Dose-response relationship between weekly physical activity level and the frequency of colds in Chinese middle-aged and elderly individuals.

Background: Engaging in appropriate physical activity can significantly lower the risk of various diseases among middle-aged and older adults. Investigating optimal levels of physical activity (PA) is crucial for enhancing the health of this demographic. This study aims to explore the dose-response relationship between weekly PA levels and the frequency of colds among Chinese middle-aged and elderly individuals, identifying the necessary PA level to effectively diminish the risk of colds. Methods: We conducted a cross-sectional study using a web-based survey targeting individuals aged 40 and older (n = 1, 683) in China. The survey collected information on PA and the frequency of colds. Data was analyzed using Kruskal-Wallis test and the χ2 test. We explored the dose-response relationship between weekly PA and cold frequency over the past year through an ordered multivariate logistic regression model and a restricted cubic spline model. Results: (1) Brisk walking emerged as the preferred physical exercise for those over 40. The findings suggest that engaging in moderate (odds ratio (OR) = 0.64, P < 0.001, 95% confidence interval (CI) [0.50-0.81]) and high (OR = 0.64, P < 0.001, 95% CI [0.51-0.79]) levels of PA weekly significantly reduces the risk of catching a cold. Individuals with one (OR = 1.47, P < 0.001, 95% CI [1.20-1.80]) or multiple chronic diseases (OR = 1.56, P < 0.001, 95% CI [1.21-2.00]) were at increased risk. Those residing in central (OR = 1.64, P < 0.001, 95% CI [1.33-02.01]) and western China (OR = 1.49, P = 0.008, 95% CI [1.11-02.00]) faced a higher risk compared to their counterparts in eastern China. (2) According to the restricted cubic spline model, adults who experienced one cold in the past year had a weekly PA level of 537.29 metabolic equivalent-minutes per week (MET-min/wk) with an OR value of 1. For those reporting two or more colds, the PA level was 537.76 MET-min/wk with an OR of 1. Conclusions: (1) Brisk walking is the most favored exercise among the Chinese middle-aged and elderly, with the prevalence of colds being affected by the number of chronic diseases and the geographic location. (2) Regular, moderate exercise is linked to a lower risk of colds. To effectively reduce cold frequency, it is recommended that middle-aged and elderly Chinese individuals engage in a minimum of 538 MET-min/wk of exercise.

Construction of An Orthotopic Xenograft Model of Non-small Cell Lung Cancer Mimicking Disease Progression and Predicting Drug Activities.

Non-small cell lung cancer (NSCLC) is a highly lethal disease with a complex and heterogeneous tumor microenvironment. Currently, common animal models based on subcutaneous inoculation of cancer cell suspensions do not recapitulate the tumor microenvironment in NSCLC. Herein we describe a murine orthotopic lung cancer xenograft model that employs the intrapulmonary inoculation of three-dimensional multicellular spheroids (MCS). Specifically, fluorescent human NSCLC cells (A549-iRFP) were cultured in low-attachment 96-well microplates with collagen for 3 weeks to form MCS, which were then inoculated intercostally into the left lung of athymic nude mice to establish the orthotopic lung cancer model. Compared with the original A549 cell line, MCS of the A549-iRFP cell line responded similarly to anticancer drugs. The long-wavelength fluorescent signal of the A549-iRFP cells correlated strongly with common markers of cancer cell growth, including spheroid volume, cell viability, and cellular protein level, thus allowing dynamic monitoring of the cancer growth in vivo by fluorescent imaging. After inoculation into mice, the A549-iRFP MCS xenograft reliably progressed through phases closely resembling the clinical stages of NSCLC, including the expansion of the primary tumor, the emergence of neighboring secondary tumors, and the metastases of cancer cells to the contralateral right lung and remote organs. Moreover, the model responded to the benchmark antilung cancer drug, cisplatin with the anticipated toxicity and slower cancer progression. Therefore, this murine orthotopic xenograft model of NSCLC would serve as a platform to recapitulate the disease's progression and facilitate the development of potential anticancer drugs.

Composite Aerogel Scaffolds Containing Flexible Silica Nanofiber and Tricalcium Phosphate Enable Skin Regeneration.

