19 cinnamamide/ester-triazole compounds were designed, synthesized and evaluated for their anti-Alzheimer's disease (AD) activity. Among them, compound 4f displayed excellent anti-β-amyloid protein (Aβ)-mediated cytotoxicity (EC₅₀ = 2.03 ± 2.45 μmol·L^-1) in APPswe cells and acetylcholinesterase inhibiton (IC₅₀ = 4.88 ± 4.70 μmol·L^-1). Further study indicated that, at dosages of (1, 5 and 25 mg·kg^-1), compound 4f was effective in improving spatial learning and memory deficits in Aβ_1-42-impaired mice, which was achieved by promoting the nonamyloidogenic signaling and inhibiting the amyloidogenic pathway, along with the suppression of Aβ-induced Tau phosphorylation. All animal experiments in this study were approved by the Experimental Animal Care and Use Committee of the Institute of Medicinal Biotechnology (IMB-20220908D701). In conclusion, compound 4f holds promise as a lead candidate for AD treatment, and the present study lays the foundation for its subsequent development.

Background: Delivering a poor prognosis to patients and their families is critically challenging in pediatric populations. The application of palliative care (PC) provides a bridge between accepting the occurrence of mortality and offering lifelong support.However, little is known about the specifics of PC. This study aims to explore the unmet need for PC in pediatric populations. Methods: We retrospectively reviewed the medical records of mortality cases in the Department of Pediatric Hematology and Oncology at Chang Gung Memorial Hospital. Statistical tests, including Chi-square and Student’s t-tests, were applied to determine the differences between early and late intervention groups in terms of the timing of PC introduction. Results: During the study period, 41 patients were included. Their median age was 11.8 years (IQR, 7.6-15.9). The majority of the disease statuses were refractory or relapsing (R/R). The incidence of memento application was significantly higher in the early intervention group (47.6% vs. 10%, P=0.0081). Vital signs variations tended to be end-of-life (EoL) indicators in this study. Conclusion The early introduction of PC encourages families to accompany their beloved child. EoL signs in the pediatric population include vital sign variations. With the presence of relevant EoL signs, clinical physicians can apply PC earlier to meet the needs.

Objectives: . Endotype-based interventions have shown promise in the treatment of patients with obstructive sleep apnea, and upper airway surgery is a key therapeutic option. However, responses to surgery vary among patients with obstructive sleep apnea. This study aims to examine changes in endotypic traits following upper airway surgery and to explore their association with surgical outcomes. Methods: . We prospectively recruited 25 patients with obstructive sleep apnea who visited a single sleep center for upper airway surgery. These patients underwent polysomnographic studies both before and after surgical intervention. During non-rapid eye movement and rapid eye movement sleep, we estimated endotypic traits—including collapsibility (Vpassive), arousal threshold, loop gain, and upper airway compensation—with the phenotyping using polysomnography method. Based on improvements in the apnea-hypopnea index, patients were classified as either responders or non-responders. We compared the preoperative endotypic traits between these groups using Mann-Whitney tests. Additionally, we compared changes in endotypic traits pre- and post-surgery between responders and non-responders using generalized linear mixed models. Results: . We identified 12 responders and 13 non-responders. Compared to non-responders, responders exhibited improved collapsibility during rapid eye movement sleep (22.3 vs. −8.2%eupnea in Vpassive, P=0.01), and their arousal threshold decreased during non-rapid eye movement sleep (−22.4%eupnea, P=0.02). No endotypic trait predicted surgical response; however, the apnea-hypopnea index during rapid eye movement sleep was higher among responders than non-responders (51.8/hr vs. 34.4/hr, P=0.05). Conclusion . Upper airway surgery significantly reduced collapsibility during rapid eye movement sleep in responders. The target pathology for upper airway surgery is a compromised upper airway during rapid eye movement sleep.

