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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

Background: Adolescent substance abuse is a growing public health concern. Adolescence is the starting point for adult substance misuse. The likelihood of acquiring dependence in adulthood is significantly decreased when substance use is not initiated during adolescence. The purpose of this study was to estimate the prevalence of substance use among teenagers, as well as to determine the age of initiation and identify the factors that are linked to substance use. Methods: A community-based cross-sectional study was conducted in an urban community in Vellore by a tertiary care teaching hospital. A structured questionnaire was administered by the principal investigator to all adolescent boys aged between 10 and 19 years residing in that area for the past year who gave informed consent/assent to assess the prevalence of substance use among teenagers. Results: The total number of adolescent boys enrolled in the study was 266. The mean (standard deviation [SD]) age of the participants was 16.14 (2.2) years, with a median age of 16 years. Out of the 266 adolescent boys, 33.8% are currently using substances and 15% were past users. The common substance used was smoking tobacco (30%), followed by alcohol consumption (29%). The minimum age of initiation of smoking tobacco and ganja use was 9 and 7 years, respectively. Significant predictors of substance usage included the participant’s educational background and the substance use of their parents. Conclusion: According to this community-based study’s findings, smoking tobacco was the most frequently used substance by teenagers, with a higher prevalence of current substance use. Substance misuse in the family was substantially associated with increased drug usage among teenagers. Notwithstanding having an adequate comprehension of the negative results of substance utilisation, teenagers develop this habit, which they might carry into adulthood. It is therefore necessary to establish comprehensive prevention and control programs in schools and the community that target teenagers and their parents.

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

Background: Physical exercise (PE) can regulate inflammation, cardiovascular health, sarcopenia, anaemia, and bone health in the chronic kidney disease (CKD) population. Experimental and clinical studies both help us better understand the mechanisms that underlie the beneficial effects of the exercise, especially in renal anaemia and CKD-mineral bone disorders (CKD-MBDs). Here, we summarize this evidence, exploring the biological pathways involved, locally released substances, and crosstalk between tissues, but also the shortcomings of current knowledge. Summary: Anaemia: Both in healthy and CKD subjects, PE may mimic hypoxia, inhibiting PHDs; so hydroxylate HIF-α subunits may be translocated into the nucleus, resulting in dimerization of HIF-1α and HIF-1β, recruitment of p300 and CBP, and ultimately, binding to HREs at target genes to cause activation. However, in CKD subjects acute PE causes higher levels of lactate, leading to iron restriction by upregulating hepatic hepcidin expression, while chronic PE allows an increased lactate clearance and HIF-α and VEGFα levels, stimulating both erythropoiesis and angiogenesis. CKD-MBD: PE may improve bone health decreasing bone resorption and increasing bone formation throughout at least three main pathways: (a) increasing osteoprotegerin and decreasing RANKL system; (b) decreasing cytokine levels; and (c) stimulating production of myokines and adipokines. Key Messages: Future research needs to be defined to develop evidence-based exercise guidance to provide optimal benefit for CKD using exercise interventions as adjuvant therapy for CKD-related complications such as anaemia and CKD-MBD.

