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Introduction: Peritonitis is a significant complication of peritoneal dialysis (PD). Additionally, in severe or prolonged cases of peritonitis, the structure and function of the peritoneum may change, making it difficult to continue PD. Thus, identifying the causative agent and early administration of antibiotics are essential to minimize the risk of treatment failure. Meanwhile, bacterial peritonitis caused by nontuberculous Mycobacteria (NTM) are difficult to identify. NTM are also among the most difficult organisms to eradicate. Oftentimes, removal of the peritoneal catheter and multiple antibiotics are required to eradicate NTM infections. Case Presentation: Herein, we report a case of peritonitis caused by Mycobacterium fortuitum in a 3-year-old boy undergoing PD. The patient had a history of an initial PD catheter exit site infection caused by M. fortuitum that led to PD-associated peritonitis. Consequently, the catheter was removed, and the patient was switched to hemodialysis and treated with multiple antibiotics. Conclusion: This rare cause of peritonitis is associated with a high mortality and severe morbidity and usually requires removal of the PD catheter as well as prolonged treatment with multiple antibiotics. When there is NTM infection around the PD catheter, such as in an ulcer, it is necessary to remove the catheter and transition to a hemodialysis until the infection has healed.

Purpose: To discuss theoretically the ‘biopsychosocial model’ when relating to more existential and spiritually oriented approaches to health and Health Humanities and to display a new non-therapeutic and philosophical dialogue approach to Art & Health. Method: The article uses a heuristic approach to ponder philosophically on the question: How would a concept of holistic health be conceptualized theoretically if we investigate the perspective of a ‘non-therapy setting’ approach to health humanities from within the dialogical and existential philosophy of Hans-Georg Gadamer and Martin Buber? Findings: Arguments are made for developing a concept of ‘Existential Health’ and ‘Spiritual Recovery,’ when working with the interplay between culture and health, and especially when wanting to focus on the existential and spiritual dimensions of health humanities. This also leads to a new concept of ‘Wonder-and-Phenomenon-centred’ healthcare as something other than ‘Human- and-person-centred’ healthcare. Originality: Such a way of thinking expands the current use of the concept of ‘holistic health’ in health humanities research through a dialogical and existential philosophy approach, and it provides a new concept of wonder-and-phenomenon-centered healthcare, which could give new access to the existential and spiritual dimensions in health humanities.

Peiran Guo,1,2,&ast; Yuting Tan,1,2,&ast; Li Feng,3 Cui Liu,4 Jin Sun,5 Rong Cheng,1,2 Yanling Xiao,1 Xingxin Zhan,6 Lingjie Yang,1 Zhixia Zhang1 1Tianyou Hospital, Wuhan University of Science and Technology, Wuhan, Hubei, People’s Republic of China; 2Wuhan University of Science and Technology School of Medicine, Institute of Nursing Research, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, Wuhan, Hubei, People’s Republic of China; 3School of Public Health and Nursing, Hubei University of Science and Technology, Xianning, Hubei, People’s Republic of China; 4Geriatric Hospital Affiliated with Wuhan University of Science and Technology, Wuhan, Hubei, People’s Republic of China; 5Yiling Hospital of Yichang City, Yichang, Hubei, People’s Republic of China; 6School of Public Health, Xinyu University, Xinyu, Jiangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhixia Zhang, Tianyou Hospital, Wuhan University of Science and Technology, No. 9, Tujialing, Dingzhiqiao, Wuchang District, Wuhan, Hubei, People’s Republic of China, Tel +8613476805827, Email zzx13476805827@126.comPurpose: The development of “Internet + nursing services” can effectively solve the problem of population aging, and grassroots nurses are the primary providers of such services in rural areas. This study aimed to analyze the factors affecting grassroots nurses’ risk perception of “Internet + nursing services” and construct a predictive model.Patients and Methods: A multicenter cross-sectional study of 2220 nurses from 27 secondary hospitals and 36 community health centers in Hubei Province was conducted from August to December 2023 using a multi-stage cluster sampling method. Information was collected through a structured anonymous questionnaire. A Chi-square test, a Welch t-test, and binary logistic regression analyses were employed to determine independent risk factors for grassroots nurses’ risk perception of “Internet + nursing services”, and a nomogram was constructed. Receiver operating characteristic curves, calibration curves, and decision curves were plotted to evaluate the discrimination, calibration, and clinical effectiveness of the nomogram.Results: A total of 2050 valid questionnaires were collected, demonstrating that 51.95% of grassroots nurses thought that “Internet + nursing services” was a medium-high risk. Age, other sources of income, knowledge about “Internet + nursing services”, personal safety, physical function, occupational exposure, social psychosocial, and time risk (P< 0.05) were independent risk factors for grassroots nurses’ risk perception. The area under the receiver operating characteristic curve of the nomogram was 0.939. The calibration and decision curve analyses demonstrated good calibration ability and clinical application values.Conclusion: The prediction model constructed in this study has good prediction ability. Most grassroots nurses believe that “Internet + nursing services” are risky and influenced by several factors. It is suggested that the government and hospitals should formulate a unified charging standard, improve the safety guarantee, and gradually eliminate the concerns of grassroots nurses.Keywords: grassroots nurse, Internet + nursing services, risk perception, predictive model

Gayenell S Magwood,1,2 Charles Ellis Jr,3 Chanita Hughes Halbert,4 Ebony Allen Toussaint,1 Jewel Scott,1 Lynne S Nemeth1,2 1Department of Biobehavioral Health and Nursing Science, University of South Carolina, Columbia, SC, USA; 2College of Nursing, Medical University of South Carolina, Charleston, SC, USA; 3Department of Speech, Language, and Hearing Sciences, University of Florida, Gainesville, FL, USA; 4Department of Population and Public Health Sciences, University of Southern California, Los Angeles, CA, USACorrespondence: Gayenell S Magwood, Professor and Myrtle Irene Brown Endowed Chair, Department of Biobehavioral Health and Nursing Science College of Nursing, University of South Carolina, Columbia, SC, 29208, USA, Email magwoodg@sc.eduIntroduction: Many research activities have focused on SARS-CoV-2 infection and subsequent COVID-19 respiratory illness during the pandemic. However, significant racial inequities emerged months after the COVID-19 pandemic began. The similarity between racial/ ethnic disparities in COVID-19 and those for other diseases raised awareness about the context for risk exposure and healthcare access. The purpose of this study is to examine social and structural determinants of health among COVID-19 survivors, carepartners, and the perspectives of healthcare stakeholders who experienced disruption during the early pandemic.Material and methods: A purposive sample of interviews (n=9) and focus groups (n=10) were used to collect data regarding knowledge of barriers to effective COVID-19 risk mitigation, recovery, and chronic disease self-management. This included nurses, physicians, COVID-19 survivors and their carepartners, public health, and community leaders connected with the healthcare systems in rural counties of South Carolina.Results: Five major themes were identified across the subgroups. The themes: The COVID-19 Illness Trajectory Added Major Health Challenges and Stressors, Access to Care Is Lacking, Support is Needed for COVID-19 Survivors and Care Partners, Support Must be Distributed Equitably, and Racism and Structural Issues Affect Stress reflect the strengths, opportunities, and inequities perceived within these groups.Conclusion: This research is the first qualitative study focused on COVID-19 survivor-carepartner dyads that consider the intersectionality of race/ ethnicity, geography, and health that is known to occur when engaging healthcare systems. The themes illustrate the need for infectious disease prevention at all socioecological levels: structural/ systemic, community, organizational/ institutional, interpersonal, and individual.Keywords: COVID-19, health equity, rural, African American, chronic disease, dyads

Ahmet Cemal Pazarl&inodot;,1 Hüseyin Alper K&inodot;z&inodot;lo&gbreve;lu,2 Handan Inönü Köseo&gbreve;lu1 1Department of Pulmonary Diseases, Tokat Gaziosmanpasa University Faculty of Medicine, Tokat, Turkey; 2Department of Radiology, Tokat Gaziosmanpasa University Faculty of Medicine, Tokat, TurkeyCorrespondence: Ahmet Cemal Pazarl&inodot;, Department of Pulmonary Diseases, Tokat Gaziosmanpa&scedil;a University Faculty of Medicine, Tokat, Turkey, Tel +90 05053696860, Fax +90 0356 2129500, Email dracp60@gmail.comAim: Pneumoconiosis describes diseases caused by the accumulation of inorganic dust particles in the lungs, leading to tissue damage. The diagnosis relies on a history of exposure and compatible radiological findings.Background: We aimed to investigate the radiological findings in individuals exposed to antimony-inert dust relative to their working periods.Objective: Fifty-six symptomatic male antimony miners were retrospectively evaluated for demographics and chest computed tomography (CT) scans.Methods: The demographic and radiological data of patients with a history of antimony mining, who presented at our pulmonary clinic between June 2017 and June 2023, were analyzed according to the duration of exposure.Results: The study included 56 male patients with a mean age of 58.5± 13.02 years and a mean exposure duration of 13.63 ± 6.82 years. CT scans showed that 73.2% (n=41) had upper and middle lung zone involvement, and 55.4% (n=31) had extensive involvement. Micronodules with centriacinar ground-glass opacities were the most common finding (n=37, 66.1%), followed by nodular opacities with irregular margins (n=22, 39.3%) and solid micronodules (n=20, 35.7%). Patients with over 20 years of exposure had significantly higher rates of respiratory and cardiovascular disease (p< 0.05). Increased exposure time correlated with more extensive parenchymal involvement and higher rates of calcification in mediastinal lymph nodes, solid micronodules, nodular opacities with irregular margins, honeycombing, and conglomerate mass appearance.Conclusion: Radiological findings in pneumoconiosis generally worsen with longer exposure. Given the scarcity of up-to-date information on antimony pneumoconiosis, further studies focusing on radiological findings and chemical analyses of those exposed to antimony mine dust are essential to identify related pathologies.Keywords: rare lung diseases, antimony, pneumoconiosis, computerized thorax tomography, ground-glass opacities, lymph nodes

Dennis To,1 Mariana Blanco Massani,1 Débora C Coraça-Huber,2 Anna Seybold,3 Fabrizio Ricci,1,4 Katrin Zöller,1 Andreas Bernkop-Schnürch1 1Center for Chemistry and Biomedicine, Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Innsbruck, Austria; 2Research Laboratory for Implant Associated Infections (BIOFILM LAB), Experimental Orthopaedics, University Hospital for Orthopaedics and Traumatology, Medical University Innsbruck, Innsbruck, Austria; 3Department of Zoology, University of Innsbruck, Innsbruck, Austria; 4Thiomatrix Forschungs- und Beratungs GmbH, Innsbruck, AustriaCorrespondence: Andreas Bernkop-Schnürch, Email Andreas.Bernkop@uibk.ac.atPurpose: The eradication of bacterial biofilms poses an enormous challenge owing to the inherently low antibiotic susceptibility of the resident microbiota. The complexation of antibiotics with polyphosphate can substantially improve antimicrobial performance.Methods: Nanoparticular complexes of the model drug colistin and polyphosphate (CP-NPs) were developed and characterized in terms of their particle size and morphology, polydispersity index (PDI), zeta potential, and cytotoxicity. Enzyme-triggered monophosphate and colistin release from the CP-NPs was evaluated in the presence of alkaline phosphatase (AP). Subsequently, antimicrobial efficacy was assessed by inhibition experiments on planktonic cultures, as well as time-kill assays on biofilms formed by the model organism Micrococcus luteus.Results: The CP-NPs exhibited a spherical morphology with particle sizes < 200 nm, PDI < 0.25, and negative zeta potential. They showed reduced cytotoxicity toward two human cell lines and significantly decreased hemotoxicity compared with native colistin. Release experiments with AP verified the enzymatic cleavage of polyphosphate and subsequent release of monophosphate and colistin from CP-NPs. Although CP-NPs were ineffective against planktonic M. luteus cultures, they showed major activity against bacterial biofilms, outperforming native colistin treatment. Strongly elevated AP levels in the biofilm state were identified as a potential key factor for the observed findings.Conclusion: Accordingly, polyphosphate-based nanocomplexes represent a promising tool to tackle bacterial biofilm. Keywords: polyphosphate, colistin, antimicrobial, nanoparticle, nanocomplex

Christina Ciaccio,1 Jessica Dunne,2 Andrea Bever,2 Karissa Johnston,2 Stacey Kowal,3 Arpamas Seetasith,3 Andrew Lloyd,4 Alexis Mickle2 1The University of Chicago, Chicago, IL, USA; 2Broadstreet Health Economics & Outcomes Research, Vancouver, British Columbia, Canada; 3Genentech, Inc., South San Francisco, CA, USA; 4Acaster Lloyd Consulting Ltd, London, UKCorrespondence: Christina Ciaccio, Department of Pediatrics and Medicine, The University of Chicago, 5841 South Maryland Avenue, Chicago, IL, 60637, USA, Tel +1-773-834-4010, Email cciaccio@bsd.uchicago.eduPurpose: The quality of life (QoL) impact of food allergies extends beyond severe allergic reactions, as food avoidance can permeate the daily lives of individuals with food allergies and their caregivers. People with multiple food allergies may experience a greater impact on QoL than people with a single food allergy, but there is limited evidence available. The aim of the study was to provide insight into the lived experiences of adults, teenagers, children, and caregivers of children with multiple food allergies.Methods: Semi-structured interviews were conducted of people with multiple food allergies and their caregivers (n = 20) in the United States, including 10 adults, 5 teenagers, and 5 caregivers of children. Patterns in responses were explored using reflexive thematic analysis.Results: Four themes were developed by the researchers to convey the experiences of people with food allergies and QoL impact: preparedness and allergen avoidance results in a loss of spontaneity; emotional impact varies by person and for each person; participating in society involves speaking up and trusting others; and food is more than nutrition. In addition, 3 themes were identified that convey the experiences of caregivers: looking out for your child’s safety is an emotional balancing act; limitations on what you can do on your own and as a family; and creating a safe and fulfilling environment can be time-consuming and costly.Conclusion: These findings highlight that people with multiple food allergies experience social limitations, stress about food safety and allergen avoidance, and restrictions on freedom. Caregiver QoL is impacted by the need to navigate social, emotional, and practical implications of caring for a child with multiple food allergies.Plain Language Summary: People with food allergies must constantly make an effort to avoid the foods they are allergic to. Having an allergy to more than 1 type of food (for example, peanuts, eggs, or milk) can be even more difficult. In this study, we interviewed adults and teenagers with food allergies, as well as parents of children with food allergies, about how having an allergy to more than 1 type of food affects their daily lives. We found that people with more than 1 food allergy often had stress and anxiety. They also had to change the way they traveled or socialized. Parents caring for a child with food allergies were also impacted. Parents had to look out for their child’s safety and made changes to family plans and activities. The lives of people with food allergies and their families may be improved by treatments or interventions that can lower the risk of allergic reactions.Keywords: food hypersensitivity, quality of life, patients, caregivers, multiple food allergies

