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Purpose: The study aimed to investigate the effect of a Western classical symphonic concert on mental wellbeing in war veterans compared to a general audience. Methods: A quasi-experimental pre-post measurement study assessed psychological stress with the Immediate Stress State VAS scale. The Music Experience Questionnaire captured perceived bodily, emotional, and mental changes. Findings: Twenty-one veterans and a general audience of n = 405 participated in the study. Both groups found reduced stress from before to after the concert; in the general audience, it was significant (p < .001). 47% of the veterans experienced a high-stress state before the concert compared to 19% after the concert (versus 15% and 5% in the general audience). The veterans perceived significantly more safety, relaxation, and calm after the concerts and indicated a positive bodily state and presence change. In contrast, the public emphasized the aesthetical impact of the concert. Originality: The unique contribution of this study lies in its collaboration with veterans in the organization of the concerts. This adds significant value to the study, enlightening the audience with new knowledge in an underresearched field: the impact of music experiences on the wellbeing of veterans.

Ting-ting Li,1 Jin-hua Yang,1 Meng-jie Jiang,1 Hao-peng Cui,1 Xiao-mei Yang,2 Xiao-ling Lu,2 Ai-qun Liu1 1Department of Gastroenterology and Respiratory Medicine & Endoscopy Center, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, 530021, People’s Republic of China; 2Guangxi Key Laboratory of Nanobody Research, Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of ChinaCorrespondence: Ai-qun Liu; Xiao-ling Lu, Email Liuaiqun_2004@163.com; luxiaoling@gxmu.edu.cnBackground: Our previously described a nanobody precisely targeting CTLA-4 and demonstrated that it can promote the antitumor response of adoptive T cells. Here we examined whether fusing it to the IgG1 Fc region would induce stronger, longer-lasting T-cell immune responses after exposure to the dendritic-tumor cell fusions.Methods: The fusion of nanobody to Fc region was overexpressed in E. coli. Next, the proliferation, activation and cytotoxicity of the CD8+ T cells stimulated by the fusion protein and dendritic-tumor cell fusions was assessed in vitro, and the antitumor activity was evaluated in nude mice bearing xenografts of each type of solid tumor.Results: Proliferation, activation and cytotoxicity of CD8+ T cells in vitro were significantly greater in the presence of the fusion protein than those in other groups. Consistently, different types of xenografts growth were significantly slower and animal survival significantly longer when the injected CD8+ T cells had been activated in vitro in the presence of the fusion protein.Conclusion: Fusing our anti-CTLA-4 nanobody to the IgG1 Fc region potentiates its ability to induce strong, persistent CD8+ T cell responses against solid tumors in mice. This fusion strategy has the potential to realize clinical transformation and application to clinical treatment.Keywords: nanobody, CTLA-4, therapeutic antibody derivative, cell fusion, adoptive immunotherapy

Teng-Yue Zhao,1,2 Bing-Jie Wang,3 Jiang Liu,1 Chu Liu,1 Ji-Qiang Bu,1 Yu Liu,1 Fang Yan,1 Wen-Li Zhang,1 Zi-Ying Chen,1 Yu-Ming Wu2 1Department of Cardiac Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000, People’s Republic of China; 2Department of Physiology, Hebei Medical University, Shijiazhuang, 050000, People’s Republic of China; 3Department of Anesthesiology, The Third Hospital of Hebei Medical University, Shijiazhuang, 050000, People’s Republic of ChinaCorrespondence: Zi-Ying Chen, Department of Cardiac Surgery, The Second Hospital of Hebei Medical University, No. 215 of Heping West Road, Xinhua District, Shijiazhuang, 050000, People’s Republic of China, Tel +86 15803210520, Email ziyingchenorg@126.com Yu-Ming Wu, Department of Physiology, Hebei Medical University, No. 361 of Zhong Shan East Road, Shijiazhuang, 050017, People’s Republic of China, Tel +8631186261288, Email wuym@hebmu.edu.cnObjective: The employment of the no-touch technique in harvesting the great saphenous vein (GSV) for coronary artery bypass grafting has been associated with a significant improvement in clinical patency rates. Despite these advantages, such grafts may predispose patients to complications in the lower limbs. This study endeavors to evaluate the incidence of complications in the lower extremities by deploying an enhanced protocol for the no-touch harvesting technique.Methods: The historical control group in this study included patients who underwent coronary artery bypass grafting (CABG) with the no-touch technique for GSV harvesting at our institution from August 2018 to April 2020, in compliance with ethical standards. The intervention group consisted of patients who received CABG and were subjected to an optimized no-touch technique for GSV harvesting from May 2020 to June 2022. Technical modifications were applied to reduce lower limb complications, including limited use of electrocautery, minimization of extravascular tissue preservation, relaxation of postoperative elastic compression bandages, and elevation of the lower extremities. These measures aimed to decrease the incidence of postoperative lower limb complications, such as pain, numbness, edema, exudation, and delayed healing. The occurrences of postoperative complications were meticulously documented, compared, and analyzed between the two groups.Results: The adoption of the optimized no-touch technique resulted in a significant decrease in the incidence of postoperative lower extremity incisional complications among patients subjected to off-pump CABG (p < 0.05).Conclusion: The results of this study substantiate that the application of an optimized no-touch technique to harvest the GSV significantly diminishes the incidence of postoperative lower limb complications in patients receiving CABG. These results highlight the importance of adopting and integrating this optimized technique into clinical protocols, emphasizing its critical role in advancing patient care outcomes.Keywords: historical controlled study, lower limb complications, no-touch great saphenous vein, off-pump coronary artery bypass grafting, propensity score matching

Zhitao Hou1– 5 1College of Basic Medical and Sciences, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, 150040, People’s Republic of China; 2Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA; 3Department of Neurology, the Second Hospital Affiliated with Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, 150010, People’s Republic of China; 4Department of Neurology, the First Hospital Affiliated with Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, 150010, People’s Republic of China; 5Institute of Shaanxi Key Laboratory of Ultrasonics, Shaanxi Normal University, Xi’an, 710119, People’s Republic of ChinaCorrespondence: Zhitao Hou, Email 18745020244@139.com.Abstract: Understanding the physiology and pathology of neural circuits is crucial in neuroscience research. A variety of techniques have been utilized in medical research, with several established methods applied in clinical therapy to enhance patient’ neurological functions. Traditional methods include generating electric fields near neural tissue using electrodes, or non-contact modulation using light, chemicals, magnetic fields, and ultrasound. The advent of nanotechnology represents a new advancement in neural modulation techniques, offering high precision and the ability to target specific cell types. Smart nanomaterials enable the conversion of remote signals (such as light, magnetic, or ultrasound) into local stimuli (eg, electric fields or heat) for neurons. Surface treatment technologies of nanomaterials have enhanced biocompatibility, making targeted delivery to specific cell types possible and paving the way for precise neural modulation. This perspective will explore neural modulation techniques supported by nanomedical materials, focusing on photoelectric, photothermal, magnetoelectric, magnetothermal, and acoustoelectric conversion mechanisms, and looking forward to their medical applications.Keywords: neurodegenerative diseases, neural modulation, nanomaterials

Meili Xu,1,2 Hongliu Chen,1,2 Jianjing Chen,3 Rongzong Ye,4 Huan Xiao,1,2 Jingwen Li,4 Chaoqian Li1,2 1Department of Emergency, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 2Guangxi University Key Laboratory of Emergency Medicine, Nanning, Guangxi, People’s Republic of China; 3Department of Medical Ultrasound, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 4Guangxi Medical University, Nanning, Guangxi, People’s Republic of ChinaCorrespondence: Chaoqian Li, Department of Emergency, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning, Guangxi, 530021, People’s Republic of China, Email lichaoqiangood@163.comObjective: This study aimed to explore the factors influencing pulmonary fibrosis in patients with acute diquat poisoning through logistic regression analysis.Methods: A retrospective analysis was conducted on 68 cases of acute diquat poisoning due to suicidal intent admitted to our hospital from February 2020 to March 2023. Patients were divided into a combined group (28 cases with pulmonary fibrosis) and an acute diquat poisoning group (40 cases without). A healthy control group consisted of 40 individuals. General data were compared among the three groups, and laboratory indicators were analyzed. Single and multiple logistic regression analyses were performed to identify risk factors for pulmonary fibrosis.Results: There were no significant differences in gender, age, BMI, poisoning status, or treatment timing among the groups (P > 0.05). The combined group had significantly higher diquat ingestion dose, SIRS score, SOFA score, and APACHE II score compared to the poisoning group (P < 0.05). In the acute poisoning group, these scores were also higher than in the healthy controls (P < 0.05). Laboratory indicators, including Hb, PLT, ALP, DBil, ALB, BUN, Glu, BNP, and pH, showed no significant differences (P > 0.05). However, WBC, ALT, TBil, DBil, Cr, K+, Tn I, and Lac levels were significantly higher in the combined group compared to the acute poisoning group (P < 0.05). Logistic regression analysis identified factors influencing pulmonary fibrosis as diquat ingestion dose, K+, ALT, PaO2, Lac, and HCO3-.Conclusion: The factors influencing pulmonary fibrosis in acute diquat poisoning include diquat ingestion dose, K+, ALT, PaO2, Lac, and HCO3-. These findings enhance understanding of pulmonary fibrosis pathogenesis and may inform clinical management for affected patients.Keywords: acute diquat poisoning, pulmonary fibrosis, K+, ALT, PaO2