Poor hemostatic ability and less vascularization at the injury site could hinder wound healing as well as adversely affect the quality of life (QOL). An ideal wound dressing should exhibit certain characteristics: (a) good hemostatic ability, (b) rapid wound healing, and (c) skin appendage formation. This necessitates the advent of innovative dressings to facilitate skin regeneration. Therapeutic ions, such as silicon ions (Si4+) and calcium ions (Ca2+), have been shown to assist in wound repair. The Si4+ released from silica (SiO2) can upregulate the expression of proteins, including the vascular endothelial growth factor (VEGF) and alpha smooth muscle actin (α-SMA), which is conducive to vascularization; Ca2+ released from tricalcium phosphate (TCP) can promote the coagulation alongside upregulating the expression of cell migration and cell differentiation related proteins, thereby facilitating the wound repair. The overarching objective of this study was to exploit short SiO2 nanofibers along with the TCP to prepare TCPx@SSF aerogels and assess their wound healing ability. Short SiO2 nanofibers were prepared by electrospinning and blended with varying proportions of TCP to afford TCPx@SSF aerogel scaffolds. The TCPx@SSF aerogels exhibited good cytocompatibility in a subcutaneous implantation model and manifested a rapid hemostatic effect (hemostatic time 75 s) in a liver trauma model in the rabbit. These aerogel scaffolds also promoted skin regeneration and exhibited rapid wound closure, epithelial tissue regeneration, and collagen deposition. Taken together, TCPx@SSF aerogels may be valuable for wound healing.

FAM53B promotes pancreatic ductal adenocarcinoma metastasis by regulating macrophage M2 polarization.

BACKGROUND: Our study investigated the role of FAM53B in regulating macrophage M2 polarization and its potential mechanisms in promoting pancreatic ductal adenocarcinoma (PDAC) metastasis. AIM: To further investigate the role of FAM53B in regulating macrophage M2 polarization and its potential mechanism in promoting PDAC metastasis. Our goal is to determine how FAM53B affects macrophage M2 polarization and to define its underlying mechanism in PDAC metastasis. METHODS: Cell culture and various experiments, including protein analysis, immunohistochemistry, and animal model experiments, were conducted. We compared FAM53B expression between PDAC tissues and healthy tissues and assessed the correlation of FAM53B expression with clinical features. Our study analyzed the role of FAM53B in macrophage M2 polarization in vitro by examining the expression of relevant markers. Finally, we used a murine model to study the role of FAM53B in PDAC metastasis and analyzed the potential underlying mechanisms. RESULTS: Our research showed that there was a significant increase in FAM53B levels in PDAC tissues, which was linked to adverse tumor features. Experimental findings indicated that FAM53B can enhance macrophage M2 polarization, leading to increased anti-inflammatory factor release. The results from the mouse model further supported the role of FAM53B in PDAC metastasis, as blocking FAM53B prevented tumor cell invasion and metastasis. CONCLUSION: FAM53B promotes PDAC metastasis by regulating macrophage M2 polarization. This discovery could lead to the development of new strategies for treating PDAC. For example, interfering with the FAM53B signaling pathway may prevent cancer spread. Our research findings also provide important information for expanding our understanding of PDAC pathogenesis.

Differentially expressed genes of esophageal tissue in male acute and chronic sleep deprivation mice.

Gastroesophageal reflux disease (GERD) is associated with sleep disturbances. However, mechanisms underlying these interactions remain unclear. Male acute and chronic sleep deprivation (SD) mice were used for this study. Mice in the chronic SD group exhibited anxiety- and depression-like behaviors. We further performed high-throughput genome sequencing and bioinformatics analysis to screen for featured differentially expressed genes (DEGs) in the esophageal tissue. The acute SD group, comprised 25 DEGs including 14 downregulated and 11 upregulated genes. Compared with the acute SD group, more DEGs were present in the chronic SD group, with a total of 169 DEGs, including 88 downregulated and 81 upregulated genes. Some DEGs that were closely related to GERD and associated esophageal diseases were significantly different in the chronic SD group. Quantitative real-time polymerase chain reaction verified the downregulation of Krt4, Krt13, Krt15 and Calml3 and upregulation of Baxl1 and Per3. Notably, these DEGs are involved in biological processes, which might be the pathways of the neuroregulatory mechanisms of DEGs expression.

Collaborative Modeling to Compare Different Breast Cancer Screening Strategies: A Decision Analysis for the US Preventive Services Task Force.

