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1.
Microsyst Nanoeng ; 10: 54, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38654844

RESUMO

In implantable electrophysiological recording systems, the headstage typically comprises neural probes that interface with brain tissue and integrated circuit chips for signal processing. While advancements in MEMS and CMOS technology have significantly improved these components, their interconnection still relies on conventional printed circuit boards and sophisticated adapters. This conventional approach adds considerable weight and volume to the package, especially for high channel count systems. To address this issue, we developed a through-polymer via (TPV) method inspired by the through-silicon via (TSV) technique in advanced three-dimensional packaging. This innovation enables the vertical integration of flexible probes, amplifier chips, and PCBs, realizing a flexible, lightweight, and integrated device (FLID). The total weight of the FLIDis only 25% that of its conventional counterparts relying on adapters, which significantly increased the activity levels of animals wearing the FLIDs to nearly match the levels of control animals without implants. Furthermore, by incorporating a platinum-iridium alloy as the top layer material for electrical contact, the FLID realizes exceptional electrical performance, enabling in vivo measurements of both local field potentials and individual neuron action potentials. These findings showcase the potential of FLIDs in scaling up implantable neural recording systems and mark a significant advancement in the field of neurotechnology.

2.
J Biophotonics ; : e202400023, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38576140

RESUMO

Light exposure has been proven to have a significant impact on human health. As a result, researchers are increasingly exploring its potential benefits and drawbacks. With advancements in understanding light and the manufacturing of light sources, modern health lighting has become widely utilized in daily life and plays a critical role in the prevention and treatment of various illnesses. The use of light in healthcare is a global trend, with many countries actively promoting the development and application of relevant scientific research and medical technology. This field has gained worldwide attention and support from scientists and doctors alike. In this review, we examine the application of lighting in human health and recent breakthroughs in light exposure related to pathology, therapeutic strategies, molecular changes, and more. Finally, we also discuss potential future developments and areas of application.

3.
J Nanobiotechnology ; 22(1): 150, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38575923

RESUMO

Dental pulp regeneration is a promising strategy for addressing tooth disorders. Incorporating this strategy involves the fundamental challenge of establishing functional vascular networks using dental pulp stem cells (DPSCs) to support tissue regeneration. Current therapeutic approaches lack efficient and stable methods for activating DPSCs. In the study, we used a chemically modified microRNA (miRNA)-loaded tetrahedral-framework nucleic acid nanostructure to promote DPSC-mediated angiogenesis and dental pulp regeneration. Incorporating chemically modified miR-126-3p into tetrahedral DNA nanostructures (miR@TDNs) represents a notable advancement in the stability and efficacy of miRNA delivery into DPSCs. These nanostructures enhanced DPSC proliferation, migration, and upregulated angiogenesis-related genes, enhancing their paracrine signaling effects on endothelial cells. This enhanced effect was substantiated by improvements in endothelial cell tube formation, migration, and gene expression. Moreover, in vivo investigations employing matrigel plug assays and ectopic dental pulp transplantation confirmed the potential of miR@TDNs in promoting angiogenesis and facilitating dental pulp regeneration. Our findings demonstrated the potential of chemically modified miRNA-loaded nucleic acid nanostructures in enhancing DPSC-mediated angiogenesis and supporting dental pulp regeneration. These results highlighted the promising role of chemically modified nucleic acid-based delivery systems as therapeutic agents in regenerative dentistry and tissue engineering.


Assuntos
MicroRNAs , MicroRNAs/genética , MicroRNAs/metabolismo , Células Endoteliais , Polpa Dentária , Células-Tronco , Diferenciação Celular , Regeneração , DNA/metabolismo , Proliferação de Células/fisiologia
4.
Anal Chem ; 96(10): 4205-4212, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38433457