Jiong Li,1 Dongqin Lei,1 Yanbing Cao,2,3 Fuli Xin,2,3 Zhenxi Zhang,1 Xiaolong Liu,2,3 Ming Wu,2,3 Cuiping Yao1 1Key Laboratory of Biomedical Information Engineering of Ministry of Education, Institute of Biomedical Photonics and Sensing, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an, 710049, People’s Republic of China; 2The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, People’s Republic of China; 3Mengchao Med-X Center, Fuzhou University, Fuzhou, 350116, People’s Republic of ChinaCorrespondence: Ming Wu, Mengchao Hepatobiliary Hospital of Fujian Medical University, 312 Xi Hong Road, Fuzhou, 350025, People’s Republic of China, Email wmmj0419@163.com Cuiping Yao, School of Life Science and Technology, Xi’an Jiaotong University, 28 Xian Ning West Road, Xi’an, 710049, People’s Republic of China, Email zsycp@xjtu.edu.cnIntroduction: Photodynamic therapy (PDT) has attracted increasing attention in the clinical treatment of epidermal and luminal tumors. However, the PDT efficacy in practice is severely impeded by tumor hypoxia and the adverse factors associated with hydrophobic photosensitizers (PSs), including low delivery capacity, poor photoactivity and limited ROS diffusion. In this study, Pt nanozymes decorated two-dimensional (2D) porphyrin metal-organic framework (MOF) nanosheets (PMOF@HA) were fabricated and investigated to conquer the obstacles of PDT against hypoxic tumors.Materials and Methods: PMOF@HA was synthesized by the coordination of transition metal iron (Zr4+) and PS (TCPP), in situ generation of Pt nanozyme and surface modification with hyaluronic acid (HA). The abilities of hypoxic relief and ROS generation were evaluated by detecting the changes of O2 and 1O2 concentration. The cellular uptake was investigated using flow cytometry and confocal laser scanning microscopy. The SMMC-7721 cells and the subcutaneous tumor-bearing mice were used to demonstrate the PDT efficacy of PMOF@HA in vitro and in vivo, respectively.Results: Benefiting from the 2D structure and inherent properties of MOF materials, the prepared PMOF@HA could not only serve as nano-PS with high PS loading but also ensure the rational distance between PS molecules to avoid aggregation-induced quenching, enhance the photosensitive activity and promote the rapid diffusion of generated radical oxide species (ROS). Meanwhile, Pt nanozymes with catalase-like activity effectively catalyzed intratumoral overproduced H2O2 into O2 to alleviate tumor hypoxia. Additionally, PMOF@HA, with the help of externally coated HA, significantly improved the stability and increased the cell uptake by CD44 overexpressed tumor cells to strengthen O2 self-supply and PDT efficacy.Conclusion: This study provided a new strategy of integrating 2D porphyrin MOF nanosheets with nanozymes to conquer the obstacles of PDT against hypoxic tumors.Keywords: 2D porphyrin MOF, hypoxic relief, Pt nanozyme, photodynamic therapy

Kiran Shahbaz,1 Alamgeer,1 Vibhu Paudyal,2 Maryam Zubair,3 Maryam Zahra Safdar,4 Momina Tahir,4 Laraib Akram,4 Salamat Ali4 1Department of Pharmacology, University College of Pharmacy, University of the Punjab Lahore, Pakistan; 2Institute of Clinical Sciences, University of Birmingham, Edgbaston Birmingham, UK; 3Faculty of Experimental Medicine Orebro University, Sweden; 4Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, GC University Faisalabad, Faisalabad, PakistanCorrespondence: Salamat Ali, Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, GC University Faisalabad, Faisalabad, Pakistan, Tel +00-92-3004189052; +00-92-041-9201036, Email drsalamatali@gcuf.edu.pkBackground: Prevalence of psychological disorders among individuals with diabetes is significantly higher as compared to the general population.Aim: This study aimed to assess the prevalence and impact of psychological disorders on pharmacotherapy of diabetes patients.Methodology: This cross-sectional study was conducted at two primary care hospitals in Pakistan from April to June 2023. The nine-item Patient Health Care Questionnaire (PHQ-9) scale was used to assess depression in the study’s population, and its effects on pharmacotherapy of diabetes. Chi-square test was used to evaluate relationship between ordinal variables/categorical variables and depression whereas; Student’s t-test was used to assess the relationship between numerical variables with depression.Results: A total of 320 patients were assessed, comprising 120 (37.5%) males and 200 (62.5%) females, with a mean age of 52.5 (SD± 11.8) years. The average duration of diabetes is 7.0 (SD± 5.4). The average PHQ-9 score was 8.3 (SD± 5.5). Depression was found to be prevalent in 43.7% of the study population. Gender (female) (p-value 0.002), advanced age (p-value 0.002), lower income (p-value 0.001), education levels (p-value 0.001), longer duration of diabetes (p-value 0.001), poor diabetes control according to BSR value (p-value 0.001), usage of injectable insulin (p-value 0.005), and concomitant diseases (p-value 0.001) were found to be independently linked with depression. Significant association was observed between depression and treatment adherence (p-value 0.0025), number of missed doses (p-value 0.045), and difficulty in diabetes management (p-value 0.0015).Conclusion: Our study highlights significant prevalence of depression in study population and the prevalent depression negatively impacts on treatment adherence. It also revealed that depression complicates diabetes management resulting in poor medication adherence, poor diabetes control and diabetes related complications, making diabetes control more challenging and difficult.Keywords: psychological disorders, diabetes, pharmacotherapy, PHQ-9

Abdullah A Alrasheed,1,2 Abdulrahman M Alammar3 1Department of Family and Community Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia; 2King Saud University Medical City, King Saud University, Riyadh, Saudi Arabia; 3King Saud University, King Saud University Medical City, Family and Community Medicine department, Riyadh, Saudi ArabiaCorrespondence: Abdullah A Alrasheed, Email aalrasheed1@ksu.edu.saBackground: CT scan utilizes ionizing radiation poses a danger to the patient’s health. Thus, telling the patient about ionizing radiation would be critical in promoting shared decision-making and improving patient-doctor communication. However, few studies have examined this topic broadly.Objective: The study was conducted to identify the frequency of physicians informing patients about the radiation risk before ordering a CT scan, as well as to examine the association between patients’ demographic characteristics and their awareness of the radiation risks associated with CT scans.Methods: A cross-sectional study was conducted among 387 patients who had undergone CT scans at a tertiary hospital in Riyadh, Saudi Arabia. Data were collected via phone interviews using a structured questionnaire. Chi-squared tests were employed to assess associations between patients’ demographic characteristics and their awareness of CT scan radiation risks.Results: When examining knowledge, 58% of patients knew that CT involves harmful radiation. This knowledge was significantly associated with higher education level and previous experience with CT scans. Regarding doctors’ practice of providing information to patients about the scan, 344 (88.9%) patients indicated that their doctor had explained to them why they needed the scan. Only 28 (7.2%) patients stated that their doctor had mentioned the amount of radiation, and 74 (19.1%) patients indicated that doctors mentioned the risks associated with the radiation of the scan. Almost all patients (96.9%) preferred to be told about why they needed a CT scan.Conclusion: The vast majority of patients who underwent CT scans did not receive enough information about the harm of the scans. However, most of them preferred to know about this harm.Keywords: CT radiation exposure, patient preferences, informed consent, doctor-patient communication, radiation risks, cross-sectional study

Laila A Alharbi,1 Mohamed Cheikh,2 Manal E Alotaibi,1 Amal A Alkhotani,1 Hussam M Alim,1 Fahd Almalki,1 Mohammed S Samannodi,1 Hadeel A Khadawardi,1 Ahmad A Imam,1 Yosra A Turkistani,1 Fozya B Bashal,1 Abdullah Tawakul,1 Adeeb A Bulkhi,1 Mohammad S Dairi,1 Rania Zaini,3 Hani M Almoallim1 1Department of Medicine, Umm Al-Qura University (UQU), Makkah, Saudi Arabia; 2Department of Medicine, Al Salama Hospital, Jeddah, Saudi Arabia; 3Department of Community Medicine, Umm Al-Qura University (UQU), Makkah, Saudi ArabiaCorrespondence: Hani M Almoallim, Department of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia, Email hmmoalim@uqu.edu.saBackground: Entrustable professional activities (EPAs) define the core tasks that a graduating rheumatologist needs to perform independently in practice. The objective of this study was to develop and validate EPAs for rheumatology fellowship training programs in Saudi Arabia.Methods: Experts met to develop an initial set of potential end-of-training EPAs by conducting a comprehensive literature review of EPAs and studying the Saudi rheumatology fellowship curriculum. Then, to validate the EPAs, we conducted two rounds of the modified Delphi technique among rheumatology experts in Saudi Arabia. A response rate of 80% was considered and the minimum number of experts needed to be 25 to 30. Descriptive statistics were utilized to describe participants’ demographic characteristics and group responses to each statement in all rounds. The experts were asked to rate the relevancy of each EPA using a 5-point Likert scale in both Delphi rounds.Results: In the preliminary phase, four rheumatologists developed an initial set of 36 core EPAs for rheumatology training program in Saudi Arabia. For the two-rounds Delphi techniques, 32 experts were invited to complete the study. The response rate of the first and second round were, 78.12% (25) and 93.75% (30), respectively. The first-round Delphi resulted in a robust consensus on 31 EPAs for rheumatology training. Five EPAs were excluded, and one new EPA was proposed. In the subsequent round, all 32 EPAs achieved strong consensus. The eliminated EPAs likely fell short in one or more of the following areas: relevance to rheumatology practice in Saudi Arabia, overlapping with other EPAs, or practical challenges in the implementation.Conclusion: We have developed and validated a core set of EPAs for rheumatology fellowship training programs in Saudi Arabia. Mapping and identifying milestones for these EPAs are essential steps to follow to enhance workplace curriculum development.Keywords: entrustable professional activities, EPAs, rheumatology, training programs, fellowship, Saudi Arabia, curriculum, workplace

Lobna Gharaibeh,1 Mohammed Liswi,2 Reem Al-Ajlouni,3 Dina Shafei,3 Rasha Ezzaldeen Fakheraldeen3 1Biopharmaceutics and Clinical Pharmacy Department, Al-Ahliyya Amman University, Amman, Jordan; 2Civilian Research and Development Foundation (CRDF) Global, Amman, Jordan; 3Jordan Breast Cancer Program, King Hussein Cancer Foundation, Amman, JordanCorrespondence: Lobna Gharaibeh, Biopharmaceutics and Clinical Pharmacy Department, Al-Ahliyya Amman University, Amman, Jordan, Tel +962796939977, Email l.gharaibeh@ammanu.edu.jo Reem Al-Ajlouni, Jordan Breast Cancer Program, King Hussein Cancer Foundation, Amman, Jordan, Tel +962797070722, Email R.al-ajlouni@jbcp.joPurpose: Mammography is the gold standard screening technique for early detection of breast cancer. This study aimed to assess the knowledge of community pharmacists of different aspects emphasized by the JBCP programs. This study also identifies the attitudes and barriers towards promoting early detection services.Patients and Methods: This study was a cross-sectional survey of community pharmacists in Jordan. Pharmacists were randomly selected and asked to complete an electronic questionnaire. Inclusion criteria: a pharmacist with a bachelor’s degree or higher and registered at the JPA working in a community pharmacy. The questionnaire included demographic and socioeconomic information, knowledge, attitudes towards breast cancer screening mammography services, and barriers towards participation in the promotion of these services.Results: A total of 1,088 community pharmacists were approached, 1,000 (91.8%) completed the questionnaire. Participants had an average age of 34 years ± 10.8 and average experience of 9.1 ± 9.5 years. Only 48 (37.8%) of the female pharmacists aged 40 years or older underwent a mammogram. Knowledge of symptoms of breast cancer was the highest with a score of 755, followed by knowledge of risk factors (670) and finally early detection of breast cancer (540). Many barriers were reported by the community pharmacists including lack of educational materials and time constraints. Pharmacists with higher educational levels (p< 0.001), of female gender (p< 0.001), attended continuous cancer-related education (p< 0.001), encountered a higher percentage of female customers (p< 0.001), in a certain geographic location (p=0.003), underwent mammography (p=0.014), and encountered high frequency of inquiries on mammogram by the customers (p< 0.001) were all associated with higher knowledge scores.Conclusion: Despite the reported barriers and insufficient knowledge in certain aspects of early detection of breast cancer, community pharmacists have positive attitudes and can be a valuable asset for awareness-raising efforts.Keywords: mammography, breast cancer, knowledge, attitude, barriers, Jordan breast cancer program, screening

