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

Rong Yang,1,&ast; Qing Ma,1,2,&ast; Xiaolin Zhang,3 Qian Zhao,1,4,5 Suilan Zeng,6 Hechun Yan,7 Yi Lei,1,5 Shanye Yi,1 Xin Chen,8 Nianxi Wu9 1General Practice Ward/International Medical Center Ward, General Practice Medical Center, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 2West China School of Nursing, Sichuan University, Chengdu, People’s Republic of China; 3Preventive Health Section, Dayi County Shaqu Street Community Health Service Center, Chengdu, People’s Republic of China; 4Teaching & Research Section, General Practice Medical Center, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 5General Practice Medical Center and General Practice Research Institute, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 6Guan Ge Center Health Center, Guangan, People’s Republic of China; 7Department of Gynecology and Obstetrics, West China Second Hospital, Sichuan University, Chengdu, People’s Republic of China; 8Big Buddha Street Community Health Service Center, Leshan, People’s Republic of China; 9Chongqing Magic MedTech Co., Ltd., Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qian Zhao, Email 27355151@qq.comPurpose: Osteoporosis is a major health concern among the elderly, underscoring the importance of investigating its prevalence across different geographical regions. There is a current research gap regarding the incidence of osteoporosis and its variation by altitude within Sichuan, China. This study aimed to assess the prevalence of osteoporosis among populations residing at different altitudes in western Sichuan Province.Basic Procedures: This study utilized data from a population-based cohort in Sichuan, China. Representative locations were selected, and cluster random sampling was employed to conduct cohort studies across multiple sites in southwestern China. T Baseline data were collected from populations in Mianzhu, Kangting, and Sertar between July 2020 and August 2021. To assess differences in osteoporosis incidence among populations at different altitudes and with varying characteristics, we applied Chi-square and rank-sum tests.Main Findings: The study involved 4074 participants, including 1404 males (34.46%) and 791 individuals diagnosed with osteoporosis (19.42%). The prevalence of osteopenia in mid-altitude and high-altitude regions was 20.05% and 16.28%, respectively, while the prevalence of osteoporosis was significantly different, at 25.85% in mid-altitude areas compared to 13.00% in high-altitude areas (P < 0.001). Further analysis identified statistically significant differences in the prevalence of osteopenia and osteoporosis among females (P< 0.001), middle-aged (P=0.015) and elderly populations (P=0.038), as well as among individuals who were underweight (P=0.011), normal weight (P< 0.001), overweight (P< 0.001), and obese (P=0.038). As altitude increased, the prevalence of osteoporosis decreased in all groups except the elderly, while the prevalence of osteopenia decreased among women and across various BMI categories, but increased among middle-aged and elderly individuals. Additionally, in high-altitude regions, Kangting recorded an 18.10% prevalence of osteopenia and a 14.26% prevalence of osteoporosis, compared to Sertar, which exhibited a 6.54% prevalence of osteopenia and a 6.23% prevalence of osteoporosis, indicating significant differences (P< 0.001).Conclusion: This study demonstrates that higher altitudes are associated with a decreased prevalence of osteopenia and osteoporosis, particularly among females and middle-aged individuals. These results emphasize the importance of developing region-specific osteoporosis prevention strategies.Keywords: osteoporosis, aging, prevalence, altitude, Sichuan province

Letao Zhu,1 Yanfeng Li,1 Qingshi Zhao,1 Changyu Li,1 Zongbi Wu,2 Youli Jiang1 1Department of Neurology, People’s Hospital of Longhua, Shenzhen, 518109, People’s Republic of China; 2Nursing Department, Shenzhen Traditional Chinese Medicine Hospital, The Fourth Clinical Medical School of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, 518033, People’s Republic of ChinaCorrespondence: Youli Jiang, Department of Neurology, People’s Hospital of Longhua, No. 38, Jinglong Jianshe Road, Longhua District, Shenzhen, Tel +8618545403739, Fax +86 27741585-8500, Email h2362120381@163.com Zongbi Wu, Nursing Department, Shenzhen Traditional Chinese Medicine Hospital, The Fourth Clinical Medical School of Guangzhou University of Chinese Medicine, No. 1, Fuhua Road, Futian District, Shenzhen, People’s Republic of China, Tel +8615384435576, Fax +86 0755-88359899, Email wuzongbi2016@126.comBackground: Acute ischemic stroke (AIS) is increasingly affecting younger populations, necessitating prompt thrombolytic therapy within a narrow therapeutic window. Pre-hospital delays are prevalent, particularly in China, yet targeted research on the youth population remains scarce.Methods: In this retrospective cohort study, data from AIS patients aged 18– 50 admitted to Longhua District People’s Hospital, Shenzhen from December 2021 to December 2023 were analyzed using XGBoost and Random Forest machine learning algorithms, coupled with SHAP visualization, to identify factors contributing to pre-hospital delays.Results: Among 1954 AIS patients, 528 young patients were analyzed. The median time to hospital arrival was 8.34 hours, with 82.0% experiencing delays. Analysis of different age subgroups showed that young patients aged 36– 50 years old had a higher delay rate than patients under 36 years old. Machine learning algorithms identified stroke awareness, age, TOAST classification, ambulance arrival, dysarthria, mRS on admission, dizziness, wake-up stroke, etc. as important determinants of delay.Conclusion: This study highlights the necessity of machine learning in identifying delay risk factors in young stroke patients. Enhanced public education, particularly regarding stroke symptoms and the use of emergency services, is crucial for reducing pre-hospital delays and improving patient outcomes.Keywords: acute ischemic stroke, onset-to-door time, young adults, machine learning, emergency medical services

Mu Yuan,1,2,&ast; Weijun Wan,1,2,&ast; Wei Xing,1,2 Chengxiu Pu,1,2 Xiaofeng Wu,1,2 Zhikang Liao,3 Xiyan Zhu,3 Xueting Hu,1,2 Zhan Li,1,2 Qing Zhao,1,2 Hui Zhao,3,&ast; Xiang Xu1,2,&ast; 1Department of Stem Cell and Regenerative Medicine, National Key Laboratory of Trauma and Chemical Poisoning, Daping Hospital, Army Medical University, Chongqing, 400042, People’s Republic of China; 2Central Laboratory, State Key Laboratory of Trauma, Burn and Combined Injury, Daping Hospital, Army Medical University, Chongqing, 400042, People’s Republic of China; 3Research Department Fourth Laboratory, Daping Hospital, Army Medical University, Chongqing, 400042, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiang Xu, Stem Cell and Regenerative Medicine Department, Daping Hospital, Army Medical University, Chongqing, No. 10, Changjiang Road, Yuzhong District, Chongqing, 400042, People’s Republic of China, Email xiangxu@tmmu.edu.cn Hui Zhao, Research Department Fourth Laboratory, Daping Hospital, Army Medical University, Chongqing, 400042, People’s Republic of China, Email Zhaohui@tmmu.edu.cnPurpose: We aimed to investigate whether peripheral blood biomarkers B2M related to immune response can serve as indicators of HAPE pathophysiological characteristics or disease progression.Patients and Methods: Bioinformatics technology was used to explore the peripheral blood pathophysiological mechanisms and immune hub genes related to the occurrence of HAPE. The hub gene was verified through animal experiments, and its function and correlation between its expression level and the diagnosis, treatment effect and prognosis of HAPE were explored.Results: The GSVA results showed that the occurrence of HAPE was related to the down-regulation of immune response pathways by RUNX3 and STING. WGCNA results showed that the peripheral blood immune gene module related to the development of HAPE was related to the decrease of immune function and the increase of immune checkpoint molecule PD-L1 gene expression, and the expression of immune checkpoint genes LILRB2 and SIGLEC15 increased. Cytoscape software, RT-qPCR and WB confirmed that the hub gene B2M is a specific peripheral blood biomarker of HAPE. ROC, DCA, RT-qPCR, HE and Masson results showed that the expression of peripheral blood B2M has the ability to indicate the diagnosis, treatment effect and prognosis of HAPE. The decreased expression of B2M protein in peripheral blood leukocytes may be a marker of HAPE. Single-gene GSEA confirmed that the reduced expression of B2M in peripheral blood may be involved in the down-regulation of the antigen presentation pathway mediated by MHC class I molecules, was positively correlated with the down-regulation of the TNF signaling pathway, and was negatively correlated with the expression of LILRB2 and SIGLEC15.Conclusion: The occurrence of HAPE may be related to decreased immune function and immune tolerance. Peripheral blood B2M may be involved in the related pathways, its expression level can prompt the diagnosis, treatment and prognosis of HAPE. Keywords: high altitude pulmonary edema, immune tolerance, biomarker, B2M, prognosis

