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Mehmet Sertac Cekuc,1 Yasemin Sude Ergul,1 Alexa K Pius,1 Makarcyzk Meagan,2 Issei Shinohara,1 Masatoshi Murayama,1 Yosuke Susuki,1 Chao Ma,1 Mayu Morita,1 Simon Kwoon-Ho Chow,1 Bruce A Bunnell,3 Hang Lin,2 Qi Gao,1 Stuart B Goodman1 1Orthopaedic Research Laboratories, Department of Orthopaedic Surgery, Stanford University School of Medicine, Stanford, CA, 94304, USA; 2Center for Cellular and Molecular Engineering, Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15219, USA; 3Department of Microbiology, Immunology and Genetics, University of North Texas Health Science Center, Fort Worth, TX, 76107, USACorrespondence: Stuart B Goodman; Qi Gao, Email goodbone@stanford.edu; qigao7@stanford.eduBackground: Corticosteroids provide well-established therapeutic benefits; however, they are also accompanied by adverse effects on bone. Metformin is a widely used medication for managing type 2 diabetes mellitus. Recent studies have highlighted additional therapeutic benefits of metformin, particularly concerning bone health and oxidative stress.Objective: This research investigates the effects of prednisolone on cellular metabolic functions and bone formation using a 3D in vitro model. Then, we demonstrate the potential therapeutic effects of metformin on oxidative stress and the formation of calcified matrix due to corticosteroids.Methods: Human mesenchymal stem cells (MSCs) and macrophages were cultured in a 3D GelMA scaffold and stimulated with prednisolone, with and without metformin. The adverse effects of prednisolone and metformin’s therapeutic effect(s) were assessed by analyzing cell viability, osteogenesis markers, bone mineralization, and inflammatory markers. Oxidative stress was measured by evaluating reactive oxygen species (ROS) levels and ATP production.Results: Prednisolone exhibited cytotoxic effects, reducing the viability of MSCs and macrophages. Lower osteogenesis potential was also detected in the MSC group. Metformin positively affected cell functions, including enhanced osteoblast activity and increased bone mineralization. Furthermore, metformin effectively reduced oxidative stress, as evidenced by decreased ROS levels and increased ATP production. These findings indicate that metformin protects against oxidative damage, thus supporting osteogenesis.Conclusion: Metformin exhibits promising therapeutic potential beyond its role in diabetes management. The capacity to alleviate oxidative stress highlights the potential of metformin in supporting bone formation in inflammatory environments.Keywords: corticosteroid, osteogenesis, inflammation, bone, metformin

Fei-Yi Zhao,1– 3,* Li Li,4,* Peijie Xu,5,* Gerard A Kennedy,2,* Zhen Zheng,2 Yan-Mei Wang,3 Wen-Jing Zhang,3 Li-Ping Yue,1 Yuen-Shan Ho,6 Qiang-Qiang Fu,7 Russell Conduit2 1Department of Nursing, School of International Medical Technology, Shanghai Sanda University, Shanghai, 201209, People’s Republic of China; 2School of Health and Biomedical Sciences, RMIT University, Bundoora, VIC, 3083, Australia; 3Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200071, People’s Republic of China; 4Shanghai Changning Center for Disease Control and Prevention, Shanghai, 200335, People’s Republic of China; 5School of Computing Technologies, RMIT University, Melbourne, VIC, 3000, Australia; 6School of Nursing, Faculty of Health and Social Sciences, The Hong Kong Polytechnic University, Hong Kong SAR, People’s Republic of China; 7Yangpu Hospital, School of Medicine, Tongji University, Shanghai, 200090, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yuen-Shan Ho, School of Nursing, Faculty of Health and Social Sciences, The Hong Kong Polytechnic University, Hong Kong SAR, People’s Republic of China, Tel +852 2766 6410, Fax +852 2364 9663, Email janice.ys.ho@polyu.edu.hk Qiang-Qiang Fu, Yangpu Hospital, School of Medicine, Tongji University, Shanghai, 200090, People’s Republic of China, Tel + 86 021-6569 0520, Fax +86 021-6569 6249, Email qiangqiang.fu@tongji.edu.cnBackground and Aims: Increasing interest in hypnotherapy’s application for a wide range of health conditions has spurred a rise in global research and publications. This study aims to visualize development patterns and current research hotspots in clinical hypnotherapy practice using scientometric methods, and to predict future research directions based on the keyword trending topics analysis.Methods: Data on hypnotherapy applications and mechanisms in clinical settings between 1994 and 2023 were gathered from Scopus, Web of Science, and PubMed, followed by analysis and visualization using the VOSviewer, Bibliometrix package in R, and CiteSpace.Results: A total of 1,549 publications were examined, indicating a steady annual increase with an average growth rate of 8.5%, reaching a high of 134 publications in 2022. The United States was the primary research hub. Collectively, 1,464 distinct institutions involving 3,195 scholars contributed to this research theme. Collaboration was predominantly confined to the same country, institution, and/or research team. High-frequency keywords included “Pain”, “Irritable Bowel Syndrome (IBS)”, and “Anxiety”. Systematic review and/or meta-analysis have emerged as favored research methods. fMRI and EEG were commonly used techniques for exploring the neuropsychological mechanisms underlying hypnotherapy. “Self-Hypnosis”, “Virtual Reality”, and “Meditation” were predicted as trending topics, indicating that patients’ self-managed hypnosis practice, virtual reality hypnotherapy, and exploration of the variations in mechanisms between meditation and hypnotherapy might be emerging topics and/or future key research directions within the current field.Conclusion: The use of hypnotherapy for diverse clinical issues, particularly pain, IBS, and comorbid anxiety, is garnering global attention. The evidence-based approach is widely used to assess the quality of clinical evidence for hypnotherapy. Researchers are keen on innovating traditional hetero-hypnosis, with a shift towards more cost-effective self-hypnosis and immersive virtual reality hypnotherapy. Promoting and reinforcing collaborative research efforts across countries, institutions, and teams is warranted.Keywords: scientometrics, VOSviewer, Citespace, hypnosis, anxiety, pain, irritable bowel syndrome, complementary and alternative medicine

Lwin Moe Aung,1 Ting-Yi Renn,1 Jerry Chin-Yi Lin,1,2 Eisner Salamanca,1 Yi-Fan Wu,1,3 Yu-Hwa Pan,1,4,5 Nai-Chia Teng,1,6 Haw-Ming Huang,1 Ying-Sui Sun,7 Wei-Jen Chang1,8 1School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan; 2Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, MA, USA; 3Department of Biomedical Engineering, Ming-Chuan University, Taoyuan, Taiwan; 4Department of Dentistry, Chang Gung Memorial Hospital, Taipei, Taiwan; 5School of Dentistry, College of Medicine, China Medical University, Taichung, Taiwan; 6Department of Dentistry, Taipei Medical University Hospital, Taipei, Taiwan; 7School of Dental Technology, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan; 8Dental Department, Shuang-Ho Hospital, Taipei Medical University, Taipei, TaiwanCorrespondence: Wei-Jen Chang; Ying-Sui Sun, Email cweijen1@tmu.edu.tw; yingsuisun@tmu.edu.twPurpose: Nano-engineering techniques have significantly enhanced the various aspects of dentistry, with notable advancements, especially in dental implant surface modification. Dental implants are among the most significant and highly successful developments in contemporary dentistry. The use of nanotechnology for surface modification of zirconia ceramic implant increases interaction with surrounding bone cells, and ultimately leading to increase osseointegration.Materials and Methods: Glow discharge plasma was utilized to graft allylamine and fibronectin nanoproteins onto the surface of zirconia implants. A total of 18 implants were placed in right and left femurs of nine New Zealand rabbits. Implant stability test (IST), 3D bone reconstruction and micro-CT (μCT) analysis, bone-implant contact (BIC) from histomorphometry analysis, and osteogenic gene expression were analyzed after scarification at 4, 8, and 12 weeks.Results: IST results demonstrated a significant secondary stability gain at the end of 12 weeks. The surface-treated group obtained a gradual increase in marginal bone level. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis revealed increased expression of osteogenic genes of alkaline phosphatase (ALP) and transcription factor SP7 (SP7) biomarkers at 4 weeks. Osteoprotegerin (OPG) expression increased at 8 weeks, while runt-related transcription factor 2 (RUNX2), collagen 1A1 (COL1), bone sialoprotein (BSP), and receptor activator of nuclear factor κ B (RANK) exhibited the highest expression at 12 weeks. Importantly, histomorphometric analysis of BIC indicated that new bone formation was significantly higher in the A50F10 group compared to the control group at 12 weeks (P < 0.001).Conclusion: Based on the above findings, we conclude that the nanorough zirconia implant surface grafted with fibronectin nanoproteins prominently stimulated cellular activity and improved osseointegration properties. These results evidence its potential for future applications in dental implant surface modifications. Keywords: nano-roughness, surface modification, glow discharge plasma, zirconia implants, osseointegration, fibronectin

L Jay Katz,1,2 Jonathan S Myers,1 Leon W Herndon Jnr,3 Yocheved Shira Kresch,4 Fritz H Hengerer5,6 1Wills Eye Hospital, Philadelphia, PA, USA; 2Glaukos Corporation, Aliso Viejo, CA, USA; 3Duke University Eye Center, Durham, NC, USA; 4Department of Ophthalmology, Wayne State University School of Medicine, Detroit, MI, USA; 5Department of Ophthalmology, Buergerhospital, Frankfurt, Germany; 6University Eye Hospital, University of Heidelberg, Heidelberg, GermanyCorrespondence: L Jay Katz, Glaukos Corporation, One Glaukos Way, Aliso Viejo, CA, 92656, USA, Tel +01 949-367 9600, Fax +01 949 367 9984, Email jkatz@glaukos.comAbstract: Glaucoma treatment is beginning to undergo an evolution, moving away from topical medication-based therapies toward more proactive minimally invasive interventions. This shift towards an “interventional glaucoma” treatment paradigm has been shown to benefit patients, providers, and society. A key component of effectively implementing this approach is education about the importance of glaucoma diagnosis and treatment, as well as the various treatment modalities available. Such education is relevant not only for patient but also patients’ support networks, ophthalmologists, optometrists, third-party payers, and policy-makers. Education can occur both within and outside the clinical setting. The present article provides an overview of the diverse educational methods available for glaucoma patients, including those based on patient-provider interactions and those based on internet and printed material. Examples of the former could include general and specific verbal instruction, motivational interviewing, or community-based educational workshops, while examples of the latter could include office-based movies or printed materials, virtual reality headset educational videos, artificial intelligence-assisted education, or self-directed internet videos and articles. By empowering patients with knowledge and an up-to-date awareness of treatment options, effective education can be a valuable part of making an interventional glaucoma treatment paradigm possible.Keywords: MIGS, education, intervention/interventional, glaucoma, surgery

Bartholomeo Nicholaus Ngowi,1– 3 Alex Mremi,1,4 Mshangama Juma Seif,2 Yudathadeus Sebastian Kyara,3 Vaileth Kien Mteta,1 Frank Bright,2 Orgeness Jasper Mbwambo,1,2 Modesta Paschal Mitao,3 Mramba Nyindo,1 Kien Alfred Mteta,1,2 Blandina Theophil Mmbaga3 1Faculty of Medicine, Kilimanjaro Christian Medical University College, Moshi, Tanzania; 2Department of Urology, Kilimanjaro Christian Medical Centre, Moshi, Tanzania; 3Kilimanjaro Clinical Research Institute, Moshi, Tanzania; 4Department of Pathology, Kilimanjaro Christian Medical Centre, Moshi, TanzaniaCorrespondence: Bartholomeo Nicholaus Ngowi, Email baltonnic@yahoo.comBackground: Serum prostate-specific antigen (PSA) is a widely used maker for prostate cancer (PCa) screening. However, its correlation with PCa varies, partly due to ethnic differences. This study investigated the correlation between PSA and PCa diagnosis as well as the burden of the disease in the Tanzanian community.Methods: This community-based PCa screening took place in Northern Tanzania from May 2022 to September 2022, where men aged ≥ 40 years were involved. Each participant provided 5 milliliters of venous blood for PSA determination. Those with PSA levels > 4 ng/mL underwent prostate biopsy. Two pathologists independently evaluated the biopsies. The correlation between PSA and biopsy results was assessed using STATA version 17.0.Results: The study included 6164 African men with a mean age of 60± 11 years. Of these, 912 (14.8%) had PSA > 4 ng/mL, and hence 581 (63.7%) underwent prostate biopsy. A total of 179 men (30.8%) were histologically diagnosed with prostatic adenocarcinoma, whereby 46 (25.7%) had Gleason scores 8– 9. Among participants with PSA > 20 ng/mL, over 2/3 (64.7%) had PCa, rising to nearly 100% at PSA > 100 ng/mL. A positive correlation between PSA levels and PCa/aggressive disease was observed. PSA sensitivity decreased with rising levels, hitting 78.2% at > 10ng/mL and 24.6% at > 100ng/mL, while specificity increased, peaking at 99.8% for > 100ng/mL from 73.9% at > 10ng/mL. The optimal PSA cut point was > 10ng/mL. PSA demonstrated an 84% overall ability to predict PCa and a 71% ability to predict aggressive disease.Conclusion: This study found a notable presence of intermediate-high grade PCa within the community, suggesting the need for regular screening and management. Moreover, PSA demonstrated clinically useful ability in predicting PCa among African men aged 40 years and older.Keywords: correlation, PSA and prostate cancer

Young Sang Lyu,1 Hongyup Ahn,2 Sangmo Hong,3 Cheol-Young Park4 1Division of Endocrinology and Metabolism, Department of Internal Medicine, Chosun University Hospital, Gwangju, Republic of Korea; 2Department of Statistics, Dongguk University, Seoul, Republic of Korea; 3Department of Internal Medicine, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Republic of Korea; 4Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of KoreaCorrespondence: Cheol-Young Park, Division of Endocrinology and Metabolism, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 29 Saemunan-ro,Jongno-gu, Seoul, 03181, Republic of Korea, Email cydoctor@skku.eduPurpose: To investigate the safety and effectiveness of naltrexone-bupropion in Korean adults with obesity.Patients and methods: This was a prospective, observational multicenter study from April 29, 2016, to April 28, 2022. Individuals with obesity with a body mass index of ≥ 30 kg/m2 or ≥ 27 kg/m2 who had obesity-related comorbidities were included. The naltrexone-bupropion dose was gradually titrated weekly from 8/90 to 32/360 mg and maintained at the maximum tolerated dose. In total, 612 and 300 individuals were evaluated for safety and effectiveness, respectively.Results: In total, 41.34% individuals reported drug-related adverse reactions, such as nausea (19.12%), headache (7.68%), and dizziness (5.23%). Older age and comorbidities were significantly associated with adverse events. At 12 weeks after reaching the maintenance dose, naltrexone-bupropion 32/360 mg resulted in the greatest weight reduction (− 7.21%) compared with other doses, which persisted at week 24 (− 7.69%). The naltrexone-bupropion 16/180 mg resulted in significant weight reduction, achieving − 5.99% and − 9.18% reductions at weeks 12 and 24, similar to that with naltrexone-bupropion 32/360 mg. Young age and no comorbidities were significantly associated > 5% weight reduction.Conclusion: Naltrexone-bupropion demonstrated marked stability and weight loss effectiveness, particularly in young individuals with obesity without comorbidities. Therefore, individualized treatment is necessary when prescribing naltrexone-bupropion.Keywords: naltrexone-bupropion, obesity management, post-marketing survey, weight loss efficacy, adverse events