Gamze Erta&scedil;,1 Hamiyet &Scedil;enol Çakmak,1 Sevda Akdeniz,1 Alparslan Yurtbay,2 Ebru Polat,2 Yavuz Yigit,3,4 Nezih Sertöz,5 Serkan Tulgar1 1Department of Anesthesiology, Samsun University Faculty of Medicine, Samsun Training and Research Hospital, Samsun, Turkiye; 2Department of Orthopedic Surgery, Samsun University Faculty of Medicine, Samsun Training and Research Hospital, Samsun, Turkiye; 3Department of Emergency Medicine, Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar; 4Blizard Institute, Queen Mary University, London, UK; 5Department of Anesthesiology and Reanimation, Ege University, Faculty of Medicine, &Idot;zmir, TurkiyeCorrespondence: Yavuz Yigit, Hamad Medical Corporation,Hamad General Hospital, Department of Emergency Medicine, Hamad General Hospital, Emergency Department, Doha, 3050, Qatar, Tel +97430616054, Email yyigit@hamad.qaIntroduction: Hip fracture surgeries in patients present significant challenges, particularly in managing pain during spinal anesthesia positioning. The Pericapsular Nerve Group Block (PENG) has shown promise in addressing this issue, but the ideal volume of local anesthetic for PENG is still uncertain. In our study, we aimed to analyze the effects of administering PENG block with two different volumes on analgesic quality for patients undergoing hip fracture surgery.Methods: In this prospective, randomized controlled trial, the effects of administering a PENG block with 20 mL versus 30 mL of local anesthetic in patients undergoing hip fracture surgery under spinal anesthesia were compared. The primary outcome was pain during spinal anesthesia positioning, and secondary outcomes included postoperative pain scores and opioid consumption.Results: A total of 60 patients were analyzed, with 30 in each group. Critical parameters such as the time of spinal anesthesia administration and the satisfaction of the anesthesiologist showed no significant differences (p=0.918; p=0.741, respectively). NRS scores recorded before, during, and after the positioning for spinal anesthesia exhibited similar patterns (p=0.290; p=0.247; p=0.288, respectively). The cumulative opioid requirements did not exhibit a statistically significant difference at 24 hours (p = 0.098). Quadriceps weakness was significantly more in the PENG-30 group 6 hours after surgery but had recovered by the 9th hour (p= 0.004).Conclusion: In patients undergoing hip fracture surgery, the effects of applying the PENG block with 20 mL or 30 mL of local anesthetic are comparable in terms of positioning for spinal anesthesia and postoperative analgesic requirements.Keywords: hip fracture surgery, pericapsular nerve group block, PENG, spinal anesthesia positioning, postoperative analgesia, local anesthetic volume

Jing Zhong,1 Hua Zhang,1 Jie Wu,2 Bosen Zhang,2,3 Liubing Lan1,2 1Department of Obstetrics, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of China; 2Department of Prenatal Diagnostic Center, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of China; 3Department of Ultrasound, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of ChinaCorrespondence: Liubing Lan, Department of Prenatal Diagnostic Center, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, No. 63 huangtang Road, Meijiang District, Meizhou, People’s Republic of China, Email lanliubing@126.comObjective: Gestational diabetes mellitus (GDM) is a complication of abnormal glucose tolerance during pregnancy, with incidence is on the rise. There are inconsistent results on the risks of GDM and it has not been reported in our region. The purpose of this study is to explore the risk factors of GDM.Methods: A total of 383 pregnant women were analyzed, including 67 (17.5%) pregnant women with GDM and 316 (82.5%) with normal glucose tolerance (NGT). The relationship of personal history, family history and reproductive history of pregnant women, the levels of alpha-fetoprotein (AFP), human chorionic gonadotropin (HCG), inflammatory markers in blood cell analysis at the first prenatal examination, and fetal ultrasound indices and the risk of GDM were analyzed.Results: The fetal biparietal diameter, head circumference, and femur length were negatively correlated with HCG level, but not inflammatory markers. The proportion of pregnant women aged ≥ 30 years old, body mass index (BMI) in early pregnancy≥ 24.0 kg/m2, history of polycystic ovary syndrome (PCOS), cesarean section, adverse pregnancy, and oral contraceptive use, and pregnant women who conceived through assisted reproduction in GDM group were higher than those in NGT group. Logistic regression analysis showed that age of pregnant woman ≥ 30 years old (≥ 30 vs < 30 years old, odds ratio (OR): 2.142, 95% confidence interval (CI): 1.183– 3.878, p=0.012), BMI≥ 24.0 kg/m2 (≥ 24.0 kg/m2 vs 18.5– 23.9 kg/m2, OR: 1.887, 95% CI: 1.041– 3.420, p=0.036), history of adverse pregnancy (yes vs no, OR: 1.969, 95% CI: 1.022– 3.794, p=0.043), and history of oral contraceptive use (yes vs no, OR: 2.868, 95% CI: 1.046– 7.863, p=0.041) were associated with GDM.Conclusion: Age of pregnant woman ≥ 30 years old, BMI≥ 24.0 kg/m2, history of adverse pregnancy and oral contraceptive use were independent risk factors for GDM.Keywords: gestational diabetes mellitus, advanced age, overweight, history of adverse pregnancy, history of oral contraceptive use

Shinye Kim,1 Yuki Shigemoto2 1Department of Counseling Psychology, University of Wisconsin-Madison, Madison, WI, 53706, USA; 2Department of Psychology, University of Florida, Gainesville, FL, 3261, USACorrespondence: Shinye Kim, Department of Counseling Psychology, University of Wisconsin-Madison, 335B Education Building 1000, Bascom Mall, Madison, WI, 53706, USA, Email shinye.kim@wisc.edu

Yunze Feng,1,&ast; Wencan Zhang,1,&ast; Kunpeng Li,1 Xiangyu Lin,1 Chen Liu,1 Chongyi Wang,1 Bingtao Hu,1 Kaibin Wang,1 Wanlong Xu,1 Haipeng Si1,2 1Department of Orthopedics, Qilu Hospital, Shandong University, Jinan, Shandong, 250000, People’s Republic of China; 2Key Laboratory of Qingdao in Medicine and Engineering, Department of Orthopedics, Qilu Hospital (Qingdao), Shandong University, Qingdao, Shandong, 266035, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haipeng Si, Key Laboratory of Qingdao in Medicine and Engineering, Department of Orthopedics, Qilu Hospital (Qingdao), Shandong Universityl, Qingdao, Shandong, 266035, People’s Republic of China, Email sihaipeng1978@email.sdu.edu.cn Wanlong Xu, Department of Orthopedics Qilu Hospital, Shandong University, Jinan, Shandong, 250000, People’s Republic of China, Email xuwanlong20082008@163.comPurpose: One-hole Split Endoscopy (OSE) is a newer surgical modality that can be applied to posterior cervical foraminotomy (PCF), lumbar discectomy, laminectomy, and decompression. It incorporates intervertebral foraminotomy, open surgery, and other lumboendoscopic techniques with a wide observation field, free space, and compatibility with various spinal surgical techniques and instruments. This study investigated the clinical efficacy of minimally invasive posterior cervical nucleus pulposus removal for cervical spondylotic radiculopathy (CSR) by OSE-Keyhole technique.Patients and Methods: This was a retrospective study of 63 patients treated with OSE keyhole treatment for CSR between May 2021 and September 2023 at Qilu Hospital of Shandong University, Qilu Hospital of Shandong University (Qingdao, China), and Second Hospital of Shandong University, respectively. Clinical outcomes included patients’ preoperative and postoperative visual analogue scale (VAS) - arm and neck, Japanese Orthopaedic Association Assessment Treatment Score (JOA) - cervical spine, which were collected at baseline, two days postoperatively, one month postoperatively, and three months postoperatively after the last follow-up visit for evaluation, and perioperative indicators, including intraoperative bleeding, length of hospital stay, postoperative complications, and reoperations, which were also collected.Results: Statistical analyses were performed for the baseline data and follow-up results of 63 patients. Compared to the preoperative baseline values, the follow-up results two days, one month and three months after surgery showed significant improvements in vas-arm, neck and JOA scores in the operated patients (P< 0.05) as well as a reduction in all perioperative-related indices.Conclusion: In the treatment of cervical pain and disability due to radiculopathy, OSE keyhole removal of the posterior cervical nucleus pulposus is a better clinical option as it is less invasive and recovers better postoperatively.Keywords: nerve root type cervical spondylosis, unilateral cervical disc herniation, posterior cervical laminectomy, single-channel endoscopy

Background: Orbital cellulitis is an acute inflammatory disorder of the orbit. It results from an acute infection spread from the blood, adjacent sinuses and facial skin. Cavernous sinus thrombosis (CST) typically occurs due to an infection originating from regions such as the face, sphenoid and ethmoid sinuses, or the oral cavity. Case report: An eleven-year-old girl was brought by her parents to our hospital with a complaint of right nasal discharge and fever for the last 10 days. She developed right-sided periorbital oedema for the past six days. She was under treatment at a local hospital. After that her parents noticed an increase in swelling associated with redness in her right peri-orbital region, so she came to our hospital. MRI brain showed changes of cavernous sinus thrombosis. A functional endoscopic sinus surgery (FESS) was performed for right nasal blockage on the second day of admission and about 10 ml of pus was drained. Fragmented fibrovascular tissue bits received from the frontal sinus and maxillary sinus revealed numerous pus cells with Gram-positive bacterial cocci on the third day. She responded to treatment as she was without fever by the day fourth on admission. The aerobic culture of the pus swab was positive and the organism detected was staphylococcus aureus on the eighth day after admission. Conclusion: Cavernous sinus thrombosis is a serious complication of orbital cellulitis with high morbidity and mortality. Unusually, orbital cellulitis occurs as sequelae of cavernous sinus thrombosis. Gram-positive bacteria noted on the nasal lesion's histopathology helped in starting antibiotics in the patient before the culture report was positive.

Background: There is a clear association between ABO blood group status and levels of Von Willebrand factor (vWF). Blood group O is related with lower expression of vWF which leads to relative bleeding tendency. Thus, relationships between Bleeding time (BT), Clotting time (CT) and blood groups are important in certain conditions like epistaxis, surgery, thrombosis etc. Aims and Objectives: i)To determine the blood group, of the students and to determine their relationship with BT and CT. Materials and Methods: Institution based cross-sectional observational study done in Department of Physiology, Tripura Medical College & Dr. BRAM Teaching Hospital. BT and CT were done by Duke’s Method and Capillary glass tube method respectively. Blood groups were determined on basis of presence or absence of agglutination. Qualitative data was expressed in percentage and quantitative data in frequency, mean and standard deviations. Chi-square test was applied. P value of 6 minutes found to be maximum in blood group O (53. 8%).Gender wise distribution showed CT > 6minutes in 39% females as compared to 34 %males (p value: 0.5826). Conclusion: In our study, CT was > 6 minutes and BT was > 4 minutes’ maximum in number in blood group O. Gender-wise BT and CT were higher in females than males. Our study showed that O blood group females are prone to certain diseases like epistaxis bleeding etc.

Background: Periprosthetic Joint Infection (PJI) is a nightmare for both patient and surgeon. Despite advances made in arthroplasty still incidence is 1-2%. Many of our understanding regarding PJI come from registry data. Despite performing large number of joint replacement surgeries there is a lack of optimal registry data from this part of world. We retrospectively analysed PJI data in four NABH accredited hospital of around 5370 patients and tried to identify common risk factors in them and proposed a clinical scoring system for assessing risk of PJI. Materials and Methods: The study population was patients requiring surgical intervention in the form of arthroplasty. PJIs were defined as patients requiring procedure at the operated site within 2 years of index surgery. We retrospectively analysed patients’ data from hospital records and lab investigations done at the time of surgery. Results: We found that statistical significant risk factor in our study were number of joint replacement performed, poor blood glucose and serum albumin, increase duration and complexity of surgeries, Rheumatoid Arthritis (RA), Chronic Kidney Disease (CKD) and chronic liver disease and use of allogenic blood transfusion. Relative risk (RR) of diabetes (RR 2.4), liver disease (RR 1.6), connective tissue and rheumatic diseases (RR 1.5), serum albumin (RR 2.1), allogenic blood transfusion (RR 2.3), Increase duration for surgery (RR2.1), CKD (RR1.3) was there with PJI. Conclusions: Our research consistently identified the most significant risk factors for PJI across all cases. We propose a patient-based scoring system to estimate individual PJI risk. By addressing modifiable risk factors before joint replacement, we can potentially reduce the incidence of PJI.

Shuli Hu, Yaling Li, Xuepeng Fan Department of Intensive Care Unit, Wuhan No. 1 Hospital, Wuhan, 430022, People’s Republic of ChinaCorrespondence: Xuepeng Fan, Email dcbpc888@126.comObjective: To explore how non-surgical esophageal cancer patients can identify high-risk factors for radiation-induced pneumonitis after receiving radiotherapy.Methods: We retrospectively included 228 esophageal cancer patients who were unable to undergo surgical treatment but received radiotherapy for the first time. By retrospective analysis and identifying potential risk factors for symptomatic radiation-induced pneumonitis (ie ≥grade 2), as well as delineating the affected lung as an area of interest on localized CT and extracting radiomics features, along with extracting dosimetric parameters from the affected lung area. After feature screening, patients were randomly divided into training and testing sets in a 7-to-3 ratio, and a prediction model was established using machine learning algorithms. Finally, the receiver operating characteristic (ROC) curve and decision curve analysis (DCA) were used to validate the predictive performance of the model.Results: A total of 54 cases of symptomatic radiation pneumonitis occurred in this study, with a total incidence rate of 23.68%. The results of multivariate analysis showed that the occurrence of symptomatic radiation pneumonitis was significantly correlated with the mean lung dose (MLD), esophageal PTVD90, esophageal PTVV50, V5, V10, V15, and V20 in patients. The machine learning prediction model constructed based on candidate prediction variables has a prediction performance interval between 0.751 (95% CI: 0.700– 0.802) and 0.891 (95% CI: 0.840– 0.942) in the training and validation sets, respectively. Among them, the RFM algorithm has the best prediction performance for radiation-induced pneumonitis, with 0.891 (95% CI: 0.840– 0.942) and 0.887 (95% CI: 0.836– 0.938) in the training and validation sets, respectively.Conclusion: The combination of localization CT radiomics features and diseased lung dosimetry parameters has good predictive value for radiation-induced pneumonitis in esophageal cancer patients after radiotherapy. Especially, the radiation-induced pneumonitis prediction model constructed using RF algorithm can be more effectively used to guide clinical decision-making in esophageal cancer patients.Keywords: esophageal cancer, radiotherapy, radiation pneumonitis, radiomics, prediction model

