Search

Yong Zheng, Yonggui Luo, Kuihan Tang Department of Orthopedics, Beijing Jishuitan Hospital Guizhou Hospital, Guiyang, 550014, People’s Republic of ChinaCorrespondence: Kuihan Tang, Email tkh5200520@163.comBackground: Endoplasmic reticulum stress (ERS) is closely associated with Osteoporosis (OP). In order to explore the role of ERS related genes in OP and its molecular mechanism.Methods: OP-related transcriptome data were retrieved from the Gene Expression Omnibus (GEO) database. Weighted gene co-expression network analysis (WGCNA) was applied to screen OP-related genes. Differentially expressed ERS-related genes (DE-ERSGs) between OP and controls were identified by overlapping OP-related, differentially expressed genes (DEGs), and ERS-related genes. ERS-related genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted to explore their functions. Receiver operating characteristic (ROC) curves assessed the diagnostic value of DE-ERSGs, and comparative toxicogenomics database (CTD) was used to predict targeting agents for key DE-ERSGs. Finally, biomarker expression was verified by real time quantitative polymerase chain reaction (RT-qPCR).Results: A total of 10 DE-ERSGs were screened in OP patients. GO and KEGG analyses indicated their enrichment in Alcoholic liver disease, Endometrial cancer, and Glycerolipid metabolism. ROC curve analysis revealed that RPN2, FOXO3, ERGIC2, and MYO9A had significant diagnostic value, thus being identified as key DE-ERSGs. Moreover, the key DE-ERSGs-drug interaction network showed that some drugs such as bisphenol A, Cisplatin, Cyclosporine, and Valproic Acid might play roles by targeting key DE-ERSGs in OP. The expression validation analysis of key DE-ERSGs revealed that RPN2, ERGIC2, and MYO9A was significantly expressed in the GSE62402. Ultimately, The blood samples RT-qPCR verification results show that RPN2, ERGIC2, and MYO9A were significantly lower in OP samples compared to normal samples (p < 0.05), whereas there was no difference in the expression levels of FOXO3.Conclusion: RPN2, FOXO3, ERGIC2 and MYO9A as the biomarkers associated with ERS in OP by bioinformatics analysis, which may provide new biological targets for clinical treatment.Keywords: osteoporosis, endoplasmic reticulum stress, bioinformatics analysis, biomarkers

Rui Huang,1– 3,&ast; Qingning Huang,1– 3,&ast; Yuhua Lei1– 3 1Cardiovascular Disease Center, Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, People’s Republic of China; 2Hubei Selenium and Human Health Institute, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, People’s Republic of China; 3Hubei Provincial Key Laboratory of Selenium Resources and Bioapplications, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuhua Lei, Email yuhualei0319@163.comAbstract: A 60-year-old woman was admitted to the hospital with “repeated loss of consciousness for 20 years.” An electrocardiogram performed revealed sinus rhythm, and echocardiography, head/chest CTs, and a laboratory examination yielded no significant abnormalities. Besides, there were no positive results from the head-up tilt test. The subsequent decrease in heart rate and blood pressure following the ingestion of chili pepper indicated a potential case of vasovagal syncope(VVS) with cardioinhibition. Following cardioneuroablation, there was an observed increase in heart rate compared to pre-procedure levels. Furthermore, no recurrence of similar symptoms was reported during the one-year follow-up period.Keywords: Cardioneuroablation, Vasovagal syncope, chili pepper stimulation, VVS

Marta Szukalska,1 Bartosz F Grze&sacute;kowiak,2 Magdalena J Bigaj-Józefowska,2 Marta Witkowska,3,4 Emilia Cicha,5 Patrycja Sujka-Kordowska,6 Izabela Miechowicz,7 Micha&lstrok; Nowicki,6 Rados&lstrok;aw Mrówczy&nacute;ski,3,4 Ewa Florek1 1Laboratory of Environmental Research, Department of Toxicology, Poznan University of Medical Sciences, Pozna&nacute;, Poland; 2NanoBioMedical Centre, Adam Mickiewicz University, Pozna&nacute;, Poland; 3Faculty of Chemistry, Adam Mickiewicz University, Pozna&nacute;, Poland; 4Centre for Advanced Technologies, Adam Mickiewicz University, Pozna&nacute;, Poland; 5Laboratory of Experimental Animals, Poznan University of Medical Sciences, Pozna&nacute;, Poland; 6Department of Histology and Embryology, Poznan University of Medical Sciences, Pozna&nacute;, Poland; 7Department of Computer Science and Statistics, Poznan University of Medical Sciences, Pozna&nacute;, PolandCorrespondence: Marta Szukalska, Laboratory of Environmental Research, Department of Toxicology, Poznan University of Medical Sciences, Rokietnicka 3 Street, Poznan, 60-806, Poland, Email martan@ump.edu.plPurpose: Polydopamine nanoparticles (PDA NPs) have great potential in medicine. Their applications being widely investigated in cancer therapy, imaging, chemotherapy, photodynamic therapy (PDT), photothermal therapy (PTT), and tissue repair. The aim of our study was to assess the in vivo toxicity and changes in oxidative stress biomarkers in organs of animals treated with mesoporous PDA NPs modified with iron (MPDAFe NPs), coated with the cancer cell membrane and loaded with doxorubicin (DOX), and subsequently subjected to PTT.Methods: Liver and kidney homogenates were obtained from BALB/c nude mice with xenograft HepG2 human hepatoma cells, treated with iron modified mesoporous PDA nanoparticles, coated with the cancer cell membrane and loaded with doxorubicin (MPDAFe@DOX@Mem NPs), and subjected to PTT. These samples were used for histological evaluation and measurement of oxidative stress biomarkers, including total protein (TP), reduced glutathione (GSH), nitric oxide (NO), S-nitrosothiols (RSNO), thiobarbituric acid reactive substances (TBARS), trolox equivalent antioxidant capacity (TEAC), catalase (CAT), glutathione S-transferase (GST), and superoxide dismutase (SOD).Results: In the kidney, MPDAFe@DOX@Mem NPs in combination with PTT increased GSH (43%), TBARS (32%), and CAT (27%), while SOD decreased by 20% compared to the control group. Additionally, CAT activity in the liver increased by 79%.Conclusion: Significant differences in oxidative stress parameters and histological changes after administration with MPDAFe@DOX@Mem NPs and PTT were observed in the kidneys, showing more pronounced changes than the liver, indicating potential kidney toxicity. Our research provides insights into oxidative stress and possible toxic effects after in vivo administration of mesoporous PDA NPs combined with chemotherapy-photothermal therapy (CT-PTT), which is extremely important for their future applications in anticancer therapies. Keywords: polydopamine nanoparticles, oxidative stress, liver cancer model, in vivo toxicity, chemo- and photothermal therapy

Jia-Hao Weng,1 Feng-Gang Hou,2 Xue Wang,1 Zi-Yang Wang,1 Mei-Ping Wu1,3 1Department of Cardiology, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200071, People’s Republic of China; 2Department of Oncology, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200071, People’s Republic of China; 3School of Integrated Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of ChinaCorrespondence: Mei-Ping Wu, School of Integrated Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, No. 1200 of Cailun Road, Pudong District, Shanghai, 201203, People’s Republic of China, Tel +86 136 6197 7245, Email meipingwu2024@126.comObjective: This study evaluates the therapeutic effects of the Yangxin Huoxue Formula in the management of stable angina pectoris associated with Qi deficiency and blood stasis syndrome, co-occurring with anxiety and depressive disorders. The primary objective is to determine its efficacy in enhancing cardiac function and reducing emotional symptoms.Methods: A randomized, single-blind, placebo-controlled clinical trial was conducted with 94 individuals with stable angina pectoris. Participants were randomly allocated to either a treatment group receiving Yangxin Huoxue Formula granules or a placebo group receiving placebo granules, administered twice daily over a 12-week period. Primary outcome measures included assessments of cardiac function, angina frequency, PHQ-9 and GAD-7 scores, traditional Chinese medicine (TCM) syndrome improvements, and inflammatory markers.Results: The treatment group exhibited significantly greater improvements in cardiac output and reductions in peripheral vascular resistance compared to the placebo group. Additionally, a significant decrease in the frequency and duration of angina episodes was observed in the treatment group. Improvements in TCM syndrome scores and GAD-7 scores were also notably superior in the treatment group. No significant adverse reactions were recorded during the safety assessment of the treatment group.Conclusion: The Yangxin Huoxue Formula demonstrates efficacy in improving cardiac function, alleviating symptoms of anxiety and depression, reducing inflammatory mediator release, and enhancing quality of life in individuals with stable angina pectoris. The treatment was well-tolerated, confirming both its safety and therapeutic effectiveness.Keywords: Anxiety and depression disorders, qi deficiency and blood stasis, stable angina pectoris, traditional Chinese medicine treatment, Yangxin Huoxue Formula

Moyan Zhao,1 Zixuan Zhou,2 Amir Sherchan,1 Weizhong Yuan,2 Xiaoyun Xie,3 Maoquan Li1,3 1Shanghai Tenth People’s Hospital, School of Medicine, Tongji University, Shanghai, 200092, People’s Republic of China; 2Key Laboratory of Advanced Civil Materials of Ministry of Education, School of Materials Science and Engineering, Tongji University, Shanghai, 201804, People’s Republic of China; 3Department of Intervention and Vascular Surgery, Shanghai Tenth People’s Hospital, Shanghai, 200092, People’s Republic of ChinaCorrespondence: Maoquan Li, Department of Intervention and Vascular Surgery, Shanghai Tenth People’s Hospital, Shanghai, 200092, People’s Republic of China, Email cjr.limaoquan@vip.163.comPurpose: Bone marrow mesenchymal stem cells (BMSCs) have emerged as promising candidate for postoperative therapeutics in chronic limb-threatening ischemia (CLTI). Nevertheless, their effectiveness is limited by their low survival rate and impaired functionality in the ischemic microenvironment. To overcome these challenges, we have devised an innovative delivery approach to support the utilization of BMSCs in CLTI therapy.Methods: We synthesized oxygen-releasing nanospheres and self-healing hydrogels. The in vivo functionality of the hydrogel-nanosphere delivery system was evaluated via a multimodality animal live imaging system. A unilateral lower limb ischemia model was established in mice, and a delivery system loaded with BMSCs was administered. The experimental groups included normal mice, ischemic mice, ischemic mice treated with BMSCs in PBS, and ischemic mice treated with BMSCs in the delivery system. Blood perfusion was quantitatively measured via a laser doppler flowmeter (LDF). Immunofluorescence, Masson’s trichrome staining, immunohistochemistry and enzyme-linked immunosorbent assay (ELISA) were also used.Results: For cell viability analysis 80 μg.mL− 1 was considered the optimal concentration for cell survival. In vivo, 18 days after injection, the cell membrane fluorescence signal in the delivery system was significantly greater (5.65510± 8.2268) p/s/cm²/sr than that in the other groups (p=0.043). Ischemic mice treated with BMSCs in the delivery system presented an improved limb salvage rate (0.926± 0.12)% compared with that of ischemic mice treated with BMSCs in PBS (0.841± 0.029)% at the 5th week after ischemia establishment (p=0.0033).Conclusion: Our findings suggest that the survival time of BMSCs is prolonged in this innovative delivery system. The combination of nanospheres and hydrogels effectively restored vascular blood perfusion while exerting minimal toxicity on BMSCs. This novel approach combining oxygen-releasing nanospheres and self-healing hydrogels as a delivery system represents an advancement in enhancing the functionality of BMSCs to treat CLTI. Keywords: nanoscale microsphere, stem cell therapy, delivery system, chronic vascular disease, revascularization, tissue recovery

Miao Shen,1,2 Zhinong Jiang1 1Department of Pathology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou City, Zhejiang Province, 310000, People’s Republic of China; 2Department of Pathology, Deqing People’s Hospital, Huzhou City, Zhejiang Province, 313200, People’s Republic of ChinaCorrespondence: Zhinong Jiang, Department of Pathology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, No. 3 Qingchun East Road, Shangcheng District, Hangzhou City, Zhejiang Province, 310000, People’s Republic of China, Tel +86 15105729672, Email jiangzn2003@163.comAbstract: Lymphoma, a heterogeneous group of blood cancers, presents significant diagnostic and therapeutic challenges due to its complex subtypes and variable clinical outcomes. Artificial intelligence (AI) has emerged as a promising tool to enhance the accuracy and efficiency of lymphoma pathology. This review explores the potential of AI in lymphoma diagnosis, classification, prognosis prediction, and treatment planning, as well as addressing the challenges and future directions in this rapidly evolving field.Keywords: artificial intelligence, machine learning, deep learning, lymphoma, digital pathology

