Search

Since the first plasma realized in 2020, a series of key systems on HL-3 (known as HL-2M before) tokamak have been equipped/upgraded, including in-vessel components (the first wall, lower divertor, and toroidal cryogenic/water-cooling/baking/glow discharge systems, etc.), auxiliary heating system of 11 MW, and 28 diagnostic systems (to measure the plasma density electron temperature, radiation, magnetic field, etc.). Magnet field systems were commissioned firstly for divertor plasma discharges. During the 2nd experimental campaign of HL-3 tokamak, several great progresses have been achieved. Firstly, the successful operation with plasma current larger than 1 MA was achieved under a divertor configuration. Secondly, the advanced divertor concept with two distinct snowflake configurations was realized. It is found that the distribution of ion saturation current and heat flux on bottom plate becomes wide due to magnetic surface expansion, demonstrating the advantage of such configuration in the heat flux mitigation. In addition, using the combination of NBI, ECRH and LHCD, the standard sawtoothing high confinement mode of megampere plasma was firstly accessed on the HL-3. The successful commissioning of HL-3 is beneficial for the initial operation of ITER.

Liver X receptor-α (LXRα) regulates cellular cholesterol abundance and potently activates hepatic lipogenesis. Here we show that at least 1 in 450 people in the UK Biobank carry functionally impaired mutations in LXRα, which is associated with biochemical evidence of hepatic dysfunction. On a western diet, male and female mice homozygous for a dominant negative mutation in LXRα have elevated liver cholesterol, diffuse cholesterol crystal accumulation and develop severe hepatitis and fibrosis, despite reduced liver triglyceride and no steatosis. This phenotype does not occur on low-cholesterol diets and can be prevented by hepatocyte-specific overexpression of LXRα. LXRα knockout mice exhibit a milder phenotype with regional variation in cholesterol crystal deposition and inflammation inversely correlating with steatosis. In summary, LXRα is necessary for the maintenance of hepatocyte health, likely due to regulation of cellular cholesterol content. The inverse association between steatosis and both inflammation and cholesterol crystallization may represent a protective action of hepatic lipogenesis in the context of excess hepatic cholesterol.

The density of wood is a key indicator of the carbon investment strategies of trees, impacting productivity and carbon storage. Despite its importance, the global variation in wood density and its environmental controls remain poorly understood, preventing accurate predictions of global forest carbon stocks. Here we analyse information from 1.1 million forest inventory plots alongside wood density data from 10,703 tree species to create a spatially explicit understanding of the global wood density distribution and its drivers. Our findings reveal a pronounced latitudinal gradient, with wood in tropical forests being up to 30% denser than that in boreal forests. In both angiosperms and gymnosperms, hydrothermal conditions represented by annual mean temperature and soil moisture emerged as the primary factors influencing the variation in wood density globally. This indicates similar environmental filters and evolutionary adaptations among distinct plant groups, underscoring the essential role of abiotic factors in determining wood density in forest ecosystems. Additionally, our study highlights the prominent role of disturbance, such as human modification and fire risk, in influencing wood density at more local scales. Factoring in the spatial variation of wood density notably changes the estimates of forest carbon stocks, leading to differences of up to 21% within biomes. Therefore, our research contributes to a deeper understanding of terrestrial biomass distribution and how environmental changes and disturbances impact forest ecosystems.

The direction of individual B8 solar neutrinos has been reconstructed using the SNO+ liquid scintillator detector. Prompt, directional Cherenkov light was separated from the slower, isotropic scintillation light using time information, and a maximum likelihood method was used to reconstruct the direction of individual scattered electrons. A clear directional signal was observed, correlated with the solar angle. The observation was aided by a period of low primary fluor concentration that resulted in a slower scintillator decay time. This is the first time that event-by-event direction reconstruction in high light-yield liquid scintillator has been demonstrated in a large-scale detector.

Yonghui An,1,2 Jia Li,1,2 Yongqian Li,1,2 Yong Shen1,2 1Department of Orthopaedic Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China; 2The Key Laboratory of Orthopedic Biomechanics of Hebei Province, The Third Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China Background: The purpose of this study was to evaluate characteristics of Modic changes in cervical kyphosis (CK) and their association with axial neck pain. Methods: Study participants included 286 asymptomatic or symptomatic patients with CK (mean age = 54.2 ± 12.2 years) who were consecutively enrolled from March 2009 to October 2015. Clinical and radiographic evaluations were performed at a university outpatient department. CK was classified as global type, reverse sigmoid type, or sigmoid type. Results: There were 138 participants with global type CK, 103 with reverse sigmoid type CK, and 45 with sigmoid type CK. Of the 286 participants, 102 had Modic changes (Modic-1 in 38 segments and Modic-2 in 75 segments). Spinal cord compression grade and disc degeneration occurred more frequently in the group with axial neck pain compared to the group without pain. Angular motion was decreased in those with axial neck pain (mean ± standard deviation [SD] 7.8°±4.6°) compared to those who were asymptomatic (mean ± SD 8.9°±5.1°; P

Aim: Ecological and anthropogenic factors shift the abundances of dominant and rare tree species within local forest communities, thus affecting species composition and ecosystem functioning. To inform forest and conservation management it is important to understand the drivers of dominance and rarity in local tree communities. We answer the following research questions: (1) What are the patterns of dominance and rarity in tree communities? (2) Which ecological and anthropogenic factors predict these patterns? And (3) what is the extinction risk of locally dominant and rare tree species?. Location: Global. Time period: 1990–2017. Major taxa studied: Trees. Methods: We used 1.2 million forest plots and quantified local tree dominance as the relative plot basal area of the single most dominant species and local rarity as the percentage of species that contribute together to the least 10% of plot basal area. We mapped global community dominance and rarity using machine learning models and evaluated the ecological and anthropogenic predictors with linear models. Extinction risk, for example threatened status, of geographically widespread dominant and rare species was evaluated. Results: Community dominance and rarity show contrasting latitudinal trends, with boreal forests having high levels of dominance and tropical forests having high levels of rarity. Increasing annual precipitation reduces community dominance, probably because precipitation is related to an increase in tree density and richness. Additionally, stand age is positively related to community dominance, due to stem diameter increase of the most dominant species. Surprisingly, we find that locally dominant and rare species, which are geographically widespread in our data, have an equally high rate of elevated extinction due to declining populations through large-scale land degradation. Main conclusions: By linking patterns and predictors of community dominance and rarity to extinction risk, our results suggest that also widespread species should be considered in large-scale management and conservation practices.

Forests are a substantial terrestrial carbon sink, but anthropogenic changes in land use and climate have considerably reduced the scale of this system1. Remote-sensing estimates to quantify carbon losses from global forests2-5 are characterized by considerable uncertainty and we lack a comprehensive ground-sourced evaluation to benchmark these estimates. Here we combine several ground-sourced6 and satellite-derived approaches2,7,8 to evaluate the scale of the global forest carbon potential outside agricultural and urban lands. Despite regional variation, the predictions demonstrated remarkable consistency at a global scale, with only a 12% difference between the ground-sourced and satellite-derived estimates. At present, global forest carbon storage is markedly under the natural potential, with a total deficit of 226 Gt (model range = 151-363 Gt) in areas with low human footprint. Most (61%, 139 Gt C) of this potential is in areas with existing forests, in which ecosystem protection can allow forests to recover to maturity. The remaining 39% (87 Gt C) of potential lies in regions in which forests have been removed or fragmented. Although forests cannot be a substitute for emissions reductions, our results support the idea2,3,9 that the conservation, restoration and sustainable management of diverse forests offer valuable contributions to meeting global climate and biodiversity targets.

Peer review is a core component of scientific practice. Although peer review ideally improves research and promotes rigor, it also has consequences for what types of research are published and cited and who wants to (and is able to) advance in research-focused careers. Despite these consequences, few reviewers or editors receive training or oversight to ensure their feedback is helpful, professional, and culturally sensitive. Here, we critically examine the peer-review system in psychology and neuroscience at multiple levels, from ideas to institutions, interactions, and individuals. We highlight initiatives that aim to change the normative negativity of peer review and provide authors with constructive, actionable feedback that is sensitive to diverse identities, methods, topics, and environments. We conclude with a call to action for how individuals, groups, and organizations can improve the culture of peer review. We provide examples of how changes in the peer-review system can be made with an eye to diversity (increasing the range of identities and experiences constituting the field), equity (fair processes and outcomes across groups), and inclusion (experiences that promote belonging across groups). These changes can improve scientists' experience of peer review, promote diverse perspectives and identities, and enhance the quality and impact of science. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Yao-Hsiang Chen,1,2 Yu-Shan Hsieh2 1Department of Nursing, Tri-Service General Hospital Songshan Branch, Taipei City, Taiwan; 2School of Nursing, National Taipei University of Nursing and Health Sciences, Taipei City, TaiwanCorrespondence: Yu-Shan Hsieh, National Taipei University of Nursing and Health Sciences, No. 365, Ming-te Road, Peitou Dist, Taipei City, 112303, Taiwan, Tel +886-2-28227101, Email 228455300teresa@gmail.comAbstract: Long COVID refers to symptoms that appear 3 months after initial infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative virus of Coronavirus disease 2019 (COVID-19), and last for at least 2 months, not attributable to other diagnoses. This health issue significantly burdens patients’ quality of life, the economy, and society. Improving the af-termath of COVID-19 is a crucial global health issue in the post-pandemic era. According to current results, it is evident that developing a simple, low-cost respiratory training method that can be easily used at home by themselves with long Coronavirus disease 2019 symptoms (long COVID) is an important and urgent issue. The incentive spirometer is widely used in physical, speech, and respiratory therapy, as well as in preventing postoperative pulmonary infections and improving sputum clearance. However, to date, the role of incentive spirometer respiratory training in long COVID symptoms is still limited. In this literature review is presented to explore the effectiveness of incentive spirometer respiratory training in alleviating symptoms among individuals recovering from long COVID. We also compile non-invasive assessment methods, with the aim to enable individuals to undergo training and assessments conveniently at home or in the community. In this review, a literature review approach was utilized to explore the effectiveness of incentive spirometer intervention in alleviating long-term COVID symptoms. This study is to synthesize the findings of articles published during January 2019 and December 2023 retrieved from PubMed/CINAHL/MEDLINE/ Google Scholar without re-strictions on study type. We ultimately identified seven articles and have summarized similar past studies. This review could contribute to improving symptoms related to long COVID by incentive spirometer respiratory training and serve as practical reference material for clinical medical staff and provide insights for healthcare policymakers in de-veloping guidelines for future research directions, clinical guidance, and educational strategies in the context of nursing care.Keywords: COVID-19, long COVID, incentive spirometer respiratory training, respiratory training, incentive Spirometer