Yang-Da Chen,1 Zhi-Gao Wen,1 Jun-Jie Long,1 Yong Wang2 1Department of Emergency Medicine, Shenzhen Luohu Hospital Group Luohu People’s Hospital (The Third Affiliated Hospital of Shenzhen University), Shenzhen, People’s Republic of China; 2Department of Cardiology, Shenzhen Luohu Hospital Group Luohu People’s Hospital (The Third Affiliated Hospital of Shenzhen University), Shenzhen, People’s Republic of ChinaCorrespondence: Yong Wang, Email drwangyong2016@163.comBackground: Inflammation plays a key role in the pathogenesis of slow coronary flow phenomenon (SCFP). SCFP is a condition that can complicate the management of ischemia and no obstructive coronary arteries (INOCA), making it essential to identify reliable predictors. Although the systemic inflammation response index (SIRI) has been proven to relate to various cardiovascular diseases. However, the predictive value of SIRI for SCFP in patients with INOCA remains unclear.Methods: A total of 1422 patients with INOCA were consecutively included in this study. 89 individuals were diagnosed with SCFP (the SCFP group). A 1:2 age- and -sex-matched patients with INOCA and normal blood flow were selected as the control group (n=178). Plasma neutrophil, monocyte, and lymphocyte counts were collected so as to determine the value of SIRI.Results: Patients with SCFP had an elevated level of body mass index (BMI) and an increased incidence of smoking and diabetes. The SIRI was significantly higher in the SCFP group than in the controls (2.3± 1.3 vs 1.8± 1.3, p=0.002). The SIRI increased as the number of coronary arteries involved in the SCFP increased. Univariate analyses showed that BMI, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and SIRI were associated with SCFP. Multivariate logistic regression analysis revealed that BMI and SIRI were independent predictors of SCFP occurrence. The ROC curve showed that when the SIRI was > 1.140, the sensitivity and specificity were 87.6% and 60.1%, respectively, and the area under the ROC curve (AUC) was 0.644 (95% CI: 0.578– 0.710, P < 0.001).Conclusion: The findings demonstrated that an increased SIRI may have a potential role in distinguishing SCFP in patients with INOCA. SIRI could improve the predictive value of SCFP compared to neutrophils, monocytes, and lymphocytes alone.Keywords: systemic inflammation response index, slow coronary flow phenomenon, ischemia and no obstructive coronary arteries, predictors

Ziyad F Al Nufaiei,1,2 Reem H Alluhibi,1,2 Mashael B Alsabiti,1,2 Haya Onaybisi,1,2 Lama M Alahmadi,1,2 Shatha A Jabal,1,2 Raid M Al Zhranei1,2 1Respiratory Therapy Department, College of Applied Medical Sciences, King Saud bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia; 2King Abdullah International Medical Research Center, Jeddah, Saudi ArabiaCorrespondence: Ziyad F Al Nufaiei, Department of Respiratory Therapy College of Applied Medical Sciences-Jeddah King Saud bin Abdulaziz University for Health Sciences, P.O.Box.9515, Mail Code 6610, Jeddah, 21423, Saudi Arabia, Tel +966551600060 Ext 46125, Email nufaieiz@ksau-hs.edu.saBackground: Obstructive sleep apnea (OSA), if left untreated, can have major negative effects on health, such as an elevated risk of diabetes, heart disease, and stroke. Increasing people’s knowledge of this illness might lessen the stigma associated with sleep problems and motivate them to get treatment if they think they might have OSA.Aim of the Study: This study aims to assess the knowledge and awareness of OSA among patients’ families in Saudi Arabia.Methods: A phenomenological-oriented study with in-depth interviews was used to collect data from 28 participants.Results: Two themes and subthemes emerged from the interviews, revealing significant knowledge gaps, especially regarding the health risks and management of OSA. Only a few participants were aware of the serious health implications of untreated OSA. Furthermore, many did not know about effective management strategies for OSA.Conclusion: The level of awareness and knowledge among participants was poor, with participants’ lifestyles significantly affected by having relatives with OSA. They expressed concerns about challenges with CPAP adherence and recommended various coping techniques to support affected individuals.Keywords: obstructive sleep apnea, lifestyles, knowledge & awareness, qualitative design, snoring, health literacy

Shiyu Zhang, Fanting Kong, Lei Zheng, Xiaowei Li, Lining Jia, Lixian Yang Department of Breast Surgery, Xingtai People’s Hospital, Xingtai, Hebei, 054000, People’s Republic of ChinaCorrespondence: Lixian Yang, Department of Breast Surgery, Xingtai People’s Hospital, No. 818 Xiangdu District, Xingtai, Hebei, 054000, People’s Republic of China, Email yanglixian@hebmu.edu.cnBackground: The role of Semaphorin 7a (SEMA7A) in the initiation and progression of different types of cancerous lesions has been extensively studied. However, the prognostic significance of SEMA7A, specifically in breast cancer (BC), lacks clarity.Methods: We conducted an evaluation on the relationship between SEMA7A and the prognosis, immune invasion and tumor mutation burden in different types of cancer by analyzing data from The Cancer Genome Atlas database. The present study focused on investigating the expression level, mutation, immune correlation and coexpression of SEMA7A in BC, utilizing various databases such as the University of Alabama at Birmingham Cancer data analysis portal, cBioPortal and tumor immune estimation resource. Survival analysis was carried out using the Kaplan-Meier Plotter. Furthermore, we employed the R software package to generate receiver operating characteristic (ROC) curves and nomograms. Notably, P< 0.05 was considered to indicate statistical significance.Results: Using pancancer analysis, it has been observed that the expression of SEMA7A is elevated in various types of cancer and is strongly correlated with the prognosis of different cancer types. SEMA7A also exhibits a significant association with the tumor mutation burden of diverse types of cancer. Moreover, SEMA7A displays a notable increase in BC cases, and was indicated to have a substantial association with the abundance of immune infiltration. In-depth survival analysis demonstrated that elevated levels of SEMA7A expression are notably linked to shorter overall survival and distant metastasis-free survival among patients with BC. The efficiency of SEMA7A as a reliable prognostic biomarker for BC has been substantiated by the validation of ROC curves and nomograms.Conclusion: SEMA7A has the potential to function as a prognostic indicator for BC, and its correlation with immune infiltration in BC is significant.Keywords: SEMA7A, breast cancer, biomarker, prognosis, methylation, immune infiltration, nomogram, bioinformatics

Ben Wang,1,2 Peilin Cheng,2 Bingjie Jin,2 Ying Jiang,2 Qingcai Wang,1 Hongwei Xu2 1Department of Gastroenterology, The Affiliated Taian City Central Hospital of Qingdao University, Taian, People’s Republic of China; 2Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of ChinaCorrespondence: Hongwei Xu, Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of China, Email xuhongwei@sdfmu.edu.cnBackground & Aims: The metabolic pathways of tryptophan (TRP) have been implicated in the pathophysiology of irritable bowel syndrome (IBS), positing that the strategic modulation of TRP consumption may exert regulatory effects on serotonin levels, consequently altering the clinical manifestation of IBS. This systematic review was meticulously orchestrated to evaluate the effect of TRP restriction on IBS.Methods: A comprehensive search of the MEDLINE/PubMed, Cochrane Library, and Embase databases was conducted. Controlled trials that compared the efficacy of TRP restriction in IBS patients were scrutinized. The primary outcomes were gastrointestinal symptoms, quality of life, and pain, whereas the secondary outcomes included anxiety, mood, and safety. The risk of bias was meticulously assessed according to the guidelines recommended by the Cochrane Collaboration.Results: A total of five trials, enrolling 135 participants, were incorporated into the qualitative synthesis. Low-TRP intake attenuated gastrointestinal discomfort and enhanced psychological well-being in IBS patients, while the effects of acute TRP depletion were controversial. Safety data from one randomized controlled trial reported no occurrence of adverse events.Conclusion: This systematic review suggests that moderating, rather than depleting, TRP intake may potentially be a feasible and safe adjunctive treatment for patients with IBS. Future research incorporating a high-quality study design and consensus on clinical outcome measurements for IBS is warranted.Keywords: irritable bowel syndrome, reduced tryptophan diet, acute tryptophan depletion, systematic review

Hailei He,1 Zhen Wang,2 Cuilin Fang,3 Junfeng Yan4 1Department of Oral and Maxillofacial Surgery, Ganzhou People’s Hospital, Ganzhou, Jiangxi, 341000, People’s Republic of China; 2Department of Stomatology, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou, Zhejiang, 324000, People’s Republic of China; 3Department of Medicine and Equipment, Ganzhou Cancer Hospital, Ganzhou, Jiangxi, 341005, People’s Republic of China; 4Department of Stomatology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of ChinaCorrespondence: Junfeng Yan, Department of Stomatology, The First Affiliated Hospital of Nanchang University, No. 17, Yongwaizheng Street, Donghu District, Nanchang, Jiangxi, 330006, People’s Republic of China, Email yanjunfengd@163.comPurpose: LIPH4 has been identified as an oncogenic lncRNA in different malignant diseases. This research aims to elucidate the link between the expression of LIPH4 and its prognostic application in tongue squamous cell carcinoma (TSCC).Methods: To assess the expression of LIPH4, 142 TSCC and normal cases, respectively, which met the selection parameters, were used for qRT-PCR analysis. Furthermore, the association of LIPH4 expression with TSCC’s clinicopathological features was identified via the Chi-square test. Moreover, the Kaplan–Meier test was used for calculating the survival rates, whereas the association of patient survival with prognostic factors was assessed with the help of Cox proportional hazard analysis.Results: The data indicated upregulated LIPH4 levels in TSCC samples than healthy samples. Furthermore, LIPH4 expression was associated with TSCC differentiation and stage, where increased expression indicated reduced disease-free survival (DFS) and overall survival (OS) rates. Additionally, advanced TSCC individuals with enhanced LIPH4 expression had reduced OS and DFS rates than those with reduced LIPH4 expression. Serum LIPH4 could be a promising diagnostic bio-index for TSCC, with an area under the curve of 0.8920 (95% CI = 0.8540– 0.9299). These data revealed that the overexpression of LIPH4 might be a substantial prognostic factor for independently predicting the OS and DFS rates of TSCC patients.Conclusion: Altogether, this research revealed that the expression of LIPH4 expression is closely associated with TSCC progression and, therefore, can be employed as a biomarker for its prognosis.Keywords: lncRNA, LIPH4, biomarker, tongue squamous cell carcinoma (TSCC)

Amr J Halawani,1 Hisham I Abu-Tawil,2,3 Salah Alharbi,4 Bandar S Almalki,5 Fawaz M Majmi,6 Renad A Miny,1 Nada G Alghoribi,1 Sulaiman S Alabsi,7 Saeed M Kabrah,1 Haneen O Alhaj,8 Musaed M Alshahrani,9 Nora Y Hakami10 1Department of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences, Umm Al-Qura University, Makkah, Saudi Arabia; 2Department of Laboratory and Blood Bank, Prince Mohammed Bin Nasser Hospital, Ministry of Health, Jazan, Saudi Arabia; 3Department of Laboratory and Blood Bank, King Faisal Medical City for Southern Regions, Ministry of Health, Abha, Saudi Arabia; 4Armed Forces Hospital in Jazan, Ministry of Defence, Jazan, Saudi Arabia; 5General Medical Committee, tDirectorate General of Health Affairs, Jazan, Saudi Arabia; 6Department of Pharmacy, Ahad Al Masarihah General Hospital, Ministry of Health, Jazan, Saudi Arabia; 7King Abdulaziz Medical City, Jeddah, Saudi Arabia; 8Kholoud Laboratory for Medical Analysis, Makkah, Saudi Arabia; 9Blood Bank Laboratory, Prince Sultan Military Medical City, Saudi Arabia; 10Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi ArabiaCorrespondence: Amr J Halawani, Department of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences Umm Al-Qura University, Makkah, Saudi Arabia, Email ajjhalawani@uqu.edu.saPurpose: Jazan Province in Saudi Arabia is notable for its high prevalence of inherited hemoglobinopathies, including sickle cell disease and thalassemia, necessitating frequent blood transfusions for affected individuals. To mitigate risks such as RBC alloimmunization and hemolytic transfusion reactions, ensuring blood compatibility is crucial. The Kell (KEL) blood group system, pivotal alongside the ABO and RH systems, encompasses multiple antigens implicated in these complications. This study aimed to investigate the frequencies of KEL blood group antigens (K, k, Kpa, and Kpb) and determine KEL phenotypes (K/k and Kpa/Kpb) among Saudi blood donors living in Jazan Province.Methods: A total of 138 anonymous healthy Saudi blood donors from Prince Mohammed bin Nasser Hospital in Jazan Province, Saudi Arabia, were enrolled in this study. Anticoagulated blood was analyzed using the gel card technique to assess K, k, Kpa, and Kpb antigens.Results: The prevalence of KEL antigens was as follows: K (n = 9, 6.52%), k (n = 137, 99.28%), Kpa (n = 1, 0.72%), and Kpb (n = 138, 100%). KEL phenotypes observed were K+k+ (n = 8, 5.80%), K+k− (n = 1 0.72%), K−k+ (n = 129, 93.48%), Kp(a+b+) (n = 1, 0.72%), and Kp(a−b+) (n = 137, 99.28%).Conclusion: This study provides insights into the prevalence of KEL blood group antigens and phenotypes in Jazan Province, Saudi Arabia. These findings may contribute to the establishment of a national blood group database and guide transfusion practices to ensure compatibility and minimize alloimmunization risks.Keywords: Kell blood group, blood transfusion, immunohematology, Saudi Arabia