RESUMO

Accurate identification of single-nucleotide mutations in circulating tumor DNA (ctDNA) is critical for cancer surveillance and cell biology research. However, achieving precise and sensitive detection of ctDNAs in complex physiological environments remains challenging due to their low expression and interference from numerous homologous species. This study introduces single-nucleotide-specific lipidic nanoflares designed for the precise and visible detection of ctDNA via toehold-initiated self-priming DNA polymerization (TPP). This system can be assembled from only a single cholesterol-conjugated multifunctional molecular beacon (MMB) via hydrophobicity-mediated aggregation. This results in a compact, high-density, and nick-hidden arrangement of MMBs on the surface of lipidic micelles, thereby enhancing their biostability and localized concentrations. The assay commences with the binding of frequently mutated regions of ctDNA to the MMB toehold domain. This domain is the proximal holding point for initiating the TPP-based strand-displacement reaction, which is the key step in enabling the discrimination of single-base mutations. We successfully detected a single-base mutation in ctDNA (KRAS G12D) in its wild-type gene (KRAS WT), which is one of the most frequently mutated ctDNAs. Notably, coexisting homologous species did not interfere with signal transduction, and small differences in these variations can be visualized by fluorescence imaging. The limit of detection was as low as 10 amol, with the system functioning well in physiological media. In particular, this system allowed us to resolve genetic mutations in the KRAS gene in colorectal cancer, suggesting its high potential in clinical diagnosis and personalized medicine.


Assuntos
DNA Tumoral Circulante , Proteínas Proto-Oncogênicas p21(ras) , Proteínas Proto-Oncogênicas p21(ras)/genética , Nucleotídeos , Polimerização , Mutação , DNA Tumoral Circulante/genética
5.
Adv Healthc Mater ; : e2303143, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38306368

RESUMO

The primary challenges posed by oral mucosal diseases are their high incidence and the difficulty in managing symptoms. Inspired by the ability of bioelectricity to activate cells, accelerate metabolism, and enhance immunity, a conductive polyacrylamide/sodium alginate crosslinked hydrogel composite containing reduced graphene oxide (PAA-SA@rGO) is developed. This composite possesses antibacterial, anti-inflammatory, and antioxidant properties, serving as a bridge to turn the "short circuit" of the injured site into a "completed circuit," thereby prompting fibroblasts in proximity to the wound site to secrete growth factors and expedite tissue regeneration. Simultaneously, the PAA-SA@rGO hydrogel effectively seals wounds to form a barrier, exhibits antibacterial and anti-inflammatory properties, and prevents foreign bacterial invasion. As the electric field of the wound is rebuilt and repaired by the PAA-SA@rGO hydrogel, a 5 × 5 mm2 wound in the full-thickness buccal mucosa of rats can be expeditiously mended within mere 7 days. The theoretical calculations indicate that the PAA-SA@rGO hydrogel can aggregate and express SOX2, PITX1, and PITX2 at the wound site, which has a promoting effect on rapid wound healing. Importantly, this PAA-SA@rGO hydrogel has a fast curative effect and only needs to be applied for the first three days, which significantly improves patient satisfaction during treatment.

6.
Clin Trials ; 21(2): 171-179, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38311901

RESUMO

BACKGROUND: Pivotal evidence of efficacy of a new drug is typically generated by (at least) two clinical trials which independently provide statistically significant and mutually corroborating evidence of efficacy based on a primary endpoint. In this situation, showing drug effects on clinically important secondary objectives can be demanding in terms of sample size requirements. Statistically efficient methods to power for such endpoints while controlling the Type I error are needed. METHODS: We review existing strategies for establishing claims on important but sample size-intense secondary endpoints. We present new strategies based on combined data from two independent, identically designed and concurrent trials, controlling the Type I error at the submission level. We explain the methodology and provide three case studies. RESULTS: Different strategies have been used for establishing secondary claims. One new strategy, involving a protocol planned analysis of combined data across trials, and controlling the Type I error at the submission level, is particularly efficient. It has already been successfully used in support of label claims. Regulatory views on this strategy differ. CONCLUSIONS: Inference on combined data across trials is a useful approach for generating pivotal evidence of efficacy for important but sample size-intense secondary endpoints. It requires careful preparation and regulatory discussion.