Zhenren Peng,1– 6,&ast; Jie Wei,1,2,&ast; Xiuning Huang,1,2,&ast; Biyan Chen,1,2 Lifang Liang,1,2 Baoying Feng,1,2 Pengshu Song,1,2 Jiajia He,1,2 Ting Que,1,2 Jingjue Lan,1,2 Jie Qin,1,2 Sheng He,1– 6 Qiufen Wei1– 6 1Birth Defects Research Laboratory, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530002, People’s Republic of China; 2Birth Defects Research Laboratory, Birth Defects Prevention and Control Institute of Guangxi Zhuang Autonomous Region, Nanning, 530002, People’s Republic of China; 3Birth Defects Research Laboratory, Guangxi Key Laboratory of Reproductive Health and Birth Defect Prevention, Nanning, 530002, People’s Republic of China; 4Birth Defects Research Laboratory, Guangxi Key Laboratory of Birth Defects Research and Prevention, Nanning, 530002, People’s Republic of China; 5Birth Defects Research Laboratory, Guangxi Clinical Research Center for Fetal Diseases, Nanning, 530002, People’s Republic of China; 6Birth Defects Research Laboratory, Guangxi Clinical Research Center for Pediatric Diseases, Nanning, 530002, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Sheng He; Qiufen Wei, Birth Defects Research Laboratory, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, No. 59 Xiangzhu Avenue, Nanning, Guangxi Zhuang Autonomous Region, 530002, People’s Republic of China, Email heshengbiol@163.com; Wqf2024@163.comPurpose: To explore the changing trends in the prevalence and epidemiological characteristics of congenital heart defects (CHDs) in perinatal infants (PIs) in Guangxi, China.Patients and Methods: During 2016 and 2020, the Guangxi Birth Defects Monitoring Network (GXBDMN) monitored a total of 3627108 PIs in this study. The CHDs data for PIs can be obtained from the GXBDMN. The study analyzed the changing trends of total CHDs prevalence and each subtype of CHDs prevalence per year using prevalence-rate ratios (PRR). The correlation between characteristics (such as year, infant gender, maternal age, and quarter) and the prevalence of CHDs was also examined by the PRR.Results: Between 2016 and 2020, 10817 PIs were diagnosed with CHDs, resulting in an overall CHDs prevalence of 29.82 [95% confidence intervals (CI): 29.26– 30.38] per 10000 PIs. CHDs accounted for 24.50% of all types of BDs, making them the most common type of BDs. Atrial septal defect / patent foramen ovale (ASD/PFO), patent ductus arteriosus (PDA), ventricular septal defect (VSD), atrioventricular septal defect (AVSD), persistent left superior vena cava (PLSVC), and tetralogy of Fallot (TOF) were the 6 most common subtypes of CHDs. Together they accounted for 86.24% of all CHDs cases, with a total prevalence of 25.72 (95% CI: 25.20– 26.24) per 10000 PIs. The study period saw a significant increase in the prevalence of CHDs (PRR = 1.300, 95% CI: 1.283– 1.318), and the maternal age also played a significant role in this increase (PRR = 2.738, 95% CI: 2.428– 3.087).Conclusion: The prevalence of CHDs in Guangxi is rising and has an upward trend with maternal age. ASD/PFO, PDA, VSD, AVSD, PLSVC, and TOF were the top six subtypes of CHDs.Keywords: congenital heart defects, perinatal infants, pregnant women, prevalence

Abdullah M Aloraini,1 Abdurahman Khalid Addweesh,2 Mohammed Basem Beyari,2 Munib Nader Alkhateb,2 Maram Basem Beyari,3 Majd Nader Alkhateeb,3 Reham Abdulrahman Al Ahmed,3 Abdullah Thamar Alotaibi,3 Abdulmajeed Altoijry4 1Department of Surgery, College of Medicine, King Saud University, Riyadh, Saudi Arabia; 2Medical Intern, College of Medicine, King Saud University, Riyadh, Saudi Arabia; 3Medical Student, College of Medicine, King Saud University, Riyadh, Saudi Arabia; 4Division of Vascular Surgery, Department of Surgery, College of Medicine, King Saud University, Riyadh, Saudi ArabiaCorrespondence: Abdurahman Khalid Addweesh, Medical intern, College of Medicine, King Saud University, Riyadh, 12371, Saudi Arabia, Email a.adwish1@gmail.comIntroduction: Surgeon attire significantly affects patients’ perceptions and can improve patient-surgeon relationships, which are crucial for patient comfort, experience, satisfaction, and treatment adherence. Understanding patient preferences for surgeon attire is essential, particularly in Saudi Arabia, for establishing appropriate dress codes in healthcare institutions. This national cross-sectional study aimed to fill this gap by assessing patient preferences for surgeon attire and its impact on patients’ confidence in their surgeons across various medical settings.Methods: The study used a questionnaire with 16 questions and images of surgeons in different attire styles, focusing on trust, care, approachability, and comfort ratings. The questionnaire included options like scrubs with a white coat, formal attire, and traditional Saudi attire for male surgeons, and various options including niqab and skirts for female surgeons. The survey had four sections covering ratings, attire preferences, opinions on white coats, and demographic data.Results: A total of 612 patients completed the questionnaires, mainly aged 35– 54 (33%). Skirt and niqab and white coat attire for females received the highest ratings. Attire other than scrubs, especially jeans and heels with a white coat, had significantly lower ratings. Scrubs and white coats were the most preferred attire for male (23.7%) and female (17%) surgeons. Additionally, 71.24% of participants agreed that surgeons should wear white coats.Conclusion: In Saudi Arabia, male surgeons are preferred in scrubs and white coats, while female surgeons are preferred in skirts with white coats and niqabs. These preferences reflect notions of formality, professionalism, and cultural influences. Jeans received the lowest ratings, possibly due to perceptions of informality. Patients favor scrubs and white coats for hygiene benefits and conveying dedication and expertise. Future research should validate these findings across diverse cultures and medical fields.Keywords: surgeon attire, public perception, infection control, health policy, patient-physician relationship

Kaiqiang Li,1,2,&ast; Jing Jin,3,&ast; Yimin Yang,4,&ast; Xuling Luo,4 Yaling Wang,1 Aibo Xu,1 Ke Hao,1,2 Zhen Wang1,2 1Laboratory Medicine Center, Allergy Center, Department of Transfusion Medicine, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, 310014, People’s Republic of China; 2Key Laboratory of Biomarkers and In Vitro Diagnosis Translation of Zhejiang Province, Hangzhou, Zhejiang, 310063, People’s Republic of China; 3Laboratory Medicine Center, Zhejiang Center for Clinical Laboratories, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, 310014, People’s Republic of China; 4College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou, Zhejiang, 310014, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ke Hao; Zhen Wang, Email haokehaokehaoke@aliyun.com; wangzhen@hmc.edu.cnAbstract: Allergen Immunotherapy (AIT) is the only etiological therapeutic method available for allergic rhinitis (AR). Currently, several options for AIT in the market, such as subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT), have different routes of administration. These traditional methods have achieved encouraging outcomes in clinic. However, the side effects associated with these methods have raised the need for innovative approaches for AIT that improve safety, shorten the course of treatment and increase local drug concentration. Nanoparticles (NPs) are particles ranging in size from 1 to 100 nm, which have been hired as potential adjuvants for AIT. NPs can be employed as agents for modulating immune responses in AR or/and carriers for loading proteins, peptides or DNA molecules. This review focuses on different kinds of nanoparticle delivery systems, including chitosan nanoparticles, exosomes, metal nanoparticles, and viral nanoparticles. We summarized the advantages and limitations of NPs for the treatment of allergic rhinitis. Overall, NPs are expected to be a therapeutic option for AR, which requires more in-depth studies and long-term therapeutic validation. Keywords: allergen immunotherapy, nanoparticles, allergic disease, subcutaneous immunotherapy

Katherine McDermott,1,2 Alexander Mattia Presciutti,1,2 Nadine Levey,1 Julie Brewer,1 Christina L Rush,1,2 Natalia Giraldo-Santiago,1,3 Tony V Pham,1,2 Roger Pasinski,4 Neda Yousif,4 Milton Gholston,4 Vidya Raju,4 Jonathan Greenberg,1,3 Christine S Ritchie,2,3 Ana-Maria Vranceanu1,2 1Center for Health Outcomes and Interdisciplinary Research, Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA; 2Harvard Medical School, Boston, MA, USA; 3Center for Aging and Serious Illness, Massachusetts General Hospital, Boston, MA, USA; 4MGH Revere HealthCare Center, Revere, MA, USACorrespondence: Ana-Maria Vranceanu, Center for Health Outcomes and Interdisciplinary Research, Department of Psychiatry, Massachusetts General Hospital/Harvard Medical School, One Bowdoin Square, 1st Floor, Suite 100, Boston, MA, 02114, USA, Email avranceanu@mgh.harvard.eduPurpose: Chronic pain is highly prevalent and disabling for older adults, particularly those from underserved communities. However, there is an absence of research on how contextual (eg, community/societal) factors interact with pain for these patients. Informed by the socio-ecological model, this study aimed to elucidate the individual, interpersonal, community, and societal factors associated with chronic pain from the perceptions of older adult patients and medical staff in a community clinic.Patients and Methods: In this qualitative study, we conducted four focus groups and two interviews with medical staff (n=25) and three focus groups and seven individual interviews with older adult patients with chronic pain (n=18). Participants were recruited using purposive sampling from an ethnically and economically diverse primary care clinic in the greater Boston community. We transcribed assessments and thematically analyzed data using a hybrid deductive-inductive approach.Results: At the individual level, we identified three themes: (1) older adults with complex care needs, (2) impact of pain (including on physical, emotional, work, and identity functioning), and (3) coping with pain. At the interpersonal level, complex relationships with (1) social supports and (2) medical staff emerged as themes. The need for (1) resources and (2) culturally informed care was identified at the community level, and socioeconomic status impacting the availability of resources for managing chronic pain emerged for the societal domain.Conclusion: Findings underscore the intersection of factors contributing to the experience of pain among older adults from underserved communities. Our findings highlight the need to develop and implement treatments that fully address the experience of older adults with chronic pain at the individual, interpersonal, community, and societal levels.Keywords: community clinic, pain, health disparities

Wentao Ge,1,2 Wei Bian,2 Lu Wang,2 Lizhen Duan,1 Jiaying Guo,1 Lihua Wang2 1Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Third Hospital of Shanxi Medical University, Tongji Shanxi Hospital, Taiyuan, People’s Republic of China; 2Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, People’s Republic of ChinaCorrespondence: Lihua Wang, Hospital Administration Office, Southwest Hospital, Third Military Medical University (Army Medical University), 29 Gaotanyan Street, Shapingba District, Chongqing, 400038, People’s Republic of China, Email yiwa@tmmu.edu.cnObjective: To develop a medication literacy intervention program for glaucoma and test its effects on medication literacy, medication self-efficacy and medication adherence.Methods: The intervention was constructed according to the Information-Motivation-Behavioral skills Model and the Health Belief Model. Preliminary protocols were revised through expert group meetings and pre-experiments to form a formal intervention plan. Subsequently, 66 patients with glaucoma were enrolled and randomly assigned to the control and intervention groups. The control group was received with routine follow-up and education for glaucoma patients, while the intervention group was given an 8-weeks medication literacy intervention for glaucoma patients. Before the implementation of the intervention and at the end of the 8th week of the intervention, the Chinese Version of the Medication Literacy Scale, the Short Version of the Glaucoma Medication Self-Efficacy Questionnaire and the Chinese version of the Morisky Medication Adherence Scale-8 were used to evaluate the medication literacy level, medication self-efficacy and medication adherence of glaucoma patients in the intervention group and the control group.Results: We developed an 8-weeks multi-component medication literacy intervention for glaucoma. Before the start of the intervention, there were no statistically significant differences in the scores of medication literacy, medication self-efficacy and medication adherence between the control group and the intervention group. After the intervention, the medication literacy, medication self-efficacy, and medication adherence of the intervention patients were significantly better than those of the control group (P< 0.05).Conclusion: The 8-weeks multi-component intervention for glaucoma patients can improve their medication literacy, medication self-efficacy, and medication adherence.Keywords: glaucoma, medication adherence, medication literacy, nursing evaluation research, self-efficacy

Palanisamy Amirthalingam,1 Abdulrahman Sulaiman Alruwaili,2 Omar Ahmed Albalawi,2 Fayez Mohammed Alatawi,2 Saleh F Alqifari,1 Ahmed D Alatawi,3 Ahmed Aljabri4 1Department of Pharmacy Practice, Faculty of Pharmacy, University of Tabuk, Tabuk, Saudi Arabia; 2Pharm.D Program, Faculty of Pharmacy, University of Tabuk, Tabuk, Saudi Arabia; 3Department of Clinical Pharmacy, College of Pharmacy, Jouf University, Sakaka, Saudi Arabia; 4Department of Pharmacy Practice, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi ArabiaCorrespondence: Palanisamy Amirthalingam, Department of Pharmacy Practice, Faculty of Pharmacy, University of Tabuk, P.O. Box 741, Tabuk, 71491, Saudi Arabia, Email pchettiar@ut.edu.saIntroduction: The adoption of automated drug dispensing systems (ADDS) in hospital pharmacies is a global trend, driven by its potential to reduce dispensing errors, minimize prescription filling time, and ultimately, improve patient care services. However, a significant research gap exists in the field, as a comprehensive assessment of patient satisfaction with ADDS is currently lacking. This study, with its comprehensive approach, aims to fill this gap by comparing patient satisfaction between hospital pharmacies implementing ADDS and traditional drug dispensing systems (TDDS).Patients and Methods: The cross-sectional study was conducted in hospitals adopting ADDS and TDDS. All the outpatients aged 18 or above who visited the pharmacy were included, and severely ill patients were excluded from the study. A 17-item, 5-point Likert scale questionnaire assessed the participant’s satisfaction. The questionnaire has four domains: pharmacy administration, dispensing practice, patient education, and dispensing system.Results: The demographics of the study participants were normally distributed between ADDS and TDDS according to chi-square analysis. The mean participant satisfaction was significantly (P< 0.05) higher in ADDS than in TDDS regarding all the items of dispensing practice and dispensing system domains. Three items related to the pharmacy administration domain showed significant participant satisfaction with ADDS. However, the participants’ satisfaction showed no significant difference (p=0.176) between ADDS and TDDS in terms of the cleanliness of the pharmacy. Also, the participant’s satisfaction between ADDS and TDDS was not statistically significant regarding the pharmacist’s explanation of the side effects (p=0.850) and provision of all necessary information to the patient (p=0.061) in the patient education domain.Conclusion: Patient satisfaction was higher in the ADDS participants than in TDDS regarding pharmacy administration, patient education, dispensing practice, and systems. However, pharmacists in ADDS need to be motivated to transfer the advantages of ADDS to patient care, including comprehensive patient education, particularly on side effects.Keywords: automated drug dispensing system, dispensing practice, dispensing system, patient satisfaction, pharmacy administration, traditional drug dispensing system