Yan-Hua Liu,1,* Jin-Wen Su,2,* Jing Jiang,3 Bing-Fen Yang,1 Zhi-Hong Cao,1 Fei Zhai,1 Wen-Na Sun,1 Ling-Xia Zhang,1 Xiao-Xing Cheng1 1Beijing Key Laboratory of New Techniques of Tuberculosis Diagnosis and Treatment, Institute of Tuberculosis Research, Senior Department of Tuberculosis, the Eighth Medical Center of PLA General Hospital, Beijing, 100091, People’s Republic of China; 2Division of Critical Care Medicine, Senior Department of Tuberculosis, the Eighth Medical Center of PLA General Hospital, Beijing, 100091, People’s Republic of China; 3Institute of Research, Beijing Key Laboratory of Organ Transplantation and Immune Regulation, Senior Department of Respiratory and Critical Care Medicine, the Eighth Medical Center of PLA General Hospital, Beijing, 100091, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiao-Xing Cheng; Ling-Xia Zhang, Beijing Key Laboratory of New Techniques of Tuberculosis Diagnosis and Treatment, Institute of Tuberculosis Research, Senior Department of Tuberculosis, Eighth Medical Center of PLA General Hospital, 17 hei Shan Hu Road, Haidian, Beijing, 100091, People’s Republic of China, Fax +86 10 51520496 ; +86 10 66775969, Email xcheng79@outlook.com; zhanglingxia7@163.comPurpose: Tuberculosis (TB) is a major global health threat and its diagnosis remains challenging. This study aimed to develop a nomogram that incorporated peripheral blood transcriptional signatures and other blood tests for the diagnosis of tuberculosis.Patients and Methods: Patients with TB, patients with other definite pulmonary diseases (OPD), individuals with latent tuberculosis infection (LTBI), and healthy controls (HC) were retrospectively enrolled between May 2017 and April 2018. The results of the interferon-γ release assay (IGRA) and blood counts were obtained from medical records, and the transcripts of 10 genes were detected using reverse transcription polymerase chain reaction (RT-PCR). Variable selection was performed using least absolute shrinkage and selection operator regression (LASSO) and multivariate logistic regression was performed for the optimal prediction model with backward direction. The model was displayed as a nomogram, and its performance was evaluated for discrimination ability, calibration ability, and clinical usefulness. Internal validation of the prediction model was conducted using bootstrap resampling.Results: A total of 185 participants were enrolled, including 84 patients with TB and 101 controls. A prediction nomogram composed of IGRA, percentage of neutrophils, and expression levels of CD64, granzyme A (GZMA), and PR/SET domain 1 (PRDM1) was established. The nomogram demonstrated good discrimination, with an unadjusted area under the curve (AUC) of 0.914 (95% CI: 0.875– 0.954) and a bootstrap-corrected AUC of 0.914 (95% CI: 0.874– 0.947). With a cutoff value of 0.519, the sensitivity and specificity for discriminating PTB from controls were 0.81 and 0.871, respectively. The nomogram also showed good calibration with the Hosmer–Lemeshow test (P=0.58) and good clinical practicality displayed by the decision curve analysis.Conclusion: A nomogram composed of IGRA, percentage of neutrophils, and expression of CD64, GZMA, and PRDM1 was established. The nomogram demonstrated a sensitivity and specificity of 81% and 87%, respectively, for differentiating TB from controls.Keywords: tuberculosis, prediction model, peripheral blood, interferon gamma release assay, transcripts of gene

Lian Chen,1,* Yu-Huan Jiang,2,* Mei-Yong Li,3 Bo Huang,3 Lei Yuan,2 Jin-Hua Wan,2 Ting-Yu Qin,2 Ting-Ting Zeng,2 Qing-Gen Chen2 1Department of Ultrasound Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 2Department of Clinical Laboratory, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 3Department of Clinical Laboratory, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China*These authors contributed equally to this studyCorrespondence: Qing-Gen Chen, Department of Clinical Laboratory, the First Affiliated Hospital of Nanchang University, Nanchang, 330006, People’s Republic of China, Tel/Fax +86 0791-86319420, Email 272880243@qq.comPurpose: The aim of the present study was to identify more effective laboratory markers to assess the severity of corona virus disease 2019 and predict the progression of the disease by collecting more laboratory markers and variables.Patients and Methods: In this study, most risk factors, including epidemiological characteristics, blood cell counts, cytokines, and infection markers, were collected from 126 patients with COVID-19 to assess their predictive value.Results: The area under curve (AUC) of Albumin (Alb) to fibrinogen (Fib) ratio (AFR) (0.791), Lactate dehydrogenase (LDH) (0.792), myoglobin (MYO) (0.795), C-reactive protein (CRP) (0.801) and lymphocyte count (0.859) were higher than other markers to distinguish severe from non-severe patients in receiver operating characteristic (ROC) analysis. In the univariate logistic regression analysis, thirty-six out of 46 risk factors, including 34 laboratory markers, were significantly associated with increased odds of severe patients. Multivariate logistic regression analysis showed that the CD19+ lymphocyte count, MYO, LDH, and AFR were associated with increased odds of severe disease. Moreover, Lymphocyte count and AFR levels increased, LDH and CRP levels decreased during hospitalization in recovered severe patients, whereas severe lymphocytopenia and continuously increasing LDH levels were observed in deteriorated patients. AFR level increased and CRP level decreased before the disease worsened in the deteriorated patients; however, when the patients deteriorated, AFR decreased and CRP increased significantly.Conclusion: CD19+ lymphocyte count, MYO, LDH, and AFR are independent biomarkers for early identification of severe COVID-19. Lymphocyte count, AFR, LDH, and CRP levels were helpful in predicting the clinical progression of the disease.\. Keywords: Albumin to fibrinogen ratio, C-reactive protein, Lymphocyte, Coronavirus Disease 2019, Inflammation

Yair Humberto González-Tuyub,1 Karla Daniela González-Iñiguez,1 Paula Catalina Lizarazo-Guiza,2 Sergio Ricardo García-García3 1Clinical Immunology and Allergy Service, ISSSTE Hospital Regional General, Ignacio Zaragoza, Ciudad de México, México; 2Medical Scientific Liaison, AstraZeneca, Ciudad de México, México; 3Clinical Research, HS Estudios Farmacoeconómicos SA de CV, Ciudad de México, MéxicoCorrespondence: Yair Humberto González-Tuyub, Clinical Immunology and Allergy Service, ISSSTE Hospital Regional General, Calz, Ignacio Zaragoza, 1840, Juan Escutia, Iztapalapa, 09100 Iztapalapa, Ciudad de México, México, Email yair.gonzalezz@gmail.comBackground: Asthma is a health condition with worldwide relevance, evaluated based on the necessary treatment to control symptoms and exacerbations. Severe asthma is uncontrolled despite high doses of ICS-LABA and treatment for triggering factors. Severe eosinophilic asthma is characterized by an increase in eosinophils in the peripheral circulation, walls, and passages of the respiratory tract. Biologic treatments such as benralizumab have demonstrated effectiveness as aids in decreasing respiratory tract inflammation and improving the management of symptoms in patients living with asthma.Objective: To assess the efficacy and safety of benralizumab as an add-on therapy for patients with severe, uncontrolled asthma and elevated blood eosinophil counts.Methods: Observational, analytic and ambispective study in 21 patients diagnosed with severe eosinophilic asthma treated with benralizumab, to determine the treatment’s effectiveness through the change in estimated respiratory function by spirometry through the forced expiratory volume in one second (FEV1) value, reduction in second controlling treatment, serum eosinophil reduction, change in the Asthma Control Test score and the Asthma Control Questionnaire test at 6 and 16 months of treatment.Results: An average difference of 241.43 mL (± 461.43) in FEV1 at 6 months was found, as well as an average FeNO reduction of 49.8 ppm and eosinophil reduction of 612.78 cells at 12 months of treatment, additionally, CSI requirements were reduced in 95% of patients.Conclusion: Benralizumab improved respiratory function as well as key biomarkers such as eosinophil count, exhaled nitric oxide fraction (FeNO), which reflected in a decreased requirement of inhaled corticosteroids and improved symptom control.Keywords: asthma, eosinophils, benralizumab, biologics, CSI-LABA therapy

Wonnam Kim,1,* Yeon-Cheol Park,2,3,* Bonhyuk Goo,2 Jung-Hyun Kim,2 Dongwoo Nam,3,4 Eunseok Kim,5,6 Hyun-Jong Lee,7 Dong-Hyun Pyun,8,9 Hae Sun Suh,8– 10 Yoonsung Lee,11 Man S Kim,11 Byung-Kwan Seo,2,3 Yong-Hyeon Baek2,3 1Division of Pharmacology, School of Korean Medicine, Pusan National University, Yangsan, Republic of Korea; 2Department of Acupuncture & Moxibustion, Kyung Hee University College of Korean Medicine, Kyung Hee University Hospital at Gangdong, Seoul, Republic of Korea; 3Department of Acupuncture & Moxibustion, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea; 4Department of Acupuncture & Moxibustion, Kyung Hee University College of Korean Medicine, Kyung Hee University Medical Center, Seoul, Republic of Korea; 5Division of Clinical Medicine, School of Korean Medicine, Pusan National University, Yangsan, Republic of Korea; 6Department of Acupuncture and Moxibustion Medicine, Pusan National University Korean Medicine Hospital, Yangsan, Republic of Korea; 7Department of Acupuncture & Moxibustion, College of Korean Medicine, Daegu Haany University, Daegu, Republic of Korea; 8Department of Regulatory Science, Graduate School, Kyung Hee University, Seoul, Republic of Korea; 9Institute of Regulatory Innovation Through Science (IRIS), Kyung Hee University, Seoul, Republic of Korea; 10College of Pharmacy, Kyung Hee University, Seoul, Republic of Korea; 11Clinical Research Institute, Kyung Hee University Hospital at Gangdong, School of Medicine, Kyung Hee University, Seoul, Republic of Korea*These authors contributed equally to this workCorrespondence: Yong-Hyeon Baek, Department of Acupuncture & Moxibustion, College of Korean Medicine, Kyung Hee University, Seoul, 02447, Republic of Korea, Tel +82 2 440 6099, Fax +82 2 440 714, Email byhacu@khu.ac.krPurpose: Knee osteoarthritis (KOA) is one of the most prevalent degenerative joint diseases worldwide. The herbal decoction, Dokhwalgisaeng-tang (DHGST), has been commonly used in East Asia to treat osteoarthritis. However, there is insufficient evidence to draw clear conclusions concerning its effectiveness and safety for patients with KOA. We aim to determine the efficacy, safety, and economic feasibility of DHGST compared with Celecoxib, an oral COX-2 inhibitor, for patients with degenerative KOA.Trial Design and Methods: This multicenter, randomized, noninferiority trial, involving 160 participants who will be randomized using block randomization with 1:1 allocation, will compare DHGST and Celecoxib. The total trial period is 24 weeks after random allocation, comprising 12 weeks of treatment and 12 weeks of follow-up. Participants with KOA will be administered 200 mg of DHGST (treatment group) or Celecoxib capsules (control group) for 12 weeks. Efficacy and safety evaluations will be conducted at weeks 0, 4, 8, and 12, and 24. The primary outcome measurement is the Korean Western Ontario McMaster score at week 12. Changes in pain intensity using a 100 mm visual analog scale, changes in quality of life using a EuroQol 5-dimension 5-level self-report survey, and patient satisfaction will also be measured to evaluate effectiveness between the two groups. A trial-based economic feasibility evaluation will be conducted to analyze treatment cost-effectiveness from societal and healthcare system perspectives. Drug safety will be assessed through adverse reactions and laboratory test findings.Discussion: This trial protocol has the following limitations. Applying a double-dummy design is not possible, as the tablet and granule forms can easily be distinguished visually, and achieving participant blinding is challenging. The trial findings are intended to inform participants, physicians, and other stakeholders in determining whether DHGST could be used as an alternative therapeutic option for KOA.Trial Registration Number: KCT0008424 (Clinical Research Information Service of the Republic of Korea), registered on 12 May 2023.Keywords: degenerative joint disease, Dokhwalgisaeng-tang, noninferiority trial, randomized controlled trial

Jia-Yu Liu,1 Chia-Hung Yen,2,3 Ya-Fan Lin,4 Yin-Hsun Feng,5 Yi-Ping Fang1,6,7 1School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan; 2Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan; 3Drug Development and Value Creation Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan; 4Department of Chemistry, National Dong Hwa University, Hualien, Taiwan; 5Division of Hematology and Oncology, Department of Internal Medicine, ChiMei Medical Center, Tainan, Taiwan; 6Regeneration Medicine and Cell Therapy Research Center, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 7Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, TaiwanCorrespondence: Yi-Ping Fang, School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, 100, Shih-Chuan 1st Road, San Ming District, Kaohsiung, 80708, Taiwan, Tel +886 7 3121101 ext. 2261, Email ypfang@kmu.edu.twBackground: Belinostat, a histone deacetylase inhibitor used for hematological cancer treatments, however, it caused thrombocytopenia, poor solubility, and rapid clearance. To mitigate these issues, human serum albumin (HSA) was utilized as the core material for its high protein binding affinity and self-binding capabilities. The study focused on developing belinostat-loaded HSA nanoparticles to improve solubility, extend circulation time, and reduce adverse effects.Methods: Belinostat-loaded HSA nanoparticles were synthesized using a desolvation method, optimized for size, charge, and entrapment efficiency, and characterized by molecular docking and Fourier-transform infrared spectroscopy (FTIR). Cytotoxicity was assessed in vitro against HuT-78 cells, and in vivo pharmacokinetics and toxicology studies were conducted to evaluate therapeutic efficacy and safety.Results: The prepared belinostat–HSA nanoparticles exhibited the size of 150 nm with a charge of ~− 50 mV and a high entrapment efficiency (90%). Molecular docking confirmed that belinostat and HSA had a strong binding affinity (− 9.5 kcal mol− 1), and the entrapment of belinostat within HSA nanoparticles was also confirmed via FTIR. Belinostat–HSA nanoparticles were cytotoxic against HuT-78 with the dose–response relation (1– 100 μM). The highly concentrated (100 μM) belinostat–HSA nanoparticles maintained the viability of the peripheral blood mononuclear cells with 50% survival, which did not survive when exposed to belinostat (100 μM). The belinostat–HSA nanoparticles proved suitable for intravenous administration without causing hemolysis, exhibited prolonged circulation times, and improved in vivo platelet counts significantly (p < 0.05).Conclusion: In conclusion, the belinostat-loaded HSA nanoparticles significantly enhance the solubility and half-life of belinostat, reduce its adverse hematological effects, and maintain sustained drug release. These attributes underscore the potential of belinostat-HSA nanoparticles as a viable intravenous option for the treatment of hematological malignancies. Keywords: belinostat, human serum albumin nanoparticles, peripheral T-cell lymphoma, thrombocytopenia, pharmacokinetics

