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Yan Wang,1– 4,* He Zhao,2– 4,* Kun Zhao,1– 4,* Huhuifen He,1– 4,* Xinyu Li,5 Jingjing Qiu,2– 4 Limei Cui,2– 4 Liang Chen,2– 4 Wenjing Shang,6,7 Yan Sun2– 4 1The Second Medical College, Binzhou Medical University, Yantai, Shandong, People’s Republic of China; 2Department of Otolaryngology and Head and Neck Surgery, Yantai Yuhuangding Hospital, Qingdao University, Yantai, Shandong, People’s Republic of China; 3Shandong Provincial Clinical Research Center for Otorhinolaryngologic Diseases, Yantai, Shandong, People’s Republic of China; 4Yantai Key Laboratory of Otorhinolaryngologic Diseases, Yantai, Shandong, People’s Republic of China; 5The First Medical College, Binzhou Medical University, Yantai, Shandong, People’s Republic of China; 6Key Laboratory for Genetic Hearing Disorders in Shandong, Binzhou Medical University, Yantai, Shandong, 264003, People’s Republic of China; 7Department of Biochemistry and Molecular Biology, Binzhou Medical University, Yantai, Shandong, 264003, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yan Sun; Wenjing Shang, Email entsunyan@126.com; wenjshang@bzmc.edu.cnIntroduction: Age-related hearing loss (ARHL) is a degenerative condition that involves both peripheral and central auditory system pathologies. There is a close relationship between chronic inflammation and ARHL, but there is currently a lack of in-depth exploration of this relationship, particularly regarding causality.Methods: Using age-appropriate mice for basic experiments to examine changes in central auditory nervous system inflammation, a cohort study was conducted to select relevant clinical data and observe inflammation changes in the elderly population with ARHL. Mendelian randomization was employed to investigate the causal relationship between chronic inflammation and ARHL.Results: Clinical results indicate that CRP levels in the ARHL group are significantly higher than those in the normal group. Chronic inflammation also occurs in the auditory centers. Mendelian randomization studies provide causal evidence that genetic chronic inflammation factors do not increase the risk of ARHL.Discussion: This article provides reliable causal evidence of the relationship between chronic inflammation and ARHL, confirming the accumulation of inflammatory factors in the auditory center, which provides a basis for the prevention and treatment of ARHL and has a good prevention prospect. However, due to the differences of research objects, this study has limitations and needs further research.Keywords: CRP, TNF-α, chronic inflammation, age-related hearing loss, Mendelian randomization

Ani Zhao,1,&ast; Yanchun Peng,2,&ast; Baolin Luo,2 Yaqin Chen,1 Liangwan Chen,3,4 Yanjuan Lin2,3 1School of Nursing, Fujian Medical University, Fuzhou, Fujian, People’s Republic of China; 2Department of Nursing, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, 350001, People’s Republic of China; 3Department of Cardiovascular Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, 350001, People’s Republic of China; 4Key Laboratory of Cardio-Thoracic Surgery (Fujian Medical University) Fujian Province University, Fuzhou, Fujian Province, 350001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Liangwan Chen; Yanjuan Lin, Email fjxhlwc@163.com; fjxhyjl@163.comPurpose: Acute Type A aortic dissection (ATAAD) is a rare and life-threatening aortic disease. This study was aimed at the potential of the D-dimer to platelet count ratio (DPR) as a prognostic indicator of ATAAD.Patients and Methods: This study retrospectively analyzed ATAAD patients who were admitted to the Department of Cardiac Surgery, Fujian Medical University Union Hospital from January 2022 to April 2023. Patients were divided into survival (n = 173) and death (n = 24) groups based on whether death occurred. The primary outcome was death, and the secondary outcome was adverse hospitalization, including new postoperative arrhythmias, acute renal insufficiency, acute liver insufficiency, pleural effusion, length of ICU stay, mechanical ventilation length, and length of stay. The logistic regression model was used to analyze the relationship between DPR and in-hospital death, and the receiver operating characteristic curve (ROC) was drawn to analyze the predictive value of DPR for in-hospital death of ATAAD patients.Results: Of the 197 patients included, 24 died, and the in-hospital mortality rate was 12.2%. There was a significant difference in diastolic blood pressure (P < 0.05). In terms of laboratory indexes, total bilirubin, direct bilirubin, indirect bilirubin, D-dimer, red blood cell volume distribution width, and DPR in the death group were higher than those in the survival group, with statistical significance (P < 0.05). Operation duration, hospital stay, ICU stay, mechanical ventilation time, and acute renal insufficiency in the death group were higher than those in the survival group (P < 0.05). Univariate analysis and multivariate analysis showed that DPR > 0.0305 ug/mL was an independent risk factor for death in ATAAD patients.Conclusion: Increased DPR is independently associated with in-hospital death in patients with ATAAD.Keywords: acute type A aortic dissection, death, D-dimer/platelet ratio, prognosis

Lian Chen,1,&ast; Yu-Huan Jiang,2,&ast; Mei-Yong Li,3 Bo Huang,3 Lei Yuan,2 Jin-Hua Wan,2 Ting-Yu Qin,2 Ting-Ting Zeng,2 Qing-Gen Chen2 1Department of Ultrasound Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 2Department of Clinical Laboratory, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 3Department of Clinical Laboratory, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China&ast;These authors contributed equally to this studyCorrespondence: Qing-Gen Chen, Department of Clinical Laboratory, the First Affiliated Hospital of Nanchang University, Nanchang, 330006, People’s Republic of China, Tel/Fax +86 0791-86319420, Email 272880243@qq.comPurpose: The aim of the present study was to identify more effective laboratory markers to assess the severity of corona virus disease 2019 and predict the progression of the disease by collecting more laboratory markers and variables.Patients and Methods: In this study, most risk factors, including epidemiological characteristics, blood cell counts, cytokines, and infection markers, were collected from 126 patients with COVID-19 to assess their predictive value.Results: The area under curve (AUC) of Albumin (Alb) to fibrinogen (Fib) ratio (AFR) (0.791), Lactate dehydrogenase (LDH) (0.792), myoglobin (MYO) (0.795), C-reactive protein (CRP) (0.801) and lymphocyte count (0.859) were higher than other markers to distinguish severe from non-severe patients in receiver operating characteristic (ROC) analysis. In the univariate logistic regression analysis, thirty-six out of 46 risk factors, including 34 laboratory markers, were significantly associated with increased odds of severe patients. Multivariate logistic regression analysis showed that the CD19+ lymphocyte count, MYO, LDH, and AFR were associated with increased odds of severe disease. Moreover, Lymphocyte count and AFR levels increased, LDH and CRP levels decreased during hospitalization in recovered severe patients, whereas severe lymphocytopenia and continuously increasing LDH levels were observed in deteriorated patients. AFR level increased and CRP level decreased before the disease worsened in the deteriorated patients; however, when the patients deteriorated, AFR decreased and CRP increased significantly.Conclusion: CD19+ lymphocyte count, MYO, LDH, and AFR are independent biomarkers for early identification of severe COVID-19. Lymphocyte count, AFR, LDH, and CRP levels were helpful in predicting the clinical progression of the disease.\. Keywords: Albumin to fibrinogen ratio, C-reactive protein, Lymphocyte, Coronavirus Disease 2019, Inflammation

Guansheng Zeng,1,&ast; Jian Xu,1,&ast; Huadong Zeng,1 Cuilan Wang,1 Lichang Chen,2 Huapeng Yu1 1Department of Pulmonary and Critical Care Medicine, Shenzhen Hospital, Southern Medical University, Shenzhen, People’s Republic of China; 2Department of Pulmonary and Critical Care Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Huapeng Yu, Department of Pulmonary and Critical Care Medicine, Shenzhen Hospital, Southern Medical University, Shenzhen, People’s Republic of China, Email huapengyu1960@163.com Lichang Chen, Department of Pulmonary and Critical Care Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, People’s Republic of China, Email 519744491@qq.comPurpose: To investigate the differential clinical significance of fractional concentration of exhaled nitric oxide measured at a flow rate of 200 mL/s (FENO200) and concentration of nitric oxide in alveolar (CANO) in asthma, chronic obstructive pulmonary disease (COPD) or asthma-COPD Overlap (ACO).Methods: A total of 178 patients were included, with 82 patients in asthma group, 47 patients in COPD group and 49 patients in ACO group. Data for demographic data, spirometry and exhaled nitric oxide were collected for comparative analysis, correlation analysis and discriminant canonical analysis.Results: The values of FENO200 in asthma, COPD and ACO groups were 11.0(7.0– 22.3), 8.0(6.0– 11.0) and 9.0(6.5– 19.5) ppb, respectively. In the asthma group, FENO200 exhibited negative correlations with FEV1/FVC, MMEF and MEF50. No significant correlation was observed between CANO and pulmonary function parameters. In the COPD group, both FENO200 and CANO showed negative correlation with pulmonary function parameters including FVC, FEV1, PEF, MMEF, MEF75, MEF50. In the ACO group, FENO200 demonstrated no significant correlation with pulmonary function parameters, while CANO was correlated with FEV1, PEF, MMEF and MEF50. In COPD group, ΔFEV1 in the bronchodilator test was correlated with FENO200. As for the ACO group, ΔFEV1 was correlated with CANO. In the discriminant canonical analysis, four parameters including gender, age, MEF75 and FENO50 discriminated between the three groups of asthma, COPD and ACO.Conclusion: In asthma, COPD and ACO, FENO200 has demonstrated a robust correlation with CANO. Elevated FENO200 levels are predominantly indicative of pulmonary function impairment in asthma and COPD, whereas elevated CANO levels are mainly correlated with pulmonary function impairment in COPD and ACO. Compared with FENO200 and CANO, FENO50 may have a better discriminatory ability in distinguishing asthma, COPD and ACO.Keywords: FENO200, CANO, ACO, asthma, chronic obstructive pulmonary disease

JianJiang Pan,1,&ast; XiXuan Cai,1,&ast; JieRu Chen,1 MingYing Xu,1 JingYu Hu,1 YueChun Mao,1 Tao Chen,2 LuSha Li,1 MengQi Jin,1 LiYing Chen1 1Department of General Practice, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310020, People’s Republic of China; 2Department of General Practice, Jianqiao Community Health Service Center, Hangzhou, Zhejiang, 310021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: LiYing Chen, Department of General Practice, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of China, Email 3197020@zju.edu.cnPurpose: Understanding the role of systemic inflammation in the development of Metabolic Syndrome (MetS) is crucial for identifying individuals at a higher risk of this cluster of conditions that increase the risk of heart disease, stroke, and diabetes.Patients and Methods: A retrospective cohort study was conducted with 4,312 participants who were free from MetS at the study’s onset and had high-sensitivity C-reactive protein (hsCRP) levels measured. Latent class trajectory modeling was utilized to identify distinct hsCRP trajectory patterns. Multivariable regression and proportional hazards analyses were employed to evaluate the predictive value of hsCRP trajectories for the development of MetS.Results: During the 1.63-year follow-up period, 1,308 participants developed metabolic syndrome (MetS). Individuals with high hsCRP levels exhibited a significantly increased risk of developing MetS compared to those with low hsCRP levels (HR = 1.062, 95% CI 1.103– 1.113). The hsCRP trajectory analysis identified three distinct groups: low-stable, increasing, and decreasing. The decreasing and increasing hsCRP trajectory groups demonstrated a 1.408-fold (95% CI 1.115– 1.779) and a 1.618-fold (95% CI 1.288– 2.033) increased risk of MetS, respectively.Conclusion: This study suggests that participants with higher baseline hsCRP levels and increasing hsCRP trajectories are associated with a progression toward MetS. Long-term hsCRP trajectories may serve as useful tools for identifying individuals at higher risk of MetS who could benefit from targeted preventive and therapeutic interventions.Keywords: high-sensitivity C-reactive protein, metabolic syndrome, trajectory analysis, retrospective cohort study, risk prediction

Yu Sun,1 Zhaoyong Li,1 Jiahao Duan,1 Enxu Liu,1 Fei Sun,1 Lei Yang,2 Long Chen,2 Shaofeng Yang2 1Graduate School of Hunan University of Chinese Medicine, Changsha, Hunan, 410208, People’s Republic of China; 2Department of Orthopedics, the First Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, 410007, People’s Republic of ChinaCorrespondence: Shaofeng Yang, Department of Orthopedics, the First Affiliated Hospital of Hunan University of Chinese Medicine, No. 300 Xue-Shi Road, Yuelu District, Changsha, 410007, Hunan, People’s Republic of China, Tel +86 18391076233, Email a18391076233@163.comAbstract: The gut microbiome (GM), often referred to as the second genome of the human body, plays a crucial role in various metabolic processes and mediates the development of numerous diseases. Intervertebral disc degeneration (IDD) is an age-related degenerative spinal disease characterized by the loss of disc height, hydration, and integrity, leading to pain and reduced mobility. Although the pathogenesis of IDD is not fully understood, recent studies suggest that dysbiosis of the gut microbiome may accelerate the progression of IDD through multiple mechanisms. This article begins by discussing the potential relationship between GM dysbiosis and human diseases, followed by a comprehensive review of the regulatory mechanisms of GM in skeletal diseases within the gut-disc axis framework. Furthermore, it explores three potential pathways through which GM dysbiosis may mediate the development of IDD: immunomodulation, bacterial translocation and colonization, and the decomposition and absorption of intestinal metabolites. These pathways can disrupt disc cell homeostasis and promote degenerative changes. Finally, this paper summarizes for the first time the potential therapeutic approaches for delaying IDD by targeting the gut-disc axis, providing new insights into the pathogenesis and regenerative repair strategies for IDD.Keywords: intervertebral disc degeneration, microbiome, inflammation, immunity, metabolism