Importance: The effects of breast cancer incidence changes and advances in screening and treatment on outcomes of different screening strategies are not well known. Objective: To estimate outcomes of various mammography screening strategies. Design, Setting, and Population: Comparison of outcomes using 6 Cancer Intervention and Surveillance Modeling Network (CISNET) models and national data on breast cancer incidence, mammography performance, treatment effects, and other-cause mortality in US women without previous cancer diagnoses. Exposures: Thirty-six screening strategies with varying start ages (40, 45, 50 years) and stop ages (74, 79 years) with digital mammography or digital breast tomosynthesis (DBT) annually, biennially, or a combination of intervals. Strategies were evaluated for all women and for Black women, assuming 100% screening adherence and "real-world" treatment. Main Outcomes and Measures: Estimated lifetime benefits (breast cancer deaths averted, percent reduction in breast cancer mortality, life-years gained), harms (false-positive recalls, benign biopsies, overdiagnosis), and number of mammograms per 1000 women. Results: Biennial screening with DBT starting at age 40, 45, or 50 years until age 74 years averted a median of 8.2, 7.5, or 6.7 breast cancer deaths per 1000 women screened, respectively, vs no screening. Biennial DBT screening at age 40 to 74 years (vs no screening) was associated with a 30.0% breast cancer mortality reduction, 1376 false-positive recalls, and 14 overdiagnosed cases per 1000 women screened. Digital mammography screening benefits were similar to those for DBT but had more false-positive recalls. Annual screening increased benefits but resulted in more false-positive recalls and overdiagnosed cases. Benefit-to-harm ratios of continuing screening until age 79 years were similar or superior to stopping at age 74. In all strategies, women with higher-than-average breast cancer risk, higher breast density, and lower comorbidity level experienced greater screening benefits than other groups. Annual screening of Black women from age 40 to 49 years with biennial screening thereafter reduced breast cancer mortality disparities while maintaining similar benefit-to-harm trade-offs as for all women. Conclusions: This modeling analysis suggests that biennial mammography screening starting at age 40 years reduces breast cancer mortality and increases life-years gained per mammogram. More intensive screening for women with greater risk of breast cancer diagnosis or death can maintain similar benefit-to-harm trade-offs and reduce mortality disparities.

Brisk walking improves motor function and lower limb muscle strength in Chinese women aged 80 years and older.

This study investigates the effects of a 12-week brisk walking exercise regimen on motor function improvements in elderly women. Twenty-six elderly women, aged 84.2 ± 3.2 years, participated in a 12-week brisk walking exercise program. Fitness assessments and blood biomarker analyses (including CHO, HDLC, LDLC, TC) were conducted pre- and post-intervention. Additionally, targeted metabolomics was employed to measure short-chain fatty acids, amino acids, and vitamin metabolites. The intervention led to significant enhancements in participants' flexibility (p < 0.05), lower limb muscle strength (p < 0.01), and cardiorespiratory endurance (p < 0.01), while muscle mass showed no significant changes. Fifteen significant differential metabolites were identified (VIP > 1.0, FC > 1.2 or < 0.8, and p < 0.05), with arginine, ornithine, aspartic acid, glutamine, phenylalanine, tyrosine, and pantothenic acid playing key roles across seven metabolic pathways. A 12-week brisk walking exercise program significantly enhanced flexibility, lower limb muscle strength, and cardiorespiratory endurance among elderly women. These improvements did not extend to muscle mass or upper limb muscle strength. The observed enhancement in exercise capacity may be attributed to improved regulation of neurotransmitters.

PTPLAD1 Regulates PHB-Raf Interaction to Orchestrate Epithelial-Mesenchymal and Mitofusion-Fission Transitions in Colorectal Cancer.

Colorectal cancer (CRC) remains one of the leading causes of cancer-related death worldwide. The poor prognosis of this malignancy is attributed mainly to the persistent activation of cancer signaling for metastasis. Here, we showed that protein tyrosine phosphatase-like A domain containing 1 (PTPLAD1) is down-regulated in highly metastatic CRC cells and negatively associated with poor survival of CRC patients. Systematic analysis reveals that epithelial-to-mesenchymal transition (EMT) and mitochondrial fusion-to-fission (MFT) transition are two critical features for CRC patients with low expression of PTPLAD1. PTPLAD1 overexpression suppresses the metastasis of CRC in vivo and in vitro by inhibiting the Raf/ERK signaling-mediated EMT and mitofission. Mechanically, PTPLAD1 binds with PHB via its middle fragment (141-178 amino acids) and induces dephosphorylation of PHB-Y259 to disrupt the interaction of PHB-Raf, resulting in the inactivation of Raf/ERK signaling. Our results unveil a novel mechanism in which Raf/ERK signaling activated in metastatic CRC induces EMT and mitochondrial fission simultaneously, which can be suppressed by PTPLAD1. This finding may provide a new paradigm for developing more effective treatment strategies for CRC.