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

Abstract Background Peritoneal metastases frequently occur in epithelial ovarian cancer (EOC), resulting in poor prognosis and survival rates. Tumor-associated-macrophages (TAMs) massively infiltrate into ascites spheroids and are multi-polarized as protumoral M2-like phenotype, orchestrating the immunosuppression and promoting tumor progression. However, the impact of omental conditioned medium/ascites (OCM/AS) on TAM polarization and its function in tumor progression remains elusive. Methods The distribution and polarization of TAMs in primary and omental metastatic EOC patients’ tumors and ascites were examined by m-IHC, FACS analysis, and immunofluorescence. QPCR, immunofluorescence, FACS analysis, lipid staining assay, ROS assay, and Seahorse real-time cell metabolic assay characterized TAMs as being polarized in the ascites microenvironment. The oncogenic role of TAMs in tumor cells was demonstrated by co-cultured migration/invasion, proliferation, and spheroid formation assays. Mechanistic studies of the regulations of TAM polarization were performed by using RNA-Seq, GTPase pull-down, G-LISA activation assays, and other biochemical assays. A Yap1 macrophages (MФs) conditional knockout (cKO) mouse model demonstrated the roles of YAP1 in TAM polarization status and its pro-metastatic function. Finally, the anti-metastatic potential of targeting TAMs through restoring YAP1 by pharmacological agonist XMU MP1 was demonstrated in vitro and in vivo. Results Abundant polyunsaturated fatty acids (PUFAs) in OCM/AS suppressed RhoA-GTPase activities, which, in turn, downregulated nuclear YAP1 in MФs, leading to increased protumoral TAM polarization accompanied by elevated OXPHOS metabolism. Abolishment of YAP1 in MФs further confirmed that a higher M2/M1 ratio of TAM polarization could alleviate CD8+ T cell infiltration and cytotoxicity in vivo. Consistently, the loss of YAP1 has been observed in EOC metastatic tissues, suggesting its clinical relevance. On the contrary, restoration of YAP1 expression by pharmaceutical inhibition of MST1/2 induced conversion of M2-to-M1-like polarized MФs, elevating the infiltration of CD8+ T cells and attenuating tumor growth. Conclusion This study revealed that PUFAs-enriched OCM/AS of EOC promotes M2-like TAM polarization through RhoA-YAP1 inhibition, where YAP1 downregulation is required for accelerating protumoral M2-like TAM polarization, thereby causing immunosuppression and enhancing tumor progression. Conversion of M2-to-M1-like polarized MФs through Yap1 activation inhibits tumor progression and contributes to developing potential TAMs-targeted immunotherapies in combating EOC peritoneal metastases.

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

Background: Perinatal mortality rate is very high in North Eastern Nigeria mainly due to a large number of still births. The causes and factors related need to be identified so as to proffer solutions with a view to improving obstetric practice and perinatal survival. Objectives: To identify the causes and factors related to stillbirths in Dukku Local Government Area of Gombe state. Methodology: A prospective study that was both hospital and community based, in which parturients were recruited in their last trimester and followed up till delivery. The fetal outcome was recorded and still birth rate calculated. Results: Five hundred and two parturient mothers were recruited. They delivered a total of 520 babies, amongst whom were eighteen sets of twins; five hundred of these were live births. There were 20 still births, giving a stillbirth rate of 38.5/1000. Causes of stillbirth include unbooked and early pregnanacies as well as deliveries unattended to by trained health personnel. Conclusion: Lack of antenatal Care, home delivery and teenage pregnancy were important factors contributing to high still birth rate in Dukku LGA of Gombe State.

Background: Childhood obesity is a complex condition resulting from an inter play of genetic predisposition, environmental factors and socio-economic status. The prevalence has been increasing all over the world, probably due to economic transition and rapid urbanization as well as globalisation. This relationship should be well established for Improved Health Planning in Gombe State and Nigeria. Objectives: To establish the prevalence of Childhood Obesity and it`s relationship with the Socio-Economic Status of Parents and guardians. Methodology:Anthropometric measurements of children and adolescents in both public and private schools from primary to secondary levels were taken and their BMI calculated. The socioeconomic statuses of their parents, as well as the lifestyle of the children were assessed. Results: Overweight and obesity were more prevalent in children whose parents belonged to the middle and upper socio-economic class; these children had televisions and computers in their rooms and were driven to school Conclusion: The picture is completely the reverse of what is obtainable in the developed and industrialised nations where overweight and obesity are more prevalent in children of the lower socio-economic class. Authors` contribution: The first author is the lead researcher and is a staff of Federal Teaching Hospital Gombe while the second author, a staff of University of Maiduguri is the first supervisor who gave guidelines and made corrections. The second and the third authors are members of staff of the University of Melbourne in Australia; the third author provided a template on which the questionaire was based while the fourth author who is also the second supervisor, is a tutor of the European Society for Pediatric Endocrinology; she facilitated the acceptance of the proposal and the sponsorship for the research. The research was carried out in Gombe, the capital of Gombe State in North Eastern Nigeria