XiaoLe Chen, Lili Xiao, Daozhu Wu, Saida Pan Department of Ultrasonic Diagnosis, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Saida Pan, Department of Ultrasonic Diagnosis, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, No. 109, Xue-Yuan West Road, Wenzhou, Zhejiang, People’s Republic of China, Email psdbird511@163.comObjective: This study aimed to investigate factors influencing fetal growth restriction (FGR) occurrence and assess the clinical significance of fetal cardiac parameters in FGR prediction.Methods: Pregnant women with clinically suspected FGR (n=179) and uncomplicated pregnancies (n=53) were included. All had undergone routine obstetric ultrasonography and fetal echocardiography. Umbilical artery flow (UAF) and fetal cardiac parameters (left atrial transverse diameter (LAd), right atrial transverse diameter (RAd), left ventricular transverse diameter (LVd), right ventricular transverse diameter (RVd), foramen ovale width, atrial septum diameter, interventricular septal thickness, left ventricular posterior wall thickness, right ventricular free wall thickness, aortic diameter, pulmonary artery diameter, mitral E velocity, mitral A velocity, tricuspid E velocity, tricuspid A velocity, aortic valve peak flow velocity, and pulmonary valve peak flow velocity) were detected. Follow up was conducted until birth, various fetal clinical parameters were collected: maternal body mass index (BMI), hypertensive disorders complicating pregnancy (HDCP), abnormal umbilical artery flow, placental or umbilical cord anomalies, low amniotic fluid volume, preterm birth, emergency cesarean delivery, maternal height, maternal age, gestational diabetes mellitus (GDM), hypothyroidism, assisted reproductive technology (ART), parity, and neonatal gender. Participants were categorized into confirmed FGR (n=119) and control (n=113) groups based on neonatal birth weight.Results: Significant differences were observed between groups in maternal BMI, HDCP, abnormal UAF, placental or umbilical cord anomalies, low amniotic fluid volume, preterm birth, and emergency cesarean delivery. FGR was positively related to abnormal UAF, placental or umbilical cord anomalies, preterm birth and emergency cesarean delivery and negatively to maternal BMI (r=− 0.276). Compared to the control group, the FGR group exhibited significantly larger RAd, RVd, RA/LA, and RV/LV.Conclusion: Fetal growth-restricted fetuses have enlarged right heart structures. Fetal cardiac examinations are valuable for early FGR diagnosis, potentially improving neonatal body weight and reducing adverse pregnancy outcomes.Keywords: fetal growth restriction, fetal echocardiography, cardiac remodeling

Jiangtao Dong,1– 4,&ast; Wenjuan Zhang,5,&ast; Qianwen Chen,1– 3,6 Lingfeng Zha1– 3 1Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 2Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 3Hubei Provincial Engineering Research Center of Immunological Diagnosis and Therapy for Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 4Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 5Department of Geriatrics, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 6Department of Pediatric Cardiology, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430070, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lingfeng Zha, Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, People’s Republic of China, Tel +86-15827177185, Email zhalf@hust.edu.cnObjective: Restrictive cardiomyopathy (RCM) is a heterogenous cardiomyopathy with various causes, and genetic variants take an important part of the pathogenesis. Whole-exome sequencing (WES) is effective to discover genes that cause genetic diseases. By using WES, we attempted to identify the genetic cause of an RCM family and clarify the clinical diagnosis of the patient and then provide a personalized treatment plan.Materials and Methods: Blood samples were obtained from the proband and his healthy parents. WES and Sanger sequencing were performed to identify the possible pathogenic gene. Co-segregation analysis was conducted for candidate variants, and the allele frequency was checked in databases including Ensembl, Exome Aggregation Consortium (ExAC) and Human Gene Mutation Database (HGMD). Furthermore, the potential effect of variant was predicted using various-free software such as SIFT, Polyphen-2 and Mutation Taster and the conservation was tested using multiple sequence alignments by ClustalX.Results: The proband was a 20 years old boy with severe heart failure symptoms including dyspnea, massive ascites, edema of both lower limbs and chest congestion. Echocardiography showed significant biatrial enlargement, normal left ventricular wall thickness and preserved systolic function of both ventricles. A missense mutation in FLNC (c.6451G>A, p.G2151S), encoded filamin-C was detected in proband by WES and Sanger sequencing, while it was not be found in his parents, we supposed that the FLNC mutation (c.6451G>A, p.G2151S) may be a de-novo mutation. Through multiple functional predictions, we found that it is a deleterious mutation and the mutation in filamin-C could alter its structure and normal function, contributing to RCM.Conclusion: Here, an FLNC missense mutation (c.6451G>A, p.G2151S) known to be pathogenic in hypertrophic cardiomyopathy, was found to be associated with RCM, indicating the genetic overlap among cardiomyopathies. This study provides insights into Phenotype-Genotype Correlations of RCM in patients with FLNC mutations.Keywords: restrictive cardiomyopathy, whole-exome sequencing, filamin-C, FLNC

Yongfeng Fan, Xiulun Liu, Zhongkui Li, Daokang Xiang Department of Cardiac Surgery, Guizhou Provincial People’s Hospital, Guizhou, 550499, People’s Republic of ChinaCorrespondence: Daokang Xiang, Email dao57115973@163.comObjective: To investigate the impact of surgical intervention on hemodynamic parameters and postoperative delirium in Stanford Type A aortic dissection patients.Methods: A retrospective analysis was conducted on 139 patients who underwent surgery for Stanford Type A aortic dissection from February 2022 to February 2024. Hemodynamic parameters, including maximum ascending aortic diameter (MAAD), left ventricular end-diastolic diameter (LVEDd), and ejection fraction (LVEF), were compared pre- and post-surgery. Patients were divided into two groups based on delirium occurrence postoperatively: Group A (n=49, with delirium) and Group B (n=90, without delirium). Differences in surgical factors and intensive care conditions were analyzed, and risk factors for postoperative delirium were identified. Group sizes differ due to retrospective categorization based on observed outcomes rather than controlled sampling.Results: ① Hemodynamic parameters: Postoperative MAAD and LVEDd were significantly reduced, while LVEF increased compared to preoperative levels (P < 0.05). ② Surgical and postoperative conditions: Group A had longer surgery, cardiopulmonary bypass, and deep hypothermic circulatory arrest times than Group B (P < 0.05). ③ Univariate analysis of baseline data: Group A had higher rates of patients aged ≥ 60, hypertension, history of stroke, and elevated preoperative D-dimer levels (P < 0.05). ④ Multivariate logistic analysis: Independent risk factors for postoperative delirium included age ≥ 60, hypertension, history of stroke, surgery time > 6 hours, cardiopulmonary bypass time > 3 hours, and deep hypothermic circulatory arrest time > 40 minutes (OR > 1, P < 0.05).Conclusion: Surgical treatment of Stanford Type A aortic dissection has a good effect, significantly improving long-term cardiac function. However, the incidence of postoperative delirium is relatively high and is closely related to factors such as age, hypertension, history of stroke, surgery time, cardiopulmonary bypass time, and deep hypothermic circulatory arrest time.Keywords: Stanford Type A aortic dissection, surgical intervention, hemodynamic parameters, postoperative delirium, impact, investigation

Juan Gao,1 Jianyi Li,2,3 Yuqing Geng,1 Yan Yan1 1School of Business, Shanghai Dianji University, Shanghai, People’s Republic of China; 2Nursing Department, Guizhou Nursing Vocational College, Guizhou, People’s Republic of China; 3Institute of Innovative Development, Shanghai Dianji University, Shanghai, People’s Republic of ChinaCorrespondence: Jianyi Li, Email lijianyikf@foxmail.comAbstract: This study offers new insights into college students’ health education (CSHE) regarding its research status, hot spots, and trends by conducting a comprehensive bibliometric analysis of this field in the past decade (2014 to 2024). Specifically, we analyzed publication trends and used the bibliometric method with CiteSpace software to explore collaborative networks, detailed co-citation status, and co-occurrence dynamics based on 1358 Web of Science Core Collection articles. Our results indicate increased relevant publications and the collaboration networks show complex institutional and regional partnerships. At the same time, co-citation and co-occurrence analyses highlight interdisciplinary research themes that encompass public health. The study particularly underscores the emerging importance of mental health, global health, and innovative educational approaches. These findings reveal trends in CSHE research and provide crucial insights for future studies, stressing the need for interdisciplinary collaboration and creative strategies to tackle student health challenges. Moreover, in practice, this study contributes to promoting and practicing targeted health intervention policies and countermeasures aimed at enhancing student well-being, such as establishing dedicated health education courses, providing specialized training for teachers, conducting regular health assessments, and providing funding for CSHE.Keywords: college student, health education, global health, CiteSpace, systematic review

Yang Zhang,1 Minjie Zhang,2 Mengying Li,2 Maomao Miao,2 Dan Shou,2 Peijian Tong1 1Institute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, 310053, People’s Republic of China; 2School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, People’s Republic of ChinaCorrespondence: Dan Shou; Peijian Tong, Email shoudanok@163.com; peijiantong@zcmu.edu.cnBackground: Infected bone defects pose a challenging clinical issue due to an imbalance of osteoclasts (OC) and osteoblasts (OB). Exosomes are crucial for intercellular signaling of OC and OB in bone repair. Icariin, has been shown to regulate the balance between OC and OB. However, the specific mechanisms by which icariin influences exosomes derived from osteoclasts, and subsequently impacts osteoblast activity, remain unclear. This study aims to investigate the effects of icariin-treated osteoclast-derived exosomes (ICA-OC-Exo) on osteoblast function and bone repair in cases of infected bone defects.Methods: We investigated the exosome profile and localization of multivesicular bodies (MVB) and quantification of intraluminal vesicles (ILVs) in osteoclasts by using transmission electron microscopy. Additionally, the expressions of Rab27A and MITF, which are associated with exosome release, were determined through immunofluorescence staining and Western blot. The profiling of exosomal miRNA expression was conducted via miRNA-sequencing. The effects of ICA-OC-Exo on osteoblast differentiation were determined using RT-qPCR, Western blot, alkaline phosphatase staining. Additionally, ICA-OC-Exo was administered into the localized bone defect of the infected bone rat models, and bone formation was assessed using Micro-CT.Results: Icariin increased the presence of MVBs in the cytoplasm through modulation of the MITF/Rab27A signaling pathway, resulting in higher number of ICA-OC-Exo compared to OC-Exo. Additionally, miR-331-3p expression in ICA-OC-Exo was found to be elevated compared to OC-Exo. ICA-OC-Exo was observed to stimulate osteoblast function by targeting FGF23, reducing DKK1, and subsequently upregulating ALP. In the in vivo study, ICA-OC-Exo exhibited the capacity to enhance bone healing at the site of a local bone defect following anti-infection treatment.Conclusion: Icariin enhanced the quantification of OC-Exo and the expression of miRNA-331-3p in OC-Exo, leading to the regulation of osteoblast function via activation of the miRNA-331-3p/FGF23/DKK1 pathway. ICA-OC-Exo demonstrated potential clinical applicability in bone repair of infected bone defects. Keywords: infected bone defects, icariin, osteoclast, exosomes, osteoblast