Chen Zhao, Dan Wang, Junxiao Zhang, Shaowen Ge, Zhaojun Zhan, Li Xu, Shengkai Liao Department of Stomatology, First Affiliated Hospital of Bengbu Medical University, Bengbu, 233004, People’s Republic of ChinaCorrespondence: Li Xu; Shengkai Liao, Department of Stomatology, First Affiliated Hospital of Bengbu Medical University, Bengbu, 233004, People’s Republic of China, Email kqxuli@163.com; lsk3166@163.comBackground and Purpose: Periodontitis is the leading cause of tooth loss in adults worldwide. The functional loss, nutritional deficiencies, and psychological barriers it causes, as well as its impact on overall health and quality of life, are all significant. The prevalence of periodontal disease is high in China. Our study aimed to determine the intricate relationship between periodontal disease status, dental anxiety, self-rated oral health (SROH), self-efficacy for oral care, perceived social support, socioeconomic status (SES), and the oral health-related quality of life (OHRQoL) among periodontitis patients.Methods: This cross-sectional study used purposive sampling to identify 247 patients with periodontitis who entered the First Affiliated Hospital of Bengbu Medical University between October 2022 and October 2023. 247 participants underwent a periodontal clinical examination combined with imaging, adhering to the “ 2018 world new classification of periodontal and peri⁃implant diseases and conditions”. Participants also completed a detailed questionnaire in paper format, which included OHRQoL, sociodemographic details, dental anxiety, SROH, self-efficacy in oral care, perceived social support, and subjective SES.Results: Dental anxiety, self-efficacy for oral care, and SROH all had a direct and significant effect on OHRQoL. OHRQoL was indirectly related to SROH mediated by dental anxiety and subjective SES, perceived social support and self-efficacy for oral care, respectively. SROH was directly related to subjective SES, and at the same time, they had a direct effect on dental anxiety. Furthermore, patient’s age, gender, annual household income, and education level were significantly associated with the degree of periodontal disease.Conclusion: OHRQoL and periodontal status was influenced by socio-demographics characteristics, dental anxiety, SROH, self-efficacy for oral care, perceived social support, subjective SES in periodontitis patients. These insights underscore the importance of adopting a holistic approach in the management and treatment of periodontal diseases.Keywords: periodontitis, oral health-related quality of life, self-rated oral health, structural equation modeling

Takanobu Hirosawa,1,&ast; Tomoharu Suzuki,2,&ast; Tastuya Shiraishi,3,&ast; Arisa Hayashi,1,&ast; Yoichi Fujii,4,&ast; Taku Harada,1,4,&ast; Taro Shimizu1,&ast; 1Department of Diagnostic and Generalist Medicine, Dokkyo Medical University, Tochigi, Japan; 2Department of Hospital Medicine, Urasoe General Hospital, Okinawa, Japan; 3Higashinihonbashinaika clinic, Tokyo, Japan / Ubie, inc, Tokyo, Japan; 4General Medicine, Nerima Hikarigaoka Hospital, Tokyo, Japan&ast;These authors contributed equally to this workCorrespondence: Takanobu Hirosawa, Department of Diagnostic and Generalist Medicine, Dokkyo Medical University, 880 Kitakobayashi, Mibu-cho, Simotsuga-gun Tochigi, Tochigi, 321-0293, Japan, Tel +81-282-86-1111, Fax +81-282-86-4775, Email hirosawa@dokkyomed.ac.jpPurpose: Artificial intelligence (AI) holds great potential for revolutionizing health care by providing clinicians with data-driven insights that support more accurate and efficient clinical decisions. However, applying AI in clinical settings is often challenging due to the complexity and vastness of medical information. This perspective article explores how AI development methodologies can be adapted to support clinicians in their decision-making processes, emphasizing the importance of a hybrid approach that combines AI capabilities with clinicians’ expertise.Patients and Methods: We developed a conceptual framework designed to integrate AI-driven hybrid intelligence into clinical practice to enhance decision-making. This framework focuses on adapting key AI concepts, such as backpropagation, quantization, and avoiding overfitting, to help clinicians better interpret complex medical data and improve diagnosis and treatment planning.Results: Several AI methodologies were adapted to enhance clinical decision-making. First, backpropagation allows clinicians to refine initial assessments by revisiting them as new data emerges, improving diagnostic accuracy over time. Second, quantization helps break down complex medical problems into manageable components, enabling clinicians to prioritize critical elements of care. Finally, avoiding overfitting encourages clinicians to balance rare diagnoses with more common explanations, reducing the risk of diagnostic errors and unnecessary complexity.Conclusion: The integration of AI-driven hybrid intelligence has the potential to enhance clinical decision-making. By adapting AI methodologies, clinicians can enhance their ability to analyze data, prioritize treatments, and make more accurate diagnoses while preserving the essential human aspect of health care. This framework highlights the importance of combining AI’s strengths with clinicians’ expertise for more effective and balanced decision-making in clinical practice. This perspective highlights the value of hybrid intelligence in achieving more balanced, effective, and patient-centered decision-making in health care.Keywords: artificial intelligence, clinical reasoning, diagnostic accuracy, digital health, internal medicine, natural language processing

Xiangjun Chen,&ast; Weiwei Li,&ast; Qing Fan, Xiao Liu, Xuanxiang Zhai, Xiaoyi Shi, Wenting Li, Wei Hong School of Pharmacy, Shandong Engineering Research Center of New-Type Drug Loading & Releasing Technology and Preparation, Binzhou Medical University, Yantai, Shandong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Hong; Wenting Li, Email hongwei_sy@bzmc.edu.cn; liwenting1003@163.comIntroduction: Pseudomonas aeruginosa (P. aeruginosa)-induced pneumonia is marked by considerable infiltration of inflammatory cells and biofilm formation, which causes acute and transient lung inflammation and infection. Nevertheless, the discovery of alternative preventative and therapeutic methods is essential due to the high mortality rates in clinical settings and the resistance of P. aeruginosa infection to multiple medications.Purpose: In this research, we constructed amphiphilic Janus nanoparticles (JNPs, denoted as SSK1@PDA/CaP@CIP), loaded with hydrophobic SSK1, a β-galactosidase (β-gal)-activated prodrug for reducing macrophages, and hydrophilic ciprofloxacin (CIP), a classic antibiotic for treating infection. SSK1@PDA/CaP@CIP was designed to effectively attenuate inflammation, eradicate biofilms, and combat planktonic P. aeruginosa.Results: As expected, SSK1@PDA/CaP@CIP was able to target the infection site and demonstrated outstanding efficacy in treating P. aeruginosa strain PAO1-induced pneumonia by regulating macrophage infiltration to reduce inflammation and removing planktonic bacteria and biofilms to control infection. Additionally, the primary organs did not exhibit any discernible pathological changes following treatment with SSK1@PDA/CaP@CIP, which indicates superior biocompatibility throughout the treatment course.Discussion: In conclusion, our investigation introduced a promising approach to the treatment of pneumonia associated with PAO1.Keywords: Pseudomonas aeruginosa, pneumonia, inflammatory responses, β-galactosidase (β-gal)-activated prodrug, amphiphilic Janus nanoparticles

Jiekee Lim,1 Jieyun Li,1 Mi Zhou,1 Xinang Xiao,1 Zhaoxia Xu1,2 1School of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Shanghai Key Laboratory of Health Identification and Assessment, Shanghai, People’s Republic of ChinaCorrespondence: Zhaoxia Xu, School of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China, Email zhaoxia7001@shutcm.edu.cnBackground: Integrating Traditional Chinese Medicine (TCM) knowledge with modern technology, especially machine learning (ML), has shown immense potential in enhancing TCM diagnostics and treatment. This study aims to systematically review and analyze the trends and developments in ML applications in TCM through a bibliometric analysis.Methods: Data for this study were sourced from the Web of Science Core Collection. Data were analyzed and visualized using Microsoft Office Excel, Bibliometrix, and VOSviewer.Results: 474 documents were identified. The analysis revealed a significant increase in research output from 2000 to 2023, with China leading in both the number of publications and research impact. Key research institutions include the Shanghai University of Traditional Chinese Medicine and the China Academy of Chinese Medical Sciences. Major research hotspots identified include ML applications in TCM diagnosis, network pharmacology, and tongue diagnosis. Additionally, chemometrics with ML are highlighted for their roles in quality control and authentication of TCM products.Conclusion: This study provides a comprehensive overview of ML applications’ development trends and research landscape in TCM. The integration of ML has led to significant advancements in TCM diagnostics, personalized medicine, and quality control, paving the way for the modernization and internationalization of TCM practices. Future research should focus on improving model interpretability, fostering international collaborations, and standardized reporting protocols.Keywords: artificial intelligence, bibliometric, machine learning, review, traditional Chinese medicine

Zhichao Zhu,&ast; Weiheng Zheng,&ast; Nan Tang, Weimei Zhong Human Resource Department, Shenzhen Children’s Hospital, Shenzhen, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Nan Tang; Weimei Zhong, Email phoebetn@outlook.com; zhongweimei_023@163.comAbstract: Background: Hospital manpower management (HRM) is vital for effective healthcare delivery. Unique challenges, such as managing diverse staff, ensuring clear communication, and optimizing resources, complicate HRM. Rising operational costs, workforce shortages, and employee burnout necessitate strategic approaches to manpower management. This review aims to provide a comprehensive understanding of manpower management in hospitals, focusing on identifying core components and discussing innovative strategies to address current challenges, particularly those related to workforce shortages. A literature review was conducted using databases such as PubMed, Scopus, and Google Scholar. Key terms included “hospital manpower management”, “HRM challenges in healthcare”, and “workforce shortages”, selected for their relevance to the core focus of this review. Relevant articles published from 2019 to 2023 were selected for analysis. The review identified core components of manpower management: recruitment and staffing, workforce planning, training and development, performance management, and compensation and benefits. Strategies to address workforce shortages included strategic hiring and enhancing employee engagement. The integration of technology and ongoing training emerged as critical for maintaining high-quality patient care. Effective manpower management is essential for the sustainability of healthcare systems. This review highlighted the importance of innovative HRM strategies to tackle workforce shortages and improve employee satisfaction. By focusing on comprehensive HRM practices, healthcare organizations could enhance workforce efficiency and provide better patient care. Future research should explore the long-term impacts of these strategies on healthcare.Keywords: hospital manpower management, workforce shortages, HRM challenges in healthcare, workforce planning

Erik Briffault,1,2 Ricardo Reyes,2,3 Patricia Garcia-Garcia,1,2 Helena Rouco,1 Luis Diaz-Gomez,4 Maria Rosa Arnau,2,5 Carmen Evora,1,3 Patricia Diaz-Rodriguez,2,4 Araceli Delgado1,2 1Department of Chemical Engineering and Pharmaceutical Technology, Universidad de La Laguna, La Laguna, 38206, Spain; 2Institute of Biomedical Technologies (ITB), Universidad de La Laguna, La Laguna, 38320, Spain; 3Department of Biochemistry, Microbiology, Cell Biology and Genetics, Universidad de La Laguna, La Laguna, 38200, Spain; 4Department of Pharmacology, Pharmacy and Pharmaceutical Technology, I+D Farma Group (GI-1645), Facultad de Farmacia, Instituto de Materiales (iMATUS) and Health Research Institute of Santiago de Compostela (IDIS), Universidade de Santiago de Compostela, Santiago de Compostela, 15782, Spain; 5Servicio de Estabulario, Universidad de La Laguna, La Laguna, 38206, SpainCorrespondence: Patricia Diaz-Rodriguez; Araceli Delgado, Email patricia.diaz.rodriguez@usc.es; adelgado@ull.edu.esIntroduction: Osteoporosis is a metabolic disorder characterized by the loss of bone mass and density. Nucleic acid-based therapies are among the most innovative approaches for osteoporosis management, although their effective delivery to bone tissue remains a challenge. In this work, SFRP1-silencing GampeR loaded-nanoparticles were prepared and functionalized with specific moieties to improve bone targeting and, consequently, therapeutic efficacy. SFRP1-silencing would promote osteoblastic differentiation by enhancing the WNT/β-catenin pathway and thus diminishing the progression of osteoporosis.Methods: A nucleic acid-based delivery system consisting of lipid-polymer hybrid nanoparticles (LPNPs) loading a GapmeR for SFRP1 silencing was developed and further functionalized with two bone-targeting moieties: a specific aptamer (Apt) for murine mesenchymal stem cells and an antiresorptive drug, namely alendronate (ALD). These systems were tested in vivo in osteoporotic mice at different dosage regimens to analyze dose dependence in bone-forming activity and potential toxicity. The quality of trabecular and cortical bone was assessed by both micro computed tomography (micro-CT) and histological and histomorphometric analyses. Early and late osteogenesis were quantified by immunohistochemistry.Results: Results showed that functionalizing LPNPs loaded with an SFRP1-silencing GapmeR using both Apt and ALD improved bone quality and enhanced osteogenesis following a dose–effect relationship, as revealed by micro-CT, histological and immunohistochemical analyses. In contrast, non-functionalized LPNPs did not produce these effects.Conclusion: These findings highlight the relevance of proper targeting and dosage in nucleic acid-based therapeutics, proving to be crucial for exerting their therapeutic effect: a deficient targeting strategy and/or dosage may result in the therapeutic failure of an adequate gene therapy agent. Keywords: osteoporosis, bone targeting, nanoparticle dose-effect, gene therapy, aptamer, alendronate, micro-CT