Ran Zhao,1,&ast; Dexiang Ji,1,&ast; Yulan Zhou,1,2 Ling Qi,1,2 Fei Li1,2 1Jiangxi Provincial Key Laboratory of Hematological Diseases, Department of Hematology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China; 2Jiangxi Clinical Research Center for Hematologic Disease, Nanchang, Jiangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fei Li, Email yx021021@sina.comBackground: Immunosuppressive therapy (IST) with horse or rabbit anti-human thymocyte immunoglobulin (h-/r-ATG) and hematopoietic stem cell transplantation (HSCT) are two baseline treatments for severe aplastic anemia (SAA) and transfusion-dependent non-severe aplastic anemia (TD-NSAA) patients. Addition of thrombopoietin receptor agonists (TPO-RAs) to standard IST therapy (h-/r-ATG) has greatly improved the survival of SAA, whereas porcine anti-lymphocyte globulin (p-ALG) combined with TPO-RAs still had a matter of debate.Methods: We retrospectively compared the data of 48 AA patients in our center between 2020 and 2022, 23 AA patients received with p-ALG ± TPO-RAs, 25 AA patients underwent matched sibling donor (MSD-) or haploidentical (haplo-) HSCT.Results: For patients in the HSCT group, the ORR was 90.9% which was significantly higher than that in the IST±TPO-RAs group (45.5%, P = 0.001) at 3 months; moreover, patients who underwent HSCT achieved faster transfusion independence, better CR rate, shorter time of recovery normal blood routine, and the percentage of normal blood routine (all P < 0.05) compared with IST±TPO-RAs group. However, the ORR were similary at 6 months in the two groups (95.5% vs 81.8% P = 0.342), with a median follow up of 19.8 months (range, 0.3– 38.2 months), the 2-year FFS and OS in the two cohorts has no different. Subgroup analysis further indicated that the 2-year FFS and OS were similar between IST+TPO-RAs and haplo-HSCT subgroups, as well as in IST+TPO-RAs and MSD-HSCT cohorts. Moreover, the first-time hospitalizations were much more expensive in the HSCT group than in the IST±TPO-RAs group (402 756 vs. 292 902 yuan, P = 0.002).Conclusion: P-ALG-based-IST±TPO-RAs is a good treatment option with similar FFS and OS compared to allo- HSCT for AA patients without the opportunity of HSCT.Keywords: porcine anti-human thymocyte immunoglobulin, thrombopoietin receptor agonist, hematopoietic stem cell transplantation, aplastic anemia

Chao Yang,1 Haitao Xiao,1 Qizhi Yang,1 Zhendong Zhao,1 Yifan Liu1,2 1Department of Urology, 302 Hospital of China Guizhou Aviation Industry Group, Anshun City, Guizhou Province, 561400, People’s Republic of China; 2Department of Urology, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou City, Guangdong Province, 510000, People’s Republic of ChinaCorrespondence: Yifan Liu, Department of Urology, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou City, Guangdong Province, 510000, People’s Republic of China, Email doctorhorse2008@foxmail.comObjective: This study aimed to assess the association between preoperative neutrophil–lymphocyte ratio (NLR) and febrile urinary tract infection (fUTI) in patients who underwent percutaneous nephrolithotomy (PCNL).Patients and Methods: The clinical data of patients who underwent PCNL at our hospital between March 2020 and May 2023 were retrospectively analyzed. According to whether fUTI occurs after operation, collected data were divided to the patients into fUTI and non-fUTI. Univariate analysis, relative operating characteristic (ROC) curves and multivariate logistic regression analysis were performed on the data.Results: A total of 405 patients were enrolled in the study. The procedure was successfully performed in all patients, and the incidence of fUTI was 8.4% (34/405). Eight patients eventually developed sepsis, and the incidence of sepsis in fUTI patients was 23.5%. The result shows a significant correlation between NLR and fUTI (95% confidence interval [CI],1.21– 1.83, Odds ratio [OR]=1.49, p< 0.001). The predictive ability of NLR on the occurrence of fUTI was assessed by plotting relative operating characteristic (ROC) curves. The area under the curve (AUC) in the ROC curve for NLR was 0.718 according to the Youden index, and the best cut-off value of NLR was 2.71. Furthermore, logistic multiple regression model adjustment was carried out to further confirm the robustness of the relationship between NLR and fUTI. The results indicated robustness regardless of whether NLR was a continuous variable or a categorical variable.Conclusion: NLR can be used as a simple and effective preoperative indicator for the prediction of fUTI in patients undergoing PCNL.Keywords: percutaneous nephrolithotomy, febrile urinary tract infection, neutrophil–lymphocyte ratio

Hisham Mohamed Hussein,1,2 Amsha Alhumaidi Alshammari,3 Hand Zamel M Alshammari,4 Monira I Aldhahi,5 Yahya Ali Hamad Suwaidi,6 Ahmed Abdelmoniem Ibrahim1 1Department of Physical Therapy, College of Applied Medical Sciences, University of Ha’il, Ha’il, Saudi Arabia; 2Department of Basic Sciences for Physical Therapy, Faculty of Physical Therapy, Cairo University, Giza, Egypt; 3Medical Rehabilitation Department of Physical Therapy in Maternity and Children Hospital in Hail in the Kingdom of Saudi Arabia, Ha’il, Saudi Arabia; 4Department of Physical Therapy, Hayati Center Day Care, Ha’il, Saudi Arabia; 5Department of Rehabilitation Sciences, College of Health and Rehabilitation Sciences, Princess Nourah bint Abdulrahman University (PNU), Riyadh, 11671 Saudi Arabia; 6Department of Physical Therapy, Home Health Care, Jazan General Hospital, Jazan, Saudi ArabiaCorrespondence: Ahmed Abdelmoniem Ibrahim, Email a.abdalmoniem@uoh.edu.sa; boodytwo48@gmail.comBackground: Children diagnosed with spastic diplegic Cerebral Palsy (CP) usually demonstrate hypertonicity of the lower limb muscles which affects the normal alignments and weight reception by the feet. These impairments could be correlated to the limitations in gross motor function such as standing and walking abilities. Understanding these relationships can contribute to developing more effective rehabilitation strategies and improving overall motor outcomes for affected children.Objective: The current study was designed to explore the relationship between plantar surface area, weight distribution on the plantar surface, and gross motor function (namely, standing and walking abilities) in spastic diplegic CP children.Methods: Seventy-one spastic diplegic CP children aged 8– 14 years joined this cross-sectional study. The Person’s correlation coefficient and regression tests were used to assess the correlation between variables, namely, Gross Motor Function (GMFM), Calf Muscle Tone, Plantar surface area (PSA), and Peak pressure on mid and hind feet (PPMF, PPHF, respectively). These variables were assessed using the GMFM-88 scale, Modified Ashworth scale, and foot scan plantar pressure detection system, respectively.Results: The correlation analysis demonstrated a strong to moderate positive correlation between PSA, PPMF, PPHF, and GMFM-D and GMFM-E. Additionally, regression model showed prediction levels equal to 0.791 for the GMFM-D and 0.720 for the GMFM-E categories, respectively.Conclusion: Standing and walking abilities were positively correlated (r ≥ .6) with the increased plantar surface area and higher peak pressure on mid and hind feet in spastic diplegic CP. Future longitudinal studies should investigate changes in gross motor function in relation to improvement in plantar surface area and peak pressure values.Keywords: spastic diplegia, gross motor function, calf muscle, plantar surface area

Chen Qu,1,&ast; Fei Xia,2,&ast; Ling Chen,1 Hong-Jian Li,2 Wei-Min Li1 1Department of Ultrasonography, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, People’s Republic of China; 2Department of Ultrasonography, Huai’an Cancer Hospital, Huai’an, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hong-Jian Li, Department of Ultrasonography, Huai’an Cancer Hospital, Huai’an, Jiangsu, 223232, People’s Republic of China, Tel +8613511507565, Email 492938595@qq.com Wei-Min Li, Department of Ultrasonography, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, 214000, People’s Republic of China, Tel +8613912362309, Email 1005342597@qq.comPurpose: : To explore the diagnostic value of artificial intelligence (AI)-based on real-time dynamic ultrasound imaging system for minimal breast lesions.Patients and Methods: Minimal breast lesions with a maximum diameter of ≤ 10mm were selected in this prospective study. The ultrasound equipment and AI system were activated Simultaneously. The ultrasound imaging video is connected to the server of AI system to achieve simultaneous output of AI and ultrasound scanning. Dynamic observation of breast lesions was conducted via ultrasound. And these lesions were evaluated and graded according to the Breast Imaging Reporting and Data System (BI-RADS) classification system through deep learning (DL) algorithms in AI. Surgical pathology was taken as the gold standard, and ROC curves were drawn to determine the area under the curve (AUC) and the optimal threshold values of BI-RADS. The diagnostic efficacy was compared with the use of a BI-RADS category > 3 as the threshold for clinically intervening in diagnosing minimal breast cancers.Results: 291 minimal breast lesions were enrolled in the study, of which 228 were benign (78.35%) and 63 were malignant (21.65%). The AUC of the ROC curve was 0.833, with the best threshold value > 4A. When using >BI-RADS 3 and >BI-RADS 4A as threshold values, the sensitivity and negative predictive value for minimal breast cancers were higher for >BI-RADS 3 than >BI-RADS 4A (100% vs 65.08%, 100% vs 89.91%, P values < 0.001). However, the corresponding specificity, positive predictive value, and accuracy were lower than those for >BI-RADS 4A (42.11% vs 85.96%, 32.31% vs 56.16%, and 54.64% vs 81.44%, P values < 0.001).Conclusion: The AI-based real-time dynamic ultrasound imaging system shows good capacity in diagnosing minimal breast lesions, which is helpful for early diagnosis and treatment of breast cancer, and improves the prognosis of patients. However, it still results in some missed diagnoses and misdiagnoses of minimal breast cancers.Keywords: Breast cancer, ultrasound, artificial intelligence, diagnostic

Zhongsheng Zhu1,2 1Department of Cardiology, Guangming Traditional Chinese Medicine Hospital of Pudong New Area, Shanghai, 201321, People’s Republic of China; 2Department of Cardiology, Shanghai Pudong Hospital Affiliated to Fudan University, Shanghai, 201300, People’s Republic of ChinaCorrespondence: Zhongsheng Zhu, Department of Cardiology, Guangming Traditional Chinese Medicine Hospital of Pudong New Area, 339 Dongmen Ave, Pudong, Shanghai, 201321, People’s Republic of China, Tel +86-18117209753, Email drzzs66@163.comBackground: Arterial stiffness is associated with accelerated progression of atherosclerosis and plaque rupture. Lysyl oxidase-like 2 (LOXL2) plays a vital role in inflammatory responses, matrix deposition and arterial stiffness. This study assessed the correlation between the serum LOXL2 concentration and disease severity, inflammation, and endothelial dysfunction of coronary artery disease (CAD).Methods: The study included 143 CAD patients and 150 non-CAD patients who underwent coronary angiography. Medical records, demographic and clinical baseline parameters were collected. Serum LOXL2 levels were measured using an ELISA kit.Results: CAD patients had higher serum LOXL2 levels than non-CAD patients, and LOXL2 levels were associated with severity of coronary lesions. Serum LOXL2 level was positively correlated with low-density lipoprotein cholesterol (LDL-C) (r=0.161, P=0.054), systolic blood pressure (SBP) (r=0.175, P=0.036), high-sensitivity C-reactive protein (hs-CRP) (r=0.177, P=0.035), intima-media thickness (IMT) (r=0.190, P=0.023), and brachial-ankle pulse wave velocity (baPWV) (r=0.203, P=0.015), while negatively associated with high-density lipoprotein cholesterol (HDL-C) (r=− 0.191, P=0.023) and flow-mediated dilation (FMD) (r=− 0.183, P=0.028) in CAD patients. Multivariate logistic regression showed that LOXL2 is independently correlated with LDL-C (OR=3.380; 95% CI=1.258– 9.082; P=0.016), hs-CRP (OR=10.988; 95% CI=1.962– 61.532; P=0.006), TC (OR=2.229; 95% CI=1.005– 4.944; P=0.049), IMT (OR=72.719; 95% CI=2.313– 2286.008; P=0.015), and baPWV (OR=1.002; 95% CI=1.001– 1.004; P=0.005) in CAD patients. The receiver operating characteristic (ROC) curve showed that the best cut-off for CAD as serum LOXL2 is 275.35 pg/mL, with sensitivity and specificity of 77.6% and 84%, respectively.Conclusion: Our data demonstrated that LOXL2 could be a potential biomarker and independent risk factor for CAD patients.Keywords: coronary artery disease, CAD, atherosclerosis, endothelial dysfunction, arterial stiffness, LXOL2

Guomiao Su,&ast; Zifan Xu,&ast; Shiyue Liu,&ast; Dou Hao, Yanxi Li, Guoqing Pan Department of Pathology, the First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guoqing Pan, Department of Pathology, the First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, People’s Republic of China, Email guoqing_pan@163.comPurpose: Semaphorin 5A (SEMA5A) and autophagy-related genes (ARGs) are pivotal in the pathogenesis of gastric cancer (GC). However, the potential regulatory role of SEMA5A in autophagy via its associated ARGs and the underlying molecular mechanisms remain unresolved.Patients and Methods: GC-related datasets from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were analyzed to identify differentially expressed genes (DEGs) between GC and control samples. The intersection of DEGs with ARGs produced candidate genes, which were further analyzed using Spearman correlation with SEMA5A to identify signature genes. Stratification of GC samples based on signature gene expression, followed by Kaplan-Meier survival analysis, identified key genes. Subsequent analyses, including gene set enrichment analysis (GSEA), immune infiltration, and immune checkpoint evaluation, were conducted on the key genes and SEMA5A. The mRNA expression level was quantified using real-time quantitative polymerase chain reaction (RT-qPCR).Results: Ninety candidate genes were identified for Spearman correlation with SEMA5A, revealing TNFSF11, BMP6, ITPR1, and DLC1 with correlation coefficients exceeding 0.3. Survival analysis underscored DLC1 and BMP6 as key genes due to significant prognostic differences. GSEA implicated SEMA5A, BMP6, and DLC1 in the ECM receptor interaction pathway. Immune infiltration analysis indicated a negative correlation of SEMA5A and BMP6 with M1 macrophages, while DLC1 exhibited the strongest association with the immune checkpoint PDCD1LG2 (p < 0.05, cor = 0.43). The mRNA expression level of SEMA5A was significantly upregulated in AGS parental cells compared to GES-1 cells (p < 0.01), whereas DLC1 and BMP6 mRNA levels were markedly downregulated in AGS parental cells relative to GES-1 (p < 0.0001).Conclusion: ARGs BMP6 and DLC1, associated with SEMA5A, were identified, and their prognostic significance in GC was demonstrated. Additionally, their regulatory mechanisms were further elucidated through immune infiltration analysis and molecular network construction, providing a theoretical foundation for future research on the molecular mechanisms in patients with GC.Keywords: GC, SEMA5A, autophagy, ARGs, bioinformatics analysis