Assuntos
Projetos de Pesquisa , Humanos , Tamanho da Amostra
7.
Comput Biol Med ; 168: 107803, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38064854

RESUMO

Medical image segmentation faces current challenges in effectively extracting and fusing long-distance and local semantic information, as well as mitigating or eliminating semantic gaps during the encoding and decoding process. To alleviate the above two problems, we propose a new U-shaped network structure, called CFATransUnet, with Transformer and CNN blocks as the backbone network, equipped with Channel-wise Cross Fusion Attention and Transformer (CCFAT) module, containing Channel-wise Cross Fusion Transformer (CCFT) and Channel-wise Cross Fusion Attention (CCFA). Specifically, we use a Transformer and CNN blocks to construct the encoder and decoder for adequate extraction and fusion of long-range and local semantic features. The CCFT module utilizes the self-attention mechanism to reintegrate semantic information from different stages into cross-level global features to reduce the semantic asymmetry between features at different levels. The CCFA module adaptively acquires the importance of each feature channel based on a global perspective in a network learning manner, enhancing effective information grasping and suppressing non-important features to mitigate semantic gaps. The combination of CCFT and CCFA can guide the effective fusion of different levels of features more powerfully with a global perspective. The consistent architecture of the encoder and decoder also alleviates the semantic gap. Experimental results suggest that the proposed CFATransUnet achieves state-of-the-art performance on four datasets. The code is available at https://github.com/CPU0808066/CFATransUnet.


Assuntos
Aprendizagem , Semântica , Processamento de Imagem Assistida por Computador
8.
BMC Public Health ; 23(1): 2140, 2023 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-37915047

RESUMO

BACKGROUND: The purpose of this study was to describe the knowledge, protective behaviours, and psychological impact of COVID-19 on Chinese residents in Canada, as the emotional and behavioural impacts of the pandemic have not been intensively studied amongst these populations. It was important to determine whether having dependent school-age children (DSAC) aged 16 or under was associated with adverse psychological impacts amongst the Chinese residents living in the country. METHODS: In April 2020, 757 eligible participants were recruited through a snowball sampling to complete an online survey related to the COVID-19 pandemic. Psychological, behavioural, and sociodemographic variables were collected and first analyzed using descriptive and univariate statistics. Multiple logistic regression analyses were performed to further confirm the observed significant associations in bivariate analyses for selected psychological outcome variables. RESULTS: Seven hundred forty-two participants who responded to the "dependent school-age children" question were included in the analysis. Most of them identified as females (65.8%) and 77.2% included receiving a university degree or higher. There were no significant differences in COVID-19 knowledge between those living with or without DSAC. However, participants with DSAC were more likely to perceive themselves as being at greater risk of contracting COVID-19 (p = .023); therefore, having a higher chance of adopting protective behaviours (e.g., hand washing, sanitizing frequently or disinfecting work and living spaces (p < .05), elevated risks of depression (p = .007), and stress (p = .010), compared to those without DSAC. CONCLUSIONS: Predominantly, the Chinese residents in Canada with dependent school-age children were more likely to report the negative psychological impacts of the pandemic. These findings warrant further investigations that may contribute to informing key stakeholders about the identification and implementation of policies and interventions to support the needs of parents with young children, during and after the pandemic.


Assuntos
COVID-19 , População do Leste Asiático , Criança , Feminino , Humanos , Canadá/epidemiologia , COVID-19/epidemiologia , Estudos Transversais , População do Leste Asiático/psicologia , Pandemias/prevenção & controle , Adolescente , Masculino
9.
Nat Metab ; 5(11): 1887-1910, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37903887

RESUMO

Senescent cells remain metabolically active, but their metabolic landscape and resulting implications remain underexplored. Here, we report upregulation of pyruvate dehydrogenase kinase 4 (PDK4) upon senescence, particularly in some stromal cell lines. Senescent cells display a PDK4-dependent increase in aerobic glycolysis and enhanced lactate production but maintain mitochondrial respiration and redox activity, thus adopting a special form of metabolic reprogramming. Medium from PDK4+ stromal cells promotes the malignancy of recipient cancer cells in vitro, whereas inhibition of PDK4 causes tumor regression in vivo. We find that lactate promotes reactive oxygen species production via NOX1 to drive the senescence-associated secretory phenotype, whereas PDK4 suppression reduces DNA damage severity and restrains the senescence-associated secretory phenotype. In preclinical trials, PDK4 inhibition alleviates physical dysfunction and prevents age-associated frailty. Together, our study confirms the hypercatabolic nature of senescent cells and reveals a metabolic link between cellular senescence, lactate production, and possibly, age-related pathologies, including but not limited to cancer.