Xudong Che, Baixue Wu, Hongxia Zhang, Dengzhi Jiang, Wenqiao Fu, Zhaohui He Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Zhaohui He, Email geno_he@163.comBackground: Hemoglobin decrement is a common complication after aneurysmal subarachnoid hemorrhage (aSAH) and is associated with poor outcome. However, the mediating variables on the causal pathway between hemoglobin decrement and poor outcome in aSAH are not clear.Methods: This is a single-center retrospective observational study containing all consecutive patients with aSAH admitted to our hospital between January 1, 2019, and June 30, 2022. Hemoglobin decrement was defined as the hemoglobin at admission minus the minimum hemoglobin during hospitalization. Calculation of cutoff value using ROC curve Youden index. The main exposure of interest was a hemoglobin decrement greater than the cutoff value. The primary outcome was poor outcome at 3 months (mRS 4– 6).Results: A total of 480 patients with aSAH were included in the study, 414 (71.1%) had a favorable and 66 (28.9%) had a poor outcome at 3 months. The cut-off value for calculating the degree of hemoglobin decrease using the ROC curve was 12.5 g/l. Hemoglobin decrement greater than the cutoff value was significantly associated with pneumonia (OR 3.12; 95% CI 1.78– 5.57; p < 0.001), cerebral infarction (OR 3.06; 95% CI 1.80– 5.30; p < 0.001), and poor prognosis (OR 2.88; 95% CI 1.44– 5.92; p = 0.003) at 3 months. The mediation effect was significant for both pneumonia and cerebral infarction, with the average causal mediation effect (ACME) were 0.04 (95% CI 0.02– 0.08; p < 0.05) and 0.05 (95% CI 0.02– 0.08; p < 0.001), respectively.Conclusion: Hemoglobin decrement during hospitalization was significantly associated with poor prognosis after aSAH, and the increased risk of cerebral infarction and pneumonia might mediate this effect. Avoiding hemoglobin decrement greater than 12.5g/l may improve the prognosis of patients with aSAH.Keywords: aneurysmal subarachnoid hemorrhage, hemoglobin decrement, cerebral infarction, pneumonia

Pilong Shi,1,&ast; Yuetong Sha,1,&ast; Xinran Wang,1,&ast; Tao Yang,1 Jiawei Wu,1 Jiajun Zhou,1 Kai Liu,1 Xue Guan,2 Song Wang,1 Yongsheng Liu,1 Jingquan Gao,3 Hongli Sun,1 Tao Ban,1 Yonggang Cao1 1Department of Pharmacology, Harbin Medical University, Heilongjiang, 163319, People’s Republic of China; 2Morphological Experiment Center, Harbin Medical University, Heilongjiang, 163319, People’s Republic of China; 3Department of Nursing, School of Medicine, Lishui University, Lishui, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yonggang Cao; Hongli Sun, Email 437343482@qq.com; sunhongli@hmudq.edu.cnPurpose: Myocardial ischemia-reperfusion injury (MI/RI) is associated with increased oxidative damage and mitochondrial dysfunction, resulting in an elevated risk of mortality. MI/RI may be alleviated by protecting cardiomyocytes from oxidative stress. Lutein, which belongs to a class of carotenoids, has proven to be effective in cardiovascular disease treatment due to its remarkable antioxidant properties, but its application is limited due to its poor stability and low bioavailability in vivo.Methods: In this study, a delivery system was developed based on distearoyl phosphatidyl ethanolamine (DSPE)-thiol-ketone (TK)-PEG2K (polyethylene glycol 2000) (abbreviated as DTP) and PCM-SH (CWLSEAGPVVTVRALRGTGSW) to deliver lutein (abbreviated as lutein@DTPP) to damaged myocardium. First, lutein, lutein@DTP, or lutein@DTPP were injected through the tail vein once a day for 3 days and then MI/RI model rats were established by exposing rats to ischemia for 45 min and reperfusion for 6 h. We employed a range of experimental techniques including qRT-PCR, Western blotting, transmission electron microscopy, immunohistochemistry, immunofluorescence, flow cytometry, immunoprecipitation, molecular docking, and molecular dynamics simulations.Results: Lutein@DTPP exhibited good myocardial targeting and ROS-responsive release. Our data suggested that lutein@DTPP effectively suppresses ferroptosis in cardiomyocytes. Mechanistically, we observed an upregulation of mouse double minute-2 (MDM2) in the hearts of MI/RI models and cardiomyocytes exposed to hypoxia/reoxygenation (H/R) conditions. In addition, NADH-ubiquinone oxidoreductase 75 kDa Fe-S protein 1 (NDUFS1) translocation from the cytosol to the mitochondria was inhibited by MDM2 upregulation. Notably, no significant variation in the total NDUFS1 expression was observed in H/R-exposed cardiomyocytes following treatment with siMDM2. Further study indicated that lutein facilitates the translocation of NDUFS1 from the cytosol to mitochondria by directly binding and sequestering MDM2, thereby improving mitochondrial function and inhibiting ferroptosis.Conclusion: Lutein@DTPP promoted the mitochondrial translocation of NDUFS1 to restore mitochondrial function and inhibited the ferroptosis of cardiomyocytes by directly binding and sequestering MDM2. Keywords: myocardial ischemia-reperfusion injury, lutein, ROS, MDM2, NDUFS1, ferroptosis

Maodong Wu,1 Wenchao Yi,2 Qinglun Su,1 Yiming Huang,1 Qin Zhao,1,&ast; Shouguo Liu2,&ast; 1Department of Rehabilitation Medicine, The First Affiliated Hospital of Kangda College of Nanjing Medical University/The First People’s Hospital of Lianyungang, Lianyungang, 222000, People’s Republic of China; 2Department of Rehabilitation Medicine, The First Affiliated Hospital of Nanjing Medical University/Jiangsu Province Hospital, Nanjing, 210029, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shouguo Liu, Department of Rehabilitation Medicine, The First Affiliated Hospital of Nanjing Medical University/Jiangsu Province Hospital, 300 Guangzhou Road, Nanjing, Jiangsu Province, 210029, People’s Republic of China, Tel +86-13675155937, Email liushouguo2002@163.com Qin Zhao, Department of Rehabilitation Medicine, The First Affiliated Hospital of Kangda College of Nanjing Medical University/The First People’s Hospital of Lianyungang, No. 6 Zhenhua East Road, Lianyungang, 222000, People’s Republic of China, Tel +86-18961322279, Email zhaozihe@163.comPurpose: This study aims to examine the predictive value of Craniocervical Flexion Test (CCFT) scores in individuals with chronic non-specific neck pain (CNNP) and to identify factors that may affect CCFT scores.Methods: This case-control study included 73 patients with CNNP and 127 healthy controls. We assessed baseline information such as demographics, duration and frequency of CNNP onset, Neck Disability Index (NDI), and Visual Analog Scale (VAS) scores. All subjects were evaluated by the same rater for CCFT, maximal muscle strength, and endurance of the deep cervical flexors. Head and neck posture was measured using two-dimensional videography, capturing sagittal head angle (SHA), forward head angle (FHA), and protracted shoulder angle (PSA). The predictive capacity of CCFT for CNNP was evaluated using the ROC curve and area under the curve (AUC). Univariate and multivariate ordered logistic regression models were employed to analyze factors influencing CCFT scores.Results: The final analysis included 70 participants in the CNNP group and 123 in the control group. The CNNP group demonstrated lower CCFT scores, reduced maximal muscle strength, and decreased endurance of the deep cervical muscles (P< 0.05). Among maximum muscle strength, endurance, and CCFT scores, the latter exhibited the highest AUC. Univariate and multivariate ordered logistic regression analyses revealed that maximal muscle strength, muscle endurance, FHA, and lower NDI scores significantly increased the likelihood of higher CCFT scores (P< 0.05), while SHA significantly decreased this likelihood (P< 0.05).Conclusion: CCFT demonstrates good predictive value for CNNP, surpassing muscle strength and endurance. Maximal muscle strength, muscle endurance, FHA, and lower NDI scores were positive influencing factors for CCFT scores, whereas SHA was a negatively influencing factor.Plain Language Summary: As the population of patients with chronic non-specific neck pain (CNNP) increases, there is a growing clinical need for an assessment tool to predict the occurrence of CNNP. The Craniocervical Flexion Test (CCFT) is a widely used assessment tool for this condition and may be instrumental in identifying affected patients. However, the predictive value of CCFT for CNNP remains unclear, and no research has yet examined the factors that may influence CCFT scores in this context. To address this gap, we conducted a case-control study to investigate the predictive ability of CCFT for CNNP, and explore the factors that may affect CCFT scores. Our results indicated that CCFT has good predictive value for CNNP, with influencing factors including maximal muscle strength, muscle endurance, sagittal head angle, forward head angle, and the Neck Disability Index. Therefore, we suggest that CCFT has a good application value in the diagnosis and management of CNNP.Keywords: chronic non-specific neck pain, craniocervical flexion test, neck maximal muscle strength, neck muscle endurance, forward head angle

Sheng Wang,1,&ast; Demeng Xia,2,3,&ast; Wenxue Dou,4,&ast; Aimin Chen,1 Shuogui Xu2 1Department of Traumatic Orthopedics, Shanghai Fourth People’s Hospital, School of Medicine, Tongji University, Shanghai, 200434, People’s Republic of China; 2Department of Traumatic Orthopedics, Changhai Hospital, Naval Medical University, Shanghai, 200433, People’s Republic of China; 3Department of Clinical Medicine, Hainan Health Vocational College, Haikou, 570100, People’s Republic of China; 4Department of Stomatology, Shanghai East Hospital, Tongji University, Shanghai, 200120, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shuogui Xu, Department of Emergency, Changhai Hospital, Naval Medical University, Xiangyin Road, Shanghai, 200433, People’s Republic of China, Email 18516116672@163.com Aimin Chen, Department of traumatic orthopedics, Shanghai Fourth People’s Hospital, School of Medicine, Tongji University, Shanghai, 200434, People’s Republic of China, Email chenaimin2023@163.comBackground: Delayed healing and non-healing of bone defects pose significant challenges in clinical practice, with metal materials increasingly recognized for their significance in addressing these issues. Among these materials, Strontium (Sr) and Zinc (Zn) have emerged as promising agents for promoting bone repair. Building upon this insight, this research evaluates the impact of a porous Sr@Zn@SiO2 nanocomposite implant on bone regeneration, aiming to advance the field of bone repair.Methods: The preparation of the Sr@Zn@SiO2 composite implant involves various techniques such as roasting, centrifugation, and washing. The material’s composition is examined, and its microstructure and element distribution are analyzed using TEM and elemental scanning technology. In vitro experiments entail the isolation and characterization of BMSCs followed by safety assessments of the implant material, evaluation of cell migration capabilities, and relevant proliferation markers. Mechanistically, this study delves into key targets associated with significant changes in the osteogenic process. In vivo experiments involve establishing a rat femur bone defect model, followed by assessment of the osteogenic potential of Sr@Zn@SiO2 using Micro-CT imaging and tissue section staining.Results: Through in vivo and in vitro investigations, we validate the osteogenic efficacy of the Sr@Zn@SiO2 composite implant. In vitro analyses demonstrate that porous Sr@Zn@SiO2 nanocomposite materials upregulate BMP-2 expression, leading to the activation of Smad1/5/9 phosphorylation and subsequent activation of downstream osteogenic genes, culminating in BMSCs osteogenic differentiation and bone proliferation. And the migration of BMSCs is closely related to the high expression of CXCL12/CXCR4, which will also provide the conditions for osteogenesis. In vivo, the osteogenic ability of Sr@Zn@SiO2 was also confirmed in rats.Conclusion: In our research, the porous Sr@Zn@SiO2 composite implant displays prominent osteogenic effect and promotes the migration and differentiation of BMSCs to promote bone defect healing. This bioactive implant has surgical application potential in the future. Keywords: bioactive porous composite, differentiation and migration, bone reconstruction, smad1/5/9