A-Mei Luo,1 Yuan-Sheng Yang,2 Yan Zhong,1 Rong-Fang Zeng,1 Qiao-Huo Liao,1 Jing Yuan,3 Wan-Ling Xiao,4 Lu-Lu Sun1 1Department of Paediatrics, The Third People’s Hospital of Shenzhen, Shenzhen, 518000, People’s Republic of China; 2Department of Hematology, The Third People’s Hospital of Shenzhen, Shenzhen, 518000, People’s Republic of China; 3Department of Infectious Disease, The Third People’s Hospital of Shenzhen, Shenzhen, 518000, People’s Republic of China; 4Department of Nursing, The Third People’s Hospital of Shenzhen, Shenzhen, 518000, People’s Republic of ChinaCorrespondence: Lu-Lu Sun, Department of Paediatrics, the Third People’s Hospital of Shenzhen, No. 29 of Bulan Road, Longgang District, Shenzhen, 518000, People’s Republic of China, Tel + 86 13510332310, Fax + 0755 61238983, Email sunlulusl@126.com Wan-Ling Xiao, Department of Nursing, The Third People’s Hospital of Shenzhen, No. 29 of Bulan Road, Longgang District, Shenzhen, 518000, People’s Republic of China, Tel +86 13 500 054 520, Fax +0755 61 238 983, Email wanling_x01@126.comObjective: To explore the factors that lead to occupational burnout among nurses in pediatric infectious disease wards after two consecutive years of frontline anti-epidemic work since the admission of COVID-19 patients in January 2020, in order to lay a scientific basis for reducing nurse occupational burnout.Methods: A total of 12 nurses who working in pediatric infection units were included in the study. Utilizing qualitative research methodologies, we used semi-structured interviews as the primary data collection method. The interview data underwent meticulous organization and were subjected to descriptive analysis.Results: 12 nurses assigned to pediatric infection wards frequently encounter occupational burnout, primarily attributed to increased work intensity, nurse-patient relationships, occupational frustration, psychological pressure, hospital infections, and various other contributing factors.Conclusion: We found that the severity of occupational burnout among nurses specializing in pediatric infectious diseases is noteworthy. Our recommendations include heightened consideration of this issue by government authorities and hospital administrators.Keywords: nurses, children, healthcare personnel, infectious infection area, occupational burnout, qualitative investigation

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

Jheng-Ting Luo,1 Yung-Chun Hung,1,2 Gina Jinna Chen,3 Yu-Shiang Lin1 1In-Service Master Program in Artificial Intelligence in Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 2School of Health Care Administration, College of Management, Taipei Medical University, Taipei, Taiwan; 3Department of Electronic and Electrical Engineering, Southern University of Science and Technology, Shenzhen, People’s Republic of ChinaCorrespondence: Yu-Shiang Lin, In-Service Master Program in Artificial Intelligence in Medicine, College of Medicine, Taipei Medical University, No. 250, Wuxing St., Xinyi District, Taipei City, 11031, Taiwan, Email eriklin@tmu.edu.twPurpose: Facial nerve paralysis, particularly Bell’s palsy, manifests as a rapid onset of unilateral facial weakness or paralysis. Despite most patients recovering within three to six months, a significant proportion experience poor recovery. This study utilized six machine learning models to investigate the effectiveness of early treatment in Bell’s palsy.Patients and Methods: We applied data from 17 hospitals in Scotland to predict treatment outcomes. Patients were randomized into four groups: Prednisolone (corticosteroids), Acyclovir (antivirals), both, and placebo. Outcomes, defined as full resolution of symptoms, were assessed using the House-Brackmann scale at 3 and 9 months post-treatment. We employed six different machine learning models to predict recovery outcomes and evaluated model performance using AUC, precision, recall, and F1-score.Results: Among 493 patients, 72.6% recovered after three months and 89.5% after nine months. Logistic regression demonstrated the highest predictive performance for both 3-month (AUC = 0.751) and 9-month recovery (AUC = 0.720). Additionally, several models achieved Precision levels exceeding 0.9. We further employed the best-performing logistic regression for feature ranking, indicating that the patient’s age and prednisolone administration are the most significant predictors of recovery.Conclusion: The results highlight the potential of machine learning models in predicting the effectiveness of early treatment. This study conducted a comprehensive comparison of six different machine learning models, with the logistic regression showing the highest predictive performance for both 3-month and 9-month recovery. Additionally, feature ranking using logistic regression supported the importance of Prednisolone in treatment. Notably, our findings revealed the significance of age in prognosis evaluation for the first time. This suggests that future research should further develop age-specific prognostic models, enabling clinicians to tailor individualized treatment strategies more effectively. This previously unrecognized discovery provides a foundation for prognostic analysis in Bell’s palsy patients.Keywords: Bell’s palsy, machine learning, prognostic prediction, feature ranking

Rong-Rong Huang,1 Yu-Sheng Xie,2 Gui-Ru Chen,3 Zhao-Qing Liu2 1Department of Burns and Plastic Surgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, People’s Republic of China; 2School of Nursing, Guizhou Medical University, Guiyang, Guizhou, People’s Republic of China; 3Department of Infectious Diseases, The People’s Hospital of Aba Tibetan and Qiang Autonomous Prefecture, Aba, Sichuan, People’s Republic of ChinaCorrespondence: Gui-Ru Chen, Department of Infectious Diseases, The People’s Hospital of Aba Tibetan and Qiang Autonomous Prefecture, No. 176 Majiang Road, Maerkang, Aba Tibetan and Qiang Autonomous Prefecture, Sichuan, 624000, People’s Republic of China, Email 2017283030185@whu.edu.cnAim: The Barriers to Error Disclosure Assessment (BEDA) tool is used to measure barriers to the disclosure of medical errors by healthcare professionals. This study aimed to evaluate the psychometric properties of the Chinese version of the BEDA (C-BEDA).Background: The culture of disclosure and transparency in response to medical errors has been recommended in recent years. However, there are no relevant assessment tools for measuring barriers to disclosing medical errors in China.Methods: The C-BEDA tool underwent translation, back translation, cross-cultural adaptation in a pilot study. It was tested with 1254 healthcare professionals in Guizhou and Sichuan Provinces, China. The content validity index (CVI) was used to evaluate the content validity of the C-BEDA, and exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were used to evaluate its structural validity. The Cronbach’s α coefficient and test-retest reliability were evaluated to determine its reliability.Results: Three factors were extracted by EFA that explained 65.892% of the total variance of the C-BEDA tool. CFA showed a good fit for a three-factor structure with acceptable values: goodness-of-fit index=0.939; adjusted goodness-of-fit index=0.911; incremental fit index=0.967; comparative fit index=0.967; partial least squares path modeling for confirmatory factor analysis=0.735; and root mean square error of approximation=0.058. The item-level content validity index ranged from 0.86 to 1.00, and the average scale-level content validity index was 0.98. The Cronbach’s α coefficient (0.909) and test-retest reliability (0.86) were acceptable.Conclusion: The C-BEDA toolis a valid and reliable tool for assessing the extent of barriers to error disclosure among Chinese healthcare professionals.Keywords: patient safety, medical error, disclosure, risk management

Khalid M Alshamrani,1– 3 Dana A Alzahrani,1 Yara S Alghamdi,1 Lama M Aljohani,1 Ziyad F Al Nufaiei1– 3 1College of Applied Medical Sciences, King Saud bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia; 2King Abdullah International Medical Research Center, Jeddah, Saudi Arabia; 3Ministry of the National Guard - Health Affairs, Jeddah, Saudi ArabiaCorrespondence: Khalid M Alshamrani, College of Applied Medical Sciences, King Saud bin Abdulaziz University for Health Sciences, P. O. Box 9515, Internal Mail Code 6610, Jeddah, 21423, Saudi Arabia, Tel +966-12-2266666 Ext 46396, Email alshamranik@ksau-hs.edu.saBackground: Occupational hazards among healthcare workers (HCWs) present serious risks, from infectious diseases to physical and chemical dangers, along with psychological stress, all of which threaten their health and safety. This study aims to identify the unique challenges and hazards encountered by radiology technologists in in Saudi Arabia by assessing the key factors contributing to these risks.Methods: A descriptive questionnaire study was conducted in January-February 2023, targeting 75 radiology technologists at King Abdulaziz Medical City (KAMC), Jeddah, with participants recruited via non-probability convenience sampling and invited to complete a widely recognized questionnaire previously used among radiographers. Descriptive statistics were calculated, and the Kruskal–Wallis H-test was conducted to examine the relationships between demographic factors and different aspects of occupational hazards.Results: Of the 75 technologists contacted, 63 responded, resulting in an 84% participation rate. Workload, work shifts, and patient-related factors are major contributors to occupational hazards, surpassing technologist-specific and organizational elements. Additionally, 68.3% cited rigid leadership and unequal treatment as aggravating factors, while insufficient staffing, inadequate protective devices, and patient interaction were also significant concerns. Over 60% identified bending, lifting heavy patients, prolonged radiation exposure, and frequent walking as major hazard sources.Conclusion: Key occupational hazards factors facing radiology technologists include high workloads, work shifts, and patient-related issues, with 68.3% citing rigid leadership and unequal treatment as exacerbating risks. Insufficient staffing and protective devices, along with demanding work conditions, further heighten these hazards. This study emphasizes the need for targeted interventions in staffing, resources, and culture to improve radiology technologists’ safety. Keywords: healthcare workers, Kingdom of Saudi Arabia, occupational health, professional risk, radiologic technology, safety

Yu-Sen Feng,1,&ast; Zheng-Yun Sun,2,&ast; Fei Jiang,3 Peng-Cheng Ma,1 Xing-Rui Liu,1 Yuan-Yuan Meng,2 Cheng-De Liao,1 Gui-Fang Sun1 1Department of Radiology, Kunming Yan’an Hospital, Kunming, 650051, People’s Republic of China; 2Department of Radiology, Lincang First People’s Hospital, Lincang, 677000, People’s Republic of China; 3Department of Radiology, Wenshan First People’s Hospital, Wenshan, 663599, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Gui-Fang Sun, Department of Radiology, Kunming Yan’an Hospital, No. 245 Renmin East Road, Panlong District, Kunming, Yunnan, 650051, People’s Republic of China, Tel +86 13759518529, Email guifang_sun07@126.comObjective: This study aims to evaluate the relationship between the pericoronary fat attenuation index (FAI), derived from coronary artery computed tomography angiography, and post-lipid management levels of low-density lipoprotein cholesterol in patients with coronary artery disease (CAD). Additionally, the study investigates coronary inflammation across different lipid management strategies.Methods: We selected a cohort comprising 521 CAD patients who met the inclusion criteria. Patients were categorized into well-managed (LDL-C< 2.6 mmol/L) and poorly managed (LDL-C≥ 2.6 mmol/L) groups based on lipid management efficacy. We collected anthropometric measures (height, weight, body mass index, and body surface area) and clinical indicators, including Gensini score, and FAI-related parameters for coronary atherosclerotic lesions. We analyzed the interrelations along these parameters and lipid management using statistical methods and assessed diagnostic value via receiver operating characteristic (ROC) curve analysis of these parameters was assessed through.Results: The poorly managed group exhibited significantly higher levels of total cholesterol, triglycerides, and lower levels of high-density lipoprotein compared to the well-managed group (P < 0.05). Significant differences were observed between the groups in terms of lesion length in the proximal segment of the left anterior descending artery, FAI value in the proximal segment of lesions in the right coronary artery (RCA), volume thickness in the middle segment of RCA lesions, and lesion length in the distal segment of RCA (P < 0.05). ROC curve analysis revealed areas under the curve ranging from 0.484 to 0.660 for the parameters, indicating limited diagnostic efficacy.Conclusion: The FAI in the RCA varies with lipid management strategies, suggesting it as a valuable metric for monitoring both perivascular inflammation and lipid status in CAD patients. However, its current diagnostic efficacy is limited, indicating the need for further research to improve its clinical utility.Keywords: coronary artery CT angiography, coronary atherosclerotic heart disease, coronary inflammation, lipids, low-density lipoprotein cholesterol, pericoronary fat attenuation index

Leecarlo Millano Lumban Gaol,1– 3 Ambrosius Purba,1 Rizki Diposarosa,1,2 Yuni Susanti Pratiwi1 1Faculty of Medicine Padjadjaran University, Bandung, Indonesia; 2Dr. Hasan Sadikin General Hospital, Bandung, Indonesia; 3Faculty of Medicine Krida Wacana Christian University, Jakarta, IndonesiaCorrespondence: Leecarlo Millano Lumban Gaol, Faculty of Medicine Padjadjaran University, Raya Bandung Sumedang Street No. 21, Hegarmanah, Jatinangor, Sumedang, Bandung, West Java, 45363, Indonesia, Email millanoleecarlo@gmail.comBackground: Fecal incontinence (FI) is the inability to control bowel movements, resulting in fecal leakage. If left untreated, FI can seriously impact the long-term well-being of individuals affected. Recently, using secretome has become a promising new treatment method. The secretome combines growth factors released outside cells during stem cell development, such as mesenchymal stem cells. It consists of soluble proteins, nucleic acids, fats, and extracellular vesicles, which contribute to different cell processes. The primary aim is to assess the impact of hypoxic secretome administration on accelerating wound healing through the HIF-1α pathway in a post-sphincterotomy rat model.Methods: The study was conducted with two distinct groups of 10 rats each, the control and treatment groups, which were injected with hypoxic secretome at 0.3 mL. The inclusion criteria for the rats were as follows: male gender, belonging to the Sprague-Dawley strain, aged between 12 to 16 weeks, with an average body weight ranging from 240 to 250 grams.Results: There was an increase in HIF-1α gene expression in both groups. The treatment group 37 was significantly higher on day 42 (p = 0.001). VEGF increased significantly in the treatment 38 group on day 42 (p = 0.015). The neovascularization score increased significantly in the treatment 39 group during the first 24 hours (p = 0.004). The fibroblast score increased significantly in the 40 treatment group in the first 24 hours (p = 0.000) and 42 days (p = 0.035). After being given secretome, there was a higher increase in % collagen area and collagen area (μm2) in the treatment group compared to the control group (27,77 vs 11.01) and (419.027,66 vs 186.694,16).Conclusion: The use of hypoxic secretome has a significant effect as a choice for the treatment of anal sphincter injury after sphincterotomy through the HIF-1α-VEGF-Fibroblast pathway.Keywords: fecal incontinence, fibroblast, HIF-1α, hypoxic secretome, neovascularization, VEGF