Objective: Discharge Against Medical Advice (DAMA) is a major problem in health care delivery in Nigeria. Children, especially neonates, who can neither understand nor contribute to decision concerning their own health, are the most commonly affected. The objective of this study was to identify the reasons proffered for DAMA in neonates and persons involved in making such decisions. Materials and methods: A descriptive study of consecutive neonates who were discharged against medical advice from the Special Care Baby Unit at Federal Teaching Hospital (FTH), Gombe from January 2016 to December 2017. Patients’ Biodata, Diagnosis, Socio demographic characteristics of both parents, relationship of the person signing DAMA with the patient and the reason (s) for signing DAMA were recorded in a proforma. Results: Out of the 1,110 neonates admitted during the study period, 103 were discharged against medical advice giving a DAMA rate of 9.3%: Male 50(48.5%) and Female 53(51.5%). Majority 98(95.1%) of DAMA cases were signed by the father and the main reason stated for DAMA was financial constraint 62(60.2%). Conclusion: Financial constraint was the main stated reason for DAMA and the father was the signatory to DAMA in majority of newborn in FTH, Gombe.

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

This article aims to answer why the tiger dance in Kerinci Regency, Jambi Province, has not developed widely despite being preserved for more than 30 years and becoming a popular dance in Jambi Province. Qualitative research methods were used to carry out this study. In-depth interviews and uninvolved observation of the artists’ activities were used to collect the data. The analysis focused on the development of the tiger dance and the preservation discourse created by the artists and residents of Pulau Tengah Village. This study discovered that the extinct Ngagoah Imo ritual was transformed into the tiger dance. The “tiger man” myth, which the Kerinci people still hold dear, forms the basis of the tiger ritual and dance. Initially, the tiger dance was not sacred but was made sacred due to encouragement from various parties. Because of its uniqueness, the tiger dance soon became popular in Jambi and became a cure for the longing of the Kerinci people for the Ngagoah Imo ritual. Realizing the potential of tiger dance as an economic resource and as Kerinci’s regional identity, the artists then created a discourse of property rights over tiger dance. They prohibited other villagers from learning or imitating it. This discourse is slowly making tiger dance endangered because it is only controlled by a small group of artists. Such a discourse on cultural property rights needs to be straightened out. Apart from being contrary to the dynamic character of Malay culture, it is also contrary to various principles of cultural preservation.

Introduction: Adult T-cell leukemia/lymphoma (ATLL) is a mature, peripheral T-cell neoplasm caused by HTLV-1 and its lifetime risk is estimated as 4-7% among HTLV-1 carriers. Acute and lymphoma subtypes are highly aggressive diseases, characterized by shorter survival rates and a high risk of central nervous system involvement (iCNS) compared to other peripheral T-cell lymphomas. Currently, the treatment of ATLL remains a challenging. Our recent study on PTCL epidemiology and outcomes in Latin America (Thais et al. 2023 ASH Meeting) highlighted ATLL (18%) as the second most frequent subtype of PTCL, likely influenced by our distinct viral epidemiology. Objective: It is to assess the prevalence, clinical features, risk factors, and outcomes of iCNS in ATLL in Latin America. Methodology: Patients (pts) aged ≥18 years with newly diagnosed ATLL from GELL (n = 208, 2000-2023, retrospective) and TCBP (n = 83, 2015-2022, ambispective). Overall survival (OS) and progression free survival (PFS) were our endpoints. REDcap Platform (by Vanderbilt) was used to collect and store data, whereas for statistical analysis IBM-SPSS v.24. This trial is registered at Clinical trials (NCT03207789). Results: It was enrolled 291 pts, the prevalence of iCNS in ATLL was 7.9% (23/291), considering only aggressive forms (acute 40% and 60% lymphomatous). Pts'characteristics were similar between those without and with iCNS. There was a high frequency of advanced stage (90% vs 82%); ECOG ≥ 2 (45% vs 43%); B symptoms (74% vs 56%); elevated LDH (84% vs 78%); and IPI ≥3 (82% vs 65%) in the iCNS group. Treatment was heterogeneous including: IFN+AZT (74%) for acute subtypes, and CHOP (52%), CHOEP (26%) and EPOCH (2%), for lymphoma subtypes. Less than 30% of both groups achieved complete response at end of first treatment. Two clinical features were identified as possibly associated to iCNS: median age at diagnosis (55 [20-95] vs 44 [23-65]; p < 0.0001) and extra nodal involvement ≥ 2 (32% vs 65%, p = 0.005). The entire cohort of ATLL had 60- month OS and PFS of 16% [95% CI: 12-20%] and 9% [95% CI: 5-13%]; with median time of OS and PFS of 7 months (6-9) and 5 months (4-6). iCNS did not have an impact on survival outcomes (60 months OS 14% iCNS (n = 23) vs 16% no iCNS (n = 254), p = 0.91; PFS 12% vs 9% no iCNS, p = 0.61;) despite being a devastating complication. Outcomes in pts with lymphoma subtypes were slightly better than acute (60 months OS 19% vs 10%, p < 0.0001; PFS 12% vs 5%, p < 0.0001, respectively). Conclusion: Unlike other lymphoma subtypes, iCNS in ATLL does not appear to significantly impact outcomes. This paradoxical finding underscores the complexity of ATLL and may reflect the limitations of existing treatment options and the absence of standardized therapeutic protocols for this aggressive malignancy. The lack of significant survival difference, despite the severity of iCNS, points to an urgent need for innovative therapies and more effective treatment strategies. Our analysis identified median age at diagnosis and extranodal involvement as potential risk factors for iCNS, suggesting avenues for future prospective studies to further elucidate their role in disease progression. Given the high prevalence of ATLL in Latin America, there is a unique opportunity to advance our understanding of this disease through region-specific research. Collaborative efforts in this region could pave the way for breakthroughs in the management of ATLL and potentially offer insights applicable on a global scale.