Development and applications of peri-implantitis mouse models.

OBJECTIVE: Peri-implantitis is one of the most common complications of implants. However, its pathogenesis has not been clarified. In recent years, mouse models are gradually being used in the study of peri-implantitis. This review aims to summarize the methods used to induce peri-implantitis in mice and their current applications. METHOD: Articles of peri-implantitis mouse models were collected. We analyzed the various methods of inducing peri-implantitis and their application in different areas. RESULTS: Most researchers have induced peri-implantitis by silk ligatures. Some others have induced peri-implantitis by Pg gavage and LPS injection. Current applications of peri-implantitis mouse models are in the following areas: investigation of pathogenesis and exploration of new interventions, comparison of peri-implantitis with periodontitis, the interaction between systemic diseases and peri-implantitis, etc. CONCLUSION: Silk ligature for 2-4 weeks, Pg gavage for 6 weeks, and LPS injection for 6 weeks all successfully induced peri-implantitis in mice. Mice have the advantages of mature gene editing technology, low cost, and short time to induce peri-implantitis. It has applications in the study of pathogenesis, non-surgical treatments, and interactions with other diseases. However, compared with large animals, mice also have a number of disadvantages that limit their application.

Protein-rich foods, sea foods, and gut microbiota amplify immune responses in chronic diseases and cancers - Targeting PERK as a novel therapeutic strategy for chronic inflammatory diseases, neurodegenerative disorders, and cancer.

The endoplasmic reticulum (ER) is a cellular organelle that is physiologically responsible for protein folding, calcium homeostasis, and lipid biosynthesis. Pathological stimuli such as oxidative stress, ischemia, disruptions in calcium homeostasis, and increased production of normal and/or folding-defective proteins all contribute to the accumulation of misfolded proteins in the ER, causing ER stress. The adaptive response to ER stress is the activation of unfolded protein response (UPR), which affect a wide variety of cellular functions to maintain ER homeostasis or lead to apoptosis. Three different ER transmembrane sensors, including PKR-like ER kinase (PERK), activating transcription factor 6 (ATF6), and inositol-requiring enzyme-1 (IRE1), are responsible for initiating UPR. The UPR involves a variety of signal transduction pathways that reduce unfolded protein accumulation by boosting ER-resident chaperones, limiting protein translation, and accelerating unfolded protein degradation. ER is now acknowledged as a critical organelle in sensing dangers and determining cell life and death. On the other hand, UPR plays a critical role in the development and progression of several diseases such as cardiovascular diseases (CVD), metabolic disorders, chronic kidney diseases, neurological disorders, and cancer. Here, we critically analyze the most current knowledge of the master regulatory roles of ER stress particularly the PERK pathway as a conditional danger receptor, an organelle crosstalk regulator, and a regulator of protein translation. We highlighted that PERK is not only ER stress regulator by sensing UPR and ER stress but also a frontier sensor and direct senses for gut microbiota-generated metabolites. Our work also further highlighted the function of PERK as a central hub that leads to metabolic reprogramming and epigenetic modification which further enhanced inflammatory response and promoted trained immunity. Moreover, we highlighted the contribution of ER stress and PERK in the pathogenesis of several diseases such as cancer, CVD, kidney diseases, and neurodegenerative disorders. Finally, we discuss the therapeutic target of ER stress and PERK for cancer treatment and the potential novel therapeutic targets for CVD, metabolic disorders, and neurodegenerative disorders. Inhibition of ER stress, by the development of small molecules that target the PERK and UPR, represents a promising therapeutic strategy.

Classification Algorithm for fNIRS-based Brain Signals Using Convolutional Neural Network with Spatiotemporal Feature Extraction Mechanism.

