Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.570
Filtrar
1.
Food Chem ; 369: 130894, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-34455322

RESUMO

Fast and convenient matrix purification is an important prerequisite for high-throughput analysis of drug multiresidues in food. In this study, a silanized melamine sponge was prepared and first applied in the rapid determination of multiclass veterinary drugs in eggs by ultrahigh-performance liquid chromatography-tandem mass spectrometry. Within five seconds, fast, convenient and efficient matrix separation could be achieved through simple soaking and squeezing. Compared to other matrix adsorbents, the developed material demonstrated equivalent or better purification performance. Good validation results were obtained in terms of drug recoveries (61.5%~97.0%, relative standard deviation (RSD) ≤ 10.8%), and linearities (R2 ≥ 0.999), as well as low limits of quantitation (0.3 ~ 10.9 µg·kg-1) and detection (0.1 ~ 3.8 µg·kg-1). By analyzing 52 egg samples, high concentrations of ofloxacin, trimethoprim, metronidazole, and dimetridazole were found at 542.9, 121.2, 66.1 and 58.0 µg·kg-1, respectively. The silanized melamine sponge has shown its great potential for rapid analysis of multiclass residues in food safety.

2.
Artigo em Inglês | MEDLINE | ID: mdl-34593685

RESUMO

OBJECTIVES: The purpose of this study was to evaluate the relationship between blood glucose level and the prevalence and frequency of stress urinary incontinence (SUI) in women. METHODS: We conducted a cross-sectional study of female participants in the National Health and Nutrition Examination Survey database between 2007 and 2016. Dose-response analysis curves and univariate and multivariate logistic regressions were used to determine the relationship between blood glucose level and the prevalence and frequency of SUI. RESULTS: A total of 10,771 participants were included in this study, of which 6,466 (60.0%) reported no SUI, 4,305 (31.1%) reported monthly SUI, and 953 (8.8%) reported weekly SUI. We found that the blood glucose levels were higher in the weekly SUI group than in the monthly SUI and no SUI groups. Based on blood glucose levels, participants were divided into 3 groups: ≤86.0 mg/dL group, >86.0 to 98.0 mg/dL group, and >98.0 mg/dL group. Dose-response curves showed a nonlinear positive correlation between blood glucose levels and the prevalence and extent of SUI, and participants in the glucose >98.0 mg/dL group had a 15.2% higher risk (adjusted odds risk, 1.152; 95% confidence interval, 1.027-1.293; P = 0.016) of SUI prevalence and 12.5% higher risk (adjusted odds risk 1.125; 95% confidence interval, 1.009-1.255; P = 0.034) of SUI frequency than participants in the glucose ≤86.0 mg/dL group. CONCLUSIONS: We found that the prevalence and frequency of SUI in women were positively correlated with blood glucose levels, and these findings warrant further study and application to clinical practice to control SUI in women.

3.
Artigo em Inglês | MEDLINE | ID: mdl-34618789

RESUMO

STUDY DESIGN: A Biomechanical in vitro Investigation. OBJECTIVE: To evaluate the function and stability of self-designed biomimetic artificial atlanto-odontoid joint(BAAOJ) replacement on the atlantoaxial joint. SUMMARY OF BACKGROUND DATA: Upper cervical fusion surgery is a common treatment for various atlantoaxial disorders, and favorable clinical outcome has been achieved. However, the fusion surgery results in loss of atlantoaxial motion as well as adjacent segments degeneration, reducing the quality of life of patients and might produce severe neurological symptoms. Non-fusion technology is expected to solve the above problems, but various designed devices have certain defects and are still in the exploratory phase. METHODS: Biomechanical tests were conducted on 10 fresh human cadaveric craniocervical specimens in the following sequence:(1) intact condition, (2) after the BAAOJ arthroplasty, (3) after BAAOJ fatigue test, (4) after odontoidectomy, and (5) after anterior rigid plate fixation. Three-dimensional movements of the C1-C2 segment were evaluated to investigate the function and stability of BAAOJ arthroplasty compared with the intact condition after the BAAOJ fatigue test, odontoidectomy, and rigid plate fixation. RESULTS: Comparing the BAAOJ implantation to the intact state, the ROM and neutral zone (NZ) were slightly reduced in all directions (P>0.05). Compared with the rigid plate fixation, the BAAOJ implantation significantly increased the ROM and NZ in all directions, especially in the axial rotation (P<0.05). CONCLUSION: We designed a BAAOJ for correcting atlantoaxial disorders arising from atlantoaxial instability. As a non-fusion device, the most critical feature of BAAOJ replacement is the retention of flexion-extension, lateral bending, and axial rotation range of motion similar to the normal state. It can also stabilize the atlantoaxial complex, and the BAAOJ itself has a good initial stability.Level of Evidence: 4.