Assuntos
Ácido Láctico , Neoplasias , Proteínas Quinases , Regulação para Cima , Senescência Celular
11.
Front Pediatr ; 11: 1212658, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37601133

RESUMO

Background: Since the outbreak of coronavirus disease 2019 (COVID-19), public's awareness of infection prevention and control has increased overall, and various prevention and control measures have been adopted. These measures may also have a certain impact on the occurrence of other infectious diseases. Therefore, we collected information on children with several respiratory infectious diseases in Jinan Children's Hospital in China from 2016 to 2022 and analyzed their changes. Method: We collected data on age, sex and number of cases of pertussis, measles, scarlet fever, pulmonary tuberculosis, mumps and influenza, which were diagnosed by clinical and laboratory criteria, from 1 January 2016 to 31 December 2022 in Jinan Children's Hospital in Jinan, Shandong Province, China. Data on the number of people affected by these diseases in China from the Chinese Center for Disease Control and Prevention were compared. Then, we processed the data by using WPS Excel 2019 and SPSS. Results: A total of 12,225 cases were included in this study in Jinan Children's Hospital, which consisted of 3,688 cases of pertussis (2,200 cases before COVID-19 and 1,488 during COVID-19), 680 cases of measles (650 cases before COVID-19 and 30 during COVID-19), 4,688 cases of scarlet fever (4,001 cases before COVID-19 and 687 during COVID-19), 114 cases of tuberculosis (86 cases before COVID-19 and 28 during COVID-19), 449 cases of mumps (340 cases before COVID-19 and 109 during COVID-19) and 2,606 cases of influenza (1,051 cases before COVID-19 and 1,555 during COVID-19). The numbers of children in the hospital with pertussis, measles, scarlet fever, mumps and influenza decreased substantially during COVID-19 in 2020-2022 compared with numbers in 2016-2019, while numbers of patients in China with all six respiratory infectious diseases, including pulmonary tuberculosis, declined during the pandemic. A rebound of pertussis, scarlet fever and influenza was observed in 2021 and 2022. Conclusions: The study found that viral pathogens such as those causing measles, mumps and influenza all decreased during the pandemic, after which influenza rebounded. Infection diseases caused by bacteria such as scarlet fever and pertussis also decreased during COVID-19, and then a rebound occurred. However, tuberculosis stayed relatively constant.

12.
Front Cell Infect Microbiol ; 13: 1181633, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37637457

RESUMO

With the widespread use of macrolide antibiotics in China, common pathogens causing children's infections, such as Streptococcus pneumoniae, Streptococcus (including Group A streptococcus, Group B streptococcus), Staphylococcus aureus, Bordetella pertussis, and Mycoplasma pneumoniae, have shown varying degrees of drug resistance. In order to provide such problem and related evidence for rational use of antibiotics in clinic, we reviewed the drug resistance of common bacteria to macrolides in children recent 20 years.


Assuntos
Antibacterianos , Bactérias , Infecções Bacterianas , Farmacorresistência Bacteriana , Macrolídeos , Macrolídeos/farmacologia , Macrolídeos/uso terapêutico , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bactérias/efeitos dos fármacos , Bactérias/isolamento & purificação , Bactérias/patogenicidade , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/microbiologia , Humanos , Criança , China
13.
J Thorac Dis ; 15(6): 3133-3142, 2023 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-37426117

RESUMO

Background: Although it is known that a history of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is the most important predictor of future risk of AECOPD and readmission to hospitals, there is no scientific evidence that an event of only one chronic obstructive pulmonary disease (COPD)-related admission is a high risk of future readmission. We retrospectively analyzed the association of an incident of one COPD-related admission with future readmission risk. Methods: This is a retrospective study. The data of AECOPD-related admissions and readmissions during 5 years were obtained and analyzed for the admission frequencies of patients with AECOPD and an association of the admission history with a future readmission risk. Results: The admission frequency of patients with frequent admission (3 or more admissions within 5 years) was 4.1 times that of those with non-frequent admission (0.95 vs. 0.23 times per person per year). In each calendar year during the 5-year study period, most patients (88.2%) were hospitalized only once, and 11.8% had two or more admissions. Nevertheless, their average number of admissions in each calendar year was 3.3 times that of those who only had one admission each year (3.33 vs. 1.00 times per person per year). More importantly, the positive predictive value for future readmission due to AECOPD was only 14.8% in those who had one admission in the previous year. The patients with the greater readmission risk were those with two or more admissions due to AECOPD in the previous year [crude odds ratio (OR): 4.10, 95% confidence interval (CI): 1.24-13.58 and 7.51, 95% CI: 3.81-16.68]. Conclusions: There is a subtype of frequent admission due to AECOPD, and it can be distinguished by having three or more admissions in the past 5 years or two or more admissions in the previous year. Nevertheless, an incident of admission once a year is not a good predictor of future readmission.