Xiangan Gong,1,2 Qian Zhao,1,2 Huimin Zhang,1,2 Rui Liu,1,2 Jie Wu,1,2 Nanxin Zhang,3 Yuanxian Zou,1,2 Wen Zhao,1,2 Ran Huo,1,2,4 Rongtao Cui1– 4 1Department of Burn and Plastic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of China; 2Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, People’s Republic of China; 3School of Clinical Medicine, Shandong Second Medical University, Weifang, People’s Republic of China; 4Department of Burn and Plastic Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of ChinaCorrespondence: Rongtao Cui, Department of Burn and Plastic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of China, Tel +86 18653170822, Email cuirt1986@outlook.comAbstract: Pathological scarring results from aberrant cutaneous wound healing due to the overactivation of biological behaviors of human skin fibroblasts, characterized by local inordinate inflammation, excessive extracellular matrix and collagen deposition. Yet, its underlying pathogenesis opinions vary, which could be caused by increased local mechanical tension, enhanced and continuous inflammation, gene mutation, as well as cellular metabolic disorder, etc. Metabolic reprogramming is the process by which the metabolic pattern of cells undergoes a systematic adjustment and transformation to adapt to the changes of the external environment and meet the needs of their growth and differentiation. Therefore, the abnormality of metabolic reprogramming in cells within wounds and scars attaches great importance to scar formation. Mesenchymal stem cells-derived exosomes (MSC-Exo) are the extracellular vesicles that play an important role in tissue repair, cancer treatment as well as immune and metabolic regulation. However, there is not a systematic work to detail the relevant studies. Herein, we gave a comprehensive summary of the existing research on three main metabolisms, including glycometabolism, lipid metabolism and amino acid metabolism, and MSC-Exo regulating metabolic reprogramming in wound healing and scar formation for further research reference.Keywords: mesenchymal stem cells-derived exosomes, metabolic reprogramming, scar, wound healing, fibroblast

Qinying Zhao,&ast; Ziyue Zhang,&ast; Shuo Li, Ming Liu Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ming Liu, Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, Tianjin, 300052, People’s Republic of China, Email mingliu@tmu.edu.cnAim: Although the interplay of insulin resistance (IR) and low muscle mass is increasingly recognized, it remains unknown whether the triglyceride-glucose (TyG) index, as an indicator of IR, is associated with low muscle mass in patients with type 2 diabetes (T2D). Our study aimed to investigate the association between TyG index and low muscle mass in hospitalized T2D patients.Methods: This cross-sectional study involved 2687 hospitalized participants with T2D. The TyG index was calculated by fasting plasma glucose (FPG) and triglyceride levels. The outcome variables were defined as appendicular skeletal muscle mass index (ASMI) and low muscle mass. To explore the relationship between TyG index and low muscle mass, we conducted the multivariate linear regression, multivariate logistic regression, and subgroup analysis.Results: In the fully adjusted multivariate linear regression, there was a negative correlation between TyG index (β=− 0.10, 95% CI: − 0.14, − 0.06) and ASMI. TyG index (OR = 1.34, 95% CI: 1.08, 1.65) had a more significant association with low muscle mass compared to FPG (OR = 1.05, 95% CI: 1.01, 1.09) and glycated hemoglobin A1c (OR = 1.07, 95% CI: 0.99, 1.15). The statistical significance of the trend persisted among the TyG index quartile groups. Subgroup analysis revealed stronger positive associations between TyG index and low muscle mass in females, individuals aged 60 years or older, those with a body mass index of 28kg/m2 or higher, and HbA1c levels of 6.5% or higher, as well as those with hypertension and dyslipidemia.Conclusion: A higher TyG index level is positively associated with a higher risk of low muscle mass, suggesting that TyG index could be a potential biomarker of low muscle mass in hospitalized T2D patients.Keywords: triglyceride-glucose index, low muscle mass, type 2 diabetes, insulin resistance, cross-sectional study

Dan Ye,1 Ding Ding,1 Ling-Yun Pan,2 Qing Zhao,3 Long Chen,2 Min Zheng,1 Tong Zhang,1 Bing-Liang Ma1 1Department of Pharmacology, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 2Experiment Center for Science and Technology, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 3Department of Pharmacy, Jing’an District Zhabei Central Hospital, Shanghai, 200070, People’s Republic of ChinaCorrespondence: Bing-Liang Ma; Tong Zhang, Department of Pharmacology, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, No. 1200 Cai Lun Road, Pudong New District, Shanghai, 201203, People’s Republic of China, Tel +86-021-5132 2199 ; +86-021-5132 2318, Fax +86-021-5132 2192, Email bingliang.ma@hotmail.com; zhangtongshutcm@hotmail.comPurpose: Docetaxel (DTX) is a valuable anti-tumor chemotherapy drug with limited oral bioavailability. This study aims to develop an effective oral delivery system for DTX using natural nanoparticles (Nnps) derived from Coptidis Rhizoma extract.Methods: DTX-loaded self-assembled nanoparticles (Nnps-DTX) were created using an optimized heat-induction strategy. Nnps-DTX’s shape, size, Zeta potential, and in vitro stability were all carefully examined. Additionally, the study investigated the encapsulation efficiency, loading capacity, crystal form, and intermolecular interactions of DTX in Nnps-DTX. Subsequently, the solubility, release, cellular uptake, metabolic stability, and preclinical pharmacokinetics of DTX in Nnps-DTX were systematically evaluated. Finally, the cytotoxicity of Nnps-DTX was assessed in three tumor cell lines.Results: Nnps-DTX was spherical in shape, 138.6 ± 8.2 nm in size, with a Zeta potential of − 20.8 ± 0.6 mV, a DTX encapsulation efficiency of 77.6 ± 8.5%, and a DTX loading capacity of 6.8 ± 1.9%. Hydrogen bonds, hydrophobic interactions, and electrostatic interactions were involved in the formation of Nnps-DTX. DTX within Nnps-DTX was in an amorphous form, resulting in enhanced solubility (23.3 times) and release compared to free DTX. Following oral treatment, the mice in the Nnps-DTX group had DTX peak concentrations 8.8, 23.4, 44.6, and 5.7 times higher in their portal vein, systemic circulation, liver, and lungs than the mice in the DTX group. Experiments performed in Caco-2 cells demonstrated a significant increase in DTX uptake by Nnps-DTX compared to free DTX, which was significantly inhibited by indomethacin, an inhibitor of caveolae-mediated endocytosis. Furthermore, compared to DTX, DTX in Nnps-DTX demonstrated better metabolic stability in liver microsomes. Notably, Nnps-DTX significantly reduced the viability of MCF-7, HCT116, and HepG2 cells.Conclusion: The novel self-assembled nanoparticles considerably enhanced the cellular absorption, solubility, release, metabolic stability, and pharmacokinetics of oral DTX and demonstrated strong cytotoxicity against tumor cell lines. Keywords: docetaxel, oral delivery, self-assembly, nanoparticles, pharmacokinetics, coptidis rhizoma