Liying Lu,1,2 Mengdan Pang,1,2 Tingting Chen,1,2 Yingying Hu,1,2 Likai Chen,3 Xiaoyue Tao,1,2 Shangqin Chen,1,2 Jianghu Zhu,1,2 Mingchu Fang,1,2 XiaoLing Guo,1,4 Zhenlang Lin1,2,4 1Department of Pediatrics, The Second School of Medicine, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China; 2Key Laboratory of Perinatal Medicine of Wenzhou, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China; 3Elson S. Floyd College of Medicine at Washington State University, Spokane, WA, USA; 4Basic Medical Research Center, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of ChinaCorrespondence: XiaoLing Guo; Zhenlang Lin, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, 109 Xueyuan West Road, Wenzhou, Zhejiang, 325027, People’s Republic of China, Tel +00-86-138-0668-9800, Fax +86-0577-88002198, Email guoxling@hotmail.com; linzhenlang@hotmail.comIntroduction: Neonatal hypoxic-ischemic encephalopathy (HIE), caused by perinatal asphyxia, is characterized by high morbidity and mortality, but there are still no effective therapeutic drugs. Mitochondrial biogenesis and apoptosis play key roles in the pathogenesis of HIE. Protopine (Pro), an isoquinoline alkaloid, has anti-apoptotic and neuro-protective effects. However, the protective roles of Pro on neonatal hypoxic-ischemic brain injury remain unclear.Methods: In this study, we established a CoCl2-induced PC12 cell model in vitro and a neonatal rat hypoxic-ischemic (HI) brain damage model in vivo to explore the neuro-protective effects of Pro and try to elucidate the potential mechanisms.Results: Our results showed that Pro significantly reduced cerebral infarct volume, alleviated brain edema, inhibited glia activation, improved mitochondrial biogenesis, relieved neuron cell loss, decreased cell apoptosis and reactive oxygen species (ROS) after HI damage. In addition, Pro intervention upregulated the levels of p-AMPK/AMPK and PGC1α as well as the downstream mitochondrial biogenesis related factors, such as nuclear respiratory factor 1 (NRF1) and mitochondrial transcription factor A (TFAM), but the AMPK inhibitor compound c (CC) could significantly reverse these effects of Pro.Discussion: Pro may exert neuroprotective effects on neonatal hypoxic-ischemic brain damage via activation of the AMPK/PGC1α pathway, suggesting that Pro may be a promising therapeutic candidate for HIE, and our study firstly demonstrate the neuro-protective roles of Pro in HIE models.Keywords: neonatal hypoxic-ischemic brain damage, protopine, reactive oxygen species, apoptosis, mitochondrial biogenesis

Haoxiang Wen,1,2,&ast; Ruiming Liang,3,&ast; Xiaofei Liu,4 Yang Yu,1 Shuirong Lin,1 Zimin Song,1 Yihao Huang,1 Xi Yu,1 Shuling Chen,5 Lili Chen,6 Baifeng Qian,1 Jingxian Shen,7 Han Xiao,8 Shunli Shen1 1Center of Hepato-Pancreatico-Biliary Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong Province, People’s Republic of China; 2Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital and Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, Guangdong Province, People’s Republic of China; 3Department of Medical Statistics, Clinical Trials Unit, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong Province, People’s Republic of China; 4Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-senUniversity, Guangzhou, Guangdong Province, People’s Republic of China; 5Precision Medicine Institute, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong Province, People’s Republic of China; 6Department of Pathology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong Province, People’s Republic of China; 7Department of Radiology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong Province, People’s Republic of China; 8Division of Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shunli Shen, Center of Hepato-Pancreatico-Biliary Surgery, The First Affiliated Hospital of Sun Yat-sen University, No. 58 Zhong-Shan Road2, Guangzhou, Guangdong Province, People’s Republic of China, Email Shenshli@mail.sysu.edu.cn Han Xiao, Division of Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-sen University, No. 58 Zhongshan Road2, Guangzhou, Guang- Dong Province, People’s Republic of China, Email xiaoh69@mail.sysu.edu.cnPurpose: Predicting the pathological response after neoadjuvant conversion therapy for initially unresectable hepatocellular carcinoma (HCC) is essential for surgical decision-making and survival outcomes but remains a challenge. We aimed to develop a radiomics model to predict pathological responses.Methods: We included 203 patients with HCC who underwent hepatectomy after neoadjuvant conversion therapy between 2015 and 2023 and separated them into a training set (100 patients from Center A) and a validation set (103 patients from Center B). Pathological complete response (pCR)-related radiomic features were extracted from the largest tumor layer in the arterial and portal vein phases of the CT. A synthetic minority oversampling technique (SMOTE) was used to balance the minority groups in the training set. The SMOTE radiomics model was constructed using a logistic regression model in the SMOTE training set and its performance was verified in the validation set.Results: The AUC of the preoperative modified response evaluation criteria in solid tumors (mRECIST) assessment for pCR was 0.656 and 0.589 in the training and validation sets, respectively. The SMOTE radiomics model was established based on ten radiomic features and showed good pCR-predictive performance in the SMOTE training set (AUC, 0.889; accuracy, 87.7%) and the validation set (AUC: 0.843, accuracy: 86.4%). The RFS of the radiomics-predicted-pCR group was significantly better than that of the predicted-non-pCR group in the training cohort (P = 0.001, 2-year RFS: 69.5% and 30.1% respectively) and the validation cohort (P = 0.012, 2-year RFS: 65.9% and 38.0% respectively).Conclusion: The SMOTE radiomics model has great potential for predicting pathological response and evaluating RFS in patients with unresectable HCC after neoadjuvant conversion therapy.Keywords: hepatocellular carcinoma, radiomics, pathological complete response, neoadjuvant conversion therapy

Yaning Gao, Liang Chen, Zhengjun Wen, Huiying Jiang, Jing Feng Respiratory and Critical Care Medicine Department, Beijing Jingmei Group General Hospital, Beijing, People’s Republic of ChinaCorrespondence: Liang Chen, Email huxike000111@sohu.comPurpose: Our aim was to determine the risk factors for multidrug resistance in patients with carbapenem-resistant Klebsiella pneumoniae (CRKP).Methods: The information of 196 patients with Klebsiella pneumoniae infection was collected. The patients were subsequently assigned to the carbapenem-resistant, multidrug-resistant, and non-multidrug-resistant groups. The risk factors for multidrug resistance in CRKP patients were assessed via least absolute shrinkage and selection operator and logistic regression analyses. Moreover, a nomogram was constructed dependent on the identified risk factors, and calibration and decision curves were plotted to detect its accuracy.Results: Length of stay (LOS) [odds ratio (OR) and 95% confidence interval (CI): 4.558 (1.157– 17.961), P = 0.030], intensive care unit (ICU) stay within 30 days [OR and 95% CI: 12.643 (3.780– 42.293), P < 0.001], Glasgow Coma Scale (GCS) score [OR and 95% CI: 13.569 (2.738– 67.236), P = 0.001], fungal infection [OR and 95% CI: 6.398 (1.969– 20.785), P = 0.002], and cardiovascular disease (CVD) [OR and 95% CI: 3.871 (1.293– 11.592), P = 0.016] were identified as risk factors for multidrug resistance in CRKP patients. The concordance index (C-index) of the constructed nomogram was 0.950 (95% CI: 0.945– 0.955). Moreover, decision curve analysis elucidated the nomogram utilization across a wide range of probability thresholds, ranging from 1% to 100%. Finally, internal validation using random data validated the robustness of the predictive model, yielding a C-index of 0.937.Conclusion: The LOS, ICU stay within 30 days, GCS score, fungal infection, and CVD were recognized as risk factors for multidrug resistance in CRKP patients. The constructed nomogram could accurately predict multidrug-resistant CRKP infections in patients.Plain Language Summary: The LOS, ICU stay within 30 days, GCS, fungal infection, and CVD were identified as risk factors for multidrug resistance in CRKP patients.The nomogram constructed in this study had high predictive accuracy.This study provides a reference for the formulation of personalized prevention and therapy strategies.Keywords: Klebsiella pneumoniae, multidrug resistance, carbapenem, prediction model, risk factors

Yu Pan,1,&ast; Lili Cao,2,&ast; Libing Chen,1,&ast; Linjuan Gao,2 Xia Wei,1 Honglei Lin,1 Lei Jiang,1 Yinghui Wang,1,2 Hui Cheng1,2 1Department of Prosthodontics, Institute of Stomatology & Research Center of Dental Esthetics and Biomechanics, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, Fujian, People’s Republic of China; 2Department of Prosthodontics, Fujian Key Laboratory of Oral Diseases & Fujian Provincial Engineering Research Center of Oral Biomaterial & Stomatological Key Laboratory of Fujian College and University, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, Fujian, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yinghui Wang; Hui Cheng, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, Fujian, People’s Republic of China, Email wyh9519@fjmu.edu.cn; ch.fj@fjmu.edu.cnPurpose: The study was intended to compare the surface properties and the bacterial and biofilm adhesion resistance of two potential antibacterial nanometer titanium dioxide (nano-TiO2) coatings on dental titanium (Ti) abutments prepared by atomic layer deposition (ALD) and the anodic oxidation (AO) techniques.Methods: Nano-TiO₂ coatings were developed using ALD and AO techniques and applied to Ti surfaces. The surface properties and the bacterial and biofilm adhesion resistance of these coatings were evaluated against commonly used Ti and Zirconia (ZrO₂) surfaces. The chemical compositions, crystalline forms, surface topography, roughness and hydrophilicity were characterized. The antibacterial performance was assessed by the scanning electron microscope (SEM), the Colony-forming unit (CFU) assay and the 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide (MTT) assay using in vitro models of Staphylococcus aureus (S. aureus), Streptococcus mutans (S. mutans), and Porphyromonas gingivalis (P. gingivalis) in both single- and mixed-species bacterial compositions.Results: ALD-prepared nano-TiO₂ coatings resulted in a dense, smooth, and less hydrophilic surface with an anatase phase, significantly reducing the adhesion of the three bacteria by over 50%, comparable to ZrO₂. In contrast, AO-prepared coatings led to a less hydrophilic surface, characterized by various nano-sized pores within the oxide film. This alteration, however, had no impact on the adhesion of the three bacteria. The adhesion patterns for mixed-species bacteria were generally consistent with single-species results.Conclusion: ALD-prepared nano-TiO₂ coatings on Ti abutments demonstrated promising antibacterial properties comparable to ZrO₂ surfaces, suggesting potential in preventing peri-implantitis. However, the bacterial and biofilm adhesion resistance of AO-produced nano-TiO₂ coatings was limited. Keywords: atomic layer deposition, anodic oxidation, titanium dioxide, dental abutment, surface properties, antibacterial effect

Dan Kuai,1,2 Jiayu Wei,1,2 Mengying Li,1,2 Lu Chen,3 Dongcan Zhang,1,2 Xiaoyan Li,1,2 Ying He,1,2 Shiqi Liu,1,2 Huiying Zhang,1,2 Wenyan Tian,1,2 Yingmei Wang1,2 1Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital, Tianjin, 300052, People’s Republic of China; 2Tianjin Key Laboratory of Female Reproductive Health and Eugenics, Tianjin Medical University General Hospital, Tianjin, 300052, People’s Republic of China; 3Department of Gynecology and Obstetrics, The First People’s Hospital of Datong City, Datong, Shanxi, 037000, People’s Republic of ChinaCorrespondence: Wenyan Tian; Yingmei Wang, Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital, No. 154, Anshan Road, He Ping District, Tianjin, People’s Republic of China, 300052, Tel +86 60362277; 86-022-60362255, Email tianwenyan1108@163.com; wangyingmei1978@126.comObjective: To evaluate the therapeutic outcomes of weight loss and metformin use in patients with endometrial hyperplasia (EH), and to identify the factors influencing treatment efficacy.Methods: This study included data from patients diagnosed with either EH or endometrial atypical hyperplasia (EAH). Patients selected a progestin treatment regimen based on their diagnosis. Those with concurrent obesity or insulin resistance received additional weight management support and metformin therapy. Follow-up assessments were conducted every 3– 6 months.Results: A total of 202 patients were included. The metformin group exhibited significantly greater improvement in abnormal uterine bleeding (91.5% vs 57.1%, p < 0.001) and in ultrasound findings (91.5% vs 66.7%, p < 0.001) than the non-metformin group. Patients who achieved > 3% weight loss and those using metformin showed a significantly higher rate of disease reversal than those with ≤ 3% weight loss (91.2% vs 77.6%, p = 0.034) and the non-metformin group (93.2% vs 52.4%, p < 0.001). At follow-up durations exceeding 12 months, metformin use was associated with a significantly higher disease reversal rate (82.1% vs 42.9%, p = 0.048) and a lower recurrence rate (12.8% vs 28.6%, p = 0.048). Weight loss of > 3% (odds ratio: 0.041, 95% confidence interval: 0.004– 0.437, p = 0.008) and metformin use (odds ratio: 0.059, 95% confidence interval: 0.011– 0.311, p = 0.001) were both independently associated with improved reversal rates in patients with EH/EAH.Conclusion: Combining progestin therapy with weight loss and metformin is more effective in reversing EH than progestin alone. Regular metformin use, alongside weight loss, serves as a protective factor in EH management, with the protective effect of metformin increasing with longer use.Keywords: endometrial hyperplasia without atypia, comprehensive management, weight management, metformin