14.
Microsyst Nanoeng ; 9: 88, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37448967

RESUMO

Advancements in microscale electrode technology have revolutionized the field of neuroscience and clinical applications by offering high temporal and spatial resolution of recording and stimulation. Flexible neural probes, with their mechanical compliance to brain tissue, have been shown to be superior to rigid devices in terms of stability and longevity in chronic recordings. Shuttle devices are commonly used to assist flexible probe implantation; however, the protective membrane of the brain still makes penetration difficult. Hidden damage to brain vessels during implantation is a significant risk. Inspired by the anatomy of the mosquito mouthparts, we present a biomimetic neuroprobe system that integrates high-sensitivity sensors with a high-fidelity multichannel flexible electrode array. This customizable system achieves distributed and minimally invasive implantation across brain regions. Most importantly, the system's nonvisual monitoring capability provides an early warning detection for intracranial soft tissues, such as vessels, reducing the potential for injury during implantation. The neural probe system demonstrates exceptional sensitivity and adaptability to environmental stimuli, as well as outstanding performance in postoperative and chronic recordings. These findings suggest that our biomimetic neural-probe device offers promising potential for future applications in neuroscience and brain-machine interfaces. A mosquito mouthpart-like bionic neural probe consisting of a highly sensitive tactile sensor module, a flexible microelectrode array, and implanted modules that mimic the structure of mosquito mouthparts. The system enables distributed implantation of electrode arrays across multiple brain regions while making the implantation minimally invasive and avoiding additional dural removal. The tactile sensor array can monitor the implantation process to achieve early warning of vascular damage. The excellent postoperative short-term recording performance and long-term neural activity tracking ability demonstrate that the system is a promising tool in the field of brain-computer interfaces.

15.
Biomed Opt Express ; 14(2): 866-882, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36874478

RESUMO

Popularizing community and home early caries screening is essential for caries prevention and treatment. However, a high-precision, low-cost, and portable automated screening tool is currently lacking. This study constructed an automated diagnosis model for dental caries and calculus using fluorescence sub-band imaging combined with deep learning. The proposed method is divided into two stages: the first stage collects imaging information of dental caries in different fluorescence spectral bands and obtains six-channel fluorescence images. The second stage employs a 2-D-3-D hybrid convolutional neural network combined with the attention mechanism for classification and diagnosis. The experiments demonstrate that the method has competitive performance compared to existing methods. In addition, the feasibility of transferring this approach to different smartphones is discussed. This highly accurate, low-cost, portable method has potential applications in community and at-home caries detection.

