Retinal neovascularization (RNV), a typical pathological manifestation involved in most neovascular diseases, causes retinal detachment, vision loss, and ultimately irreversible blindness. Repeated intravitreal injections of anti-VEGF drugs were developed against RNV, with limitations of incomplete responses and adverse effects. Therefore, a new treatment with a better curative effect and more prolonged dosage is demanding. Here, we induced macrophage polarization to anti-inflammatory M2 phenotype by inhibiting cGAS-STING signaling with an antagonist C176, appreciating the role of cGAS-STING signaling in the retina in pro-inflammatory M1 polarization. C176-loaded and phosphatidylserine-modified dendritic mesoporous silica nanoparticles were constructed and examined by a single intravitreal injection. The biosafe nanoparticles were phagocytosed by retinal macrophages through a phosphatidylserine-mediated "eat me" signal, which persistently release C176 to suppress STING signaling and thereby promote macrophage M2 polarization specifically. A single dosage can effectively alleviate pathological angiogenesis phenotypes in murine oxygen-induced retinopathy models. In conclusion, these C176-loaded nanoparticles with enhanced cell uptake and long-lasting STING inhibition effects might serve as a promising way for treating RNV.
Infectious keratitis is among the major causes of global blindness. Anterior segment optical coherence tomography (AS-OCT) images allow the characterizing of cross-sectional structures in the cornea with keratitis thus revealing the severity of inflammation, and can also provide 360-degree information on anterior chambers. The development of image analysis methods for such cases, particularly deep learning methods, requires a large number of annotated images, but to date, there is no such open-access AS-OCT image repository. For this reason, this work provides a dataset containing a total of 1168 AS-OCT images of patients with keratitis, including 768 full-frame images (6 patients). Each image has associated segmentation labels for lesions and cornea, and also labels of iris for full-frame images. This study provides a great opportunity to advance the field of image analysis on AS-OCT images in both two-dimensional (2D) and three-dimensional (3D) and would aid in the development of artificial intelligence-based keratitis management.
Deep Learning , Keratitis , Tomography, Optical Coherence , Humans , Keratitis/diagnostic imaging , Imaging, Three-Dimensional , Cornea/diagnostic imaging , Image Processing, Computer-Assisted
OBJECTIVES: The vast majority of children with Attention-Deficit Hyperactivity Disorder (ADHD) do not have access to proper diagnosis and treatment in China. The goal of this project is to identify the challenges and facilitators in implementing a Canadian ADHD Shared Care Pathways program in pediatric settings in Shanghai region. METHODS: Purposive semi-structured focus groups were conducted on a total of 13 healthcare practitioners from the Shanghai Xinuha, Ninghai and Chongming hospitals. Two independent researchers conducted a thematic analysis of the data with themes emerging based on the Consolidated Framework for Implementation Research (CFIR). RESULTS: Notable barriers identified by participants included: (1) lack of knowledge in the management of ADHD, primarily among general practitioners; (2) lack of resources such as lack of staff, time, and medication for ADHD; (3) challenges in implementing an international multicentre intervention (such as communication difficulties between teams and integration of resources available in different hospitals); and (4) mental health stigma, difficulties in identifying ADHD patients, and logistical problems related to medication procurement rules put in place by provincial governments. Notable facilitators included: (1) the strong motivation of stakeholders and their confidence in their ability to learn and subsequently execute action plans to achieve the implementation goal; (2) the compatibility between the values and goals of the stakeholders and those of the program despite some cultural tension, a positive learning climate, strong tensions for change, and the high interest of organization leaders in engaging in the program (3) the perceived benefits of the program, such as standardization of the diagnostic and treatment process, and engaging primary care providers in ADHD management; and (4) the strong relationship between participating institutions and schools as well as provincial health initiatives available to support collaborative models of care. Mixed factors to implementation were also explored. CONCLUSIONS: Appropriate training of health care providers, cultural adaptation of the program, increase public awareness about ADHD to decrease stigma, as well as strong project management and guidelines that clearly describe the role and expectations of each team member appeared essential to successful implementation.