Lijuan Chen,1,&ast; Mingbo Liu,2,&ast; Yunjuan Wang,3,4,&ast; Wei Wei,1 Yaqiong Li,5 Yan Bai,1 Xuan Yu,1 Lei Jiao,6 Meiyun Wang1,4 1Department of Medical Imaging, Henan Provincial People’s Hospital & the People’s Hospital of Zhengzhou University, Zhengzhou, Henan, 450003, People’s Republic of China; 2Department of Radiotherapy, Henan Provincial People’s Hospital & the People’s Hospital of Zhengzhou University, Zhengzhou, Henan, 450003, People’s Republic of China; 3School of Life Sciences, Henan University, North Section of Jinming Avenue, Kaifeng, Henan, 475004, People’s Republic of China; 4Institute of Biomedicine, Henan Academy of Sciences, Zhengzhou, Henan, 450046, People’s Republic of China; 5Department of Pharmacy, Henan Provincial People’s Hospital & the People’s Hospital of Zhengzhou University, Zhengzhou, Henan, 450003, People’s Republic of China; 6Institute of Molecular Metrology, College of Chemistry and Chemical Engineering, Qingdao University, Qingdao, Shandong, 266071, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Meiyun Wang, The Department of Medical Imaging, Henan Provincial People’s Hospital & the People’s Hospital of Zhengzhou University, No. 7, WeiWu Road, Zhengzhou, Henan, 450003, People’s Republic of China, Email mywang@zzu.edu.cnPurpose: Radiotherapy (RT) is currently recognized as an important treatment for glioblastoma (GBM), however, it is associated with several challenges. One of these challenges is the radioresistance caused by hypoxia, whereas the other is the low conversion efficiency of the strongly oxidized hydroxyl radical (•OH), which is produced by the decomposition of water due to high-energy X-ray radiation. These factors significantly limit the clinical effectiveness of radiotherapy.Results: To address these limitations, we developed a highly stable and efficient nanoplatform (MnO2/Pt@BSA). Compared to MnO2@BSA, this platform demonstrates high stability, a high yield of oxygen (O2), enhanced production of •OH, and reduced clearance of •OH. The system exhibited increased O2 production in vitro and significantly improved oxygen production efficiency within 100 s at the Pt loading of 38.7%. Furthermore, compared with MnO2, the expression rate of hypoxia-inducible factor (HIF-1α) in glioma cells treated with MnO2/Pt decreased by half. Additionally, the system promotes •OH generation and consumes glutathione (GSH), thereby inhibiting the clearance of •OH and enhancing its therapeutic effect. Moreover, the degradation of the nanoplatform produces Mn2+, which serves as a magnetic resonance imaging (MRI) contrast agent with a T1-weighted enhancement effect at the tumor site. The nanoplatform exhibited excellent biocompatibility and performed multiple functions related to radiotherapy, with simpler components. In U87 tumor bearing mice model, we utilized MnO2/Pt nanocatalysis to enhance the therapeutic effect of radiotherapy on GBM.Conclusion: This approach represents a novel and effective strategy for enhancing radiotherapy in gliomas, thereby advancing the field of catalytic radiotherapy and glioma treatment.Keywords: radiotherapy, glioblastoma, MnO2/Pt@BSA nanoplatform, nanocatalysis

Song Wen,1,2 Yanyan Li,1 Chenglin Xu,1 Jianlan Jin,1 Zhimin Xu,1 Yue Yuan,1 Lijiao Chen,1 Yishu Ren,1 Min Gong,1 Congcong Wang,1 Meiyuan Dong,1 Yingfan Zhou,3 Xinlu Yuan,1 Fufeng Li,4 Ligang Zhou1,2,5 1Department of Endocrinology, Shanghai Pudong Hospital, Fudan University, Pudong Medical Center, Shanghai, 201399, People’s Republic of China; 2Fudan Zhangjiang Institute, Fudan University, Shanghai, 201203, People’s Republic of China; 3Medical School of Tianjin University, Tianjin, 300072, People’s Republic of China; 4Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 5Shanghai Key Laboratory of Vascular Lesions Regulation and Remodeling, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, People’s Republic of ChinaCorrespondence: Ligang Zhou, Department of Endocrinology, Shanghai Pudong Hospital, Fudan University, Pudong Medical Center, Shanghai, 201399, People’s Republic of China, Tel +8613611927616, Email zhouligang1n1@163.com Fufeng Li, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China, Email li_fufeng@aliyun.comObjective: We aim to examine and reestablish the correlational and linear regression relationships, as well as the predictive value, between the significant facial and tongue features and the metabolic parameters in type 2 diabetes mellitus (T2DM).Materials and Methods: From March to May 2024, we studied 269 patients with T2DM in the endocrinology department of Shanghai Pudong Hospital. The patients’ facial and tongue characteristics were sampling by a tongue imaging device equipped with artificial intelligence (AI) (XiMaLife, Sinology, China) of automated and advanced machine learning algorithms. Then, the imaging features were examined in relation to the blood examination.Results: Multiple facial and tongue features, as well as dimensional facial and tongue color parameters, were significantly correlated with glycated hemoglobin A1c (HbA1c) (r < 0.3, p < 0.05), glycated albumin (GA) (− 0.20 < 0.30, p < 0.05), C-peptide (− 0.20.20, p < 0.05), plasma insulin (r < 0.30, p < 0.05), fasting plasma glucose (FPG) (r < 0.3, p < 0.05), significant hepatic and renal function indicators (− 0.30 < r < 0.20, p< 0.05), cardiac injury markers (− 0.30 < r < 0.30, p < 0.05), tumor markers (− 0.5 < r < 0.5, p < 0.05), thyroid function (− 0.15 < r < 0.55, p < 0.05), and blood cell count, including white blood cells (r < 0.2, p < 0.05), and hemoglobin (Hb) (− 0.30 < r < 0.3, 0.0001. The correlational results demonstrated that the tongue’s characteristics and signs may be linked with the dynamic of the metabolic status of T2DM. In order to examine the causal relationships, we performed linear regression analyses, which revealed that various facial and tongue imaging parameters partially determined the metabolic indicators. The predictive value of imaging features was evaluated by receiver operating characteristic curve (ROC) to assess metabolic status in T2DM.Conclusion: This study demonstrated that metabolic status, renal and hepatic, cardiac, and thyroid function, the proportion of blood cells, and Hb in T2DM were intimately associated with facial and tongue features. The precise analysis of facial and tongue features through AI and advanced machine learning could be used to predict T2DM’s conditions and progression.Keywords: type 2 diabetes, tongue imaging, face imaging, cardiovascular disease, machine learning

Bohan Hua,1,2 Mingzi An,2 Liping Chen,2 Huadong Ni,2 Chaobo Ni,1,2 Ming Yao1,2 1Anesthesia Medicine, Zhejiang Chinese Medical University, Hangzhou City, Zhejiang, People’s Republic of China; 2Department of Anesthesiology and Pain medicine, Affiliated Hospital of Jiaxing University, Jiaxing City, Zhejiang, People’s Republic of ChinaCorrespondence: Ming Yao; Chaobo Ni, Anesthesia Medicine, Zhejiang Chinese Medical University, Hangzhou City, Zhejiang, 310053, People’s Republic of China, Tel +86 137 5839 4990, Email jxyaoming@zjxu.edu.cn; jxnichaobo@zjxu.edu.cnPurpose: To investigate the correlation between the level of glycosylated hemoglobin (HbA1c) and postherpetic neuralgia (PHN).Patients and Methods: This cohort study included 100 patients with herpes zoster (HZ) undergoing treatment with pulsed radiofrequency (PRF). Patients with comorbid type 2 diabetes mellitus (T2DM) were divided into three groups based on their glycemic control levels: good [HbA1c < 7% (53.01 mmol/mol), group D1], fair [7% (53.01 mmol/mol) ≤ HbA1c < 9% (74.86 mmol/mol), group D2], and poor [9% (74.86 mmol/mol) ≤ HbA1c, group D3]. The control group (group N) consisted of patients without T2DM. The main outcome measured was the occurrence of PHN in the four groups.Results: A total of 90 patients were included in the cohort. The occurrence of PHN was found to be higher in groups D2 and D3 when compared to group N (N vs D2, P = 0.007; N vs D3, P < 0.001). Furthermore, the occurrence of PHN was higher in groups D2 and D3 in comparison to group D1 (D1 vs D2, P = 0.022; D1 vs D3, P < 0.001), with the incidence of PHN in group D3 being greater than in group D2 (P < 0.001).Conclusion: Preoperative HbA1c predicts the incidence of PHN after PRF in T2DM patients.Keywords: herpes zoster, postherpetic neuralgia, pulsed radiofrequency, type 2 diabetes mellitus, HbA1c

Lingyu Lin,1,&ast; Zhuling Gao,2,&ast; Yanchun Peng,2 Sailan Li,1 Liangwan Chen,1,3 Yanjuan Lin1,2 1Department of Cardiovascular Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, 350001, People’s Republic of China; 2Department of Nursing, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, 350001, People’s Republic of China; 3Key Laboratory of Cardio-Thoracic Surgery(Fujian Medical University), Fujian Province University, Fuzhou, Fujian Province, 350001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yanjuan Lin, Department of Nursing, Fujian Medical University Union Hospital, No. 29 Xinquan Road, Fuzhou, 350001, Fujian Province, People’s Republic of China, Tel +86059186218581, Fax +8683344034, Email fjxhyjl@163.com Liangwan Chen, Department of Cardiovascular Surgery, Fujian Medical University Union Hospital, No. 29 Xinquan Road, Fuzhou, 350001, Fujian Province, People’s Republic of China, Fax +86059183301393, Email fjxhlwc@163.comPurpose: Many shift nurses experience poor sleep quality, and the effect on nurses’ cognitive function remains unclear. The study aims to investigate sleep status and explore its association with cognitive function.Methods: This descriptive cross-sectional study was conducted in a tertiary care hospital in Fujian, China between March and September 2022. By convenience sampling method, 588 shift nurses participated in this study. The Pittsburgh Sleep Quality Index (PSQI) and Bergen Shift Work Sleep Questionnaire (BSWSQ) were used to assess sleep quality, while the Chinese version of Ascertain Dementia-8 (AD-8) was used to evaluate cognitive function. A PSQI score ≤ 7 is classified as good sleep quality, and a score > 7 indicates poor sleep quality. An AD-8 score≥ 2 is considered indicative of memory impairment. Multivariate logistic regression analysis was conducted to explore the association between sleep status and memory impairment.Results: A total of 310 (52.6%) participants presented poor sleep quality. Among them, 52.2% of participants had day shift-related sleep problems, 45.9% had evening shift-related sleep problems, 61.9% had night shift-related sleep problems, and 15.0% reported rest-day/vacation-related sleep problems. The prevalence of poor sleep quality and each shift-related sleep problem in the memory impairment group were higher than in the normal memory group (P< 0.05). Multivariate logistic regression analysis indicated that poor sleep quality (OR=2.073, 95% CI: 1.398~3.072), evening shift-related sleep problems (OR=1.707, 95% CI: 1.028~2.835), night shift-related sleep problems (OR=1.859, 95% CI:1.104~3.129), and rest-day/vacation-related sleep problems (OR=2.069, 95% CI:1.170~3.659) was significantly associated with memory impairment.Conclusion: This study highlights the prevalence of poor sleep quality among clinical nurses and identifies poor sleep quality and shift-related sleep problems (excluding day shift) as risk factors for memory impairment. Nurse managers should prioritize sleep quality and focus on cognitive function to enhance nurses’ occupational health.Keywords: nurse, sleep disturbance, memory, cognitive function

Haifan Xu,1,2,&ast; Xiaoshuang Wang,1,3,&ast; Miao Feng,1 Liqun Chen1 1Department of Nephrology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Department of Nephrology, The People’s Hospital of Kaizhou District, Chongqing, People’s Republic of China; 3Department of Nephrology, Yubei District People’s Hospital, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Liqun Chen, Email cqll1970@163.comObjective: To investigate the correlation between background factors and blood pressure variability (BPV), and the prognostic value of intra-dialytic BPV metrics for cardiovascular death and all-cause mortality in hemodialysis (HD) patients.Methods: A retrospective study of 264 hD patients was followed up for 36 months. The intra-dialytic BP during the 3-month period for each patient was used to calculate BPV metrics, including standard deviation (SD), coefficient of variation (CV), average real variability (ARV), blood pressure change (ΔBP), and percent change in blood pressure (ΔBP/pre-BP). The primary outcomes were CVD death and all-cause mortality.Results: Age, body mass index (BMI), predialysis blood pressure, inter-dialytic weight gain rate (IDWG%), α- blockers, and cholesterol levels were positively correlated with intra-dialytic BPV. Hemoglobin and albumin are negatively associated with intra-dialytic BPV. In Cox regression analysis, SBP-ARV, ΔSBP, and ΔSBP/pre-SBP were independent risk factors for CVD death (HR: 1.087, 95% CI: 1.001– 1.181, p = 0.047; HR: 1.072, 95% CI: 1.016– 1.131, p = 0.011; HR: 1.107, 95% CI: 1.011– 1.211, p = 0.028). SBP-ARV showed the largest AUC of 0.593 (p = 0.022) in predicting all-cause death. SBP-ARV, ΔSBP, and ΔSBP/pre-SBP showed relatively large area (AUC = 0.631, 0.639, and 0.620; p = 0.007, 0.004, and 0.013 respectively) in predicting CVD death.Conclusion: Age, BMI, IDWG%, predialysis blood pressure, albumin, hemoglobin, α- blockers, and total cholesterol were significantly correlated with intra-dialytic BPV. SBP-ARV, ΔSBP, and ΔSBP/pre-SBP were independent risk factors for CVD mortality, and there were no differences in prognostic value among various BPV metrics.Keywords: hemodialysis, blood pressure variability, influencing factors, all-cause mortality, cardiovascular death

Li Chen,1,2 Xi-Le Peng,1,2 Zhi-Xuan Chen,1,2 Lu-Ming Qi,1,2 Ting-Ting Deng,2,3 Li-Na Xia1,2 1School of Health Preservation and Rehabilitation, Chengdu University of TCM, Chengdu, Sichuan, People’s Republic of China; 2Key Laboratory of Traditional Chinese Medicine Regimen and Health Industry Development, State Administration of TCM, Chengdu, Sichuan, People’s Republic of China; 3School of Nursing, Chengdu University of TCM, Chengdu, Sichuan, People’s Republic of ChinaCorrespondence: Li-Na Xia, School of Health Preservation and Rehabilitation, Chengdu University of TCM, Chengdu, Sichuan, People’s Republic of China, Email xialina@cdutcm.edu.cnBackground: Excessive salt consumption has been associated with detrimental health consequences, including hypertension, colitis, and autoimmune disorders. However, recent studies have proposed that high salt diet (HSD) can both stimulate the immune system, affecting the differentiation of immune cells, promoting or inhibiting cytokine secretion to fight cancer or elicit a more potent autoimmune response, and exerting an immunosuppressive effect to influence disease development, providing mechanistic insights into the direction of immune regulation in which HSD affects disease.Objective: This paper reviews the immunomodulatory effects of HSD on various innate immune and adaptive cells, especially macrophages, dendritic cells, and T cells, in relation to disease development.Methods: We identified papers by electronically searching the Web of Science (WOS) database from inception through March 2023.Results: A growing number of animal experiments and in vitro cell culture studies have shown that HSD can regulate the differentiation and activation of a variety of immune cells, and promote or inhibit different cytokines to mediate the development of a variety of diseases, including nephropathy, hypertension, cancer, inflammatory bowel disease, and a number of autoimmune diseases. These findings provide a new mechanism for pathological changes in the direction of immune regulation and suggest that HSD is a predisposing factor for a variety of diseases, providing new mechanistic insights into dietary health modification.Conclusion: HSD mediates the development of multiple diseases by regulating the differentiation and activation of a variety of immune cells, and the underlying mechanisms may be related to gut microbes and their metabolites.Keywords: HSD, immune dysregulation, disease pathogenesis, mechanistic insights, review