Rong Huang,1,&ast; Rui Zheng,2,&ast; Shui Fu,1 Zuo Jie Li3 1Clinical Laboratory Department, First People’s Hospital of Linping District, Hangzhou, Zhejiang Province, People’s Republic of China; 2Department of Central Laboratory, Taizhou Hospital of Zhejiang Province, Taizhou, People’s Republic of China; 3Clinical Laboratory Department, The People’s Hospital of Cangnan Zhejiang, Wenzhou, Zhejiang Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zuo Jie Li, Clinical Laboratory Department, The People’s Hospital of Cangnan Zhejiang, No. 2288 Yucang Road, Cangnan County, Wenzhou, Zhejiang Province, 325800, People’s Republic of China, Tel +86 577-64810162, Email 15088908102@163.comObjective: Pertussis is a highly contagious respiratory disease, and early diagnosis and timely treatment are crucial for reducing complications and transmission. In this study, we analyzed the prevalence of pertussis and assessed the value of the WBC and lymphocyte percentage in its screening.Methods: A retrospective analysis was conducted on global pertussis data from the past decade. Patients who recently underwent pertussis nucleic acid detection and complete blood count (CBC) in our hospital were selected. Based on the results, 538 patients were classified into the pertussis group, and 595 into the control group. White blood count (WBC) and lymphocyte percentages were compared, diagnostic efficacy was calculated, and evaluate their application value in the diagnosis of pertussis.Results: In the past decade, the global incidence of pertussis first decreased, then increased. In China and Zhejiang province, it fluctuated but showed an upward trend recently. In Zhejiang Province, pertussis was more prevalent in summer and winter and rose last year. Between 2018 and 2020, most pertussis cases in China were infants under 1 year old. Last year, only 1.12% of patients in our hospital were infants, with more patients over 5 years old. WBC, lymphocyte percentage, and platelet count (PLT) was higher in the pertussis group (P < 0.05). Logistic regression showed that WBC, lymphocyte percentage, and PLT were correlated with pertussis infection. Sequential analysis showed that the WBC, lymphocyte percentage, and Youden’s index for both combined were 0.124, 0.082, and 0.044, respectively.Conclusion: The global incidence of pertussis is rising, with significant increases among adolescents and adults. Improved prevention and control strategies are needed. WBC and lymphocyte percentage serve as auxiliary diagnostic indicators, but their efficacy is limited.Keywords: pertussis, epidemiology, WBC, lymphocyte percentage, diagnostic competence

Malwina Sosnowska,1 Mateusz Wierzbicki,1 Barbara Nasi&lstrok;owska,2 Totka Nikolaeva Bakalova,3 Klara Piotrowska,4 Barbara Strojny-Cie&sacute;lak,1 Ewa Sawosz,1 Marta Kutwin1 1Department of Nanobiotechnology, Institute of Biology, Warsaw University of Life Sciences, Warsaw, Poland; 2Biomedical Engineering Center, Institute of Optoelectronics, Military University of Technology, Warsaw, Poland; 3Department of Material Science, Faculty of Mechanical Engineering, Technical University of Liberec, Liberec, Czech Republic; 4Department of Animal Nutrition, Institute of Animal Sciences, Warsaw University of Life Sciences, Warsaw, PolandCorrespondence: Malwina Sosnowska, Department of Nanobiotechnology, Institute of Biology, Warsaw University of Life Sciences, st. Ciszewskiego 8, Warsaw, 02-786, Poland, Tel +48 22 593 66 71, Email malwina_sosnowska@sggw.edu.plIntroduction and Objective: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters the nasal cavity, penetrates the nasal epithelial cells through the interaction of its spike protein with the host cell receptor angiotensin-converting enzyme 2 (ACE2) and then triggers a cytokine storm. We aimed to assess the biocompatibility of fullerenol nanoparticles C60(OH)40 and ectoine, and to document their effect on the protection of primary human nasal epithelial cells (HNEpCs) against the effects of interaction with the fragment of virus - spike protein. This preliminary research is the first step towards the construction of a intranasal medical device with a protective, mechanical function against SARS-CoV-2 similar to that of personal protective equipment (eg masks).Methods: We used HNEpCs and the full-length spike protein from SARS-CoV-2 to mimic the first stage of virus infection. We assessed cell viability with the XTT assay and a spectrophotometer. May–Grünwald Giemsa and periodic acid–Schiff staining served to evaluate HNEpC morphology. We assessed reactive oxygen species (ROS) production by using 2′,7′-dichlorofluorescin diacetate and commercial kit. Finally, we employed reverse transcription polymerase chain reaction, Western blotting and confocal microscopy to determine the expression of angiotensin-converting enzyme 2 (ACE2) and inflammatory cytokines.Results: There was normal morphology and unchanged viability of HNEpCs after incubation with 10 mg/L C60(OH)40, 0.2% ectoine or their composite for 24 h. The spike protein exerted cytotoxicity via ROS production. Preincubation with the composite protected HNEpCs against the interaction between the spike protein and the host membrane and prevented the production of key cytokines characteristic of severe coronavirus disease 2019, including interleukin 6 and 8, monocyte chemotactic protein 1 and 2, tissue inhibitor of metalloproteinases 2 and macrophage colony-stimulating factor.Conclusion: In the future, the combination of fullerenol and ectoine may be used to prevent viral infections as an intranasal medical device for people with reduced immunity and damaged mucous membrane. Keywords: ACE2, cytokine storm, ectoine, nasal epithelium, polyhydroxylated fullerene, spike

Shuang Wu,1,2,&ast; Xing-chen Zhou,1,2,&ast; Tao Li,1,2,&ast; Jia-yu Sun,1,2 Long-hao Chen,1,2 Zi-cheng Wei,1,2 Kai-zheng Wang,1,2 Shuang-wei Hong,1,2 Hui-nan Xu,1,2 Zhi-zhen Lv,1,2 Li-jiang Lv1,2 1The Third Affiliated Hospital of Zhejiang, Chinese Medical University (Zhongshan Hospital of Zhejiang Province), Hangzhou, Zhejiang, People’s Republic of China; 2The Third School of Clinical Medicine (School of Rehabilitation Medicine), Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhi-zhen Lv; Li-jiang Lv, The Third School of Clinical Medicine (School of Rehabilitation Medicine), Zhejiang Chinese Medical University, No. 548, Binwen Road, Hangzhou, 310053, People’s Republic of China, Tel +86-13750821128; +86-13958107858, Email lvzhizhen1992@163.com; lvlijiang0288@163.comBackground: Previous metabolomics studies have indicated a close association between blood metabolites and pain. However, the causal relationship between blood metabolites and spinal pain (SP) remains unclear. This study employs a bidirectional two-sample Mendelian randomization (MR) analysis to evaluate the causal relationship between 452 blood metabolites and SP.Methods: We used bidirectional two-sample MR analysis to assess the causal relationship between blood metabolites and SP, including neck pain (NP), thoracic spine pain (TSP), low back pain (LBP), and back pain (BP). Genome-wide association studies (GWAS) data for 452 metabolites (7,824 participants) were used as exposure variables. Summary data for NP were obtained from the UK Biobank, for TSP from the FinnGen Biobank, and for LBP from both the UK Biobank and the FinnGen Biobank. Summary data for BP were obtained from the UK Biobank. Inverse-variance weighting (IVW) was used to estimate the causal relationships between metabolites and SP, complemented by various sensitivity analyses to account for pleiotropy and heterogeneity, ensuring robust results.Results: The IVW analysis identified 155 metabolites associated with SP risk and 142 metabolites influenced by SP. No significant heterogeneity or horizontal pleiotropy was observed through other analytical methods.Conclusion: This study demonstrates potential causal effects between blood metabolites and SP, providing new insights into the pathogenesis of SP. These findings lay a theoretical foundation for preventing and treating SP through targeted interventions on specific blood metabolites, potentially elucidating underlying biological mechanisms.Keywords: spinal pain, neck pain, thoracic spine pain, low back pain, back pain, blood metabolites, Mendelian randomization, causality

Gitishree Das,1 Han-Seung Shin,2 Kyung-Jik Lim,2 Jayanta Kumar Patra1 1Research Institute of Integrative Life Sciences, Dongguk University-Seoul, Goyangsi, Republic of Korea; 2Department of Food Science & Biotechnology, Dongguk University-Seoul, Goyangsi, Republic of KoreaCorrespondence: Jayanta Kumar Patra, Research Institute of Integrative Life Sciences, Dongguk University-Seoul, Goyangsi, 10326, Republic of Korea, Email jkpatra@dongguk.eduBackground: Bio-based synthesis of metallic nanoparticles has garnered much attention in recent times owing to their non-toxic, environmentally friendly, and cost-effective nature.Methods: In this study, gold nanoparticles (S4-GoNPs) were synthesized by a simple and environmentally friendly technique using an aqueous extract of jamun leaves (JLE) as an effective capping, stabilizer, and reducing agent. JLE was screened for the presence of phytochemicals followed by synthesis, characterization, and evaluation of their antibacterial, antidiabetic, antioxidant, and photocatalytic degradation potentials using standard established procedures.Results: The phytochemical profile of JLE was found to be rich in flavonoids, tannins, terpenoid phenols, anthraquinones, and cardiac glycosides. Its GC-MS analysis revealed the presence of compounds majorly of them as the (1R)-2,6,6-Trimethylbicyclo[3.1.1]hept-2-ene (5.141%), 2(10)-pinene (4.119%), α-cyclopene (5.274%) α,α-muurolene (7.525%), naphthalene, 1,2,3,4,4a,5,6,8a-octahydro-7-methyl-4-methylene-1-(1-methylethyl)-(1.alpha.,4a.beta.,8a.alpha) (8.470%), delta-cadinene (23.246), α-guajene (3.451%), and gamma-muurolene (4.379%). The visual morphology and UV–Vis spectral surface plasmon resonance at 538 nm confirmed the successful synthesis of S4-GoNPs. The average particle size was determined as 120.5 nm with Pdi = 0.152, and − 27.6 mV zeta potential. Using the Scherrer equation, the average crystallite size was calculated as 35.69 nm. S4-GoNPs displayed significant antidiabetic properties, with 40.67% of α-amylase and 91.33% of α-glucosidase inhibition activity. It also exhibited promising antioxidant potential in terms of the DPPH (91.56%) ABTS (76.59%) scavenging. It displayed 31.04% tyrosinase inhibition at 0.1 mg/mL. Moreover, it also demonstrated encouraging antibacterial effects with zones of inhibition ranging from 11.02 – 14.12 mm as compared to 10.55– 16.24 mm by the reference streptomycin (at 0.01 mg/disc). In addition, S4-GoNPs also showed potential for the photocatalytic degradation of the industrial dye, methylene blue.Conclusion: In conclusion, these results suggest the promising applicability of green-synthesized S4-GoNPs in various sectors, including the biomedical, cosmetic, food, and environmental waste management industries.Keywords: gold nanoparticles, antidiabetic, antioxidant, antibacterial, tyrosinase inhibition