Attention Deficit Disorder with Hyperactivity , Focus Groups , Humans , Attention Deficit Disorder with Hyperactivity/therapy , China , Canada , Child , Male , Female , Health Services Accessibility , Qualitative Research , Attitude of Health Personnel
Empowering independent control of optical and acoustic modes and enhancing the photon-phonon interaction, integrated photonics boosts the advancements of on-chip stimulated Brillouin scattering (SBS). However, achieving acoustic waveguides with low loss, tailorability, and easy fabrication remains a challenge. Here, inspired by the optical anti-resonance in hollow-core fibers and acoustic anti-resonance in cylindrical waveguides, we propose suspended anti-resonant acoustic waveguides (SARAWs) with superior confinement and high selectivity of acoustic modes, supporting both forward and backward SBS on chip. Furthermore, this structure streamlines the design and fabrication processes. Leveraging the advantages of SARAWs, we showcase a series of breakthroughs for SBS within a compact footprint on the silicon-on-insulator platform. For forward SBS, a centimeter-scale SARAW supports a large net gain exceeding 6.4 dB. For backward SBS, we observe an unprecedented Brillouin frequency shift of 27.6 GHz and a mechanical quality factor of up to 1960 in silicon waveguides. This paradigm of acoustic waveguide propels SBS into a new era, unlocking new opportunities in the fields of optomechanics, phononic circuits, and hybrid quantum systems.
Advancements in photonic integration technology have enabled the effective excitation of simulated Brillouin scattering (SBS) on a single chip, boosting Brillouin-based applications such as microwave photonic signal processing, narrow-linewidth lasers, and optical sensing. However, on-chip circuits still require large pump power and centimeter-scale waveguide length to achieve a considerable Brillouin gain, making them both power-inefficient and challenging for integration. Here, we exploit the slow-light effect to significantly enhance SBS, presenting the first, to the best of our knowledge, demonstration of a slow-light Brillouin-active waveguide on the silicon-on-insulator (SOI) platform. By integrating a Bragg grating with a suspended ridge waveguide, a 2.1-fold enhancement of the forward Brillouin gain coefficient is observed in a 1.25 mm device. Furthermore, this device shows a Brillouin gain coefficient of 1,693 m-1W-1 and a mechanical quality factor of 1,080. The short waveguide length reduces susceptibility to inhomogeneous broadening, enabling the simultaneous achievement of a high Brillouin gain coefficient and a high mechanical quality factor. This approach introduces an additional dimension to enhance acousto-optic interaction efficiency in the SOI platform and holds significant potential for microwave photonic filters and high spatial resolution sensing.
The acousto-optic interaction known as stimulated Brillouin scattering (SBS) has emerged as a fundamental principle for realizing crucial components and functionalities in integrated photonics. However, the main challenge of integrating Brillouin devices is how to effectively confine both optical and acoustic waves. Apart from that, the manufacturing processes for these devices need to be compatible with standard fabrication platforms and streamlined to facilitate their large-scale integration. Here, we demonstrate a novel, to the best of our knowledge, suspended nanowire structure that can tightly confine photons and phonons. Furthermore, tailored for this structure, we introduce a loading-effect-based three-dimensional microfabrication technique, compatible with complementary metal-oxide-semiconductor (CMOS) technology. This innovative technique allows for the fabrication of the entire structure using a single-step lithography exposure, significantly streamlining the fabrication process. Leveraging this structure and fabrication scheme, we have achieved a Brillouin gain coefficient of 1100 W-1m-1 on the silicon-on-insulator platform within a compact footprint. It can support a Brillouin net gain over 4.1 dB with modest pump powers. We believe that this structure can significantly advance the development of SBS on chip, unlocking new opportunities for a large-scale integration of Brillouin-based photonic devices.