16.
Lancet ; 401(10378): 747-761, 2023 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-36746171

RESUMO

BACKGROUND: Few therapeutic options are available for patients with moderate-to-severe hidradenitis suppurativa. We aimed to assess the efficacy of secukinumab in patients with moderate-to-severe hidradenitis suppurativa in two randomised trials. METHODS: SUNSHINE and SUNRISE were identical, multicentre, randomised, placebo-controlled, double-blind phase 3 trials done in 219 primary sites in 40 countries. Patients aged 18 years old or older with the capacity to provide written informed consent and with moderate-to-severe hidradenitis suppurativa (defined as a total of ≥5 inflammatory lesions affecting ≥2 distinct anatomical areas) for at least 1 year were eligible for inclusion. Included patients also agreed to daily use of topical over-the-counter antiseptics on the areas affected by hidradenitis suppurativa lesions while on study treatment. Patients were excluded if they had 20 or more fistulae at baseline, had ongoing active conditions requiring treatment with prohibited medication (eg, systemic biological immunomodulating treatment, live vaccines, or other investigational treatments), or met other exclusion criteria. In both trials, patients were randomly assigned (1:1:1) by means of interactive response technology to receive subcutaneous secukinumab 300 mg every 2 weeks, subcutaneous secukinumab 300 mg every 4 weeks, or subcutaneous placebo all via a 2 mL prefilled syringe in a double-dummy method as per treatment assignment. The primary endpoint was the proportion of patients with a hidradenitis suppurativa clinical response, defined as a decrease in abscess and inflammatory nodule count by 50% or more with no increase in the number of abscesses or in the number of draining fistulae compared with baseline, at week 16, assessed in the overall population. Hidradenitis suppurativa clinical response was calculated based on the number of abscesses, inflammatory nodules, draining fistulae, total fistulae, and other lesions in the hidradenitis suppurativa affected areas. Safety was assessed by evaluating the presence of adverse events and serious adverse events according to common terminology criteria for adverse events, which were coded using Medical Dictionary for Regulatory Activities terminology. Both the SUNSHINE, NCT03713619, and SUNRISE, NCT03713632, trials are registered with ClinicalTrials.gov. FINDINGS: Between Jan 31, 2019, and June 7, 2021, 676 patients were screened for inclusion in the SUNSHINE trial, of whom 541 (80%; 304 [56%] women and 237 [44%] men; mean age 36·1 years [SD 11·7]) were included in the analysis (181 [33%] in the secukinumab every 2 weeks group, 180 [33%] in the secukinumab every 4 weeks group, and 180 [33%] in the placebo group). Between the same recruitment dates, 687 patients were screened for inclusion in the SUNRISE trial, of whom 543 (79%; 306 [56%] women and 237 [44%] men; mean age 36·3 [11·4] years) were included in the analysis (180 [33%] in the secukinumab every 2 weeks group, 180 [33%] in the secukinumab every 4 weeks group, and 183 [34%] in the placebo group). In the SUNSHINE trial, significantly more patients in the secukinumab every 2 weeks group had a hidradenitis suppurativa clinical response (rounded average number of patients with response in 100 imputations, 81·5 [45%] of 181 patients) compared with the placebo group (60·7 [34%] of 180 patients; odds ratio 1·8 [95% CI 1·1-2·7]; p=0·0070). However, there was no significant difference between the number of patients in the secukinumab every 4 weeks group (75·2 [42%] of 180 patients) and the placebo group (1·5 [1·0-2·3]; p=0·042). Compared with the placebo group (57·1 [31%] of 183 patients), significantly more patients in the secukinumab every 2 weeks group (76·2 [42%] of 180 patients; 1·6 [1·1-2·6]; p=0·015) and the secukinumab every 4 weeks group (83·1 [46%] of 180 patients; 1·9 [1·2-3·0]; p=0·0022) had a hidradenitis suppurativa clinical response in the SUNRISE trial. Patient responses were sustained up to the end of the trials at week 52. The most common adverse event by preferred term up to week 16 was headache in both the SUNSHINE (17 [9%] patients in the secukinumab every 2 weeks group, 20 [11%] in the secukinumab every 4 weeks group, and 14 [8%] in the placebo group) and SUNRISE (21 [12%] patients in the secukinumab every 2 weeks group, 17 [9%] in the secukinumab every 4 weeks group, and 15 [8%] in the placebo group) trials. No study-related deaths were reported up to week 16. The safety profile of secukinumab in both trials was consistent with that previously reported, with no new or unexpected safety findings detected. INTERPRETATION: When given every 2 weeks, secukinumab was clinically effective at rapidly improving signs and symptoms of hidradenitis suppurativa with a favourable safety profile and with sustained response up to 52 weeks of treatment. FUNDING: Novartis Pharma.


Assuntos
Hidradenite Supurativa , Masculino , Humanos , Feminino , Adolescente , Adulto , Idoso , Hidradenite Supurativa/induzido quimicamente , Hidradenite Supurativa/tratamento farmacológico , Abscesso/tratamento farmacológico , Resultado do Tratamento , Anticorpos Monoclonais Humanizados/uso terapêutico , Método Duplo-Cego
17.
FEBS Open Bio ; 13(3): 570-581, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36732060