4.
J Environ Manage ; 301: 113912, 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34628281

RESUMO

The increase in coal consumption and its impact on the environment has become a bottleneck that hinders sustainable development. This paper discusses the effect of economic growth and coal intensity on China's coal consumption during 2005-2017 using the Laspeyres index decomposition method. The decoupling of coal consumption from economic growth was examined in conjunction with the Tapio elasticity index, and the decoupling contributions of economic growth and coal intensity are further determined. The results indicated that economic growth drives an increase in coal consumption; however, the contribution rate declines gradually with decrease in economic growth rate in each province. Further research showed that the secondary industry is the main contributor to the increment, and the rapid development of tertiary industry increases indirect coal consumption. Coal intensity has a positive impact on curbing coal consumption, but it is not sufficient to offset the increment generated by the economic effect. Moreover, in each province, the curbing effect gradually decreased as the decline in coal intensity weakened in the secondary industry. Furthermore, coal consumption is weakly decoupled from economic growth over the long term, and the secondary industry will determine the future trend of decoupling.

5.
Food Funct ; 2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34647561

RESUMO

Aging is the leading cause of human morbidity and death worldwide. Pyrroloquinoline quinone (PQQ) is a water-soluble vitamin-like compound that has strong anti-oxidant capacity. Beneficial effects of PQQ on lifespan have been discovered in the model organism Caenorhabditis elegans (C. elegans), yet the underlying mechanisms remain unclear. In the current study, we hypothesized that the longevity-extending effect of PQQ may be linked to autophagy and insulin/IGF1 signaling (IIS) in C. elegans. Our data demonstrate that PQQ at a concentration of 1 mM maximally extended the mean life of C. elegans by 33.1%. PQQ increased locomotion and anti-stress ability, and reduced fat accumulation and reactive oxygen species (ROS) levels. There was no significant lifespan extension in PQQ-treated daf-16, daf-2, and bec-1 mutants, suggesting that these IIS- and autophagy-related genes may mediate the anti-aging effects of the PQQ. Furthermore, PQQ raised mRNA expression and the nuclear localization of the pivotal transcription factor daf-16, and then activated its downstream targets sod-3, clt-1, and hsp16.2. Enhanced activity of the autophagy pathway was also observed in PQQ-fed C. elegans, as evidenced by increased expression of the key autophagy genes including lgg-1, and bec-1, and also by an increase in the GFP::LGG-1 puncta. Inactivation of the IIS pathway-related genes daf-2 or daf-16 by RNAi partially blocked the increase in autophagy activity caused by PQQ treatment, suggesting that autophagy may be regulated by IIS. This study demonstrates that anti-aging properties of PQQ, in the C. elegans model, may be mediated via the IIS pathway and autophagy.

6.
Appl Opt ; 60(25): 7634-7639, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34613231

RESUMO

A fiber-optic probe consisting of a section of graded-index multimode fiber (GIMF) fused onto a few-mode fiber (FMF) is proposed in this paper. The orbital angular momentum (OAM) mode guided by the FMF was launched into the GIMF, and a focused OAM beam profile was obtained by tailoring the length of the GIMF. Based on the analysis of the propagation trajectory, the intensity distributions, and the phase distributions of the vortex beam in GIMF, the focusing properties of the OAM mode were investigated. It is found that there exists a maximum working distance at an optimal GIMF length, and a trade-off between the beam size and working distance should be taken into account for optical tweezer applications. These results are expected to be applied to optical fiber tweezers for more flexible and efficient optical manipulation of particles.