Yan Jiang,1,&ast; Baolin Luo,2,&ast; Wen Lu,1 Yaqin Chen,1 Yanchun Peng,2 Liangwan Chen,3,4 Yanjuan Lin2,3 1School of Nursing, Fujian Medical University, Fuzhou, Fujian, People’s Republic of China; 2Department of Nursing, Fujian Medical University Union Hospital, Fuzhou, Fujian, People’s Republic of China; 3Department of Cardiovascular Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, People’s Republic of China; 4Fujian Provincial Special Reserve Talents Laboratory, Fuzhou, Fujian, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Liangwan Chen, Department of Cardiovascular Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, People’s Republic of China, Email fjxhlwc@163.com Yanjuan Lin, Department of Nursing, Fujian Medical University Union Hospital, Fuzhou, Fujian, People’s Republic of China, Email fjxhyjl@163.comPurpose: The Aggregate Index of Systemic Inflammation (AISI) has emerged as a novel marker for inflammation and prognosis, but its role in patients with acute myocardial infarction has not been studied. Therefore, this study aimed to investigate the impact of different AISI levels on the clinical outcomes of patients with acute myocardial infarction.Patients and Methods: This study was a retrospective study, including 1044 patients with acute myocardial infarction (AMI) who were treated at the Fujian Medical University Affiliated Union Hospital, China from May 2017 to December 2022. The patients were divided into high and low AISI groups based on the median value (Q1 Group, ≤ 416.15, n=522; Q2 Group, ≥ 416.16, n=522), and the differences in baseline characteristics and clinical outcomes between the two groups were analyzed. The primary outcome included major adverse cardiovascular and cerebrovascular events (MACCEs), while the secondary outcomes included contrast-induced nephropathy (CIN) risk and all-cause rehospitalization rate.Results: The findings of the single-factor analysis suggest that a significant association between high AISI levels and the occurrence of MACCEs in AMI patients. After adjusting for confounding factors, the results indicated that compared to Q1, patients in the Q2 group had a higher risk of all-cause mortality [adjusted odds ratio (aOR) 4.64; 95% CI 1.37– 15.72; p=0.032], new-onset atrial fibrillation (aOR 1.75; 95% CI 1.02– 3.00; p=0.047), and CIN (aOR 1.75; 95% CI 1.02– 3.01; p=0.043), with all differences being statistically significant.Conclusion: In the population of AMI patients, an elevated AISI level is significantly associated with an increased risk of cardiovascular death and can serve as an early marker for adverse prognosis.Keywords: acute myocardial infarction, inflammation index, clinical outcomes, MACCEs

Zuo Wang,1,2,&ast; Siqi Guo,3,&ast; Chong He,2,4,&ast; Lingling Chen,5 Jinxia Wang,2 Wenbo Xiu,2 Gao Zhang,2 Yang Chen,2 An Li,2 Xiong Zhu,6 Xiao Xiao,2 Ling Yu,3 Fang Lu2,4,7 1Department of Clinical Laboratory, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, People’s Republic of China; 2Clinical Immunology Translational Medicine Key Laboratory of Sichuan Province, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China; 3Department of Ophthalmology, Daping Hospital, Army Medical Center, Army Medical University, Chongqing, People’s Republic of China; 4Medico-Engineering Cooperation on Applied Medicine Research Center, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China; 5Department of Immunology, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, People’s Republic of China; 6Department of Prenatal Diagnosis, Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China; 7Health Management Center, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ling Yu; Fang Lu, Email oculistlingyu@hotmail.com; lufangfang@126.comObjective: Evidence suggests that dysbiosis of the gut microbiota plays a pivotal role in the development of glaucoma. This dysbiosis is commonly associated with chronic intestinal inflammation and increased intestinal permeability. However, the understanding of intestinal inflammation and permeability in glaucoma remains insufficient. This study aims to investigate the potential relationship between fecal inflammation and permeability markers and glaucoma.Methods: We recruited 114 glaucoma patients and 75 healthy controls. Levels of fecal lactoferrin (Lf) and alpha-1 antitrypsin (AAT) were quantified using enzyme linked immunosorbent assay (ELISA) to compare both biomarkers between groups and across different severity grades of glaucoma. Logistic regression analysis was used to assess the association between these fecal biomarkers and glaucoma. The severity of glaucoma was assessed based on the mean deviation (MD) in the visual field.Results: In this study, we observed elevated levels of fecal Lf and AAT in glaucoma patients. The proportion of glaucoma patients with abnormal fecal Lf levels (≥ 7.25 μg/g) was significantly higher than that of the controls (p = 0.012). A positive correlation was noted between fecal Lf and AAT (rho = 0.20, p = 0.006). After adjusting for age and sex, multivariable logistic regression analysis indicated that both fecal Lf (OR = 1.11, 95% CI: 1.01– 1.21, p = 0.026) and AAT (OR = 1.01, 95% CI: 1.01– 1.02, p < 0.001) positively correlated with glaucoma. These biomarkers might reflect glaucoma severity, with significant differences in fecal Lf levels observed between moderate and severe stages, but not in the early stage. Furthermore, increasing levels of fecal AAT correlated with greater severity of glaucomatous injury and a larger vertical cup-to-disc ratio (VCDR) (p < 0.05).Conclusion: This study suggests an increase in intestinal inflammation and permeability in glaucoma, further indicating the importance of the ‘gut-retina axis’ in the pathogenesis of the disease and potentially offering new therapeutic avenues.Keywords: fecal lactoferrin, fecal alpha-1 antitrypsin, glaucoma, intestinal inflammation, intestinal permeability, intestinal barrier

Liping Chen,1 Tongwei Xiang,2 Jing Xing,2 Xinan Lu,2 Shan Wei,2 Huaying Wang,2 Jipeng Li,1 Wanjun Yu2 1Department of Central Laboratory, The Affiliated People’s Hospital of Ningbo University, Ningbo, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, The Affiliated People’s Hospital of Ningbo University, Ningbo, People’s Republic of ChinaCorrespondence: Liping Chen; Wanjun Yu, Email Chenliliy@outlook.com; nbyuwanjun@163.comBackground: It has been increasingly recognized that circular RNAs (circRNAs) act as a pivotal factor in the onset and progression of human malignancies. Yet, the specific activities and mechanistic roles of these RNAs in the context of lung adenocarcinoma (LUAD) are not fully understood.Methods: Microarray analysis identified a novel LUAD-associated circular RNA, termed hsa_circ_0006357 (also referred to as circEZH2). Reverse transcription–quantitative polymerase chain reaction (RT-qPCR) was utilized for the analysis of circEZH2 expression in tissues and cell lines. The characteristics of circEZH2 were verified by RNase R treatment and fluorescence in situ hybridization (FISH) assays. The functions of circEZH2 were detected by Cell Counting Kit-8 (CCK-8), colony formation, wound healing, and Transwell assays. The molecular mechanism of circEZH2 was clarified through bioinformatics analysis as well as RNA pulldown, dual-luciferase reporter, RT-qPCR, and immunoblotting assays. The role of circEZH2 in vivo was investigated using a xenograft model.Results: This investigation revealed that circEZH2 expression was elevated in LUAD cell lines and tumor samples. This elevation was associated with enhanced cell proliferation, migratory capacity, epithelial–mesenchymal transition (EMT), and invasion in vitro. Conversely, silencing of circEZH2 in vivo resulted in a notable decrease in LUAD tumorigenesis, whereas its overexpression led to the opposite effects. Mechanistically, circEZH2 appeared to act as a sponge for miR-495-3p, facilitating the upregulation of tumor protein D52 (TPD52) and triggering the nuclear factor kappa B (NF-κB) signaling pathway, thus contributing to the progression of LUAD.Conclusion: These findings indicate that circEZH2 may function as a competitive endogenous RNA (ceRNA), driving the progression of LUAD by manipulating the miR-495-3p/TPD52 axis and activating the NF-κB pathway.Keywords: lung adenocarcinoma, circular RNA, nuclear factor kappa B, tumor protein D52, miR-495-3p

Ruyu Han,1,&ast; Leijuan Gan,1,&ast; Liyu Sun,1 Mengran Lang,2 Xindi Tian,1 Kangwei Zhu,1 Lu Chen,1 Guangtao Li,1 Tianqiang Song1 1Department of Hepatobiliary Cancer, Liver Cancer Center, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin Key Laboratory of Digestive Cancer, Tianjin, 300060, People’s Republic of China; 2Hepatobiliary Surgery Department, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tianqiang Song, Department of Hepatobiliary Cancer, Liver Cancer Center, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin Key Laboratory of Digestive Cancer, Tianjin, 300060, People’s Republic of China, Tel +86-22-23340123, Fax +86-22-23537796, Email songtianqiangtj@163.comPurpose: This study aimed to investigate the benefit of conversion therapy for patients with unresectable hepatocellular carcinoma (HCC).Patients and Methods: A retrospective cohort study was conducted involving 40 patients initially deemed unresectable HCC (uHCC). They received surgery following successful conversion therapy involving lenvatinib. The patients were matched in a 1:1 ratio to with a control group who underwent direct surgery, based on pre-treatment clinical data.Results: The median recurrence-free survival (RFS) duration for the conversion therapy cohort was notably longer than that of the direct surgery cohort (25 months vs 11 months). Furthermore, the 1- and 2-year RFS rates were significantly higher in the conversion therapy group compared to the direct surgery group (1 year: 70.5% vs 40.1%; 2 years: 49.0% vs 19.1%). The survival curves indicated a statistically significantly longer RFS in the conversion therapy cohort compared to the direct surgery cohort (P = 0.007). While patients achieving good remission based on both RECIST 1.1 and mRECIST criteria showed superior median RFS, no significant disparity was observed in the survival curves. The subgroup analysis revealed significantly improved prognosis among patients in the conversion therapy group who were male, older, had a history of alcohol consumption, were non-smokers, had liver cirrhosis, possessed Child-Pugh A liver function, had a tumor diameter exceeding 5 cm, and had an AFP ≥ 400 ng/mL. Among the cohort of 40 patients, only 8 individuals encountered severe adverse reactions, which were managed through dose reduction. None of the patients experienced multiple severe adverse reactions concurrently.Conclusion: For patients with unresectable hepatocellular carcinoma, conversion therapy offers a significantly better prognosis than direct surgery for uHCC patients.Keywords: hepatocellular carcinoma, conversion therapy, recurrence-free survival, hepatic resection

Li Ding,1,&ast; Cong Li,1,&ast; Lu Chen,1 Pei-Yu Huang,1 Fei-Fei Bian2 1Emergency Ward, The Affiliated Taizhou People’s Hospital of Nanjing Medical University, Taizhou, Jiangsu, 225300, People’s Republic of China; 2Department of Surgical, The Affiliated Taizhou People’s Hospital of Nanjing Medical University, Taizhou, Jiangsu, 225300, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lu, Chen; Pei-Yu Huang, Emergency Ward, The Affiliated Taizhou People’s Hospital of Nanjing Medical University, No. 366 Taihu Road, Taizhou Pharmaceutical High-Tech District, Taizhou, Jiangsu, 225300, People’s Republic of China, Tel +86 13641589385 ; +86 18705267452, Email chenluchen29@126.com; huangpeiyuh@126.comObjective: The objective of this study is to systematically explore and summarize the best evidence on intervention programs for patients with kinesophobia following percutaneous coronary intervention (PCI) to provide a comprehensive reference for clinical practice interventions.Methods: Evidence on interventions for kinesophobia post-PCI was retrieved from Chinese and international integrated databases, treatment guidelines, and websites of professional associations, including systematic reviews and expert consensuses. The evidence considered in this study extends up to May 2022, encompassing information available since the inception of the databases. Two researchers independently evaluated the articles included in the review and extracted and summarized the available evidence.Results: By extracting and integrating data from the 14 articles included in this review, we identified six categories: pre-intervention assessment, psychological intervention, health education, rehabilitation training, social support, and quality control. A total of 21 pieces of evidence were summarized, including mental health assessment, physical fitness evaluation, timing and content of health education, development of personalized exercise prescriptions, and risk control.Conclusion: In clinical settings, using evidence-based practices requires developing feasible intervention programs based on comprehensive consideration of hospital resources, allocation of medical personnel, and consideration of patients’ preferences to reduce the kinesophobia of patients post-PCI and improve their compliance with exercise rehabilitation.Keywords: evidence-based nursing, evidence summary, intervention, kinesophobia, post-PCI

Dong Liu,1,&ast; Jianmin Wu,2,&ast; Han Wang,3 Hui Dong,3 Lei Chen,4 Ningyang Jia1 1Department of Radiology, The Third Affiliated Hospital of Naval Medical University, Shanghai, 200433, People’s Republic of China; 2Shanghai Key Laboratory of Metabolic Remodeling and Health, Institute of Metabolism and Integrative Biology, Fudan University, Shanghai, 200438, People’s Republic of China; 3Department of Pathology, The Third Affiliated Hospital of Naval Medical University, Shanghai, 200433, People’s Republic of China; 4The International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, 201805, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ningyang Jia; Lei Chen, Email ningyangjia@163.com; chenlei@smmu.edu.cnObjective: To investigate the role of eosinophil counts (EC) in microvascular invasion (MVI) for enhancing the radiomics based diagnostic model. Additionally, its correlation with early recurrence and tumor immune microenvironment was explored.Methods: Propensity score matching was employed to evaluate on 462 cases whether EC was an independent risk factor for MVI. Subgroup analyses examined EC’s effect on MVI across varying hypersplenism degrees. Univariate-multivariate logistic regression identified MVI’s independent factors to develop a diagnostic model. Univariate-multivariate COX regression determined early recurrence factors. Co-detection by indexing (CODEX) constructed the immune score (IS), and Spearman correlation analyzed its association with peripheral immunity.Results: EC was an independent risk factor for MVI (p=0.038, OR=1.304 (95% CI: 1.014– 1.677)), and its effect on MVI disappeared with the severity of hypersplenism. The diagnostic model with EC was significantly improved (AUC=0.787 (95% CI: 0.737– 0.836) vs AUC=0.748(95% CI: 0.694– 0.802, p=0.005)). MVI was an independent risk factor for early recurrence (p< 0.001, HR = 2.254 (95% CI: 1.557– 3.263)). IS was negatively correlated with lymphocyte counts (R=− 0.311, p=0.022), and positively correlated with EC (R=0.301, p=0.027) and RS (R = 0.315, p = 0.018).Conclusion: EC was an independent risk factor for MVI and was related to the tumor immune microenvironment. EC should be included in the diagnosis of MVI to improve diagnostic efficiency.Keywords: hepatocellular carcinoma, eosinophils, radiomics