Sara S Berggren,1,2 Stefan Bergman,3,4 Gerd Almquist-Tangen,1,5 Jovanna Dahlgren,1,6 Josefine Roswall,1,5 Julia S Malmborg4,7 1Department of Pediatrics, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; 2Health Center Hyltebruk, Halland, Sweden; 3General Practice/Family Medicine, School of Public Health and Community Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; 4Spenshult Research and Development Centre, Halmstad, Sweden; 5Department of Pediatrics, Halland Hospital Halmstad, Halmstad, Sweden; 6Västra Götaland County, Department of Pediatrics, Queen Silvia Children’s Hospital, Gothenburg, Sweden; 7School of Health and Welfare, Halmstad University, Halmstad, SwedenCorrespondence: Sara S Berggren, Email sara.berggren@gu.sePurpose: Adults with neurodevelopmental disorders have an increased risk for chronic pain. This study aimed to describe the prevalence of frequent and multisite pain among children with symptoms of attention deficit hyperactivity disorder (ADHD) and explore potential sex differences in pain prevalence.Participants and Methods: Children born in 2008 included in the “Halland Health and Growth Study” were invited to a follow-up (n = 1186) in 2018– 19. Parents received a digital screening questionnaire, the Swanson, Nolan and Pelham Rating Scale (SNAP-IV) for ADHD, and the children answered a pain questionnaire that included a pain mannequin. The main outcome was pain experience, and children with symptoms of ADHD were compared to children without these symptoms.Results: In this general population of 10– 11-year-old Swedish children, weekly pain was reported in 52.5% of children with symptoms of ADHD combined type, compared to 36.2% of children without these symptoms (p < 0.05). Hyperactivity and impulsivity were significant contributors to the increased risk for frequent pain (OR 2.33 95% CI 1.30 to 4.17, p = 0.004), but inattention was not a significant contributor (OR 1.17 95% CI 0.74 to 1.87, p = 0.497). Multisite pain was more common among girls with hyperactivity compared to boys with hyperactivity (51.4 vs 27.9%, p = 0.036). Weekly headache and/or abdominal pain was reported by a quarter of girls with symptoms of ADHD combined type, and up to a fifth of boys, compared to 11– 13% of children without these symptoms.Conclusion: Frequent pain was more common for children with symptoms of ADHD compared to children without symptoms of ADHD. Hyperactivity and impulsivity had a stronger association to pain than had inattention-related problems. Clinicians should be aware of the frequent occurrence and the association between pain and neurodevelopmental disorders among children, and that it could complicate both the clinical picture and the treatment.Keywords: attention deficit hyperactivity disorder, ADHD, birth cohort, children, multisite pain, sex differences

Ching-Yun Hsu,1,2,&ast; Tse-Hung Huang,2– 6,&ast; Zih-Chan Lin,7 Chih-Jung Chen,8– 10 Erica Hwang,11 Wei-Jhang Chen,12 Jia-You Fang2,12,13 1Department of Nutrition and Health Sciences, Chang Gung University of Science and Technology, Kweishan, Taoyuan, Taiwan; 2Research Center for Food and Cosmetic Safety and Research Center for Chinese Herbal Medicine, Chang Gung University of Science and Technology, Kweishan, Taoyuan, Taiwan; 3Department of Traditional Chinese Medicine, Chang Gung Memorial Hospital, Keelung, Taiwan; 4School of Traditional Chinese Medicine, Chang Gung University, Kweishan, Taoyuan, Taiwan; 5Department of Chemical Engineering and Graduate Institute of Biochemical Engineering, Ming Chi University of Technology, New Taipei City, Taiwan; 6Department of Traditional Chinese Medicine, Xiamen Chang Gung Memorial Hospital, Xiamen, People’s Republic of China; 7Chronic Diseases and Health Promotion Research Center, Chang Gung University of Science and Technology, Puzi, Chiayi, Taiwan; 8Department of Pathology and Laboratory Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; 9School of Medicine, Chung Shan Medical University, Taichung, Taiwan; 10Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan; 11Department of Dermatology, Yale School of Medicine, Yale University, New Haven, CT, USA; 12Pharmaceutics Laboratory, Graduate Institute of Natural Products, Chang Gung University, Kweishan, Taoyuan, Taiwan; 13Department of Anesthesiology, Chang Gung Memorial Hospital, Linkou, Taiwan&ast;These authors contributed equally to this workCorrespondence: Jia-You Fang, Pharmaceutics Laboratory, Graduate Institute of Natural Products, Chang Gung University, 259 Wen-Hwa 1st Road, Kweishan, Taoyuan, 333, Taiwan, Email fajy@mail.cgu.edu.twPurpose: Injectable deoxycholic acid (DA) has been approved for removing excess submental fat and is off-label for local adipose tissue reduction. Conventional DA injections fail to control fat reduction and generate severe adverse effects in adjacent non-adipose tissues. We designed squarticles as lipid-based nanoparticles for DA delivery to reduce fat accumulation.Methods: The liquid lipid phase of the squarticles was composed of squalene, which was previously reported to sequester the toxicity of overdosed drugs. Rhein, a natural anti-adipogenic compound, was incorporated into the squarticles for combined fat-lowering.Results: The squarticles had an average diameter of 93 nm and high rhein encapsulation (96%). The nanoparticles were easily internalized into mature adipocytes and were located in the lysosomes. DA induces adipocyte death via apoptosis and necrosis; however, nanoencapsulation can decrease cell death. Compared to free DA, squarticles showed superior mitigation of cytotoxicity against non-targeted cells (skin fibroblasts). Oil Red O staining indicated that squarticles loaded with DA or rhein alone inhibited lipid droplets by 42% and 17%, respectively. DA and rhein worked together in squarticles to further suppress fat accumulation by 50%. Dual administration of DA and rhein to the nanocarriers downregulated adipokines. The intraperitoneal administration of squarticles loaded with DA and rhein significantly decreased body weight, total cholesterol, and adipokine release. Histological analysis revealed that squarticles reduced adipocyte hypertrophy in the groin and epididymis by 11% and 53%, respectively. We examined the toxicity of the combination of DA+rhein in healthy rats that received a dose three-fold higher than that used in the pharmacological assessment. The survival rate of the overdosed DA+rhein increased from 50% to 100% after nanoencapsulation. Free compounds induce ascites, liver size reduction, AST/ALT elevation (1.5-fold), and potassium imbalance in rats. Nanoencapsulation significantly reduced these adverse effects.Conclusion: Our findings highlight the potential of squarticles for treating obesity. Keywords: deoxycholic acid, rhein, squarticle, lipid-based nanoparticle, obesity, adverse effect

Donatella Delle Cave,1,&ast; Maria Mangini,2,&ast; Chiara Tramontano,3,&ast; Luca De Stefano,3 Marco Corona,1 Ilaria Rea,3 Anna Chiara De Luca,2 Enza Lonardo1 1National Research Council, Institute of Genetics and Biophysics, Naples, 80131, Italy; 2National Research Council, Institute for Experimental Endocrinology and Oncology “G. Salvatore”, Second Unit, Naples, 80131, Italy; 3National Research Council, Institute of Applied Sciences and Intelligent Systems, Unit of Naples, Naples, 80131, Italy&ast;These authors contributed equally to this workCorrespondence: Ilaria Rea; Anna Chiara De Luca, Email ilaria.rea@na.isasi.cnr.it; annachiara.deluca@cnr.itBackground: Metastasis-initiating cells are key players in progression, resistance, and relapse of colorectal cancer (CRC), by leveraging the regulatory relationship between Transforming Growth Factor-beta (TGF-β) signaling and anti-L1 cell adhesion molecule (L1CAM).Methods: This study introduces a novel strategy for CRC targeted therapy and imaging based on the use of a hybrid nanosystem made of gold nanoparticles-covered porous biosilica further modified with the (L1CAM) antibody.Results: The nanosystem intracellularly delivers galunisertib (LY), a TGF-β inhibitor, aiming to inhibit epithelial-mesenchymal transition (EMT), a process pivotal for metastasis. Anti-L1CAM antibody-functionalized nanoparticles (NPs) target tumor-initiating cells expressing L1CAM, inhibiting cancer growth. The number of antibody molecules conjugated to the single NP is precisely quantified, revealing a high surface coverage that facilitates the tumor targeting. The therapeutic efficacy of the nanosystem is investigated in organoid-like cultures of CRC cells and in vivo mouse models, showing a significant reduction in tumor growth. The spatial distribution of NPs within CRC tumors from mice is investigated using a label-free optical approach based on Raman micro-spectroscopy.Conclusion: This research highlights the multifunctional capabilities of engineered biosilica NPs, which offer new insights in targeted CRC therapy and imaging, improving patient outcomes and paving the way for personalized therapies.Keywords: targeted drug delivery, Raman imaging, antibody quantification, biosilica nanoparticle, in vivo treatment, colorectal cancer

Tianjie Zhang,1 Yan Liu,1 Dongwei Xu,2 Rui Dong,1 Ye Song1 1Department of Ultrasonography, Shanghai University of Medicine and Health Sciences Affiliated Zhoupu Hospital, Shanghai, 201318,People’s Republic of China; 2Department of Critical Care Medicine, Shanghai University of Medicine and Health Sciences Affiliated Zhoupu Hospital, Shanghai, People’s Republic of ChinaCorrespondence: Ye Song, Email songy_18@sumhs.edu.cnBackground: This study aims to evaluate the predictive value of bedside ultrasound evaluation of diaphragmatic dynamics in determining successful extubation outcomes for patients eligible for weaning.Methods: This prospective observational study was conducted on patients who were mechanically ventilated and ready for weaning during the spontaneous breathing trial (SBT). The diaphragm contraction and motion-related parameters of patients such as end inspiratory diaphragm thickness (DT-insp), end respiratory diaphragm thickness (DT-exp), diaphragm thickening fraction (DTF), diaphragmatic thickening fraction rapid shallow breathing index (DTF-RSBI), diaphragmatic excursion (DE), diaphragmatic excursion rapid shallow breathing index (DE-RSBI) were recorded and the association with failure in ventilatory extubation was analyzed. A receiver operating characteristic (ROC) curve was conducted to analyze the prediction of successful weaning.Results: Out of 95 patients, 14 (14.74%) died, and 68 (71.58%) were successfully extubated. There were significant differences between the two groups in all parameters except DT-exp. The results indicated that duration of mechanical ventilation (OR = 0.850, 95% CI: 0.770– 0.938, P = 0.001), DTF (OR = 1.214, 95% CI: 1.108– 1.330, P = 0.000), DTF-RSBI (OR = 0.917, 95% CI: 0.880– 0.954, P = 0.000), DE (OR = 127.02, 95% CI: 15.004– 1075.291, P = 0.000), DE-RSBI (OR = 0.752, 95% CI: 0.657– 0.861, P = 0.000) had predictive value for weaning. DTF and DE had a high sensitivity of 91.18%, 100%, respectively. Whereas, duration of mechanical ventilation, DTF-RSBI, DE-RSBI showed a high specificity of 81.48,85.19%, 81.48%. Considering all the above factors, the sensitivity was 88.24% and the specificity was 88.89%.Conclusion: Bedside ultrasound assessment of diaphragmatic parameters enables the detection of diaphragmatic dysfunction, thus proving valuable in predicting extubation success and facilitating a favorable weaning outcome.Keywords: diaphragmatic dynamics, bedside ultrasound, extubation, intensive care unit

Xiao Wang,1,&ast; Ying Cao,2,&ast; Jing Hu,3 Lian-Cheng Jia,4 Bo Li,3 Baoli Liu,5 Wei-Hai Yao,2 Xiao-Lu Pei,6 Wei Peng,2 Shuang Wang,2 Cun-Zhi Liu,1,7 Jian-Feng Tu,1,7 Zhi-Cheng Qu2 1School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2Emergency Department, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, People’s Republic of China; 3Evidence Based Medicine Center, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, People’s Republic of China; 4Urinary Surgery, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, People’s Republic of China; 5Nephrology Department, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, People’s Republic of China; 6Nursing Department, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, People’s Republic of China; 7International Acupuncture and Moxibustion Innovation Institute, Beijing University of Chinese Medicine, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhi-Cheng Qu, Emergency Department, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, 23 Meishuguanhou Street, Dongcheng District, Beijing, 100010, People’s Republic of China, Email qzhch0824@163.com Jian-Feng Tu, School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, No. 11, Bei San Huan Dong Lu, Chaoyang District, Beijing, 100029, People’s Republic of China, Email tujianfeng1@126.comIntroduction: Analgesia is often delayed for suspected acute renal colic due to urinary calculi (ARCUC) even in emergency department. Acupuncture has a rapid onset and is effective for analgesia, however, evidence about early-acupuncture for suspected ARCUC is limited. This trial aims to evaluate the efficacy of early-intervention acupuncture compared with sham acupuncture on pain relief among emergency department suspected ARCUC patients.Methods and Analysis: A total of 84 eligible patients who are suspected diagnosed with ARCUC will be randomly allocated to the acupuncture group or the sham acupuncture group. Each patient will receive 1 session of acupuncture or sham acupuncture before diagnostic imaging. The primary outcome will be the response rate at 10 min after needle manipulation, defined as the proportion of patients whose Numeric Rating Scale (NRS) score decrease by at least 50% from baseline. Secondary outcomes will include pain intensity assessed by NRS, further analgesia requirement, revisit rate, surgical intervention rate, satisfaction evaluation, and adverse events. The final diagnosis rate determined by radiography will be recorded and reported. All patients who receive randomization will be included in the intention-to-treat analysis.Conclusion: This study’s findings are anticipated to evaluate the analgesic effect of early-intervention acupuncture for acute renal colic in emergency department, which could be useful for moving the timing of analgesia forward and aligning pain management for acute renal colic more with the guidelines.Trial Registration Number: ChiCTR2100049069 (https://www.chictr.org.cn/showproj.html?proj=125338).Keywords: acupuncture, complementary medicine, pain management, emergency medicine, renal colic