7.
Int J Immunopathol Pharmacol ; 35: 20587384211048265, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34608813

RESUMO

INTRODUCTION: Increasing evidence indicates that lncRNA TUG1 represents an oncogenic factor in cancer. But, the mechanisms by which lncRNA TUG1 contributes to lung adenocarcinoma (LAC) remain undocumented. METHODS: The relationship between lncRNA TUG1/miR-138-5p expression and clinical outcomes in patients with LAC was indicated by qPCR, FISH, and TCGA cohort. Gain- or loss-of-function experiments and in vivo tumorigenesis were used to assess the role of lncRNA TUG1 in LAC. The interplay between TUG1 and miR-138-5p was validated by luciferase gene report and RIP assays. qPCR and Western blot analyses were used to investigate the effects of TUG1 on miR-138-5p/HIF1A axis in LAC cells. RESULTS: We found that upregulation of TUG1 or downregulation of miR-138-5p was associated with lymph node or distant metastasis and indicated a poor survival in LAC. Reduced expression of TUG1 restrained the growth of LAC cells, while restored expression of TUG1 had the opposite effects. TUG1 was identified to negatively regulate miR-138-5p expression, and miR-138-5p reversed TUG1-induced cell proliferation by targeting HIF1A. Elevated expression of HIF1A predicted a poor survival in LAC. CONCLUSION: Our findings demonstrate that lncRNA TUG1 promotes the growth of LAC by regulating miR-138-5p-HIF1A axis.

8.
Artigo em Inglês | MEDLINE | ID: mdl-34606459

RESUMO

Production of functional forces by human motor systems require coordination across multiple muscles. Grip and pinch are two prototypes for grasping force production. Each grasp plays a role in a range of hand functions and can provide an excellent paradigm for studying fine motor control. Despite previous investigations that have characterized muscle synergies during general force production, it is still unclear how intermuscular coordination differs between grip and pinch and across different force outputs. Traditional muscle synergy analyses, such as non-negative matrix factorization or principal component analysis, utilize dimensional reduction without consideration of nonlinear characteristics of muscle co-activations. In this study, we investigated the novel method of multiplex recurrence networks (MRN) to assess the inter-muscular coordination for both grip and pinch at different force levels. Unlike traditional methods, the MRN can leverage intrinsic similarities in muscle contraction dynamics and project its layers to the corresponding weighted network (WN) to better model muscle interactions. Twenty-four healthy volunteers were instructed to grip and pinch an apparatus with force production at 30%, 50%, and 70% of their respective maximal voluntary contraction (MVC). The surface electromyography (sEMG) signals were recorded from eight muscles, including intrinsic and extrinsic muscles spanning the hand and forearm. The sEMG signals were then analyzed using MRNs and WNs. Interlayer mutual information ( I ) and average edge overlap ( ω ) of MRNs and average shortest path length ( L ) of WNs were computed and compared across groups for grasp types (grip vs. pinch) and force levels (30%, 50% and 70% MVC). Results showed that the extrinsic, rather than the intrinsic muscles, had significant differences in network parameters between both grasp types ( ), and force levels ( ), and especially at higher force levels. Furthermore, I and ω were strengthened over time ( ) except with pinch at 30% MVC. Results suggest that the central nervous system (CNS) actively increases cortical oscillations over time in response to increasing force levels and changes in force production with different sustained grasping types. Muscle coupling in extrinsic muscles was higher than in intrinsic muscles for both grip and pinch. The MRNs may be a valuable tool to provide greater insights into inter-muscular coordination patterns of clinical populations, assess neuromuscular function, or stabilize force control in prosthetic hands.