Wenbin Guo,1,&ast; Lin Sun,1,&ast; Huijun Yue,1,&ast; Xueqin Guo,1 Lin Chen,1 Jinhong Zhang,1 Zhuqi Chen,1 Yiming Wang,1 Jiao Wang,2 Wenbin Lei1 1Otorhinolaryngology Hospital, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, 510080, People’s Republic of China; 2School of Public Health, Sun Yat-sen University, Guangzhou, Guangdong, 510080, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiao Wang, School of Public Health, Sun Yat-sen University, Guangzhou, 510080, Guangdong, People’s Republic of China, Email wangj836@mail.sysu.edu.cn Wenbin Lei, Otorhinolaryngology Hospital, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, Guangdong, People’s Republic of China, Email leiwb@mail.sysu.edu.cnPurpose: Clinical studies focusing on the association between the gut microbiota and obstructive sleep apnea (OSA) are limited. This study aimed to explore the relationship between intermittent hypoxia and the composition of gut microbiota in adults by analyzing the differences in the characteristics and functional distribution of gut microbiota between patients with different severities of OSA and healthy individuals.Patients and Methods: A cohort of 113 individuals from the First Affiliated Hospital of Sun Yat-sen University underwent overnight polysomnography from July 2019 to August 2021. The individuals included 16 healthy controls and 97 patients with OSA, categorized by the apnea-hypopnea index into mild, moderate, and severe groups. Fecal samples were analyzed using high-throughput sequencing of the 16S rRNA V3–V4 region to assess gut microbiota composition and function. Correlation analysis was used to evaluate the association between clinical indicators and microbiota markers.Results: In patients with OSA, the gut microbiota diversity and the abundance of specific microbes that produce short-chain fatty acids decreased (P< 0.05). The phyla Verrucomicrobia and Candidatus Saccharibacteria, genera Gemmiger and Faecalibacterium, and the species Gemmiger formicilis exhibited decreasing abundance with increasing OSA severity. Correlation analysis revealed a robust association between the proportion of total sleep time, characterized by nighttime blood oxygen saturation below 90%, and the alterations in the gut microbiota, demonstrating that elevated levels of desaturation are correlated with pronounced microbiota dysbiosis (P< 0.05).Conclusion: Compared to the control group, the intermittent hypoxia exhibited by patients with OSA may be related to alterations in the composition and structure of the gut microbiota. Our results demonstrate the importance of monitoring hypoxia indicators in future clinical practice.Keywords: obstructive sleep apnea, gut microbiota, 16S rRNA, intermittent hypoxia

Liling Chen,1 Cunqing Zheng,1 Honglin Luan,2 Xinyuan Chen3 1Department of Clinical Laboratory, Wenzhou Seventh People’s Hospital, Wenzhou, Zhejiang Province, People’s Republic of China; 2Department of Psychiatry, Wenzhou Seventh People’s Hospital, Wenzhou, Zhejiang Province, People’s Republic of China; 3Department of Clinical Laboratory, Wenzhou Central Hospital, Wenzhou, Zhejiang Province, People’s Republic of ChinaCorrespondence: Xinyuan Chen, Department of Clinical Laboratory, Wenzhou Central Hospital, Bailidonglu Street, Lucheng District, Wenzhou, 325000, People’s Republic of China, Tel +8615858805715, Fax +86057788070190, Email 742846523@qq.comPurpose: This study aimed to assess High-density Lipoprotein (HDL)-based Inflammatory Indices and lipid profile changes in antipsychotic-naive first-episode schizophrenia (AN-FES) patients, chronic schizophrenia (CS) patients, and explore the clinical and predictive value of these parameters for schizophrenia.Patients and Methods: The study cohort included 52 AN-FES patients, 46 CS patients, and 52 healthy controls (HCs), with an average age of 24 years. Upon admission, patients underwent complete blood count and lipid profile analyses. Various ratios were calculated, including neutrophil-to-HDL (NHR), monocyte-to-HDL (MHR), lymphocyte-to-HDL (LHR), and platelet-to-HDL (PHR), as well as lipid ratios like triglycerides/HDL, non-HDL/HDL, total cholesterol/HDL, and low-density lipoprotein/HDL. For the AN-FES group, these evaluations were repeated after two months of treatment with atypical antipsychotics. Statistical analyses included correlation analysis, Receiver Operating Characteristic (ROC) curve analysis, and univariate and multivariate regression.Results: Compared to HCs, CS patients exhibited significantly higher MHR and NHR values, while AN-FES patients showed elevated levels of PHR, MHR, and NHR. No significant differences were observed in LHR or lipid ratios across the three groups. In the AN-FES cohort, MHR correlated positively with neutrophil counts, and NHR with monocyte counts. Additionally, white blood cell counts were positively associated with both MHR and NHR. Following treatment, NHR levels decreased, whereas TG/HDL ratios increased, with MHR and PHR remaining elevated. ROC analysis highlighted NHR as the most diagnostically valuable parameter (AUC = 0.799), with 86.5% specificity at an optimal cutoff of 3.534, outperforming MHR and PHR. Regression analyses recognized NHR (OR=2.225) as an independent risk factor for schizophrenia, even after adjusting for confounders.Conclusion: HDL-based inflammatory indices, particularly NHR, may serve as valuable diagnostic and prognostic markers in young adults with schizophrenia, even though significant alterations in lipid ratios were not observed in this demographic.Keywords: neutrophil-to-HDL ratio, NHR, monocyte-to-HDL ratio, MHR, platelet-to-HDL ratio, PHR, lipid ratios, schizophrenia, inflammatory indices

Xiaowu Wang,1,2 Tuantuan Li,1,2 Yan Liu,1,2 Yilang Zhu,1,2 Lichang Chen,1,2 Yong Gao1,2 1Department of Clinical Laboratory, The Second People’s Hospital of Fuyang City, Fuyang, Anhui, People’s Republic of China; 2Department of Clinical Laboratory, Fuyang Infection Disease Clinical College of Anhui Medical University, Fuyang, Anhui, People’s Republic of ChinaCorrespondence: Yong Gao, The Second People’s Hospital of Fuyang City, No. 1088, West Yinghe Road, Fuyang, Anhui, People’s Republic of China, Email fyeryuangy8@126.comObjective: We retrospectively review consecutive patients with nontuberculous mycobacterium (NTM) pulmonary disease reported from a designated hospital for infectious diseases in the Fuyang district of China to determine the clinical characteristics of these patients.Methods: This research enrolled 234 patients with NTM pulmonary disease between January 2018 and May 2023 in the Fuyang district of China. Data were collected from the electronic medical records. The NTM strain composition and clinical characteristics of NTM pulmonary disease were retrospectively analyzed.Results: 73 (31.20%) patients had previous tuberculosis (TB) or TB exposure history and bronchiectasis. Mixed NTM infection accounted for 12.39%. Mycobacterium intracellulare strain was detected in 132 patients (49.62%). Women were found to be more affected by Mycobacterium avium infection, and men by Mycobacterium abscessus infection. Mycobacterium avium (34.21%) and Mycobacterium abscessus (33.33%) strains were most common in people with previous TB or TB exposure history. Among respiratory tract-related diseases, patients with bronchiectasis had the highest isolation rate of Mycobacterium avium (55.36%). Women were susceptible to bronchiectasis (P < 0.01). The median of mononuclear-to-lymphocyte ratio (MLR) was higher in men than in women (P < 0.01). The serum albumin (ALB) level was lower in patients with TB or TB exposure history than in those without TB history (P = 0.034). The prognostic nutritional index (PNI) was lower in patients with TB or TB exposure history than in those without tuberculosis history (P = 0.021). Patients with NTM lung disease were poorly treated.Conclusion: Clinical symptoms of the disease were not species-specific. Mycobacterium intracellulare and Mycobacterium avium strains were predominant in the Fuyang district of China. Previous TB or TB exposure history immensely enhanced the risk of NTM disease.Keywords: NTM, clinical symptoms, tuberculosis exposure history, bronchiectasis

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

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

Wenyu Li,1 Yanqiu Hou,1 Jiayu An,1 Linxuan Chen,1 Shan Lu1,2 1School of Medicine and Health Management, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2Research Centre for Rural Health Service, Key Research Institute of Humanities & Social Sciences of Hubei Provincial Department of Education, Wuhan, People’s Republic of ChinaCorrespondence: Shan Lu, School of Medicine and Health Management, Tongji Medical College, Huazhong University of Science and Technology, Hang Kong Road 13, Wuhan, 430030, People’s Republic of China, Tel +86 15827079650, Email shanlu@hust.edu.cnPurpose: The objective of this study was to explore the connection between family doctor contract services and preventable hospitalizations. Additionally, we sought to examine the role of primary health care quality as a mediating factor in the link between family doctor contract services and preventable hospitalizations among patients with hypertension.Patients and Methods: This cross-sectional study was performed in Dangyang (Hubei Province, Central China) and Xishui (Guizhou Province, Western China) counties in July–August 2023. Participants comprised 625 patients selected via a multi-stage sampling method. Causal mediation analysis was conducted to explore the effect of family doctor contract services on preventable hospitalizations and the mediating effect of primary healthcare quality on this relationship.Results: Utilization rate of family doctor contract services of hypertensive patients was 58.6%, score of primary health service quality was 70.75 and incidence of preventable hospitalizations was 28.2%. Amongst hypertensive patients, utilization of family doctor contract services decreased the occurrence of preventable hospitalizations, with a total effect of − 0.22 (p < 0.001). Primary healthcare quality mediates the association, with a mediate effect of − 0.05 (p < 0.001), explaining 22.73% of the total effect.Conclusion: Improving the utilization of family doctor contract services and primary healthcare quality may result in lower rates of preventable hospitalizations amongst hypertensive patients.Keywords: family doctor contract services, preventable hospitalizations, primary healthcare quality, hypertension, mediation analysis

Chunrong Huang,1,2,&ast; Yulian Gao,1,2,&ast; Hongxia Lin,1– 3,&ast; Qinmei Fan,4,&ast; Ling Chen,1,2 Yun Feng1,2 1Department of Respiratory and Critical Care Medicine, Ruijin Hospital Affiliated Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China; 2Institute of Respiratory Diseases, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200025, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, 610000, People’s Republic of China; 4Department of Respiratory and Critical Care Medicine, The First People’s hospital of Jin Zhong, JinZhong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ling Chen; Yun Feng, Email co840608@hotmail.com; fy01057@163.comBackground: To evaluate the clinical features of patients with Acinetobacter baumannii bloodstream infection (BSI).Methods: Totally 200 inpatients with Acinetobacter baumannii BSI were included, clinical features of Acinetobacter baumannii BSI inpatients between 90-day survival and 90-day mortality groups, between 30-day survival and 30-day mortality groups, between patients infected with multidrug-resistant (MDR group) and sensitive Acinetobacter baumannii (sensitive group) were analyzed. The prognostic factors of 90-day mortality were analyzed by univariate logistic regression and multivariate logistic regression. The survival curve in bloodstream infectious patients with multidrug-resistant (MDR group) and sensitive Acinetobacter baumannii (sensitive group) was analyzed by Kaplan–Meier analysis.Results: The 90-day mortality patients had significantly higher carbapenem-resistant bacterial infection and critical care unit (ICU) admission. The 90-day and 30-day mortality groups showed higher C-reactive protein (CRP) and serum creatinine (Scr) levels and lower red blood cells (RBC) and albumin (ALB) levels than their survival counterparts, respectively. Critical surgery, ICU admission and delayed antibiotic treatment were independently prognostic risk predictors for 90-day mortality in Acinetobacter baumannii BSI patients, while critical surgery and diabetes were independently prognostic risk predictors for 90-day mortality in carbapenem-resistant Acinetobacter baumannii BSI patients. Compared with sensitive group, MDR group showed significantly longer ICU and whole hospital stay, lower levels of lymphocytes, RBC, hemoglobin, lactate dehydrogenase and ALB, higher frequency of infection originating from the skin and skin structure. Moreover, patients in the MDR group had a significantly worse overall survival than the sensitive group.Conclusion: We identified the prognostic factors of Acinetobacter baumannii BSI and carbapenem-resistant Acinetobacter baumannii BSI patients. Critical surgery, ICU admission, delayed antibiotic treatment or diabetes were significantly associated with the mortality of those patients. Moreover, aggressive measures to control MDR Acinetobacter baumannii could lead to improved outcomes. Keywords: Acinetobacter baumannii, bloodstream infection, mortality, prognostic predictors, multidrug-resistance