Brain Computer Interface (BCI) is a highly promising human-computer interaction method that can utilize brain signals to control external devices. BCI based on functional near-infrared spectroscopy (fNIRS) is considered a relatively new and promising paradigm. fNIRS is a technique of measuring functional changes in cerebral hemodynamics. It detects changes in the hemodynamic activity of the cerebral cortex by measuring oxyhemoglobin and deoxyhemoglobin (HbR) concentrations and inversely predicts the neural activity of the brain. At the present time, Deep learning (DL) methods have not been widely used in fNIRS decoding, and there are fewer studies considering both spatial and temporal dimensions for fNIRS classification. To solve these problems, we proposed an end-to-end hybrid neural network for feature extraction of fNIRS. The method utilizes a spatial-temporal convolutional layer for automatic extraction of temporally valid information and uses a spatial attention mechanism to extract spatially localized information. A temporal convolutional network (TCN) is used to further utilize the temporal information of fNIRS before the fully connected layer. We validated our approach on a publicly available dataset including 29 subjects, including left-hand and right-hand motor imagery (MI), mental arithmetic (MA), and a baseline task. The results show that the method has few training parameters and high accuracy, providing a meaningful reference for BCI development.

The Development and Evaluation of a Prediction Model for Kidney Transplant-Based Pneumocystis carinii Pneumonia Patients Based on Hematological Indicators.

BACKGROUND: This study aimed to develop a simple predictive model for early identification of the risk of adverse outcomes in kidney transplant-associated Pneumocystis carinii pneumonia (PCP) patients. METHODS: This study encompassed 103 patients diagnosed with PCP, who received treatment at our hospital between 2018 and 2023. Among these participants, 20 were categorized as suffering from severe PCP, and, regrettably, 13 among them succumbed. Through the application of machine learning techniques and multivariate logistic regression analysis, two pivotal variables were discerned and subsequently integrated into a nomogram. The efficacy of the model was assessed via receiver operating characteristic (ROC) curves and calibration curves. Additionally, decision curve analysis (DCA) and a clinical impact curve (CIC) were employed to evaluate the clinical utility of the model. The Kaplan-Meier (KM) survival curves were utilized to ascertain the model's aptitude for risk stratification. RESULTS: Hematological markers, namely Procalcitonin (PCT) and C-reactive protein (CRP)-to-albumin ratio (CAR), were identified through machine learning and multivariate logistic regression. These variables were subsequently utilized to formulate a predictive model, presented in the form of a nomogram. The ROC curve exhibited commendable predictive accuracy in both internal validation (AUC = 0.861) and external validation (AUC = 0.896). Within a specific threshold probability range, both DCA and CIC demonstrated notable performance. Moreover, the KM survival curve further substantiated the nomogram's efficacy in risk stratification. CONCLUSIONS: Based on hematological parameters, especially CAR and PCT, a simple nomogram was established to stratify prognostic risk in patients with renal transplant-related PCP.

Clinical and radiographic outcomes of lateral sinus floor elevation with simultaneous hydrophilic implants placement: A retrospective study of 2-5 years.

AIMS: To investigate the clinical and radiographic outcomes of a chemically modified sandblasted large-grit acid-etched implant (hydrophilic) in lateral sinus floor elevation (LSFE), compared with a conventional one (hydrophobic). MATERIALS AND METHODS: A retrospective study design was adopted. Patients who received LSFE with simultaneous implant placement were recruited. According to different types of implant surfaces, patients were divided into two groups (the hydrophilic group and the hydrophobic group). Implant survival rate (SR), endo-sinus bone stability on the radiographs, mean probing depths, percentage of bleeding on probing, marginal bone loss, and patient satisfaction were evaluated. RESULTS: A total of 106 patients with 180 implants (hydrophilic:101, hydrophobic:79) in 119 maxillary sinuses were included. The follow-up period ranged from 2 to 5 years. Three hydrophobic implants and one hydrophilic implant in four different patients failed. The SR of the hydrophilic group was higher than that of the hydrophobic group but without a significant difference (p > .05). The change and change rate of endo-sinus bone height (ΔESBH and RΔESBH) and bone volume (ΔESBV and RΔESBV) in the hydrophilic group were less than those in the hydrophobic group, with a significant difference at 6 months after implantation. No other significant difference was found between the two groups. CONCLUSION: Within the limitations of this study, both hydrophilic and hydrophobic implants were suitable for LSFE with predictable clinical outcomes. Meanwhile, hydrophilic implants could contribute to the grafted endo-sinus bone stability during healing time.

Bioinspired polysaccharide-based nanocomposite membranes with robust wet mechanical properties for guided bone regeneration.