Yan-Shan Duan, Yi-Ran Wang, Bin-Yan Li, Zi-Tong Fu, Jian-Feng Tu, Hang Zhou, Yu Wang, Li-Qiong Wang, Cun-Zhi Liu International Acupuncture and Moxibustion Innovation Institute, School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing, People’s Republic of ChinaCorrespondence: Li-Qiong Wang; Cun-Zhi Liu, International Acupuncture and Moxibustion Innovation Institute, School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, No. 11, Bei San Huan Dong Lu, Beijing, Chaoyang District, 100029, People’s Republic of China, Email lcz623780@126.com; wangliqiongwork@163.comObjective: To evaluate the reporting quality of randomized controlled trials (RCT) of acupuncture for knee osteoarthritis and explore factors associated with the reporting.Study Design and Setting: Eight databases were searched from inception to August 2024 to assess the quality of acupuncture for knee osteoarthritis RCTs based on the CONSORT, the STRICTA, and the CONSORT-Outcomes. We performed regression analyses on pre-specified study characteristics to explore factors associated with reporting quality.Results: One hundred and seventy-four RCTs were evaluated by 69 items from 3 checklists. Seventeen of 37 items on the CONSORT were under-reported (reported in less than 20% of RCTs), and the weakest reported item was why the trial ended or was stopped (0%). Four of 17 items on the STRICTA were under-reported, and the weakest reported item was the number of needle insertions per subject per session (9.2%). Eight of 17 items on the CONSORT-Outcomes were under-reported, and the weakest reported item was identifying any outcomes that were not pre-specified in a trial registry or trial protocol (0.6%). RCT locations include countries other than China, published in English, or funded were more likely to have better reporting.Conclusion: RCTs of acupuncture for knee osteoarthritis need to focus more on reporting details of acupuncture interventions, the reporting of protocol amendment, and the complete reporting of outcome-related content. Journals should encourage authors to adhere strictly to reporting guidelines, which is necessary to improve the quality of reporting, which is very important for Chinese journals.Keywords: randomized controlled trials, acupuncture, knee osteoarthritis, CONSORT, STRICTA, outcomes

Fengjiao Bu,1,2,&ast; Yong-Soon Cho,3,4,&ast; Qingfeng He,1 Xiaowen Wang,1 Saurav Howlader,3,4 Dong-Hyun Kim,3,4 Mingshe Zhu,5 Jae Gook Shin,3,4 Xiaoqiang Xiang1,6 1Department of Clinical Pharmacy and Pharmacy Administration, School of Pharmacy, Fudan University, Shanghai, People’s Republic of China; 2Department of Pharmacy, Eye and ENT Hospital, Fudan University, Shanghai, People’s Republic of China; 3Department of Pharmacology and Pharmacogenomics Research Center, Inje University College of Medicine, Busan, Republic of Korea; 4Center for Personalized Precision Medicine of Tuberculosis, Inje University College of Medicine, Busan, Republic of Korea; 5Department of DMPK, MassDefect Technologies, Princeton, NJ, USA; 6Department of Preclinical Evaluation, Quzhou Fudan Institute, Quzhou, Zhejiang Province, 324002, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jae Gook Shin; Xiaoqiang Xiang, Email phshinjg@gmail.com; xiangxq@fudan.edu.cnBackground: Anlotinib was approved as a third line therapy for advanced non-small cell lung cancer in China. However, the impact of concurrent administration of various clinical drugs on the drug–drug interaction (DDI) potential of anlotinib remains undetermined. As such, this study aims to evaluate the DDI of anlotinib as a victim by establishing a physiologically based pharmacokinetic (PBPK) model.Methods: The PBPK model of anlotinib as a victim drug was constructed and validated in the Simcyp® incorporating parameters derived from in vitro studies, pre-clinical investigations, and clinical research encompassing patients with cancer. Subsequently, plasma exposure of anlotinib in cancer patients was predicted for single- and multi-dose co-administration with typical perpetrators mentioned in Food and Drug Administration (FDA) industrial guidance.Results: Based on predictions, the CYP3A potent inhibitor ketoconazole demonstrated the most significant DDI with anlotinib, regardless of whether anlotinib is administered as a single dose or multiple doses. Ketoconazole increased the area under the concentration-time curve (AUC) and maximum concentration (Cmax) of single-dose anlotinib to 1.41-fold and 1.08-fold, respectively. In contrast, rifampicin, a potent inducer of CYP3A enzymes, exhibited a relatively higher level of DDI, with AUCR and CmaxR values of 0.44 and 0.79, respectively.Conclusion: Based on the PBPK modeling, there is a low risk of DDI between anlotinib and potent CYP3A/1A2 inhibitors, but caution and enhanced monitoring for adverse reactions are advised. To mitigate the risk of anti-tumor treatment failure, it is recommended to avoid concurrent use of strong CYP3A inducers. In conclusion, our study enhances understanding of anlotinib’s interaction with medications, aiding scientists, prescribers, and drug labels in gauging the expected impact of CYP3A/1A2 modulators on anlotinib’s pharmacokinetics. Keywords: anlotinib, DDIs, CYP3A, CYP1A2, PBPK

Yin-shan Jin,&ast; Yuan-qing Cui,&ast; Yan-ping Xu,&ast; Jie Chen, Xue-bao Zhang, Xiong Wang Department of Reproductive Medicine, Yantai Yuhuangding Hospital, Yantai, 264000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiong Wang, Department of Reproductive Medicine, Yantai Yuhuangding Hospital, No. 20, Yuhuangding East Road, Yantai, 264000, People’s Republic of China, Email wangxiong01903@163.comIntroduction: Varicocele is a dilatation of the internal spermatic vein and it is generally recognized as one cause of male infertility. This study aimed to analyze the roles of activating transcription factor 6 (ATF-6) in experimental varicocele-induced epididymal epithelial cells.Methods: Experimental left varicocele was established in rats through partial left renal vein ligation. At 8 weeks after surgery, the left epididymal damage was observed using H&E and TUNEL staining. The expressions of neutral α-glucosidase (NAG), ATF-6, tumor necrosis factor (TNF)-α, and phospho-nuclear factor (p-NF)-κB p65 (S536) in the left epididymis were measured by immunohistochemistry. ATF-6 silence in rat epididymal epithelial cells was established by ATF-6 siRNA transfection. The cells were treated with hypoxia for 24 h, and cell viability was measured by CCK-8, levels of NAG, TNF-α, and interleukin (IL)-8 in cells were measured by ELISA, levels of p-NF-κB p65 (S536)/NF-κB p65 protein in cells were measured by Western blotting.Results: The results showed that the experimental left varicocele induced hypertrophy and apoptosis of epididymal epithelial cells (p< 0.05), and decreased the expressions of NAG in the epididymal epithelial cells compared with the sham-operated control rats (p< 0.01). Meanwhile, the expressions of ATF-6, TNF-α, and p-NF-κB p65 (S536) were increased in the epididymal epithelial cells after the experimental left varicocele compared with the sham-operated control rats (p< 0.05). In the hypoxia-treated cells, ATF-6 silence increased the cell viability and decreased the levels of TNF-α, IL-8, and p-NF-κB p65 (S536) compared with the control cells (p< 0.05).Discussion: The ATF-6 pathway was activated in a rat’s left varicocele-induced epididymal damage. Inhibition of the ATF-6 pathway might be a possible novel therapeutic approach for left varicocele-induced epididymal damage.Keywords: epididymal neutral α-glucosidase, hypoxia, left varicocele, nuclear factor-kappa B p65, NF-κB p65

Xiao-Fang Dong,1 Qiang Zhang,2 Jia-Ning Wei,2 Qian-Yu Zhou,3 Fan-Jia-Yi Yang,2 Yan-Jin Liu,4 Yu-Sheng Li,5 Chang-Qing Sun2,3 1Department of Endocrinology and Metabolic Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 2School of Nursing and Health, Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 3Department of Epidemiology and Biostatistics, Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 4Department of Nursing, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 5Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of ChinaCorrespondence: Chang-Qing Sun, School of Nursing and Health, Zhengzhou University, NO. 101 Kexue Road, High-Tech Development Zone of District, Zhengzhou, Henan, People’s Republic of China, Email suncq@zzu.edu.cnObjective: Our research explores how leisure-time sedentary behavior (SB) correlates with stroke risk. Additionally, we utilize the isotemporal substitution model (ISM) to examine how replacing brief durations of leisure-time SB with light physical activity (LPA), moderate physical activity (MPA), vigorous physical activity (VPA), and sleep might influence the risk of stroke.Methods: This investigation tracked 478,198 participants from the UK Biobank. Data regarding individual leisure-time SB and PA were collected through a standardized questionnaire. A Cox proportional hazards model, alongside an isotemporal substitution model (ISM), was utilized.Results: We identified 10,003 cases of incident stroke over 12.7 years. When compared to participants who engaged in leisure-time SB for less than 4 hours per day, the hazard ratios (HRs) for stroke incidence increased with more prolonged leisure-time SB: HRs were 1.06 (95% CI: 1.01 to 1.11) for 4– 6 h/d, 1.16 (95% CI: 1.10 to 1.23) for 6– 8 h/d, and 1.24 (95% CI: 1.15 to 1.33) for over 8 h/d. According to the ISM analysis, substituting leisure-time SB with various forms of PA could markedly reduce stroke risk. For individuals sleeping ≤ 8h/d, replacing one hour of leisure-time SB with an equivalent duration of LPA, VPA, or sleep corresponded to a 3.0%, 7.0%, and 22.0% decrease in stroke risk, respectively. Meanwhile, for those already sleeping more than 8h/d, substituting one hour of leisure-time SB with an equivalent duration of LPA or VPA resulted in a notable decrease in the risk of stroke by 6.0% and 18.0%, respectively.Conclusion: The findings demonstrate that leisure-time SB and unhealthy sleep durations are confirmed risk factors for stroke. For individuals sleeping 8 hours or less per day, and for those who sleep more than 8 hours, substituting SB with an adequate amount of sleep or engaging in VPA, respectively, emerges as an effective strategy for reducing stroke risk.Keywords: stroke, isotemporal substitution model, physical activity, sedentary behavior, sleep

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

Ali Attiq,1 Sheryar Afzal,2 Habibah A Wahab,1 Waqas Ahmad,1 Mahmoud Kandeel,2,3 Yassir A Almofti,2,4 Ahmed O Alameen,2,5 Yuan Seng Wu6,7 1School of Pharmaceutical Sciences, Universiti Sains Malaysia, Gelugor, Penang, 11800, Malaysia; 2Department of Biomedical Sciences, College of Veterinary Medicine, King Faisal University, Al Ahsa, 31982, Saudi Arabia; 3Department of Pharmacology, Faculty of Veterinary Medicine, Kafrelsheikh University, Kafrel Sheikh, 6860404, Egypt; 4Department of Biochemistry, Molecular Biology and Bioinformatics, College of Veterinary Medicine, University of Bahri, Khartoum, 12217, Sudan; 5Department of Physiology, Faculty of Veterinary Medicine, University of Khartoum, Shambat, 13314, Sudan; 6Sunway Microbiome Centre, School of Medical and Life Sciences, Sunway University, Subang Jaya, Selangor, 47500, Malaysia; 7Department of Biological Sciences, School of Medical and Life Sciences, Sunway University, Subang Jaya, Selangor, 47500, MalaysiaCorrespondence: Sheryar Afzal, Department of Biomedical Sciences, College of Veterinary Medicine, King Faisal University, Al Ahsa, 31982, Saudi Arabia, Email safzal@kfu.edu.sa Ali Attiq, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Gelugor, 11800, Penang, Malaysia, Email aliattiq@usm.myAbstract: Angiotensin-converting enzyme 2 receptors (ACE2R) are requisite to enter the host cells for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). ACE2R is constitutive and functions as a type I transmembrane metallo-carboxypeptidase in the renin-angiotensin system (RAS). On thyroid follicular cells, ACE2R allows SARS-CoV-2 to invade the thyroid gland, impose cytopathic effects and produce endocrine abnormalities, including stiff back, neck pain, muscle ache, lethargy, and enlarged, inflamed thyroid gland in COVID-19 patients. Further damage is perpetuated by the sudden bursts of pro-inflammatory cytokines, which is suggestive of a life-threatening syndrome known as a “cytokine storm”. IL-1β, IL-6, IFN-γ, and TNF-α are identified as the key orchestrators of the cytokine storm. These inflammatory mediators upregulate transcriptional turnover of nuclear factor-kappa B (NF-κB), Janus kinase/signal transducer and activator of transcription (JAK/STAT), and mitogen-activated protein kinase (MAPK), paving the pathway for cytokine storm-induced thyroid dysfunctions including euthyroid sick syndrome, autoimmune thyroid diseases, and thyrotoxicosis in COVID-19 patients. Targeted therapies with corticosteroids (dexamethasone), JAK inhibitor (baricitinib), nucleotide analogue (remdesivir) and N-acetyl-cysteine have demonstrated effectiveness in terms of attenuating the severity and frequency of cytokine storm-induced thyroid dysfunctions, morbidity and mortality in severe COVID-19 patients. Here, we review the pathogenesis of cytokine storms and the mechanisms and pathways that establish the connection between thyroid disorder and COVID-19. Moreover, cross-talk interactions of signalling pathways and therapeutic strategies to address COVID-19-associated thyroid diseases are also discussed herein.Keywords: COVID-19, cytokine storm, signalling pathways, inflammation, thyroid disorders, cross talks