Andie MacNeil,1,2 Aneisha Taunque,2 Sarah N Leo,1 Grace Li,3 Margaret de Groh,4 Ying Jiang,4 Esme Fuller-Thomson1,2 1Factor-Inwentash Faculty of Social Work, University of Toronto, Toronto, Ontario, Canada; 2Institute for Life Course and Aging, University of Toronto, Toronto, Ontario, Canada; 3Department of Sociology, University of Victoria, Victoria, British Columbia, Canada; 4Applied Research Division, Center for Surveillance and Applied Research, Public Health Agency of Canada, Ottawa, Ontario, CanadaCorrespondence: Esme Fuller-Thomson, Institute for Life Course & Aging, Factor-Inwentash Faculty of Social Work Cross-Appointed to Faculties of Medicine & Nursing, University of Toronto, 246 Bloor St. West, Toronto, ON, M5S 1V4, Canada, Tel +1 (416) 978-3269, Fax +1 (416) 978-7072, Email esme.fuller.Thomson@utoronto.caBackground: Individuals with migraine are recognized to have a heightened risk of depression compared to the general population. The COVID-19 pandemic and associated public health restrictions exacerbated several known risk factors for depression, but limited longitudinal research has examined the impact of the pandemic on the mental health of people with migraine.Aim: To examine the cumulative incidence of depression and recurrent depression among older adults with migraine, and to identify factors associated with depression among older adults with migraine during the pandemic.Methods: Data came from four waves of the Canadian Longitudinal Study on Aging’s comprehensive cohort (n=2181 with migraine). The outcome of interest was a positive screen for depression based on the CES-D-10 during the autumn of 2020. Bivariate and multivariate logistic regression analyses were conducted.Results: Older adults with migraine, both with and without a history of depression, experienced increases in depression when compared to pre-pandemic levels, and when compared to older adults without migraine. The risk of incident and recurrent depression was higher among those who felt lonely and those who experienced an increase in family conflict during the pandemic. The risk of incident depression only was higher among those who experienced difficulty accessing healthcare and those who experienced other family challenges, such as increased caregiving responsibilities. The risk of recurrent depression only was higher among those who felt left out socially, those with functional limitations, and those whose income did not satisfy their basic needs.Conclusion: Targeted interventions are needed to support the mental health of older adults with migraine.Keywords: migraine, depression, COVID-19, older adults, CLSA

Hawraa Ali-Jerman,1 Zainab Al-Quraishi,1 Ashish Muglikar,1 Yvonne Perrie,1 Rothwelle J Tate,1 Margaret Mullin,2 Gayle McNeill,1 Graeme Mackenzie,1 Christine Dufès1 1Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, G4 0RE, UK; 2Cell Analysis Facility, Medical and Veterinary & Life Sciences Shared Research Facilities, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, G12 8QQ, UKCorrespondence: Christine Dufès, Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow, G4 0RE, UK, Tel +44 1415483796, Fax +44 1415522562, Email C.Dufes@strath.ac.ukBackground: Gene therapy is a promising therapeutic approach for treating various disorders by introducing modified nucleic acids to correct cellular dysfunctions or introduce new functions. Despite significant advancements in the field, the effective delivery of nucleic acids remains a challenge, due to biological barriers and the immune system’s ability to target and destroy these molecules. Due to their branched structure and ability to condense negatively charged nucleic acids, cationic dendrimers have shown potential in overcoming these challenges. Despite this, standardized scalable production methods are still lacking. This study investigates the use of microfluidics to formulate generation 3-diaminobutyric polypropylenimine (DAB) dendriplexes and compares their characteristics and in vitro gene delivery efficacy to those prepared using conventional manual mixing.Methods: DAB dendriplexes were produced by both microfluidic and manual approaches and characterized. Their cellular uptake and gene expression were evaluated on C6 glioma cancer cells in vitro.Results: Dendriplexes formed using microfluidics at the optimal flow rate and ratio demonstrated enhanced DNA condensation over time, achieving up to 97% condensation at 24 hours. Both preparation methods produced positively charged dendriplexes, indicating stable formulations. However, dendriplexes prepared through hand mixing resulted in smaller particle sizes, significantly higher cellular uptake and gene expression efficacy compared to those prepared by microfluidics. Nonetheless, microfluidic preparation offers the advantage of standardized and scalable production, which is essential for future applications.Conclusion: This study highlights the potential of microfluidic technology to improve precision and scalability in gene delivery, paving the way for future advancements in gene therapy. Our findings suggest that, with further optimization, microfluidic systems could provide superior control over dendriplex formation, expanding their potential use in gene therapy applications. Keywords: polypropylenimine dendrimer, dendriplex, glioma, microfluidics, cellular uptake, transfection

Yang Zheng,1,2,&ast; Limei Cui,1,2,&ast; Haoran Lu,1,2,&ast; Zhen Liu,1,2 Zhaoxue Zhai,2,3 Huikang Wang,1,2 Liting Shao,1,2 Zhaoyang Lu,2,3 Xicheng Song,1,2,4 Yu Zhang1,2,4 1Department of Otorhinolaryngology, Head and Neck Surgery, Yantai Yuhuangding Hospital, Qingdao University, Yantai, People’s Republic of China; 2Shandong Provincial Clinical Research Center for Otorhinolaryngologic Diseases, Yantai, People’s Republic of China; 3Second Clinical Medicine College, Binzhou Medical University, Yantai, People’s Republic of China; 4Shandong Provincial Key Laboratory of Neuroimmune Interaction and Regulation, Yantai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yu Zhang, Department of Otolaryngology, Head and Neck Surgery. Yantai Yuhuangding Hospital, Qingdao University, No. 20, East Road, Zhifu District, Yantai, 264000, People’s Republic of China, Tel +86535 6691999, Fax +86535 6240341, Email superzhang013@163.com Xicheng Song, Department of Otolaryngology, Head and Neck Surgery. Yantai Yuhuangding Hospital, Qingdao University, Yantai, 264000, People’s Republic of China, Tel +86535 6691999, Fax +86535 6240341, Email drxchsong@163.comAbstract: The intranasal (IN) route of drug delivery can effectively penetrate the blood-brain barrier and deliver drugs directly to the brain for the treatment of central nervous system (CNS) disorders via intra-neuronal or extra-neuronal pathways. This approach has several advantages, including avoidance of first-pass metabolism, high bioavailability, ease of administration, and improved patient compliance. In recent years, an increasing number of studies have been conducted using drugs encapsulated in solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs), and delivering them to the brain via the IN pathway. SLNs are the first-generation solid lipid nanocarriers, known for their excellent biocompatibility, high drug-loading capacity, and remarkable stability. NLCs, regarded as the second-generation SLNs, not only retain the advantages of SLNs but also exhibit enhanced stability, effectively preventing drug leakage during storage. In this review, we examined in vivo studies conducted between 2019 and 2024 that used SLNs and NLCs to address CNS disorders via the IN route. By using statistical methods to evaluate pharmacokinetic parameters, we found that IN delivery of SLNs and NLCs markedly enhanced drug accumulation and targeting within the brain. Additionally, pharmacodynamic evaluations indicated that this delivery method substantially improved the therapeutic effectiveness of the drugs in alleviating symptoms in rat models of CNS diseases. In addition, methods for enhancing the efficacy of nose-to-brain delivery of SLNs and NLCs are discussed, as well as advances in clinical trials regarding SLNs and NLCs.Plain Language Summary: Traditional drug administration routes for the treatment of central nervous system diseases have many limitations due to the existence of the blood-brain barrier (BBB). The intranasal drug administration route crosses the BBB through intra-neuronal pathways as well as extra-neuronal pathways and delivers drugs directly to the brain. Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) are a type of nanoparticles whose surface is covered by amphoteric surfactants and whose interior is filled with a lipid core. They have the advantages of good biocompatibility, strong drug loading capacity, and strong stability, and can be obtained through a variety of reliable preparation methods. Encapsulating therapeutic drugs into SLNs and NLCs for intranasal delivery can significantly increase drug delivery efficiency and enhance efficacy. In addition, there are various ways to further enhance drug delivery of SLNs and NLCs, such as using gel systems such as chitosan to encapsulate the nanoparticles, piggybacking cell-penetrating peptides onto the surface of the nanoparticles, and modifying the nanoparticles, surface charge of particles, etc. Keywords: solid lipid nanoparticle, nanostructured lipid carrier, intranasal delivery, central nervous system diseases