Background: Delivering a poor prognosis to patients and their families is critically challenging in pediatric populations. The application of palliative care (PC) provides a bridge between accepting the occurrence of mortality and offering lifelong support.However, little is known about the specifics of PC. This study aims to explore the unmet need for PC in pediatric populations. Methods: We retrospectively reviewed the medical records of mortality cases in the Department of Pediatric Hematology and Oncology at Chang Gung Memorial Hospital. Statistical tests, including Chi-square and Student’s t-tests, were applied to determine the differences between early and late intervention groups in terms of the timing of PC introduction. Results: During the study period, 41 patients were included. Their median age was 11.8 years (IQR, 7.6-15.9). The majority of the disease statuses were refractory or relapsing (R/R). The incidence of memento application was significantly higher in the early intervention group (47.6% vs. 10%, P=0.0081). Vital signs variations tended to be end-of-life (EoL) indicators in this study. Conclusion The early introduction of PC encourages families to accompany their beloved child. EoL signs in the pediatric population include vital sign variations. With the presence of relevant EoL signs, clinical physicians can apply PC earlier to meet the needs.

Objectives: . Endotype-based interventions have shown promise in the treatment of patients with obstructive sleep apnea, and upper airway surgery is a key therapeutic option. However, responses to surgery vary among patients with obstructive sleep apnea. This study aims to examine changes in endotypic traits following upper airway surgery and to explore their association with surgical outcomes. Methods: . We prospectively recruited 25 patients with obstructive sleep apnea who visited a single sleep center for upper airway surgery. These patients underwent polysomnographic studies both before and after surgical intervention. During non-rapid eye movement and rapid eye movement sleep, we estimated endotypic traits—including collapsibility (Vpassive), arousal threshold, loop gain, and upper airway compensation—with the phenotyping using polysomnography method. Based on improvements in the apnea-hypopnea index, patients were classified as either responders or non-responders. We compared the preoperative endotypic traits between these groups using Mann-Whitney tests. Additionally, we compared changes in endotypic traits pre- and post-surgery between responders and non-responders using generalized linear mixed models. Results: . We identified 12 responders and 13 non-responders. Compared to non-responders, responders exhibited improved collapsibility during rapid eye movement sleep (22.3 vs. −8.2%eupnea in Vpassive, P=0.01), and their arousal threshold decreased during non-rapid eye movement sleep (−22.4%eupnea, P=0.02). No endotypic trait predicted surgical response; however, the apnea-hypopnea index during rapid eye movement sleep was higher among responders than non-responders (51.8/hr vs. 34.4/hr, P=0.05). Conclusion . Upper airway surgery significantly reduced collapsibility during rapid eye movement sleep in responders. The target pathology for upper airway surgery is a compromised upper airway during rapid eye movement sleep.

Background: Delivering a poor prognosis to patients and their families is critically challenging in pediatric populations. The application of palliative care (PC) provides a bridge between accepting the occurrence of mortality and offering lifelong support.However, little is known about the specifics of PC. This study aims to explore the unmet need for PC in pediatric populations. Methods: We retrospectively reviewed the medical records of mortality cases in the Department of Pediatric Hematology and Oncology at Chang Gung Memorial Hospital. Statistical tests, including Chi-square and Student’s t-tests, were applied to determine the differences between early and late intervention groups in terms of the timing of PC introduction. Results: During the study period, 41 patients were included. Their median age was 11.8 years (IQR, 7.6-15.9). The majority of the disease statuses were refractory or relapsing (R/R). The incidence of memento application was significantly higher in the early intervention group (47.6% vs. 10%, P=0.0081). Vital signs variations tended to be end-of-life (EoL) indicators in this study. Conclusion The early introduction of PC encourages families to accompany their beloved child. EoL signs in the pediatric population include vital sign variations. With the presence of relevant EoL signs, clinical physicians can apply PC earlier to meet the needs.