Polysaccharide-based membranes with excellent mechanical properties are highly desired. However, severe mechanical deterioration under wet conditions limits their biomedical applications. Here, inspired by the structural heterogeneity of strong yet hydrated biological materials, we propose a strategy based on heterogeneous crosslink-and-hydration (HCH) of a molecule/nano dual-scale network to fabricate polysaccharide-based nanocomposites with robust wet mechanical properties. The heterogeneity lies in that the crosslink-and-hydration occurs in the molecule-network while the stress-bearing nanofiber-network remains unaffected. As one demonstration, a membrane assembled by bacterial cellulose nanofiber-network and Ca2+-crosslinked and hydrated sodium alginate molecule-network is designed. Studies show that the crosslinked-and-hydrated molecule-network restricts water invasion and boosts stress transfer of the nanofiber-network by serving as interfibrous bridge. Overall, the molecule-network makes the membrane hydrated and flexible; the nanofiber-network as stress-bearing component provides strength and toughness. The HCH dual-scale network featuring a cooperative effect stimulates the design of advanced biomaterials applied under wet conditions such as guided bone regeneration membranes.

Exosomal circ_0037104 derived from Hu-MSCs inhibits cholangiocarcinoma progression by sponging miR-620 and targeting AFAP1.

Exosomes are membrane-enclosed nanovesicles that shuttle active cargoes, such as circular RNAs (circRNAs) and microRNAs (miRNAs), between different cells. Human umbilical cord-derived mesenchymal stem cells (Hu-MSCs) can migrate to tumor sites and exert complex functions throughout tumor progression. In this study, we successfully isolated Hu-MSCs from human umbilical cords based on their surface marker expression. Hu-MSC-derived exosomes significantly reduced the invasion, migration, and proliferation of cholangiocarcinoma (CCA) cells. Furthermore, circ_0037104 was downregulated in CCA and inhibited the proliferation and metastasis of CCA cells. Then, we investigated the effect of Hu-MSC-derived exosomal circ_0037104 on CCA. Circ_0037104 mainly regulates miR-620 and enhances APAF1 expression, inhibiting CCA cell proliferation and metastasis. Overall, Hu-MSC exosomal circ_0037104 contributes to the progression and stemness of CCA cells via miR-620/APAF1. In conclusion, Hu-MSC-derived exosomal circ_0037104 sponges miR-620 directly and negatively targets APAF1 to suppress CCA.

Nisin and ε-polylysine combined treatment enhances quality of fresh-cut jackfruit at refrigerated storage.

This study investigated the effects of nisin combined with ε-polylysine on microorganisms and the refrigerated quality of fresh-cut jackfruit. After being treated with distilled water (control), nisin (0.5 g/L), ε-polylysine (0.5 g/L), and the combination of nisin (0.1 g/L) and ε-polylysine (0.4 g/L), microporous modified atmosphere packaging (MMAP) was carried out and stored at 10 ± 1°C for 8 days. The microorganisms and physicochemical indexes were measured every 2 days during storage. The results indicated that combined treatment (0.1 g/L nisin, 0.4 g/L ε-polylysine) had the best preservation on fresh-cut jackfruit. Compared with the control, combined treatment inhibited microbial growth (total bacterial count, mold and yeast), reduced the weight loss rate, respiratory intensity, polyphenol oxidase and peroxidase activities, and maintained higher sugar acid content, firmness, and color. Furthermore, it preserved higher levels of antioxidant compounds, reduced the accumulation of malondialdehyde and hydrogen peroxide, thereby reducing oxidative damage and maintaining high nutritional and sensory qualities. As a safe application of natural preservatives, nisin combined with ε-polylysine treatment has great application potential in the fresh-cut jackfruit industry.

Longitudinal Characteristics of Choroidal Neovascular Membrane in Pediatric Patients.