Yeeun Kim,1,2,&ast; Min-A Je,1,2,&ast; Myeongguk Jeong,1,2 Hyeokjin Kwon,1,2 Aelee Jang,3 Jungho Kim,1,2 Go-Eun Choi1,2 1Department of Clinical Laboratory Science, College of Health Sciences, Catholic University of Pusan, Busan, 46252, Republic of Korea; 2Next-Generation Industrial Field-Based Specialist Program for Molecular Diagnostics, Brain Busan 21 Plus Project, Graduate School, Catholic University of Pusan, Busan, 46252, Republic of Korea; 3Department of Nursing, University of Ulsan, Ulsan, 44610, Republic of Korea&ast;These authors contributed equally to this workCorrespondence: Go-Eun Choi; Jungho Kim, Department of Clinical Laboratory Science, College of Health Sciences, Catholic University of Pusan, Busan, 46252, Republic of Korea, Tel +82-51-510-0563 ; +82-51-510-0660, Fax +82-51-510-0568, Email gechoi@cup.ac.kr; jutosa70@cup.ac.krBackground: Paclitaxel (PTX) can induce chemotherapy-induced peripheral neuropathy (CIPN) as a side effect. The aim of this study was to understand the neurochemical changes induced by NGF/TrkA signaling in PTX-induced neuropathic pain.Methods: The PTX-induced CIPN mouse model was evaluated using nerve conduction velocity (NCV) and behavioral tests. Protein expression in mouse DRG was observed by Western blotting and immunohistochemistry. Nerve growth factor (NGF), IL-6, and IL-1β mRNA levels were determined using qRT-PCR by isolating total RNA from whole blood.Results: PTX showed low amplitude and high latency values in NCV in mice, and induced cold allodynia and thermal hyperalgesia in behavioral assessment. Activating transcription factor 3 (ATF3) and MAPK pathway related proteins (ERK1/2), tropomyosin receptor kinase A (TrkA), calcitonin gene related peptide (CGRP) and transient receptor potential vanilloid 1 (TRPV1) were upregulated 7th and 14th days after 2 mg/kg and 10 mg/kg of PTX administration. Protein kinase C (PKC) was upregulated 7th days after 10 mg/kg PTX treatment and 14th days after 2 mg/kg and 10 mg/kg PTX administration. NGF, IL-6, and IL-1β fold change values also showed a time- and dose-dependent increase.Conclusion: Taken together, our findings may improve our understanding of the nociceptive symptoms associated with PTX-induced neuropathic pain and lead to the development of new treatments for peripheral neuropathy.Keywords: Chemotherapy-induced peripheral neuropathy, paclitaxel, nerve growth factor, tropomyosin receptor kinase A, transient receptor potential vanilloid 1

Fengyan Song,1,2 Yuting Yang,1,2 Juan Xue1,3 1Nursing Department, The Third Xiangya Hospital of Central South University, Hunan, People’s Republic of China; 2Xiangya School of Nursing, Central South University, Hunan, People’s Republic of China; 3Department of Outpatient, The Third Xiangya Hospital of Central South University, Hunan, People’s Republic of ChinaCorrespondence: Juan Xue, Nursing Department, The Third Xiangya Hospital of Central South University, Department of Outpatient, The Third Xiangya Hospital of Central South University, Hunan, 410013, People’s Republic of China, Email juan_xue@outlook.comObjective: This study aimed to examine the global scientific output of research on patient delay and explore the hotspots and frontiers from 2000 to 2023 through bibliometric analysis.Methods: Publications regarding patient delay published from 2000 to 2023 were extracted from the Web of Science Core Collection (WOSCC). Subsequently, CiteSpace, VOSviewer, and Bibliometrix Online Analysis Platform were used to analyze publications, countries, institutions, authors, journals, and keywords.Results: A total of 721 papers were included in the study. The publication output increased from 20 papers in 2000 to 64 papers in 2023, a remarkable 220.00% growth. The USA (138 papers) and University of California San Francisco (21 papers) were identified as the most productive country and institution, respectively. Moser (10 papers), and Dracup (10 papers) are the most productive authors. “BMC Public Health” (24 publications) is the most productive journal. “Patient Delay” was the most cited keyword, with high-frequency keywords such as “Prehospital Delay”, “Symptoms”, “Time”, “Care”, “Diagnosis”, “Acute Myocardial-infarction”, and “Mortality” signaling hot topics in Patient Delay.Conclusion: There are increasingly many papers on patient delay. However, there has been limited development of cooperation between countries and institutions. In the future, collaboration between countries and institutions should be strengthened. In addition, 3 hotspots and 3 frontiers are summarized in this study to provide researchers with future research directions.Keywords: patient delay, bibliometrics, VOSviewer, CiteSpace, hotspots, frontiers, web of science

Xiaolong Li,1 Xinyi Hou,2 Siqin Zhang,1 Jianming Xiong,1 Yuanyuan Li,2,3 Wenjun Miao1,4 1School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing, 211816, People’s Republic of China; 2School of Pharmacy, Hainan Medical University, Haikou, Hainan, 571199, People’s Republic of China; 3NHC Key Laboratory of Tropical Disease Control, Hainan Medical University, Haikou, Hainan, 571199, People’s Republic of China; 4State Key Laboratory of Materials-Oriented Chemical Engineering, Nanjing Tech University, Nanjing, 211816, People’s Republic of ChinaCorrespondence: Yuanyuan Li, School of Pharmacy, Hainan Medical University, Haikou, Hainan, 571199, People’s Republic of China, Tel/Fax +86-0898-66968120, Email liyuanyuan@hainmc.edu.cn Wenjun Miao, School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing, 211816, People’s Republic of China, Tel/ Fax +86-25-58139942, Email miaowj@njtech.edu.cnPurpose: Compared to conventional photodynamic therapy (PDT), oxygen-affording PDT represents a promising strategy for treating multidrug-resistant (MDR) gram-negative bacterial infections due to its enhanced sensitization ability towards bacteria and amplified therapeutic efficacy. Over the last decade, various nanoplatforms for the co-delivery of oxygen and photosensitizers have been developed. However, their application in the treatment of infectious diseases is hampered by their poor stability and easy clearance by the reticuloendothelial system (RES).Methods: To address these obstacles, we reported an erythrocyte membrane (EM) camouflaged nanoemulsion containing chlorin e6 (Ce6) and perfluorocarbon (FDC), named ECF, showing good colloidal stability and long-circulating potential, making it suitable for fighting against MDR Gram-negative bacterial infections. The nanoemulsion was fabricated and characterized. The oxygen loading and release performance, photodynamic activity, and bactericidal performance of ECF against Acinetobacter baumannii (A. baumannii) were evaluated. Furthermore, the antiphagocytosis profile was tested in vitro using Raw 264.7 cells. In addition, the pharmacokinetic behavior and therapeutic efficiency of ECF were studied in vivo.Results: ECF exhibited superior oxygen loading and release behavior, potent photodynamic activity, and negligible toxicity to mammalian cells. Upon light irradiation, the antibacterial rate of preoxygenated-ECF reached 98% at 40 μg mL− 1 of Ce6 and the bactericidal activity of preoxygenated-ECF and Gen was 3.3 folds higher than that of Gen. Furthermore, ECF could effectively inhibit uptake by phagocytes and circulate in the blood 1.5-fold longer than that of nanoemulsion without EM modification (CF) following intravenous administration. In addition, preoxygenated-ECF combined with antibiotic plus light irradiation showed prominent therapeutic efficacy in treating A. baumannii-induced acute peritonitis, accompanied by good biocompatibility in vivo.Conclusion: Our results provide a novel paradigm for evading immune clearance, prolonging retention time and improving synergetic bactericidal capacity in combination with PDT and antibiotic therapy against planktonic bacteria and gram-negative bacterial infections.Keywords: Gram-negative bacterial infection, multidrug-resistant, photodynamic therapy, oxygen affording, long circulation

Xiaochen Ma,1 Yubo Cui,2 Min Zhang,1 Qinghua Lyu,2 Jun Zhao2 1The Second Clinical Medical College, Jinan University, Shenzhen, Guangdong, People’s Republic of China; 2Department of Ophthalmology, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, Guangdong, People’s Republic of ChinaCorrespondence: Qinghua Lyu; Jun Zhao, Department of Ophthalmology, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, 518020, People’s Republic of China, Email a0129473@u.nus.edu; doctorzhaojun@163.comIntroduction: Oxidant stress, abnormal angiogenesis, and inflammation are three key factors contributing to the development of ocular neovascular diseases (ONDs). This study aims to develop a multifunctional nanodrug, DEX@MPDA-Arg@Si (DMAS), which integrates mesoporous polydopamine, vascular endothelial growth factor (VEGF)-siRNA, and dexamethasone (DEX) to address these therapeutic targets.Methods: Physicochemical properties of DMAS were measured using transmission electron microscopy and a nanoparticle size analyzer. The encapsulation efficiency and drug loading capacity of DMAS were measured using a UV-visible spectrophotometer. The in vivo therapeutic efficacy and ocular safety of DMAS were evaluated using three established mouse models, including the alkali burn-induced corneal neovascularization (CoNV) model, the oxygen-induced retinopathy (OIR) model, and the laser-induced choroidal neovascularization (CNV) model.Results: The DMAS nanoparticles demonstrated a uniform bowl-like shape with an average size of 264.9 ± 2.5 nm and a zeta potential of − 28.2 ± 4.2 mV. They exhibited high drug-loading efficiency (36.04 ± 3.60% for DEX) and excellent biocompatibility. In vitro studies confirmed its potent antioxidant, anti-inflammatory, and anti-apoptotic properties. In vivo, DMAS treatment led to significant therapeutic effects across all models. It effectively inhibited CoNV, promoted corneal repair, and modulated inflammation in the alkali burn model. In the OIR model, DMAS reduced retinal neovascularization by decreasing VEGF expression. In the laser-induced CNV model, it significantly reduced the CNV area and lesion thickness.Conclusion: This research developed a multifunctional nanodrug, DMAS, capable of co-delivering VEGF-siRNA and DEX, offering synergistic therapeutic benefits for treating ONDs. The DMAS nanodrug demonstrates promising anti-inflammatory, antioxidative, and anti-angiogenic effects, highlighting its potential as a versatile and effective treatment for multiple ocular conditions.Keywords: mesoporous polydopamine, nano-delivery platform, ocular neovascular diseases, dexamethasone, VEGF-siRNA