Li Zhao,1 Tuo Zhang,2 Xunliang Li,3 Li Chen,1 Shenglin Zhou,1 Zhaoli Meng,1 Wei Fang,1 Jianle Xu,4 Jicheng Zhang,1 Man Chen1,2 1Department of Critical Care Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, People’s Republic of China; 2Department of Critical Care Medicine, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250021, People’s Republic of China; 3Department of Intensive Care Unit, Central Hospital Affiliated to Shandong First Medical University, Jinan, 250013, People’s Republic of China; 4Department of Statistics and Medical Records Management, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, People’s Republic of ChinaCorrespondence: Jicheng Zhang; Man Chen, Department of Critical Care Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 324 Jingwu Weiqi Road, Jinan, Shandong, 250021, People’s Republic of China, Email zhangjicheng2023@126.com; chenman_slyy@163.comPurpose: Sepsis-associated acute kidney injury (S-AKI) is associated with increased morbidity and mortality. We aimed to develop a nomogram for predicting the risk of S-AKI patients.Patients and Methods: We collected data from septic patients admitted to the Provincial Hospital Affiliated with Shandong First Medical University from January 2019 to September 2022. Septic patients were divided into two groups based on the occurrence of AKI. A nomogram was developed by multiple logistic regression analyses. The performance of the nomogram was evaluated using C-statistics, calibration curves, and decision curve analysis (DCA). The validation cohort contained 70 patients between December 2022, and March 2023 in the same hospital.Results: 198 septic patients were enrolled in the training cohort. Multivariate logistic regression analysis showed that neutrophil gelatinase-associated lipocalin (NGAL), platelet-to-lymphocyte ratio (PLR), and vasopressor use were independent risk factors for S-AKI. A nomogram was developed based on these factors. C-statistics for the training and validation cohorts were respectively 0.873 (95% CI 0.825– 0.921) and 0.826 (95% CI 0.727– 0.924), indicating high prediction accuracy. The calibration curves showed good concordance. DCA revealed that the nomogram was of great clinical value.Conclusion: The nomogram presents early and effective prediction for the S-AKI patients, and provides optimal intervention to improve patient outcomes.Keywords: sepsis, acute kidney injury, neutrophil gelatinase-associated lipocalin, platelet-to-lymphocyte ratio, vasopressor use, nomogram

Na Cui,1 Xue Li,1 Xin Wen,1 JingJing Xu,2 Li Chen1 1Department of Obstetrics and Gynecology, Baoding No.1 Central Hospital, Baoding City, Hebei Province, 071000, People’s Republic of China; 2Department of Ultrasound, Baoding No.1 Central Hospital, Baoding City, Hebei Province, 071000, People’s Republic of ChinaCorrespondence: Li Chen, Department of Obstetrics and Gynecology, Baoding No.1 Central Hospital, No. 320 Changcheng North Street, Baoding City, Hebei Province, 071000, People’s Republic of China, Email chenliphd1407@outlook.comObjective: Analyze women treated with underwent cold knife conization (CKC) to remove advanced squamous intraepithelial lesions (CIN) of the cervix. The histopathological upgrading of the lesions previously detected on vaginal biopsy and postoperative pregnancy outcomes of were investigated, to identify high-risk subgroups in women.Methods: A retrospective study was conducted at the First Central Hospital of Baoding City from June 2019 to December 2022 to analyze confirmed cases of Cervical Intraepithelial Neoplasia CIN-II and CIN-III. Investigation of pathological changes in postoperative pathological tissues, and to perform binary logistic analysis to identify risk factors for histopathological escalation in postoperative lesions. We analyze the effects of CKC surgery on pregnancy outcomes in patients by comparing against a control group of healthy pregnant women.Results: Out of the 176 patients diagnosed with CIN-II who underwent cervical biopsy, 39 (22.16%) were found to have a final specimen diagnosis of CIN-III, while 7 (3.98%) were downgraded to CIN-I. Among the 108 patients diagnosed with CIN-III who underwent cervical biopsy, 7 cases (6.48%) were ultimately confirmed to have CIN-III. Ki67-positive, p16-positive (OR = 1.13, 95% CI 1.01– 1.15), and colposcopy biopsy for CIN-II (OR = 1.59, 95% CI 1.33– 3.6) were independent risk factors for pathological upgrade after CKC. Compared with healthy pregnant women, CIN patients had higher rates of premature birth (14.4%), premature rupture of the fetal membrane (13.6%), and cesarean section (37.5%) (P < 0.05). The mode of conception, abortion rate, ectopic pregnancy rate, and postpartum hemorrhage were not different between healthy pregnant women and CIN patients (P > 0.05).Conclusion: Following cervical multi-point biopsy or CKC, along with pathological examination, the accurate diagnosis of cervical lesions is crucial as it allows for more precise identification of such lesions. Additionally, CKC increases the risk of premature birth, premature rupture of membranes, and the need for cesarean section.Keywords: cervical intraepithelial neoplasia, cold knife conization, pregnant women, colposcopy biopsy

Hao Wang,1 Yinbo Xiao,1 Yumeng Cai,1 Yang Zhou,1 Longyun Chen,1 Jianbin Guo,2 Xiaohua Shi,1 Zhiyong Liang1 1Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, 100730, People’s Republic of China; 2Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, 100730, People’s Republic of ChinaCorrespondence: Zhiyong Liang; Xiaohua Shi, Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, No. 1 Shuaifuyuan, Dongcheng District, Beijing, Tel +86 10-69159353 ; +86 10-69159365, Email liangzy@pumch.cn; shixiaohua3762@foxmail.comIntroduction: This study used single-center data to analyze the clinicopathological features of site-specific endometrial cancer.Methods: Patients with endometrial carcinoma who had undergone surgery at Peking Union Medical College Hospital, China, between March 2016 and January 2022 were enrolled. Clinical information and pathological characteristics were summarized, and microsatellite status was analyzed using the immunohistochemical method. Patient prognoses were measured in terms of the rates of overall survival and progression-free survival.Results: The mean patient age was 49 years (ranging: from 25 to 76 years old), and there was no difference in clinicopathological features between endometrioid and type II endometrial carcinoma in LUSC. The ER and PR expression ratios were 80.4% and 64.3%, respectively, in this LUSC cohort, and the MMR deficiency ratio was 33.9%, including 39.6% in endometrioid carcinoma and 15.4% in type II endometrial carcinoma. Combined MSH2&MSH6 loss was more common than combined MLH1&PMS2 being unexpressed (16.1% vs 12.5%), and dMMR patients differed significantly from the pMMR group in terms of vascular invasion (P=0.003). The combination of chemotherapy and radiotherapy did not provide a statistically significant improvement in prognosis compared to chemotherapy alone.Conclusion: The results of this study showed that LUSC patients tended to be younger and their tumors had less expression of hormone markers. The biological behavior of both endometrioid cancer and type II EC may be similar when EC occurs in this area. Furthermore, this type of tumor also showed a higher incidence of vascular invasion, and the combination of chemotherapy and radiotherapy did not provide significant improvement. Thus, successful treatment of LUSC tumors requires aggressive surgical intervention and a more effective postoperative treatment approach.Keywords: endometrial cancer, lower uterine segment, prognosis

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

Xinyu Han,1 Tian Qiang Wu,1 Ruiting Yao,1 Chang Liu,1 Lu Chen,2 Xiaoling Feng2 1Department of First Clinical Medical College, Heilongjiang University of Chinese Medicine, Harbin, People’s Republic of China; 2Department of Gynecology, The First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, People’s Republic of ChinaCorrespondence: Xiaoling Feng, Department of Gynecology, The First Affiliated Hospital of Heilongjiang University, No. 26, Heping Road, Xiang-Fang District, Harbin City, Heilongjiang Province, People’s Republic of China, Email Doctorfxl@163.comBackground: Observational studies have established a connection between Gastroesophageal reflux disease (GERD) and preterm birth (PTB). Nevertheless, these correlations can be affected by residual confounding or reverse causality, resulting in ambiguity regarding the connection. The objective of this study was to assess the relationship between genetically predicted GERD and PTB.Methods: Initially, we performed bidirectional univariate Mendelian randomization (UVMR) analysis utilizing publicly accessible genome-wide association studies (GWAS) data. The primary analytical approach employed to determine the causal impact between GERD and PTB is the inverse variance weighted technique (IVW). Subsequently, we utilized multivariate Mendelian randomization (MVMR) to adjust for potential factors that could influence the results, such as body mass index (BMI), maternal smoking around birth, educational attainment, household income, and Townsend deprivation index (TDI). Furthermore, we performed a sequence of comprehensive sensitivity analyses to assess the reliability of our MR findings.Results: The UVMR analysis results showed a significant correlation between GERD and PTB (odds ratio [OR]: 1.810; 95% confidence interval [CI]: 1.344– 2.439; P=9.60E-05) in the IVW model, and the Weighted median method (OR=1.591, 95% CI=1.094– 2.315, P=0.015) revealed consistent results. The inverse MR findings suggest no causal link between PTB and the incidence of GERD. In addition, the sensitivity analysis did not detect heterogeneity or horizontal pleiotropy, and the “leave-one-out” examination confirmed that the causal estimation is unlikely to be influenced by the single nucleotide polymorphisms (SNPs) effect. The MVMR analysis demonstrated that the causal association between GERD and PTB still existed after considering BMI, maternal smoking around birth, educational attainment, household income, and TDI (OR=1.921, 95% CI=1.401– 2.634, P=5.08E-05).Conclusion: This study presents evidence indicating that genetically predicted GERD can heighten the risk of PTB. Therefore, it is advisable to perform focused screening for pregnant women with GERD in order to find the initial signs of PTB and promptly apply intervention strategies to extend the duration of pregnancy.Keywords: Mendelian randomization, gastroesophageal reflux disease, preterm birth, causality

Liang Chen,1,2 Zeqiang Xie,1,2 Jiyong Jian1,2 1Clinical Laboratory Medicine, Beijing Shijitan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Beijing Key Laboratory of Urinary Cellular Molecular Diagnostics, Beijing, People’s Republic of ChinaCorrespondence: Jiyong Jian, Clinical Laboratory Medicine, Beijing Shijitan Hospital, Capital Medical University, NO. 10, Tie Yi Road, Yang Fang Dian, Beijing, Haidian District, People’s Republic of China, Email jianjiyong3137@bjsjth.cnPurpose: We investigated the Epidemiology, risk factors and outcomes of Candida bloodstream infection.Methods: The electronic laboratory records data of patients with candidemia (2015– 2022) were collected. We used univariate and multivariate logistic regression to determine the risk factors of candidemia.Results: Of the 134 patients with candidemia, the most prevalent species were Candida albicans (37.2%), followed by Candida glabrata (27.7%), Candida parapsilosis (18.9%), and others. The mean annual incidence was 0.33/1000 admissions. The overall resistance rate of Candida spp. against fluconazole and voriconazole were 4.9% (7/142) and 5.9% (6/101), while Candida tropicalis showed high resistance to fluconazole (38.8%) and voriconazole (27.8%). The 30-day mortality rate was 32.8%. On multivariate analysis, age ≥ 65 (odds ratio [OR] = 3.874, 95% confidence interval [CI]: 1.146, 13.092; P = 0.029), high Acute Physiology and Chronic Health Evaluation II (APACHE II) score (OR = 12.384, 95% CI: 2.963, 51.762; P = 0.001), shock (OR = 3.428, 95% CI: 1.097, 10.719; P = 0.034), initial antifungal therapy (OR = 0.057, 95% CI: 0.011, 0.306; P = 0.001) and White blood cells (OR = 1.129, 95% CI: 1.016, 1.255; P = 0.024) were the independent risk factors with mortality within 30 day in patients with candidemia.Conclusion: The incidence rate and the mortality rate of candidemia are high, and lower azole susceptibility was found in Candida tropicalis. Age≥ 65 years, Shock, high APACHE II score, Antifungal therapy and White blood cells count were independently associated with 30-day mortality.Keywords: Candidemia, Epidemiology, Antifungal susceptibility, Mortality, Risk factors

Yuzhu Mu, Ting Pan, Lingling Chen Department of Dermatology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Suzhou, Jiangsu, 215000, People’s Republic of ChinaCorrespondence: Lingling Chen, Email chenlingling031@126.comAbstract: Vitiligo and alopecia areata are both autoimmune skin diseases, and the chances of co-occurrence are very low. Conventional treatments often include glucocorticoids, which have many adverse reactions with long-term use and are difficult to achieve satisfactory results. Upadacitinib has been found to be effective in both vitiligo and alopecia areata due to partial overlap in pathogenic pathways. We report the successful treatment of vitiligo combined with alopecia areata in a nine-year-old child with upadacitinib in combination with UVB. The area of vitiligo and alopecia areata decreased significantly, and satisfactory results were obtained. It provides a new idea for the treatment of vitiligo complicated with alopecia areata in children.Keywords: vitiligo, alopecia areata, JAK inhibitor, children

Xijing Yu,1,&ast; Yaqin Chen,1,&ast; Yanchun Peng,2 Liangwan Chen,3,4 Yanjuan Lin2,3 1School of Nursing, Fujian Medical University, Fuzhou, Fujian, People’s Republic of China; 2Department of Nursing, Fujian Medical University Union Hospital, Fuzhou, Fujian, People’s Republic of China; 3Department of Cardiac Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, People’s Republic of China; 4Key Laboratory of Cardio-Thoracic Surgery, Fujian Medical University, Fuzhou, Fujian, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yanjuan Lin, Department of Nursing, Union Hospital, Fujian Medical University, No. 29 Xinquan Road, Fuzhou, Fujian Province, 350001, People’s Republic of China, Tel +86059186218336, Fax +86059183344034, Email fjxhyjl@163.com Liangwan Chen, Department of Cardiac Surgery, Union Hospital, Fujian Medical University, No. 29 Xinquan Road, Fuzhou, Fujian Province, 350001, People’s Republic of China, Tel +86059186218336, Fax +86059183301393, Email fjxhlwc@163.comPurpose: The inflammatory response of the body is intimately linked to the quick onset and high in-hospital mortality of Acute Type A Aortic Dissection (ATAAD). The purpose of the study was to examine the connection between in-hospital mortality in patients with ATAAD upon admission and the Pan-Immune-Inflammation Value (PIV).Patients and Methods: 308 patients who were diagnosed with ATAAD between September 2018 and October 2021 at Fujian Provincial Center for Cardiovascular Medicine had their clinical data retrospectively examined. PIV was assessed at the time of study population admission, with in-hospital mortality serving as the main outcome measure. Patients were divided into two groups, the high PIV group (PIV > 1807.704) and the low PIV group (PIV < 1807.704), based on the PIV ROC curve and the best threshold of the Youden index. The clinical results of the two groups were then compared.Results: Among ATAAD patients, postoperative in-hospital mortality was higher in the high PIV group (54.7% vs 10.6%, P < 0.001), and the high PIV group had significantly higher rates of postoperative acute kidney injury, acute liver insufficiency, and gastrointestinal hemorrhage (P < 0.05). Additionally, the high PIV group’s ICU stays lasted longer than the low PIV group’s (P < 0.05). The results of multifactorial logistic regression analysis, which controlled for other variables, indicated that the mechanical ventilation time (OR = 1.860, 95% CI: 1.437, 2.408; P < 0.001), the high PIV group (> 1807.704) (OR = 1.939, 95% CI: 1.257, 2.990; P = 0.003), the cardiopulmonary bypass time (OR = 1.011, 95% CI: 1.004, 1.018; P = 0.002), and the white blood cell count (OR = 1.188, 95% CI: 1.054, 1.340; P = 0.005) were independent risk factors for postoperative in-hospital mortality in ATAAD patients.Conclusion: Postoperative death in ATAAD patients was independently predicted by high PIV levels at admission. Patients should be informed about their preoperative inflammatory status and actively participate in prompt clinical decision-making and treatment.Keywords: Acute Type A Aortic Dissection, the Pan-Immune-Inflammation Value, Inflammation, Cardiac surgery, In-hospital mortality

