancement mechanism between IAC and H2S was considered by DFT and ESI-MS. Overall, IAC was successfully applied in cell imaging.
Subject(s)
Fluorescent Dyes/chemistry , Hydrogen Sulfide/analysis , Hydrogen Sulfide/chemistry , Molecular Imaging/methods , Coumarins/chemistry , Density Functional Theory , Fluorescent Dyes/pharmacokinetics , Fluorescent Dyes/toxicity , Fresh Water/analysis , Fresh Water/chemistry , HEK293 Cells , Humans , Hydrogen Sulfide/pharmacology , Limit of Detection , Microscopy, Confocal/instrumentation , Spectrometry, Fluorescence , Spectrometry, Mass, Electrospray Ionization , Spectrophotometry, Ultraviolet , Time FactorsABSTRACT
Development of high performance fluorescent chemosensors for the detection of ClO- in vitro and in vivo is very desirable, because many human diseases are caused by ClO-. In this paper, a highly selectivity and sensitive fluorescent probe, EDPC, based on 3-acetylcoumarin, was synthesized, which could respond to ClO- and exhibit an "off-on" mode in Tris-HCl buffer (pH = 7.2, 10 mM, 50% C2H5OH) solutions. The detection limit of the EDPC probe for ClO- was as low as 1.2 × 10-8 M. Moreover, the high selectivity and high sensitivity of EDPC towards ClO- are attributed to the oxidation reaction between the C-O of the coumarin lactone and the C[double bond, length as m-dash]C formed by aldol condensation and the mechanism was further verified using ESI-MS and DFT. Additionally, the concentrations of ClO- in real water were also calculated using the EDPC probe and showed good recovery. Finally, the distribution of intracellular endogenous ClO- was gained by confocal fluorescence microscopy in living HEK293T cells.
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This work, two turn-on fluorescent probes (3-acetyl-2H-chromen-2-one (ACO) & (1E)-1-(1-(2-oxo-2H-chromen-3-yl)ethylidene)thiosemicarbazide (CETC)) based on coumarin have been designed and synthesized, which could selectively and sensitively recognize ClO- with fast response time. ACO &CETC were almost non fluorescent possibly due to both the lacton form of coumarin and unbridged CN bonds which can undergo a nonradiative decay process in the excited state. Upon the addition of ClO-, ACO &CETC were oxidized to ring - opened by cleavage the CO and CN and the fluorescence intensity were increased considerably. Fluorescence titration experiments showed that the detection limit ACO &CETC is as low as 22â¯nm and 51â¯nm respectively. In particular, some relevant reactive species, including OH, 1O2, H2O2, KO2, some anions and cations cannot be interference with the test. In live cell experiments, ACO &CETC were successfully applied to image exogenous ClO- in HepG2 cells. Therefore, ACO &CETC not only could image ClO- in living cells but also proved that CO and CN can be cleavage by ClO-.
Subject(s)
Benzopyrans/chemistry , Fluorescent Dyes/chemistry , Hypochlorous Acid/analysis , Molecular Imaging/methods , Semicarbazides/chemistry , Benzopyrans/chemical synthesis , Fluorescent Dyes/chemical synthesis , Hep G2 Cells , Humans , Oxidation-Reduction , Semicarbazides/chemical synthesis , Sensitivity and Specificity , Spectrometry, Fluorescence/methods , Spectrophotometry, UltravioletABSTRACT
It is necessary to develop simple and highly sensitive methods for the detection of hypochlorous acid (HOCl)/hypochlorite (ClO-) to ravel its relationship with disease. In this paper, a novel bio-compatible fluorescent (Z)-8-(hydrazonomethyl)-7-hydroxy-4-methyl-2H-chromen-2-one (probe 1b) based on coumarin was synthesized and used for detecting ClO- in PBS buffer (pHâ¯=â¯7.2, 10â¯mM, 60% C2H5OH). Probe 1b showed a remarkable fluorescence change from yellow to blue with the limit of detection as low as 2.4â¯×â¯10-9â¯M-1 when ClO- was added. The coexisted anions, metal ions and reactive oxygen species (â¢OH, 1O2, H2O2, KO2) showed any competitiveness towards ClO-. In response to ClO-, the fluorescence emission intensity of probe 1b was obviously enhanced within 20â¯s. The mechanism was confirmed by the ESI - MS and density functional theory calculations (DFT) to reveal that the coumarin lactone bonds C - O was cleavaged by oxidation of ClO-. What's more, probe 1b could be used in practical water samples and showed well recovery. Additionally, the cell imaging experiment was demonstrated that probe 1b could be effectively exploited to imaging exogenous ClO- in vitro.