Shuai Tang,1– 4 Wenyu Feng,2– 4 Zekun Li,1 Xinjuan Liu,1 Tong Yang,1– 4 Fulan Wei,2– 4 Gang Ding1 1School of Stomatology, Shandong Second Medical University, Weifang, Shandong, 261053, People’s Republic of China; 2Department of Orthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, People’s Republic of China; 3Shandong Key Laboratory of Oral Tissue Regeneration, Shandong University, Jinan, Shandong, 250012, People’s Republic of China; 4Shandong Provincial Clinical Research Center for Oral Diseases, Shandong University, Jinan, Shandong, 250012, People’s Republic of ChinaCorrespondence: Gang Ding, School of Stomatology, Shandong Second Medical University, Baotong West Street No. 7166, Weifang, Shandong, 261053, People’s Republic of China, Email dinggang@sdsmu.edu.cn Fulan Wei, Department of Orthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, Wenhua West Road No. 44-1, Jinan, Shandong, 250012, People’s Republic of China, Email weifl@sdu.edu.cnIntroduction: Inflammatory bowel disease is a complex chronic inflammatory condition characterized by dysbiosis of the gut microbiota and dysregulation of immune system. In recent years, extracellular vesicles (EVs) derived from mesenchymal stem cells have garnered significant attention for their beneficial potentials in immune modulation and tissue repair. This study aims to evaluate the therapeutic effects and underlying mechanisms of EVs derived from lipopolysaccharide (LPS)-pretreated periodontal ligament stem cells (PDLSCs) in mice with colitis.Methods: A mouse model of colitis was established using 3.0% dextran sulfate sodium (DSS). Following the induction of colitis, mice were treated via tail vein injection with either conventional PDLSC-derived EVs (P-EVs) or LPS-pretreated PDLSC-derived EVs (LPS pre-EVs). The EVs were characterized using transmission electron microscopy, nanoparticle tracking analysis, and Western blot analysis. The therapeutic effects and mechanisms were evaluated through a combination of small animal live imaging, disease activity index (DAI) scoring, histopathological staining, qRT-PCR, 16S rRNA gene sequencing, and mass spectrometry analysis.Results: The LPS pre-EVs exhibited typical EVs characteristics in terms of morphology, particle size distribution, and marker protein expression. Compared to P-EVs, LPS pre-EVs significantly ameliorated weight loss, DAI scores, colon length, and perianal symptoms in DSS-induced murine colitis. Additionally, LPS pre-EVs up-regulated the expression of Arginase-1, a typical M2 macrophage marker, and tight junction proteins, including ZO-1, Occludin, and Claudin-1, enhanced gut microbial diversity, and significantly regulated intestinal protein expression and activation of the PI3K/AKT signaling pathway.Conclusion: LPS pre-EVs exhibit significant anti-inflammatory and tissue repair effects in a mouse model of colitis. The underlying mechanisms may involve the regulation of macrophage polarization, maintenance of intestinal barrier function, modulation of the gut microbiota, and activation of the PI3K/AKT signaling pathway. Keywords: inflammatory bowel disease, periodontal ligament stem cells, extracellular vesicles, gut microbiota, PI3K/AKT signaling pathway

Kang-Xin Li,1,&ast; Hui Yuan,1,&ast; Jing Zhang,2,3 Xiao-bin Peng,1 Wei-Fen Zhuang,1 Wen-Tao Huang,1 Hui-Xin Liang,1 Ying Lin,1 Ying-Zhen Huang,1 Shu-Lan Qin1 1Department of Endocrinology, The Fifth Affiliated Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 2State Key Laboratory for the Modernization of Classical and Famous Prescriptions of Chinese Medicine, Jiangxi University of Chinese Medicine, Nanchang, Jiangxi, 330004, People’s Republic of China; 3China Resources Jiangzhong Pharmaceutical Group Co., Ltd., Nanchang, Jiangxi, 330004, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shu-Lan Qin, Email qinshulan@smu.edu.cnIntroduction: Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterised by insulin resistance, hyperglycaemia, and inflammation, with oxidative stress contributing to its progression. Curcumin (CUR), known for its anti-inflammatory, antioxidant, and insulin sensitising effects, has shown potential for the treatment of T2DM but is limited by low solubility and bioavailability. This study investigated long-circulating curcumin-loaded liposomes (CUR-LPs) to improve curcumin stability, solubility, and circulation and assessed their effect on insulin resistance in a murine model of T2DM.Methods: CUR-LPs were prepared using the ethanol injection method and characterized for morphology, particle size, zeta potential, encapsulation efficiency, drug-loading capacity, and in vitro release. Cell viability was tested on murine L929 cells. In a T2DM murine model, after four weeks of CUR-LP treatment, inflammatory markers TNF-α and IL-6 were measured by real-time polymerase chain reaction, and liver tissues were analyzed for glutathione (GSH) and superoxide dismutase (SOD) via colorimetry.Results: CUR-LPs were spherical, with an average diameter of (249 ± 2.3) nm and a zeta potential of (− 33.5 ± 0.8) mV. They exhibited an encapsulation efficiency of (99.2 ± 0.5) %and a drug-loading capacity of (1.63 ± 0.02) %. CUR embedding in liposomes significantly maintained CUR release. In L929 cells, over 80% viability was maintained at 12 uM CUR concentration after 24 h. In HFD/STZ-induced T2DM mice, CUR-LPs improved blood glucose and insulin levels more efficiently than free CUR, and CUR-LPs also reduced hepatic inflammation (TNF-α, IL-6), enhanced hepatic GSH and SOD, and attenuated liver injury.Conclusion: CUR-LPs improved glucose metabolism and insulin resistance in HFD/STZ-induced T2DM mice, which may be associated with a decrease in liver inflammation and oxidative stress.Keyworks: T2DM, curcumin, liposomes, insulin resistance, glucose metabolism, oxidative stress

Hessah Alshammari,1 Sameerah Shaheen,2 Shimaa Mahmoud,2 Amal Al-Rabiah,2 Khaleel Alyahya2 1Department of Cardiac Sciences, King Saud University, Riyadh, Saudi Arabia; 2Department of Anatomy, King Saud University, Riyadh, Saudi ArabiaCorrespondence: Hessah Alshammari, Department of Cardiac Sciences, King Saud, University, Riyadh, Saudi Arabia, Email healshammari@ksu.edu.saIntroduction: The COVID-19 pandemic forced educational institutions worldwide to shift to online learning as a means to continue education during lockdowns and social distancing measures. This study investigates the effectiveness of online learning in comparison to traditional on-campus learning, specifically within the context of medical education.Methods: Two hundred and three first- and second-year medical students at King Saud University participated in this randomized experimental study. The research employed written exams to evaluate learning outcomes, with a focus on the understanding of lecture content. Data analysis was performed using the Statistical Package for Social Studies (SPSS 22).Results: The findings reveal that while online learning attained similar learning outcomes to on-campus learning for content related to the early parts of the lecture, significantly lower outcomes were achieved by the online learners as the lecture progressed. Moreover, a smaller percentage of online students demonstrated a full understanding of the lecture material compared to on-campus students.Conclusion: This study emphasizes the importance of assessing the effectiveness of online learning methods, particularly in medical education, to address students’ needs better and improve the quality of online learning systems.Keywords: online learning, COVID-19 pandemic, medical education, learning outcomes, student assessment, educational effectiveness

Agata Rocka,1 Maria Suchcicka,2 Aleksandra M Jankowska,2 Magdalena M Wo&zacute;niak,1 Monika Lejman3 1Pediatric Radiology, Medical University of Lublin, Medical University of Lublin, Prof. Antoni G&eogon;bali 6, Lublin, 20-093, Poland; 2Student Scientific Society of Independent Laboratory of Genetic Diagnostics, Medical University of Lublin, Prof. Antoni G&eogon;bali 6, Lublin, 20-093, Poland; 3Independent Laboratory of Genetic Diagnostics, Medical University of Lublin, Prof. Antoni G&eogon;bali 6, Lublin, 20-093, PolandCorrespondence: Agata Rocka, Pediatric Radiology, Medical University of Lublin, Medical University of Lublin, Prof. Antoni G&eogon;bali 6, Lublin, 20-093, Poland, Email agatarocka2@gmail.comAbstract: The aim of this study is to analyze available research on targeting signaling pathways for the development of new drugs in patients with T-cell acute lymphoblastic leukemia (T-ALL). This analysis focuses specifically on the role of LCK tyrosine kinase and mTOR signaling pathways in pediatric patients. Outcome: Current literature suggests that these pathways play a significant role in the regulation of T-cell cycles, making them potential therapeutic targets. However, despite promising findings, there remains a need for further research, particularly in pediatric populations, to fully understand the therapeutic implications and to optimize drug development. The conclusion drawn from this analysis highlights the significant influence of LCK and mTOR on T-cell cycle regulation, underscoring the importance of continued investigation in this area.Keywords: T-ALL, pediatric, signaling pathways, targeted therapy

Objective To explore the role and mechanism of RNA demethylase fat mass and obesity-associated protein (FTO) in the ferroptosis in testicular interstitial cells induced by di (2-ethylhexyl) phthalate (DEHP). Methods Forty 3-week-old C57BL/6 male mice were randomly divided into a control group (corn oil) and 3 dosed DEHP treatment groups (5, 250 and 500 mg/kg), and received an intragastric infusion of corresponding agents for 35 d, respectively. After mouse testicular interstitial TM3 cells was treated with 0, 100, 200 and 400 μmol/L mono-2-ethylhexyl phthalate (MEHP) for 24 h, corresponding plasmids were transfected to construct Fto overexpressing TM3 cells. Serum testosterone level was detected by ELISA, expression of testicular proteins was detected with immunohistochemical assay, and contents of Fe2+, malondialdehyde (MDA) and lipid peroxides in the testicle were detected by colorimetry. Methylated RNA immunoprecipitation, RT-PCR, and Western blotting were used to detect the level of N6-methyladenosine (m6A) modification. Results In the mice exposed to 250 and 500 mg/kg DEHP, the serum testosterone level was significantly reduced (P < 0.01), contents of Fe2+, MAD and lipid peroxides in testicular tissue were obviously increased (P < 0.01), and protein levels of RNA demethylase FTO, and ferroptosis related molecules ferritin heavy chain 1 (FTH1) and glutathione peroxidase 4 (GPX4) were significantly down-regulated (P < 0.05), while those of transferrin receptor (TFRC), ferroportin (FPN), cyclooxygenase-2 (COX-2), and acyl-CoA synthetase long-chain family member 4 (ACSL4) were notably up-regulated (P < 0.05). MEHP treatment for 24 h resulted in remarkably decreased cell viability in the TM3 cells, increased production of intracellular reactive oxygen species (ROS), reduced mitochondrial membrane potential (MMP) (P < 0.01), down-regulated mRNA and protein levels of Fto (P < 0.01), and the changes in other ferroptosis related proteins were consistent with the trend in testicular tissue, indicating ferroptosis in testicular interstitial cells. Intervention with ferroptosis inhibitor Fer-1 or overexpression of Fto significantly inhibited MEHP-induced toxicity and ferroptosis in TM3 cells (P < 0.05), and overexpression of Fto reduced the m6A modification of Gpx4 and Fth1 mRNA (P < 0.05). Conclusion Abnormal m6A modification of Gpx4 and Fth1 caused by inhibiting FTO expression may be the mechanism of ferroptosis in testicular interstitial cells induced by DEHP.

Objective To investigate the mechanisms underlying the reduced biomechanical properties and impaired wound healing in the dorsal skin of streptozocin (STZ)-induced type 1 diabetes mellitus (T1DM) mice. Methods Forty male C57BL/6 mice (8 weeks old, weighing 20~25 g) were randomly divided into wild-type (WT, n=20) and T1DM (n=20) groups. After the mice were inflicted with full-thickness skin resection (circular, 1 cm in diameter, in both sides of the back midline), atomic force microscopy (AFM) and scanning electron microscopy (SEM) were employed to assess the Young's modulus, relaxation rate, and collagen arrangement of the skin, and HE, Masson's trichrome, Sirius red, Gordon-Sweet, and Victoria blue staining were all applied to evaluate the epidermis and granulation tissue, total collagen content, ratio of type Ⅲ to type Ⅰ collagen, reticular fiber content, and elastic fiber content. Immunohistochemical assay and Western blotting were conducted to quantify the expression of type Ⅰ and type Ⅲ collagen proteins. Flow cytometry and immunofluorescence staining of paraffin sections were performed to detect the transformation of myofibroblast in wound tissues. Results On day 21 post-wounding, the dorsal skin of T1DM mice exhibited significantly reduced stiffness, strength, and resilience compared to the conditions in the WT group (P < 0.05). During and after healing, T1DM mice showed decreased collagen and elastic fibers, an increased ratio of type Ⅲ to type Ⅰ collagen, and increased reticular fibers, all with statistical significance (P < 0.05). Additionally, there was a significant reduction in myofibroblast transformation during the early stages of wound healing in the T1DM group (P < 0.05). Conclusion T1DM inhibits the transformation of fibroblasts into myofibroblasts, leading to impaired wound healing and reduced biomechanical properties in the dorsal skin of mice.

Objective To explore the protective role of DNA damage induced transcription factor 4 (DDIT4) in oxidative stress injury in dermal papilla cells and its underlying mechanisms. Methods Dermal papilla cells were exposed to UVA and H2O2 to establish cellular model of oxidative stress. CCK-8 assay was used to detect cell viability under different treatment conditions, and the production of intracellular reactive oxygen species (ROS) was detected using 2′, 7′-dichlorofluorescein diacetate (DCFH-DA). Autophagic vesicles were observed with electron microscopy. Western blotting was employed to measure the expression of DDIT4 and autophagy-related molecules, including microtubule-associated protein 1 light chain 3 (LC3), ubiquitin-binding protein (P62), mammalian target of rapamycin (mTOR), and p-mTOR. Results UVA and H2O2 resulted in more production of ROS (P < 0.05) and decreased viability of dermal papilla cells (P < 0.05). DDIT4 expression was increased in dermal papilla cells under oxidative stress (P < 0.05), and the antioxidant N-acetyl-L-cysteine (NAC) could effectively inhibit this effect (P < 0.05). After treatment with UVA or H2O2, cell autophagy was enhanced in dermal papilla cells, characterized by an increase in the number of autophagosomes and an increased LC3Ⅱ/Ⅰ ratio (P < 0.05), a decrease in P62 expression (P < 0.05), and 3-methyladenine (3-MA) blocking autophagy led to further reduced cell viability (P < 0.05) and increased intracellular ROS production (P < 0.05). Conversely, rapamycin (RAPA) increased autophagy level and improved the viability of dermal papilla cells under oxidative conditions (P < 0.05), and reduced the generation of intracellular ROS (P < 0.05). Additionally, down-regulation of DDIT4 weakened autophagy in dermal papilla cells under oxidative stress, reduced LC3Ⅱ/Ⅰ (P < 0.05), increased p-mTOR/mTOR and P62 (P < 0.05), inhibited cell viability (P < 0.05), and enhanced intracellular ROS production (P < 0.05). Conclusion DDIT4 may alleviate oxidative stress injury in dermal papilla cells through autophagy.