Objectives: . Endotype-based interventions have shown promise in the treatment of patients with obstructive sleep apnea, and upper airway surgery is a key therapeutic option. However, responses to surgery vary among patients with obstructive sleep apnea. This study aims to examine changes in endotypic traits following upper airway surgery and to explore their association with surgical outcomes. Methods: . We prospectively recruited 25 patients with obstructive sleep apnea who visited a single sleep center for upper airway surgery. These patients underwent polysomnographic studies both before and after surgical intervention. During non-rapid eye movement and rapid eye movement sleep, we estimated endotypic traits—including collapsibility (Vpassive), arousal threshold, loop gain, and upper airway compensation—with the phenotyping using polysomnography method. Based on improvements in the apnea-hypopnea index, patients were classified as either responders or non-responders. We compared the preoperative endotypic traits between these groups using Mann-Whitney tests. Additionally, we compared changes in endotypic traits pre- and post-surgery between responders and non-responders using generalized linear mixed models. Results: . We identified 12 responders and 13 non-responders. Compared to non-responders, responders exhibited improved collapsibility during rapid eye movement sleep (22.3 vs. −8.2%eupnea in Vpassive, P=0.01), and their arousal threshold decreased during non-rapid eye movement sleep (−22.4%eupnea, P=0.02). No endotypic trait predicted surgical response; however, the apnea-hypopnea index during rapid eye movement sleep was higher among responders than non-responders (51.8/hr vs. 34.4/hr, P=0.05). Conclusion . Upper airway surgery significantly reduced collapsibility during rapid eye movement sleep in responders. The target pathology for upper airway surgery is a compromised upper airway during rapid eye movement sleep.

Background: Delivering a poor prognosis to patients and their families is critically challenging in pediatric populations. The application of palliative care (PC) provides a bridge between accepting the occurrence of mortality and offering lifelong support.However, little is known about the specifics of PC. This study aims to explore the unmet need for PC in pediatric populations. Methods: We retrospectively reviewed the medical records of mortality cases in the Department of Pediatric Hematology and Oncology at Chang Gung Memorial Hospital. Statistical tests, including Chi-square and Student’s t-tests, were applied to determine the differences between early and late intervention groups in terms of the timing of PC introduction. Results: During the study period, 41 patients were included. Their median age was 11.8 years (IQR, 7.6-15.9). The majority of the disease statuses were refractory or relapsing (R/R). The incidence of memento application was significantly higher in the early intervention group (47.6% vs. 10%, P=0.0081). Vital signs variations tended to be end-of-life (EoL) indicators in this study. Conclusion The early introduction of PC encourages families to accompany their beloved child. EoL signs in the pediatric population include vital sign variations. With the presence of relevant EoL signs, clinical physicians can apply PC earlier to meet the needs.