Jia-wei Xu,1,2,&ast; Fang-fang Chen,1,&ast; Ying-hui Qv,1,&ast; Cong-cong Sun,1 Dong Zhang,1,2 Zhi Guo,1 Yu-jiao Wang,3 Jun-fei Wang,4 Tian Liu,4 Liang Dong,1,2 Qian Qi1,2 1Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Institute of Respiratory Diseases, Shandong Characteristic Laboratory of Clinical Transformation of Respiratory Biological Immunity and Regenerative Medicine, Jinan, Shandong Province, 250014, People’s Republic of China; 2Department of Pulmonary and Critical Care Medicine, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong Province, 250014, People’s Republic of China; 3Department of Clinical Laboratory Medicine, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Medicine and Health Key Laboratory of Laboratory Medicine, Jinan, Shandong Province, 250014, People’s Republic of China; 4Department of Pulmonary and Critical Care Medicine, Qilu Hospital, Shandong University, Jinan, Shandong Province, 250012, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qian Qi, Department of Pulmonary and Critical Care Medicine, the First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, &num;16766, Jingshi Road, Jinan City, Shandong Province, 250014, People’s Republic of China, Tel +86 13706380314, Email qiqianqlh@163.comPurpose: Bronchiectasis patients are prone to Pseudomonas aeruginosa infection due to decreased level of sphingosine in airway. Adiponectin receptor agonist AdipoRon activates the intrinsic ceramidase activity of adiponectin receptor 1 (AdipoR1) and positively regulates sphingosine metabolism. This study aimed to investigate the potential therapeutic benefit of AdipoRon against Pseudomonas aeruginosa infection.Methods: A mouse model of Pseudomonas aeruginosa lung infection and a co-culture model of human bronchial epithelial cells with Pseudomonas aeruginosa were established to explore the protective effect of AdipoRon. Liquid chromatography-mass spectrometry was used to detect the effect of AdipoRon on sphingosine level in lung of Pseudomonas aeruginosa-infected mouse models.Results: The down-regulation of adiponectin and AdipoR1 in airway of bronchiectasis patients was linked to Pseudomonas aeruginosa infection. By activating AdipoR1, AdipoRon reduced Pseudomonas aeruginosa adherence on bronchial epithelial cells and protected cilia from damage in vitro. With the treatment of AdipoRon, the load of Pseudomonas aeruginosa in lung significantly decreased, and peribronchial inflammatory cell infiltration was lessened in vivo. The reduced level of sphingosine in the airway of Pseudomonas aeruginosa infected mice was replenished by AdipoRon, thus playing a protective role in the airway. Moreover, AdipoRon activated P-AMPKα/PGC1α, inhibited TLR4/P-NF-κB p65, and reduced expression of pro-apoptotic bax. However, the protective effect of AdipoRon on resisting Pseudomonas aeruginosa infection was weakened when AdipoR1 was knocked down.Conclusion: AdipoRon protects bronchial epithelial cells and lung by enhancing their resistance to Pseudomonas aeruginosa infection. The mechanism might be modulating sphingosine metabolism and activating P-AMPKα/PGC1α while inhibiting TLR4/P-NF-κB p65.Keywords: AdipoRon, Pseudomonas aeruginosa, bronchiectasis, AdipoR1, sphingosine metabolism

Li Luo,1 Xi-Jiao Liu,2 Dong-Ling Chen,1 Xiao-Ya Deng,1 Yong-Hong Pan,1 Sheng Li1 1Department of Respiratory Medicine, Shapingba Hospital affiliated to Chongqing University (Shapingba District People’s Hospital of Chongqing), Chongqing, Shapingba District, 400040, People’s Republic of China; 2Bishan Hospital of Chongqing Medical University (Bishan Hospital of Chongqing), Chongqing, Bishan District, 402760, People’s Republic of ChinaCorrespondence: Sheng Li, Email linwo3696347@163.comObjective: This study aims to evaluate the clinical efficacy of integrated traditional Chinese and Western medicine rehabilitation treatment during the recovery period of COVID-19, providing a scientific basis for developing more effective rehabilitation protocols.Methods: The study included 120 COVID-19 (novel coronavirus) recovery patients treated at our hospital from November 2021 to April 2022. After registration, patients were randomly divided into two groups, namely the study group and the control group. The control group received conventional rehabilitation treatment, while the study group underwent integrated traditional Chinese and Western medicine rehabilitation treatment, with 60 cases in each group. The clinical observation indicators in this study include the results of the 6-minute walk test (6MWT), respiratory and circulatory parameters, pulmonary function, changes in respiratory muscle strength, and quality of life in both groups of patients.Results: The 6MWT distance increased significantly in both groups, with the study group showing a larger improvement (P < 0.05). SpO2 and PaO2 values improved significantly in both groups, with greater increases in the study group (P < 0.05). Lung function parameters (FEV1 and FEV1/FVC) improved significantly in the study group compared to the control group (P < 0.05). Diaphragmatic thickness and mobility were also significantly higher in the study group (P < 0.05). The SF-36 quality of life scores were significantly better in the study group (P < 0.05).Conclusion: Integrated traditional Chinese and Western medicine rehabilitation treatment has achieved significant efficacy during the recovery period of COVID-19. The complementary use of traditional Chinese medicine’s differential diagnosis and treatment and modern medical approaches from Western medicine provides patients with comprehensive and personalized rehabilitation services, offering new ideas and methods to improve the quality of patient recovery.Keywords: COVID-19, novel coronavirus, recovery period, integrated traditional Chinese and Western medicine rehabilitation treatment, efficacy

Bo-Chieh Chang,1 Meng-Hsuan Kuo,1 Chi-Hui Lee,1 Ya-Lan Chu,1 Kuang-Peng Chen,2 Chun-Liong Tung,2 Ya-Hui Yang,3 Chuan-Sheng Hung,4 Jui-Hsiu Tsai,2,5 Hung-Yi Chuang6 1Department of Pharmacy, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan; 2Department of Psychiatry, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan; 3Department of Long-Term Care and Health Management, Cheng Shiu University, Kaohsiung, Taiwan; 4Department of Computer Science and Engineering, National Sun Yat-Sen University, Kaohsiung, Taiwan; 5School of Medicine, Tzu Chi University, Hualien, Taiwan; 6Department of Environmental and Occupational Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, TaiwanCorrespondence: Jui-Hsiu Tsai, Department of Psychiatry, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, No. 2, Min-Sheng Road, Dalin Town, Chiayi, 622, Taiwan, Email faanvangogh@gmail.comIntroduction: Poor adherence to antipsychotics in patients with schizophrenia is a leading cause of relapse and functional deterioration. Long-acting injectable paliperidone may reduce relapse risks, health-care utilisation, and health-care costs in these patients.Methods: In this 24-month mirror-image study, we compared health-care utilization and costs before and after the initiation of paliperidone palmitate 3-monthly (PP3M) treatment in patients with schizophrenia spectrum disorders. Before the initiation of PP3M, the patients received paliperidone 1-monthly (PP1M) treatment. The primary study outcomes were changes in health-care utilisation and costs over the study period.Results: This study included 34 patients with schizophrenia spectrum disorders. During the 12-months period after the initiation of PP3M treatment, the mean duration of hospitalisation decreased from 57.7 to 28.5 days (p = 0.03). Moreover, significant reductions were noted in emergency room visits (PP1M vs PP3M: 0.3 vs 0.0, respectively; p = 0.05) and health-care costs (PP1M vs PP3M: 107,328.8 vs 57,848.6, respectively; p = 0.03).Conclusion: PP3M may significantly reduce hospitalisation duration, emergency room visits, and health-care costs in patients with schizophrenia.Keywords: schizophrenia, long-acting injectable antipsychotics, paliperidone palmitate, health-care cost, health-care utilisation

Eva Raphael,1,2 Lorenzo Argante,3 Elisa Cinconze,3 Sara Nannizzi,3 Cheyenne Belmont,1 Claire F Mastrangelo,4 Yuan Hu Allegretti,5 Michele Pellegrini,3 Johannes E Schmidt3 1Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, USA; 2Department of Family and Community Medicine, University of California, San Francisco, CA, USA; 3Clinical Research and Development Center, GSK, Siena, Italy; 4Division of Infectious Diseases and Vaccinology, School of Public Health - University of California, Berkeley, CA, USA; 5Division of Epidemiology, School of Public Health - University of California, Berkeley, CA, USACorrespondence: Johannes E Schmidt, GSK, Clinical Research and Development Center, Via Fiorentina, 1, 53100, Siena, Italy, Tel +393487052179, Email johannes.e.schmidt@gsk.comPurpose: Urinary tract infections (UTIs) are among the most common bacterial infections, with uropathogenic Escherichia coli (UPEC) as the main etiologic agent of uncomplicated UTIs (uUTIs). The prevalence of uUTis caused by organisms with antimicrobial resistance (AMR) is increasing worldwide, complexifying the disease management and increasing the risk of complications. In efforts to develop new strategies for uUTI prevention, it is imperative to understand factors associated with the occurrence of new episodes.Patients and Methods: This retrospective cohort study aimed to assess the incidence of uUTIs caused by UPEC (UPEC-uUTIs) or unknown etiology (untested uUTIs) in adults aged ≥ 18 years receiving care in a San Francisco healthcare system.Results: During 2014– 2019, 1087 UPEC-uUTI and 4106 untested uUTI cases were documented, of which 324 (29.8%; 95% confidence interval: 27.1%– 32.6%) and 1030 (25.1%; 95% confidence interval: 23.8%– 26.4%) were followed by ≥ 1 new episode of uUTI within 12 months. In the UPEC-uUTI cohort, male gender, diagnosis of diabetes mellitus, and prior uUTI were risk factors for new episodes of uUTI. At the time of first UPEC-uUTI diagnosis, antimicrobial prescriptions were retrieved for 41.1% of cases. When tested, AMR was most frequently reported for trimethoprim/sulfamethoxazole or trimethoprim/sulfamethoxazole prescribed with other antimicrobials.Conclusion: Our study provides important information on the incidence and risk of repeated episodes of uUTIs, as well as on AMR related to them. Keywords: uncomplicated urinary tract infection, urinary tract infection risk factors, antimicrobial resistance, urinary tract infection prevention