Fei-Yi Zhao,1– 3,&ast; Li Li,4,&ast; Peijie Xu,5,&ast; Wen-Jing Zhang,3,&ast; Gerard A Kennedy,2 Zhen Zheng,2 Yan-Mei Wang,3 Li-Ping Yue,1 Yuen-Shan Ho,6 Qiang-Qiang Fu,7 Russell Conduit2 1Department of Nursing, School of International Medical Technology, Shanghai Sanda University, Shanghai, 201209, People’s Republic of China; 2School of Health and Biomedical Sciences, RMIT University, Bundoora, VIC, 3083, Australia; 3Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200071, People’s Republic of China; 4Shanghai Changning Center for Disease Control and Prevention, Shanghai, 200335, People’s Republic of China; 5School of Computing Technologies, RMIT University, Melbourne, VIC, 3000, Australia; 6School of Nursing, Faculty of Health and Social Sciences, The Hong Kong Polytechnic University, Hong Kong, SAR, People’s Republic of China; 7Yangpu Hospital, School of Medicine, Tongji University, Shanghai, 200090, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuen-Shan Ho, School of Nursing, Faculty of Health and Social Sciences, The Hong Kong Polytechnic University, Hong Kong, SAR, People’s Republic of China, Tel +852 2766-6410, Fax +852 2364-9663, Email janice.ys.ho@polyu.edu.hk Qiang-Qiang Fu, Yangpu Hospital, School of Medicine, Tongji University, Shanghai, 200090, People’s Republic of China, Tel + 86 021-6569 0520, Fax + 86 021-6569 6249, Email qiangqiang.fu@tongji.edu.cnBackground: Acupuncture is popular in the treatment of mental illness. This study determined its feasibility and role in managing postpartum depression (PPD) using a network meta-analysis.Methods: We systematically searched seven databases up to May 2024 for randomized controlled trials (RCTs) appraising acupuncture’s efficacy and safety against waitlist-control, placebo, standard control, or as an add-on treatment. Cochrane criteria were followed.Results: Thirteen studies encompassing 872 participants underwent analysis. Both pairwise and network meta-analysis indicated that acupuncture, psychotherapy, and antidepressants were comparable in clinical efficacy rate and in reducing Hamilton Depression Scale and Edinburgh Postnatal Depression Scale scores. Acupuncture and psychotherapy also effectively mitigated concurrent anxiety symptoms. Combining acupuncture with antidepressants augmented therapeutic efficacy and reduced reported gastrointestinal adverse effects associated with antidepressant use. Acupuncture combined with psychotherapy offered similar benefits with superior safety profile. However, the quality of evidence ranged from very low to low due to significant risks of bias and limited sample sizes. The efficacy of psychotherapy and the combination of acupuncture and psychotherapy might be underestimated, as most RCTs used supportive therapy or individual counseling as positive controls instead of recommended approaches like interpersonal psychotherapy (IPT) or cognitive behavioral therapy (CBT) per PPD guidelines.Conclusion: Current evidence precludes strong recommendations of administering acupuncture in PPD. Rigorous RCTs are essential to validate promising outcomes observed in comparisons between acupuncture, antidepressants, and their combined application. It remains inconclusive whether acupuncture’s antidepressive effect is specific or non-specific. Given that psychotherapy is a recommended first-line treatment, investigating the potential efficacy enhancement of combining acupuncture with IPT/CBT is paramount to ascertain the preferred therapeutic approach for PPD.Keywords: postpartum depression, acupuncture, antidepressants, interpersonal psychotherapy, cognitive behavioral therapy, clinical trials

Nithya Boopathiraj,1 Isabella V Wagner,1 Paul Connor Lentz,2 Christian Draper,3 Chelsey Krambeer,1 Yazan S Abubaker,1 Bryan Chin Hou Ang,1,4,5 Darby D Miller,1 Syril Dorairaj1 1Department of Ophthalmology, Mayo Clinic, Jacksonville, FL, USA; 2Department of Ophthalmology, Mayo Clinic Alix School of Medicine, Jacksonville, FL, USA; 3Department of Ophthalmology, Eye Consultants, Spokane, WA, USA; 4Department of Ophthalmology, Tan Tock Seng Hospital, National Healthcare Group Eye Institute, Singapore; 5Department of Ophthalmology, Woodlands Health, National Healthcare Group Eye Institute, SingaporeCorrespondence: Syril Dorairaj, Department of Ophthalmology, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA, Tel +1-904-953-2377, Fax +1-904-953-7040, Email dorairaj.syril@mayo.eduPurpose: To compare the safety and effectiveness of standalone Kahook Dual Blade (KDB) excisional goniotomy to standalone ab-interno Xen gel stent implantation in eyes with moderate-to-severe open-angle glaucoma (OAG).Methods: A single-center, retrospective study including eyes with moderate-to-severe OAG undergoing standalone KDB goniotomy or Xen gel stent implantation was conducted. Intraocular pressure (IOP), the number of antiglaucoma medications taken daily, and best-corrected visual acuity (BCVA) were recorded at baseline and for up to 36-months. Primary outcomes assessed included changes from baseline in IOP and the number of antiglaucoma medications taken. Intergroup comparisons were conducted using independent-samples Student’s t-tests. The incidence of intraoperative and postoperative adverse events and the need for glaucoma surgical re-interventions were also recorded.Results: Eyes receiving standalone KDB (n=26) or Xen gel stent (n=45) surgery were analyzed. The baseline mean IOP and number of antiglaucoma medications in both groups were as follows: KDB: 23.2 ± 6.0 mmHg, 2.2 ± 1.4 medications; Xen: 22.7 ± 8.8 mmHg, 3.0 ± 1.0 medications. At 36 months, IOP was reduced to 16.6 ± 5.4 mmHg in KDB eyes (n=23, − 23.5%; p=0.0004) and 15.3 ± 5.6 mmHg in Xen gel stent eyes (n=15, − 22.1%; p=0.006), while number of antiglaucoma medications was reduced to 1.1 ± 0.7 (− 30.8%; p=0.0005) and 2.2 ± 1.4 (− 25.6%; p=0.01), respectively. Three eyes (11.5%) in the KDB group and 19 eyes (42.2%) in the Xen gel stent group required additional surgery before month 36 due to refractory high IOP.Conclusion: Both KDB goniotomy and Xen gel stent implantation significantly lowered the IOP and antiglaucoma medication burden in patients with moderate-to-severe OAG. While the Xen gel stent is frequently used to treat moderate-to-severe OAG patients with uncontrolled IOP, standalone KDB goniotomy may be equally effective as a long-term intervention, reducing the need for subsequent glaucoma surgery.Keywords: kahook dual blade, micro-invasive glaucoma surgery, open angle glaucoma, xen gel stent

Ji-Hyun Kang,1,2,&ast; Jin-Hyuk Jeong,1,&ast; Yong-Bin Kwon,1 Young-Jin Kim,1 Dae Hwan Shin,1 Yun-Sang Park,3 Soonsil Hyun,1 Dong-Wook Kim,4 Chun-Woong Park1 1College of Pharmacy, Chungbuk National University, Cheongju, 28160, Republic of Korea; 2School of Pharmacy, Institute of New Drug Development, and Respiratory Drug Development Research Institute, Jeonbuk National University, Jeonju, Republic of Korea; 3Research & Development Center, P2K Bio, Cheongju, Republic of Korea; 4College of Pharmacy, Wonkwang University, Iksan, 54538, Republic of Korea&ast;These authors contributed equally to this workCorrespondence: Chun-Woong Park, College of Pharmacy, Chungbuk National University, Cheongju, 28160, Republic of Korea, Tel +82-43-261-3330, Fax +82-43-268-2732, Email cwpark@cbnu.ac.kr Dong-Wook Kim, College of Pharmacy, Wonkwang University, Iksan, 54538, Republic of Korea, Tel +82-63-229-7130, Fax +82-63-850-7309, Email pharmengin@gmail.comPurpose: Effective mucosal delivery of drugs continues to pose a significant challenge owing to the formidable barrier presented by the respiratory tract mucus, which efficiently traps and clears foreign particulates. The surface characteristics of micelles dictate their ability to penetrate the respiratory tract mucus. In this study, polymeric micelles loaded with insulin (INS) were modified using mucus-penetrative polymers.Methods: We prepared and compared polyethylene glycol (PEG)-coated micelles with micelles where cell-penetrating peptide (CPP) is conjugated to PEG. Systematic investigations of the physicochemical and aerosolization properties, performance, in vitro release, mucus and cell penetration, lung function, and pharmacokinetics/pharmacodynamics (PK/PD) of polymeric micelles were performed to evaluate their interaction with the respiratory tract.Results: The nano-micelles, with a particle size of < 100 nm, exhibited a sustained-release profile. Interestingly, PEG-coated micelles exhibited higher diffusion and deeper penetration across the mucus layer. In addition, CPP-modified micelles showed enhanced in vitro cell penetration. Finally, in the PK/PD studies, the micellar solution demonstrated higher maximum concentration (Cmax) and AUC0-8h values than subcutaneously administered INS solution, along with a sustained blood glucose-lowering effect that lasted for more than 8 h.Conclusion: This study proposes the use of mucus-penetrating micelle formulations as prospective inhalation nano-carriers capable of efficiently transporting peptides to the respiratory tract.Keywords: insulin, polyethylene glycol, cell-penetrating peptide, aerodynamic properties, mucus penetration

Amrita Muralikrishnan,1 Mahendran Sekar,1 Vinoth Kumarasamy,2 Siew Hua Gan,1 Subban Ravi,3 Vetriselvan Subramaniyan,4 Ling Shing Wong,5 Yuan Seng Wu,6 Farrah Syazana Khattulanuar,7 Nur Najihah Izzati Mat Rani7 1School of Pharmacy, Monash University Malaysia, Bandar Sunway, Selangor Darul Ehsan, Malaysia; 2Department of Parasitology & Medical Entomology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur, 56000, Malaysia; 3Department of Chemistry, Karpagam Academy of Higher Education, Coimbatore, Tamil Nadu, India; 4Department of Medical Sciences, School of Medical and Life Sciences, Sunway University, Bandar Sunway, Selangor 47500, Malaysia; 5Faculty of Health and Life Sciences, INTI International University, Nilai, 71800, Malaysia; 6Sunway Microbiome Centre & Department of Biological Sciences, School of Medical and Life Sciences, Sunway University, Bandar Sunway, Selangor, 47500, Malaysia; 7Faculty of Pharmacy and Health Sciences, Royal College of Medicine Perak, Universiti Kuala Lumpur, Ipoh, Perak, 30450, MalaysiaCorrespondence: Mahendran Sekar, School of Pharmacy, Monash University Malaysia, Bandar Sunway, Selangor Darul Ehsan, Malaysia, Email mahendran.sekar@moansh.edu Vinoth Kumarasamy, Department of Parasitology & Medical Entomology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Cheras, Kuala Lumpur, 56000, Malaysia, Email vinoth@ukm.edu.myAbstract: Decursin is a pyranocoumarin compounds which are rare secondary metabolic plant products, isolated from the roots of Angelica gigas (A. gigas). The native Korean species Angelica gigas Nakai (AGN) is widely used as a remedy for a variety of medical conditions including hematopoiesis, improving women’s circulation, as sedatives, analgesics and tonic. It is unique because of the presence of substantial amounts of pyranocoumarins including decursin, decursinol, and decursinol angelate. In this review, we provide a comprehensive insight into the distribution, morphology, and chemical composition of A. gigas. A detailed discussion regarding the biological applications of decursin based on the literature retrieved from PubMed, ScienceDirect, Scopus, and Google Scholar from 2000 to the present has been discussed. Both in vitro and in vivo studies have demonstrated that decursin has potential neuroprotective, anti-inflammatory, anti-melanogenic, anti-angiogenic, antioxidant, and anti-visceral properties. Mechanistic findings establish its significance in regulating important signalling pathways, triggering apoptosis, and preventing metastasis in different cancer types. The review additionally addressed the isolation methods, biosynthesis, physiochemical characteristics, toxicity and pharmacokinetic profile of decursin. The present state of clinical studies including A. gigas is investigated, emphasizing its advancements and possibilities in the field of translational medicine. Keywords: decursin, Angelica gigas, pyranocoumarins, biosynthesis, pharmacology

Aathira Sujathan Nair,1 Mahendran Sekar,1 Siew Hua Gan,1 Vinoth Kumarasamy,2 Vetriselvan Subramaniyan,3 Yuan Seng Wu,4 Nur Najihah Izzati Mat Rani,5 Subban Ravi,6 Ling Shing Wong7 1School of Pharmacy, Monash University Malaysia, Bandar Sunway, Subang Jaya, Selangor, 47500, Malaysia; 2Department of Parasitology & Medical Entomology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur, 56000, Malaysia; 3Department of Medical Sciences, School of Medical and Life Sciences, Sunway University, Bandar Sunway, Selangor, 47500, Malaysia; 4Sunway Microbiome Centre & Department of Biological Sciences, School of Medical and Life Sciences, Sunway University, Bandar Sunway, Selangor, 47500, Malaysia; 5Faculty of Pharmacy and Health Sciences, Royal College of Medicine Perak, Universiti Kuala Lumpur, Ipoh, Perak, 30450, Malaysia; 6Department of Chemistry, Karpagam Academy of Higher Education, Coimbatore, Tamil Nadu, India; 7Faculty of Health and Life Sciences, INTI International University, Nilai, 71800, MalaysiaCorrespondence: Mahendran Sekar, School of Pharmacy, Monash University Malaysia, Bandar Sunway, Subang Jaya, Selangor, 47500, Malaysia, Email mahendran.sekar@monash.edu Vinoth Kumarasamy, Department of Parasitology & Medical Entomology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Cheras, Kuala Lumpur, 56000, Malaysia, Email vinoth@ukm.edu.myAbstract: Lawsone, a naturally occurring organic compound also called hennotannic acid, obtained mainly from Lawsonia inermis (Henna). It is a potential drug-like molecule with unique chemical and biological characteristics. Traditionally, henna is used in hair and skin coloring and is also a medicinal herb for various diseases. It is also widely used as a starting material for the synthesis of various drug molecules. In this review, we investigate on the chemistry, biosynthesis, physical and biological properties of lawsone. The results showed that lawsone has potential antioxidant, anti-inflammatory, antimicrobial and antitumor properties. It also induces cell cycle inhibition and programmed cell death in cancer, making it a potential chemotherapeutic agent. Additionally, inhibition of pro-inflammatory cytokine production makes it an essential treatment for inflammatory diseases. Exploration of its biosynthetic pathway can pave the way for its development into targets for new drug development. In future, well-thought-out clinical studies should be made to verify its safety and efficacy. Keywords: lawsone, Lawsonia inermis, henna, antitumor, antioxidant, anti-inflammatory, antimicrobial

Matthew E Sprong,1,2 Heaven Hollender,3 Bob Blankenberger,2 Stuart Rumrill,4 Yu-Sheng Lee,5 Travis Bland,2 Jeremiah Bailey,6 Kenneth Weber,1 James Gilbert,1 Ken Kriz,2 Frank D Buono7 1Edward Hines Jr. VA Medical Center, Hines, IL, USA; 2University of Illinois Springfield, School of Public Management and Policy, Springfield, IL, USA; 3Indiana University - Indianapolis, School of Health & Human Services, Indianapolis, IN, USA; 4Univerity of Illinois Urbana-Champaign, Department of Kinesiology and Community Health, Champaign, IL, USA; 5University of Illinois Springfield, School of Integrated Sciences, Sustainability, and Public Health, Springfield, IL, USA; 6Florida Agricultural and Mechanical University, Department of Sociology and Criminal Justice, Tallahassee, FL, USA; 7Yale School of Medicine, New Haven, CT, USACorrespondence: Matthew E Sprong, Email mspro2@uis.eduIntroduction: Veterans diagnosed with mental health and/or substance use disorders (SUD) often face significant barriers to employment and reintegration into civilian society. In the current study, we investigated whether how the VA healthcare system for mental health and/or SUD treatment predicted program enrollment into vocational rehabilitation, simultaneous mental health and/or SUD treatment while enrolled in vocational rehabilitation predicted employment at discharge, and mental health and/or SUD treatment continues and employment remain 60-days-post-vocational-rehabilitation discharge.Methods: An outcome-based, summative program evaluation design to measure quality assurance of vocational rehabilitation services provided to 402 veteran patients enrolled in a VA healthcare located within the Great Lakes Health Care System – Veterans Integrated Services Network.Results: Multivariable logistic regression analyses showed psychological empowerment (confidence in one’s ability to work or find work) is a significant factor determining whether a veteran is enrolled in the vocational rehabilitation program, prior mental health treatment (yes/no) and frequency of mental health treatment did not predict program enrollment, and frequency of SUD VA system treatment 60 days prior did not predict program enrollment. Other findings showed that simultaneous mental health and/or SUD treatment while enrolled in vocational rehabilitation did not predict employment at discharge, and employment at discharge did not predict continued mental health and/or SUD treatment post-discharge from vocational rehabilitation. However, veterans with both SUD and mental health and continued mental health treatment were less likely to be employed.Conclusion: Utilization of real-world program evaluation data from an actual VHA vocational rehabilitation program enhances the study’s ecological validity, offering practical implications for policymakers and practitioners in the field. The findings support the importance of veterans enrolling in mental health and/or SUD treatment simultaneously while enrolled in vocational rehabilitation services, as integrating vocational rehabilitation with mental health and SUD treatment services can lead to improved vocational and health outcomes for veterans (eg, development of targeted interventions to support veterans’ successful reintegration into the workforce and society).Keywords: substance use disorders, mental health, veterans affairs, health administration, veterans, vocational rehabilitation, treatment access