Taiyu Song,&ast; Lulu Yao,&ast; Angang Zhu,&ast; Guangling Liu, Beibei Zhu, Qian Zhao, Yue Zhao, Jinya Wang Department of Pediatrics, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jinya Wang, Email jinyawang@vip.163.comIntroduction: Asthma, a chronic respiratory disease closely associated with inflammation, presents ongoing treatment challenges. IALLIPF (le-Ala-Leu-Leu-Ile-Pro-Phe) is one of millet prolamins peptides (MPP) which shows anti-oxidant bioactivity by reducing the production of reactive oxygen species (ROS). Tryptophan (Trp, W) is an amino acid that has been demonstrated to possess anti-inflammatory effects. We introduce a novel cathepsin B-activatable bioactive peptides nanocarrier, PEG-IALLIPF-GFLG-W (MPP-Trp), designed for immunotherapy of asthma.Methods: MPP-Trp is synthesized, purified, and its characteristics are investigated by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The yield of nitric oxide (NO) and pro-inflammatory cytokines (TNF-α, IL-6 and IL-1β) are examined to evaluate anti-inflammatory effects of IALLIPF, Trp and MPP-Trp. The immunomodulatory effects of IALLIPF, Trp and MPP-Trp on Th1/Th2 cell populations and cytokines are investigated by flow cytometry, qRT-PCR and ELISA assays. We explore the therapeutic effect of MPP-Trp in the mouse model of asthma by the analysis of lung histology and ELISA. It is necessary to study the biocompatibility of MPP-Trp by CCK8 assay and histopathologic analysis using hematoxylin and eosin (HE) staining.Results: In asthmatic peripheral blood mononuclear cells (PBMCs), IALLIPF, Trp and MPP-Trp are able to significantly alleviate inflammation by inhibiting the yield of nitric oxide (NO) and pro-inflammatory cytokines (TNF-α, IL-6 and IL-1β), especially MPP-Trp. MPP-Trp significantly upregulates Th1 cell levels while notably reducing Th2 cell levels. Furthermore, MPP-Trp effectively elevates the expression and production of interferon-gamma (IFN-γ), an essential cytokine from Th1 cells. Additionally, MPP-Trp markedly diminishes the mRNA expression and levels of key asthma pathogenesis cytokines, such as interleukin-4 (IL-4), interleukin-13 (IL-13), and interleukin-5 (IL-5), in asthma PBMCs. MPP-Trp ameliorates pulmonary pathological alterations and significantly inhibits OVA-induced inflammation in mice with asthma. It has little influence on the cell viability in Asthma-PBMCs treated with various concentrations or durations of MPP-Trp. No pathological changes, including in the heart, liver, spleen, lung, and kidney tissues, are observed in non-sensitized and non-challenged mice treated with MPP-Trp (20 mg/kg).Discussion: Our research demonstrates that MPP-Trp has immunomodulatory effects on Th1/Th2 cell populations, essential in managing asthma. It considerably alleviates OVA-induced asthma by shifting the immune response towards a Th1-dominant profile, thereby reducing Th2-driven inflammation. Therefore, this novel bioactive peptide nanocarrier, MPP-Trp, holds promise as a candidate for asthma immunotherapy.Keywords: asthma, cathepsin B, bioactive peptide nanocarrier, MPP-Trp, immunomodulatory

Yongsheng Zhao,&ast; Xianlei Xin,&ast; Bin Wang, Lei He, Qinghua Zhao, Weizheng Ren Faculty of Hepato-Pancreato-Biliary Surgery, First Medical Center, Chinese PLA General Hospital, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Weizheng Ren; Qinghua Zhao, Faculty of Hepato-Pancreato-Biliary Surgery, First Medical Center, Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing, 100853, People’s Republic of China, Email rwz301@163.com; zhaoqinghuabj@163.comPurpose: In this paper, we observed the use of contezolid in patients with complex intra-abdominal infections in the intensive care unit of the Hepatobiliary Surgery department at the Chinese PLA General Hospital.Patients and Methods: The study collected data on complex intra-abdominal infections patients who received the antibiotic contezolid between January 2022 and April 2023.Results: Contezolid was administered to 12 patients, including 8 with severe acute pancreatitis, 3 with intra-abdominal infections following abdominal surgery, and 1 with complicated intra-abdominal infection after trauma. Gram-positive bacteria, such as Enterococcus faecium, Enterococcus casseliflavus, Staphylococcus capitis, and Staphylococcus haemo-lytica, were detected in 11 patients. All patients who received contezolid had previously been treated with other anti-Gram-positive agents, including linezolid for 9 patients, teicoplanin for 6 patients, and vancomycin for 3 patients. The treatment with contezolid began 20.0 (15.0, 34.5) days after admission and lasted for 8.0 (6.0, 10.0) days. At the end of the treatment, the patients’ body temperature showed a significant decrease. After concomitant therapy, IL-6 levels decreased, and platelet count increased.Conclusion: Contezolid has shown potential in treating complex intra-abdominal infections caused by Gram-positive bacteria by reducing fever and inflammatory response.Keywords: intra-abdominal infection, contezolid, multiple drug-resistant bacteria, gram-positive bacteria

Kun Li,1 Ahmad Alhaskawi,2 Haiyin Zhou,2 Yanzhao Dong,2 QingFang Zhao,3 Chenxi Wang,4 Hui Lu2 1Department of Critical Care Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, People’s Republic of China; 2Department of Orthopaedics, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, People’s Republic of China; 3Department of Plastic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, People’s Republic of China; 4Medical Department, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, People’s Republic of ChinaCorrespondence: Kun Li, Department of Critical Care Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, No. 79, Qingchun Road, Shangcheng District, Hangzhou, Zhejiang, People’s Republic of China, Email Likicu@zju.edu.cn Hui Lu, Department of Orthopaedics, The First Affiliated Hospital, Zhejiang University School of Medicine, No.79, Qingchun Road, Shangcheng District, Hangzhou, Zhejiang Province, People’s Republic of China, Email HuiLu@zju.edu.cnObjective: This retrospective study examines risk factors and electromyographic (EMG) characteristics associated with acquired weakness in critically ill patients and assesses their impact on patient prognosis.Methods: Ninety-seven critically ill patients, ventilated for over 48 hours, were included. Patient data, encompassing general condition, medical history, Medical Research Council (MRC) scores, serum markers (c-reactive protein, calcitonin gene, albumin, brain natriuretic peptide, urea nitrogen, creatinine), EMG characteristics, respiratory treatment modalities, and parameters, were recorded. Mechanical ventilation duration, ICU stay duration, hospitalization duration, and patient prognosis were documented. Based on MRC scores, patients were categorized into the ICU-acquired weakness (ICU-AW) group (MRC < 48 points) and the non-ICU-AW group (MRC ≥ 48 points).Results: The study comprised 47 ICU-AW and 50 non-ICU-AW patients. Significant differences (p < 0.05) were observed in age, MRC scores, albumin levels, c-reactive protein, calcitonin gene, brain natriuretic peptide, urea nitrogen, creatinine, mechanical ventilation duration, ICU stay duration, and hospitalization duration between groups. In the ICU-AW group, nerve conduction examinations revealed slow conduction velocity, reduced wave amplitude, and in severe cases, a complete loss of motor and sensory potentials. Multivariate logistic analysis identified low serum albumin levels and MRC scores as potential ICU-AW risk factors.Conclusion: This study suggests that low serum albumin levels and MRC scores may contribute to ICU-AW risk. The ICU-AW group exhibited varied peripheral nerve damage and slow conduction velocities on EMG. Additionally, severe systemic inflammatory responses, renal function, brain natriuretic peptide levels, prolonged mechanical ventilation, and peripheral nerve damage may be associated with ICU-AW. Follow-up studies are essential for further understanding these complex interactions.Keywords: ICU-acquired weakness, risk factor, critical care, therapy, respiratory failure, electromyography