Chien-Hui Pan,1,2 Tzen-Yuh Chiang,2 Hui-Chi Hsieh,1 Ya-Huei Wang3,4 1Education Center, National Cheng Kung University Hospital, Tainan, Taiwan; 2Department of Life Sciences, National Cheng Kung University, Tainan, Taiwan; 3Department of Applied Foreign Languages, Chung Shan Medical University, Taichung, Taiwan; 4Department of Medical Education, Chung Shan Medical University Hospital, Taichung, TaiwanCorrespondence: Ya-Huei Wang, Chung Shan Medical University, Department of Applied Foreign Languages, 110, Sec. 1, Jian-Koa N. Road, Taichung, 402, Taiwan, Tel +886-4-24730022 Ex 12003, Email yhuei@csmu.edu.twObjective: In Taiwanese clinical and healthcare environments, there is a dearth of appropriate and effective tools to evaluate clinical teachers’ occupational well-being. Therefore, this study aimed to develop a culturally adapted scale, a Taiwanese version of the Clinical Teachers’ Occupational Well-Being Dimensions Scale (CTOWDS), to accurately measure the occupational well-being of clinical teachers in Taiwan.Methods: Following a comprehensive literature review and expert panel discussions, the study developed the CTOWDS and conducted exploratory factor analysis (EFA) with 346 participants using SPSS to identify its underlying dimensional structure and psychometric properties. Confirmatory factor analysis (CFA) was then performed with 255 participants using AMOS to validate the EFA results. The study also assessed internal consistency, convergent and discriminant validities, and goodness-of-fit indexes to ensure that the scale was valid and reliable in the Taiwanese cultural setting.Results: The EFA refined the scale from 51 to 29 items across five dimensions: personal qualities (11 items), academic research and career development pressure (6 items), teaching experience (4 items), learning experience (4 items), and teaching and communication pressure (4 items). These five dimensions explained 65.279% of the total variance. The CFA confirmed the five dimensions and 29 items, with good convergent and discriminant validities, goodness-of-fit indexes, and Cronbach’s alpha values exceeding 0.70.Conclusion: The findings affirm the utility of the developed CTOWDS as a reliable and culturally relevant instrument for assessing the occupational well-being of clinical teachers.Keywords: occupational well-being, clinical teachers, scale development, psychometric validation

Chin-Hsuan Yeh,1,&ast; Chia-Hsuan Lin,2,&ast; Tien-Li Ma,3 Tzu-Yu Peng,4 Thi Thuy Tien Vo,5 Wei-Ning Lin,6 Yu-Hsu Chen,7,8 I-Ta Lee4 1Division of Oral and Maxillofacial Surgery, Department of Dentistry, Taipei Medical University Hospital, Taipei, Taiwan; 2Department of Family Medicine, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan, Taiwan; 3School of Dental Technology, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan; 4School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan; 5Faculty of Dentistry, Nguyen Tat Thanh University, Ho Chi Minh City, 700000, Vietnam; 6Graduate Institute of Biomedical and Pharmaceutical Science, Fu Jen Catholic University, New Taipei City, Taiwan; 7Department of Orthopedic Surgery, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan, Taiwan; 8Department of Biology and Anatomy, National Defense Medical Center, Taipei, Taiwan&ast;These authors contributed equally to this workCorrespondence: I-Ta Lee, School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan, 250 Wuxing St, Taipei, 11031, Taiwan, Tel +886-2-27361661 ext. 5162, Fax +886-2-27362295, Email itlee0128@tmu.edu.twAbstract: This integrative literature review evaluates the effectiveness of power toothbrushes (PTBs) compared to manual toothbrushes (MTBs) across various populations, focusing on plaque removal, gingival health, calculus reduction, and stain removal. PTBs equipped with advanced technologies such as oscillating-rotating and high-frequency sonic mechanisms have been examined for their potential to enhance oral hygiene. Special attention is given to vulnerable groups, including the elderly and individuals with intellectual disabilities, to assess how PTBs meet their specific oral health needs. A comprehensive literature search was conducted in databases including PubMed, Cochrane Library, Embase, and Google Scholar using keywords such as “power toothbrush”, “electric toothbrush”, “manual toothbrush”, “plaque removal”, “gingivitis”, “calculus”, “dental stains”, “oral hygiene”, “elderly”, and “intellectual disabilities”. Studies published between 2000 and 2024 were selected based on their relevance to the PTB and MTB comparison, with an emphasis on outcomes related to oral hygiene efficacy. As this review is narrative rather than systematic, it focuses on synthesizing existing knowledge without applying strict inclusion or exclusion criteria. The results indicate that PTBs generally outperform MTBs in reducing plaque, gingivitis, and stains, though the benefits for special populations are less pronounced but still significant. However, practical issues such as user experience and mechanical reliability of PTBs warrant further investigation. In conclusion, this review enhances the understanding of PTB effectiveness, guides consumer choices, and informs future technological advancements in dental care practices.Keywords: power toothbrushes, manual toothbrushes, plaque removal, gingival health, dental calculus, oral hygiene

Ling-ling Zhu,1 Yan-hong Wang,2 Jian-hua Feng,3 Quan Zhou2 1VIP Geriatric Ward, Division of Nursing, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, People’s Republic of China; 2Department of Pharmacy, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, People’s Republic of China; 3Department of Pediatrics, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, People’s Republic of ChinaCorrespondence: Quan Zhou, Department of Pharmacy, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Jiefang Road No. 88, Hangzhou, 310009, Zhejiang Province, People’s Republic of China, Email zhouquan142602@zju.edu.cn Jian-hua Feng, Department of Pediatrics, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Jiefang Road No. 88, Hangzhou, 310009, Zhejiang Province, People’s Republic of China, Email hzhz87083886@zju.edu.cnBackground: Bacterial lysates are known for having immunomodulatory properties and have been used mainly for the prevention and treatment of respiratory tract infections (RTIs). However, rigorous studies are needed to confirm the clinical efficacy of bacterial lysates with various bacterial antigen components, preparation methods, administration routes and course of treatment. OM-85, an oral standardized lysate prepared by alkaline lysis of 21 strains from 8 species of common respiratory tract pathogens, is indicated as immunotherapy for prevention of recurrent RTIs and acute infectious exacerbations of chronic bronchitis. OM-85 acts on multiple innate and adaptive immune targets and can restore type 1 helper T (Th1)/Th2 balance. Sporadic studies have shown advances in pharmacology and therapeutics of OM-85, and thus an update review is necessary.Methods: Literature was retrieved by searching PubMed, Web of science, Embase, CNKI, and Full Text Database of Chinese Medical Journals.Results: New roles of OM-85 were discovered in prevention and treatment of lung cancer, pulmonary tuberculosis, SARS-CoV-2 infection, allergic rhinitis, pulmonary fibrosis, atopic dermatitis, and nephrotic syndrome. Pharmacoeconomic values of OM-85 were demonstrated in prophylaxis and treatment of RTIs, chronic obstructive pulmonary disease, asthma, chronic bronchitis, rhinosinusitis and allergic rhinitis. Two consecutive courses of OM-85 (6 or 12 months apart) could prevent recurrent RTIs in children. Maternal OM-85 treatment could offer benefits for offspring. Product-specific response was observed. The efficacy of OM-85 may be associated with patient’s characteristics (eg, severity of the disease, age, immune response pattern, malignancy risk stratification).Conclusion: OM-85 can improve effectiveness of standard care for some primary diseases, and carry significant pharmacoeconomic implications. The benefits shown by OM-85 in vitro and in vivo, when extrapolated to humans, are exciting but also require caution. Individualized treatment may need to be considered. It is necessary to compare the efficacy and safety of various bacterial lysate preparations.Keywords: airway inflammatory disease, allergic diseases, bacterial lysates, immunomodulator, OM-85, pharmacoeconomic evaluation

Emanuela Foglia,1 Federica Asperti,1 Grazia Antonacci,2,3 Yogini H Jani,4 Elisabetta Garagiola,1 Daniele Bellavia,1 Lucrezia Ferrario1 1LIUC - University Cattaneo, Healthcare Datascience LAB, Castellanza, Varese, 21053, Italy; 2Department of Primary Care and Public Health, Imperial College London, National Institute of Health Research (NIHR) Applied Research Collaboration (ARC) Northwest London, London, UK; 3Business School, Centre for Health Economics and Policy Innovation (CHEPI), Imperial College London, London, UK; 4Centre for Medicines Optimisation Research and Education, University College London Hospitals NHS Foundation Trust, London, UKCorrespondence: Elisabetta Garagiola, Healthcare Datascience Laboratory - HD LAB, LIUC-Università Cattaneo, Corso G. Matteotti, 22, Castellanza, VA, 21053, Italy, Tel +39.0331.572.467, Email egaragiola@liuc.itBackground: Automated Drug Dispensing (ADD) systems are considered to be strategic hospital assets used to reduce errors and enhance economic and organizational sustainability. With regards to efficacy and safety, the literature evidence demonstrates the incremental benefits of centralised or decentralised systems compared to manual dispensing. Analyses about organisational and economic sustainability are still lacking and the present study aims to perform a Health Technology Assessment (HTA), producing multidimensional evidence on the use of ADD systems within hospitals.Methods: In 2023, a comprehensive HTA draws insights from healthcare professionals across six European nations: Italy, France, Germany, the Netherlands, the United Kingdom, and Belgium. This appraisal juxtaposed four drug dispensing scenarios: manual methods, centralized ADD systems, decentralized ADD systems, and integrated solutions employing cutting-edge technologies in both central pharmacies and wards. The study deployed an Activity-Based Costing approach that was combined with a cost-effectiveness and Budget Impact Analysis to evaluate economic impacts. Qualitative questionnaires were implemented to assess ethical, legal, organizational, safety, and efficacy aspects.Results: From a multidimensional perspective, healthcare professionals acknowledged ADD manifold advantages of ADD systems. From an organizational perspective and within a 12-month timeframe, transitioning to automation may face initial challenges that are attributed to potential resistance from professionals and significant investments. However, 36 months past its adoption, automation’s superiority over manual methods was recognized. Economically, savings burgeoned from +17.9% in UK to +26.6% in Belgian hospitals that adopted integrated systems in comparison to traditional manual approaches.Conclusion: Compared to traditional methods, implementing ADD systems could improve the logistic management of drug in the hospital setting, thereby enhancing safety and efficacy, streamlining the healthcare professionals’ workflow, and bolstering financial stability.Keywords: automated drug dispensing systems, HTA, economic impact, drug logistic management, efficiency

Shin-Kai Chou,1 Song-Seng Loke,2 Chieh Lan,1 Chong-Fong Sun,1 Yun-Hwa Huang,3 Chih-Fang Huang3,4 1Department of Family Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan; 2Division of Geriatric Medicine, Department of Family Medicine, Kaohsiung Chang Gung Memorial Hospital; School of Medicine, College of Medicine, National Sun Yat-sen University, Kaohsiung, Taiwan; 3Departments of Family Medicine, Kaohsiung Municipal Feng Shan Hospital, Kaohsiung, Taiwan; 4Department of Long Term Care and Management, Chung Hwa University of Medical Technology, Tainan, TaiwanCorrespondence: Song-Seng Loke, Division of Geriatric Medicine, Department of Family Medicine, Kaohsiung Chang Gung Memorial Hospital; School of Medicine, College of Medicine, National Sun Yat-Sen University, 123, Dapi Road, Niaosong District, Kaohsiung, 833, Taiwan, Tel +886-7-7317123, Fax +886-7-738762, Email loke@cgmh.org.twPurpose: Previous studies revealed an inconclusive association between dyslipidemia and decreased vitamin D levels. This study aims to investigate the association between dyslipidemia parameters and decreased serum vitamin D levels among the southern Taiwanese population during a health examination.Patients and Methods: A retrospective cross-sectional study was conducted from January 2020 to December 2020, enrolling 2430 subjects in a southern Taiwanese medical center. We performed logistic regression to examine the association between lipid profiles and vitamin D insufficiency or deficiency.Results: The prevalence of vitamin D sufficiency was higher in males (65.9%). Compared to individuals with total cholesterol (TC)