Pawe&lstrok; Radkowski,1– 3 Maria Agnieszka Derkaczew,2 Micha&lstrok; Adam Jacewicz,4,5 Dariusz Onichimowski1,2 1Department of Anaesthesiology and Intensive Care, Regional Specialist Hospital in Olsztyn, Olsztyn, Poland; 2Department of Anaesthesiology and Intensive Care, Faculty of Medicine, Collegium Medicum University of Warmia and Mazury in Olsztyn, Olsztyn, Poland; 3Hospital zum Heiligen Geist, Fritzlar, Germany; 4Regional Specialist Hospital in Olsztyn, Olsztyn, Poland; 5Department of Pharmacology and Toxicology, Faculty of Medicine, Collegium Medicum University of Warmia and Mazury in Olsztyn, Olsztyn, PolandCorrespondence: Maria Agnieszka Derkaczew, Department of Anaesthesiology and Intensive Care, Faculty of Medicine, Collegium Medicum University of Warmia and Mazury in Olsztyn, Olsztyn, Poland, Email m.derkaczew@gmail.comAbstract: The prevalence of morbid obesity in today’s population around the world is alarming. Morbid obesity involves substantial changes in body composition and function, which can affect the pharmacodynamics and pharmacokinetics of many drugs. This paper aims to discuss the application of muscle relaxants and their reversing agents in patients with morbid obesity. This work is based both on the available literature and the author’s personal experience. Dosage recommendations for muscle relaxants in morbidly obese patients are as follows: non-depolarizing relaxants like rocuronium, vecuronium, atracurium, and cisatracurium should be based on ideal body weight. Succinylcholine dosage should be adjusted to total body weight with a 200 mg maximum, while mivacurium should also be based on total body weight. Pancuronium is not used due to its long duration. Neostigmine dosing remains uncertain, but some suggest using total body weight. When it comes to Sugammadex opinions of the authors are divided, some indicate that it should be dosed based on ideal body weight, but more recent studies show that it should be based on 40% of corrected body weight.Keywords: muscle relaxants, muscle relaxants reversal agents, succinylcholine, sugammadex, morbid obesity, obese patients

Xueya Chen,1,&ast; Zhiling Yan,2,&ast; Weipeng Liu,1 Lili Guo,1 Jinmei Xu,2 Li Shi,3 Yufeng Yao1 1Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming, People’s Republic of China; 2Department of Gynaecologic Oncology, The No. 3 Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China; 3Department of Immunogenetics, Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li Shi, Department of Immunogenetics, Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming, Yunnan, 650118, People’s Republic of China, Email shili.imb@gmail.com Yufeng Yao, Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming, Yunnan, 650118, People’s Republic of China, Email leoyyf@gmail.com; yufeng_yao@imbcams.com.cnPurpose: Cervical cancer (CC) poses a significant threat to women’s health worldwide, and multiple signaling pathways have been confirmed to be involved in its development. The AMPK signaling pathway plays a central role in maintaining energy homeostasis, and its dysregulation is closely associated with the occurrence of CC. Changes in microRNA (miRNA) expression levels might be related to the AMPK signaling pathway. Single nucleotide polymorphisms (SNPs) can affect the function of miRNA and result in the development of CC. To investigate the association between the SNPs of AMPK pathway-associated miRNAs and CC in a Han Chinese population, we selected eight miRNA genes located in the AMPK pathway and analyzed nine SNP loci within these genes to explore whether they are associated with genetic susceptibility to cervical intraepithelial neoplasia (CIN) and CC.Methods: A total of 2,220 subjects were included in this study, including 928 healthy controls, 421 CIN patients, and 871 CC patients. Nine candidate SNPs (rs895819 in miR-27a, rs10061133 in miR-449b, rs41291179 in miR-216a, rs76481776 in miR-182, rs10406069 in miR-5196, rs12803915 and rs550894 in miR-612, rs66683138 in miR-3622b, and rs2620381 in miR-627) were genotyped using the TaqMan method.Results: The results showed significant differences in the allele distribution of rs41291179 and rs12803915 between the control group and the CIN group, as well as between the control group and the CC group (all P values < 0.005). The A allele of rs41291179 and the G allele of rs12803915 were associated with decreased risk of CIN (OR = 0.05, 95% CI: 0.01– 0.39; OR = 0.61, 95% CI: 0.49– 0.76) and CC (OR = 0.08, 95% CI: 0.01– 0.66; OR = 0.71, 95% CI: 0.59– 0.86), respectively.Conclusion: Our results suggest that polymorphisms in miRNA genes of the AMPK signaling pathway are associated with the development of CC.Keywords: genotyping, SNP, gene enrichment, genetic susceptibility

Longqing Xia,1 Mengmeng Yang,1 Nan Zang,1– 4 Jia Song,1– 4 Jun Chen,1– 4 Huiqing Hu,1 Kewei Wang,1 Yingyue Xiang,1 Jingwen Yang,1 Liming Wang,1 Ying Zou,1 Xiaoyu Lv,1 Xinguo Hou,1– 4 Li Chen1– 4 1Department of Endocrinology, Qilu Hospital of Shandong University, Jinan, 250012, People’s Republic of China; 2Institute of Endocrine and Metabolic Diseases of Shandong University, Jinan, 250012, People’s Republic of China; 3Key Laboratory of Endocrine and Metabolic Diseases, Shandong Province Medicine & Health, Jinan, 250012, People’s Republic of China; 4Jinan Clinical Research Center for Endocrine and Metabolic Disease, Jinan, 250012, People’s Republic of ChinaCorrespondence: Li Chen, Department of Endocrinology, Qilu Hospital of Shandong University, Shandong, People’s Republic of China, Email chenli3@email.sdu.edu.cnBackground: The depletion of β cell mass is widely recognized as a significant contributor to the progression of type 2 diabetes mellitus (T2DM). Exosomes derived from mesenchymal stem cells (MSC-EXOs) hold promise as cell-free therapies for treating T2DM. However, the precise effects and mechanisms through which MSC-EXO affects β cell function remain incompletely understood, and the limited ability of MSC-EXO to target β cells and the short blood circulation time hampers its therapeutic effectiveness.Methods: The effects of MSC-EXO were investigated in T2DM mice induced by a high-fat diet combined with STZ. Additionally, the high glucose-stimulated INS-1 cell line was used to investigate the potential mechanism of MSC-EXO. Michael addition reaction-mediated chemical coupling was used to modify the surface of the exosome membrane with a β-cell-targeting aptamer and polyethylene glycol (PEG). The β-cell targeting and blood circulation time were evaluated, and whether this modification enhanced the islet-protective effect of MSC-EXO was further analyzed.Results: We observed that the therapeutic effects of MSC-EXO on T2DM manifested through the reduction of random blood glucose levels, enhancement of glucose and insulin tolerance, and increased insulin secretion. These effects were achieved by augmenting β cell mass via inhibiting nuclear factor erythroid 2–related factor 2 (NRF2)-mediated ferroptosis. Mechanistically, MSC-EXOs play a role in the NRF2-mediated anti-ferroptosis mechanism by transporting active proteins that are abundant in the AKT and ERK pathways. Moreover, compared to MSC-EXOs, aptamer- and PEG-modified exosomes (Apt-EXOs) were more effective in islet protection through PEG-mediated cycle prolongation and aptamer-mediated β-cell targeting.Conclusion: MSC-EXO suppresses NRF2-mediated ferroptosis by delivering bioactive proteins to regulate the AKT/ERK signaling pathway, thereby improving the function and quantity of β cells. Additionally, Apt-EXO may serve as a novel drug carrier for islet-targeted therapy.Keywords: exosome, type 2 diabetes mellitus, β-cell-targeting, polyethylene glycol modification, ferroptosis

David C Klonoff,1 Brian L Levy,2 Michael J Jaasma,3 Manish Bharara,3 Deborah R Edgar,4 Christian Nasr,5 David L Caraway,3 Erika A Petersen,6 David G Armstrong7 1Diabetes Research Institute, Mills-Peninsula Medical Center, San Mateo, CA, USA; 2New York University Grossman School of Medicine, New York, NY, USA; 3Nevro Corp, Redwood City, CA, USA; 4Commexus Ltd, Dunblane, Scotland, UK; 5Division of Endocrinology, Department of Internal Medicine, The University of Arizona College of Medicine - Phoenix, Phoenix, AZ, USA; 6Department of Neurosurgery, University of Arkansas for Medical Sciences, Little Rock, AR, USA; 7Department of Surgery, Keck School of Medicine of University of Southern California, Los Angeles, CA, USACorrespondence: David C Klonoff, Diabetes Research Institute, Mills-Peninsula Medical Center, 100 South San Mateo Drive, Room 1165, San Mateo, CA, 94401, USA, Tel +1650-218-1142, Email dklonoff@diabetestechnology.orgPurpose: The recent SENZA-PDN study showed that high-frequency (10kHz) spinal cord stimulation (SCS) provided significant, durable pain relief for individuals with painful diabetic neuropathy (PDN), along with secondary benefits, including improved sleep quality and HRQoL. Given that metabolic factors and chronic neuropathic pain are related, we evaluated potential secondary effects of 10kHz SCS on hemoglobin A1c (HbA1c) and weight in SENZA-PDN participants with type 2 diabetes (T2D).Patients and Methods: This analysis included 144 participants with T2D and lower limb pain due to PDN who received 10kHz SCS during the SENZA-PDN study. Changes in HbA1c, weight, pain intensity, and sleep were evaluated over 24 months, with participants stratified according to preimplantation HbA1c (> 7% and > 8%) and body mass index (BMI; ≥ 30 and ≥ 35 kg/m2).Results: At 24 months, participants with preimplantation HbA1c > 7% and > 8% achieved clinically meaningful and statistically significant mean reductions in HbA1c of 0.5% (P = 0.031) and 1.1% (P = 0.004), respectively. Additionally, we observed a significant mean weight loss of 3.1 kg (P = 0.003) across all study participants. In subgroups with BMI ≥ 30 and ≥ 35 kg/m2, weight reductions at 24 months were 4.1 kg (P = 0.001) and 5.4 kg (P = 0.005), respectively. These reductions were accompanied by a mean pain reduction of 79.8% and a mean decrease in pain interference with sleep of 65.2% at 24 months across all cohorts.Conclusion: This is the first study of SCS to demonstrate long-term, significant, and clinically meaningful reductions in HbA1c and weight in study participants with PDN and T2D, particularly among those with elevated preimplantation HbA1c and BMI. Although the mechanism for these improvements has yet to be established, the results suggest possible direct and indirect metabolic benefits with 10kHz SCS in addition to durable pain relief.Trial Registration: ClincalTrials.gov Identifier, NCT03228420.Keywords: diabetic peripheral neuropathy, painful diabetic neuropathy, spinal cord stimulation, neuromodulation, neuropathic pain

Abdifatah Abdullahi Jalei,1 Abdifetah Ibrahim Omar,1,2 Shafie Abdulkadir Hassan,1 Yahye Sheikh Abdulle Hassan,1 Nur Rashid Ahmed1,2 1Faculty of Medicine and Health Sciences, Jamhuriya University of Science and Technology, Mogadishu, Somalia; 2Jamhuriya Research Center, Jamhuriya University of Science and Technology, Mogadishu, SomaliaCorrespondence: Abdifatah Abdullahi Jalei, Faculty of Medicine and Health Sciences, Jamhuriya University of Science and Technology, Mogadishu, Somalia, Tel +252617000684, Email Jeele301@gmail.comIntroduction: Reference intervals (RIs) are crucial for the accurate interpretating of laboratory test results in clinical settings, serving as benchmarks for evaluating individual health status. This study investigates the influence of sex and age on common liver function tests (LFTs) and renal function tests (RFTs) in healthy adults in Mogadishu, Somalia.Methods: A community-based cross-sectional study was carried out from October 2022 to January 2023 on a randomly selected sample of 255 healthy participants from Mogadishu, Somalia. Approximately 5 mL of whole blood was collected from each participant and processed screening of hepatitis B and C, and human immunodeficiency virus, and then biochemical analyses were conducted for common liver and kidney parameters.Results: The study found significant sex and age-related differences in the measured LFTs and RFTs parameters. For LFTs, males had higher levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) compared to females (ALT: 11.5 vs 7.5 U/L; AST: 25.5 vs 19.1 U/L; both p < 0.001). Age-related differences were also observed, with individuals aged 30 and above had higher levels of ALT and AST compared to those aged 18– 29 (ALT: 10.9 vs 8.5 U/L; AST: 24.3 U/L vs 21.0 U/L, both p < 0.001). For RFTs, males had higher levels of creatinine (0.9 vs 0.7 mg/dL), urea (23.1 vs 16.1 mg/dL), and uric acid (5.2 vs 4.2 mg/dL) than females, all with p < 0.001.Conclusion: The study established population specific RIs for common liver and renal function parameters and revealed significant variations across sex and age groups. These findings underscore the importance of developing and using local RIs to ensure accurate clinical interpretation and effective patient management. Further research with larger sample sizes and in diverse regions of Somalia is highly recommended.Keywords: reference intervals, liver function tests, renal function tests, Mogadishu, Somalia

Wajd A Alhadi,1,&ast; Ebtihaj Yahya Alshehry,2,&ast; Nouf A Hamood,1,&ast; Lama Dafer Albishri,1,&ast; Ghaida Mohammed Al Hunaif,1,&ast; Roaa M Al Murayyi,1,&ast; Zainah Al-Qahtani,2,&ast; Syed Esam Mahmood3,&ast; 1College of Medicine, King Khalid University, Abha, 61421, Saudi Arabia; 2Neurology Department, Asir Central Hospital, Abha, 61421, Saudi Arabia; 3Department of Family and Community Medicine, College of Medicine, King Khalid University, Abha, Saudi Arabia&ast;These authors contributed equally to this workCorrespondence: Syed Esam Mahmood, Email smahmood@kku.edu.saBackground: The current annual incidence of cerebral venous thrombosis (CVT) is 3– 4 cases per one million population. CVT manifests itself with varying degrees of clinical presentation that may cause vital or morbid consequences if not treated and managed promptly. Studies have suggested varied levels of CVT public awareness.Aim: To assess the level of knowledge and public perception of CVT across the different socio-economic strata of the Saudi Adult population.Methods: A descriptive cross-sectional study was conducted using a mixed-method approach (an electronic questionnaire and phone interviews) for collecting the data. A validated questionnaire was distributed to consenting study participants and filled out to the best of their ability. The study setting was a nationwide survey conducted in Saudi Arabia and involved a representative portion of the study population.Results: A total of 1912 participants were included in this study. Overall, the majority of study participants (67.2%) had a low knowledge level of CVT on assessment, and only 2.6% had a high knowledge level of CVT. Younger age, female gender, working adults, higher education level, marital status, Saudi nationals, and place of residency were significantly associated with knowledge of CTV (p < 0.001).Conclusion: This study indicates a lower index of knowledge of CVT which offers an opportunity for much improvement in public perception and awareness of CVT in the study population. Our results can be utilized to target the demographics with the lowest knowledge via the most popular ways to gain information.Keywords: cerebral venous thrombosis, knowledge, cross-sectional, Saudi Arabia