As an indispensable part of the human sensory system, visual acuity may be impaired and even develop into irreversible blindness due to various ocular pathologies. Among ocular diseases, fundus neovascularization diseases (FNDs) are prominent etiologies of visual impairment worldwide. Intravitreal injection of anti-vascular endothelial growth factor drugs remains the primary therapy but is hurdled by common complications and incomplete potency. To renovate the current therapeutic modalities, nanomedicine emerged as the times required, which is endowed with advanced capabilities, able to fulfill the effective ocular fundus drug delivery and achieve precise drug release control, thus further improving the therapeutic effect. This review provides a comprehensive summary of advances in nanomedicine for FND management from state-of-the-art studies. First, the current therapeutic modalities for FNDs are thoroughly introduced, focusing on the key challenges of ocular fundus drug delivery. Second, nanocarriers are comprehensively reviewed for ocular posterior drug delivery based on the nanostructures: polymer-based nanocarriers, lipid-based nanocarriers, and inorganic nanoparticles. Thirdly, the characteristics of the fundus microenvironment, their pathological changes during FNDs, and corresponding strategies for constructing smart nanocarriers are elaborated. Furthermore, the challenges and prospects of nanomedicine for FND management are thoroughly discussed.
The relationship between social support and mortality, especially cardio-cerebrovascular mortality, still has some limitations in the assessment of social support, sample selection bias, and short follow-up time. We used the data from 2005 to 2008 National Health and Nutrition Examination Survey to examine this relationship. The study analyzed a total of 6776 participants, divided into Group 1, Group 2, and Group 3 according to the social support score (0-1; 2-3; 4-5). Multivariable adjusted COX regression analyses of our study showed that Group 3 and Group 2 had a reduced risk of all-cause and cardio-cerebrovascular mortality (Group 3 vs 1, HR: 0.55, P < 0.001; HR: 0.4, P < 0.001; Group 2 vs 1, HR: 0.77, P = 0.017; HR: 0.58, P = 0.014) compared with Group 1. The same results were observed after excluding those who died in a relatively short time. Additionally, having more close friends, being married or living as married, and enough attending religious services were significantly related to a lower risk of mortality after adjustment. In brief, adequate social support is beneficial in reducing the risk of all-cause mortality and cardio-cerebrovascular mortality in middle-aged and older adults, especially in terms of attending religious services frequency, the number of close friends, and marital status.
Friends , Social Support , Middle Aged , Humans , Aged , Nutrition Surveys , Regression Analysis
Background: The relative prognostic importance of handgrip strength (HGS) in comparison with other risk factors for mortality remains to be further clarified, and thresholds used for best identify high-risk individuals in health screening are not yet established. Using machine learning and nationally representative data from the China Health and Retirement Longitudinal Study (CHARLS), the study aimed to investigate the prognostic importance of HGS and establish sex-specific thresholds for health screening. Methods: A total of 6,762 participants from CHARLS were enrolled. A random forest model was built using 30 variables with all-cause mortality as outcome. SHapley Additive exPlanation values were applied to explain the model. Cox proportional hazard models and Harrell's C index change were used to validate the clinical importance of the thresholds. Results: Among the participants, 3,102 (45.9%) were men, and 622 (9.1%) case of death were documented follow-up period of 6.78 years. The random forest model identified HGS as the fifth important prognostic variable, with thresholds for identifying high-risk individuals were < 32 kg in men and < 19 kg in women. Low HGS were associated with all-cause mortality [HR (95% CI): 1.77 (1.49-2.11), p < 0.001]. The addition of HGS thresholds improved the predictive ability of an established office-based risk score (C-index change: 0.022, p < 0.001). Conclusion: On the basis of our thresholds, low HGS predicted all-cause mortality better than other risk factors and improved prediction of a traditional office-based risk score. These results reinforced the clinical utility of measurement of HGS in health screening.