Dongzhu Lu,1,&ast; Huapeng Yu,2,&ast; Lichang Chen,3 Jinlan Lin,1 Shijie Chen,1 Yunjian Huang1 1Department of Thoracic Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, People’s Republic of China; 2Department of Respiratory Medicine, Shenzhen Hospital, Southern Medical University, Shenzhen, People’s Republic of China; 3Department of Pulmonary and Critical Care Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yunjian Huang, Department of Thoracic Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, People’s Republic of China, Tel +86 13805099580, Email yunjian13@126.comPurpose: We compared pulmonary function indices and quantitative CT parameters of airway remodeling, air trapping, and emphysema in asthmatic patients and patients with COPD and asthma–COPD overlap (ACO) and explored their relationships with airflow limitation.Patients and Methods: Patients with asthma (n=48), COPD (n=52), and ACO (n=30) and controls (n=54) who completed pulmonary function tests and HRCT scans were retrospectively enrolled in our study. Quantitative CT analysis software was used to assess emphysema (LAA%), airway wall dimensions (wall area (WA), luminal area (LA), and wall area percentage (WA%)), and air trapping ((relative volume change of − 860 HU to − 950 HU (RVC− 860 to-950) and the expiration-to-inspiration ratio of the mean lung density (MLDE/I))). Differences in pulmonary function and HRCT parameters were compared among the groups. Spearman correlation analysis and regression analysis were utilized to explore structure‒function relationships.Results: The LAA% in COPD and ACO patients was significantly greater than that in asthmatic patients and controls. The WA% and WA in COPD and ACO patients were greater than those in controls, whereas the WA% and LA between asthmatic patients and controls reached statistical significance. The RVC− 860 to − 950 levels decreased in the following order: ACO, COPD, and asthma. RVC− 860 to − 950 independently predicted FEV1% in asthmatic patients; LAA% and MLDE/I in COPD patients; and LAA%, WA% and RVC− 860 to − 950 in ACO patients.Conclusion: Comparable emphysema was observed in patients with COPD and ACO but not in asthmatic patients. All patients exhibited proximal airway remodeling. The bronchi were thickened outward in COPD and ACO patients but are thickened inward in asthmatic patients. Furthermore, air trapping in ACO patients was the most severe among all the groups. Indirect lung densitometry measurements might be more predictive of the degree of airflow limitation than direct airway measurements in obstructive airway diseases.Keywords: asthma, COPD, asthma-COPD overlap, quantitative HRCT, structure-function relationship

Tao Chen,1– 3,&ast; Yumeng Wei,1– 3,&ast; Suyu Yin,1– 3,&ast; Wen Li,1– 3 Yuxiang Wang,1– 3 Chao Pi,1– 3 Mingtang Zeng,3,4 Xiaodong Wang,5 Ligang Chen,6 Furong Liu,7 Shaozhi Fu,8 Ling Zhao2,3 1Key Laboratory of Medical Electrophysiology, Ministry of Education, School of Pharmacy, Southwest Medical University, Luzhou, 646000, People’s Republic of China; 2Luzhou Key Laboratory of Traditional Chinese Medicine for Chronic Diseases Jointly Built by Sichuan and Chongqing, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University; Luzhou, Sichuan, 646000, People’s Republic of China; 3Central Nervous System Drug Key Laboratory of Sichuan Province, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of China; 4Department of Pharmacy, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 5Department of Hepatobiliary Diseases, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of China; 6Department of neurosurgery, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of China; 7Department of Oncology, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of China; 8Department of Oncology, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shaozhi Fu, Department of Oncology, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, People’s Republic of China, Tel +86 830-3165698, Fax +86 830-3165690, Email shaozhifu513@163.com Ling Zhao, Luzhou Key Laboratory of Traditional Chinese Medicine for Chronic Diseases Jointly Built by Sichuan and Chongqing, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, No. 182, Chunhui Road, Longmatan District, Luzhou, Sichuan, 646000, China, Tel +86 830 2681630, Email zhaoling@swmu.edu.cnPurpose: The present study aimed to develop a lipid nanoplatform, denoted as “BAL-PTX-LN”, co-loaded with chiral baicalin derivatives (BAL) and paclitaxel (PTX) to promote the anti-lung cancer efficacy of paclitaxel and reduce the toxicity of chemotherapeutic drugs.Methods: BAL-PTX-LN was optimized through central composite design based on a single-factor experiments. BAL-PTX-LN was evaluated by TEM, particle size, encapsulation efficiency, hemolysis rate, release kinetics and stability. And was evaluated by pharmacokinetics and the antitumor efficacy studied both in vitro and in vivo. The in vivo safety profile of the formulation was assessed using hematoxylin and eosin (HE) staining.Results: BAL-PTX-LN exhibited spherical morphology with a particle size of 134.36 ± 3.18 nm, PDI of 0.24 ± 0.02, and with an encapsulation efficiency exceeding 90%, BAL-PTX-LN remained stable after 180 days storage. In vitro release studies revealed a zero-order kinetic model of PTX from the liposomal formulation. No hemolysis was observed in the preparation group. Pharmacokinetic analysis of PTX in the BAL-PTX-LN group revealed an approximately three-fold higher bioavailability and twice longer t1/2 compared to the bulk drug group. Furthermore, the IC50 of BAL-PTX-LN decreased by 2.35 times (13.48 μg/mL vs 31.722 μg/mL) and the apoptosis rate increased by 1.82 times (29.38% vs 16.13%) at 24 h compared to the PTX group. In tumor-bearing nude mice, the BAL-PTX-LN formulation exhibited a two-fold higher tumor inhibition rate compared to the PTX group (62.83% vs 29.95%), accompanied by a ten-fold decrease in Ki67 expression (4.26% vs 45.88%). Interestingly, HE staining revealed no pathological changes in tissues from the BAL-PTX-LN group, whereas tissues from the PTX group exhibited pathological changes and tumor cell infiltration.Conclusion: BAL-PTX-LN improves the therapeutic effect of poorly soluble chemotherapeutic drugs on lung cancer, which is anticipated to emerge as a viable therapeutic agent for lung cancer in clinical applications. Keywords: baicalin derivative, paclitaxel, chemotherapy, lung cancer, lipid nano platform, combination therapy

Ziwei Jiang,&ast; Lianglong Chen,&ast; Lei Huang, Shengxiang Yu, Jiabao Lin, Mengyao Li, Yanbin Gao, Lei Yang Department of Burns, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lei Yang, Department of Burns, Nanfang Hospital, Southern Medical University, Jingxi Street, Baiyun District, Guangzhou, 510515, People’s Republic of China, Tel +86-20-6164-1841, Email yuanyang@smu.edu.cnAbstract: Endogenous stem cell homing refers to the transport of endogenous mesenchymal stem cells (MSCs) to damaged tissue. The paradigm of using well-designed biomaterials to induce resident stem cells to home in to the injured site while coordinating their behavior and function to promote tissue regeneration is known as endogenous regenerative medicine (ERM). ERM is a promising new avenue in regenerative therapy research, and it involves the mobilizing of endogenous stem cells for homing as the principal means through which to achieve it. Comprehending how mesenchymal stem cells home in and grasp the influencing factors of mesenchymal stem cell homing is essential for the understanding and design of tissue engineering. This review summarizes the process of MSC homing, the factors influencing the homing process, analyses endogenous stem cell homing studies of interest in the field of skin tissue repair, explores the integration of endogenous homing promotion strategies with cellular therapies and details tissue engineering strategies that can be used to modulate endogenous homing of stem cells. In addition to providing more systematic theories and ideas for improved materials for endogenous tissue repair, this review provides new perspectives to explore the complex process of tissue remodeling to enhance the rational design of biomaterial scaffolds and guide tissue regeneration strategies.Keywords: endogenous stem cell homing, in situ tissue regeneration, biomimetic design, wound healing, bioactive materials

Li Chen,1,&ast; Pooja Khamar,2,&ast; Ying Wang,3 Hong Fu,1 Rohit Shetty2 1Johnson & Johnson Surgical Vision, Inc., Milpitas, CA, USA; 2Narayana Nethralaya Eye Hospital, Bangalore, India; 3Johnson & Johnson Surgical Vision, Inc., Irvine, CA, USA&ast;These authors contributed equally to this workCorrespondence: Li Chen, Johnson & Johnson Surgical Vision, Inc., 510 Cottonwood Drive, Milpitas, CA, 95035, USA, Tel +1 408 273 4062, Email lchen185@its.jnj.comPurpose: To evaluate the changes of higher-order wavefront aberrations following the Smooth Incision Lenticular Keratomileusis (SILKTM) procedure for correction of myopic refractive errors with and without astigmatism, using the ELITATM Femtosecond Platform.Methods: This prospective study included 24 eyes that underwent SILK procedure using one ELITA femtosecond laser system for the correction of myopic refractive errors with and without astigmatism. Preoperative and postoperative 1-day, 1-week, 1-month, 3-month, and 9-month eye exams were measured with a commercial wavefront aberrometer (iDESIGN® Refractive Studio, Johnson & Johnson Surgical Vision, Inc). Wavefront aberrations up to the 6th order Zernike coefficients, including coma Z(3, − 1) and Z(3, 1), spherical aberration Z(4, 1), and the wavefront error of all higher-order aberrations (HOAs RMS), were evaluated across a 6 mm pupil.Results: The mean manifest refractive spherical equivalent changed from the preoperative refractions − 3.82 ± 1.26 D (range − 6.00 to − 2.25 D) to the postoperative refractions − 0.20 ± 0.15 D (range − 0.50 to 0.00 D) at the 9-month follow-up. Compared to baseline preoperative HOAs, the mean postoperative HOAs were significantly increased at the 1-day follow-up. On average, at the 9-month postoperative assessment the vertical coma Z(3, − 1) was − 0.054 ± 0.186 μm, horizontal coma Z(3, 1) was 0.016 ± 0.124 μm, spherical aberration Z(4, 0) was 0.046 ± 0.163 μm, and HOAs RMS was 0.363 ± 0.115 μm across a 6 mm pupil. There is no significant difference in the mean HOAs starting at 1-week follow-up for the horizontal coma (P = 0.346) and spherical aberration (P = 0.095).Conclusions: The visual outcomes demonstrated that the SILK procedure for refractive lenticule extraction using ELITA femtosecond laser system is effective and predictable for the correction of myopic refractive errors with and without astigmatism. The ELITA femtosecond laser system induced minimal HOAs in surgical eyes following the SILK procedures. These results demonstrate fast corneal recovery starting at 1-week follow-up, and spherical aberration was not induced.Keywords: wavefront aberrations, corneal refractive surgery, laser-assisted lenticule extraction, smooth incision lenticular keratomileusis

Wei Zhang, Haiqing Liu, Tuantuan Li, Ying Jiang, Xiaoyu Cao, Li Chen, Lili Zhou The Second People’s Hospital of Fuyang City, Fuyang, Anhui, People’s Republic of ChinaCorrespondence: Lili Zhou, The Second People’s Hospital of Fuyang City, No. 1088, West Yinghe Road, Fuyang, Anhui, People’s Republic of China, Email zw2314160@163.comObjective: Investigate the differences in clinical manifestations, imaging features, and associated inflammatory markers between Nontuberculous Mycobacterial Pulmonary Disease (NTM-PD) and Pulmonary Tuberculosis (PTB), identify potential risk factors for NTM-PD, and establish a logistic regression model to evaluate its diagnostic value.Methods: Baseline data were collected from 145 patients with NTM-PD and 206 patients with PTB. Propensity score matching (PSM) was utilized to achieve a 1:1 match between the two groups, resulting in 103 matched pairs. The differences in comorbidities, imaging features, and inflammatory markers were compared between the two groups. Multivariate binary logistic regression analysis was conducted to identify independent influencing factors, and the diagnostic value of the established model was evaluated.Results: After matching, significant differences were observed between the NTM-PD group and the PTB group in terms of diabetes, bronchiectasis, chronic obstructive pulmonary disease(COPD), cystic and columnar changes, lung cavity presentation, and monocyte percentage (MONO%), lymphocyte count (LYMPH&num;), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) (P

Lifeng Tang,1,2 Wei Zhang,3 Long Chen2 1Department of Oncology, Liuzhou People’s Hospital, Liuzhou, Guangxi, 545006, People’s Republic of China; 2Department of Radiotherapy, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, 530021, People’s Republic of China; 3Department of Radiology, Liuzhou People’s Hospital, Liuzhou, Guangxi, 545006, People’s Republic of ChinaCorrespondence: Long Chen; Wei Zhang, Email clong6@126.com; holly2yang@126.comBackground: Research on the sequencing of brain radiotherapy and targeted chemotherapy after brain metastasis (BM) in HER2-positive breast cancer patients is limited and inconclusive. This study investigated the efficacy of sequential delivery of radiotherapy and targeted therapy in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer with BM.Methods: Fifty-seven patients were categorized into two groups: the targeted-radiotherapy group (receiving 2– 8 cycles of anti-HER2-targeted therapy followed by radiotherapy after BM) and the radiotherapy-targeted group (undergoing radiotherapy first, followed by regular anti-HER2-targeted therapy). The study endpoints were intracranial progression-free survival (iPFS) and overall survival. Factors associated with intracranial progression and mortality were assessed by univariate and multivariate Cox proportional hazards analysis.Results: Patients in the radiotherapy-targeted group had better iPFS (P < 0.001), while there was no significant difference in overall survival between the two groups (P = 0.145). Multivariate Cox analysis showed that different sequential treatment groups were independent prognostic factors for iPFS. In patients with a modified breast graded prognostic assessment score of 3.5– 4.0, the median survival time was 26 months in the radiotherapy-targeted group and 22 months in the targeted-radiotherapy group (P = 0.019).Conclusion: Overall, radiotherapy followed by targeted therapy may improve survival in HER2-positive breast cancer patients with BM, particularly in those with a modified breast graded prognostic assessment score of 3.5– 4.0.Keywords: HER2, breast cancer, brain metastasis, craniocerebral radiotherapy, HER2-targeted drugs