Pingyu An,1 Qiyue Zhao,2 Siyu Hao,3 Xiaodong Wang,4 Jiangtian Tian,5,6 Zhiqiang Ma3 1Basic Medical College, Harbin Medical University, Harbin, People’s Republic of China; 2School of Nursing, Southern Medical University, Guangzhou, People’s Republic of China; 3Department of Dermatology, the Second Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China; 4Department of Ultrasound, Harbin Medical University Cancer Hospital, Harbin, People’s Republic of China; 5Department of Cardiology, the Second Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China; 6The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, People’s Republic of ChinaCorrespondence: Zhiqiang Ma, Department of Dermatology, The Second Affiliated Hospital of Harbin Medical University, No. 246, Xuefu Road, Nangang District, Harbin, 150081, People’s Republic of China, Tel +86 18845139619, Email zhiqiangma@hrbmu.edu.cnAbstract: Psoriasis is an immune-mediated inflammatory skin disease where topical therapy is crucial. While various dosage forms have enhanced the efficacy of current treatments, their limited permeability and lack of targeted delivery to the dermis and epidermis remain challenges. We reviewed the evolution of topical therapies for psoriasis and conducted a bibliometric analysis from 1993 to 2023 using a predictive linear regression model. This included a comprehensive statistical and visual evaluation of each model’s validity, literature profiles, citation patterns, and collaborations, assessing R variance and mean squared error (MSE). Furthermore, we detailed the structural features and penetration pathways of emerging drug delivery systems for topical treatment, such as lipid-based, polymer-based, metallic nanocarriers, and nanocrystals, highlighting their advantages. This systematic overview indicates that future research should focus on developing novel drug delivery systems characterized by enhanced stability, biocompatibility, and drug-carrying capacity.Keywords: psoriasis, bibliometric, drug delivery, topical treatment, nanoparticle, nanocarriers

Fengxing Huang,1,2,&ast; Youwei Wang,1,2,&ast; Yu Shao,1,2,&ast; Runan Zhang,1,2 Mengting Li,1,2 Lan Liu,1,2,&ast; Qiu Zhao1,2,&ast; 1Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, People’s Republic of China; 2Hubei Clinical Center and Key Laboratory of Intestinal and Colorectal Diseases, Wuhan, 430071, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lan Liu; Qiu Zhao, Email lliugi@whu.edu.cn; qiuzhao@whu.edu.cnIntroduction: Immune cell interactions and metabolic changes are crucial in determining the tumor microenvironment and affecting various clinical outcomes. However, the clinical significance of metabolism evolution of immune cell evolution in colorectal cancer (CRC) remains unexplored.Methods: Single-cell RNA sequencing (scRNA-seq) and bulk RNA sequencing data were acquired from TCGA and GEO datasets. For the analysis of macrophage differentiation trajectories, we employed the R packages Seurat and Monocle. Consensus clustering was further applied to identify the molecular classification. Immunohistochemical results from AOM and AOM/DSS models were used to validate macrophage expression. Subsequently, GSEA, ESTIMATE scores, prognosis, clinical characteristics, mutational burden, immune cell infiltration, and the variance in gene expression among different clusters were compared. We constructed a prognostic model and nomograms based on metabolic gene signatures identified through the MEGENA framework.Results: We found two heterogeneous groups of M2 macrophages with various clinical outcomes through the evolutionary process. The prognosis of Cluster 2 was poorer. Further investigation showed that Cluster 2 constituted a metabolically active group while Cluster 1 was comparatively metabolically inert. Metabolic variations in M2 macrophages during tumor development are related to tumor prognosis. Additionally, Cluster 2 showed the most pronounced genomic instability and had highly elevated metabolic pathways, notably those associated with the ECM. We identified eight metabolic genes (PRELP, NOTCH3, CNOT6, ASRGL1, SRSF1, PSMD4, RPL31, and CNOT7) to build a predictive model validated in CRC datasets. Then, a nomogram based on the M2 risk score improved predictive performance. Furthermore, our study demonstrated that immune checkpoint inhibitor therapy may benefit patients with low-risk.Discussion: Our research reveals underlying relationships between metabolic phenotypes and immunological profiles and suggests a unique M2 classification technique for CRC. The identified gene signatures may be key factors linking immunity and tumor metabolism, warranting further investigations. Keywords: CRC, macrophages, metabolic classification, tumor immunity, prognosis model

Yiyue Xu,1,&ast; Haoqian Li,1,&ast; Xiaoqing Wang,2 Butuo Li,1 Aiqin Gao,1 Qian Zhao,1 Linlin Yang,1 Wenru Qin,1 Linlin Wang1 1Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, People’s Republic of China; 2Department of Portal Hypertension, Shandong Public Health Clinical Center, Shandong University, Jinan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Linlin Wang, Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, 440 JiYan Road, Jinan, 250117, People’s Republic of China, Tel +86-13793187739, Email wanglinlinatjn@163.comBackground: COVID-19 has spread worldwide, becoming a global threat to public health and can lead to complications, especially pneumonia, which can be life-threatening. However, in lung cancer patients, the prediction of pneumonia and severe pneumonia has not been studied. We aimed to develop effective models to assess pneumonia after SARS-CoV-2 infection in lung cancer patients to guide COVID-19 management.Methods: We retrospectively recruited 621 lung cancer patients diagnosed with COVID-19 via SARS-CoV-2 RT-PCR analysis in two medical centers and divided into training and validation group, respectively. Univariate and multivariate logistic regression analysis were used to identify independent risk factors of all-grade pneumonia and ≥ grade 2 pneumonia in the training group. Nomograms were established based on independent predictors and verified in the validation group. C-index, ROC curves, calibration curve, and DCA were used to evaluate the nomograms. Subgroup analyses in immunotherapy or thoracic radiotherapy patients were then conducted.Results: Among 621 lung cancer patients infected with SARS-CoV-2, 203 (32.7%) developed pneumonia, and 66 (10.6%) were ≥ grade 2. Multivariate logistic regression analysis showed that diabetes, thoracic radiotherapy, low platelet and low albumin at diagnosis of COVID-19 were significantly associated with all-grade pneumonia. The C-indices of the prediction nomograms in the training group and validation group were 0.702 and 0.673, respectively. Independent predictors of ≥ grade 2 pneumonia were age, KPS, thoracic radiotherapy, platelet and albumin at COVID 19 diagnosis, with C-indices of 0.811 and 0.799 in the training and validation groups. In the thoracic radiotherapy subgroup, 40.8% and 11% patients developed all-grade and ≥grade 2 pneumonia, respectively. The rates in the immunotherapy subgroup were 31.3% and 6.6%, respectively.Conclusion: We developed nomograms predicting the probability of pneumonia in lung cancer patients infected with SARS-CoV-2. The models showed good performance and can be used in the clinical management of COVID-19 in lung cancer patients. Higher-risk patients should be managed with enhanced protective measures and appropriate intervention.Keywords: COVID-19, pneumonia, lung cancer, risk factor, nomogram

XiaoLang Miao,1 Yanxia Han,1 Zhenyun Wu,1 Xiaoliang Jin,1 Mei’e Niu,1 Qian Zhao,1 Xiangmin Lu2 1Department of Respiratory Medicine, First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 2School of Nursing, Soochow University, Suzhou, People’s Republic of ChinaCorrespondence: Mei’e Niu, Department of Respiratory Medicine, The First Affiliated Hospital of Soochow University, 899th, Pinghai Road, Suzhou, 215006, People’s Republic of China, Tel +86 13812671786, Email meniu_123@163.comPurpose: To translate a disease-specific anxiety questionnaire on chronic obstructive pulmonary disease (COPD) and test its reliability and validity in China.Patients and Methods: The German version of the revised COPD Anxiety Questionnaire (CAF-R) was initially validated using step-by-step translation, back-translation, and cross-cultural adaptation. The reliability and validity of the Chinese version of the CAF-R (CAF-R-CN) were tested among 448 patients with COPD (mean age =71.42± 9.33 years, 17.2% female) from four medical institutions in Suzhou, Jiangsu Province, using convenience sampling, from April 2022 to June 2023.Results: The CAF-R-CN included six dimensions with a total of 25 items. The item-level content validity index was 0.860– 1.000; the scale-level content validity index was 0.920. The structural validity χ2/df was 2.326, the root mean square error of approximation was 0.077, the comparative fit index was 0.924, and the Tucker–Lewis index was 0.912. The six-dimensional internal consistency index Cronbach’s α coefficient was 0.696– 0.910, and the test–retest reliability was 0.949. An optimal cut-off score of 50.5 was selected with a sensitivity of 0.786 and specificity of 0.870.Conclusion: The CAF-R-CN had satisfactory reliability and validity and can be used to identify and assess anxiety in COPD patients with a Chinese cultural background.Keywords: fear, scale, specificity, chronic respiratory disease, Chinese translation, assessment