Wenzhi Zhu,1,&ast; Jiaonan Yang,1,&ast; Xiaoyi Wang,2 Xinqiang Ji,2 Hongyu Tan1 1Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Anesthesiology, Peking University Cancer Hospital & Institute, Beijing, People’s Republic of China; 2Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Medical Record Statistics, Peking University Cancer Hospital& Institute, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongyu Tan, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Anesthesiology, Peking University Cancer Hospital & Institute, No. 52 Fucheng Road, Haidian District, Beijing, 100142, People’s Republic of China, Tel +86-13693564036, Email galaxyspark@163.comBackground: People in China have gradually entered old age society, and the number of lung cancer cases is expected to increase annually among the elderly. This study aimed to retrospectively explore the association between perioperative factors and short-term outcomes in elderly patients with non-small cell lung cancer (NSCLC).Methods: A total of 490 elderly patients with NSCLC between January 1, 2003, and December 31, 2009, were selected. Perioperative factors were grouped and analyzed according to postoperative complications (PPCs) and length of hospital stay. A logistic regression analysis model was used to screen for the independent predictors of patient prognosis. The primary endpoint was postoperative complications and the secondary endpoint was postoperative hospital stay.Results: Of all patients, 344 (70.2%) developed postoperative complications, and the average length of stay after surgery was 14.0± 5.6 days. Perioperative fentanyl equivalents> 28.7μg/kg and duration of surgery> 4.4h were associated were associated with an increased risk of postoperative complications (P < 0.05); intraoperative blood loss (IBL) > 200 mL was associated with extended hospital stay (P < 0.05).Conclusion: This study suggested that Perioperative factors may affect the short-term prognosis of elderly NSCLC patients after surgery. Perioperative fentanyl equivalents> 28.7μg/kg, surgery duration, and IBL may be independent predictors of short-term outcomes in elderly patients.Keywords: perioperative factor, NSCLC, outcome, opioid, the elderly

Jiale Wu,1,2 Kaihong Shi,1,2 Wei Chao,1,2 Zeyu Qin,1,2 Youhui Hu,1,2 Yihua Yang,1,2 Yuan He,1,2 Yabing Hua,1,2 Ziming Zhao1,2 1Department of Pharmacy, Xuzhou Medical University, Xuzhou, People’s Republic of China; 2Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, People’s Republic of ChinaCorrespondence: Yabing Hua; Ziming Zhao, Department of Pharmacy, Xuzhou Medical University, Xuzhou, PR China; Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, People’s Republic of China, Email huayabing@xzhmu.edu.cn; zmzhao@xzhmu.edu.cnBackground: The immunotherapeutic approach utilizing Natural Killer (NK) cells for cancer treatment has garnered significant interest owing to its inherent cytotoxicity, immunomodulatory properties, demonstrated safety in in vivo studies. However, multiple immunosuppressive mechanisms in the tumor microenvironment (TME) suppress the anticancer effect of NK cells in the treatment of solid tumors. Herein, a smart NK cell drug delivery system (DDS) with photo-responsive and TME-responsive properties was designed.Methods: The NK cell DDS consists of two parts: the carrier is living NK cell with pH-low (abbreviated as NKpH) insertion peptide on its surface, the cargo is reductive-responsive nanogel (NG) encapsulated siRNA and photosensitizer (abbreviated as SP-NG), the final carrier was abbreviated as SP-NG@ NKpH. Firstly, pHLip helped artificially modified NK cell target and anchor onto cancer and exert the efficacy of cellular immunotherapy. Then, the strategy of combining photoactivation and bioreduction responsiveness achieved the precise release of cargos in cancer cells. Finally, the DDS combined the effect of the immunotherapy of NK cell, the gene therapy of siRNA, and the photodynamic therapy of photosensitizer.Results: Under near-infrared laser irradiation, SP-NG@NKpH induced an increase in reactive oxygen species (ROS) within cells, exacerbated cell membrane permeability, and allowed for rapid drug release. Within the tumor microenvironment (TME), NG exhibits highly sensitive reducibility for drug release. The SP-NG released from NK cells can be uptaken by tumor cells. When exposed to near-infrared laser irradiation, SP-NG@NKpH demonstrates significant tumor-targeting specificity and cytotoxicity.Discussion: The combined effect of the immunotherapy of NK cell, the gene therapy of siRNA, and the photodynamic therapy of photosensitizer obtained a stronger cancer killing effect in vitro and in vivo. Therefore, this versatile NK cell DDS exhibits a good clinical application prospect. Keywords: natural killer cells, photo-responsive, TME-responsive, anticancer, cellular immunotherapy, nanogel

Xiangbo Zeng,1,2,&ast; Dingrui Nie,1,3,&ast; Zhen Liu,2 Xueting Peng,1 Xianfeng Wang,1 Kangjie Qiu,1 Shuxin Zhong,1 Ziwei Liao,4 Xianfeng Zha,1,5 Yangqiu Li,1,2 Chengwu Zeng1 1Key Laboratory for Regenerative Medicine of Ministry of Education, Institute of Hematology, School of Medicine, Jinan University, Guangzhou, 510632, People’s Republic of China; 2Department of Hematology, First Affiliated Hospital, Jinan University, Guangzhou, 510632, People’s Republic of China; 3Department of Hematology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, People’s Republic of China; 4Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, 510180, People’s Republic of China; 5Department of Clinical Laboratory, First Affiliated Hospital, Jinan University, Guangzhou, 510632, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yangqiu Li; Chengwu Zeng, Jinan University, No. 601, West Huangpu Avenue, Guangzhou, Guangdong, People’s Republic of China, Email yangqiuli@hotmail.com; bio-zcw@163.comIntroduction: T-cell acute lymphoblastic leukemia (T-ALL) is a malignant hematological disease with limited targeted therapy options. Overexpression of B-cell lymphoma/leukemia 11B is frequently observed in T-ALL and contributes to leukemogenesis. Knockdown of BCL11B inhibits T-ALL cell proliferation and induces apoptosis, making it a potential therapeutic target. However, the clinical application of siRNA therapies is hindered by challenges such as poor delivery efficiency and limited clinical outcomes.Methods: We developed a targeted delivery system for BCL11B siRNA (siBCL11B) using generation 5 polyamidoamine (G5-PAMAM) dendrimers conjugated with the sgc8 aptamer, which specifically binds to the T-ALL cell membrane protein PTK7. This nanoparticle, designated G5-sgc8-siBCL11B, was designed to selectively deliver siRNA to T-ALL cells. In vitro and in vivo experiments were conducted to evaluate its therapeutic efficacy and safety.Results: We demonstrate that sgc8-conjugated siBCL11B nanoparticles selectively and efficiently target BCL11B-overexpressing T-ALL cells, significantly inhibiting cell viability and promoting apoptosis while exhibiting minimal impact on the viability of normal T cells. In T-ALL mouse model studies, G5-sgc8-siBCL11B and G5-siBCL11B significantly inhibited the progression of T-ALL in vivo, extending the survival of mice compared to the control (CTR), G5, and G5-sgc8 groups. Although there was no significant difference in survival between the G5-sgc8-siBCL11B and G5-siBCL11B groups, a trend towards improved survival was observed (p = 0.0993).Conclusion: The G5-sgc8-siBCL11B nanoparticle system demonstrated efficient delivery and significant therapeutic efficacy, highlighting its potential as a promising novel approach for the treatment of T-ALL.Keywords: BCL11B, T-ALL, aptamer, sgc8, siBCL11B, PAMAM

Cui Xie,1 Yang Xiang,1 You Wu,1 Youen Zhang1,2 1Institute of Clinical Medicine and Department of Cardiology, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei, 442000, People’s Republic of China; 2Arteriosclerosis Cardiovascular Disease Clinical Medical Research Center of Hubei Province, Shiyan, Hubei, 442000, People’s Republic of ChinaCorrespondence: Youen Zhang, Email zye112@hotmail.comAbstract: We present a patient of a 46-year-old female patient was admitted to our hospital due to chest tightness and shortness of breath that lasted for over a month. Echocardiography revealed left-ventricle diameter (anteroposterior) of 54 mm, electrocardiogram showed sinus bradycardia, and QRS duration of 90 ms. The patient experienced no chest tightness or shortness of breath, and there was a marked improvement in exercise tolerance and quality of life after cardiac contractility modulation implantation.Keywords: heart failure, cardiac contractility modulation, dilated cardiomyopathy, ventricular remodeling

Cunjin Wang,1– 4,&ast; Xiaowei Song,1,2,&ast; Jing Liu,1,2 Yinghao Song,1,3,4 Ju Gao1– 4 1Northern Jiangsu People’s Hospital Affiliated to Yangzhou University, Yangzhou, 225001, People’s Republic of China; 2Department of Anesthesiology, Northern Jiangsu People’s Hospital, Yangzhou, 225001, People’s Republic of China; 3Department of Pain Treatment, Northern Jiangsu People’s Hospital, Yangzhou, 225001, People’s Republic of China; 4The Yangzhou Clinical Medical College of Xuzhou Medical University, Yangzhou, 225001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Cunjin Wang, Department of Anesthesiology, Northern Jiangsu People’s Hospital, No. 98 Nan Tong Western Road, Yangzhou, Jiangsu, 225001, People’s Republic of China, Tel +86- 18051061453, Email cunjinwang@163.comPurpose: Postherpetic Neuralgia (PHN), recognized as the most common complication of Herpes Zoster, is experiencing an increasing trend in its occurrence. The goal of this study was to identify the independent risk factors for PHN and create a dynamic nomogram using routine clinical characteristics to predict PHN in patients with herpes zoster, for early identification and prevention of PHN.Patients and Methods: A total of 2420 patients were retrospectively reviewed and divided into training (n=1696) and validation (n=724) cohort using a 7:3 random allocation. Univariable, LASSO and multivariable logistic regression analysis was performed to identified independent risk factors for PHN. A dynamic nomogram was assessed through the area under the receiver operating characteristic curve (AUC), calibration curves and Hosmer-Lemeshow test. The decision curve analysis (DCA) was used to evaluate its clinical validity.Results: Multivariable logistic regression identified several independent risk factors for PHN, including age, female, diabetes mellitus, malignant tumors, and connective tissue diseases. The area under the curve was 0.698 (95% CI, 0.666– 0.730) for training cohort and 0.713 (95% CI, 0.663– 0.763) for the validation cohort. Calibration curve revealed a moderate consistency between actual observation and prediction. Decision curve analysis showed a risk threshold of 16% and demonstrated a clinically effective predictive model.Conclusion: We have developed a user-friendly dynamic nomogram to predict PHN in patients with herpes zoster, which can assist in early identification and prevention of PHN.Keywords: postherpetic neuralgia, herpes zoster, risk factors, dynamic nomogram