Triple-negative breast cancer (TNBC) is a highly aggressive disease with rapid progression and poor prognosis due to multidrug resistance (MDR). Piperine (PIP) shows promise as a P-gp inhibitor, capable of sensitizing chemotherapeutic drugs and exhibiting antitumor properties. This study explores the inhibitory mechanism of PIP on P-glycoprotein (P-gp) and its capacity to enhance the sensitivity of paclitaxel (PTX). We subsequently evaluated the efficacy and safety of albumin nanoparticles that co-encapsulate PTX and PIP (PP@AN). The results demonstrated that PIP enhanced the accumulation of PTX intracellularly, as determined with HPLC/MS/MS analysis. PIP was also found to increase cell sensitivity to PTX. Furthermore, we explored the inhibitory mechanism of PIP on P-gp, utilizing molecular docking simulations, RT-qPCR, and Western blot analysis. PIP appears to compete with the active paclitaxel binding site on P-gp, affecting ATPase activity and downregulating the MDR1 gene and P-gp expression. In summary, PIP could inhibit P-gp and act as a sensitizer in the treatment of TNBC with PTX. Moreover, stable and uniform PP@AN was successfully formulated, resulting in a significant increase in drug accumulation within cells as well as the downregulation of P-gp in tumors at the optimal ratio (PTX:PIP = 1:2). This led to an improvement in the antitumor effect in vivo while also reducing hepatotoxicity and hemototoxicity following chemotherapy. This study comprehensively investigated PIP's inhibitory effect and mechanism on P-gp. We present a new approach for co-delivering PIP and PTX using albumin nanoparticles, which reduced toxicity and improved therapeutic efficacy both in vivo and in vitro.
INTRODUCTION: Perioperative rehabilitation (PORT) has shown a positive effect on patients undergoing cardiac surgery. However, there are minimal data on the impact of short-term PORT in cardiac surgery, which is associated with higher postoperative morbidity and mortality. The trial will assess the efficacy of short-term PORT in reducing in-hospital mortality, postoperative pulmonary complications and length of stay, compared with the usual care in cardiac surgical patients. METHODS AND ANALYSIS: This is a single-centre prospective, randomised, open, controlled trial with a 1:1 ratio. Consecutive 800 adult patients undergoing elective valve surgery will be randomised to either usual care or in-hospital short-term PORT that consists of education, inspiratory muscle training, active cycle of breathing techniques and early mobilisation. The primary outcome of this study will be a composite of in-hospital all-cause mortality, incidence of postoperative pulmonary complications and the ratio of postoperative hospitalisation >7 days. ETHICS AND DISSEMINATION: The PORT study was granted by the Medical Research Ethics Committee of Guangdong Provincial People's Hospital in August 2018. Findings will be disseminated to patients, clinicians and commissioning groups through peer-reviewed publication. TRIAL REGISTRATION NUMBER: NCT03709511.
Cardiac Surgical Procedures , Postoperative Complications , Adult , Humans , Prospective Studies , Postoperative Complications/etiology , Cardiac Surgical Procedures/adverse effects , Heart , Elective Surgical Procedures , Randomized Controlled Trials as Topic
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination service system lacks standardized indicators to assess resource allocation. Moreover, data on specific vaccination-promoting measures is limited. This study aimed to evaluate vaccination accessibility and capacity and investigate convenience-related factors in China during the Omicron variant epidemic. We collected information on SARS-CoV-2 vaccination services among vaccination sites in Beijing. Analysis was performed using nearest neighbor, Ripley's K, hot spot analysis, and generalized estimating equations. Overall, 299 vaccination sites were included. The demand for the SARS-CoV-2 vaccine increased with the increase in daily new cases, and the number of staff administering vaccines should be increased in urban areas at the beginning of the epidemic. Providing vaccination for both children and adults, extending vaccination service hours, and offering a wider range of vaccine categories significantly increased the doses of vaccines administered (all P < .05). The provision of mobile vaccination vehicles effectively increased the doses of vaccines administered to individuals aged ≥ 60 years (P < .05). The allocation of SARS-CoV-2 vaccination services should be adjusted according to geographic location, population size, and vaccination demands. Simultaneous provision of vaccination services for children and their guardians, flexible service hours, prompt innovative vaccine production, and tailored vaccination strategies can foster vaccination uptake.