Introduction: PTCL accounts for 10-15% of all NHL. As previously demonstrated, Latin America has its own epidemiological distribution, with a high frequency of ATLL and ENKT, likely influenced by distinct genetic profiles and viral epidemiology. 3-year OS is about 40%. Treatment advances have also been limited, except for BV-CHP in some countries. The IPI, which includes extranodal (EN) site as a variable, has been validated for PTCL. However, the specific impact of EN involvement on nodal PTCL (such as PTCL-NOS, AIT, ALCL ALK+/ALK-) and its biological implications remain unclear. Simplification could improve the reproducibility and applicability of these models, especially in low-income countries. Objective: To evaluate number of EN sites in nodal PTCL lymphomas as a risk factors or surrogate for outcomes, as OS and PFS in Latin America cohort. Methodology: Patients (pts) aged ≥18 years with newly diagnosed nodal PTCL-NOS, AITL and ALCL ALK+/ALK-) from GELL (n = 339, 2000-2023, retrospective), TCBP (n = 427, 2015-2022, ambispective). Treatment outcome was determined by OS and PFS. REDcap Platform (by Vanderbilt) was used to collect and store data, whereas statistical analysis the IBM-SPSS v.24. This trial is registered at Clinical trials (NCT03207789). Results: 766 pts [427pts - TCBP and 339 - GELL] diagnosed with nodal PTCL were grouped according to the number of EN: no EN involvement (No EN - 383); one EN involvement (EN1 -168); and 32 (EN2 - 215). Considering all, 61% male; median age 56 y/o; 74% were staged III/IV; 69% IPI 32; 60% was PTCL-NOS, 19% ALCL ALK- and 12% AITL. 61% had B symptoms and 55% elevated LDH. CHOEP was used in 47% and 34% CHOP, and 47% achieved CR after first line; 16% used transplant as consolidation. No EN, EN1 and EN2 were similar regarding clinical characteristics, except, for stage III/IV (58% vs. 79% vs 96%; p < .0001); IPI 32 (58% vs. 59% vs. 99%; p < .0001); ECOG>1 (58% vs. 92% vs. 99%; p < .0001); BMO involvement (16% vs. 24% vs. 63%%; p