Faisal Abdi Osoble Osman,1 Ibrahim Mohamed Hirsi,2 Shuayb Moallim Ali Jama,1 Abdirisak Abdikarin Ahmed,3 Abdisalam Abdullahi Yusuf,2 Mohamed Osman Dahir1 1Radiology Department, Mogadishu Somali Turkey, Recep Tayyip Erdogan Training and Research Hospital, Mogadish, Somalia; 2Pediatric Department, Mogadishu Somali Turkey, Recep Tayyip Erdogan Training and Research Hospital, Mogadish, Somalia; 3Opthalmology Department, Mogadishu Somali Turkey, Recep Tayyip Erdogan Training and Research Hospital, Mogadish, SomaliaCorrespondence: Faisal Abdi Osoble Osman, Radiology Department, Mogadishu Somali Turkey, Recep Tayyip Erdogan Training and Research Hospital, Mogadishu, Somalia, Email Faisalosoble@gmail.comIntroduction: Septic pulmonary embolism is a serious and rare complication of orbital cellulitis. Orbital infection usually arises from adjacent soft tissue or hematogenous infections.Case: A 2-year-old girl presented with high-grade fever, cough, and bilateral eyelid swelling for 5 days preceded by edema and a perinasal facial skin furuncle. Examination revealed bilateral axial proptosis and orbital and thoracic CT bilateral orbital cellulitis, septic pulmonary embolism, and bilateral pneumothorax.Discussion: A rare but potentially fatal complication of periorbital cellulitis is septic embolism, which carries a high rate of morbidity and mortality. The infections that cause orbital cellulitis can be transmitted to the orbit through dehiscence of the bone wall or through venous drainage. This can lead to septicemia and subsequent serious complications, including septic pulmonary embolism, Cavernous sinus thrombosis, meningitis, and cerebral ischemia. Advanced and timely imaging is crucial to diagnose both orbital cellulitis and its thoracal complications.Conclusion: Early diagnosis of orbital cellulitis, timely investigations of its extracranial complications, and multidisciplinary involvement in patient management are crucial to prevent or treat complications such as septic pulmonary embolism and may improve patient prognosis.Keywords: Septic pulmonary embolism, SPE, Orbital cellulitis, OC and Pneumothorax, PTX

Tianyu Bai,&ast; E Zhou,&ast; Kai Wang, Weizheng Li, Jieyu Bi, Jiacheng Ju Department of Acupuncture and Moxibustion, Shandong Provincial Third Hospital Shandong University, Jinan, Shandong, 250031, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tianyu Bai, Email Baitianyu19820217@163.comBackground: Resting-state functional magnetic resonance imaging (rs-fMRI) is a noninvasive way to evaluate brain physiological activity by detecting blood oxygen level fluctuations. Diminished ovarian reserve (DOR) indicates ovarian aging. Before 40, patients may have menstrual abnormalities, poor reproduction, and poor assisted reproductive results. Without treatment, it can cause early ovarian failure. Studies have shown that acupuncture can ameliorate sex hormones and antral follicle count (AFC) in DOR patients.Objective: Despite limited studies on its mechanism, acupuncture have been shown to treat DOR. There is no relevant research on brain functional magnetic resonance and brain functional connectivity of acupuncture in treating DOR. We design this clinical trial to preliminarily elucidate the neuroimaging method of controlling the brain functional network and acupuncture impact in DOR patients using rs-fMRI.Methods: This study will involve 30 DOR patients and 30 healthy individuals. DOR patients will have rs-fMRI before and after 3 menstrual cycles of acupuncture, whereas healthy individuals will need one rs-fMRI scan. The primary end measures will be follicle-stimulating hormone (FSH) and AFC. In contrast, the secondary outcomes will be luteinizing hormone(LH), estradiol (E2), anti-Müllerian hormone (AMH), modified Kupperman scale, self-rating anxiety scale (SAS), self-rating depression scale (SDS), and rs-fMRI alterations.Results: This study uses rs-fMRI technology to identify the brain regions that differ between DOR patients and healthy people before and after acupuncture treatment. This study will connect brain regions, examine the effects of acupuncture on menstruation and pregnancy on DOR patients’ brain function networks, and discuss neuroimaging methods.Conclusion: Acupuncture may have the potential to regulate menstruation and increase the chances of pregnancy promotion in patients with DOR.Keywords: clinical trials, study protocol, rs-fMRI, acupuncture, DOR, brain functional networks

Abstract Background Evidence for the pathogenesis and treatment of postacute coronavirus disease 2019 (COVID‐19) (long COVID) is lacking. As long COVID symptoms are predicted to have an impact on the global economy, clarification of the pathogenesis is urgently needed. Our experiences indicated that some symptoms were complicated by diseases established before the COVID‐19 pandemic. Methods Using a retrospective, cross‐sectional study, we aimed to evaluate the diseases complicating long COVID. Using the medical records of patients with confirmed COVID‐19 exhibiting residual symptoms lasting ≥60 days postinfection who visited our clinic in January 2021–February 2023, we investigated the symptoms and diseases observed. We identified diseases that occurred after COVID‐19 and excluded those that were exacerbations of existing diseases. Results During the first visit, the most common symptoms reported in a total of 798 patients were fatigue (523 patients), anxiety (349 patients), and lack of motivation (344 patients). Complicating diseases were observed in 452 patients (57%). There were 115, 65, and 60 patients with postural tachycardia syndrome, postural syndrome without tachycardia, and mood disorders, respectively. Some diseases requiring immediate treatment included pulmonary thromboembolism, purulent shoulder arthritis, cerebellopontine angle tumors, myasthenia gravis, and cervical myelopathy. Conclusion Not all symptoms that occur after COVID‐19 should be treated as long COVID. Similar to normal medical treatment, a list of differential diagnoses should be maintained based on symptoms to obtain definitive diagnoses.

Abstract Background Anterior cutaneous nerve entrapment syndrome (ACNES) is the most common cause of abdominal wall pain. This study aimed to clarify the proportion of ACNES cases among those of abdominal pain and the clinical characteristics and prognosis of the disease in an emergency department (ED) of a Japanese general hospital. Methods The medical records of patients from January 2014 to December 2023 were reviewed, and patients aged 15 years or older with abdominal pain with positivity for Carnett's sign, a good response to trigger point injection (TPI), and an ACNES diagnosis were included. The proportion of ACNES cases among the complaints related to abdominal pain in the ED between 2020 and 2023 was then determined. The recurrence rate was also determined using data from the medical records and telephone follow‐ups. Results Twenty‐one patients were included. Their median age was 50 years (range: 16–83 years), 13 (62%) were female, and 11 (52%) had acute‐onset pain. Follow‐up data were available for 11 patients (52%), seven (64%) of whom had recurrent pain for a median period of 1 week after the index visit. The proportion of ACNES cases among those of abdominal pain was 0.11%. Conclusion ACNES might be uncommon among patients with abdominal pain in the ED setting although underdiagnosis of this condition might have led to an underestimation of the proportion of cases. Moreover, given the high recurrence rate of abdominal pain associated with ACNES, following up these patients is very important.

Abstract Background Older patients with multimorbidity often seek care from multiple health care providers and visit several medical institutions. Having a primary care provider who takes overall responsibility for their care may be beneficial. We conducted a survey to identify the characteristics of general practitioners and geriatricians who frequently assume such responsibility for older patients with multimorbidity. Methods In June 2022, we distributed by mail an anonymous questionnaire to 3300 family medicine specialists, primary care‐certified physicians, and geriatric specialists in Japan. We used a four‐point Likert‐type scale to score items related to conditions and patient backgrounds that pose challenges in treatment, key clinical factors, and important clinical strategies. Modified Poisson regression was used to identify factors associated with frequently assuming overall responsibility for medical care. Results Data from 746 physicians were included in the analysis. Factors associated with frequently assuming overall responsibility for medical care of older patients with multimorbidity included providing inpatient ward care (prevalence ratio [PR] 1.237, 95% CI 1.124–1.362), providing home medical care (PR 1.357, 95% CI 1.225–1.504), frequently treating patients over 90 years old (PR 2.043, 95% CI 1.258–3.318), and the overall score for clinical strategies (PR 1.021, 95% CI 1.010–1.033). Conclusions General practitioners and geriatricians who frequently assume overall responsibility for the care of older patients with multimorbidity tend to engage significantly in ward and home medical care, often treat patients above 90 years, and employ numerous clinical strategies.

Abstract Background The prevalence of non‐alcoholic fatty liver disease (NAFLD), which is characterized by hepatic steatosis, inflammation, and advanced fibrosis, is high among type‐2 diabetes mellitus (T2DM) patients. Empagliflozin (EMPA), a sodium‐glucose cotransporter‐2 inhibitor, has been well established to improve glycemic status in T2DM. However, evidence of the desirable effects of EMPA, when added to the standard treatment in diabetics with coexisting NAFLD, has yet to be determined. Objective The main objective of the current study is to explore the benefits of EMPA on hepatic fat content in patients with T2DM and NAFLD, who received metformin (MET) monotherapy. Methods In this open‐label clinical trial study, 60 patients with T2DM and NAFLD were assigned to either the MET + EMPA or MET group in an up‐titrated manner for 24 weeks. Anthropometric characteristics, blood glucose indices, lipid profile, liver enzymes, and steatosis grades were measured at baseline and 24 weeks after the intervention. Results The results showed that in patients with a mean age of 53.26 ± 7.64 who received MET+ EMPA, all the parameters had a greater decrease than the MET group. In addition, the reduction of FBS, BS, HbA1C, TG, and ALT had a statistically significant difference between the two groups after 24 weeks follow‐up (p

Abstract Background Low birthrates and an aging society during population decline have brought about labor shortages and increased medical care needs. Medical resources should be distributed appropriately, particularly in rural areas. High‐quality primary care can make the medical system more effective and contribute to rural residents' health. However, there are no reports on the impact of primary care on health in the rural areas of Japan. This study examined the effect of primary care quality on self‐rated health in a rural Japanese area. Methods We conducted a cross‐sectional study using a questionnaire survey of residents of a rural area in northern Shiga Prefecture in 2021. Self‐rated health (SRH) was used as the health outcome (1–5 points), and the Japanese Primary Care Assessment Tool Short Form (JPCAT‐SF) was used to measure the patients' experience of primary care (0–100 points). We conducted a multivariate analysis using logistic regression analysis and examined the association between good SRH (4 points or more) and high JPCAT‐SF scores (above average score), adjusted for sociodemographic confounding factors. Results A total of 1108 men and 1412 women responded to the survey. The mean patient age was 69.8 years. The mean JPCAT‐SF score was 51.8 points. Among the 1172 patients with chronic diseases, good SRH was associated with high JPCAT‐SF scores (odds ratio [OR] 1.32, 95% confidence interval [CI] 1.009–1.73). Conclusions Good SRH among rural residents with chronic disease was associated with high primary care quality.