PURPOSE: To report the clinical and imaging characteristics, including optical coherence tomography angiography (OCTA), and treatment outcomes of choroidal neovascular membranes (CNVMs) in children. DESIGN: Retrospective clinical cohort study. METHODS: Thirty eyes from 25 children (56% girls) with CNVM from 2 centers were examined from 2005 to 2022. Clinical features, imaging findings, treatment regimens, and outcomes are described. RESULTS: The most common causes of CNVM were idiopathic (48%) and inflammatory (20%). At diagnosis, most CNVMs were unilateral (80%), active (83.3%), and juxtafoveal (46.7%). Twenty-five eyes (83.3%) of 21 patients (84%) were treated. The most common first-line treatment was intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) (92%), with a retreatment rate of 52.2% at an average of 237 days. The average number of total injections per eye was 2.3. Injections were safely administered in the clinic (52.2%). A gain of 3 lines or 15 ETDRS (Early Treatment Diabetic Retinopathy Study) letters was observed at final visit. The average duration of follow-up was 56.46 ± 42.51 months. No ocular or systemic complication related to treatment was reported. Sixteen eyes (64%) had OCTA images at both presentation and final visit, which showed a decrease in CNVM vessel density and vessel-length density, and in the height of retinal pigment epithelium detachment (RPED). CONCLUSIONS: There are a variety of underlying etiologies for pediatric CNVMs, which are most often unilateral. Treatment with intravitreal anti-VEGF can be beneficial and does not often require frequent or chronic dosing. OCTA demonstrated a decrease in the CNVM vessel density and vessel-length density as well as in the height of RPED.

Polydopamine-Functionalized Strontium Alginate/Hydroxyapatite Composite Microhydrogel Loaded with Vascular Endothelial Growth Factor Promotes Bone Formation and Angiogenesis.

Critical-size bone defects are a common and intractable clinical problem that typically requires filling in with surgical implants to facilitate bone regeneration. Considering the limitations of autologous bone and allogeneic bone in clinical applications, such as secondary damage or immunogenicity, injectable microhydrogels with osteogenic and angiogenic effects have received considerable attention. Herein, polydopamine (PDA)-functionalized strontium alginate/nanohydroxyapatite (Sr-Alg/nHA) composite microhydrogels loaded with vascular endothelial growth factor (VEGF) were prepared using microfluidic technology. This composite microhydrogel released strontium ions stably for at least 42 days to promote bone formation. The PDA coating can release VEGF in a controlled manner, effectively promote angiogenesis around bone defects, and provide nutritional support for new bone formation. In in vitro experiments, the composite microhydrogels had good biocompatibility. The PDA coating greatly improves cell adhesion on the composite microhydrogel and provides good controlled release of VEGF. Therefore, this composite microhydrogel effectively promotes osteogenic differentiation and vascularization. In in vivo experiments, composite microhydrogels were injected into critical-size bone defects in the skull of rats, and they were shown by microcomputed tomography and tissue sections to be effective in promoting bone regeneration. These findings demonstrated that this novel microhydrogel effectively promotes bone formation and angiogenesis at the site of bone defects.

Widefield swept-source optical coherence tomography angiography metrics associated with neovascular glaucoma in patients with proliferative diabetic retinopathy.

PURPOSE: To explore the association between widefield swept-source optical coherence tomography angiography (WF SS-OCTA) metrics, including nonperfusion area (NPA) and neovascularization (NV), and presence of neovascular glaucoma (NVG) in patients with proliferative diabetic retinopathy (PDR). METHODS: A prospective, cross-sectional study was conducted from November 2018 to February 2020. A total of 85 eyes of 60 PDR patients without NVG and 9 eyes of 8 PDR patients with NVG were included. Retinal ischemic parameters (NPA; ischemia index [NPA/total retinal area]) and NV features (NV number; NV area; NV vessel density) were evaluated. Foveal avascular zone (FAZ), macular thickness/volume, and choroidal thickness/volume were obtained using the Zeiss ARI Network. WF SS-OCTA retinal and choroidal metrics, systemic, and ocular parameters were screened using Least Absolute Shrinkage and Selection Operator (LASSO) logistic regression for variable selection. Firth's bias-reduced logistic regression (outcome: presence of NVG) was subsequently used to identify parameters associated with NVG. RESULTS: After LASSO variable selection, 8 variables were significantly associated with the presence of NVG: DM duration (years), insulin (yes/no), best-corrected visual acuity (BCVA) (logMAR), IOP, ischemia index, skeletonized vessel density, macular thickness (inner inferior, outer temporal regions). Firth's bias-reduced logistic regression showed ischemia index (odds ratio [OR]=13.2, 95% confidence interval [CI]:5.3-30.7, P<0.001) and BCVA (OR=5.8, 95%CI:1.2-28.8, P<0.05) were associated with the presence of NVG. NV metrics, FAZ, and choroidal parameters were not related to NVG. CONCLUSIONS: Retinal ischemia but not NV was associated with the presence of NVG in patients with PDR using WF SS-OCTA. Larger, longitudinal studies are needed to validate imaging biomarkers associated with diabetic NVG.