Yan Guo,1,&ast; Jing-Jing Pan,2,&ast; Wen Zhu,1 Mu-Zi Wang,3 Tian-Yu Liu,4 Xiao-Xin Wang,5 Qian-Qian Wu,1 Yi-Xin Cheng,1 Yi-Sen Qian,1 Xiao-Guang Zhou,1 Yang Yang1 1Department of Neonatology, Children’s Hospital of Nanjing Medical University, Nanjing, People’s Republic of China; 2Department of Neonatology, The First Affiliated Hospital, Nanjing Medical University, Nanjing, People’s Republic of China; 3Department of Neonatology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, People’s Republic of China; 4Department of Neonatology, The Eighth Affiliated Hospital, Sun Yat-Sen University, Shenzhen, People’s Republic of China; 5Department of Pediatrics, Shandong Tumor Hospital, Jinan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiao-Guang Zhou; Yang Yang, Department of Neonatology, Children’s Hospital of Nanjing Medical University, 72 Guangzhou Road, Nanjing, Jiangsu, 210008, People’s Republic of China, Email gzzhouxg@163.com; yy860507@126.comObjective: This prospective study is to explore the role of specific circRNAs in predicting the development of bronchopulmonary dysplasia (BPD).Methods: From July 1, 2021 to December 1, 2021, peripheral blood samples were collected from 62 premature infants with gestational age (GA) ≤ 32 weeks on the 7th, 14th, and 28th day after birth. Then, on the 28th day, the included infants were divided into the BPD group and the non-BPD group according to the definition of BPD. Serum exosomal circRNAs from peripheral blood were identified, sequenced, and compared between the BPD and non-BPD groups at different time points. Specific differentially expressed circRNAs were further verified from another 42 enrolled premature infants (GA ≤ 32 weeks). The classical lung biological markers in serum were also measured simultaneously.Results: Hsa_circ_0001359 in serum exosomes showed continuous differential expression between the BPD group and the non-BPD group on the 7th, 14th, and 28th day. Compared with that, classical lung biological markers like IL-6, IL-33, KL-6, and ET-1 did not exhibit continuous differences. Moreover, the expression of hsa_circ_0001359 on day 7 had a higher predictive value in predicting BPD (area under curve:0.853, 95% CI:0.738– 0.968; adjusted odds ratio:6.033, 95% CI:2.373– 13.326). The calibration curve further showed the mean absolute error = 0.033, mean squared error = 0.00231, and quantile of absolute error = 0.058.Conclusion: Hsa_circ_0001359 in serum exosomes is a promising marker for predicting BPD in preterm infants with gestational age ≤ 32 weeks.Keywords: bronchopulmonary dysplasia, circular RNAs, high-throughput sequencing, preterm infants

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

Chun-Yan Zhang, Yu-Shen Yang, Meng-Qin Pei, Xin-Li Chen, Wei-can Chen, He-Fan He Department of Anesthesiology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian Province, People’s Republic of ChinaCorrespondence: He-Fan He, Department of Anesthesiology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian Province, People’s Republic of China, Tel +86 15860905262, Email 15860905262@163.comAbstract: Postoperative cognitive dysfunction (POCD) is a neurological complication associated with surgery and anesthesia that is commonly observed in older patients, and it can significantly affect patient prognosis and survival. Therefore, predicting and preventing POCD is important. Regional cerebral oxygen saturation (rSO2) reflects cerebral perfusion and oxygenation, and decreased intraoperative cerebral oxygen saturation has been reported to increase the risk of POCD. In this review, we elucidated the important relationship between the decline in rSO2 and risk of POCD in older patients. We also emphasized the importance of monitoring rSO2 during surgery to predict and prevent adverse perioperative cognitive outcomes. The findings reveal that incorporating intraoperative rSO2 monitoring into clinical practice has potential benefits, such as protecting cognitive function, reducing perioperative adverse outcomes, and ultimately improving the overall quality of life of older adults.Keywords: anesthesia, surgery, prognosis, perioperative adverse outcome, cognitive function

Yi Zhang,1,2,&ast; Zhang-Rui Liang,1,3,&ast; Yang Xiao,4 Yi-Shi Li,4 Bin-Jie Fu,1 Zhi-Gang Chu1 1Department of Radiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 2Department of Radiology, Chongqing Jiangjin Second People’s Hospital, Chongqing Jiangjin Cancer Hospital, Chongqing, 402260, People’s Republic of China; 3Department of Radiology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710061, People’s Republic of China; 4Department of Respiratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bin-Jie Fu; Zhi-Gang Chu, Department of Radiology, The First Affiliated Hospital of Chongqing Medical, University, 1&num; Youyi Road, Yuanjiagang, Yuzhong District, Chongqing, 400016, People’s Republic of China, Tel +86 18883851162 ; +86 18723032809, Fax +86 23 68811487, Email binjie_fu@163.com; chuzg0815@163.comPurpose: To explore the computed tomography (CT) features of bronchopneumonia caused by pepper aspiration to improve the diagnosis.Materials and Methods: 28 adult patients diagnosed with obstructive pneumonia caused by pepper aspiration from January 2016 to September 2022 were enrolled. The CT characteristics of bronchial changes and pulmonary lesions caused by pepper were analyzed and summarized.Results: Among 28 patients, the most common symptom was cough (26, 92.9%), followed by expectoration (23, 82.1%). Bronchoscopy revealed that peppers were mainly found in the bronchus of the right lower lobe (n = 18, 64.3%), followed by the bronchus of the left lower lobe (n = 5, 17.9%). In combination with bronchoscopy results, the pepper in the bronchus manifested as circular or V/U-shaped high-density, localized soft tissue, and flocculent opacification in 8 (28.6%), 16 (57.1%), and 3 (10.7%) cases on CT images, respectively. The bronchial wall around the pepper was thickened with localized occlusion (n = 19, 67.9%) and stenosis (n = 9, 32.1%). Regarding adjacent bronchi without peppers, extensive wall thickening with stenosis and/or occlusion was found in 23 (82.1%) cases. Distal pulmonary lesions frequently involved two or three segments (21, 75.0%) and mainly presented as patchy consolidation or atelectasis (24, 85.7%).Conclusion: In combination to a history of eating peppers and clinical symptoms, bronchopneumonia caused by pepper should be highly suspected if U/V-shaped and annular high-density or localized soft tissue density is detected in the bronchi of the lower lobes, accompanied by extensive bronchial wall thickening, stenosis, or occlusion, and consolidation or atelectasis in multiple distal lung segments.Keywords: obstructive pneumonia, foreign body, pepper, computed tomography

Fei-Yi Zhao,1,2,&ast; Gerard A Kennedy,3– 5,&ast; Julia Gilbert,3,&ast; Russell Conduit,4,&ast; Peijie Xu,6 Li-Ping Yue,1 Wen-Jing Zhang,2 Yan-Mei Wang,2 Yuen-Shan Ho,7 Qiang-Qiang Fu,8 Zhen Zheng4 1Department of Nursing, School of International Medical Technology, Shanghai Sanda University, Shanghai, 201209, People’s Republic of China; 2Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200071, People’s Republic of China; 3Institute of Health and Wellbeing, Federation University, Mount Helen, VIC, 3353, Australia; 4School of Health and Biomedical Sciences, RMIT University, Bundoora, VIC, 3083, Australia; 5Institute for Breathing and Sleep, Austin Health, Heidelberg, VIC, 3084, Australia; 6School of Computing Technologies, RMIT University, Melbourne, VIC, 3000, Australia; 7School of Nursing, Faculty of Health and Social Sciences, The Hong Kong Polytechnic University, Hong Kong SAR, People’s Republic of China; 8Yangpu Hospital, School of Medicine, Tongji University, Shanghai, 200090, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuen-Shan Ho, School of Nursing, Faculty of Health and Social Sciences, The Hong Kong Polytechnic University, Hong Kong SAR, People’s Republic of China, Tel +852 2766-6410, Fax +852 2364-9663, Email janice.ys.ho@polyu.edu.hk Qiang-Qiang Fu, Yangpu Hospital, School of Medicine, Tongji University, Shanghai, 200090, People’s Republic of China, Tel + 86 021-6569 0520, Fax + 86 021-6569 6249, Email qiangqiang.fu@tongji.edu.cnBackground: Growing demand exists for high-quality Traditional Chinese Medicine (TCM) care, particularly through Nurse-led TCM clinics (TCM-NLCs). Nurses with extensive experience in TCM departments represent a potential workforce for this healthcare model. This qualitative study aims to investigate the willingness of these candidates to engage in TCM-NLCs, with a specific focus on their main concerns and apprehensions when facing new challenges.Methods: Individual semi-structured face to face interviews were conducted with senior nurses from two TCM hospitals in Shanghai. Each participant had a minimum of three years of work experience in a TCM related department. Conventional qualitative content analysis was utilized.Results: Fourteen participants were interviewed and data saturation was achieved. Nurses exhibited strong interest in practicing in TCM-NLCs. They believed that such innovative TCM nursing service model not only extends nursing role, provides greater empowerment and opportunities for professional development but also meets patients’ diverse healthcare needs, reduces reliance on other healthcare providers such as doctors, and increases hospital revenue. However, challenges such as deficiencies in evidence-based TCM nursing education, the absence of standardized practice guidelines, and limited prescriptive privileges were identified as primary obstacles to engaging in TCM-NLCs practice, potentially undermining the specialization of this advanced nursing practice model.Conclusion: Although the nurses interviewed were highly motivated, they generally lacked confidence to practice independently in TCM-NLCs. A pressing priority is to address their concerns by providing appropriate resources as well as education and policy support to enhance their competency and ensure their practice autonomy, therefore building a more qualified pool of professionals for advanced TCM nursing practice.Keywords: nurse-led clinic, nurse career development, traditional Chinese medicine nursing, qualitative study, advanced nursing practice, specialist nurses

Hye-Rin Kang,1,&ast; So Jeong Kim,2,&ast; Ju Gang Nam,3 Young Sik Park,4 Chang-Hoon Lee4 1Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Veteran Health Service Medical Center, Seoul, 05368, Republic of Korea; 2Division of Pulmonology and Allergy, Hallym University Dongtan Sacred Heart Hospital, Gyeonggi-do, 18450, Republic of Korea; 3Department of Radiology, Seoul National University Hospital, Seoul, 03080, Republic of Korea; 4Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Hospital, Seoul, 03080, Republic of Korea&ast;These authors contributed equally to this workCorrespondence: Chang-Hoon Lee, Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Hospital, 101 Daehak-Ro Jongno-Gu, Seoul, 03080, Republic of Korea, Tel +82-2-2072-4743, Fax +82-2-762-9662, Email kauri670@empal.comIntroduction: Mortality differences in chronic obstructive pulmonary disease (COPD) between nonsmokers and smokers remain unclear. We compared the risk of death associated with smoking and COPD on mortality.Methods: The study included participants aged ≥ 40 years who visited pulmonary clinics and were categorised into COPD or non-COPD and smoker or nonsmoker on the basis of spirometry results and cigarette consumption. Mortality rates were compared between groups using statistical analysis for all-cause mortality, respiratory disease-related mortality, and cardiocerebrovascular disease-related mortality.Results: Among 5811 participants, smokers with COPD had a higher risk of all-cause (adjusted hazard ratio (aHR), 1.69; 95% confidence interval (CI), 1.23– 2.33) and respiratory disease-related mortality (aHR, 2.14; 95% CI, 1.20– 3.79) than nonsmokers with COPD. Non-smokers with and without COPD had comparable risks of all-cause mortality (aHR, 1.39; 95% CI, 0.98– 1.97) and respiratory disease-related mortality (aHR, 1.77; 95% CI, 0.85– 3.68). However, nonsmokers with COPD had a higher risk of cardiocerebrovascular disease-related mortality than nonsmokers without COPD (aHR, 2.25; 95% CI, 1.15– 4.40).Conclusion: The study found that smokers with COPD had higher risks of all-cause mortality and respiratory disease-related mortality compared to nonsmokers with and without COPD. Meanwhile, nonsmokers with COPD showed comparable risks of all-cause and respiratory mortality but had a higher risk of cardiocerebrovascular disease-related mortality compared to nonsmokers without COPD.Keywords: pulmonary disease, chronic obstructive, smokers, nonsmokers, cigarette smoking, comorbidity

Jong Geol Jang,&ast; Young Seok Lee,&ast; Kyung Soo Hong, June Hong Ahn Division of Pulmonology and Allergy, Department of Internal Medicine, Yeungnam University Medical Center, Yeungnam University College of Medicine, Daegu, Republic of Korea&ast;These authors contributed equally to this workCorrespondence: Jong Geol Jang; June Hong Ahn, Division of Pulmonology and Allergy, Department of Internal Medicine, College of Medicine, Yeungnam University and Regional Center for Respiratory Diseases, Yeungnam University Medical Center, 170 Hyeonchung-ro, Namgu, Daegu, 42415, Republic of Korea, Tel +82-53-620-4367 ; +82-53-640-6577, Email jang83@ynu.ac.kr; fireajh@gmail.comPurpose: The use of inhaled bronchodilators is the mainstay of treatment for patients with chronic obstructive pulmonary disease (COPD). Although the soft mist inhaler (SMI) was developed to overcome the disadvantages of pressurized metered dose and drug powder inhalers, misuse during handling has been frequently observed in many studies. However, few studies have focused on SMI misuse among patients with COPD. Thus, we aimed to assess and identify the risk factors associated with SMI misuse among patients with COPD.Patient and Methods: In this prospective, observational, cross-sectional study, we enrolled patients with COPD who were undergoing SMI treatment between January 2018 and March 2020. An advanced nurse practitioner assessed the participants’ handling of the device by using a check list.Results: Among 159 participants, 136 (85.5%) reported inhaler misuse. Duration of COPD and COPD assessment test (CAT) scores were positively associated with inhaler misuse; adherence and education level were negatively associated with inhaler misuse. In the multivariable analysis, a low educational level (less than high school), high CAT score (≥ 10), and short duration of COPD (≤ 2 years) were identified as risk factors for SMI misuse.Conclusion: SMI misuse remains common among patients with COPD. Therefore, clinicians should pay close attention to their patients using SMIs, especially in the early period after the diagnosis of COPD.Keywords: chronic obstructive pulmonary disease, bronchodilators, misuse, soft mist inhaler