9.
J Med Internet Res ; 23(10): e26486, 2021 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-34665149

RESUMO

BACKGROUND: Prior literature suggests that psychosocial factors adversely impact health and health care utilization outcomes. However, psychosocial factors are typically not captured by the structured data in electronic medical records (EMRs) but are rather recorded as free text in different types of clinical notes. OBJECTIVE: We here propose a text-mining approach to analyze EMRs to identify older adults with key psychosocial factors that predict adverse health care utilization outcomes, measured by 30-day readmission. The psychological factors were appended to the LACE (Length of stay, Acuity of the admission, Comorbidity of the patient, and Emergency department use) Index for Readmission to improve the prediction of readmission risk. METHODS: We performed a retrospective analysis using EMR notes of 43,216 hospitalization encounters in a hospital from January 1, 2017 to February 28, 2019. The mean age of the cohort was 67.51 years (SD 15.87), the mean length of stay was 5.57 days (SD 10.41), and the mean intensive care unit stay was 5% (SD 22%). We employed text-mining techniques to extract psychosocial topics that are representative of these patients and tested the utility of these topics in predicting 30-day hospital readmission beyond the predictive value of the LACE Index for Readmission. RESULTS: The added text-mined factors improved the area under the receiver operating characteristic curve of the readmission prediction by 8.46% for geriatric patients, 6.99% for the general hospital population, and 6.64% for frequent admitters. Medical social workers and case managers captured more of the psychosocial text topics than physicians. CONCLUSIONS: The results of this study demonstrate the feasibility of extracting psychosocial factors from EMR clinical notes and the value of these notes in improving readmission risk prediction. Psychosocial profiles of patients can be curated and quantified from text mining clinical notes and these profiles can be successfully applied to artificial intelligence models to improve readmission risk prediction.

10.
Curr Biol ; 2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34666004

RESUMO

Transcription initiation has long been considered a primary regulatory step in gene expression. Recent work, however, shows that downstream events, such as transcription elongation, can also play important roles.1-3 A well-characterized example from animals is promoter-proximal pausing, where transcriptionally engaged Pol II accumulates 30-50 bp downstream of the transcription start site (TSS) and is thought to enable rapid gene activation.2 Plants do not make widespread use of promoter-proximal pausing; however, in a phenomenon known as 3' pausing, a significant increase in Pol II is observed near the transcript end site (TES) of many genes.4-6 Previous work has shown that 3' pausing is promoted by the BORDER (BDR) family of negative transcription elongation factors. Here we show that BDR proteins play key roles in gene repression. Consistent with BDR proteins acting to slow or pause elongating Pol II, BDR-repressed genes are characterized by high levels of Pol II occupancy, yet low levels of mRNA. The BDR proteins physically interact with FPA,7 one of approximately two dozen genes collectively referred to as the autonomous floral-promotion pathway,8 which are necessary for the repression of the flowering time gene FLOWERING LOCUS C (FLC).9-11 In early-flowering strains, FLC expression is repressed by repressive histone modifications, such as histone H3 lysine 27 trimethylation (H3K27me3), thereby allowing the plants to flower early. These results suggest that the repression of transcription elongation by BDR proteins may allow for the temporary pausing of transcription or facilitate the long-term repression of genes by repressive histone modifications.