Objective To investigate the effects of basic fibro-blast growth factor (FGF-2) and Panax notoginseng saponins (PNS) alone or combined together on the differentiation of bone marrow mesenchymal stem cells (BMSCs) into cardiomyocytes (CMs) and the mechanism of action of PNS and FGF-2 in the differentiation. Methods BMSCs were isolated from 3-week-old SD rats (20~30 g) by whole bone marrow adherence, and then the purity of BMSCs was identified by flow cytometry. After the purity was qualified, PNS and FGF-2 alone or in combination, or combined with LY294002 (phosphatidylinositol 3 kinase inhibitor), were used to induce BMSCs to differentiate. According to the corresponding culture time, the cells were divided into control group, PNS group, FGF-2 group, and PNS+FGF-2 group. The expression levels of Desmin and Cx43 after induction were detected by immunohistochemical assay. Western blotting was used to measure the expression levels of myocardium-specific proteins, related pathway proteins, and apoptosis-related proteins. RT-qPCR was conducted to detect the expression of myocardial transcription factors. Results The expression levels of myocardium-specific proteins and genes were increased in each single induction group (PNS group and FGF-2 group) and combined induction group (PNS+FGF-2 group, P < 0.05), and the highest expression levels were observed in the combined group. PNS and FGF-2 combined with LY294002 decreased the expression levels of myocardium-specific proteins and genes, decreased the phosphorylation of pathway-related protein Akt, decreased the level of Bcl-2, increased the level of Bax, and decreased the ratio of Bcl-2/Bax when compared with the 2 single induction groups (P < 0.05). Conclusion Both PNS and FGF-2 can induce BMSCs to differentiate into CMs after induction, and the combined induction is more effective in the differentiation. The PI3K/Akt signaling pathway is involved in the differentiation process by PNS and FGF-2, and PNS and FGF-2 play a role in reducing apoptosis.

Objective To compare the therapeutic efficacy of robot-assisted laparoscopic radical prostatectomy versus conventional laparoscopic radical prostatectomy, and analyze the factors influencing treatment outcomes. Methods A retrospective cohort study was conducted on 719 patients (total cohort) who underwent radical prostatectomy in our department from June 2002 to October 2023. According to different surgical methods, they were divided into robot-assisted laparoscopic radical prostatectomy group (robotic group, n=409) and conventional laparoscopic radical prostatectomy group (conventional group, n=310). Clinical characteristics, biochemical recurrence rates, and recovery of urinary continence at 1, 3, 6, and 12 months postoperatively, as well as sexual function recovery at 6 and 12 months after surgery, were compared between the 2 groups. Additionally, the factors influencing biochemical recurrence and urinary continence recovery were analyzed across the entire cohort. Results In the cohort, the robot group demonstrated significantly larger proportions of pathological high T stages (≥pT3, P < 0.01), increased positive lymph node rate (P < 0.01), and greater number of dissected lymph nodes (P < 0.01) than the conventional group. There were no statistical differences between the 2 groups in terms of Gleason score, biochemical recurrence rate, or incidence and type of complications. The robot group exhibited significantly higher rates of urinary continence recovery at 1 (P=0.004), 3 (P < 0.01), 6 (P=0.002) and 12 months (P=0.004) postoperatively. But no obvious difference was seen in the score of International Index of Erectile Function-5 (IIEF-5) between the 2 groups at 6 and 12 months. Across the entire cohort, pathological high T stage (≥pT3, P < 0.01), high Gleason score (>7, P=0.036), fewer lymph nodes dissected (≤10, P < 0.01), and positive lymph nodes (P=0.046) were independent risk factors for biochemical recurrence. Additionally, the surgical method, specifically robot-assisted laparoscopic radical prostatectomy, was identified as a significant factor influencing urinary continence recovery at 12 months postoperatively (P=0.005). Conclusion Compared to conventional laparoscopic radical prostatectomy, robot-assisted laparoscopic radical prostatectomy shows certain effect on reducing biochemical recurrence rate and enhancing recovery of urinary continence in prostate cancer patients at 1, 3, 6 and 12 months postoperatively.

Objective To analyze the diversity and composition changes of gut fungal communities between mouse model of total parental nutrition (TPN) and normal control mice. Methods After mouse model of TPN was constructed, fresh feces were collected from TPN mice (n=5) and normal control mice (n=5). Internal transcribed spacer (ITS) DNA sequencing was applied to determine intestinal fungi, and then bioinformatics analysis was conducted to identify the differences in fungal diversity, structure, and functional properties between the 2 groups of mice. Results There were significant differences in Alpha diversity (P < 0.05) and Beta diversity (P < 0.01) of intestinal fungi between the 2 groups. In the TPN model group, the relative abundances of Candida, Penicillium, Aspergillus and Talaromyces were obviously reduced (all P < 0.01). LEfSe analysis indicated that the above 4 strains were notably enriched in the normal control mice. Conclusion TPN mice exhibit characteristic changes in the composition of gut fungal flora compared to normal control mice. Dysfunction of gut fungal community may promote the occurrence of TPN related complications, and regulating the balance of gut fungal community may become a new strategy for preventing TPN related complications.

Objective To construct an optimal prediction model for lymph node metastasis (LNM) in early gastric cancer (EGC) using machine learning techniques and assess its predictive performance. Methods Clinical data of 433 EGC patients undergoing radical surgery in our hospital from January 2015 to December 2022 were collected. They were divided into a training set and a validation set in a 7 ∶3 ratio. LASSO regression was used to screen variables and multivariate logistic regression analysis was employed to identify independent risk factors for LNM in the EGC patients. Ten machine learning models were constructed using categorical boosting (Catboost), light gradient boosting machine (LightGBM), extreme gradient boosting machine (XGboost), random forest (RF), gradient boosting machine (GBM), neural networks (NNET), support vector machine (SVM), K nearest (KNN), Naive Bayes (NB) and Logistic regression. The predictive power of the above models was evaluated and compared in terms of accuracy, precision, recall, F1 score value, sensitivity, specificity, positive predictive rate, negative predictive rate, Kappa value, area value under the receiver operating characteristic curve (AUC), calibration curve, decision curve, and precision-recall curve. Finally, SHAP (SHapley Additive exPlanations) was applied to explain the contribution of each variable in the best model for the prediction outcomes. Results Depth of tumor invasion, lymphovascular invasion and smoking history were independent risk factors for LNM in the EGC patients. Catboost model obtained the best predictive performance, and had 5 performance indicators outperforming the other models in the training set, that is, an AUC value of 0.904 (95%CI 0.868~0.940), a F1-score of 0.633, a Brier score of 0.100, a negative predictive rate of 0.975, and a Kappa value of 0.520. Finally, calculating the SHAP values of Catboost revealed that the depth of tumor invasion and lymphovascular invasion were two key characteristic variables for predicting LNM. Conclusion The depth of tumor invasion of submucosal and lymphovascular invasion and smoking history are independent risk factors for LNM in early gastric cancer. ML can be used to predict LNM risk, the Catboost model has the best predictive performance and can provide guidance for clinical diagnosis and treatment decisions.

Objective To evaluate the correction rate, accuracy of pedicle screw fixation and overall clinical efficacy of intravertebral osteotomy and internal fixation surgery with the assistance of 3D printing guide plates in treatment of severe kyphosis. Methods A single-center nonrandomized clinical pilot study was conducted on 19 patients (8 males and 11 females) with severe kyphosis undergoing intravertebral osteotomy between December 2018 and June 2023. Seven of them (CAD group) had preoperative planning with computer-aided design (CAD) and intraoperative guidance of individualized 3D printing guide plates. And another 12 patients (control group) were corrected with conventional pedicle screw placement. Postoperative evaluation included assessment of posterior Cobb angle, spinal angular correction rate, accuracy of pedicle screw placement and Oswestry Dysfunction Index (ODI) questionnaire. Results The 19 patients were at a mean age of 48.0 years, and followed up for 26.4 (9~54) months. All of them achieved relatively satisfactory corrective results, with those of the CAD group having a correction rate of 96.83% and those of the control group of 86.61%. There were no statistical differences in average intraoperative blood loss (857 vs 1 045 mL) and average operative time (344 vs 402 min), but significant difference was observed in average length of hospital stay (11 vs 18 d, P < 0.05) between the 2 groups. A total of 278 nails were placed in this study, including 70 guide-assisted pedicle screws, 97.1% of which were grade A or B. In the control group, 208 pedicle screws were placed, 93.8% of which were grade A or B. Postoperative CT/X-ray scanning displayed that both groups achieved certain correction for kyphosis. No obvious difference was found in the average spinal angular correction (43.37° vs 36.10°), and significantly higher correction rate was seen in the CAD group than the control group (96.83% vs 86.61%, P < 0.01). The ODI value was notably lower in the CAD group than the control group (P < 0.05). Conclusion CAD-assisted preoperative planning, surgical simulation and individualized 3D printing guide plates can promote surgical correction and accuracy of pedicle screw placement and improves the quality of life of patients with severe kyphotic deformity.

Objective To investigate the effects of a disintegrin and metalloprotease domain 10 (ADAM10) inhibitor on synaptic structure and blood-brain barrier (BBB) permeability in rats with autism-like behavior. Methods A total of 50 male offspring rats with prenatal exposure to valproic acid (VPA) to induce autism-like behavior were randomly divided into VPA group and ADAM10 inhibitor, TAT-Pro-ADAM10 (709-729) group (TAT-Pro group), with 25 rats in each group. And another 25 offspring male rats induced by normal saline during pregnancy served as control group (CON group). The TAT-Pro group was given intraperitoneal injection on postnatal day 20 with 3 nmol/g TAT-Pro-ADAM10 (709-729), and equal volumes of normal saline were given to the CON and VPA groups. The changes of body mass and tail length of offspring rats were measured and recorded during modeling. Western blotting was performed to detect the protein levels of ADAM10, vascular endothelial cadherin (VE-Cad), Occludin, zonula occludens-1 (ZO-1), post-synaptic density protein-95 (PSD95), and synaptophysin (SYN) in the hippocampal tissue of the offspring rats in 24 h after administration. The expression of ZO-1 protein was further verified by immunofluorescence assay. Behavioral tests were conducted from postnatal day 24, including open field, grooming, three-chamber social interaction, and water maze tests. The density of dendritic spines in hippocampal tissue in the offspring rats on postnatal day 28 was detected by Golgi staining. Results Compared with the VPA group, the TAT-Pro group showed no significant changes in body weight and tail length, but significantly improved repetitive stereotyped behaviors, social skills and learning memory ability (P < 0.05), reduced protein levels of ADAM10 and PSD95 in hippocampal tissues (P < 0.05), and elevated levels of VE-cad and Occludin (P < 0.05). The density of dendritic spines was significantly reduced (P < 0.05), and the number of immature dendritic spines also decreased in the TAT-Pro group than the VPA group. Conclusion Inhibition of ADAM10 overexpression during the critical period of synaptic development can alleviate learning and memory dysfunctions in VPA-induced rats with autism-like behavior, and has a certain restorative effect on abnormal synaptic structures and blood-brain barrier permeability.

Objective To construct vitamin E (tocopherol, VE)-based liposomes with both hydrogen peroxide-scavenging function and anticoagulant effect, and explore whether they can be used to treat acute ischemic stroke and then evaluate their in vitro anticoagulant effect. Methods Two molecules of VE were chemically bonded through peroxalate bond to obtain oxalate vitamin E (OVE). The anticoagulant unit LA-Hirudin was obtained by amidation reaction by connecting the anticoagulant drug hirudin to linoleic acid (LA). The structures of the synthesized products were characterized by using H nuclear magnetic resonance (1HNMR) and FT-IR spectra. Hirudin-Oxalic acid divitamin E ester liposome (HOL) was prepared by thin film dispersion and characterized with dynamic light scattering (DLS) and transmission electron microscopy (TEM). Mouse brain-derived endothelial cells (bEnd3) and human umbilical vein endothelial cells (HUVEC) were applied as the object of cell experiments. The levels of H2O2, and cellular inflammatory factors TNF-α, IL-6 and IL-1β were determined by ELISA to evaluate the effect of the liposomes on the severity of cellular inflammation. Cell counting kit-8 (CCK-8) assay and cell proliferation assay (5-Ethynyl-2′-deoxyuridine, Edu) were used to detect the effects of the liposomes on cell count and proliferation. The anticoagulant effect of the prepared liposomes was detected by using whole blood of mice. Results 1HNMR spectrum showed that OVE was successfully synthesized, and the FT-IR spectrum displayed that hirudin and linoleic acid were successfully bonded to obtain LA-Hirudin. The results of DLS and TEM indicated that the prepared liposomes were spheroids, in uniform distribution, with an average particle size of 161 nm. The cell experiments showed that the liposomes significantly inhibited the secretion of H2O2 and inflammatory factors, and exerted obvious antioxidant and anti-inflammatory effects in the model cells (P < 0.05). CCK-8 assay and Edu proliferation assay proved that the liposomes suppressed the decreased cell count and alleviated the inhibited cell proliferation caused by LPS (P < 0.01). Anticoagulation experiment revealed that the liposomes had significant inhibitory effect of CaCl2-induced coagulation reaction (P < 0.01). Conclusion A hydrogen peroxide-scavenging function material, OVE is synthesized, and then anticoagulant drug hirudin and OVE are used to prepare OVE thrombolytic liposomes, HOL. The liposomes have antioxidant and anti-inflammatory effects at the cellular level and also have significant anticoagulant effect.