Qiuyi Chen,&ast; Mina Wang,&ast; Feiyu Fu,&ast; Limin Nie, Quan Miao, Luopeng Zhao, Lu Liu, Bin Li Department of Acupuncture and Moxibustion, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing Key Laboratory of Acupuncture Neuromodulation, Beijing, 100010, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bin Li; Lu Liu, Department of Acupuncture and Moxibustion, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing Key Laboratory of Acupuncture Neuromodulation, No. 23 Meishuguan Houjie, Beijing, 100010, People’s Republic of China, Tel +86 18910781852 ; +86 13520788752, Email libin@bjzhongyi.com; lululalavictor1985@126.comAbstract: Migraine is a common neurological illness that causes a great burden on individuals and society. Many migraine patients seek relief through complementary and alternative therapies, with Traditional Chinese medicine (TCM) often being their preferred choice. Acupuncture, Chinese herbal medicine, and massage are important components of TCM, and are commonly used in clinical treatment of migraine. This review aims to consolidate the current knowledge regarding the mechanisms of the three TCM interventions for migraine: acupuncture, herbs, and massage, and how they relieve pain. However, the mechanisms underlying the effectiveness of TCM therapies in treating migraine remain unclear. Therefore, we reviewed the research progress on acupuncture, herbal medicine, and massage as TCM approaches for the treatment of migraine. We conducted a comprehensive search of CNKI, PubMed, Web of Science, and Cochrane databases using keywords such as migraine, acupuncture, needle, herbs, herbal, prescription, decoction, massage, Tuina, and TCM, covering the period from 2000 to 2023. The literature included in the review was selected based on specified exclusion criteria. We discussed the mechanism of TCM therapies on migraine from the perspective of modern medicine, focusing on changes in inflammatory factors, neurotransmitters, and other relevant biomarkers. TCM can relieve migraine by decreasing neuropeptide levels, inhibiting inflammation, modulating neuronal sensitization, changing brain function and structure, changing blood brain barrier permeability, regulating hormone levels, and relieving muscle tension. The purpose of this paper is to provide a basis for improving the clinical strategies of TCM for the treatment of migraine.Keywords: traditional Chinese medicine, migraine, acupuncture, herbs, massage, mechanism

Zhengguang Zhang,1,2,&ast; Min Li,3,&ast; Xiaolong Zhang,4,&ast; Fuqiong Zhou1 1Central Laboratory, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Jiangsu, Nanjing, People’s Republic of China; 2School of Medicine, Nanjing University of Chinese Medicine, Jiangsu, Nanjing, People’s Republic of China; 3Department of Oncology, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Jiangsu, Nanjing, People’s Republic of China; 4The Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Jiangsu, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhengguang Zhang; Fuqiong Zhou, Email zhengguangzhang@njucm.edu.cn; zhoufuqiong@njucm.edu.cnAbstract: Reactive oxygen species (ROS) encompass a diverse group of chemically reactive molecules or ions distinguished by their substantial oxidative potential. Empirical studies have shown that the targeted administration of high toxic concentrations of ROS can effectively induce tumor cell death in various types. Numerous bioactive ingredients derived from traditional Chinese medicine (TCM), recognized for their ROS-inducing properties, have demonstrated significant anti-tumor activity. Nonetheless, their clinical application has been hindered by challenges such as low solubility, limited bioavailability, and poor selectivity. Multifunctional nanoformulations possess the potential to overcome these challenges and enhance the anticancer efficacy of ROS-inducing active compounds. Through extensive searches of various academic databases and a thorough review and screening of relevant literature, this study aims to systematically summarize and generalize multiple active ingredients in TCM that induce ROS generation, along with their multifunctional nanoformulations, from various perspectives. The objective is to provide new insights and references for fundamental cancer research and clinical treatments. Furthermore, we acknowledge that although numerous active ingredients and their nanoformulations in TCM have demonstrated ROS-inducing and anti-tumor potentials, potentially offering novel strategies for tumor therapy, the underlying mechanisms require further comprehensive investigation.Keywords: traditional Chinese medicine, nanoformulation, reactive oxygen species, cancer

Xinbo Zhang, Bin Xu, Jiangwei Ni, Yucheng Xiang, Zhifeng He Department of Thoracic Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Zhifeng He, Department of Thoracic Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China, Email hezhifeng@wzhospital.cnPurpose: The chemotherapeutic agent doxorubicin (DOX) is limited by its cardiotoxicity, posing challenges in its application for non-small cell lung cancer (NSCLC). This study aims to explore the efficacy of polydopamine/Au nanoparticles loaded with DOX for chemotherapy and photothermal therapy in NSCLC to achieve enhanced efficacy and reduced toxicity.Methods: Hollow polydopamine (HPDA)/Au@DOX was synthesized via polydopamine chemical binding sacrificial template method. Morphology was characterized using transmission electron microscopy, particle size and potential were determined using dynamic light scattering, and photothermal conversion efficiency was assessed using near-infrared (NIR) thermal imaging. Drug loading rate and in vitro drug release were investigated. In vitro, anti-tumor experiments were conducted using CCK-8 assay, flow cytometry, and live/dead cell staining to evaluate the cytotoxicity of HPDA/Au@DOX on A549 cells. Uptake of HPDA/Au@DOX by A549 cells was detected using the intrinsic fluorescence of DOX. The in vivo anti-metastasis and anti-tumor effects of HPDA/Au@DOX were explored in mouse lung metastasis and subcutaneous tumor models, respectively.Results: HPDA/Au@DOX with a particle size of (164.26± 3.25) nm, a drug loading rate of 36.31%, and an encapsulation efficiency of 90.78% was successfully prepared. Under 808 nm laser irradiation, HPDA/Au@DOX accelerated DOX release and enhanced uptake by A549 cells. In vitro photothermal performance assessment showed excellent photothermal conversion capability and stability of HPDA/Au@DOX under NIR laser irradiation. Both in vitro and in vivo experiments demonstrated that the photothermal-chemotherapy combination group (HPDA/Au@DOX+NIR) exhibited stronger anti-metastatic and anti-tumor activities compared to the monotherapy group (DOX).Conclusion: HPDA/Au@DOX nanosystem demonstrated excellent photothermal effect, inhibiting the growth and metastasis of A549 cells. This nanosystem achieves the combined effect of chemotherapy and photothermal, making it promising for NSCLC treatment. Keywords: non-small cell lung cancer, chemotherapy, photothermal therapy, doxorubicin, Au nanoparticles

Yi Zhou,1 Weina Gao,2 Zhijiao Cao,3 Shumin Gao,2 Xutong Guo,2 Meng Liu,2 Congjie Cao4 1School of Nursing, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Orthopedics, Baoding No.1 Central Hospital, Baoding, Hebei, People’s Republic of China; 3Department of Nursing, Baoding No.1 Central Hospital, Baoding, Hebei, People’s Republic of China; 4Nursing Department, Langfang Health Vocational College, Langfang, Hebei, People’s Republic of ChinaCorrespondence: Weina Gao, Department of Orthopedics, Baoding No.1 Central Hospital, No. 320, Changcheng North Street, Lianchi District, Baoding, Hebei, 071000, People’s Republic of China, Tel +86 0312-5975023, Email gaoweina984926@163.comBackground: Kinesiophobia is common in patients after total knee arthroplasty and is an important risk factor for post-operative recovery outcomes. Little is known about the complex intercorrelations between different components of pain catastrophizing, self-efficacy, and kinesiophobia. This study aimed to identify the central components of kinesiophobia and to explore the interconnectedness between components of pain catastrophizing, self-efficacy, and kinesiophobia.Methods: A total of 216 patients after total knee arthroplasty were recruited in this study. Pain Catastrophizing Scale, Self-efficacy of Rehabilitation Outcome Scale and Tampa Scale for Kinesiophobia were used to assess pain catastrophizing, self-efficacy and kinesiophobia. R software was used to visualize the networks and analyze the centrality of the networks. The index “strength” and “bridge expected influence” were employed to identify the central components and the bridge components of the networks.Results: In the item network of kinesiophobia, three items (“Simply being careful that I do not make any unnecessary movements is the safest thing I can do to prevent my pain from worsening”, “My accident has put my body at risk for the rest of my life”, and “My body is telling me I have something dangerously wrong”) had the highest strength centrality. In the pain catastrophizing/self-efficacy–kinesiophobia network, rumination had the highest positive bridge expected influence, while coping self-efficacy had the highest negative value.Conclusion: The three central components of kinesiophobia identified in this study, as well as two bridge variables (rumination and coping self-efficacy), could be promising and effective targets for prevention and intervention of kinesiophobia.Keywords: pain catastrophizing, self-efficacy, kinesiophobia, total knee arthroplasty, network analysis

Zhengwen Feng,1 Hui Li,1 Xiaolei Chen,1 Tiancheng Zhang,2 Yanxiang Chen,3 Shuang Shao,1,&ast; Juan Du1,&ast; 1School of General Practice and Continuing Education, Capital Medical University, Beijing, People’s Republic of China; 2Department of General Practice, Dahongmen Community Health Service Center, Beijing, Fengtai District, People’s Republic of China; 3Department of general practice, Changying Community Health Service Center, Beijing, Chaoyang District, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Juan Du; Shuang Shao, School of General Practice and Continuing Education, Capital Medical University, 10 You’ Anmen Outer West 1 st Street, Beijing, 100069, People’s Republic of China, Email cuckoo@ccmu.edu.cn; shaoshuang@ccmu.edu.cnPurpose: Our study aimed to explore the current status of patient participation in medication safety from the perspectives of general practitioners (GPs), pharmacists, and outpatients in Beijing, China.Patients and Methods: A qualitative study using semi-structured in-depth individual interviews with GPs, pharmacists, and outpatients. Subjects were identified by purposive sampling until code saturation. Semi-structured qualitative interviews were conducted with GPs, pharmacists, and patients from community health service centers in three urban districts of Beijing, China. The interviews were transcribed verbatim and the text was analysed using thematic analysis techniques including familiarising with data, generating initial codes, searching for themes, reviewing themes, defining and naming themes, and producing the report.Results: A total of eight GPs, seven pharmacists, and 18 outpatients were interviewed. Data analysis led to the generation of five key themes: (1) mutual trust between patient and GP, (2) communication with healthcare professionals, (3) acquisition of knowledge about medication safety, (4) implementation of medication self-management at home, and (5) different attitudes toward participation in medication decisions. Patients participated in medication safety in multiple ways. However, insufficient knowledge about medication safety, lack of awareness of the patient’s role in ensuring medication safety, shortage of consultation lengths, and being misled by some information were problems with patient participation in medication safety.Conclusion: This exploratory study contributes to our initial understanding of patient participation in medication safety. There were still many issues and barriers in the process of patient participation. Appropriate policies and measures, such as providing various forms of patient education, ensuring sufficient physician-patient communication, giving full play to the role of pharmacists, and making judicious use of digital health tools should be taken to improve medication safety by fully utilising the role of patients.Plain Language Summary: Medication safety is a significant concern around the world. Patient participation in the medication process is effective in reducing the incidence of medication errors and improving medication safety. However, the role of outpatients with chronic conditions in ensuring medication safety is often neglected. This study aims to explore the perspectives and experiences of GPs, pharmacists, and outpatients by qualitative interviews in Beijing, China. The study involved a series of interviews with eight GPs, seven pharmacists, and 18 outpatients living with noncommunicable diseases. The interview revealed five themes: (1) mutual trust between patient and GP, (2) communication with healthcare professionals, (3) acquisition of knowledge about medication safety, (4) implementation of medication self-management at home, and (5) different attitudes toward participation in medication decisions. The findings might help propose suggestions for patient participation in medication safety. Integrating these findings into future studies can help healthcare professionals formulate interventions and better support patients in participating in the medication process.Keywords: medication safety, patient participation, patient safety, qualitative study, noncommunicable disease, community health service centers

Yan Zhao,1,2 Guang-Yao Chen,3 Meng Fang1,2 1Beijing Key Laboratory of Mental Disorders, National Clinical Research Center for Mental Disorders & National Center for Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, People’s Republic of China; 3Department of TCM Rheumatology, China-Japan Friendship Hospital, Beijing, 100029, People’s Republic of ChinaCorrespondence: Guang-Yao Chen; Meng Fang, Email chenguangyao1994@163.com; fangmeng_fm@mail.ccmu.edu.cnBackground: The co-occurrence of rheumatoid arthritis and depression typically exacerbates pain and leads to a range of adverse consequences, becoming a research hotspot in recent years. This study conducted the systematic retrieval of relevant articles within the past five years and employed bibliometric methods for scientometric analysis.Methods: Setting the keywords “Rheumatoid arthritis”, “Depression” and “Depressive Disorder”, relevant literature published between 2019 and 2023 was retrieved from the Web of Science database. Subsequently, the core information from the literature was subjected to visual analysis via CiteSpace software and bibliometric techniques.Results: A total of 974 articles related to rheumatoid arthritis and depression were identified through the search strategy, and 877 articles were retained for further analysis after duplicates. The United States (n=173), England (n=82), China (n=69), Canada (n=68), and Germany (n=54) ranked top five countries by publication count. The King’s College London was the leading institution with the highest number of publications (n = 20). LANCET PSYCHIATRY was the most frequently cited journal (n = 72) despite having only one article. The top five authors with the largest number of publications include CHARLES N BERNSTEIN (n=14), RUTH ANN MARRIE (n=13), JOHN D FISK (n=12), CAROL A HITCHON (n=12) and SCOTT B PATTEN (n=12), and all these are based in Canada. The keywords with a centrality score exceeding 0.1 were depression, rheumatoid arthritis, symptom, quality of life, impact, fibromyalgia, disease activity, prevalence, inflammation, health, anxiety, pain, fatigue, disease, arthritis and disability.Conclusion: Related research between the co-occurrence of rheumatoid arthritis and depression was a persistent hotspot, but it still lacks of international collaboration and in-depth mechanistic exploration.Keywords: rheumatoid arthritis, depression, bibliometric analysis, Web of Science, CiteSpace