Fang Fang,1,&ast; Yun Yan Chen,1,&ast; Xin-Ming Zhang,2 Jin Tang,1 Yu-Hao Liu,1 Chen-Shuo Peng,1 Yu Sun1,3 1School of Pharmacy, Wannan Medical College, Wuhu, 241002, People’s Republic of China; 2School of Chemistry and Materials Science, Anhui Normal University, Wuhu, 241002, People’s Republic of China; 3Institute of Synthesis and Application of Medical Materials, Wannan Medical College, Wuhu, 241002, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yu Sun, School of Pharmacy, Wannan Medical College, Wuhu, 241002, People’s Republic of China, Tel +86 553 3932026, Email whsunyu@163.comBackground: Epidermal growth factor receptor (EGFR) is a major target for the treatment of colorectal cancer. Thus, anti-EGFR antibody conjugated lipid-polymer hybrid nanoparticles can offer a potential means of enhancing the efficacy of chemotherapeutics in EGFR overexpressing cancers. In addition, the combination of chemotherapy and photothermal therapy is a promising strategy for cancer treatment. Hence, it is highly desirable to develop a safe and effective delivery system for colorectal tumor therapy.Methods: In this study, EGFR-targeted and NIR-triggered lipid-polymer hybrid nanoparticles (abbreviated as Cet-Iri-NPs) were prepared with copolymer PPG-PEG, lipids DSPE-PEG-Mal and lecithin as carriers, CPT-11 as an anticancer chemotherapeutic agent, indocyanine green (ICG) as a photothermal agent, and cetuximab as a surface-targeting ligand.Results: In vitro analyses revealed that Cet-Iri-NPs were spherical with size of 99.88 nm, charge of 29.17 mV, drug entrapment efficiency of 51.72%, and antibody conjugation efficiency of 41.70%. Meanwhile, Cet-Iri-NPs exhibited a remarkable photothermal effect, and pH/NIR-triggered faster release of CPT-11 with near infrared (NIR) laser irradiation, which induced enhanced cytotoxicity against SW480 cells. Furthermore, the promoted tumor-growth suppression effect of Cet-Iri-NPs on SW480 tumor xenograft nude mice was achieved under NIR laser irradiation.Conclusion: These results indicate that the well-defined Cet-Iri-NPs are a promising platform for targeted colorectal cancer treatment with chemo-photothermal therapy. Keywords: Chemo-photothermal therapy, Targeted cancer therapy, Nanoparticles, Cetuximab, Indocyanine green

Chin-Yi Yang,1,2,&ast; Ya-Ching Chang,2,&ast; Hao-Chih Tai,3 Yi-Hua Liao,4 Yu-Huei Huang,2 Rosaline Chung-Yee Hui,2 Yuan-Sung Kuo,3 Shyue-Yih Horng,3 Yi-Shuan Sheen,4 Tim-Mo Chen,5 Yuan-Sheng Tzeng,5 Chih-Hsin Wang,5 Shou-Cheng Teng,5 Chun-Kai Oscar Chang,5 Chang-Yi Chou5 1Department of Dermatology, New Taipei Municipal TuCheng Hospital, New Taipei City, 236, Taiwan; 2Department of Dermatology, Linkou Chang-Gung Memorial Hospital, Taoyuan, 333, Taiwan; 3Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, 100, Taiwan; 4Department of Dermatology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, 100, Taiwan; 5Division of Plastic Surgery, Tri-Service General Hospital, Taipei, 100, Taiwan&ast;These authors contributed equally to this workCorrespondence: Hao-Chih Tai, Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, No. 7, Zhongshan S. Road, Zhongzheng Dist, Taipei, 100225, Taiwan, Tel +886 2 2312-3456&num;65062 65520, Email taihc1@gmail.com; taihc@ntu.edu.tw Yi-Hua Liao, Department of Dermatology, National Taiwan University Hospital and National Taiwan University College of Medicine, No. 7, Zhongshan S. Road, Zhongzheng Dist, Taipei, 100225, Taiwan, Tel +886 2 2312-3456&num; 265317, Email yihualiao@ntu.edu.twPurpose: Porcine-based dermal injectable collagen is effective for nasolabial fold correction. In the present study, a new dermal injectable collagen, incorporating a novel cross-linking technology and premixed with lidocaine, was introduced. The study aimed to determine the efficacy of the new dermal injectable collagen in improving bilateral nasolabial fold wrinkles, and reducing pain during injection.Patients and Methods: This prospective, double-blind, multicenter, parallel-group, randomized trial enrolled participants with moderate-to-severe bilateral nasolabial fold wrinkles from February 2019 to March 2021. Participants were randomly assigned to the test group (new dermal injectable collagen with lidocaine featuring a novel cross-linking technology) or control group (traditionally cross-linked dermal injectable collagen with lidocaine). Participants were monitored for adverse events (AEs), and for pain using the Thermometer Pain Scale (TPS) and a visual analog scale (VAS). Efficacy was measured using the Wrinkle Severity Rating Scale (WSRS) and the Global Aesthetic Improvement Scale (GAIS).Results: On the poor or better sides, the 2 groups exhibited a significant decrease in WSRS scores at 4, 12, 24, and 36 weeks after treatment, compared to baseline WSRS scores (all, p < 0.05). Compared to the control group, the test group had a greater decrease in WSRS score (poor or better sides) at 12, 24, 36, and 52 weeks after treatment (all, p < 0.05). A similar observation was also found in the WSRS response rate and GAIS score of the 2 groups. VAS and TPS scores were not significantly different between the 2 groups (p > 0.05), indicating that pain reduction was similar in the 2 groups. All AEs were anticipated AEs associated with facial aesthetic injections, and most recovered within 0 to 30 days without sequelae. There were no differences in AEs between the 2 groups (all, p > 0.05).Conclusion: The new dermal injectable collagen with lidocaine exhibited better efficacy for correcting nasolabial fold wrinkles compared to the control group. Both relieved pain and produced only transient and tolerable AEs.Keywords: adverse event, bilateral nasolabial folds, dermal filler, pain, porcine collagen, wrinkles

Understanding what controls global leaf type variation in trees is crucial for comprehending their role in terrestrial ecosystems, including carbon, water and nutrient dynamics. Yet our understanding of the factors influencing forest leaf types remains incomplete, leaving us uncertain about the global proportions of needle-leaved, broadleaved, evergreen and deciduous trees. To address these gaps, we conducted a global, ground-sourced assessment of forest leaf-type variation by integrating forest inventory data with comprehensive leaf form (broadleaf vs needle-leaf) and habit (evergreen vs deciduous) records. We found that global variation in leaf habit is primarily driven by isothermality and soil characteristics, while leaf form is predominantly driven by temperature. Given these relationships, we estimate that 38% of global tree individuals are needle-leaved evergreen, 29% are broadleaved evergreen, 27% are broadleaved deciduous and 5% are needle-leaved deciduous. The aboveground biomass distribution among these tree types is approximately 21% (126.4 Gt), 54% (335.7 Gt), 22% (136.2 Gt) and 3% (18.7 Gt), respectively. We further project that, depending on future emissions pathways, 17-34% of forested areas will experience climate conditions by the end of the century that currently support a different forest type, highlighting the intensification of climatic stress on existing forests. By quantifying the distribution of tree leaf types and their corresponding biomass, and identifying regions where climate change will exert greatest pressure on current leaf types, our results can help improve predictions of future terrestrial ecosystem functioning and carbon cycling.

Abstract: This paper uses data from limited HL-2A Ohmic-plasma to answer the question of how turbulent transport broadens the heat flux width. A key issue in this study is the determination of the origin of SOL turbulence. We develop the concept of the energy production ratio R_a, which compares the flux of turbulence energy across the LCFS to the net, integrated energy production in the SOL. The flux of turbulence energy (i.e., spreading) is measured directly, using Langmuir probes. Experimental data is used to evaluate R_a. Results show that usually R_a>1, indicating that SOL turbulence is energized primarily by edge turbulence spreading. The exceptions – cases where R_a

Horng-Chyuan Lin,1– 3 Meng-heng Hsieh,1,2 Yu-Lun Lo,1,2 Hung-Yu Huang,1,2 Shih-Wei Huang,1,2 Chien-Da Huang,1,2 Po-Jui Chang,1,2 Chun-Yu Lo,1,2 Ting-Yu Lin,1,2 Yueh-Fu Fang,1,2 Shu-Min Lin,1,2 Chun-Yu Lin,1,2,&ast; Ying-Huang Tsai1,2,4,&ast; 1Department of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; 2College of Medicine, Chang Gung University, Taoyuan, Taiwan; 3Department of Respiratory Therapy, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; 4Department of Pulmonary and Critical Care Medicine, Xiamen Chang Gung Hospital, Xiamen, 361028, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chun-Yu Lin, Department of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, 5 Fu-Hsing Street, Kweishan, Taoyuan, 33305, Taiwan, Tel +886-3-3281200 ext. 8467, Fax +886-3-3282474, Email pitiful1984@gmail.com Ying-Huang Tsai, Department of Pulmonary and Critical Care Medicine, Linkou Chang Gung Memorial Hospital, Chang Gung Medical Foundation and Department of Respiratory Therapy, College of Medicine, Chang Gung University, 5 Fu-Hsing Street, Kweishan, Taoyuan, 33305, Taiwan, Tel +886-3-3281200 ext. 8470, Fax +886-3-3282474, Email chestmed@cgmh.org.twBackground: Non-cystic fibrosis bronchiectasis is associated with airway pathogen colonization. We planned to investigate the inflammatory markers in patients with different airway pathogens and their correlation with disease severity.Methods: We enrolled patients aged between 20 and 75 from October 2021 to August 2022. All patients had sputum evaluation for bacterial and fungal cultures before enrollment, and were classified into four groups according to the culture results.Results: Forty-four patients with non-CF bronchiectasis and six controls were enrolled and categorized as follows: Group 1, no pathogens identified in sputum cultures (n = 14); Group 2, positive fungal culture results (n = 18); Group 3, positive P. aeruginosa culture results (n = 7); and Group 4, positive culture results for both fungi and P. aeruginosa (n = 5). Group 4 had significantly higher serum defensin α 1, IL-6 and tissue inhibitors of MMP (TIMP)-1 levels than group 1 patients. The serum levels of IL-6 and TIMP-1 were positively correlated with the FACED score and negatively correlated with distance-saturation product.Conclusion: Significantly higher levels of serum IL-6 and TIMP-1 were found in the patients who had concomitant fungal and P. aeruginosa colonization, and were closely related to clinical severity and may have important roles in disease monitoring.Keywords: TIMP-1, non-cystic fibrosis bronchiectasis, clinical severity

Yong Hwa Lee,1,&ast; Dasom An,1,&ast; Youngsuk Baek,1 Kyungsook Yoo,2 Sumi Hyun,1 Sun-Kyeong Park,3 Eui-Kyung Lee1 1School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do, South Korea; 2School of Pharmacy, Kangwon National University, Chuncheon, Gangwon-do, South Korea; 3College of Pharmacy, The Catholic University of Korea, Bucheon, Gyeonggi-do, South Korea&ast;These authors contributed equally to this workCorrespondence: Sun-Kyeong Park, College of Pharmacy, The Catholic University of Korea, 43 Jibong-ro, Bucheon-si, Gyeonggi-do, 14662, South Korea, Tel +82221644094, Email sk.park@catholic.ac.kr Eui-Kyung Lee, School of Pharmacy, Sungkyunkwan University, 2066, Seobu-ro, Jangan-gu, Suwon-si, Gyeonggi-do, 16419, South Korea, Tel +82312907786, Email ekyung@skku.eduPurpose: Drug shortages directly affect the final stage in the pharmaceutical supply chain, prescription fulfillment in community pharmacies (CPs). This study investigated the current state of drug shortages, their resolution, and influencing factors within CPs.Methods: A cross-sectional online survey was conducted among pharmacists working at pharmacies in Seoul between 7 and 31 October 2022. The survey gathered data on pharmacies and pharmacists’ characteristics, drug distribution, information, communication, and administrative practices. Logistic regression was used to identify the factors influencing these rates. Regression results are presented as odds ratios (OR) and 95% confidence intervals (CIs).Results: Of the 1200 pharmacists approached, 713 participated, yielding a response rate of 59.4%. After excluding incomplete responses, data from 671 respondents were analyzed. Pharmacies with higher prescription drug sales demonstrated a lower OR for drug shortages (OR=0.66, 95% CI=0.60– 0.72) compared to those with lower sales volumes. Resolution rates were significantly higher when pharmacies were located near clinics (OR=3.30, 95% CI=2.3– 4.74) and general hospitals (OR=3.45, 95% CI=2.35– 5.07) compared to those without nearby medical facilities. Additionally, good communication with prescribers increased the resolution rates (OR=1.46, 95% CI=1.26– 1.69).Conclusion: This study examines the influence of pharmacy purchasing power on drug shortages, identifying proximity to healthcare facilities and communication with prescribers as factors affecting the resolution rates. These findings provide valuable insights for pharmacists, policymakers, and future researchers to optimize drug supply chain management and mitigate shortages in community settings.Keywords: drug shortage, drug shortage resolution, community pharmacy, pharmaceutical supply chain

