Search

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

Ye Yang,1,&ast; Lin Wang,1,&ast; Zhiyang Zeng,2 Chunmeng He,1 Yanqiu Wang,1 Ying Huang1 1Department of Gastroenterology, Children’s Hospital of Fudan University/National Children’s Medical Center, Shanghai, 201102, People’s Republic of China; 2Department of Central Laboratory, Fengxian Central Hospital Affiliated to Southern Medical University, Shanghai, 201499, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ying Huang, Department of Gastroenterology, Children’s Hospital of Fudan University/National Children’s Medical Center, No. 399 Wanyuan Road, Minhang District, Shanghai, 201102, People’s Republic of China, Tel +86-21-64931727, Email yhuang815@163.comPurpose: Spleen tyrosine kinase (Syk) is a widely-expressed cytoplasmic non-receptor tyrosine kinase involved in regulating various signaling pathways and plays an important role in chronic inflammation and autoimmune diseases. Gain-of-function SYK variants have been implicated in pediatric inflammatory bowel diseases. This study aimed to investigate the effects of gain-of-function SYK variants on the susceptibility to experimental colitis and macrophage function.Methods: Colitis was induced using dextran sodium sulfate and dinitrobenzene sulfonic acid in mice harboring a gain-of-function variant in SYK (SykS544Y). Intestinal inflammation was assessed via disease activity index, histological analysis, and Western blotting. The frequencies of macrophages, phagocytosis, and reactive oxygen species (ROS) production in bone marrow-derived macrophages (BMDM) were measured via flow cytometry. Chemokines and BMDM chemotaxis were analyzed using real-time quantitative reverse transcription polymerase chain reaction and Transwell assays. The expression of nucleotide-binding domain leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome-related proteins were detected using immunohistochemistry, enzyme-linked immunoassay and Western blotting.Results: SykS544Y mice exhibited increased susceptibility to experimental colitis, and macrophage infiltration in colon tissues significantly increased. We observed increased expression of macrophage chemokines in colon tissues and enhanced chemotaxis in SykS544Y BMDM. Additionally, we detected increased levels of fluorescent microspheres and 2.7-dichloride-hydro fluorescein diacetate-labeled ROS in SykS544Y BMDM. Moreover, enhanced levels of NLRP3 inflammasome-related proteins were observed in the colon tissues and BMDM from SykS544Y mice.Conclusion: Gain-of-function variant in SYK may contribute to the pathogenesis of pediatric inflammatory bowel diseases by promoting macrophage migration, phagocytosis, ROS production and activation of NLRP3 inflammasomes.Keywords: inflammatory bowel disease, SYK, gain-of-function variant, macrophage

Yanhua Huang,1 Hongwei Qian2,3 1Department of Ultrasound, Shaoxing People’s Hospital, Shaoxing, People’s Republic of China; 2Department of Hepatobiliary and Pancreatic Surgery, Shaoxing People’s Hospital, Shaoxing, People’s Republic of China; 3Shaoxing Key Laboratory of Minimally Invasive Abdominal Surgery and Precise Treatment of Tumor, Shaoxing, People’s Republic of ChinaCorrespondence: Hongwei Qian, Department of Hepatobiliary and Pancreatic Surgery, Shaoxing People’s Hospital, 568 Zhongxing North Road, Shaoxing, 312000, People’s Republic of China, Email qhwsxsrmyy@163.comAbstract: Hepatocellular carcinoma (HCC) is the most common primary liver cancer and is associated with high mortality rates due to late detection and aggressive progression. Peritumoral radiomics, an emerging technique that quantitatively analyzes the tissue surrounding the tumor, has shown significant potential in enhancing the management of HCC. This paper examines the role of peritumoral radiomics in improving diagnostic accuracy, guiding personalized treatment strategies, and refining prognostic assessments. By offering unique insights into the tumor microenvironment, peritumoral radiomics enables more precise patient stratification and informs clinical decision-making. However, the integration of peritumoral radiomics into routine clinical practice faces several challenges. Addressing these challenges through continued research and innovation is crucial for the successful implementation of peritumoral radiomics in HCC management, ultimately leading to improved patient outcomes.Keywords: hepatocellular carcinoma, peritumoral radiomics, diagnostic Imaging, artificial intelligence, precision medicine