Sarah A Alobaid,1 Mohammed Basem Beyari,1 Reem Bin Idris,1 Mohammed H Alhumud,1 Lamia A Alkuwaiz,2 Faisal Alsaif,3 Mansour Aljabry,4 Bandar Aljafen,5 Mona Soliman6 1College of Medicine, King Saud University, Riyadh, Saudi Arabia; 2Division of Orthopaedic Surgery, McGill University Health Centre, Montréal, Quebec, Canada; 3Fellowship and Residency Training Program, King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia; 4Pathology Department, College of Medicine, King Saud University, Riyadh, Saudi Arabia; 5Medicine Department, College of Medicine, King Saud University, Riyadh, Saudi Arabia; 6Medical Education & Physiology, Vice Dean of Academic Affairs, College of Medicine, King Saud University, Riyadh, Saudi ArabiaCorrespondence: Mona Soliman, Medical Education and Physiology, College of Medicine, King Saud University, College of Medicine, King Saud University, Riyadh, Saudi Arabia, Tel +966505468581, Email msoliman1@ksu.edu.saBackground: The Big Sibling Program is an innovative peer student mentoring method that was designed and implemented by the students’ council in 2021 to complement the faculty mentoring program of first-year medical students in the College of Medicine, King Saud University, Saudi Arabia. The aim of the study was to evaluate the medical students’ perception of the peer students “Big Sibling” mentoring program and to assess the effectiveness of the program in terms of changes in the behavior and academic performance of the students.Methods: This is a retrospective study that was conducted in 2021. A registration form that includes demographic data, personal information, and academic performance (GPA and extracurricular achievements) was sent to all second- and third-year medical students to select the Big Siblings. A total of 49 mentors “Big Siblings” were accepted (30 males, 19 females) and matched randomly with the little siblings from first-year medical students. A written consent was obtained from the participants. The survey was structured on a 5-point Likert scale, and composed of four sections of closed-ended questions, that includes: the demographic data, the students’ (little sibling) evaluation of the mentorship sessions, the little sibling perception of the Big Sibling Program and its effectiveness of the Big Sibling Program in terms of behavioral or quality effects.Results: Out of 297 first-year medical students, 284 (95.62%) responded. The majority significantly agreed that the Big Sibling was readily available and they personally benefitted from the relationship (94.36%, p< 0.001; 90.14%, p< 0.001). They significantly disagreed that the relationship requires too much time (72.54%, p< 0.001) or that they do not need a mentor (78.87%, p< 0.001). Most significantly agreed that mentoring is a good idea (94.37%, p< 0.001), the program helped reduce their stress (84.51%, p< 0.001), helped them adjust to college (89.44%, p< 0.001), and advance academically (78.52%, p< 0.001). The program also encouraged their involvement in extracurricular activities (58.10%, p< 0.0001), research (43.31%, p< 0.001), and social engagement with peers (71.48%, p< 0.001). Moreover, the majority thought the program significantly improved their self-confidence (73.94%, p< 0.001), self-awareness (84.51%), accountability (54.51%), leadership (54.93%), resilience (71.13%), punctuality (69.01%, p< 0.001), time management (75.70%), stress coping (77.82%), problem-solving (76.76%), and teamwork (75.35%).Conclusion: Peer students’ big Siblings program has succeeded in reducing first-year medical students stress levels, improving their self-confidence, self-awareness, accountability and responsibility, leadership, resilience, punctuality and engaging them in research and extracurricular activities.Keywords: Medical students, big sibling program, mentoring, peer mentoring, mentoring program

Jason Robert Guertin,1– 3 Naomi Hope Chouinard,1– 3 Amélie Forget,4,5 Lucie Blais4,5 1Centre de recherche du CHU de Québec-Université Laval, Quebec City, Canada; 2Department of Social and Preventive Medicine, Faculty of Medicine, Université Laval, Quebec City, Canada; 3Centre de recherche en organogénèse expérimentale de l’Université Laval/LOEX, Quebec City, Canada; 4Faculty of Pharmacy, Université de Montréal, Montréal, Canada; 5Centre de recherche du Centre intégré universitaire de santé et de services sociaux du Nord-de-l’Île-de-Montréal, Montréal, CanadaCorrespondence: Jason Robert Guertin, Centre de recherche du CHU de Québec – Université Laval, Hôpital du Saint-Sacrement, 1050 Chemin Sainte-Foy, Local J1-11, Quebec City, G1S 4L8, Canada, Tel +1 418-682-7511 ext 82516, Email jason.guertin@fmed.ulaval.ca

Kamil Szupryczy&nacute;ski,1 Przemys&lstrok;aw Czele&nacute;,2 Tomasz Jeli&nacute;ski,2 Beata Szefler2 1Doctoral School of Medical and Health Sciences, Faculty of Pharmacy, Collegium Medicum, Nicolaus, Copernicus University, Bydgoszcz, Poland; 2Department of Physical Chemistry, Faculty of Pharmacy, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, PolandCorrespondence: Beata Szefler, Email beatas@cm.umk.plAbstract: Over the course of several decades, anticancer treatment with chemotherapy drugs for lung cancer has not changed significantly. Unfortunately, this treatment prolongs the patient’s life only by a few months, causing many side effects in the human body. It has also been proven that drugs such as Cisplatin, Carboplatin, Oxaliplatin and others can react with other substances containing an aromatic ring in which the nitrogen atom has a free electron group in its structure. Thus, such structures may have a competitive effect on the nucleobases of DNA. Therefore, scientists are looking not only for new drugs, but also for new alternative ways of delivering the drug to the cancer site. Nanotechnology seems to be a great hope in this matter. Creating a new nanomedicine would reduce the dose of the drug to an absolute minimum, and thus limit the toxic effect of the drug; it would allow for the exclusion of interactions with competitive compounds with a structure similar to nucleobases; it would also permit using the so-called targeted treatment and bypassing healthy cells; it would allow for the introduction of other treatment options, such as radiotherapy directly to the cancer site; and it would provide diagnostic possibilities. This article is a review that aims to systematize the knowledge regarding the anticancer treatment of lung cancer, but not only. It shows the clear possibility of interactions of chemotherapeutics with compounds competitive to the nitrogenous bases of DNA. It also shows the possibilities of using nanostructures as potential Platinum drug carriers, and proves that nanomedicine can easily become a new medicinal product in personalized medicine.Keywords: fullerenes, nanotube, nanoparticles, drug delivery, personalized medicine, platinum-based drugs, cisplatin, carboplatin, oxaliplatin, nedaplatin

Erick Acocal-Juárez,1– 3 Luis Márquez-Domínguez,2 Verónica Vallejo-Ruíz,2 Lilia Cedillo,3 Gerardo Santos-López2 1Centro de Investigaciones en Ciencias Microbiológicas, Benemérita Universidad Autónoma de Puebla, Puebla Pue, Mexico; 2Laboratorio de Biología Molecular y Virología, Centro de Investigación Biomédica de Oriente, Instituto Mexicano del Seguro Social, Puebla, Mexico; 3Centro de Detección Biomolecular, Benemérita Universidad Autónoma de Puebla México, Puebla Pue, MexicoCorrespondence: Lilia Cedillo; Gerardo Santos-López, Email lilia.cedillo@correo.buap.mx; gerardo.santos.lopez@gmail.comAim: Influenza control demands multifaceted strategies, including antiviral drugs. Baloxavir, a recent addition to influenza treatment, acts as an inhibitor of the Polymerase acid (PA) component of the viral polymerase. However, mutations associated with resistance have been identified.Purpose: This study analyzed PA gene sequences of influenza A and B viruses (IAV and IBV, respectively) reported in the Americas, retrieved from databases published until May 2023, to identify primary markers of resistance to baloxavir.Patients and Methods: PA gene sequences were obtained from the GISAID and NCBI databases, focusing on countries in the Americas with 500 or more sequences for IAV, and 50 or more sequences for IBV.Results: Of the 58,816 PA sequences analyzed for IAV, only 55 (0.1%) harbored resistance markers, representing approximately 1 in 1000 occurrence. The most frequent markers were I38V (21 cases) and I38M (7 cases) at position 38 of PA, followed by E199G (9 cases) at position 199. For IBV, 14,684 sequences were analyzed, of which only eight presented a resistance marker (0.05%). Five sequences had the M34I marker, while the remaining three had the I38V marker. While frequency of resistance markers in PA is comparable to other regions, these results highlight the need for enhanced sequencing efforts, particularly in Latin America. Such efforts would serve to intensify influenza surveillance and inform public health interventions.Conclusion: While baloxavir demonstrates efficacy against influenza, resistance markers have been identified, including pre-existing ones. Our study adds eight (IAV: six and IBV: two) new spontaneously occurring substitutions to the existing literature, highlighting the need for continued surveillance. Among these, I38M stands out due to its significant tenfold reduction in drug susceptibility. Therefore, vigilant monitoring of these resistance markers in IAV and IBV remains crucial for maintaining baloxavir’s effectiveness and informing future public health interventions.Keywords: antiviral resistance, substitutions, PA protein, polymerase inhibitor

Ashok Kumar Patra,1 Shreenath Nayak,1 Anandita Moharana,1 Purusottam Ojha,1 Sanjeet Kumar Das,1 Jabed Akhtar,1 Bishwaranjan Giri,1 Sujay Singh1,2 1Protein Expression Lab, Imgenex India Pvt. Ltd. E-5, Bhubaneswar, Odisha, India; 2Sujan Biologics, Inc., San Diego, California, USACorrespondence: Ashok Kumar Patra, Director, Biologics Development, Imgenex India Pvt. Ltd, E 5, Infocity, Technology Corridor, Chandaka Industrial Area, Bhubaneswar, Odisha, India, 751024, Email apatra@imgeneindia.comPurpose: The study aimed to develop and characterize Indikizumab, a novel humanized anti-IL-17A monoclonal antibody (mAb), for potential therapeutic use in inflammatory indications such as psoriasis, psoriatic arthritis, rheumatoid arthritis, and ankylosing spondylitis.Methods: The research involved the purification of IL-17 isoforms, epitope mapping, affinity ranking, and comparative binding assessment of anti-IL-17 antibodies. The study also included cell-based neutralization assays and in vivo studies using mouse models to evaluate the efficacy of Indikizumab.Results: Indikizumab demonstrated a high binding affinity (KD=27.2 pM) and specificity for IL-17A, with comparable potency to Secukinumab. In cell-based neutralization assays, Indikizumab effectively neutralized the effects of IL-17A and demonstrated a statistically significant reduction in plasma KC (Keratinocyte) levels in a mouse model. In imiquimod-induced psoriasis mouse model, Indikizumab showed potential in reducing the psoriasis index.Conclusion: Indikizumab represents a promising therapeutic option for inflammatory indications with its high binding affinity, specificity for IL-17A, and effectiveness in neutralizing IL-17A effects in vivo.Keywords: monoclonal antibody, neutralization assay, psoriasis, inflammation. keratinocyte

Xueya Xu,&ast; Weili Lu,&ast; Hua Zhang, Xiaoying Wang, Caixia Huang, Qiuping Huang, Wen Xu, Wei Xu Pharmacy College, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoying Wang; Wei Xu, Pharmacy College, Fujian University of Traditional Chinese Medicine, 1 Qiuyang Road, Fuzhou, 350122, People’s Republic of China, Email 2003032@fjtcm.edu.cn; 2000017@fjtcm.edu.cnBackground: The combination of nanoplatform-based chemotherapy and photodynamic therapy (PDT) is a promising way to treat cancer. Celastrol (Cela) exhibits highly effective anti-hepatoma activity with low water solubility, poor bioavailability, non-tumor targeting, and toxic side effects. The combination of Cela-based chemotherapy and PDT via hepatoma-targeting and reactive oxygen species (ROS)-responsive polymeric micelles (PMs) could solve the application problem of Cela and further enhance antitumor efficacy.Methods: In this study, Cela and photosensitizer chlorin e6 (Ce6) co-loaded glycyrrhetinic acid-modified carboxymethyl chitosan-thioketal-rhein (GCTR) PMs (Cela/Ce6/GCTR PMs) were prepared and characterized. The safety, ROS-sensitive drug release, and intracellular ROS production were evaluated. Furthermore, the in vitro anti-hepatoma effect and cellular uptaken in HepG2 and BEL-7402 cells, and in vivo pharmacokinetic, tissue distribution, and antitumor efficacy of Cela/Ce6/GCTR PMs in H22 tumor-bearing mice were then investigated.Results: Cela/Ce6/GCTR PMs were successfully prepared with nanometer-scale particle size, favorable drug loading capacity, and encapsulation efficiency. Cela/Ce6/GCTR PMs exhibited a strong safety profile and better hemocompatibility, exhibiting less damage to normal tissues. Compared with Cela-loaded GCTR PMs, the ROS-responsiveness of Cela/Ce6/GCTR PMs was increased, and the release of Cela was accelerated after combination with PDT. Cela/Ce6/GCTR PMs can efficiently target liver tumor cells by uptake and have a high cell-killing effect in response to ROS. The combination of GCTR PM-based chemotherapy and PDT resulted in increased bioavailability of Cela and Ce6, improved liver tumor targeting, and better anti-hepatoma effects in vivo.Conclusion: Hepatoma-targeting and ROS-responsive GCTR PMs co-loaded with Cela and Ce6 combined with PDT exhibited improved primary hepatic carcinoma therapeutic effects with lower toxicity to normal tissues, overcoming the limitations of monotherapy and providing new strategies for tumor treatment. Keywords: ROS-responsive polymeric micelles, photodynamic therapy, hepatoma-targeting, celastrol, combination anti-hepatoma therapy