Objetivos: Analisar o perfil epidemiológico das leucemias na população pediátrica na Região Sudeste entre os anos de 2019 a 2023. Material e métodos: Trata-se de um epidemiológico de abordagem quantitativa, de caráter descritivo e retrospectivo sobre internações por leucemia pediátrica, realizado através de extração de dados no Departamento de Informática do Sistema Único de Saúde, na série temporal de 2019 a 2023. As variáveis incluíram unidade da federação, faixa etária e internações por faixa etária, sexo e ano de processamento, sendo estratificadas por região brasileira. Resultados: Durante o período analisado, um total de 31.975 pacientes tiveram diagnóstico de leucemia com internação, com um crescimento progressivo, exceto no ano de 2020, atingindo seu pico em 2023, 6.818 internações realizadas, correspondendo a 21,3%. Destaca-se, da região Sudeste analisada, o maior número de pacientes no Estado de São Paulo, o mais populoso do país, com 20.025 internações durante o período de 2019 a 2013, representando 62,6% do conjunto. No presente estudo, nota-se um predomínio entre 5-9 anos com um total de 11.702 (36,6%) crianças com diagnóstico dessa patologia, seguido por 1-4 anos, 10.670 (33,3%) e 10-14 anos, 9.033 (28,2%) respectivamente. Na análise por sexo, destaca-se predomínio do sexo masculino nas internações 18.679, correspondendo 58,4% da amostra geral. Discussão: O epidemiológico das internações por leucemia revelou padrões importantes que podem orientar políticas de saúde pública e intervenções clínicas. Ao analisar os dados, observou-se um aumento gradual do número total de internações por leucemia nos últimos cinco anos. Além disso, verificou-se uma maior prevalência de internações do sexo masculino, o que corrobora com outros estudos e dados apresentados pelo Instituto Nacional de Câncer. Na análise por faixa etária, a população com maior prevalência de internações por leucemia foi a de crianças e adolescentes entre 1 a 14 anos. Isso reflete o fato de que a leucemia é o câncer mais comum na faixa etária infanto-juvenil, representando cerca de 30% dos casos de câncer nessa população, embora, em termos gerais, ainda seja considerada uma doença rara. O ano de 2020 registrou uma queda nas internações, o que pode estar relacionada à pandemia de COVID-19 e o subdiagnóstico dessa patologia. Conclusão: O estudo do perfil epidemiológico das leucemias na população pediátrica da região Sudeste entre 2019 e 2023 evidenciou um aumento progressivo nas internações, com uma exceção notável em 2020 e com o seu maior valor de internações em 2023. O Estado de São Paulo se destacou com o maior número de casos, refletindo tanto sua maior população quanto uma possível maior capacidade de diagnóstico e tratamento. Observou-se uma maior prevalência de leucemia em crianças de 5 a 9 anos, com uma predominância de internações em meninos. A importância dos estudos epidemiológicos se reflete na capacidade de identificar padrões e tendências que orientam políticas públicas e intervenções de saúde. Estes dados são essenciais para direcionar recursos, planejar estratégias de prevenção e tratamento, e melhorar o suporte aos pacientes e suas famílias. Os achados deste estudo sublinham a necessidade de políticas de saúde específicas e intervenções clínicas direcionadas para essa população, visando melhorar o diagnóstico precoce, o tratamento e o suporte aos pacientes pediátricos com leucemia.