En-Yi Lin,1,2 Shao-Xi Hsu,1 Bing-Hua Wu,1 Yu-Chen Deng,1,3 Wei Wuli,1 Yuan-Sheng Li,3 Jui-Hao Lee,3 Shinn-Zong Lin,2,4 Horng-Jyh Harn,2,5 Tzyy-Wen Chiou1 1Department of Life Science and Graduate Institute of Biotechnology, National Dong Hwa University, Hualien, Taiwan; 2Bioinnovation Center, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan; 3Everfront Biotech Inc, Taipei, Taiwan; 4Department of Neurosurgery, Hualien Tzu Chi Hospital, Hualien, Taiwan; 5Department of Pathology, Hualien Tzu Chi Hospital, Hualien, TaiwanCorrespondence: Tzyy-Wen Chiou, Department of Life Science, National Dong Hwa University, No. 1, Sec. 2, Da Hsueh Road, Shou-Feng, Hualien, Taiwan, Tel +886-3-890-3638, Email twchiou@gms.ndhu.edu.tw Horng-Jyh Harn, Department of Pathology, Hualien Tzu Chi Hospital, Hualien, Taiwan, Tel +886-3-856-1825, Email arthewduke@gmail.comPurpose: Exosomes are membrane vesicles secreted by various cells and play a crucial role in intercellular communication. They can be excellent delivery vehicles for oligonucleotide drugs, such as microRNAs, due to their high biocompatibility. MicroRNAs have been shown to be more stable when incorporated into exosomes; however, the lack of targeting and immune evasion is still the obstacle to the use of these microRNA-containing nanocarriers in clinical settings. Our goal was to produce functional exosomes loaded with target ligands, immune evasion ligand, and oligonucleotide drug through genetic engineering in order to achieve more precise medical effects.Methods: To address the problem, we designed engineered exosomes with exogenous cholecystokinin (CCK) or somatostatin (SST) as the targeting ligand to direct the exosomes to the brain, as well as transduced CD47 proteins to reduce the elimination or phagocytosis of the targeted exosomes. MicroRNA-29b-2 was the tested oligonucleotide drug for delivery because our previous research showed that this type of microRNA was capable of reducing presenilin 1 (PSEN1) gene expression and decreasing the β-amyloid accumulation for Alzheimer’s disease (AD) in vitro and in vivo.Results: The engineered exosomes, containing miR29b-2 and expressing SST and CD47, were produced by gene-modified dendritic cells and used in the subsequent experiments. In comparison with CD47-CCK exosomes, CD47-SST exosomes showed a more significant increase in delivery efficiency. In addition, CD47-SST exosomes led to a higher delivery level of exosomes to the brains of nude mice when administered intravenously. Moreover, it was found that the miR29b-2-loaded CD47-SST exosomes could effectively reduce PSEN1 in translational levels, which resulted in an inhibition of beta-amyloid oligomers production both in the cell model and in the 3xTg-AD animal model.Conclusion: Our results demonstrated the feasibility of the designed engineered exosomes. The application of this exosomal nanocarrier platform can be extended to the delivery of other oligonucleotide drugs to specific tissues for the treatment of diseases while evading the immune system.Keywords: oligonucleotide drug, functional nanocarriers, hippocampus, SH-SY5Y, 3xTG-AD

Shi-Hua Yan,1,2 Yong Chen,3 Zhi-Qian Huang,1 Wen-Xi Zhong,1 Xiao-Tian Wang,1 Yang-Can Tang,1 Xu-Yi Zhao,1 Yu-Shan Wu,1 Chun Zhou,4 Wei Zhu,5 Wei Xiao,1,6 Xuan Li,2 Dong-Shu Zhang1,2 1School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, People’s Republic of China; 2Department of Traditional Chinese Medicine, The Tenth affiliated Hospital, Southern Medical University (Dongguan People’s Hospital), Dongguan, Guangdong, 523058, People’s Republic of China; 3Department of Rheumatology and Immunology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, 563000, People’s Republic of China; 4School of Pharmaceutical Sciences; Guangdong Provincial Key Laboratory of Shock and Microcirculation, Southern Medical University, Guangzhou, Guangdong, 510515, People’s Republic of China; 5Guangzhou Center for Disease Control and Prevention, Guangzhou, 510440, People’s Republic of China; 6Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education, Guangdong Pharmaceutical University, Guangzhou, Guangdong, 510006, People’s Republic of ChinaCorrespondence: Dong-Shu Zhang, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, People’s Republic of China, Email nyzds@sina.com Wei Xiao, Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education, Guangdong Pharmaceutical University, Guangzhou, Guangdong, 510006, People’s Republic of China, Email xw7688@smu.edu.cnPurpose: Acupoint autohemotherapy (A-AHT) has been proposed as an alternative and complementary treatment for atopic dermatitis (AD), yet the exact role of its blood component in terms of therapeutic efficacy and mechanism of action is still largely unknown.Methods: This study aimed to evaluate the therapeutic efficacies and action mechanisms of intramuscular injections of autologous whole blood (AWB) and mouse immunoglobulin G (IgG) (autologous or heterologous) at acupoints on 2,4-dinitrochlorobenzene (DNCB)-induced AD mouse models. Serum levels of total immunoglobulin E (IgE), IgG, interleukin-10 (IL-10), and interferon-gamma (IFN-γ) were measured, as well as mRNA expression levels of Forkhead box P3 (FoxP3), IL-10 and IFN-γ in dorsal skin lesions, and IL-10+, IFN-γ+ and FoxP3+CD4+T cells in murine spleen.Results: It showed that repeated acupoint injection of AWB, autologous total IgG (purified from autologous blood in AD mice) or heterologous total IgG (purified from healthy blood in normal mice) effectively reduced the severity of AD symptoms and decreased epidermal and dermal thickness as well as mast cells in skin lesions. Additionally, AWB acupoint injection was found to upregulate FoxP3+, IL-10+ and IFN-γ+ CD4+T cells in murine spleen, suppressing the production of IgE antibodies and increasing that of IgG antibodies in the serum. Furthermore, both AWB and autologous total IgG administrations significantly elevated FoxP3 expression, mRNA levels of IL-10 and IFN-γ in dorsal skin lesions. However, acupoint injection of heterologous total IgG had no effect on regulatory T (Treg) and Th1 cells modulation.Conclusion: These findings suggest that the therapeutic effects of A-AHT on AD are mediated by IgG-induced activation of Treg cells.Keywords: autologous whole blood, acupoint injection, atopic dermatitis, anti-idiotypic immunomodulation, Tregs

You-shu Hong, Lun-fei Liu, Hong-hua Hu Department of Dermatology, the Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University, Yiwu, 322000, People’s Republic of ChinaCorrespondence: Lun-fei Liu; You-shu Hong, Email 2197055@zju.edu.cn; 8021028@zju.edu.cnAbstract: Sporotrichosis is a subacute or chronic infectious disease caused by sporothrix. It is mainly caused by Sporothrix inoculation after accidental skin injury during human labor. The clinical manifestations of sporotrichosis are variable, ranging from nodules, plaques, ulcers, verrucous lesions, and subcutaneous masses. Some reports indicate that sporotrichosis can mimic psoriasis-like lesions. We herein report a case of sporotrichosis mimicking rosacea lesions. In addition, the patient had a history of nasal trauma, and we believe that the patient was inoculated with Sporothrix after the nasal skin was damaged during labor activities. The patient was given itraconazole 200 mg orally daily for 3 months, which effectively resolved the rash.Keywords: sporotrichosis, sporothrix, rosacea, itraconazole, histopathological

Emily Kemp,1 Kate Sutherland,1– 3 Yu Sun Bin,2,3 Andrew SL Chan,1– 3 Hasthi Dissanayake,2,3 Brendon J Yee,2– 5 Kristina Kairaitis,2,3,6,7 John Robert Wheatley,2,3,6,7 Philip de Chazal,2,8 Amanda J Piper,2,4 Peter A Cistulli1– 3 On behalf of the Sydney Sleep Biobank Investigators1Department of Respiratory Medicine, Royal North Shore Hospital, St Leonards, NSW, Australia; 2Charles Perkins Centre, University of Sydney, Camperdown, NSW, Australia; 3Faculty of Medicine and Health, University of Sydney, Camperdown, NSW, Australia; 4Department of Respiratory and Sleep Medicine, Royal Prince Alfred Hospital, Camperdown, NSW, Australia; 5Centre for Integrated Research and Understanding of Sleep (CIRUS), Woolcock Institute of Medical Research, Glebe, NSW, Australia; 6Ludwig Engel Centre for Respiratory Research, Westmead Institute for Medical Research, Westmead, NSW, Australia; 7Department of Respiratory and Sleep Medicine, Westmead Hospital, Westmead, NSW, Australia; 8School of Biomedical Engineering, The University of Sydney, Darlington, NSW, AustraliaCorrespondence: Peter A Cistulli, Department of Respiratory and Sleep Medicine, Level 8A, Royal North Shore Hospital, St Leonards, NSW, 2065, Australia, Tel +61 29463 2934, Fax +61 2 9463 2099, Email peter.cistulli@sydney.edu.auAim: Recent data have identified specific symptom and polysomnographic profiles associated with cardiovascular disease (CVD) in patients with obstructive sleep apnoea (OSA). Our aim was to determine whether these profiles were present at diagnosis of OSA in patients with established CVD and in those with high cardiovascular risk. Participants in the Sydney Sleep Biobank (SSB) database, aged 30– 74 years, self-reported presence of CVD (coronary artery disease, cerebrovascular disease, or heart failure). In those without established CVD, the Framingham Risk Score (FRS) estimated 10-year absolute CVD risk, categorised as “low” (< 6%), “intermediate” (6– 20%), or “high” (> 20%). Groups were compared on symptom and polysomnographic variables.Results: 629 patients (68% male; mean age 54.3 years, SD 11.6; mean BMI 32.3 kg/m2, SD 8.2) were included. CVD was reported in 12.2%. A further 14.3% had a low risk FRS, 38.8% had an intermediate risk FRS, and 34.7% had a high risk FRS. Groups differed with respect to age, sex and BMI. OSA severity increased with established CVD and increasing FRS. The symptom of waking too early was more prevalent in the higher FRS groups (p=0.004). CVD and FRS groups differed on multiple polysomnographic variables; however, none of these differences remained significant after adjusting for age, sex, and BMI.Conclusion: Higher CVD risk was associated with waking too early in patients with OSA. Polysomnographic variations between groups were explained by demographic differences. Further work is required to explore the influence of OSA phenotypic characteristics on susceptibility to CVD.Keywords: obstructive sleep apnoea, cardiovascular disease

Hong-yu Tao, Chun-yan Zhao, Ying Wang, Wei-jin Sheng, Yong-su Zhen Laboratory of Oncology, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of ChinaCorrespondence: Wei-jin Sheng; Yong-su Zhen, Email swj_zjnb@imb.cams.cn; zhenys@imb.pumc.edu.cnAbstract: Telomere is a protective structure located at the end of chromosomes of eukaryotes, involved in maintaining the integrity and stability of the genome. Telomeres play an essential role in cancer progression; accordingly, targeting telomere dynamics emerges as an effective approach for the development of cancer therapeutics. Targeting telomere dynamics may work through multifaceted molecular mechanisms; those include the activation of anti-telomerase immune responses, shortening of telomere lengths, induction of telomere dysfunction and constitution of telomerase-responsive drug release systems. In this review, we summarize a wide variety of telomere dynamics-targeted agents in preclinical studies and clinical trials, and reveal their promising therapeutic potential in cancer therapy. As shown, telomere dynamics-active agents are effective as anti-cancer chemotherapeutics and immunotherapeutics. Notably, these agents may display efficacy against cancer stem cells, reducing cancer stem levels. Furthermore, these agents can be integrated with the capability of tumor-specific drug delivery by the constitution of related nanoparticles, antibody drug conjugates and HSA-based drugs. Keywords: telomere dynamics, telomerase, alternative lengthening of telomeres (ALT), cancer therapy

Su-Hua Yang,1,&ast; Yi-Shan He,2,&ast; Shu-Qin Zheng,3 Xiu-Jun Zhang,3 Hong Dai,1,&ast; Yuan Xue2,3,&ast; 1Department of General Surgery, Changzhou Third People’s Hospital, Changzhou Medical Center, Nanjing Medical University, Changzhou, Jiangsu Province, People’s Republic of China; 2Department of Infectious Diseases, Changzhou Third People’s Hospital, Changzhou Medical Center, Nanjing Medical University, Changzhou, Jiangsu Province, People’s Republic of China; 3Institute of Hepatology, Changzhou Third People’s Hospital, Changzhou, Jiangsu Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hong Dai, Department of General Surgery, Changzhou Third People’s Hospital, Changzhou Medical Center, Nanjing Medical University, Changzhou, Jiangsu Province, People’s Republic of China, Email daihong@njmu.edu.cn Yuan Xue, Institute of Hepatology, Changzhou Third People’s Hospital, Changzhou Medical Center, Nanjing Medical University, No. 300 Lanling North Road, Changzhou, Jiangsu, 213000, People’s Republic of China, Tel +86 519 82009059, Email xueyuan@njmu.edu.cnAim: This study aimed to explore the effects of the triglyceride-glucose (TyG) index on hepatocellular carcinoma (HCC) development in patients with hepatitis B virus (HBV)-related liver cirrhosis (LC).Methods: A total of 242 patients with HBV-related LC were enrolled and followed-up. Logistic regression analysis was performed to investigate risk factors for HCC.Results: The median follow-up time was 37 months (range: 6– 123 months). At the end of the follow-up, 11 (11.3%) patients with compensated cirrhosis (CC) and 45 (31.0%) with decompensated cirrhosis (DC) developed HCC. The TyG index was higher in the HCC group than in the non-HCC group (P=0.05). Univariate analysis showed that age (P< 0.01), DC (P< 0.01), TyG index (P=0.08), albumin (ALB) level (P=0.05), platelet (PLT) count (P< 0.01), and HBV DNA positivity (P< 0.01) were associated with HCC development. Multivariate analysis revealed that age, DC, TyG index, PLT count, and HBV DNA positivity were independent risk factors for HCC development (P=0.01, 0.01, < 0.01, 0.05, and < 0.01, respectively). For patients with DC, multivariate logistic regression analysis revealed that age, TyG index, and HBV DNA positivity were independent risk factors for HCC development (all P< 0.05). A new model encompassing age, DC, TyG, PLT, and positive HBV DNA had optimal predictive accuracy in patients with DC or CC, with a cutoff value of 0.197. The areas under the receiver operating characteristic curves (AUROCs) of the model for predicting HCC development in patients with LC, DC, and CC were 0.778, 0.721, and 0.783, respectively.Conclusion: TyG index was identified as an independent risk factor for HCC development in patients with LC.Keywords: hepatocellular carcinoma, triglyceride-glucose index, insulin resistance, liver cirrhosis, decompensated cirrhosis