Jia Yi Tan,1 Yong Hao Yeo,2 Kok Hoe Chan,3 Hamid S Shaaban,4 Gunwant Guron4 1Department of Internal Medicine, New York Medical College at Saint Michael’s Medical Center, Newark, NJ, USA; 2Department of Internal Medicine/Pediatrics, Corewell Health, Royal Oak, MI, USA; 3Division of Hematology/Oncology, Department of Internal Medicine, McGovern Medical School at the University of Texas Health Science Center at Houston (UTHealth Houston), Houston, TX, USA; 4Division of Hematology/Oncology, Department of Internal Medicine, New York Medical College at Saint Michael’s Medical Center, Newark, NJ, USA Correspondence: Kok Hoe Chan, Division of Hematology/Oncology, the University of Texas Health Science Center at Houston, 7000 Fannin St, Houston, TX, 77030, Email kok.hoe.chan@uth.tmc.eduPurpose: Our study aims to describe the mortality trends and disparities among individuals with thalassemia in the United States (US).Patients and Methods: We used CDC WONDER database to calculate the age-adjusted mortality rates (AAMRs) per 1,000,000 individuals and used the Joinpoint Regression Program to measure the average annual percent change (AAPC). Subgroup evaluations were performed by sex, age, race, census region, and urbanization level.Results: From 1999 to 2020, there were 2797 deaths relatd to thalassemia in the US. The AAMR of thalassemia-related death showed a decreasing trend from 0.50 (95% CI, 0.41– 0.58) in 1999 to 0.48 (95% CI, 0.41– 0.55) in 2020 with the AAPC of − 1.42 (95% CI, − 2.42, − 0.42). Asians have the highest AAMR (1.34 [95% CI, 1.20– 1.47]), followed by non-Hispanic Blacks (0.65 [95% CI, 0.59– 0.71]), non-Hispanic Whites (0.32 [95% CI, 0.30– 0.33]), and Hispanics (0.11 [95% CI, 0.08– 0.14]). Cardiovascular disease remains the leading cause of death among individuals with thalassemia. The urban population has a higher AAMR than the rural population (0.43 [95% CI, 0.41– 0.45] vs 0.29 [95% CI, 0.26– 0.32]).Conclusion: Our study calls for targeted interventions to address the racial and geographic disparities existed among individuals of thalassemia in the US.Keywords: thalassemia, beta-thalassemia, alpha-thalassemia, epidemiology, mortality

Yen-Hao Chen,1– 4 Wan-Ting Huang,5 Wen-Chin Lee,6 Ching-Mei Chen,5 Fu-Jen Cheng,7 Chia-Te Kung,7 Chin-Chou Wang,8 Liang-Jen Wang,9 Yu-Che Ou,10 Shau-Hsuan Li1 1Division of Hematology-Oncology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, 833, Taiwan; 2School of Medicine, College of Medicine, Chang Gung University, Taoyuan, 333, Taiwan; 3School of Medicine, Chung Shan Medical University, Taichung, 402, Taiwan; 4Department of Nursing, School of Nursing, Fooyin University, Kaohsiung, 831, Taiwan; 5Department of Laboratory Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, 833, Taiwan; 6Division of Nephrology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, 833, Taiwan; 7Department of Emergency Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, 833, Taiwan; 8Department of Occupational Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, 833, Taiwan; 9Department of Child and Adolescent Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, 833, Taiwan; 10Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, 833, TaiwanCorrespondence: Shau-Hsuan Li, Division of Hematology-Oncology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung City, 833, Taiwan, Email lee.a0928@msa.hinet.netBackground: The aim of this study was to investigate the role of phthalate in patients with esophageal squamous cell carcinoma (ESCC).Methods: A total of 116 ESCC patients and 58 controls without any known histories of malignancies were enrolled. All eight urine phthalate metabolites were measured to assess phthalate levels. Clinical and urine phthalate metabolite profiles were compared between subgroups to identify differences, and the effects of phthalates on clinical ESCC outcomes were also examined.Results: The concentrations of some urine phthalate metabolites were higher in the ESCC group than in the control group, including mono-(3-carboxypropyl) phthalate (MCPP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), and mono-n-butyl phthalate (MnBP). Higher concentrations of urine phthalate metabolites were associated with clinical T3–T4 status. Patients with higher concentration of mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP), mono-2-ethylhexyl phthalate (MEHP), and MEOHP had lower 1-year and 2-year overall survival (OS) rates than those with lower concentrations of these metabolites in our univariate analysis. Multivariate analysis showed that urinary MEHP of ≥ 3 μg/L and clinical stage IVB were independent prognostic factors for worse OS.Conclusion: The results of our study showed that urine phthalate metabolites are elevated in ESCC patients and associated with advanced tumor stage, and that a high urinary concentration of MEHP is an independent prognostic factor of worse OS.Keywords: phthalate, esophageal cancer, squamous cell carcinoma, survival

Introduction: Post-operative urinary retention (POUR) is a common complication after total knee arthroplasty (TKA) and may result in severe complications such as urinary tract infection and deep joint sepsis, leading to prolonged hospital stay and increased medical costs. Hence a retrospective study was performed to identify the incidence and modifiable factors associated with POUR after elective TKA in Asian patients with the aim to prevent POUR and its undesirable consequences. Materials and methods: The medical records of 496 consecutive patients who underwent elective TKA between 1 August 2017 and 30 July 2018 were reviewed. There were 154 male (31.0%) and 342 female (69.0%) patients with an average age of 68 years old. The incidence of POUR was analysed with respect to various modifiable and non-modifiable risk factors, including patient demographics, medical comorbidities, duration of surgery, type of intra-operative anaesthesia and post-operative analgesia and early initiation of physiotherapy using univariate and multivariate analyses. Results: A total of 120 (24.2%) of the 496 patients who underwent elective TKA developed POUR. The odds of a patient with patient-controlled analgesia (PCA) and peripheral nerve block (PNB) developing POUR were 4.2 times and 4.7 times that of a patient without PCA and PNB, respectively. Age, male gender and type of anaesthesia were not found to be significant. Conclusion: In our study population, the incidence of POUR after elective TKA was 24% with major modifiable risk factors being associated with the use of PCA and PNB as post-operative anaesthesia. POUR can have deleterious effects thus alternative post-operative analgesia should be considered.

Jing Liang,1 Yu Wang,2 He Wang,3 Yu-Hsin Chen,3 Yu-Wei Wu,4 Wen-Jing Yan5 1College of Education, Hebei Normal University, Shijiazhuang, 050024, People’s Republic of China; 2Department of Education and Psychology, Tianjin University of Sport, Tianjin, 301617, People’s Republic of China; 3School of Mental Health, Wenzhou Medical University, Wenzhou, 325035, People’s Republic of China; 4Student Affairs Division, Wenzhou Business College, Wenzhou, 325035, People’s Republic of China; 5Zhejiang Provincial Clinical Research Centre for Mental Illness, Affiliated Kangning Hospital, Wenzhou Medical University, Wenzhou, People’s Republic of ChinaCorrespondence: Yu-Wei Wu, Student Affairs Division, Wenzhou Business College, Wenzhou, 325035, People’s Republic of China, Email wyw@wzbc.edu.cn Wen-Jing Yan, Zhejiang Provincial Clinical Research Centre for Mental Illness, Affiliated Kangning Hospital, Wenzhou Medical University, Wenzhou, People’s Republic of China, Email yanwj@wmu.edu.cnBackground: Shame-proneness, particularly in adolescence, is a critical psychological construct linked to aggressive behavior. This study addresses the gap in understanding the specific mechanisms of this relationship within the cultural context of Chinese adolescents.Aim: The study aims to explore the mediating roles of hostility and externalization of blame in the connection between shame-proneness and aggression among Chinese adolescents.Methods: A comprehensive sample of 1489 Chinese adolescents participated in the study. They completed the Test of Self-Conscious Affect for Adolescents to assess shame-proneness and an aggression questionnaire to measure aggressive behaviors. The study utilized network analysis and mediational analysis, to unravel the complex interactions between shame-proneness, externalization of blame, hostility, anger, and aggression.Results: The results identified two distinct pathways linking shame-proneness to aggression: one mediated by hostility and the other by externalization of blame. The pathway via hostility was particularly pronounced, marking it as a central node in the shame-aggression relationship. Interestingly, the study also revealed a direct, though less pronounced, inhibitory effect of shame-proneness on aggression, indicating a dualistic role of shame in adolescent behavior. These findings were consistent across different demographic subgroups, suggesting a generalizable pattern in the studied population.Conclusion: The dual nature of shame-proneness, as both an inhibitor and a facilitator of aggression, underscores the need for culturally sensitive approaches in psychological interventions and future research. The central role of hostility in this relationship points to potential targets for therapeutic interventions aimed at mitigating aggression in adolescents.Keywords: shame-proneness, aggression, network analysis, hostility, externalization of blame

Xiufeng Chen, Yong hong Jiang, Xiaoqin Fei, Mingjing Wang, Anqi Liu, Xuejun Li, Zhiyan Jiang Department of Pediatrics, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of ChinaCorrespondence: Zhiyan Jiang, Email jiangzhiyan@shutcm.edu.cnBackground: Asthma severely interferes with people’s lives through coughing, wheezing and inflammation of the lungs. Herbacetin is a class of natural compounds that inhibit the development of inflammation. However, whether Herbacetin inhibits asthma has not been definitively studied.Methods: Lipopolysaccharides (LPS)-induced lung epithelial (BASE-2B) cells injury model was established, and then the relief of damaged BASE-2B cells with different concentrations of Herbacetin was examined. The cell counting kit (CCK8) was used to detect the effect of Herbacetin on the proliferation ability in ovalbumin (OVA)-induced asthma mice model, and Western Blot and flow cytometry were used to detect the effect of Herbacetin on the apoptosis in OVA-induced asthma mice model. Additionally, pulmonary pathology was detected by HE and Masson staining, and serum inflammatory factors were detected by alveolar lavage fluid.Results: Herbacetin reduces BESA-2B cells induced by LPS level of inflammation, and reactive oxygen species (ROS) generation, inhibits cell apoptosis, promotes cell proliferation, OVA-induced mice lung histopathology test HE staining, serum inflammatory factors show the same results. Western Blot shows that Herbacetin regulates the expression of Caspase-3, Bax, and Bcl-2. SGK1 overexpression increased the rate of apoptosis, and Herbacetin reversed this phenomenon. By silencing the expression of SGK1, it was found that Herbacetin was an inhibitor of SGK1, which could inhibit the NF-κB/p-P65 pathway in asthmatic airway inflammation.Conclusion: Herbacetin reduces pro-inflammatory cytokine levels by inhibiting the SGK1/NF-κB pathway. Our data suggest that Herbacetin has a significant anti-inflammatory effect on asthma and can be used as a potential therapeutic agent.Keywords: asthma, herbacetin, SGK1, NF-κB, anti-inflammatory