The Brazilian Acute Myeloid Leukemia Registry (RBLMA) is a recent initiative aimed at determining the clinical and epidemiological aspects of acute myeloid leukemia (AML) in Brazil. The full comprehension of our epidemiology and clinical outcomes are fundamental for guiding the best clinical practice since the majority of epidemiology data currently available came from abroad. In this setting, early mortality is a very useful parameter for evaluating the quality of healthcare in AML, with international data suggesting this rate could be as high as 20-30%. There are still few studies evaluating this parameter in Brazilian institutions, and to date, none have compared such mortality between public and private institutions. Objective: Assessment of early mortality rate on AML patients treated in public or private services. Secondary objectives include providing clinical and epidemiological data from the initial records of the RBLMA. Methods: This study enrolled patients from the Brazilian Acute Myeloid Leukemia Registry, a national ambispective study involving patients aged 18 years or older with a diagnosis AML (excluding acute promyelocytic leukemia and leukemias of ambiguous lineage) without previous treatment The study was supported by the Brazilian Association of Hematology, Hemotherapy, and Cellular Therapy (ABHH). Prognostic stratification followed the European Leukemia Net (ELN) 2022 guidelines. Results: 216 patients were analyzed, 56,5% (n = 122) from public health care and 43,5% (n = 94) from private health care. There was a slight prevalence of female cases (51,9% versus 48,1%) and the median age of diagnosis on public setting was 56 years versus 61 on private centers. The median Charlson's Comorbidity index on patients treated in public services was 1,0 versus 2,31 on patients from private centers. The early death, defined as as mortality within 30 days of the beginning of induction chemotherapy, was 27% in public services compared to 9.6% on patients from private setting, with an odds ratio for death of 3.5 (ci 95%, 1,5-7,7, p < .002). With a median follow-up of 18 months, the median overall survival (OS) of patients treated in public services was 4 months (CI 95%, 2,2-5,7) versus 22 months (CI 05%, 14,7 – 29,2) of patients treated in private services. The progression free survival (PFS) of patients from public or private centers was 4 months and 19 months, respectively. A multivariate analysis showed a hazard ratio for death of 4.12 (CI 95%, 2.35 - 7.23, p < .001) for patients treated on public services rather than private centers. Regarding the preferred treatment protocol, anthracyclines and cytarabine-based protocols represented the majority of prescribed treatments in the public setting (84,4% of treated patients), whereas in the private setting they represented 52,1% of treatments. Venetoclax-based treatment accounted for 43.6% of treatments in the private setting and only 1.6% at public centers. Conclusions: The difference in early mortality, OS, and PFS reflects an alarming disparity between AML patients treated in the public or private setting. Even with higher comorbidity index, patients treated in private services had better clinical outcomes and lower early mortality. The study provided an initial analysis of the epidemiological profile of patients with AML in Brazil and the preferred regimens used in each setting.

Objetivo: Descrever as tendências no diagnóstico de síndrome mielodisplásica no Brasil entre o período de 2014 e 2023 e sua associação com variáveis demográficas, sexo e faixa etária. Metodologia: Refere-se a um estudo documental quantitativo, retrospectivo e descritivo, realizado com base em informações referentes aos casos de síndrome mielodisplásica diagnosticados no período de 2019 a 2023, disponíveis no banco de dados do Sistema de Informações Ambulatoriais (SIA), no banco de informações em saúde TABNET (DATASUS). Nesta pesquisa, foram utilizadas as seguintes variáveis: sexo e faixa etária, fazendo uma comparação entre regiões do país e casos por ano. Resultados: Houve um aumento de 117,8% nos diagnósticos de Síndrome Mielodisplásica (SMD) no Brasil, de 450 casos em 2014 para 980 casos em 2023. Em se tratando da distribuição por sexo, em 2023, 54,1% dos casos diagnosticados eram homens (530 casos) e 45,9% eram mulheres (450 casos). Já na análise da faixa etária, nota-se que a maioria dos casos ocorreu em indivíduos acima de 60 anos, que representaram 65% dos diagnósticos em 2023. A faixa etária de 40 a 59 anos teve 25% dos casos, enquanto os indivíduos com menos de 40 anos representaram 10% dos diagnósticos. A região Sudeste apresentou o maior número de casos em relação ao total (40%), enquanto a menor taxa é da região Norte (5%). Discussão: Este estudo epidemiológico apresentou relevancia por fortalecer o direcionamento assertivo aos cuidados de saúde em pessoas com Síndrome Mielodisplásica (SMD), sobretudo a partir da identificação da maior incidência em pessoas do sexo masculino e acima de 60 anos. Aproximadamente 65% dos pacientes com SMD têm mais de 60 anos de idade no momento do diagnóstico e a taxa de incidência dobra a cada década acima dos 40 anos de idade. Apresentando um curso clínico extremamente variável, ela se enquadra em um espectro que varia desde um curso estável da doença ao longo de 10 ou mais anos, até evolução para morte, com evolução acelerada entre alguns meses subsequente à complicações de citopenia ou transformação leucêmica. Além disso, o fato de ter um aumento no número de casos entre 2014 e 2023, sendo a maior quantidade de pacientes no Sudeste, demonstra que a SMD é uma doença que necessita de estratégias de prevenção e diagnóstico precoce. Conclusão: Diferenças étnicas e influências regionais desempenham um papel significativo na patogênese e estabelecimento da Síndrome Mielodisplásica. Sendo assim, fatores genéticos, fatores étnicos, ocupacionais, de estilo de vida e ambientais contribuem para a história natural e desenvolvimento da síndrome em questão. A compreensão desses aspectos é crucial para o desenvolvimento de estratégias eficazes de prevenção, diagnóstico precoce e manejo da SMD, visando melhorar a qualidade de vida dos pacientes e otimizar os recursos de saúde.