Guoquan Chen,1,&ast; Jiale Chen,1,&ast; Qiang Zhao,2 Yalan Zhu1 1Department of Pharmacy, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, 321000, People’s Republic of China; 2Department of Cardiology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, 321000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yalan Zhu, Department of Pharmacy, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, 321000, People’s Republic of China, Tel +86-0579-82552760, Email zhuyalan2013@163.comObjective: Atrial fibrillation (AF) is the most common abnormal heart rhythm in elderly patients. Rivaroxaban has been widely used for stroke prevention. The anticoagulant response to rivaroxaban increases with age, which may make elderly patients susceptible to adverse outcomes resulting from small differences in bioavailability between generic and brand products.Methods: We designed a cohort study of ≥ 65-year-old inpatients with AF. Sociodemographic and laboratory measures of qualified patients who received brand or generic rivaroxaban for at least 72 hours at the study hospital from January 2021 to June 2023 were collected retrospectively. The primary outcome was the incidence of bleeding.Results: A total of 1008 qualifying patients were included for analysis, with 626 (62.1%) receiving brand rivaroxaban and 382 (37.9%) receiving generic rivaroxaban. After propensity score matching and weighting to account for confounders, the odds ratios comparing brand vs generic rivaroxaban (95% confidence intervals) for the bleeding was 1.15 (0.72– 1.82). Results from subgroup analyses of patients with age ≥ 85, HAS-BLED score ≥ 3, containment of antiplatelet drugs, and female patients were consistent with the primary analysis.Conclusion: It provides evidence regarding the clinical safety outcome of generic rivaroxaban in the elderly AF population that may be particularly susceptible to adverse outcomes resulting from small allowable differences in pharmacokinetics.Keywords: bleeding, rivaroxaban, generic, brand, atrial fibrillation

Yudong Miao,1 Ruizhe Ren,1 Zhanlei Shen,1 Yi Li,1 Wanliang Zhang,1 Junwen Bai,1 Dongfang Zhu,1 Jingbao Zhang,1 Dan Guo,1,2 Clifford Silver Tarimo,3 Rongmei Liu,4 Qiuping Zhao,4 Jianping Hu,5 Xue Zhou,6 Wenyong Dong7 1College of Public Health, Zhengzhou University, Zhengzhou, People’s Republic of China; 2Department of Neurology, Henan Provincial People’s Hospital, Zhengzhou, People’s Republic of China; 3Department of Science and Laboratory Technology, Dar es Salaam Institute of Technology, Dar es Salaam, Tanzania; 4Henan Key Laboratory for Health Management of Chronic Diseases, Central China Fuwai Hospital, Zhengzhou, People’s Republic of China; 5Henan Medical Communication and Project Forward Center, Zhengzhou, People’s Republic of China; 6College of Health Management, Mudanjiang Medical University, Mudanjiang, People’s Republic of China; 7Department of Hypertension, Henan Provincial People’s Hospital, Zhengzhou, People’s Republic of ChinaCorrespondence: Rongmei Liu, Assistant research fellow. Fuwai Central China Cardiovascular Hospital, Zhengzhou University Affiliated Central China Fuwai Hospital, &num;1, Fuwai Avenue, Zhengdong New District, Zhengzhou, 450014, People’s Republic of China, Tel +8615038204525, Email liuyongmei0203@163.comObjective: To evaluate the prevalence and influencing factors of long COVID, and measure the difference in health status between long COVID and non-long COVID cases.Methods: A cross-sectional survey was conducted from February 1 to 8, 2023, using a stratified random sampling method in four regions (eastern [Changzhou], central [Zhengzhou], western [Xining] and northeastern [Mudanjiang]) of China. The survey collected COVID-19 patients’ socio-demographic characteristics and lifestyles information. The scores of lifestyles and health status range from 5 to 21 and 0 to 100 points, respectively. The criteria of “persistent health problems after 4 weeks of COVID-19 infection” issued by the US Centers for Disease Control and Prevention was used to assess long COVID. Multiple linear regression was used to analyze the influencing factors of the health. The bootstrap method was used to analyze the lifestyles’ mediating effect. Propensity score matching (PSM) was used to evaluate the net difference in health scores between long COVID and non-long COVID cases.Results: The study included 3165 COVID-19 patients, with 308 (9.73%) long COVID cases. The health score of the long COVID cases (74.79) was lower than that of the non-long COVID cases (81.06). After adjusting for potential confounding variables, we found that never focused on mental decompression was a common risk factor for the health of both groups. Lifestyles was the mediating factor on individuals’ health. After PSM, the non-long COVID cases’ health scores remained higher than that of long COVID cases.Conclusion: The proportion of long COVID cases was low, but they were worse off in health. Given the positive moderating effect of healthy lifestyles on improving the health of long COVID cases, healthy lifestyles including mental decompression should be considered as the core strategy of primary prevention when the epidemic of COVID-19 is still at a low level.Keywords: long COVID, lifestyles, self-reported health status, propensity score matching, effect of mediation

Ran Sang,1,2 Manxue Jiang,1,2 Qiuju Zhao,2 Lingti Kong1,2 1Department of Pharmacy, The First Affiliated Hospital of Bengbu Medical University, Bengbu, 233004, People’s Republic of China; 2School of Pharmacy, Bengbu Medical University, Bengbu, 233030, People’s Republic of ChinaCorrespondence: Lingti Kong, Department of Pharmacy, The First Affiliated Hospital of Bengbu Medical University, 287 Changhuai Road, Longzihu District, Bengbu, Anhui, 233004, People’s Republic of China, Tel +865523086297, Email konglingtiklt7@126.comBackground: The excessive use of intravenous infusion in China was once a serious problem, but in recent years, attention has been paid to the phenomenon, and the government has implemented several policies to solve the problem, which has been gradually improved.Aim: This study focuses on evaluating the impact of ongoing interventions and improvements in outpatient intravenous infusion therapy.Methods: From January 2016 to December 2022, we conducted a study to gather annual data on intravenous infusion prescriptions. A data questionnaire, encompassing information on departments, clinical diagnosis, and infusion drugs, was developed for this purpose. We analyzed the changing trends of Top 10 clinical departments with higher intravenous infusion usage rates and Top 10 drugs used. We also evaluated the compliance of intravenous infusion prescriptions with management regulations and drug instructions, for further intervention in the future.Results: The analysis of intravenous infusion prescription rates revealed a gradual decrease from 10.89% to 5.63%. This reduction was statistically significant (P < 0.05). High levels of intravenous infusion use were consistently observed in emergency surgery and emergency medicine. Commonly administered drugs via infusion included antibacterial drugs, tumor medications, proton pump inhibitors, and injections of traditional Chinese medicine. Inappropriate prescriptions are often characterized by issues related to drug dosage, usage, indication, and selection. Trend analysis of unreasonable types revealed significant improvements in “Diagnosis incomplete/unwritten”, “Solvent selection”, “Dosing frequency”, and “Treatment without indication” (P < 0.05).Conclusion: The findings of this study indicate a gradual improvement in the situation regarding intravenous infusion. However, there are still prevalent instances of unreasonable practices that need to be addressed.Keywords: cross-sectional study, evaluation, analysis, intravenous infusion prescriptions, outpatient