RESUMO

Deep tooth decay approaching the pulp may develop into pulpitis; to prevent this, pulp cells need to balance the rapid immune response to avoid rapid swelling of the pulp. Current treatment of deep decay that approaches the pulp involves the application of drugs that induce low-level inflammation in the dental pulp to promote its repair, but this treatment is sometimes insufficient. However, the unsuccessful treatment often resulted in pulpitis. The C5a-C5aR is the initial stage of the immune cascade response. Blocking the binding of C5a-C5aR can slow the immune response in the narrow pulp cavity, so that dental pulp cells have enough time to proliferate, migrate, and differentiate. In this study, we compared lipoteichoic acid (LTA) and lipopolysaccharides (LPS) at different concentrations and time points and used the C5aR antagonist W54011 to block the C5a-C5aR axis. The blocking effect was detected by analyzing the expression of C5a, C5aR, interleukin (IL)-6, and Toll-like receptors 2 and 4 (TLR-2, 4). Next, we determined the optimal concentration and duration of LTA and LPS treatment in combination with W54011. Based on our results, we selected 1.0 µg·mL-1 LPS treatment for 48 h to generate an inflammatory model of human dental pulp cells. We then regrouped the cells and conducted expression analyses to monitor the expression of C5a, C5aR, IL-6, and TLR-4 at the protein and mRNA levels. LPS stimulation for 48 h and treatment with W54011 for 48 h effectively inhibited inflammation and did not affect C5a expression. This study provides a basis for follow-up studies of W54011 in dental pulp cells.


Assuntos
Lipopolissacarídeos , Pulpite , Humanos , Lipopolissacarídeos/farmacologia , Complemento C5a/metabolismo , Polpa Dentária/metabolismo , Interleucina-6 , Inflamação/tratamento farmacológico
19.
Photodiagnosis Photodyn Ther ; 41: 103217, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36462702

RESUMO

PURPOSE: Precise diagnosis and identification of early dental caries facilitates timely intervention and reverses the progression of the disease. Developing an objective, accurate and rapid caries and calculus automatic identification method advances clinical application and facilitates the promotion and screening of oral health in the community and family. METHODS: In this study, based on 122 dental surfaces labeled by professional dentists, hyperspectral fluorescence imaging combined with machine learning algorithms was employed to construct a model for simultaneously diagnosing dental caries and calculus. Model trained by fusion features based on spectra, textures, and colors with the integrated learning algorithm has better performance and stronger generalization capabilities. RESULTS: The experimental results showed that the diagnostic model's accuracy, sensitivity, and specificity for identifying four different caries stages and calculus were 98.6%, 98.4%, and 99.6%, respectively. CONCLUSIONS: The proposed method can evaluate the whole tooth surface at the pixel level and provides discrimination enhancement and a quantitative parameter, which is expected to be a new approach for early caries diagnosis.


Assuntos
Cárie Dentária , Fotoquimioterapia , Dente , Humanos , Cárie Dentária/diagnóstico por imagem , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes , Aprendizado de Máquina
20.
Microsyst Nanoeng ; 8: 118, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36389054

RESUMO

The combination of optogenetics and electrophysiological recording enables high-precision bidirectional interactions between neural interfaces and neural circuits, which provides a promising approach for the study of progressive neurophysiological phenomena. Opto-electrophysiological neural probes with sufficient flexibility and biocompatibility are desirable to match the low mechanical stiffness of brain tissue for chronic reliable performance. However, lack of rigidity poses challenges for the accurate implantation of flexible neural probes with less invasiveness. Herein, we report a hybrid probe (Silk-Optrode) consisting of a silk protein optical fiber and multiple flexible microelectrode arrays. The Silk-Optrode can be accurately inserted into the brain and perform synchronized optogenetic stimulation and multichannel recording in freely behaving animals. Silk plays an important role due to its high transparency, excellent biocompatibility, and mechanical controllability. Through the hydration of the silk optical fiber, the Silk-Optrode probe enables itself to actively adapt to the environment after implantation and reduce its own mechanical stiffness to implant into the brain with high fidelity while maintaining mechanical compliance with the surrounding tissue. The probes with 128 recording channels can detect high-yield well-isolated single units while performing intracranial light stimulation with low optical losses, surpassing previous work of a similar type. Two months of post-surgery results suggested that as-reported Silk-Optrode probes exhibit better implant-neural interfaces with less immunoreactive glial responses and tissue lesions. A silk optical fiber-based Silk-Optrode probe consisting of a natural silk optical fiber and a flexible micro/nano electrode array is reported. The multifunctional soft probe can modify its own Young's modulus through hydration to achieve accurate implantation into the brain. The low optical loss and single-unit recording abilities allow simultaneous optogenetic stimulation and multichannel readout, which expands the applications in the operation and parsing of neural circuits in behavioral animals.

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