Abstract Background The coronavirus disease 2019 (COVID‐19) pandemic has markedly affected end‐of‐life care, notably increasing home deaths among cancer patients in Japan. This study investigated the characteristics of cancer patients who died at home during the pandemic and the associated factors before and during the pandemic. Methods Vital statistics from January 2015 to December 2022 were analyzed to evaluate trends in home deaths among cancer patients aged 0 to 113 years, pre‐pandemic (January 2015 to March 2020) and during the pandemic (April 2020 to December 2022). Home deaths were assessed by demographics, including age, sex, marital status, and residential location. Multivariable modified Poisson regression analyses were performed to identify factors associated with home deaths in both periods. Results Among 3,010,374 individuals, 11.6% (226,571/1,959,304) and 20.8% (218,429/1,051,070) died at home before and during the pandemic, respectively. In subgroup analysis depicting the trend of in‐home deaths by patient characteristics, only the age group showed a differential trend: the proportion of in‐home deaths was higher among older people before the pandemic, whereas it was higher among younger people during the pandemic. The multivariable analysis revealed the excess risk of in‐home deaths among people aged ≥65 years before the pandemic and among those aged

Abstract Background Age and sex differences in sarcopenic dysphagia are unknown. The purpose is to characterize age and sex differences in sarcopenic dysphagia. Methods A cross‐sectional and retrospective cohort study using information from the Japanese database on sarcopenic dysphagia was performed. We investigated age and sex differences between sarcopenic dysphagia and other forms of dysphagia. We investigated whether differences in prognosis for swallowing function, as assessed by the Food Intake Level Scale, and activities of daily living (ADL), as assessed by the Barthel Index were influenced by age and sex in patients with sarcopenic dysphagia. Results The study included 460 patients, including 229 men and 231 women, with a mean age of 81 ± 10 years. Fifty‐eight percent of the patients had sarcopenic dysphagia. Age was independently associated with sarcopenic dysphagia (odds ratio (OR): 1.056, 95% confidence interval (CI): 1.035, 1.078), although sarcopenic dysphagia could also be seen in those younger than 65 years. Sex was not independently associated with sarcopenic dysphagia. The age cut‐off for the diagnosis of sarcopenic dysphagia was 82 years in all patients (sensitivity, 0.660; specificity, 0.644), 80 years in men (sensitivity, 0.619; specificity, 0.631), and 83 years in women (sensitivity, 0.723; specificity, 0.577). Sarcopenic dysphagia showed no significant differences in the improvement of swallowing function and ADL based on age and sex. Conclusions Sarcopenic dysphagia was most common in older adults in their 80s or older. The possibility of sarcopenic dysphagia should be considered when dysphagia is present in people 80 years of age or older.

Abstract A 24‐year‐old female nurse with a 4‐month history of low back pain (LBP) was treated with acupuncture because of difficulty to her working. At the first presentation, the numerical rating scale (NRS) value was 7. After 2 weeks, the NRS value improved to 2–3, and she could bend over better, including when working night shifts. After 4 months, the NRS value remained at 1–2 so her relocating or leaving of absence from the ICU department was avoided. Acupuncture treatment for medical staff with LBP could relieve their pain and improve decreased clinical performance in hospitals or clinics.

Abstract Background Multimorbidity increases with age, leading to various adverse outcomes, including higher mortality, care dependency, hospitalizations, and healthcare costs. Polydoctoring, managing a patient with multimorbidity by multiple healthcare providers, can be a risk of fragmented care and increased healthcare expenditures. This study aims to identify patient‐related factors contributing to polydoctoring in older adults with multimorbidity. Methods This study is a cross‐sectional study using baseline data from the Kawasaki Aging and Wellbeing Project. Participants were residents of Kawasaki City aged 85–89 years, without disability in basic activities of daily living, and being able to visit study site. The regularly visited facilities (RVF) index was employed to quantify polydoctoring. Polydoctoring was defined as having two or more RVFs. Poisson regression analysis was conducted to assess the association between polydoctoring and patient demographics, including types of chronic conditions and socioeconomic factors. Results A total of, 968 participants with multimorbidity were analyzed. Increased RVF was significantly associated with eye diseases (rate ratio [RR] 1.27, 95% confidence interval [CI] 1.12–1.44), osteoporosis (RR 1.22, 95% CI 1.08–1.38), prostate diseases (RR 1.22, 95% CI 1.07–1.40), and osteoarthritis (RR 1.16, 95% CI 1.05–1.27). No significant correlation was found with educational status or financial hardship. Conclusion The study indicated that certain chronic conditions are linked to increased polydoctoring among multimorbid older adults in Japan. However, most of those conditions are considered to be within a scope of family medicine/general practice. Training general practitioners to manage these conditions could reduce healthcare costs and the treatment burden, indicating a direction for future healthcare policy and medical education.

Abstract Introduction Given the increase in the primary care nursing workforce and the need to further grow nursing roles in the community understanding how this is included in undergraduate education is important. This study aimed to explore the inclusion of primary care in the undergraduate nursing education curriculum of four countries. Method A mixed‐method design was employed to obtain a broader context of primary care nursing in nursing education and teaching approaches relating to primary care nursing. Subsequently, Australia, Canada, Spain, and Ireland were selected for this study because primary healthcare systems are established as a part of their healthcare system. Results In total, 136 nursing faculties (40 in Australia, 35 in Canada, 46 in Spain, and 15 in Ireland) were invited to participate in this study. Of these, 27 responses were obtained (19.8% response rate). Following the survey phase, in‐depth interviews were conducted with 13 participants. The results indicated that the highest number was coded within the theme of “Understanding of PHC in the curriculum” (n = 108). The second highest number (n = 87) was within the theme of “Interpretation differences of PHC in curriculum,” and the third highest (n = 31) was coded within “Policy impact on health by national government and others.” Conclusion The results emphasized the ambiguity of primary care within the undergraduate nursing curriculum and that interpretation and implementation into the curriculum largely depended on the school's intentions.

Abstract Japanese citizens of all socioeconomic statuses have benefited from the national insurance system by receiving high‐quality healthcare. However, the Japanese healthcare service is facing a severe financial crisis because of the increasing aging society and social security expenses. Many consultations raise medical expenditure and doctors' work overload, which is about to be regulated, but is questionable how the goal can be achieved without delegating doctors' working tasks. Sweden has a similar health index to that of Japan, but the system is different and is anchored by general practitioners and specialist nurses assigned to primary health care centers. They collaborate to share the workload, responsibilities, and patients' continuous care needs. As a result, the number of consultations is kept small, the length of stay in hospitals is shortened, and doctors' working hours are protected. A system change inspired by Swedish primary health care can be a potential solution for Japanese society.

Abstract The effect of neglecting imaging in aspiration pneumonia diagnosis is not well understood. In this study, the computed tomography images of 50 patients diagnosed with aspiration pneumonia were retrospectively analyzed by three radiologists at a different hospital. Among these cases, 32%–42% were not classified as aspiration pneumonia based on imaging. Thus, imaging features may not have been adequately considered for diagnosing aspiration pneumonia. Although not all patients with aspiration pneumonia can be diagnosed based on imaging, aspiration pneumonia should be considered in the diagnosis as cases that are clearly nonaspiration pneumonia can be misdiagnosed as aspiration pneumonia.

Abstract Allergic rhinitis is an inflammatory disorder affecting nasal mucosa in response to allergen exposure and is commonly assessed and managed in family medicine. In this article, we review new international guidelines on the diagnosis and management of allergic rhinitis and generate evidence‐informed recommendations for family medicine doctors.

Introduction: Children's adolescence is characterized by dynamically changing indicators of periodontal and oral health, related mainly to the eruption of the permanent dentition and stabilization of the periodontal space. This age period is also characterized by an increased incidence of gingival diseases, with the dental biofilm being the main risk factor for the inflammatory process. Aim: The aim of this study is to assess the relationship between gingival status, oral hygiene habits and knowledge on topics related to oral health in children aged 11-13. Material and methods: The subject of the study was 106 children aged 11-13 years. All children overwent a clinical periodontal examination and periodontal risk assessment at 4 levels. An electronic periodontal probe PA ON (Orangedental) with specially designed software was used to assess periodontal and oral hygiene status. The study included a survey method for assessing children's knowledge on topics related to oral health with periodontal focus. The survey consists of 38 questions divided into eight topics. Results: All the children aged 11-13 years had an initial form of gingival inflammation, against the background of plaque accumulation affecting more than 69% of tooth surfaces, unstable and irregular oral hygiene habits, as well as insufficient knowledge of oral/periodontal health. Through appropriate preventive programs, this age is best suited to create consciously motivated behavior for proper oral hygiene and oral health.

Anterior cross bite is an occlusal etiological factor for the occurrence of gingival recession and resorption of the alveolar bone. Aim: To examine the condition of the alveolar bone in relation to incisor inclination in subjects with anterior cross bite. Materials and methods: Sixty one eligible subjects, with a mean age of 25.66±10.51 years, presented with anterior cross bite of a single teeth or a group of teeth. The distribution of patients by sex is women-42.6% and men-57.4%. The inclination of the upper and lower incisors was evaluated and analysed with Steiner C method. The bone resorption in the two jaws (distance from the enamel-cement junction of the incisors up to the beginning of the alveolar bone) was measured up to 0.01 mm. Results: Protrusions constituted a higher percentage than retrusion in both jaws. The mean value of bone resorption in the maxilla of subjects with retrusion was 4.01mm, whereas in subjects with protrusion, it was 3.42mm (p = 0.062). The mean value of bone resorption in the mandible of subjects with retrusion was 4.56mm, whereas in subjects with protrusion, it was 4.36mm. The bone resorption mean of the patients with retrusion in the mandible was 0.55mm higher than the mean of the patients with retrusion in the maxilla with high statistical significance (p = 0.008). Conclusion: Higher levels of bone resorption were observed in the mandible as compared to the maxilla. A significant linear relationship was found between the inclination of the incisors and the degree of bone resorption.

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