11.
Int J Ophthalmol ; 14(10): 1602-1609, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34667739

RESUMO

AIM: To investigate the potential differences between topography-guided (TG) and wavefront-optimized (WFO) laser in situ keratomileusis (LASIK) for the treatment of myopia. METHODS: A systematic literature search was performed to determine relevant trials comparing LASIK with TG and WFO from the time of library construction to August 2020, and The PubMed, Cochrane, Web of Science, EMBASE and Chinese databases (i.e. CNKI, CBM, WAN FANG and VIP) were accessed. The data on visual acuity, refractive status and wavefront aberration were retrieved and evaluated from three to six months after surgery. STATA (version 14.0) software was used for statistical analysis. A cumulative Meta-analysis was simultaneously performed. RESULTS: Eleven studies with a total of 1425 eyes were incorporated. No statistically significant differences were evident between TG and WFO ablation in the proportion of eyes achieving an uncorrected distance visual acuity (UCVA) of 20/20 or better (P=0.377), gaining one line or more (P=0.05), postoperative cylinder (P=0.40), vertical coma (P=0.593) and horizontal coma (P=0.957). After TG ablation, the proportion of the patients' eyes of which postoperative refraction is within ±0.5 diopter of the target refraction was significantly higher than that undergoes WFO (P=0.003). As opposed to the WFO group, manifest refraction spherical equivalent (MRSE; P=0.000) was lower, and UCVA (P=0.005) was better in the TG group. The higher-order aberrations (HOAs; P=0.000), spherical aberration (P=0.000) and coma (P=0.000) were significantly lower in TG group. The cumulative Meta-analysis illustrated that the proportion of eyes achieving UCVA of 20/20 or better, postoperative refraction within ±0.5 diopter, and MRSE has steady between the two groups. CONCLUSION: Both TG-LASIK and WFO-LASIK are safe, effective, and predictable for correcting myopia. TG-LASIK may produce fewer aberration and is more precise than WFO-LASIK.

12.
Small ; : e2102907, 2021 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-34665526

RESUMO

Implant-associated bacterial infections significantly impair the integration between titanium and soft tissues. Traditional antibacterial modifications of titanium implants are able to eliminate bacteria, but the resulting pro-inflammatory reactions are usually ignored, which still poses potential risks to human bodies. Here, a dual drug-loading system on titanium has been developed via the adhesion of a catechol motif-modified methacrylated gelatin hydrogel onto TiO2 nanotubes. Then synthesized CaO2 nanoparticles (NPs) are embedded into the hydrogel, and interleukin-4 (IL-4) is loaded into the nanotubes to achieve both antibacterial and anti-inflammatory properties. The dual drug-loading system can eliminate Staphylococcus aureus (S. aureus) rapidly, attributed to the H2 O2 release from CaO2 NPs. The potential cytotoxicity of CaO2 NPs is also remarkably reduced after being embedded into the hydrogel. More importantly, with the gradual release of IL-4, the dual drug-loading system is capable of modulating pro-inflammatory reactions by inducing M2 phenotype polarization of macrophages. In a subcutaneous infection model, the S. aureus contamination is effectively resolved after 2 days, and the resulting pro-inflammatory reactions are also inhibited after 7 days. Finally, the damaged tissue is significantly recovered. Taken together, the dual drug-loading system exhibits great therapeutic potential in effectively killing pathogens and inhibiting the resulting pro-inflammatory reactions.

13.
Biomaterials ; 278: 121164, 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34601196

RESUMO

Bacterial infection treatment and subsequent tissue rebuilding are the main tasks of biomaterial research. To endow implants with antibacterial activity and biological functions, the material systems are usually very complicated and ineffective. Recently, the concept of photobiomodulation (PBM), or low-level laser therapy (LLLT), has attracted increasing attention in tissue repair applications but still has not obtained wide acceptance. Because of the same laser resource, PBM could simultaneously work with 660 nm laser triggered photodynamic therapy (PDT), which will significantly simplify the material system and achieve the multiple functions of antibacterial activity and biological modulation effects. Herein, we attempt to validate the effectiveness of PBM and combine PBM with a PDT-based material system. A catechol motif-modified methacrylated gelatin containing photosensitizer Chlorin e6-loaded mesoporous polydopamine nanoparticles was fabricated (GelMAc/MPDA@Ce6). This hydrogel could be tightly adhered to titanium surfaces to serve as surface coating materials or directly used as dressings. Because of the 660 nm laser-triggered ROS generation property of Ce6, GelMAc/MPDA@Ce6 exhibited a remarkable and rapid antibacterial activity when the laser power was 1 W cm-2. After bacterial elimination, when the power was adjusted to 100 mW cm-2, daily irradiation brought an excellent PBM effect: the fibroblast activation was realized to accelerate wound repair. According to our in vitro and in vivo results, the fabricated hydrogel coating possessed both antibacterial activity and fibroblast activation ability only by adjusting the power of laser irradiation, which will greatly strengthen the confidence of using PBM in broader fields and give a good example to combine PBM with traditional biomaterial design.