COVID-19 Vaccines , COVID-19 , Adult , Child , Humans , Beijing/epidemiology , SARS-CoV-2 , COVID-19/epidemiology , COVID-19/prevention & control , China/epidemiology , Vaccination
Artificial Intelligence (AI) has found rapidly growing applications in ophthalmology, achieving robust recognition and classification in most kind of ocular diseases. Ophthalmic surgery is one of the most delicate microsurgery, requiring high fineness and stability of surgeons. The massive demand of the AI assist ophthalmic surgery will constitute an important factor in boosting accelerate precision medicine. In clinical practice, it is instrumental to update and review the considerable evidence of the current AI technologies utilized in the investigation of ophthalmic surgery involved in both the progression and innovation of precision medicine. Bibliographic databases including PubMed and Google Scholar were searched using keywords such as "ophthalmic surgery", "surgical selection", "candidate screening", and "robot-assisted surgery" to find articles about AI technology published from 2018 to 2023. In addition to the Editorials and letters to the editor, all types of approaches are considered. In this paper, we will provide an up-to-date review of artificial intelligence in eye surgery, with a specific focus on its application to candidate screening, surgery selection, postoperative prediction, and real-time intraoperative guidance.
Objective: This study aims to explore the association between neurological dysfunction and serum levels of Interleukin-6 (IL-6) and Interleukin-1ß (IL-1ß) in patients undergoing isoflurane inhalation anesthesia. Methods: This prospective observational study enrolled a total of 88 patients who underwent isoflurane anesthesia, between April 2019 and April 2020 in our hospital's operating room. The Mini-Mental State Examination scale (MMSE) was administered on the first preoperative day (T0), the 1st postoperative day (T1), the 3rd postoperative day (T2), and the 7th postoperative day (T3). Based on the MMSE score obtained on the 1st postoperative day, patients were categorized into the neurological dysfunction group (n = 23) and the normal group (n = 65). Serum levels of IL-6 and IL-1ß were measured at T0, T1, T2, and T3, and their relationship with MMSE scores was analyzed. Results: Compared to the normal group, the neurological dysfunction group exhibited significantly higher levels of serum IL-6 and IL-1ß at all time points except T0, accompanied by notably lower MMSE scores (P < .001). Combined diagnostic parameters, including area under the curve (AUC) value, sensitivity, and specificity, showed improved performance compared to individual tests. Pearson correlation analysis revealed a negative correlation between serum IL-6 and IL-1ß levels and MMSE scores (r = -0.719, -0.408, all P < .05). Conclusions: Our findings highlight a correlation between neurological dysfunction and serum IL-6 and IL-1ß levels in patients undergoing isoflurane inhalation anesthesia. These cytokines could serve as valuable indicators for the early detection of neurological dysfunction following anesthesia.
Isoflurane , Humans , Isoflurane/adverse effects , Interleukin-6 , Interleukin-1beta , Correlation of Data , Anesthesia, Inhalation
Lung cancer is the most commonly diagnosed cancer and the leading cause of cancer-related deaths in China. Rapid and precise evaluation of tumor tissue during lung cancer surgery can reduce operative time and improve negative-margin assessment, thus increasing disease-free and overall survival rates. This study aimed to explore the potential of label-free multiphoton microscopy (MPM) for imaging adenocarcinoma tissues, detecting histopathological features, and distinguishing between normal and cancerous lung tissues. We showed that second harmonic generation (SHG) signals exhibit significant specificity for collagen fibers, enabling the quantification of collagen features in lung adenocarcinomas. In addition, we developed a collagen score that could be used to distinguish between normal and tumor areas at the tumor boundary, showing good classification performance. Our findings demonstrate that MPM imaging technology combined with an image-based collagen feature extraction method can rapidly and accurately detect early-stage lung adenocarcinoma tissues.