Yi Zhang,&ast; Yiqing Guo,&ast; Chao Gong, Junzuo Fu, Lianhua Chen Department of Anesthesiology, Shanghai General Hospital of Nanjing Medical University, Shanghai, 200080, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Junzuo Fu; Lianhua Chen, Department of Anesthesiology, Shanghai General Hospital of Nanjing Medical University, No. 100 Haining Road, Shanghai, 200080, People’s Republic of China, Tel +86-21-63240090, Email Fujunzuo021@163.com; emily19941010@126.comBackground: The positive roles of deep muscle relaxation in abdominal surgeries and transversus abdominis plane block (TAPB) in the postoperative analgesia. This study aimed to discuss the effects of TAPB on abdominal muscle relaxation, the intraoperative diaphragmatic, and the respiratory functions.Methods: The patients were randomly divided into the TAPB group who received single-shot TAPB bilaterally (n=30), and the control group who did not receive TAPB (n=30). Both groups keep the same steps for other procedures in the surgeries and anesthesia. Four time points for monitoring were defined: The moment when pneumoperitoneum pressure stabilized following endotracheal intubation and anesthetic induction (T0), appearance of the first incisure in the pressure-volume (P-V) loop (T1), appearance of the second incisure in the P-V loop (T2), and the moment with single stimulation (SS) =20% (T3). Primary observation parameters were SS1 measured by muscle relaxation monitoring at T1, and SS2 at T2. Secondary observation parameters included surgeon’s satisfaction with surgical field and respiratory dynamics at the four time points.Results: The two groups were comparable in age, gender, BMI, ASA grade, and operation time. The TAPB group had a dramatic reduction in the total dose of intraoperative sufentanil (0.73± 0.21 ug/kg) compared with the control group (0.87± 0.18 ug/kg) (P=0.023); Other use of drug did not differ between the two groups. The two groups did not differ significantly in SS at either T1 (SS1) or T2 (SS2). In either group, surgeon’s satisfaction with surgical field at T1 and T2 decreased dramatically compared with T0 and T3 (all P< 0.05). At each time point, the respiratory dynamics and the surgeon’s satisfaction with surgical field did not differ significantly between the two groups.Conclusion: TAPB reduced the use of intraoperative analgesics without altering the degree of abdominal relaxation, or affecting surgeon’s satisfaction with surgical field in the patients receiving laparoscopic colorectal surgery.Keywords: Transversus abdominis plane block, deep muscle relaxation, analgesia, laparoscopic colorectal surgery

Heng Yang, Lixia Chen, Danjuan Ye, Ying Wu, Huafang Zhang Department of Nursing, the Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University, Yiwu, 322000, People’s Republic of ChinaCorrespondence: Huafang Zhang, Department of Nursing, the Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University, N1 Shangcheng Avenue, Yiwu, Zhejiang, 322000, People’s Republic of China, Email wuyizhangyichi@zju.edu.cnPurpose: The objective of this study was to investigate latent classes of oral health and the factors associated with them in acutely admitted elderly inpatients.Patients and Methods: A cross-sectional study was conducted using purposive sampling to survey Chinese older-adult acutely inpatients. Data was collected utilizing several instruments, including a general information questionnaire, Brief Oral Health Status Examination (BOHSE), Oral Frailty Index-8 (OFI-8), Mini-Nutritional Assessment Short Form (MNA-SF), and Frailty Screening Questionnaire (FSQ). Latent class analysis was applied to identify distinct categories of oral health among elderly inpatients, and multinomial logistic regression was employed to analyze the factors associated with different oral health categories.Results: In this study, a total of 504 elderly patients were ultimately included, leading to the identification of three latent classes of oral health: “oral health-low level group (41.27%)”, “oral health-moderate level group (25.4%)”, and “oral health-high level group (33.33%)”. The findings revealed that patients with advanced age, elevated neutrophil percentage, and higher C-reactive protein (CRP) values were more likely to be classified in the low oral health group. Additionally, individuals experiencing malnutrition and frailty had a higher risk of falling into the low oral health category. Those with comorbidities and oral frailty were more prevalent in the moderate oral health group. At the same time, elderly patients with higher BMI (22.95± 3.043) ratios were more likely to be categorized in the high oral health group.Conclusion: This study sheds light on three distinct latent classes of oral health among acutely admitted elderly inpatients. These findings underscore the importance of healthcare professionals focusing on the assessment and health education of elderly patients’ oral health. Furthermore, personalized interventions should be developed to promote healthy aging, with particularly attention to enhancing oral health outcomes in this population.Keywords: emergency department, oral health, factors, older people, latent class analysis, frailty

Na Qu,1 Ke Song,2 Yating Ji,1 Mingxia Liu,1 Lijiang Chen,1 Robert J Lee,3,4 Lesheng Teng3,5 1School of Pharmacy, Liaoning University, Shenyang, 110036, People’s Republic of China; 2MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, Maastricht, 6229 ER, the Netherlands; 3School of Life Sciences, Jilin University, Changchun, 130023, People’s Republic of China; 4College of Pharmacy, The Ohio State University, Columbus, OH, 43210, USA; 5State Key Laboratory of Long-Acting and Targeting Drug Delivery System, Yantai, 264000, People’s Republic of ChinaCorrespondence: Lesheng Teng, Email tenglesheng@jlu.edu.cnAbstract: Nanoparticle-based systems are extensively investigated for drug delivery. Among others, with superior biocompatibility and enhanced targeting capacity, albumin appears to be a promising carrier for drug delivery. Albumin nanoparticles are highly favored in many disease therapies, as they have the proper chemical groups for modification, cell-binding sites for cell adhesion, and affinity to protein drugs for nanocomplex generation. Herein, this review summarizes the recent fabrication techniques, modification strategies, and application of albumin nanoparticles. We first discuss various albumin nanoparticle fabrication methods, from both pros and cons. Then, we provide a comprehensive introduction to the modification section, including organic albumin nanoparticles, metal albumin nanoparticles, inorganic albumin nanoparticles, and albumin nanoparticle-based hybrids. We finally bring further perspectives on albumin nanoparticles used for various critical diseases.Plain Language Summary: Albumin appears to be a promising carrier for drug delivery with superior biocompatibility and enhanced targeting capacity. This review focuses on the importance of albumin nanoparticles in drug delivery and concludes the recent fabrication techniques to prepare albumin nanoparticles, the modification strategies to require functional albumin nanoparticles, and critical applications of albumin nanoparticles in various diseases. The aim of this review is to help readers understand the significant potential of albumin nanoparticles in drug delivery. Keywords: albumin nanoparticle, drug delivery, fabrication, modification, application

Ying Lan,1 Die Hu,1 Shijing Huang,1 Qing Ma,1 Li Chen,2,3 Min Xu,1 Qin He1 1Department of Pharmacy, Affiliated Hospital of Southwest Jiaotong University, The Third People’s Hospital of Chengdu, Chengdu, Sichuan, 610031, People’s Republic of China; 2Department of Pharmacology, Faculty of Medicine, University of the Basque Country, UPV/EHU, Leioa, Spain; 3Department of Pharmacy and Evidence-Based Pharmacy Center, West China Second University Hospital, Sichuan University, Chengdu, People’s Republic of ChinaCorrespondence: Ying Lan; Li Chen, Email lanying0212@126.com; chenl_hxey@scu.edu.cnPurpose: This study conducted a pharmacovigilance analysis based on the FDA Adverse Event Reporting System (FAERS) database to compare the infection risk of inhaled or nasal Beclomethasone, Fluticasone, Budesonide, Ciclesonide, Mometasone, and Triamcinolone Acetonide.Methods: We used proportional imbalance analysis to evaluate the correlation between ICS /INCs and infection events. The data was extracted from the FAERS database from April 2015 to September 2023. Further analysis was conducted on the clinical characteristics, site of infection, and pathogenic bacteria of ICS and INCs infection adverse events (AEs). We used bubble charts to display their top 5 infection adverse events.Results: We analyzed 21,837 reports of infection AEs related to ICS and INCs, with an average age of 62.12 years. Among them, 61.14% of infection reports were related to females. One-third of infections reported to occur in the lower respiratory tract with Fluticasone, Budesonide, Ciclesonidec, and Mometasone; over 40% of infections reported by Triamcinolone Acetonide were eye infections; the rate of oral infections caused by Beclomethasone were 7.39%. The reported rates of fungal and viral infections caused by beclomethasone were 21.15% and 19.2%, respectively. The mycobacterial infections caused by Budesonide and Ciclesonidec account for 3.29% and 2.03%, respectively. Bubble plots showed that the ICS group had more fungal infections, oral infections, pneumonia, tracheitis, etc. The INCs group had more eye symptoms, rhinitis, sinusitis, nasopharyngitis, etc.Conclusion: Women who use ICS and INCs are more prone to infection events. Compared to Budesonide, Fluticasone seemed to have a higher risk of pneumonia and oral candidiasis. Mometasone might lead to more upper respiratory tract infections. The risk of oral infection was higher with Beclomethasone. Beclomethasone causes more fungal and viral infections, while Ciclesonide and Budesonide are more susceptible to mycobacterial infections.Keywords: data mining, FAERS, ICS, INCs, pharmacovigilance, infections

Qing Liu,1,2,&ast; Xiao-Jiao Tang,1,2,&ast; Xin-Ke Chen,1,2 Lin Chen1,2 1Department of Ophthalmology, Children’s Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, People’s Republic of China; 2International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lin Chen, Children’s Hospital of Chongqing Medical University, 136, Zhongshan 2nd Road, Yuzhong District, Chongqing, 400014, People’s Republic of China, Tel +8618623041022, Fax +86-23-63651759, Email chenlin1220@126.comObjective: To investigate the effectiveness of flipped classrooms (FC) based on outcomes-based education (OBE) on clinical ophthalmology clerkships.Methods: Ninety-nine undergraduates were non-randomly assigned to the FC based on the OBE (FC-OBE) group or traditional lecture (TL) group in the ophthalmology clerkship. Pre- and post-tests were performed to assess student learning outcomes. Anonymous questionnaires were collected to compare students’ attitudes and classroom engagements between the two groups.Results: More participants agreed FC-OBE was helpful in developing teamwork ability and knowing the work standard. Teaching staff in the FC-OBE classroom received higher evaluations. More participants in the FC-OBE group had higher classroom engagement in skills and emotions than in the TL group. The post-class test scores, mainly case analysis scores were higher in the FC-OBE group than in the TL group.Conclusion: FC-OBE classroom improves student engagement and clinical analysis competence in undergraduate ophthalmology clerkship.Keywords: ophthalmology education, OBE, flipped classroom, clinical clerkship, undergraduate

Xiao-Jiao Tang,1– 4 Jia-Tong He,5 Qing Liu,1– 4 Enmei Liu,2– 4,6 Lin Chen1– 4 1Department of Ophthalmology, Children’s Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2National Clinical Research Center for Child Health and Disorders, Chongqing, People’s Republic of China; 3Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, People’s Republic of China; 4Chongqing Key Laboratory of Child Neurodevelopment and Cognitive Disorders, Chongqing, People’s Republic of China; 5Department of Health Management, Chongqing General Hospital, Chongqing, People’s Republic of China; 6Department of Respiratory Medicine, Children’s Hospital of Chongqing Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Enmei Liu, Department of Respiratory Medicine, Children’s Hospital of Chongqing Medical University, 136 Zhongshan 2nd Road, Chongqing, Yuzhong District, 400014, People’s Republic of China, Tel +8613368070773, Email emliu186@126.com Lin Chen, Department of Ophthalmology, Children’s Hospital of Chongqing Medical University, 136 Zhongshan 2nd Road, Chongqing, Yuzhong District, 400014, People’s Republic of China, Tel +8618623041022, Email chenlin1220@126.comPurpose: To investigate the patterns of allergens in allergic conjunctivitis (AC) and the association with allergic comorbidity.Methods: This retrospective cross-sectional study enrolled 2972 children with AC. Clinical data, including sex, age, allergic comorbidities (allergic asthma, allergic rhinitis, and atopic dermatitis), and serum allergen-specific immunoglobulin E (sIgE), were collected from the electronic medical record (EMR). The categorical variables were compared with the chi-square test. The characteristics of allergens in children of different ages and comorbidities were analyzed by trend chi-square. The sensitivity level of HDM associated with AC and comorbidities was assessed by odds ratios (ORs) with 95% confidence intervals of logistic regression analysis.Results: A total of 2972 children (2015 boys and 957 girls) with AC were included in the study. The mean age was 3.78 (0.5~12) years. The most common allergen was house dust mite(HDM) (43.41%). With age, the positive rate for inhaled allergens gradually increased, and the positive rate for ingested allergens decreased. With the number of comorbidities increasing, the positive rates of sensitization were 38.33%, 74.51%, 80.72%, and 89.05%, and the incidence of polysensitization was 44.66%, 56.48%, 59.54%, and 74.59%, respectively. With the increase of HDM-sIgE level, the number of comorbidities and the risk increased gradually.Conclusion: HDM is the most common allergen in AC children of different ages. High levels of HDM-sIgE may be a predictor for allergic comorbidities. Children with polysensitization and high levels of HDM sIgE will be an important target population for future intervention in other allergy-related disease prevention.Keywords: allergic conjunctivitis, specific IgE, allergic comorbidity, house dust mite, children