14.
J Nanobiotechnology ; 19(1): 268, 2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34488792

RESUMO

BACKGROUND: Tumor-associated macrophages (TAMs) are the most abundant stromal cells in the tumor microenvironment. Turning the TAMs against their host tumor cells is an intriguing therapeutic strategy particularly attractive for patients with immunologically "cold" tumors. This concept was mechanistically demonstrated on in vitro human and murine lung cancer cells and their corresponding TAM models through combinatorial use of nanodiamond-doxorubicin conjugates (Nano-DOX) and a PD-L1 blocking agent BMS-1. Nano-DOX are an agent previously proved to be able to stimulate tumor cells' immunogenicity and thereby reactivate the TAMs into the anti-tumor M1 phenotype. RESULTS: Nano-DOX were first shown to stimulate the tumor cells and the TAMs to release the cytokine HMGB1 which, regardless of its source, acted through the RAGE/NF-κB pathway to induce PD-L1 in the tumor cells and PD-L1/PD-1 in the TAMs. Interestingly, Nano-DOX also induced NF-κB-dependent RAGE expression in the tumor cells and thus reinforced HMGB1's action thereon. Then, BMS-1 was shown to enhance Nano-DOX-stimulated M1-type activation of TAMs both by blocking Nano-DOX-induced PD-L1 in the TAMs and by blocking tumor cell PD-L1 ligation with TAM PD-1. The TAMs with enhanced M1-type repolarization both killed the tumor cells and suppressed their growth. BMS-1 could also potentiate Nano-DOX's action to suppress tumor cell growth via blocking of Nano-DOX-induced PD-L1 therein. Finally, Nano-DOX and BMS-1 achieved synergistic therapeutic efficacy against in vivo tumor grafts in a TAM-dependent manner. CONCLUSIONS: PD-L1/PD-1 upregulation mediated by autocrine and paracrine activation of the HMGB1/RAGE/NF-κB signaling is a key response of lung cancer cells and their TAMs to stress, which can be induced by Nano-DOX. Blockade of Nano-DOX-induced PD-L1, both in the cancer cells and the TAMs, achieves enhanced activation of TAM-mediated anti-tumor response.

15.
Integr Comp Biol ; 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34477864

RESUMO

Costs to producing sexual signals can create selective pressures on males to invest signaling effort in particular contexts. When the benefits of signaling vary consistently across time, males can optimize signal investment to specific temporal contexts using biological rhythms. Sea lamprey, Petromyzon marinus, have a semelparous life history, are primarily nocturnal, and rely on pheromone communication for reproduction; however, whether male investment in pheromone transport and release matches increases in spawning activity remains unknown. By measuring 1) 3keto-petromyzonol sulfate (3kPZS, a main pheromone component) and its biosynthetic precursor petromyzonol sulfate (PZS) in holding water and tissue samples at 6 points over the course of 24 hours, and 2) 3kPZS release over the course of several days, we demonstrate that 3kPZS release exhibits a consistent diel pattern across several days with elevated pheromone release just prior to sunset and at night. Trends in hepatic concentrations and circulatory transport of PZS and 3kPZS were consistent with patterns of 3kPZS release and suggest the possibility of direct upregulation in pheromone transport and release rather than observed release patterns being solely a byproduct of increased behavioral activity. Our results suggest males evolved a signaling strategy that synchronizes elevated pheromone release with nocturnal increases in sea lamprey behavior. This may be imperative to ensure that male signaling effort is not wasted in a species having a single, reproductive event.