Yu-Kai Li,1,&ast; Song Wu,2,&ast; Yu-Shan Wu,3,&ast; Wei-Hu Zhang,4,&ast; Yan Wang,5,&ast; Yue-Hua Li,1,&ast; Qiang Kang,1,&ast; Song-Quan Huang,1,&ast; Kai Zheng,1 Gai-Ming Jiang,1 Qing-Bo Wang,1 Yu-Bo Liang,1 Jin Li,1 Yawhan Lakang,1 Chen Yang,1 Jing Li,1 Jia-Ping Wang,4 Xiang Kui,5 Yang Ke1,6,7 1Department of Hepato-Biliary-Pancreatic, the Second Affiliated Hospital, Kunming Medical University, Kunming, YN, 650101, People’s Republic of China; 2Preventive Medicine Division, School of Life Science, Anhui University of Chinese Medicine, Hefei, AH, 230012, People’s Republic of China; 3The Second Clinical Medical College, Kunming Medical University, Kunming, YN, 650101, People’s Republic of China; 4Department of Radiology, the Second Affiliated Hospital, Kunming Medical University, Kunming, YN, 650101, People’s Republic of China; 5Department of Pathology, the Second Affiliated Hospital, Kunming Medical University, Kunming, YN, 650101, People’s Republic of China; 6Department of Surgical Education and Research, the Second Affiliated Hospital, Kunming Medical University, Kunming, YN, 650101, People’s Republic of China; 7Yunnan Yunke Bio-Technology Institution, Kunming, YN, 650201, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiang Kui, Department of Pathology, the Second Affiliated Hospital, Kunming Medical University, No. 374 Kunrui Road, Wuhua District, Kunming, YN, 650101, People’s Republic of China, Tel +8613708729335, Email kuixiang@foxmail.com Yang Ke, Department of Hepato-Biliary-Pancreatic, the Second Affiliated Hospital, Kunming Medical University, No. 374 Kunrui Road, Wuhua District, Kunming, YN, 650101, People’s Republic of China, Tel +8615808875159, Email keyang1218@126.comBackground: The dominant artery blood supply is a characteristic of hepatocellular carcinoma (HCC). However, it is not known whether the blood supply can predict the post-hepatectomy prognosis of patients with HCC. This retrospective study investigated the prognostic value of the portal venous and arterial blood supply estimated on triphasic liver CT (as a portal venous coefficient, PVC, and hepatic arterial coefficient, HAC, respectively) in patients with HCC following hepatectomy.Methods: HCC patients who were tested by triphasic liver CT 2 weeks before hepatectomy and received R0 hepatectomy at the Second Affiliated Hospital, Kunming Medical University between January 1, 2016 and December 31, 2020, were retrospectively screened. Their PVC and HAC, and other variables were analyzed for the prediction of overall survival (OS) and recurrence-free survival (RFS) using the least absolute shrinkage and selection operator and Cox proportional hazard regression models.Results: Four hundred and nineteen patients (53.2 ± 10.6 years of age and 370 men) were evaluated. A shorter OS was independently associated with higher blood albumin and total bilirubin grade [hazard ratio (HR) 2.020, 95% confidence interval (CI) 1.534– 2.660], higher Barcelona Clinic Liver Cancer (BCLC) stage (HR 1.514, 95% CI 1.290– 1.777), PVC ≤ 0.386 (HR 1.628, 95% CI 1.149– 2.305), and HAC > 0.029 (HR 1.969, 95% CI 1.380– 2.809). A shorter RFS was independently associated with male (HR 1.652, 95% CI 1.005– 2.716), higher serum α-fetoprotein ≥ 400 ng/mL (HR 1.672, 95% CI 1.236– 2.263), higher BCLC stage (HR 1.516, 95% CI 1.300– 1.768), tumor PVC ≤ 0.386 (HR 1.641, 95% CI 1.198– 2.249), and tumor HAC > 0.029 (HR 1.455, 95% CI 1.060– 1.997).Conclusion: Tumor PVC or HAC before hepatectomy is valuable for independently predicting postoperative survival of HCC patients. Keywords: blood supply, computed tomography, hepatectomy, hepatocellular carcinoma, recurrence, survival

Shih-Ching Chin,1,&ast; Yun-Hsuan Chang,2– 6,&ast; Chih-Chun Huang,6,7 Ting-Hsi Chou,1 Chieh-Liang Huang,8 Hsiu-Man Lin,9 Marc N Potenza10 1Department of Psychology, Asia University, Taichung, Taiwan; 2Institute of Gerontology, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 3Institute of Behavioral Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 4Department of Psychology, National Cheng Kung University, Tainan, Taiwan; 5Institute of Genomics and Bioinformatics, College of Life Sciences, National Chung Hsing University, Taichung, Taiwan; 6Department of Psychiatry, National Cheng Kung University Hospital, Douliou Branch, Yunlin, Taiwan; 7Department of Psychiatry, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 8Department of Psychiatry, Tsaotun Psychiatric Center, Ministry of Health and Welfare, Nantou, Taiwan; 9Department of Child and Adolescent Development and Mental Health, China Medical University Children’s Hospital, Taichung, Taiwan; 10Psychiatry, Child Study and Neuroscience, Center of Excellence in Gambling Research, Yale School of Medicine, New Haven, CT, USA&ast;These authors contributed equally to this workCorrespondence: Yun-Hsuan Chang, Licensed Clinical Psychologist, Institute of Gerontology, College of Medicine; Department of Psychology, National Cheng Kung University, No. 1., University Road, Tainan, Taiwan, Email z11108051@ncku.edu.tw; yh.chang.snoopy@gmail.comIntroduction: The surge in mobile gaming, fueled by smartphone and internet accessibility, lacks a comprehensive understanding of physiological changes during gameplay.Methods: This study, involving 93 participants (average age 21.75 years), categorized them into Problematic Mobile Gaming (PMG) and non-problematic Mobile Gaming (nPMG) groups based on Problematic Mobile Gaming Questionnaire (PMGQ) scores. The PMGQ is a 12-item scale developed in Taiwan to assess symptoms of problematic mobile gaming. The research delved into heart rate variability (HRV) alterations during real-time mobile gaming and self-gaming video viewing.Results: Results showed that the PMG group significantly presents a lower root mean square of successive differences (RMSSD), and High Frequency (lnHF) than does the nPMG group (F=4.73, p=0.03; F=10.65, p=0.002, respectively) at the baseline. In addition, the PMG group significantly displayed elevated HF and low-frequency to high-frequency (LF/HF) in the mobile-gaming (F=7.59, p=0.007; F=9.31, p=0.003) condition as well as in the watching self-gaming videos (F=9.75, p=0.002; F=9.02, p=0.003) than did the nPMG.Conclusion: The study suggests targeted interventions to mitigate autonomic arousal, offering a potential avenue to address adverse effects associated with problematic mobile gaming behavior. The PMG group displayed increased craving scores after real-time mobile gaming and watching self-gaming video excerpts, unlike the nPMG group. Elevated LF/HF ratios in frequent gaming cases heightened autonomic arousal, presenting challenges in relaxation after mobile gaming. These findings contribute to a nuanced understanding of the complex interplay between mobile gaming activities, physiological responses, and potential intervention strategies.Keywords: addictive behaviors, video games, internet addiction, autonomic nervous system, craving, heart rate variability, self-regulation

Yang Zhao,1,&ast; Yi-Han Wang,2,&ast; Wei-Chao Tu,1 Da-Wei Wang,1 Mu-Jun Lu,3,4 Yuan Shao1 1Department of Urology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, Shanghai, 201800, People’s Republic of China; 2Department of Urology, Sixth People’s Hospital South Campus Affiliated to Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 3Department of Urology and Andrology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 4Shanghai Institute of Andrology, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mu-Jun Lu; Yuan Shao, Email lumujun@163.com; shaoyuan10772@163.comBackground: Chronic kidney disease (CKD) is a significant worldwide health concern that leads to high mortality rates. The bioactive substance costunolide (CTD) has demonstrated several pharmacological effects and holds promise as a CKD treatment. This study aims to investigate the impact of CTD on CKD and delve into its mechanisms of action.Methods: Unilateral ureteral obstruction (UUO) methods and renal fibrosis mice models were created. Various concentrations of CTD were injected into UUO mice models to investigate the therapeutic effects of CTD on renal fibrosis of mice. Then, renal morphology, pathological changes, and the expression of genes related to fibrosis, inflammation and ferroptosis were analysed. RNA sequencing was utilized to identify the main biological processes and pathways involved in renal injury. Finally, both overexpression and inhibition of IKKβ were studied to examine their respective effects on fibrosis and inflammation in both in vitro and in vivo models.Results: CTD treatment was found to significantly alleviate fibrosis, inflammation and ferroptosis in UUO-induced renal fibrosis mice models. The results of RNA sequencing suggested that the IKKβ acted as key regulatory factor in renal injury and the expression of IKKβ was increased in vitro and in vivo renal fibrosis model. Functionally, down-regulated IKKβ expression inhibits ferroptosis, inflammatory cytokine production and collagen deposition. Conversely, IKKβ overexpression exacerbates progressive renal fibrosis. Mechanistically, CTD alleviated renal fibrosis and inflammation by inhibiting the expression of IKKβ and attenuating IKKβ/NF-κB pathway.Conclusion: This study demonstrates that CTD could mitigate renal fibrosis, ferroptosis and inflammation in CKD by modulating the IKKβ/NF-κB pathway, which indicates targeting IKKβ has an enormous potential for treating CKD. Keywords: chronic kidney disease, costunolide, renal fibrosis, IKKβ/NF-κB pathway

Jiaying Lao,1,2,&ast; Hang Tan,3,&ast; Yuyu Wu,2,&ast; Ting Ding,4 Xinqian Liu,1 Lanrong Sun,2 Xiyi Chen,2 Chongrong Zhu,2 Yiming Kang,5 Yu-Hsin Chen,2,6 Chonghui Tang,1 Fan Wang,7 Yanlong Liu2,6 1Department of Neurosurgery, Affiliated Cixi Hospital, Wenzhou Medical University, Ningbo, People’s Republic of China; 2School of Mental Health, Wenzhou Medical University, Wenzhou, People’s Republic of China; 3Department of neurosurgery, Hangzhou Mingzhou Brain Rehabilitation Hospital, Hangzhou, People’s Republic of China; 4Department of Infectious Diseases, The Affiliated Xiangshan Hospital of Wenzhou Medical University, Ningbo, People’s Republic of China; 5Psychosomatic Medicine Research Division, Inner Mongolia Medical University, Huhhot, People’s Republic of China; 6Zhejiang Provincial Clinical Research Center for Mental Disorders, The Affiliated Wenzhou Kangning Hospital, Wenzhou Medical University, Wenzhou, People’s Republic of China; 7Beijing Hui−Long−Guan Hospital, Peking University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yanlong Liu, School of Mental Health, Medical University, Wenzhou, 325035, People’s Republic of China, Email benjaminlyl@wmu.edu.cn Chonghui Tang, Department of Neurosurgery, Affiliated Cixi Hospital, Wenzhou Medical University, Ningbo, 315300, People’s Republic of China, Email tangegg@163.comObjective: Cigarette smoking and low peripheral nitric oxide synthase (NOS) levels are strongly associated with sleep disorders. However, whether cerebrospinal fluid (CSF) NOS relates to sleep disorders and whether CSF NOS mediates the relationship between cigarette smoking and sleep disorders is unclear.Methods: We measured CSF levels of total NOS (tNOS) and its isoforms (inducible NOS [iNOS] and constitutive NOS [cNOS]) in 191 Chinese male subjects. We applied the Pittsburgh Sleep Quality Index (PSQI).Results: The PSQI scores of active smokers were significantly higher than those of non-smokers, while CSF tNOS, iNOS, and cNOS were significantly lower (all p < 0.001). CSF tNOS, iNOS, and cNOS were negatively associated with PSQI scores in the general population (all p < 0.001). Mediation analysis suggested that CSF tNOS, iNOS, and cNOS mediate the relationship between smoking and PSQI scores, and the indirect effect accounted for 78.93%, 66.29%, and 81.65% of the total effect, respectively.Conclusion: Cigarette smoking is associated with sleep disorders. Active smokers had significantly lower CSF levels of tNOS, iNOS, and cNOS. Furthermore, tNOS, iNOS, and cNOS mediate the relationship between cigarette smoking and sleep quality. This study provides insights into how cigarette smoke affects sleep disorders.Keywords: cerebrospinal fluid nitric oxide synthase, cigarette smoking, Pittsburgh Sleep Quality Index, sleep disorders, mediation