Adenocarcinoma of Lung , Adenocarcinoma , Lung Neoplasms , Humans , Microscopy , Adenocarcinoma/diagnostic imaging , Adenocarcinoma/pathology , Adenocarcinoma of Lung/diagnostic imaging , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/pathology , Collagen , Microscopy, Fluorescence, Multiphoton/methods
Synthesis of buckybowls have stayed highly challenging due to the large structural strain caused by curved π surface. In this paper, we report the synthesis and properties of two trichalcogenasupersumanenes which three chalcogen (sulfur or selenium) atoms and three methylene groups bridge at the bay regions of hexa-peri-hexabenzocoronene. These trichalcogenasupersumanenes are synthesized quickly in three steps using an Aldol cyclotrimerization, a Scholl oxidative cyclization, and a Stille type reaction. X-ray crystallography analysis reveals that they encompass bowl diameters of 11.06 Å and 11.35 Å and bowl depths of 2.29 Å and 2.16 Å for the trithiasupersumanene and triselenosupersumanene, respectively. Furthermore, trithiasupersumanene derivative with methyl chains can form host-guest complexes with C60 or C70, which are driven by concave-convex π ⯠π interactions and multiple C-H ⯠π interactions between bowl and fullerenes.
Fullerenes , Fullerenes/chemistry , Crystallography, X-Ray
Exercise capacity is an important component of risk assessment for pulmonary arterial hypertension (PAH). We investigated the association of the Duke Activity Status Index (DASI) with peak oxygen consumption (peakVO2) and explored whether the DASI can discriminate the high-risk individuals in patients with PAH, according to peakVO2 < 11 mL/min/kg. A total of 89 patients were evaluated using cardiopulmonary exercise testing (CPET) and DASI. The correlation between the DASI and peakVO2 was measured by univariate analysis, and a receiver operating characteristic (ROC) curve analysis was conducted. The DASI was correlated with peakVO2 in the univariate analysis. The ROC curve analysis revealed that the DASI had a discriminative value for identifying the individuals with a high risk in PAH patients (p < 0.001), with an area under ROC curve (AUC) of 0.79 (95% CI: 0.67-0.92). Similar results were observed in patients with PAH associated with congenital heart disease (CHD-PAH), (p = 0.001), with an AUC of 0.80 (95% CI: 0.658-0.947). Therefore, DASI reflects exercise capacity in patients with PAH and has good ability to discriminate patients with a low risk and a high risk, and it may be included in the risk assessment of PAH.
Infectious keratitis (IK) is a common ophthalmic emergency that requires prompt and accurate treatment. This study aimed to propose a deep learning (DL) system based on slit lamp images to automatically screen and diagnose infectious keratitis. This study established a dataset of 2757 slit lamp images from 744 patients, including normal cornea, viral keratitis (VK), fungal keratitis (FK), and bacterial keratitis (BK). Six different DL algorithms were developed and evaluated for the classification of infectious keratitis. Among all the models, the EffecientNetV2-M showed the best classification ability, with an accuracy of 0.735, a recall of 0.680, and a specificity of 0.904, which was also superior to two ophthalmologists. The area under the receiver operating characteristics curve (AUC) of the EffecientNetV2-M was 0.85; correspondingly, 1.00 for normal cornea, 0.87 for VK, 0.87 for FK, and 0.64 for BK. The findings suggested that the proposed DL system could perform well in the classification of normal corneas and different types of infectious keratitis, based on slit lamp images. This study proves the potential of the DL model to help ophthalmologists to identify infectious keratitis and improve the accuracy and efficiency of diagnosis.
Ocular diseases seriously affect patients' vision and life quality, with a global morbidity of over 43 million blindness. However, efficient drug delivery to treat ocular diseases, particularly intraocular disorders, remains a huge challenge due to multiple ocular barriers that significantly affect the ultimate therapeutic efficacy of drugs. Recent advances in nanocarrier technology offer a promising opportunity to overcome these barriers by providing enhanced penetration, increased retention, improved solubility, reduced toxicity, prolonged release, and targeted delivery of the loaded drug to the eyes. This review primarily provides an overview of the progress and contemporary applications of nanocarriers, mainly polymer- and lipid-based nanocarriers, in treating various eye diseases, highlighting their value in achieving efficient ocular drug delivery. Additionally, the review covers the ocular barriers and administration routes, as well as the prospective future developments and challenges in the field of nanocarriers for treating ocular diseases.
Drug Carriers , Nanoparticles , Humans , Nanoparticles/therapeutic use , Drug Delivery Systems , Eye , Lipids