16.
Eur Heart J ; 2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34534287

RESUMO

AIMS: Aortic aneurysm and dissection (AAD) are high-risk cardiovascular diseases with no effective cure. Macrophages play an important role in the development of AAD. As succinate triggers inflammatory changes in macrophages, we investigated the significance of succinate in the pathogenesis of AAD and its clinical relevance. METHODS AND RESULTS: We used untargeted metabolomics and mass spectrometry to determine plasma succinate concentrations in 40 and 1665 individuals of the discovery and validation cohorts, respectively. Three different murine AAD models were used to determine the role of succinate in AAD development. We further examined the role of oxoglutarate dehydrogenase (OGDH) and its transcription factor cyclic adenosine monophosphate-responsive element-binding protein 1 (CREB) in the context of macrophage-mediated inflammation and established p38αMKOApoe-/- mice. Succinate was the most upregulated metabolite in the discovery cohort; this was confirmed in the validation cohort. Plasma succinate concentrations were higher in patients with AAD compared with those in healthy controls, patients with acute myocardial infarction (AMI), and patients with pulmonary embolism (PE). Moreover, succinate administration aggravated angiotensin II-induced AAD and vascular inflammation in mice. In contrast, knockdown of OGDH reduced the expression of inflammatory factors in macrophages. The conditional deletion of p38α decreased CREB phosphorylation, OGDH expression, and succinate concentrations. Conditional deletion of p38α in macrophages reduced angiotensin II-induced AAD. CONCLUSION: Plasma succinate concentrations allow to distinguish patients with AAD from both healthy controls and patients with AMI or PE. Succinate concentrations are regulated by the p38α-CREB-OGDH axis in macrophages.

17.
Chem Soc Rev ; 2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34570124

RESUMO

In situ monitoring of the location and transportation of bioactive molecules is essential for deciphering diverse biological events in the field of biomedicine. In addition, obtaining the in situ information of lesions will provide a clear perspective for surgeons to perform precise resection in clinical surgery. Notably, delivering drugs or operating photodynamic therapy/photothermal therapy in situ by labeling the lesion regions of interest can improve treatment and reduce side effects in vivo. In various advanced imaging and therapy modalities, optical theranostic agents based on organic small molecules can be conveniently modified as needed and can be easily internalized into cells/lesions in a non-invasive manner, which are prerequisites for in situ bioimaging and precision treatment. In this tutorial review, we first summarize the in situ molecular immobilization strategies to retain small-molecule agents inside cells/lesions to prevent their diffusion in living organisms. Emphasis will be focused on introducing the application of these strategies for in situ imaging of biomolecules and precision treatment, particularly pertaining to why targeting therapy in situ is required.

18.
J Headache Pain ; 22(1): 107, 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34503441

RESUMO

BACKGROUND: Medication-overuse headache (MOH) is a relatively frequently occurring secondary headache caused by overuse of analgesics and/or acute migraine medications. It is believed that MOH is associated with dependence behaviors and substance addiction, in which the salience network (SN) and the habenula may play an important role. This study aims to investigate the resting-state (RS) functional connectivity between the habenula and the SN in patients with MOH complicating chronic migraine (CM) compared with those with episodic migraine (EM) and healthy controls (HC). METHODS: RS-fMRI and 3-dimensional T1-weighted images of 17 patients with MOH + CM, 18 patients with EM and 30 matched healthy HC were obtained. The RS-fMRI data were analyzed using the independent component analysis (ICA) method to investigate the group differences of functional connectivity between the habenula and the SN in three groups. Correlation analysis was performed thereafter with all clinical variables by Pearson correlation. RESULTS: Increased functional connectivity between bilateral habenula and SN was detected in patients with MOH + CM compared with patients with EM and HC respectively. Correlation analysis showed significant correlation between medication overuse duration and habenula-SN connectivity in MOH + CM patients. CONCLUSIONS: The current study supported MOH to be lying within a spectrum of dependence and addiction disorder. The enhanced functional connectivity of the habenula with SN may correlate to the development or chronification of MOH. Furthermore, the habenula may be an indicator or treatment target for MOH for its integrative role involved in multiple aspects of MOH.