Long-Fei Xia,1 Jing-Bo Li,2 Guo-Sheng Tian,2 Wei-Ran Jiang,3 Yao-Shuang Li,1 Chen-Ying Lin,1 Hui-Na Qiu,2 Fan Wu,4 Jun-Jia Wang,5 Chun-Jun Li,2 Jing-Na Lin2 1Tianjin Union Medical Center, Tianjin Medical University, Tianjin, 300070, People’s Republic of China; 2Department of Endocrinology, Health Management Center, Tianjin Union Medical Center, Nankai University Affiliated Hospital, Tianjin, 300121, People’s Republic of China; 3Eastman Institute for Oral Health, University of Rochester Medical Center, Rochester, NY, USA; 4School of Medicine, Nankai University, Tianjin, 300071, People’s Republic of China; 5Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, People’s Republic of ChinaCorrespondence: Jing-Na Lin; Chun-Jun Li, Email 13207628978@163.com; li_chunjun@126.comObjective: To investigate the impact of sarcopenia on the 10-year risk of atherosclerotic cardiovascular disease (ASCVD) among individuals with type 2 diabetes mellitus (T2DM).Methods: This study included the clinical, laboratory, and body composition data of 1491 patients with T2DM who were admitted to the Department of Endocrinology and Metabolism at Tianjin Union Medical Center from July 2018 to July 2023. The China-PAR model was utilized to evaluate cardiovascular disease risk. Associations between ASCVD risk and various clinical parameters were analyzed, and the relationship between body composition parameters and ASCVD risk was assessed using logistic regression.Results: The analysis revealed that T2DM patients with sarcopenia had a higher 10-year ASCVD risk compared to those without sarcopenia, with reduced muscle mass independently predicting an increased risk of cardiovascular disease. This association was significant among female T2DM patients, while male T2DM patients with sarcopenia showed a marginally higher median ASCVD risk compared to their non-sarcopenic counterparts. ASCVD risk inversely correlated with body muscle parameters and positively correlated with fat content parameters. Specifically, height- and weight-adjusted fat mass (FM, FM%, FMI) were identified as risk factors for ASCVD. Conversely, muscle parameters adjusted for weight and fat (ASM%, SMM%, FFM%, ASM/FM, SMM/FM, FMM/FM) were protective against ASCVD risk. These findings highlight the critical role of sarcopenia in influencing cardiovascular disease risk among Chinese patients with T2DM, as predicted by the China-PAR model.Conclusion: This study highlights the importance of sarcopenia in T2DM patients, not only as an indicator of ASCVD risk, but possibly as an independent risk factor in this demographics.Keywords: atherosclerotic cardiovascular disease, ASCVD, type 2 diabetes, T2DM, sarcopenia, fat content, muscle mass

Sruthi Vijendran,1,&ast; Yogish S Kamath,1,&ast; Yash Alok,2 Neetha IR Kuzhuppilly1 1Department of Ophthalmology, Kasturba Medical College Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, India; 2Department of Community Medicine, Kasturba Medical College Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, India&ast;These authors contributed equally to this workCorrespondence: Neetha IR Kuzhuppilly, Department of Ophthalmology, Kasturba Medical College Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India, Tel +91 98861 61979, Fax +91-820-2571934, Email neetha.kir@manipal.eduPurpose: Refractive error is a major cause of visual impairment in children and its early detection can prevent ocular morbidity such as amblyopia and strabismus. Brückner test is a comprehensive test which can be easily administered in children using a direct ophthalmoscope. We aimed to determine refractive error in children by analysis of the red reflex using modified Brückner test.Patients and Methods: This prospective observational study was conducted on 683 undilated eyes of 683 children aged four to 10 years. They were evaluated with a direct ophthalmoscope from one meter in a dimly lit room. The characteristics of the red reflex and crescent obtained were compared with photoscreener refraction value and analyzed.Results: The presence of superior crescent was associated with hypermetropia (Chi square 37.11, p < 0.001, kappa = 0.15) and inferior crescent with myopia (Chi square 157.29, p < 0.001, kappa = 0.477). Superior crescent was 98.4% sensitive in detecting hypermetropia. Hypermetropia greater than +1.5D, was associated with larger superior crescent crossing horizontal midline of pupil (Chi square = 5.29, p = 0.021).Conclusion: The modified Brückner test is useful in detection and quantification of refractive error in children. It is easy, simple, quick and can be employed in the community as a screening test to detect potentially amblyogenic refractive errors.Keywords: visual impairment, pediatric refraction, hypermetropia, myopia, Brückner test, refractive error

Istianah Purnamasari, Yuyun Sri Wahyuni, Hernawati Basir Department of Pharmacy, Faculty of Medicine and Health Science, Universitas Muhammadiyah Makassar, Makassar, South Sulawesi, IndonesiaCorrespondence: Istianah Purnamasari, Department of Pharmacy, Faculty of Medicine and Health Science, Universitas Muhammadiyah Makassar, Makassar, South Sulawesi, Indonesia, Email istianahpurnamasari@unismuh.ac.id

Lizy Sonia Benjamin,1 Eddieson Pasay-an,2 Petelyne Pangket,3 Aidah Sanad Alqarni,4 Ferdinand Gonzales,4 Lailani Sacgaca,5 Dawlat Ahmed Mahmoud,1 Maysa M Mohsen,4 Yahya Showkan Ali Hamdi,6 Sumathi Robert Shanmugam7 1Department of Medical-Surgical Nursing, College of Nursing, King Khalid University, Abha, Saudi Arabia; 2Department of Nursing Administration, College of Nursing, King Khalid University, Abha, Saudi Arabia; 3Department of Medical Surgical Nursing, University of Hail, Hail City, Saudi Arabia; 4Department of Fundamental of Nursing, College of Nursing, King Khalid University, Abha, Saudi Arabia; 5Department of Nursing, Prince Sultan Military College of Health Sciences, Dhahran, Saudi Arabia; 6Nursing Service, Aseer Central Hospital, Aseer, Saudi Arabia; 7Department of Maternity and Pediatric Nursing, Princess Nourah Bint Abdulrahman University, Riyadh, Saudi ArabiaCorrespondence: Sumathi Robert Shanmugam, Department of Maternity and Pediatric Nursing, Princess Nourah Bint Abdulrahman University, Riyadh, Saudi Arabia, Email srshanmugm@pnu.edu.saIntroduction: Nursing students frequently encounter the challenge of balancing their studies with the demanding requirements of hands-on practice and this can greatly affect their mental wellbeing. This study aimed to investigate the impact of sleep and psychological well-being on the academic and clinical performance of nursing students in Saudi Arabia.Methods: This study used a cross-sectional approach with 218 student nurses selected through convenience sampling from King Khalid University, Abha, Saudi Arabia. The sleep quality, psychological wellbeing, academic performance and clinical performance questionnaires were adopted to measure the variables. The Google Forms survey was used to gather the data, which were collected in August through October 2023. t-test and chi-square were used to analyze the data.Results: The sleep quality was higher with good/very good performers (p < 0.001). There was a significant difference with academic performance on positive relations (p < 0.007) and purpose in life (p < 0.004). Additionally, there was a significant difference in autonomy (p < 0.01), environmental mastery (p < 0.026), positive relations (p < 0.001), and purpose in life (p < 0.001) with clinical performance. Among students with good academic performance, those who were older than 25 years of age (p < 0.043) and level 3 students (p < 0.001) were found to have a significant correlation. Furthermore, those who were 25 years of age (p < 0.012) and level 3 students (p < 0.001) were also found to have a significant correlation with clinical performance.Conclusion: The sleep quality, positive relations, purpose in life, autonomy, and environmental mastery are all important factors for academic and clinical success. Moreover, older students and level 3 students may be more likely to have the skills and knowledge necessary to succeed in these areas. Further research exploring factors influencing academic and clinical success must be conducted.Keywords: sleep quality, psychological well-being, academic performance, clinical performance, nursing students, Saudi Arabia

Hsin-Ying Lin,1 Chung-Han Ho,2,3 Yu-Shiuan Lin,1 Shu-Chun Kuo,1,4 Yi-Chen Chen,2 Yung-Jen Cheng5 1Department of Ophthalmology, Chi Mei Medical Center, Tainan, Taiwan; 2Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan; 3Department of Information Management, Southern Taiwan University of Science and Technology, Tainan, Taiwan; 4Department of Optometry, Chung Hwa University of Medical Technology, Tainan, Taiwan; 5Department of Radiation Oncology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, TaiwanCorrespondence: Yung-Jen Cheng, Department of Radiation Oncology, National Cheng Kung University Hospital, No. 138, Sheng Li Road, Tainan, 704, Taiwan, Email n052337@mail.hosp.ncku.edu.twPurpose: Continuous advancements in medical diagnostic technology and the growing availability of resources suggest a potential for fluctuations in the incidence rate of retinoblastoma (Rb). This study aimed to analyze incidence data of Rb patients in Taiwan from 1999 to 2018, utilizing the nationwide Taiwan Cancer Registry (TCR) database. Additionally, we investigated the treatment modalities used for these Rb patients and compared them with those observed in other countries.Patients and Methods: We conducted a retrospective cohort study utilizing data from the TCR database. The study cohort comprised individuals who were newly diagnosed with Rb between 1999 and 2018. The incidence of Rb was calculated as the number of patients with Rb per million live births, both for the entire population and for different gender groups and time periods. The trends in Rb incidence from 1999 to 2018 across various age groups and sexes were presented with the linear trend test.Results: From 1999 to 2018, a total of 248 cases of Rb were identified. The overall incidence rate over this 20-year period was 60.20 cases per million live births, corresponding to 1 case per 16,611 live births. Incidence rates for each 5-year period between 1999 and 2018 exhibited no significant differences. The study cohort was predominantly male, with 134 cases (54.03%) being males and 114 cases (45.97%) being females, resulting in an overall male-to-female sex ratio of 1.18. Females had lower relative risk than males (RR: 0.92, 95% CI: 0.72– 1.19). Primary surgical intervention was the preferred treatment modality for over 75% of the cases.Conclusion: This retrospective epidemiology study, using TCR from 1999 to 2018, indicated that no discernible trend of retinoblastoma incidence in Taiwan. Nevertheless, continuous monitoring of incidence rates and exploration of treatment strategies for retinoblastoma within the Taiwanese population are important to address potential changes in developing medical practices.Keywords: retinoblastoma, incidence rate, treatment outcome, Taiwan cancer registry

Li-Wei Zhang,1– 3,&ast; Man-Qing Luo,4,&ast; Ji-Lang Zeng,1– 3,&ast; Zhe-Bin You,2,3,5 Li-Chuan Chen,1– 3 Jun-Han Chen,1– 3 Kai-Yang Lin,1– 3 Yan-Song Guo1– 3 1Department of Cardiology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou, People’s Republic of China; 2Fujian Provincial Key Laboratory of Cardiovascular Disease, Fujian Provincial Center for Geriatrics, Fujian Provincial Clinical Research Center for Severe Acute Cardiovascular Diseases, Fuzhou, People’s Republic of China; 3Fujian Heart Failure Center Alliance, Fuzhou, People’s Republic of China; 4Department of Cardiology, Fuwai Hospital, National Clinical Research Center for Cardiovascular Diseases, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 5Department of Geriatric Medicine, Fujian Key Laboratory of Geriatrics, Fujian Provincial Hospital, Fujian Provincial Center for Geriatrics, Fujian Medical University, Fuzhou, Fujian, 350001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Kai-Yang Lin; Yan-Song Guo, Tel +86-13559355708 ; +86-059188217410, Email lky7411@sina.com; ysguo1234@126.comPurpose: The estimated glomerular filtration rate (eGFR) based on creatinine is crucial for the risk assessment of contrast-associated acute kidney injury (CA-AKI). In recent, the difference between cystatin C-based eGFR (eGFRcys) and creatinine-based eGFR (eGFRcr) has been widely documented. We aimed to explore whether intraindividual differences between eGFRcys and eGFRcr had potential value for CA-AKI risk assessment in patients undergoing elective percutaneous coronary intervention (PCI).Patients and Methods: From January 2012 to December 2018, we retrospectively observed 5049 patients receiving elective PCI. To determine eGFR, serum creatinine and cystatin C levels were measured. CA-AKI was defined as serum creatinine being increased ≥ 50% or 0.3 mg/dL within 48 h after contrast agents exposure. Chronic kidney disease (CKD) was defined as the eGFR < 60 mL/min/1.73 m2.Results: Approximately half of the participants (2479, 49.1%) had a baseline eGFRdiff (eGFRcys-eGFRcr) between − 15 and 15 mL/min/1.73 m2. Restricted cubic splines analysis revealed a nonlinear relationship between eGFRdiff and CA-AKI. Multivariable logistic regression analysis indicated that compared with the reference group (− 15 to 15 mL/min/1.73 m2), the negative-eGFRdiff group (less than − 15 mL/min/1.73 m2) had a higher risk of CA-AKI (OR, 3.44; 95% CI, 2.57– 4.64). Furthermore, patients were divided into four groups based on CKD identified by eGFRcys or eGFRcr. Multivariable logistic analysis revealed that patients with either CKDcys (OR, 2.94; 95% CI, 2.19– 3.95, P < 0.001) or CKDcr (OR, 2.44; 95% CI, 1.19– 4.63, P < 0.001) had an elevated risk of CA-AKI compared to those without CKDcys and CKDcr.Conclusion: There are frequent intraindividual differences between eGFRcys and eGFRcr, and these differences can be used to forecast the risk of CA-AKI.Keywords: estimated glomerular filtration rate, contrast-associated acute kidney injury, cystatin C, percutaneous coronary intervention