Objetivo: Descrever o perfil epidemiológico da mortalidade por mieloma múltiplo e neoplasias malignas de plasmócitos no território brasileiro. Material e métodos: Trata-se de um estudo descritivo com abordagem quantitativa acerca da mortalidade por mieloma múltiplo e neoplasias malignas de plasmócito no Brasil, no período de 2012 a 2022. Os dados foram obtidos através do Departamento de Informática do Sistema Único de Saúde (DATASUS). Para o presente estudo foram analisadas as variáveis: ano de processamento, faixa etária, cor/raça e sexo. Resultados: Observou-se que ocorreram 34.595 óbitos por residência decorrentes de mieloma múltiplo e neoplasias malignas de plasmócitos em todo o país durante a série temporal de 2012 e 2022, tendo 2012 (2.403 ou 6,9%) e 2022 (3.679 ou 10,6%) sido os anos com mais e menos registros. No que tange à idade prevalente de falecimentos, a incidência se deu entre 60 e 69 anos, com o total de 10.134 (29,3%). Além disso, foi notado que a população masculina foi a que mais pereceu em decorrência da doença, com 17.861 (51,6%). Por fim, a taxa de óbitos segundo cor/raça foi a que mais variou, com 20.013 (57,8%), 2.958 (8,6%), 165 (0,5%), 10.173 (39,4%), 42 (0,1%) e 1.244 (3,6%) sendo brancos, pretos, amarelos, pardos, indígenas e ignorados, respectivamente. Discussão: Neste estudo foi possível identificar que a faixa etária mais afetada, de 60 a 69 anos, apontando que essas neoplasias têm mais incidência nas idades mais avançadas. Com relação à cor/raça, 57,8% dos óbitos ocorreram em indivíduos brancos, o que vai de encontro com as evidências sobre a prevalência maior nessa população. Houve também um aumento considerável no número de óbitos ao longo dos anos, com um pico em 2022. Esse dado sugere tanto a melhoria no rastreio desses tipos de câncer quanto o envelhecimento da população brasileira. A predominância de óbitos entre homens (51,6%) pode indicar uma maior susceptibilidade masculina a essas doenças, bem como diferenças de acesso e resposta ao tratamento. Conclusão: Portanto, é evidente a relevância da análise dos casos de mieloma múltiplo e sua influência no Brasil. É possível ver a prevalência aumentada em indivíduos de cor branca e para as idades de 60+, indicando a importância do rastreamento para um diagnóstico precoce, aumentando assim as taxas de sobrevida. Contudo, cada caso possui sua individualidade e deve ser levado em conta durante a escolha do tratamento, para que um desfecho positivo possa ser observado.

Fracture healing is a complex event that involves the coordination of various different processes, including intramembranous and endochondral bone formation. When facing fracture nonunion or delayed union, few organizational engineering structures can achieve the desired results. The main reason for this is that they cannot recapitulate the cellular morphology, biology, and mechanical functions of natural tissues. Ten years ago, the term Development Engineering was coined to refer to the use of developmental processes as a blueprint for designing and developing engineered live implants. Different sources of cells have been used as seed cells in developmental engineering. Among them, hypertrophic chondrocytes have attracted worldwide attention. Hypertrophic chondrocytes are the terminal state of growth plate chondrocytes, leading to degenerative maturation. Hypertrophic chondrocytes mediate crosstalk by regulating cell-matrix degradation, vascularization, osteoclast recruitment, and osteoblast differentiation. Furthermore, hypertrophic chondrocytes can transdifferentiate into osteoprogenitors and mature osteoblasts, and directly promote woven bone formation. In summary, elucidating the role of hypertrophic chondrocytes will contribute to understand of the physiological mechanism of fracture healing, research and development of novel therapeutic modes of developmental engineering, and further promotion of fracture healing.

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