Objective To investigate the correlation between salivary cystatin D level and salivary gland injury in patients with primary Sjögren syndrome (pSS). Methods A total of 51 pSS patients admitted in the Department of Rheumatology and Immunology of the First Affiliated Hospital of Xi'an Jiaotong University from September 1, 2022 to June 30, 2023, and 51 age- and gender-matched healthy individuals who took physical examination in the hospital during same period were enrolled in the study. The level of salivary cystatin D was detected, and the difference in the level between the 2 groups was compared using an independent-samples t test. Pearson correlation analysis was applied to analyze the correlation between salivary cystatin D and clinical parameters in the patients. Results The pSS patients had significantly lower cystatin D level than the healthy controls (206.55±108.11 vs 374.32±172.24 pg/mL, P < 0.01). The cystatin D level in the pSS patients was positively correlated with both static (r=0.433, P=0.002) and dynamic salivary flow rates (r=0.363, P=0.009). The patients with higher score of salivary gland ultrasonography (SGUS) had obviously lower cystatin D than those with lower SGUS score (parotid gland: 160.75±85.56 vs 290.53±95.17 pg/mL, P < 0.01; submandibular gland: 157.76±87.59 vs 276.25±97.06 pg/mL, P < 0.01). The cystatin D level was also negatively correlated with peripheral blood IL-6 level (r=-0.453, P=0.001) and CD4+ T cell count (r=-0.396, P=0.005) in the pSS patients. Conclusion Salivary cystatin D level can be used as an indicator of salivary gland damage for pSS patients.

Objective To investigate the effects of amylin, also known as islet amyloid polypeptide (IAPP), on learning and memory abilities and the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway in APP/PS1 mice. Methods A total of 20 APP/PS1 mice were randomly divided into Alzheimer's disease (AD) group and IAPP group, with 10 mice in each group. The mice in the latter group were given an intraperitoneal injection of 0.5 μmol/L IAPP, and those of the former group received same dose of PBS. Both interventions were given once per day, for 10 weeks. Morris water maze test was used to measure the learning and memory abilities; HE staining was employed to observe the pathological changes in the hippocampus; Transmission electron microscopy was utilized to observe the ultrastructure of hippocampal neurons; Biochemical assay were conducted to detect the contents of glutathione peroxidase (GSH-Px), malondialdehyde (MDA) and superoxide dismutase (SOD) in hippocampal tissues; ELISA was applied to measure the levels of inflammatory factors such as IL-1β, IL-6, and TNF-α as well as content of Aβ42 in hippocampal tissues; And Western blotting was conducted to detect the expression of PI3K/Akt proteins. Results Compared with the AD group, significantly shorter platform latency (P < 0.01), increased number of traversing the platform and longer time to explore the hidden platform (P < 0.01) were observed in the IAPP group, but no such difference was seen in the swimming speed of the mice. HE staining displayed that the IAPP group had more and well-arranged nerve cells in the hippocampal tissue when compared with the AD group (P < 0.05). Lower Aβ protein expression (P < 0.01), reduced oxidative stress and decreased contents of inflammatory factors (P < 0.01) in hippocampal tissue were observed in the IAPP group than the AD group. The IAPP group showed clearer structure of neuronal mitochondria, reduced vacuolization, and better arranged microtubules and microfilaments, and elevated expression of p-PI3K/PI3K and p-Akt/Akt proteins when compared with the AD group (P < 0.01). Conclusion Amylin can reduce oxidative stress and inflammatory responses, improve learning and memory abilities in AD mice, and promote the activity of PI3K/Akt signaling pathway.

Introduction: A key trigger for many of the complications that are symptoms of cancer types is changes in the gastrointestinal environment, which is a major obstacle in the way of managing side effects. The purpose of this research was to investigate the benefits and challenges of using medicinal cannabis in reducing physical and psychological problems caused by chemotherapy and intestinal inflammation as a review study. Methods: In this review study, a comprehensive search in English was conducted in reputable scientific databases such as PubMed, ProQuest, Google, Google Scholar, Scopus, Web of Science, and CINAHL from 2019 to 2023, using a combination of keywords to find relevant sources and studies. . Based on the established inclusion and exclusion criteria, and the removal of duplicate studies, texts relevant to the objectives of this study were extracted from a total of 81 reviewed articles. Results: The studies reviewed showed that the breakdown of the mucosal barrier (mucositis) was a common and primary side effect of cancer treatments, contributed to a wide range of severe physical and psychological symptoms such as diarrhea, nausea, vomiting, infection, malnutrition, fatigue, depression, and insomnia, for which medical cannabis may be effective in alleviating these symptoms. Conclusion: Considering the potential challenges and benefits of medicinal cannabis in reducing physical and psychological problems caused by chemotherapy and intestinal inflammation, it is necessary to investigate more research in this field and if more clinical evidence is confirmed, medicinal cannabis can be used as a treatment.

Introduction: Nowadays, Cyanobacteria are one of the important candidates in the green biosynthesis of nanoparticles. Considering the detrimental effects of chemically synthesized nanoparticles, the aim of this study was the biosynthesis and antimicrobial activity of nanoparticles by aquatic cyanobacterium. Methods: Silver nanoparticles (AgNPs) were biosynthesized using three different approaches: wet biomass, boiling, and extracellular polysaccharides (EPS). Alginate coating was employed to enhance the nanoparticles' stability. Characterization of the nanoparticles was performed using UV-vis spectroscopy, Fourier transform infrared (FTIR) analysis, scanning electron microscopy (SEM), transmission electron microscopy (TEM), and zeta potential measurements. The antimicrobial properties of the nanoparticles were evaluated against fish pathogenic bacteria and fungi. Statistical analyzes were performed with SPSS version 16 software, and the significant difference between the means was performed with one-way analysis of variance with 95% confidence limits and Tukey's test, and the results were drawn as a graph with Excel software. Results: The UV-vis spectroscopy results confirmed the synthesis of AgNPs in all three methods. FTIR analysis revealed similar spectra for all three methods, indicating comparable purity and production of similar compounds. Electron microscope images showed the sphericity of nanoparticles prepared by boiling method, and the average diameter of uncoated and alginate coated nanoparticles was 38 and 180.04 nm, respectively. Zeta potential analysis indicated a positive surface charge on the nanoparticles. The highest zone of inhibition was observed for AgNPs synthesized by the boiling method and coated with alginate. Similar results were obtained for the antifungal activity, with Saprolegnia exhibiting higher sensitivity to the synthesized nanoparticles compared to the other species studied. Conclusion: The novel strain Dulcicalothrix alborzica demonstrated potential as a potent producer of AgNPs with unique properties and promising applications in microbial biotechnology.

Introduction: Social anxiety is characterized by marked anxiety, cognitive and emotional dysfunction in social situations and can lead to social avoidance behavior. The purpose of this study was to investigate the mediating role of self-criticism in the relationship between the fear of negative evaluation and self-compassion with social anxiety in Yazd medical students. Methods: A correlational research study was conducted using structural equation modeling. The statistical population of the research consisted of all students of medicine, pharmacy and dentistry of Shahid Sadougi University of Medical Sciences in Yazd in the academic year of 2021-2022. The sample size of 250 people was determined; sampling was done by voluntary sampling method. Research instruments included social anxiety scale (Jarabek, 1996), fear of negative evaluation (Leary, 1983), short form of self-compassion (Rees et al., 2011) and self-criticism (Thompson and Zaroff, 2004), which were published online. Finally, the data of 227 students were analyzed by Pearson correlation and structural equation model using SPSS16 and Amos24 software. Results: The results showed that the direct effect of fear of negative evaluation and self-criticism on social anxiety was significant (P

Introduction: Since it is necessary to detect changes in lung function for the follow-up of the patients with respiratory and functional complications caused by COVID-19, in this study, we decided to examine the results of spirometry in children over 5 years old with Covid-19. Methods: In this cross-sectional study, 52 over-five-year-old children, hospitalized due to COVID-19 for at least six past months, were examined. The participants’ demographic information, respiratory symptoms, underlying diseases, severity of COVID-19 according to WHO, severity of lung involvement in CT scan, type of lung involvement, oxygen saturation at admission as well as FEV1, FVC, and FEV1/FVC were collected and analyzed, the results were analyzed using SPSS version 16 software and t-test and Chi-square tests. Results: Of all investigated patients،, 26 were boys (50%) and 38 (73.1%) were 5-12 years old. The minimum age of the children was 5 years and the maximum was 18 years. The mean age of children was 3.41±10 years. The FEV1/FVC ranged from 61% to 79% in five patients (9.6%) and from 80% to 100% in 47 patients (90.4%). The FEV1 was lower than 80% in 28 and higher than 80% in 24 patients. FEV1/FVC had no significant relationship with the participants’ age, gender, clinical manifestations, and disease severity in terms of pulmonary involvement, but it had a significant association with blood oxygen saturation level (P: 0.001). Conclusion: The changes in pulmonary function tests vary in different months following contamination with COVID-19. In the present study, 9% of the patients, who were examined in the sixth month after infection, had abnormal pulmonary function test results. Based on the findings, the pulmonary function test results had no significant relationship with the patients’ age, gender, and clinical symptoms, while it was significantly associated with their blood oxygen saturation intensity.

Introduction: The genus Rhodococcus, first described by Zopf in 1891, comprises 56 species with validly published names. This bacterium belongs to the phylum Actinobacteria, class Actinobacteria, order Mycobacteriales, and family Nocardiaceae. Notable characteristics of this bacterial genus include: Gram-positive, partially acid-fast positive, catalase-positive, non-spore-forming, and non-motile. The use of molecular methods such as 16S rRNA gene sequencing, along with phenotypic methods, has been suggested for the identification of this bacterium. To date, nine species of the genus Rhodococcus have been reported from clinical specimens. Currently, microbroth dilution is the standard method for assessing the antibiotic susceptibility testing of Rhodococcus species. The pattern of antibiotic resistance in Rhodococcus species varies based on geographical region, and it is recommended that antibiotic susceptibility testing be performed for clinical isolates.

Introduction: Postpartum depression, a form of depression, is a relatively common but serious medical condition that occurs following the birth of a baby. This study aimed to determine the relationship between the carbohydrate diet and the occurrence of anxiety and postpartum depression symptoms in women participating in the initial phase of the Maternal and Child Health Cohort Study, Yazd, Iran. Methods: This study was conducted on the data of 1028 pregnant women from the Yazd Maternal and Child Health Cohort Study. The study tools were food frequency questionnaire (FFQ) and postpartum depression questionnaire. Data related to dietary intake at the beginning of the study were collected in the first visit after pregnancy diagnosis and data related to depression in the second month after delivery. Carbohydrate intake score was calculated for each person according to summing up assigned scores to deciles of percentages of energy from macronutrients. Multivariable logistic regression models were used to estimate the odds ratio (ORs) and 95% confidence interval (CI) of postpartum depression and anxiety across quartiles of low carbohydrate diet scores. Results: Based on the multivariable-adjusted model, there was no significant association between low carbohydrate diet score and odds of postpartum depression (P=0.08). However, multivariable-adjusted model significantly indicated an association between low carbohydrate diet score in second tertile and the odds of postpartum anxiety (P=0.02) (OR: 0.36, 95% CI: 0.15-0.86). Conclusion: After adjusting the confounders, women in the second tertile of low carbohydrate diet score might have 64% lower chance of depression versus those in the first quartile. While low or high carbohydrate intake does not affect postpartum anxiety and depression, moderate carbohydrate intake might be anxiety protective.

Introduction: Listeria monocytogenes is known as a potentially pathogen, which can cause perinatal listeriosis, results in abortion, stillbirth or premature birth. Different factors are involved in the pathogenesis, including internalin B, which mediates the internalization of bacteria into a broad range of cell lines. However, it is not clear if expression of this protein is the same between different isolates. Methods: This study was conducted with the aim to compare L. monocytogenes isolated from pregnant women (n= 7) with different pregnancy outcomes (including healthy birth, still birth or blindness) and with abortion (n= 1), regarding expression level of inlB (internalin B encoding gene) and cell invasion. Results: Despite overexpression of inlB in most of the isolates, there was heterogeneity in the expression level between different isolates and no significant association with cell invasion and/ or pregnancy outcome was found (P> 0.05). About half of the studied isolates were able to invade HepG2 cells, while invasion to HeLa cells (cervix carcinoma cell line) was found only in one isolate. However, the difference was not significant. Likewise, no meaningful association was found between cell invasion and pregnancy outcomes. Conclusion: The expression level of inlB and cell invasion, cannot explain the difference of isolates in pathogenicity. Further studies are needed to identify bacterial and possibly host determinants.