Luyang Gao,&ast; Sicheng Zhang,&ast; Zhihui Zhao, Qing Zhao, Tao Yang, Qixian Zeng, Yi Zhang, Xin Li, Zhihua Huang, Anqi Duan, Qin Luo, Zhihong Liu Center for Respiratory and Pulmonary Vascular Diseases, Fuwai Hospital, National Center for Cardiovascular Diseases, National Clinical Research Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhihong Liu; Qin Luo, Center for Respiratory and Pulmonary Vascular Diseases, Fuwai Hospital, National Center for Cardiovascular Diseases, National Clinical Research Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 167 Beilishi Road, Xicheng District, Beijing, 100037, People’s Republic of China, Tel/Fax +86-010-88396589, Email zhihongliufuwai@163.com; luoqin2009@163.comIntroduction: Mounting evidence indicates a possible connection between the systemic inflammatory response index (SIRI) and the prognosis of heart failure, but its role in idiopathic pulmonary arterial hypertension (IPAH) is not well understood. This study aimed to investigate the relationship between SIRI and variables such as functional ability, echocardiography results, hemodynamic measurements, and long-term outcomes in patients with IPAH.Methods: The study included 426 consecutive IPAH patients who underwent right heart catheterization at Fuwai Hospital from January 2013 to December 2020. SIRI was calculated using composite inflammation indicators from routine blood tests. The main outcome measure was clinical deterioration. Spearman correlation coefficients were used to assess associations between SIRI and indicators of IPAH severity. Receiver operating characteristic (ROC) curve analysis was conducted to determine the optimal SIRI threshold and predictive ability. Kaplan-Meier analysis and Cox proportional hazard models were used to examine the relationship between SIRI and clinical deterioration.Results: SIRI showed positive associations with indicators such as N-terminal pro-brain natriuretic peptide, right ventricular end-diastolic diameter, pericardial effusion, mean pulmonary arterial pressure, and pulmonary vascular resistance. Conversely, SIRI had inverse relationships with 6-minute walking distance and left ventricular end-diastolic diameter. Kaplan-Meier curves revealed a significantly higher rate of clinical deterioration in individuals with SIRI > 0.741 compared to those with SIRI ≤ 0.741 (P < 0.001). Adjusted Cox analysis showed SIRI remained an independent predictor of clinical worsening (hazard ratio 1.366, 95% confidence interval 1.073– 1.738, P = 0.011). ROC analysis demonstrated SIRI provided additional predictive value beyond the risk assessment score of the European Society of Cardiology/European Respiratory Society.Discussion: In summary, SIRI could predict the severity and prognosis of IPAH independently. It was associated with various indicators of IPAH severity and was a significant predictor of clinical deterioration. SIRI also offered additional predictive value beyond existing risk assessment scores.Keywords: prognosis, pulmonary arterial hypertension, risk factor, systemic inflammatory response index

Youli Jiang, Yao Xiong, Yue Chi, Fu Lin, Qingshi Zhao, Yanfeng Li Department of Neurology, People’s Hospital of Longhua, Shenzhen, 518109, People’s Republic of ChinaCorrespondence: Qingshi Zhao; Yanfeng Li, Email 66327285@qq.com; 308114251@qq.comPurpose: Timely medical attention is crucial for patients with Acute Ischemic Stroke (AIS), as delays can significantly impact therapeutic outcomes. These delays are influenced by a combination of socio-cultural, educational, and clinical factors.Patients and Methods: An in-depth analysis was conducted to assess the prevalence and median duration of healthcare-seeking delays in AIS patients. The study specifically investigated the independent impacts of sociocultural and clinical determinants on these delays, with a focus on immigrant status, gender disparities, and educational levels. Multivariate regression analysis was employed to identify these independent effects while controlling for potential confounding factors.Results: Among 1419 AIS patients, 82.52% (n = 1171) experienced delays exceeding 2 hours from symptom onset of symptoms to hospital arrival. The median delay was 12.3 hours. Immigrant populations encountering longer delays compared to native groups. Younger males (< 45 years) and elderly females were more prone to delay in healthcare-seeking. Identified independent risk factors for delay included male gender (OR = 1.65 [95% CI:1.14− 2.48]), self-acknowledged diabetes (OR = 2.50 [95% CI:1.21– 5.17]), small vessel (OR = 2.07 [95% CI:1.27– 3.36]), and wake stroke (OR = 7.04 [95% CI:3.69– 13.44]). Educational background (high school and above), GCS score with 3– 8 points (OR = 0.52 [95% CI:0.09– 0.69]), understanding stroke-related knowledge (OR = 0.26 [95% CI:0.09– 0.44]), conscious disturbance (OR = 0.25 [95% CI:0.10– 0.62]) and limb weakness (OR=0.21[95% CI:0.21– 0.49]) are protective factors for timely treatment.Conclusion: Immigrant populations experienced longer delays from symptom onset to hospital arrival. The crucial roles of education and knowledge about stroke underscore the need for enhanced health literacy campaigns and public awareness, with a targeted focus on younger males and elderly females.Keywords: healthcare-seeking behavior, immigrant population, educational disparity, pre-hospital delay, AIS

Shan-Mei Liu,1,&ast; Qin Zhao,1,&ast; Wen-Jun Li,2 Jian-Quan Zhao1 1Bayannur Hospital Department of Cardiology, Bayannur City, Inner Mongolia, 015000, People’s Republic of China; 2Tangshan Central Hospital, Tangshan, Hebei, 063008, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jian-Quan Zhao, Tel +13947818787, Email 1036908013@qq.comAbstract: Cardiovascular diseases represent a global health crisis, and understanding the intricate molecular mechanisms underlying cardiac pathology is crucial for developing effective diagnostic and therapeutic strategies. Mitsugumin-53 (MG53) plays a pivotal role in cell membrane repair, has emerged as a multifaceted player in cardiovascular health. MG53, also known as TRIM72, is primarily expressed in cardiac and skeletal muscle and actively participates in membrane repair processes essential for maintaining cardiomyocyte viability. It promotes k-ion currents, ensuring action potential integrity, and actively engages in repairing myocardial and mitochondrial membranes, preserving cardiac function in the face of oxidative stress. This study discusses the dual impact of MG53 on cardiac health, highlighting its cardioprotective role during ischemia/reperfusion injury, its modulation of cardiac arrhythmias, and its influence on cardiomyopathy. MG53’s regulation of metabolic pathways, such as lipid metabolism, underlines its role in diabetic cardiomyopathy, while its potential to mitigate the effects of various cardiac disorders, including those induced by antipsychotic medications and alcohol consumption, warrants further exploration. Furthermore, we examine MG53’s diagnostic potential as a biomarker for cardiac injury. Research has shown that MG53 levels correlate with cardiomyocyte damage and may predict major adverse cardiovascular events, highlighting its value as a biomarker. Additionally, exogenous recombinant human MG53 (rhMG53) emerges as a promising therapeutic option, demonstrating its ability to reduce infarct size, inhibit apoptosis, and attenuate fibrotic responses. In summary, MG53’s diagnostic and therapeutic potential in cardiovascular diseases presents an exciting avenue for improved patient care and outcomes.Keywords: Mitsugumin-53, MG53, cardiovascular disease, cell membrane repair, ischemia/reperfusion