Yun Seob Jung,1 Byung Hak Jin,2 Ju Eun Choi,2 Min Soo Park,2 Young-Woo Kim,3 Hyung Won Kang,4 Sunyoung Cho,5 Choon Ok Kim2 1Department of Pharmacology, Yonsei University College of Medicine, Seoul, Korea; 2Department of Clinical Pharmacology, Severance Hospital, Yonsei University Health System, Seoul, Korea; 3School of Korean Medicine, Dongguk University, Gyeongju, Korea; 4College of Korean Medicine, Wonkwang University, Iksan, Korea; 5IntegroMediLab Co., Ltd, Seoul, KoreaCorrespondence: Choon Ok Kim, Department of Clinical Pharmacology, Severance Hospital, Yonsei University Health System, Seoul, Korea, Tel +82-2-2228-0455, Fax +82-2-2227-7890, Email delivery98@yuhs.acPurpose: Herbal medicines are occasionally used in combination with conventional antidepressants to mitigate various depression-associated symptoms. However, there is limited information on herb–antidepressant interactions. In this study, we investigated the pharmacokinetic (PK) effects of four herbal medicines (Gami-soyosan, Banhasasim-tang, Ojeok-san, and Bojungikgi-tang) on escitalopram, a commonly used antidepressant.Patients and Methods: In this open-label, fixed-sequence, three-period, crossover study, 18 participants were enrolled and divided into two groups. Each group received a 10 mg oral dose of escitalopram in period 1. Participants took escitalopram once daily and their assigned herbal medicines thrice a day for 7 d in periods 2 (group 1: Gami-soyosan, group 2: Ojeok-san) and 3 (group 1: Banhasasim-tang; group 2: Bojungikgi-tang). The primary endpoints were Cmax,ss and AUCtau,ss of escitalopram. Cmax,ss and AUCtau,ss in period 1 were obtained using nonparametric superposition from single-dose data. The PK endpoints were classified according to the CYP2C19 phenotype.Results: Of 18 participants, 16 completed the study. Systemic exposure to escitalopram resulted in a minor increase in the presence of each herbal medicine. The geometric mean ratios (GMRs, combination with herbal medicines/escitalopram monotherapy) and their 90% confidence intervals (CIs) for Cmax,ss and AUCtau,ss were as follows: Gamisoyosan– 1.1454 (0.9201, 1.4258) and 1.0749 (0.8084, 1.4291), Banhasasim-tang– 1.0470 (0.7779, 1.4092) and 1.0465 (0.7035, 1.5568), Ojeok-san– 1.1204 (0.8744, 1.4357) and 1.1267 (0.8466, 1.4996), and Bojungikgi-tang– 1.1264 (0.8594, 1.4762) and 1.1400 (0.8515, 1.5261), respectively. Furthermore, no significant differences in the GMRs of Cmax,ss and AUCtau,ss were observed across different CYP2C19 phenotypes in any of the groups.Conclusion: The co-administration of escitalopram with Gami-soyosan, Banhasasim-tang, Ojeok-san, or Bojungikgi-tang did not exert significant PK effects on escitalopram. These findings provide valuable insights into the safe use of herbal medicines along with escitalopram.Keywords: CYP2C19 phenotype, herb–drug interaction, antidepressant, geometric mean ratio

Iis Inayati Rakhmat,1– 3 Gaga Irawan Nugraha,3,4 Eko Fuji Ariyanto,3,4 Yuni Susanti Pratiwi,3,4 Desy Linasari,5 Siti Nur Fatimah,3,6 Mohammad Ghozali,3,4 Mas Rizky AA Syamsunarno,3,4 Mohammad Rizki Akbar,3,7 Tri Hanggono Achmad3,4 1Doctoral Study Program Faculty of Medicine, Universitas Padjadjaran, Bandung, West Java, Indonesia; 2Department of Biochemistry, Faculty of Medicine, Universitas Jenderal Achmad Yani, Cimahi, West Java, Indonesia; 3Cardiometabolic Working Group Study, Faculty of Medicine, Universitas Padjadjaran, Bandung, West Java, Indonesia; 4Department of Biomedical Sciences, Faculty of Medicine, Universitas Padjadjaran, Bandung, West Java, Indonesia; 5Department of Community Medicine, Faculty of Medicine, Universitas Jenderal Achmad Yani, Cimahi, West Java, Indonesia; 6Department of Public Health, Faculty of Medicine, Universitas Padjadjaran, Bandung, West Java, Indonesia; 7Department of Cardiology and Vascular Medicine, Faculty of Medicine, Universitas Padjadjaran-Hasan Sadikin General Hospital, Bandung, West Java, IndonesiaCorrespondence: Gaga Irawan Nugraha, Department of Biomedical Sciences, Faculty of Medicine, Universitas Padjadjaran, Eycmann 38, Bandung, West Java, 40161, Indonesia, Tel/Fax +6222 2032170, Email gaga@unpad.ac.idBackground: Metabolic syndrome (MetS) is a risk factor for cardiovascular disease and is linked to obesity. Subjects with MetS who have normo-weight potentially show higher mortality and morbidity.Purpose: This study aims to reveal the critical essential metabolic parameters associated with endothelial dysfunction in MetS subjects with normo-weight compared to obese.Patients and Methods: The study was designed using a case–control approach. Ninety-nine MetS subjects (34 Normo-weight and 65 obese) from the urban population were enrolled in this study. The components of MetS are based on NCEP/ATP III criteria. Asymmetric dimethylarginine (ADMA) and vascular cell adhesion molecule 1 (VCAM-1) as markers for endothelial dysfunction were measured in both groups.Results: Fasting blood glucose (FBG) levels were higher in the normo-weight group (143.38 ± 79.8 mg/dL) compared to the obese group (120.89 ± 46.5 mg/dL). High-density lipoprotein cholesterol (HDL-c) levels in the normo-weight group were lower (42.82 ± 10.1 mg/dL) compared to obesity (45.74 ± 9.3 mg/dL), while triacylglycerol (TAG) levels were higher in the obese (197.25 ± 110.5 mg/dL) compared to the normo-weight group (167.03 ± 98.4 mg/dL), although the differences were statistically not significant (all p > 0.05). The difference between ADMA and VCAM-1 levels was statistically not significant in both groups. Correlation between MetS components with endothelial dysfunction parameters shows that metabolic parameters correlate strongly. Interestingly, a stronger correlation between FBG and ADMA was observed in normo-weight (r = 0.519) compared to obese groups (r = 0.445). In addition, TAG consistently shows a significant correlation with ADMA and VCAM-1 in normo-weight groups.Conclusion: Metabolic parameters, especially FBG and TAG, correlate strongly with endothelial dysfunction parameters in normo-weight subjects with metabolic syndrome.Keywords: ADMA, normal-weight metabolically unhealthy, VCAM-1

Rasheed K Ibdah,1 Khaled J Zaitoun,2 Rana B Altawalbeh,2 Saad H Tayyem,2 Ulla A Nazzal,2 Sukaina I Rawashdeh,1 Yousef S Khader,3 Abdel-Hameed W Al-Mistarehi,4 Basheer Y Khassawneh5 1Division of Cardiology, Department of Internal Medicine, Faculty of Medicine, Jordan University of Science and Technology, Irbid, 22110, Jordan; 2Faculty of Medicine, Jordan University of Science and Technology, Irbid, 22110, Jordan; 3Department of Community Medicine, Public Health and Family Medicine, Faculty of Medicine, Jordan University of Science and Technology, Irbid, 22110, Jordan; 4School of Medicine, Johns Hopkins Hospital, Baltimore, MD, 21287, USA; 5Department of Internal Medicine, Jordan University of Science and Technology, Irbid, 22110, JordanCorrespondence: Khaled J Zaitoun, Faculty of Medicine, Jordan University of Science and Technology, Irbid, 22110, Jordan, Tel +962798652961, Email kjzaitoun20@med.just.eud.joBackground: Obstructive Sleep Apnea (OSA) is a common respiratory disorder that causes intermittent upper airway collapse during sleep and can lead to various acute cardiovascular complications. Atrial Fibrillation (AF) is the most common sustained cardiac arrhythmia and is associated with an increased risk of cardiovascular hospitalization and all-cause mortality. Our study aimed to investigate the prevalence of individuals with AF and those considered at high risk for OSA.Methods: A cross-sectional study was conducted with a population comprising patients who had visited KAUH cardiology clinics between 2017– 2019; subjects were categorized into AF patients and general cardiology patients. Patients were surveyed for OSA using the Berlin Questionnaire to assess the degree of OSA symptoms and to classify patients into high- or low-risk groups based on their responses.Results: Of the 656 patients, 545 met our inclusion criteria, of whom 192 were diagnosed with AF. Comparable demographic characteristics were observed between the AF and non-AF groups, barring higher rates of obesity (p=0.001) and smoking (p=0.042) in the AF group. The prevalence of high-risk OSA was significantly higher in AF patients (68.2%) compared to non-AF patients (29.4%), with an adjusted odds ratio of 2.473 times (95% CI: 1.434 − 4.266, p=0.001) greater for AF. The age, gender, and BMI categories did not differ significantly between the two groups. Binary logistic regression revealed significant associations between OSA and risk factors such as asthma (OR=4.408, 95% CI: 2.634– 7.376, p=0.001).Conclusion: These results serve to display a statistically significant increase in high-risk OSA in existing AF patients, irrespective of the presence of conventional OSA risk factors; this could imply a more immediate and direct relationship between both diseases and calls to include routine screening for OSA in patients diagnosed, newly or otherwise, with AF.Keywords: Berlin questionnaire, polysomnography, cross sectional study

Juyoung Khwarg,1 Soyoung Lee,1,2 In-Jin Jang,1 Won-Ho Kang,3 Hye Jung Lee,4 Kyu Yeon Kim,4 Ki-Sun Jeong,4 Chongho Won,4 Youn Woong Choi,5 Dae Chul Ha,5 RaeHoon Jung,5 Min-Gu Han,5 Won Tae Jung,6 Kyu-Yeol Nam,6 YeSeul Kim,6 Kyung-Sang Yu,1 Jaeseong Oh1,7 1Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea; 2Integrated Major in Innovative Medical Science, Seoul National University Graduate School, Seoul, Republic of Korea; 3R&D Center, Korea United Pharm. Inc., Seoul, Republic of Korea; 4Caleb Multilab, Inc., Seoul, Republic of Korea; 5R&D Center, Korea United Pharm.Inc., Sejong, Republic of Korea; 6Global R&D, Korea United Pharm. Inc., Seoul, Republic of Korea; 7Department of Pharmacology, Jeju National University College of Medicine, Jeju, Republic of KoreaCorrespondence: Jaeseong Oh, Department of Pharmacology, Jeju National University College of Medicine, 15, Aran 13-gil, Jeju-si, Jeju-do, 63241, Republic of Korea, Email jaeseong5@jejunu.ac.krPurpose: Statins are widely used in combination with omega-3 fatty acids for the treatment of patients with dyslipidemia. The aim of this study was to compare the pharmacokinetic (PK) profiles of atorvastatin and omega-3-acid ethyl esters between fixed-dose combination (FDC) and loose combination in healthy subjects.Methods: A randomized, open-label, single-dose, 2-sequence, 2-treatment, 4-period replicated crossover study was performed. Subjects were randomly assigned to one of the 2 sequences and alternately received four FDC soft capsules of atorvastatin/omega-3-acid ethyl esters (10/1000 mg) or a loose combination of atorvastatin tablets (10 mg × 4) and omega-3-acid ethyl ester soft capsules (1000 mg× 4) for four periods, each period accompanied by a high-fat meal. Serial blood samples were collected for PK analysis of atorvastatin, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). PK parameters were calculated by a non-compartmental analysis. The geometric mean ratio (GMR) and its 90% confidence interval (CI) of the FDC to the loose combination were calculated to compare PK parameters.Results: A total of 43 subjects completed the study as planned. The GMR (90% CI) of FDC to loose combination for maximum concentration (Cmax) and area under the time-concentration curve from zero to the last measurable point (AUClast) were 1.0931 (1.0054– 1.1883) and 0.9885 (0.9588– 1.0192) for atorvastatin, 0.9607 (0.9068– 1.0178) and 0.9770 (0.9239– 1.0331) for EPA, and 0.9961 (0.9127– 1.0871) and 0.9634 (0.8830– 1.0512) for DHA, respectively. The intra-subject variability for Cmax and AUClast of DHA was 30.8% and 37.5%, respectively, showing high variability. Both the FDC and the loose combination were safe and well tolerated.Conclusion: The FDC of atorvastatin and omega-3-acid ethyl esters showed comparable PK characteristics to the corresponding loose combination, offering a convenient therapeutic option for the treatment of dyslipidemia. Keywords: pharmacokinetics, cardiovascular disease

Anna Basok,1 Elvira Romanjuk,1 Boris Rogachev,1 Yosef Shmuel Haviv,1 Ruth Shaco Halevy,2 Marina Vorobiov1 1Nephrology Department, Ben Gurion University Medical Center, Beer Sheva, Israel; 2Pathology Department, Ben Gurion University Medical Center, Beer Sheva, IsraelCorrespondence: Anna Basok, Nephrology Department, Ben Gurion University Medical Center, Uchmanit 13, Beer-Sheva, 8485283, Israel, Email basok@bgu.ac.ilAbstract: We described an extraordinary case of invasive aspergillosis (IA) after commercial kidney transplantation. Massive infestation by angiotrophic fungi with morphological features of Aspergillus caused fungal arteritis of renal blood vessels with detachment of the kidney graft from the iliac artery with ipsilateral leg ischemia, necessitating graft removal and recurrent vascular surgery to restore the blood supply to the leg. A literature review comprising various features of invasive aspergillosis and ethical aspects of commercial kidney transplantations is elucidated in this paper.Keywords: invasive aspergillosis, IA, transplant tourism, TT, galactomannan

Jia-Jia Hu,&ast; Yu-Sen Lin,&ast; Jing-Cong Zhang, Yan-Hong Wang Medical Intensive Care Unit, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yan-Hong Wang, Email wangyh28@mail.sysu.edu.cnBackground: In the context of progressively uncontrolled drug resistance of bacteria, the difficulty of treating Klebsiella (KP)-induced pneumonia increases. Searching for drugs other than antibiotics has become an urgent task. Vitamin D (VD), meanwhile, is shown to be capable of treating pneumonia. Therefore, we aimed to explore the effects and mechanisms of VD on KP-infected rats.Methods: Male Sprague Dawley rats were divided into the Control, VD, KP and KP+VD groups. A rat pneumonia model was induced using an intratracheal drop of 2.4× 108 CFU/mL KP. VD treatment was performed by gavage using 5 μg/kg. Subsequently, the survival of the rats was recorded, and the lungs, bronchoalveolar lavage fluid, and feces of the rats were collected 4 days after KP infection. Next, the water content of lung tissues was measured by the wet-to-dry weight ratio. Histopathological changes of lung tissues were observed by Hematoxylin and Eosin staining and the levels of inflammatory factors (TNF-α, IL-1β, MCP1) were detected using ELISA. The feces of rats in each group were also subjected to 16S rDNA gene analysis of intestinal microbiota.Results: Compared with the KP group, the KP+VD group showed a significant increase in survival, a significant decrease in water content and bacterial counts in the lungs, a significant improvement in lung injury, and a significant decline in the levels of TNF-α, IL-1β, and MCP1. According to the 16S rDNA sequencing, VD altered the structure of the intestinal bacterial community in the KP-infected rats and made the species richness similar to that of healthy rats. Additionally, the abundance of Anaeroglobus was significantly increased in the KP+VD group.Conclusion: VD modulates intestinal microbiota to increase the resistance of rats to pneumonia caused by Klebsiella infection.Keywords: severe pneumonia, Klebsiella, intestinal microbiota, vitamin D