Zhao Zhang, Xiu-Fen Jia, Xiao-Yu Chen, Yong-Hua Chen, Ke-Hua Pan Department of Radiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, People’s Republic of ChinaCorrespondence: Ke-Hua Pan, Department of Radiology, The First Affiliated Hospital of Wenzhou Medical University, No. 1 of Xuefu North Road, Wenzhou, Ouhai District, 325000, People’s Republic of China, Tel +86-577-8806 9618, Fax +86-577-8806 9655, Email pankehuapan@126.comObjective: The aim of this study is to develop and verify a magnetic resonance imaging (MRI)-based radiomics model for predicting the microvascular invasion grade (MVI) before surgery in individuals diagnosed with nodular hepatocellular carcinoma (HCC).Methods: A total of 198 patients were included in the study and were randomly stratified into two groups: a training group consisting of 139 patients and a test group comprising 59 patients. The tumor lesion was manually segmented on the largest cross-sectional slice using ITK SNAP, with agreement reached between two radiologists. The selection of radiomics features was carried out using the LASSO (Least Absolute Shrinkage and Selection Operator) algorithm. Radiomics models were then developed through maximum correlation, minimum redundancy, and logistic regression analyses. The performance of the models in predicting MVI grade was assessed using the area under the receiver operating characteristic curve (AUC) and metrics derived from the confusion matrix.Results: There were no notable statistical differences in sex, age, BMI (body mass index), tumor size, and location between the training and test groups. The AP and PP radiomic model constructed for predicting MVI grade demonstrated an AUC of 0.83 (0.75– 0.88) and 0.73 (0.64– 0.80) in the training group and an AUC of 0.74 (0.61– 0.85) and 0.62 (0.48– 0.74) in test group, respectively. The combined model consists of imaging data and clinical data (age and AFP), achieved an AUC of 0.85 (0.78– 0.91) and 0.77 (0.64– 0.87) in the training and test groups, respectively.Conclusion: A radiomics model utilizing-contrast-enhanced MRI demonstrates strong predictive capability for differentiating MVI grades in individuals with nodular HCC. This model could potentially function as a dependable and resilient tool to support hepatologists and radiologists in their preoperative decision-making processes.Keywords: hepatocellular carcinoma, magnetic resonance imaging, microvascular invasion, radiomics

Yue Lu,1– 3,&ast; Simin Pan,4,&ast; Wenzhen Li,5 Yao Qi,6,7 Li Li,1– 3 Yu-Hong Yan,1– 3 Jianan Wei,1– 3 Dan-Ni Yao,1– 3 Jingjing Wu,1– 3 Hao Deng,1– 3 Shuyan Ye,1– 3 Haiming Chen,1– 3 Qubo Chen,1– 3 Hengjun Gao,6,7 Ling Han,1– 3 Chuanjian Lu1– 3 1State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou, People’s Republic of China; 2Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangzhou, People’s Republic of China; 3Guangdong-Hong Kong-Macau Joint Laboratory on Chinese Medicine and Immune Disease Research, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 4The Second Clinical College, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 5The Clinical College of Acupuncture Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 6Shanghai Molecular Medicine Engineering Technology Research Center, Shanghai, People’s Republic of China; 7Shanghai National Engineering Research Center of Biochip, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ling Han; Chuanjian Lu, Email linghan99@gzucm.edu.cn; lcj@gzucm.edu.cnBackground: Psoriasis is a widespread chronic, immune-mediated skin disease with frequent recurrences, and is extremely harmful to the physical and mental health of patients, causing enormous suffering and exerting considerable economic burdens on the health care system as a whole. In more than a decade of clinical use, the optimized formula of Yinxieling (PSORI-CM01) has consistently demonstrated its effectiveness for treating psoriasis. However, its underlying mechanism remains largely unexplored.Methods: The network pharmacology analysis was conducted to predict the mechanism and protective effect of PSORI-CM01 in treating psoriasis. Subsequently, we collected blood samples from 21 patients with psoriasis as part of a randomized, double-blind, and double-dummy clinical trial for microRNA expression profiling. Finally, it was experimentally confirmed that PSORI-CM01 improved psoriasis by regulating miR-20a-3p and miR-3184-3p expression.Results: As a result of the network pharmacology analysis, PSORI-CM01 improved psoriasis through the regulation of autophagy, cellular apoptosis, cellular proliferation, and anti-inflammatory processes. In the target-miRNA regulatory network, these key targets were mainly associated with the regulation of hsa-miR-20a-3p, hsa-miR-155-5p, has-miR-3184-3p, hsa-miR-328-3p and hsa-miR-124-3p. Based on the microRNA expression profiling results, the PSORI-CM01 treatment group exhibited five up-regulated genes and 16 down-regulated genes compared with the healthy control group. In particular, miR-20a-3p and miR-3184-3p were the primary differentially expressed microRNAs, and they were significantly enriched in the signaling pathways involving autophagy, apoptosis, proliferation, and anti-inflammation. Further experiments confirmed that PSORI-CM01 effectively regulates miR-20a-3p and miR-3184-3p, resulting in increased autophagy.Conclusion: We demonstrated by combining network pharmacology and clinical studies of miRNA expression profiles in PBMCs that PSORI-CM01 effectively modulated miR-20a-3p and miR-3184-3p, leading to an increase in autophagy and a decrease in keratinocyte proliferation.Keywords: PSORI-CM01, Psoriasis vulgaris, MicroRNA expression profile, network pharmacology, autophagy

Lin Tang,1,&ast; Jian Liu,2,&ast; Hui Yang,2,&ast; Hong-Qing Zhao,3 Chao Hu,4 Si-Jing Ma,5 Yu-Hui Qing,6 Lei Yang,1 Rong-Rong Zhou,5 Shui-Han Zhang6 1Hospital-Made Preparations Center, The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan Province, People’s Republic of China; 2Medical Innovation Experiment Center, The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan Province, People’s Republic of China; 3Science & Technology Innovation Center, Hunan University of Chinese Medicine, Changsha, Hunan Province, People’s Republic of China; 4Department of Pharmacy, The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan Province, People’s Republic of China; 5The Affiliated Hospital, Hunan Academy of Traditional Chinese Medicine, Changsha, Hunan Province, People’s Republic of China; 6Institute of Chinese Medicine Resources, Hunan Academy of Chinese Medicine, Changsha, Hunan Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Rong-Rong Zhou; Shui-Han Zhang, Tel +86-0731-85920129, Email rrzhou0823@163.com; zhangshuihan0220@126.comPurpose: The Baihe Dihuang decoction (BDD) is a representative traditional Chinese medicinal formula that has been used to treat anxiety disorders for thousands of years. This study aimed to reveal mechanisms of anxiolytic effects of BDD with multidimensional omics.Methods: First, 28-day chronic restraint stress (CRS) was used to create a rat model of anxiety, and the open field test and elevated plus maze were used to assess anxiety-like behavior. Enzyme-linked immunosorbent assay (ELISA), hematoxylin–eosin staining, and immunofluorescence staining were used to evaluate inflammatory response. Besides, 16S rRNA gene sequencing assessed fecal microbiota composition and differential microbiota. Non-targeted metabolomics analysis of feces was performed to determine fecal biomarkers, and targeted metabolomics was used to observe the levels of hippocampus neurotransmitters. Finally, Pearson correlation analysis was used to examine relationships among gut microbiota, fecal metabolites, and neurotransmitters.Results: BDD significantly improved anxiety-like behaviors in CRS-induced rats and effectively ameliorated hippocampal neuronal damage and abnormal activation of hippocampal microglia. It also had a profound effect on the diversity of microbiota, as evidenced by significant changes in the abundance of 10 potential microbial biomarkers at the genus level. Additionally, BDD led to significant alterations in 18 fecal metabolites and 12 hippocampal neurotransmitters, with the majority of the metabolites implicated in amino acid metabolism pathways such as D-glutamine and D-glutamate, alanine, arginine and proline, and tryptophan metabolism. Furthermore, Pearson analysis showed a strong link among gut microbiota, metabolites, and neurotransmitters during anxiety and BDD treatment.Conclusion: BDD can effectively improve anxiety-like behaviors by regulating the gut–brain axis, including gut microbiota and metabolite modification, suppression of hippocampal neuronal inflammation, and regulation of neurotransmitters. Keywords: Baihe Dihuang decoction, 16S rRNA, metabolomics, anxiety, neurotransmitter

Abdulaziz Ibrahim Alzarea,1 Yusra Habib Khan,1 Sami I Alzarea,2 Abdullah Salah Alanazi,1 Omar Awad Alsaidan,3 Maily J Alrowily,4 Monefah Al-Shammari,5 Ziyad Saeed Almalki,6 Majed A Algarni,7 Tauqeer Hussain Mallhi1 1Department of Clinical Pharmacy, College of Pharmacy, Jouf University, Sakaka, Al-Jouf, Saudi Arabia; 2Department of Pharmacology, College of Pharmacy, Jouf University, Sakaka, Al-Jouf, Saudi Arabia; 3Department of Pharmaceutics, College of Pharmacy, Jouf University, Sakaka, Al-Jouf, Saudi Arabia; 4Department of Radiology, Aljouf Health Cluster, Domat Al-Jandal, Al-Jouf, Saudi Arabia; 5Domat Al-Jandal General Hospital, Aljouf Health Cluster, Domat Al Jandal, Al-Jouf, Saudi Arabia; 6Department of Clinical Pharmacy, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj, Saudi Arabia; 7Department of Clinical pharmacy, College of pharmacy, Taif university, Taif, Saudi ArabiaCorrespondence: Abdulaziz Ibrahim Alzarea; Tauqeer Hussain Mallhi, Email aizarea@ju.edu.sa; thhussain@ju.edu.saObjective: Chronic diseases hold the potential to worsen the overall health of patients by limiting their functional status, productivity, and capacity to live well, affecting their overall health-related quality of life (HRQoL). The purpose of the study was to assess the HRQoL of individuals with chronic diseases residing in the Al-Jouf region of Saudi Arabia. Furthermore, the current study also sought to ascertain the impact of multimorbidity and the duration of illness on HRQoL.Material and Methods: A cross-sectional study was conducted among the residents of Al-Jouf region for a period of 6 months. A self-administered EuroQoL (EQ-5D-5L) study tool was used. Appropriate statistical analysis was conducted to ascertain the relationship between various variables and HRQoL.Results: A total of 500 out of 562 participants completed the study, with a response rate of 88.97%. Participants had a mean age of 46.15 ± 16.79 years, and the majority were female (n = 299; 59.80%). A mean HRQoL score of 0.82 ± 0.20 was reported, poorest in patients with kidney failure (0.65 ± 0.26) and highest in hepatitis. However, nearly half of the participants had diabetes mellitus type II (n = 205, 39.20%). Patients aged < 30 years (OR: 0.109; p = 0.002), male participants (OR: 0.053; p < 0.001), no disability (OR: 0.143; p = 0.002), and < 2 comorbid diseases (0.84 ± 0.18; p < 0.001) reported better QoL. Additionally, comorbid conditions such as DM, prolong the duration of the overall illness (14.19 ± 7.67 years). Overall, imperfect health (n = 390, 78%) was reported by the study participants.Conclusion: The present study provided preliminary data about the current HRQoL status of individuals with imperfect health and lower HRQoL. In the future, large-scale longitudinal studies are required to investigate the most prevalent chronic diseases, their associations, and change in HRQoL, as there is a dearth of information in the Saudi population.Keywords: HRQoL, EQ-5D-5L, chronic diseases, diabetes mellitus, hypertension, Saudi Arabia, disease outcomes, quality of life

Determining the drivers of non-native plant invasions is critical for managing native ecosystems and limiting the spread of invasive species1,2. Tree invasions in particular have been relatively overlooked, even though they have the potential to transform ecosystems and economies3,4. Here, leveraging global tree databases5-7, we explore how the phylogenetic and functional diversity of native tree communities, human pressure and the environment influence the establishment of non-native tree species and the subsequent invasion severity. We find that anthropogenic factors are key to predicting whether a location is invaded, but that invasion severity is underpinned by native diversity, with higher diversity predicting lower invasion severity. Temperature and precipitation emerge as strong predictors of invasion strategy, with non-native species invading successfully when they are similar to the native community in cold or dry extremes. Yet, despite the influence of these ecological forces in determining invasion strategy, we find evidence that these patterns can be obscured by human activity, with lower ecological signal in areas with higher proximity to shipping ports. Our global perspective of non-native tree invasion highlights that human drivers influence non-native tree presence, and that native phylogenetic and functional diversity have a critical role in the establishment and spread of subsequent invasions.