Cardiovascular disease (CVD) remains one of the leading causes of mortality among adults globally, with continuously rising morbidity and mortality rates. Metabolic disorders are closely linked to various cardiovascular diseases and play a critical role in their pathogenesis and progression, involving multifaceted mechanisms such as altered substrate utilization, mitochondrial structural and functional dysfunction, and impaired ATP synthesis and transport. In recent years, the potential role of peroxisome proliferator-activated receptors (PPARs) in cardiovascular diseases has garnered significant attention, particularly peroxisome proliferator-activated receptor alpha (PPARα), which is recognized as a highly promising therapeutic target for CVD. PPARα regulates cardiovascular physiological and pathological processes through fatty acid metabolism. As a ligand-activated receptor within the nuclear hormone receptor family, PPARα is highly expressed in multiple organs, including skeletal muscle, liver, intestine, kidney, and heart, where it governs the metabolism of diverse substrates. Functioning as a key transcription factor in maintaining metabolic homeostasis and catalyzing or regulating biochemical reactions, PPARα exerts its cardioprotective effects through multiple pathways: modulating lipid metabolism, participating in cardiac energy metabolism, enhancing insulin sensitivity, suppressing inflammatory responses, improving vascular endothelial function, and inhibiting smooth muscle cell proliferation and migration. These mechanisms collectively reduce the risk of cardiovascular disease development. Thus, PPARα plays a pivotal role in various pathological processes via mechanisms such as lipid metabolism regulation, anti-inflammatory actions, and anti-apoptotic effects. PPARα is activated by binding to natural or synthetic lipophilic ligands, including endogenous fatty acids and their derivatives (e.g., linoleic acid, oleic acid, and arachidonic acid) as well as synthetic peroxisome proliferators. Upon ligand binding, PPARα activates the nuclear receptor retinoid X receptor (RXR), forming a PPARα-RXR heterodimer. This heterodimer, in conjunction with coactivators, undergoes further activation and subsequently binds to peroxisome proliferator response elements (PPREs), thereby regulating the transcription of target genes critical for lipid and glucose homeostasis. Key genes include fatty acid translocase (FAT/CD36), diacylglycerol acyltransferase (DGAT), carnitine palmitoyltransferase I (CPT1), and glucose transporter (GLUT), which are primarily involved in fatty acid uptake, storage, oxidation, and glucose utilization processes. Advancing research on PPARα as a therapeutic target for cardiovascular diseases has underscored its growing clinical significance. Currently, PPARα activators/agonists, such as fibrates (e.g., fenofibrate and bezafibrate) and thiazolidinediones, have been extensively studied in clinical trials for CVD prevention. Traditional PPARα agonists, including fenofibrate and bezafibrate, are widely used in clinical practice to treat hypertriglyceridemia and low high-density lipoprotein cholesterol (HDL-C) levels. These fibrates enhance fatty acid metabolism in the liver and skeletal muscle by activating PPARα, and their cardioprotective effects have been validated in numerous clinical studies. Recent research highlights that fibrates improve insulin resistance, regulate lipid metabolism, correct energy metabolism imbalances, and inhibit the proliferation and migration of vascular smooth muscle and endothelial cells, thereby ameliorating pathological remodeling of the cardiovascular system and reducing blood pressure. Given the substantial attention to PPARα-targeted interventions in both basic research and clinical applications, activating PPARα may serve as a key therapeutic strategy for managing cardiovascular conditions such as myocardial hypertrophy, atherosclerosis, ischemic cardiomyopathy, myocardial infarction, diabetic cardiomyopathy, and heart failure. This review comprehensively examines the regulatory roles of PPARα in cardiovascular diseases and evaluates its clinical application value, aiming to provide a theoretical foundation for further development and utilization of PPARα-related therapies in CVD treatment.

In a healthy human, the airway mucus forms a thin, protective liquid layer covering the surface of the respiratory tract. It comprises a complex blend of mucin, multiple antibacterial proteins, metabolic substances, water, and electrolytes. This mucus plays a pivotal role in the lungs' innate immune system by maintaining airway hydration and capturing airborne particles and pathogens. However, heightened mucus secretion in the airway can compromise ciliary clearance, obstruct the respiratory tract, and increase the risk of pathogen colonization and recurrent infections. Consequently, a thorough exploration of the mechanisms driving excessive airway mucus secretion is crucial for establishing a theoretical foundation for the eventual development of targeted drugs designed to reduce mucus production. Across a range of lung diseases, excessive airway mucus secretion manifests with unique characteristics and regulatory mechanisms, all intricately linked to mucin. This article provides a comprehensive overview of the characteristics and regulatory mechanisms associated with excessive airway mucus secretion in several prevalent lung diseases.
Humans ; Mucus/metabolism* ; Mucins/physiology* ; Lung Diseases/metabolism* ; Respiratory Mucosa/metabolism* ; Pulmonary Disease, Chronic Obstructive/physiopathology* ; Asthma/physiopathology* ; Cystic Fibrosis/physiopathology* ; Mucociliary Clearance/physiology*