Assuntos
Habenula , Transtornos da Cefaleia Secundários , Transtornos de Enxaqueca , Cefaleia , Transtornos da Cefaleia Secundários/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Transtornos de Enxaqueca/complicações , Transtornos de Enxaqueca/diagnóstico por imagem
19.
Med Phys ; 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34520066

RESUMO

BACKGROUND: Iodine material images (aka iodine basis images) generated from dual energy CT (DECT) have been used to assess potential perfusion defects in the pulmonary parenchyma. However, iodine material images do not provide the needed absolute quantification of the pulmonary blood pool, as materials with effective atomic numbers (Zeff ) different from those of basis materials may also contribute to iodine material images, thus confounding the quantification of perfusion defects. PURPOSE: The purposes of this work were to (i) demonstrate the limitations of iodine material images in pulmonary perfusion defect quantification and (ii) develop and validate a new quantitative biomarker using effective atomic numbers derived from DECT images. METHODS: The quantitative relationship between the perfusion blood volume (PBV) in pulmonary parenchyma and the effective atomic number (Zeff ) spatial distribution was studied to show that the desired quantitative PBV maps are determined by the spatial maps of Zeff as PBVZeff (x) = a Zeff ß (x) + b, where a, b, and ß are three constants. Namely, quantitative PBVZeff is determined by Zeff images instead of the iodine basis images. Perfusion maps were generated for four human subjects to demonstrate the differences between conventional iodine material image-based PBV (PBViodine ) derived from two-material decompositions and the proposed PBVZeff method. RESULTS: Among patients with pulmonary emboli, the proposed PBVZeff maps clearly show the perfusion defects while the PBViodine maps do not. Additionally, when there are no perfusion defects present in the derived PBV maps, no pulmonary emboli were diagnosed by an experienced thoracic radiologist. CONCLUSION: Effective atomic number based quantitative PBV maps provide the needed sensitive and specific biomarker to quantify pulmonary perfusion defects. This article is protected by copyright. All rights reserved.

20.
BMJ Open ; 11(9): e049581, 2021 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-34489283

RESUMO

OBJECTIVES: To evaluate the cost-effectiveness of four different primary screening strategies: high-risk factor questionnaire (HRFQ) alone, single immunochemical faecal occult blood test (iFOBT), double iFOBT and HRFQ+double iFOBT for colorectal cancer (CRC) screening compared with no screening using the Markov model. METHODS: Treeage Pro V.2011 software was used to simulate the Markov model. The incremental cost-effectiveness ratio, which was compared with the willingness-to-pay (WTP) threshold, was used to reflect the cost-effectiveness of the CRC screening method. One-way sensitivity analysis and probabilistic sensitivity analysis were used for parameter uncertainty. RESULTS: All strategies had greater effectiveness because they had more quality-adjusted life years (QALYs) than no screening. When the WTP was ¥435 762/QALY, all screening strategies were cost-effective compared with no screening. The double iFOBT strategy was the best-buy option compared with all other strategies because it had the most QALYs and the least cost. One-way sensitivity analysis showed that the sensitivity of low-risk adenoma, compliance with colonoscopy and primary screening cost were the main influencing factors comparing single iFOBT, double iFOBT and HRFQ+double iFOBT with no screening. However, within the scope of this study, there was no fundamental impact on cost-effectiveness. Probabilistic sensitivity analysis showed that when the WTP was ¥435 762/QALY, the probabilities of the cost-effectiveness acceptability curve with HRFQ alone, single iFOBT, double iFOBT and HRFQ+double iFOBT were 0.0%, 5.3%, 69.3% and 25.4%, respectively. CONCLUSIONS: All screening strategies for CRC were cost-effective compared with no screening strategy. Double iFOBT was the best-buy option compared with all other strategies. The significant influencing factors were the sensitivity of low-risk polyps, compliance with colonoscopy and cost of primary screening.


Assuntos
Neoplasias Colorretais , Detecção Precoce de Câncer , China , Colonoscopia , Neoplasias Colorretais/diagnóstico , Análise Custo-Benefício , Humanos , Cadeias de Markov , Programas de Rastreamento , Sangue Oculto , Anos de Vida Ajustados por Qualidade de Vida
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...