Jincheng Guan,1 Qiong Wang,2 Qingshi Zhao1 1Department of Neurology, People’s Hospital of Longhua, Shenzhen, People’s Republic of China; 2Department of Neurology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of ChinaCorrespondence: Qingshi Zhao, Department of Neurology, People’s Hospital of Longhua, 38 Jinglong Construction Road, Shenzhen, 518109, People’s Republic of China, Email zhaoqingshi1978@163.comBackground and Purpose: Acute ischemic stroke (AIS) caused by large artery occlusion (LAO) poses considerable risks in terms of mortality and disability. Endovascular treatment (EVT) has emerged as a primary intervention for this condition. However, the occurrence of futile recanalization (FR) following EVT remains common, necessitating the identification of predictive markers for treatment outcomes. Although the lymphocyte to monocyte ratio (LMR) has been linked to various diseases, its association with FR after EVT in AIS patients has not been investigated.Methods: An analysis was conducted on patients with AIS who underwent EVT within 24 hours of symptom onset. The success of reperfusion was evaluated using the modified Thrombolysis in Cerebral Infarction (mTICI) scale, with patients achieving an mTICI score of ≥ 2b being included in the study. Various clinical, radiological, and laboratory variables, including lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR), were collected. Logistic regression analysis was used to determine factors associated with FR, and receiver operating characteristic (ROC) analysis was performed to assess the predictive value of LMR.Results: Among the cohort of 101 patients, it was observed that 52.4% experienced FR. Upon admission, lower levels of lymphocyte-to-monocyte ratio (LMR) were found to be associated with older age, higher baseline NIHSS scores, lower ASPECTS, and poorer mRS scores at 90 days. Both univariate and multivariate logistic regression analyses indicated that low LMR independently predicted FR, with an adjusted odds ratio of 0.64 (95% CI = 0.412– 0.984, p = 0.042). ROC analysis further demonstrated that LMR had an area under the curve (AUC) of 0.789 for predicting FR.Conclusion: This study establishes the potential value of the lymphocyte-to-monocyte ratio (LMR) as a prognostic marker for predicting FR in patients with AIS undergoing EVT. Decreased LMR levels are associated with unfavorable clinical outcomes.Keywords: acute ischemic stroke, large artery occlusion, endovascular therapy, lymphocyte-to-monocyte ratio, futile recanalization, prognostic marker, inflammation, treatment outcomes

Dongyan Chai,1,2,&ast; Zhihui Liu,3,&ast; Liuyi Wang,3 Hongyan Duan,2,3 Chenglong Zhao,1 Chengyang Xu,2 Dongyan Zhang,1 Qiongrui Zhao,4 Peizhi Ma1 1Department of Pharmacy, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, Henan University People’s Hospital, Zhengzhou, Henan People’s Republic of China; 2International Medical Center of Henan Province, Henan Provincial People’s Hospital, Zhengzhou, Henan, People’s Republic of China; 3Department of General Practice, Henan Provincial People’s Hospital, Zhengzhou, Henan, People’s Republic of China; 4Department of Clinical Research Service Center, Henan Provincial People’s Hospital, Zhengzhou, Henan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Peizhi Ma, Department of Pharmacy, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, Henan University People’s Hospital, Weiwu Road 7, Zhengzhou, Henan, People’s Republic of China, Tel +86 18538298188, Fax +86 037165580803, Email ma18539298188@163.comBackground: Implementing medication reconciliation (MR) was complex and challenging because of the variability in the guidance provided for conducting. The processes of MR adopted in China were different from that recommended by the World Health Organization. A pilot study to inform the design of a future randomized controlled trial to determine the effectiveness of these two workflows was undertaken.Methods: Patients taking at least one home/regular medication for hypertension, diabetes, or coronary heart disease were recruited at admission, and then were randomized using a computer-generated random number in a closed envelope. In the study group, the pharmacist reviewed electronic medical record systems before communication with patients. In the control group, pharmacists communicated with patients at patient’s admission. The time investment of pharmacists for MR process, the number of unintended medication discrepancies, and physician acceptance were tested as outcome measures.Results: One hundred and forty adult patients were randomized, of which 66 patients in the intervention received MR within 24 hours, while 58 patients in control received MR at some point during admission. The most common condition in the study group was hypertension (coronary heart disease in the control group). The workflow of the study group can save an average 7 minutes per patient compared with the WHO recommended process [17.5 minutes (IQR 14.00, 28.25) vs 24.5 minutes (IQR17.75, 35.25), p = 0.004]. The number of unintended discrepancies was 42 in the study group and 34 in the control group (p = 0.33). Physicians’ acceptance in the study and control groups were 87.5% and 92.3%, respectively (p = 0.87).Conclusion: The results suggest that changes in outcome measures were in the appropriate direction and that the time limit for implementing MR can be set within 48 hours. A future multi-centre RCT study to determine the effectiveness of MR is feasible and warranted.Keywords: medication reconciliation, workflow, prospective studies, pharmacist, randomized controlled trial

Jun Wang,1,&ast; Hongmei Chen,2,&ast; Lin Yang,2 Xiuli Yu,3 Dandan Zhang,3 Qinghua Zhao,1 Mingzhao Xiao4 1Department of Nursing, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Department of Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 3Qinggang Senior Care Center, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 4Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mingzhao Xiao, Department of Urology, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Chongqing, 400016, People’s Republic of China, Tel +8613608399433, Fax +86-23-89012206, Email mingzhaoxiao@cqmu.edu.cnAbstract: This paper aims to describe a randomized controlled trial protocol evaluating the effectiveness, cost, and process of a stress process model-based program in dementia caregiving (DeCare-SPM) for family caregivers. Family caregivers of individuals with dementia will be recruited from memory clinics and community settings and randomly assigned to either DeCare-SPM or usual care. DeCare-SPM comprises three face-to-face sessions (ie, problem-based coping, emotion-based coping, meaning-based coping), and a fourth session (ie, social support) including weekly telephone-based consultation for four weeks and then monthly face-to-face boosters. Outcomes will be measured at baseline (T0), and at one (T1), three (T2), and six months (T3). The primary outcome is positive aspects of caregiving and secondary outcomes are caregiving (ie, sense of competence, caregiver burden, social support, anxiety, depression, and quality of life), dementia-related (ie, care dependency, neuropsychiatric symptoms, and quality of life), and stress-related biomarkers of blood and saliva. In addition, process and economic evaluations will be performed. Mixed-effects models will be used to assess intervention effects. Content analysis will be performed on the qualitative data. This paper described the protocol for comprehensive evaluation of the effectiveness, cost, and process of the theory-driven DeCare-SPM to inform how and why interventions work. It highlights the need to reduce challenges and enhance the positive aspects of dementia care. The DeCare-SPM will provide evidence-based insights into how to support and empower family caregivers in their important roles, thereby, leading to improved dementia care.Keywords: Alzheimer’s disease, stress coping, informal caregivers, community, psychosocial

Xuejun Tan,1 Yukun Xu,1 Sirui Zhou,1 Mingyue Pan,1 Yue Cao,1 Xiuping Cai,2 Qing Zhao,1,2,&ast; Kewei Zhao1,2,&ast; 1The Third Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 2Guangzhou Key Laboratory of Chinese Medicine Research on Prevention and Treatment of Osteoporosis, The Third Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Kewei Zhao; Qing Zhao, Department of Laboratory Medicine, The Third Affiliated Hospital of Guangzhou University of Chinese Medicine, 261 Longxi Avenue, Liwan District, Guangzhou, Guangdong, People’s Republic of China, Tel +86-13711355225 ; +86-18825144487, Email zkw2011@gzucm.edu.cn; zhaoqing900116@126.comAbstract: All humans are universally affected by inflammatory diseases, and there is an urgent need to identify new anti-inflammatory drugs with good therapeutic benefits and minimal side effects to the organism. Recently, it has been found that plant-derived vesicle-like nanoparticles (PDVLNs) have good biocompatibility, with their active ingredients exhibiting good therapeutic effects on inflammation. They can also be used as drug carriers for targeted delivery of anti-inflammatory drugs. Therefore, PDVLNs represent a popular research area for novel anti-inflammatory drugs. This paper details the origin, biological functions, isolation and purification, and identification of PDVLNs, as well as the therapeutic effects of their intrinsic bioactive components on inflammatory diseases. It also introduces their targets as drug carriers to facilitate the development and application of PDVLNs anti-inflammatory drugs.Keywords: plant, vesicle-like nanoparticles, inflammation, inflammatory diseases

Wan Miao, Jinlin Guo, Huifang Cheng, Qianqian Zhao Department of Pharmacy, Shanxi Provincial People’s Hospital, Taiyuan, Shanxi Province, People’s Republic of ChinaCorrespondence: Jinlin Guo, Department of Pharmacy, Shanxi Provincial People’s Hospital, Shuangtasi Street 59&num;, Taiyuan, Shanxi, 030001, People’s Republic of China, Fax +86-351-4960527, Email taiggll@foxmail.comPurpose: Cefoperazone/sulbactam is a β-lactam/β-lactamase inhibitor combination effective against intra-abdominal, urinary tract, and respiratory infections. Although some studies have suggested that cefoperazone/sulbactam is associated with coagulation disorders, it remains debatable whether the combination of cefoperazone/sulbactam with tigecycline or valproic acid increases the risk of bleeding, as both drugs can lead to coagulation disorders. This study aimed to explore the risk factors of cefoperazone/sulbactam-induced coagulopathy.Patients and Methods: This was a single-center, retrospective, nested case-control study. The sample groups were derived from individuals registered at the Department of Neurosurgery, Shanxi Provincial People’s Hospital. Propensity score matching (PSM) was used to adjust for demographic data. Conditional logistic regression was used to estimate the matched odds ratios representing the odds of cefoperazone/sulbactam-induced coagulopathy (CIC), and a receiver operating characteristic curve was used to determine the optimal cut-off conditions.Results: After PSM, 155 and 56 patients were included in the control and case groups, respectively. Multivariate analysis revealed that advanced age, treatment duration, and total dose were independent risk factors of cefoperazone/sulbactam-induced coagulation disorders. Concomitant use of vitamin K was an independent protective factor against CIC. The optimal cut-off for the length of treatment was 5 d, and the cut-off for the total dose was 48 g.Conclusion: Tigecycline and valproic acid were not associated with CIC. Advanced age and long treatment duration are risk factors for CIC. Supplementation with vitamin K during cefoperazone/sulbactam treatment was associated with a reduced risk.Keywords: cefoperazone/sulbactam, coagulopathy, tigecycline, valproic acid

Zhihua Huang,&ast; Anqi Duan,&ast; Zhihui Zhao, Qing Zhao, Yi Zhang, Xin Li, Sicheng Zhang, Luyang Gao, Chenhong An, Qin Luo, Zhihong Liu Center for Respiratory and Pulmonary Vascular Diseases, Department of Cardiology, Fuwai Hospital, National Clinical Research Center for Cardiovascular Diseases, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qin Luo; Zhihong Liu, Center for Respiratory and Pulmonary Vascular Diseases, Department of Cardiology, Fuwai Hospital, National Clinical Research Center for Cardiovascular Diseases, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 167 Beilishi Road, Xicheng District, Beijing, 100037, People’s Republic of China, Tel +86 010 8832859, Email luoqin2009@163.com; zhihongliufuwai@163.comPurpose: Acute pulmonary embolism (PE) poses a life-threatening risk with high mortality rates. While the coexistence of PE and obstructive sleep apnea (OSA) is gaining recognition, its influence on PE severity and prognosis remains uncertain. This study aims to investigate the associations between OSA and disease severity, as well as outcomes, in patients with acute PE.Patients and Methods: We conducted a retrospective cohort study on patients diagnosed with acute PE who had undergone previous cardiorespiratory polygraphy. OSA severity was assessed using the apnea-hypopnea index (AHI) derived from cardiorespiratory polygraphy. The severity of acute PE was evaluated using the simplified Pulmonary Embolism Severity Index (sPESI) score. Logistic regression analysis was performed to investigate the associations between AHI and the risk of belonging to the sPESI≥ 1 group. Cox regression analysis was used to examine the relationship between AHI and long-term adverse events, defined as a composite of all-cause mortality and non-fatal cardiovascular events.Results: Among 145 acute PE patients (mean age 62.2 years, 49.7% male), 94 (64.8%) had OSA. Patients with OSA had a significantly higher proportion of sPESI≥ 1 (89.4% vs 68.6%, p=0.002) than non-OSA patients. Each unit increase in AHI was associated with a 15% increased risk of severe PE (sPESI≥ 1) (odds ratio: 1.15, 95% CI 1.05– 1.26, p=0.002) after adjusting for confounders. During a median follow-up of 15.2 months, 27 (18.6%) patients experienced adverse events. Increased AHI independently predicted a higher risk of adverse events (hazard ratio: 1.03, 95% CI: 1.00– 1.05, p=0.026), even after adjusting for potential confounders. AHI ≥ 8 events/h was associated with a significantly higher adjusted hazard ratio of 2.56 (95% CI: 1.15– 5.72, p=0.022) for adverse events compared to AHI < 8 events.Conclusion: OSA is common in acute PE patients and is linked to increased disease severity and adverse outcomes. Implementing routine OSA screening and management may aid risk stratification and improve outcomes in acute PE patients.Keywords: sleep apnea, pulmonary embolism, outcomes, prognosis, cardiovascular

Jie Wu,1,2 Guangcun Zhang,3 Qiang Zhao,3 Lifeng Wang,3 Jiyong Yang,3 Junchang Cui1 1Department of Respiratory Diseases, The Eighth Medical Center, Chinese People’s Liberation Army General Hospital, Beijing, People’s Republic of China; 2Medical School of Chinese People’s Liberation Army, Beijing, People’s Republic of China; 3Laboratory Medicine Department, The First Medical Center, Chinese People’s Liberation Army General Hospital, Beijing, People’s Republic of ChinaCorrespondence: Junchang Cui, The Eighth Medical Center, Department of Respiratory Diseases, Chinese People’s Liberation Army General Hospital, No. 17 Heishanhu Road, Haidian District, Beijing, 100091, People’s Republic of China, Tel +86 010 6677 5010, Email guoguoyoumeng@163.comPurpose: To better guide clinical use, we determined the in vitro antimicrobial activity of the new drug eravacycline and other tetracycline derivatives against levofloxacin (LVFX)-non-susceptible and/or trimethoprim-sulfamethoxazole (TMP-SMZ)-resistant Stenotrophomonas maltophilia and evaluated their dosing regimens.Methods: Seventy-seven unique strains of S. maltophilia were isolated from sputa samples and airway aspirate samples that were either LVFX-non-susceptible and/or TMP-SMZ-resistant. Monte Carlo simulations were performed for different dosing regimens according to the population pharmacokinetic parameters of antibiotics in patients with respiratory tract infections at the minimum inhibitory concentration (MIC).Results: Eravacycline had excellent in vitro antibacterial activity against LVFX-non-susceptible and/or TMP-SMZ-resistant S. maltophilia. Monte Carlo simulations showed that for LVFX-non-susceptible strains, the cumulative fraction of response (CFR) of minocycline at the conventional recommended dose of 100 mg q12 h was 90.90%; for TMP-SMZ-resistant strains, the CFR of minocycline at a high dose of 200 mg q12 h was only 91.64%. For strains resistant to both LVFX and TMP-SMZ, the CFR of minocycline at a high dose of 200 mg q12 h was 89.81%. In contrast, the CFR of tigecycline was less than 40%, even at a dose of 100 mg q12 h.Conclusion: For pneumonia, minocycline is better for S. maltophilia that is non-susceptible to LVFX; for TMP-SMZ-resistant strains and strains that are not susceptible to either LVFX or TMP-SMZ, the efficiency of eravacycline requires further evaluation. Eravacycline may be a better choice for extremely resistant S. maltophilia strains that are non-susceptible to LVFX, TMP-SMZ, and minocycline.Keywords: eravacycline, tetracyclines, levofloxacin, trimethoprim, sulfamethoxazole drug combination, Stenotrophomonas maltophilia, Monte Carlo method