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

Ye Zhao,1,&ast; Xi Chen,1,&ast; Yuhan Huang,2,&ast; Zhihan Zhang,3 Kui Wang,1 Duowu Zou,1 Teng Ma2 1Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 3Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Teng Ma, Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, People’s Republic of China, Email mrmateng@126.com Duowu Zou, Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, People’s Republic of China, Email zdw_pi@163.comPurpose: This study aimed to investigate gene expression profiles, identify potential hub genes, and predict drugs for patients with erosive esophagitis (EE). Despite its clinical significance, molecular-level exploration of this condition has been limited.Patients and Methods: RNA sequencing was performed on clinical biopsy samples from eight EE patients and eight healthy controls. Integrated bioinformatic tools were then utilized to analyze the data, including functional enrichment analysis, protein-protein interaction network analysis, weighted gene co-expression network analysis, immune infiltration analysis, and identification of small-molecule compounds. Additionally, the expressions of the identified hub genes were assessed in clinical samples.Results: A total of 2801 genes with differential expression were identified, including four potential hub genes: SOX9, SPP1, TIMP1, and TLR4. Moreover, the overexpression of these hub genes was verified in clinical samples. Analysis of Immune infiltration indicated an imbalance in the distribution of immune cell types in patients with EE. Correlation analysis between immune cells and hub genes unveiled noteworthy relationships. Specifically, SOX9 exhibited a negative correlation with CD8 T cells but a positive correlation with resting memory CD4 T cells. SPP1 displayed a positive correlation with naïve B cells, while TIMP1 exhibited a negative correlation with resting dendritic cells. Furthermore, the study identified ten small-molecule drugs with potential therapeutic effects for EE, including loreclezole and mercaptopurine.Conclusion: This study provides valuable insights into the molecular understanding of EE, offering new perspectives on disease mechanisms. The findings may inspire further research leading to the development of novel treatment strategies for EE.Keywords: erosive esophagitis, RNA sequencing, bioinformatics analysis, immune infiltration, drug prediction

Qiong Chen,1,* Yanjin Huang,2,* Xiaomei Chen,3 Limin Xu1 1Department of Intensive Care Medicine, Xiamen Haicang Hospital, Xiamen, Fujian, People’s Republic of China; 2Department of Nursing, Xiamen Haicang Hospital, Xiamen, Fujian, People’s Republic of China; 3Department of Pain, Xiamen Haicang Hospital, Xiamen, Fujian, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qiong Chen, Department of Intensive Care Medicine, Xiamen Haicang Hospital, No. 89 haiyu Road, Haicang District, Xiamen, Fujian, 361026, People’s Republic of China, Tel +86 177 50612461, Email chenqiongfff@163.comPurpose: Post-traumatic stress disorder (PTSD) is a major psychiatric health issue among intensive care unit (ICU) survivors with post-intensive care syndrome (PICS). Although early PTSD intervention has been demonstrated to decrease the risk of progression from acute to chronic PTSD, information on the progression trajectory of short-term PTSD symptoms and modifiable risk factors in PICS patients is limited. This study aimed to explore the clinical progression trajectories of short-term PTSD symptoms and the associated factors in PICS patients by conducting a prospective longitudinal observational study.Patients and Methods: This study was conducted at a tertiary hospital in China. The impact of event scale-revised was used to collect data on the PTSD symptoms of patients at 1, 2, 3, and 4 months post-discharge from the ICU. The latent growth mixture model was used to construct trajectory models for PTSD symptoms and multivariate logistic regression was used to determine the factors associated with the trajectories.Results: A total of 130 ICU survivors with PICS completed the 4-month short-term follow-up. Our results showed that PTSD symptoms in PICS patients manifested as three trajectories, namely, moderate chronic (n = 17, 13.1%), recovery (n = 25, 19.2%), and resilience (n = 88, 67.7%). Compared with the resilience trajectory, age and female were identified as risk factors for the moderate chronic trajectory, while prolonged ICU stay was a risk factor for the recovery trajectory.Conclusion: Our study showed that short-term PTSD symptoms in PICS patients manifested as moderate chronic, recovery, and resilience trajectories. Additionally, our results showed that PTSD screening should be conducted for critically ill patients, especially younger, female, or long-term ICU patients, immediately after their discharge from the ICU.Keywords: post-traumatic stress disorder, latent growth mixture model, longitudinal study, post-intensive care syndrome

Jingyu Zhang,1,&ast; Shenhua Qu,2,&ast; Yuting Huang,1,&ast; Xia Zhang,1 Xiubing Tong,1 Yanping Fang,1 Tianyu Rao,1 Kezhi Liu,1 Jia Lin,1 Yuye Lin,1 Chufan Zeng,1 Guojun Zhang,1 Xianghong Jing,3 Jun Liao,1 Yu Kan1 1College of Acupuncture and Tuina, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, People’s Republic of China; 2Guangzhou Traditional Chinese Medicine Hospital, Guangzhou, 510000, People’s Republic of China; 3Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Beijing, 100700, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jun Liao; Yu Kan, Email 2007065@fjtcm.edu.cn; 2019035@fjtcm.edu.cnPurpose: Chronic cervical muscle injury is the first common cause of the development of cervical spondylosis, and Tuina can effectively promote the repair of chronic cervical muscle injury and alleviate neck pain, but the mechanism behind its efficacy is still unknown. The proliferation and differentiation of muscle satellite cells and the apoptosis of cervical myocytes play important roles in the repair of chronic cervical muscle injuries; therefore, this study aimed to explore the potential mechanisms of Tuina to promote the repair of cervical muscle injuries in terms of the proliferation and differentiation of satellite cells and the apoptosis of myocytes.Patients and Methods: Twenty-eight Wistar rats were randomly divided into control group, model group, Tuina group, and meloxicam group, with 7 rats in each group. Except for the control group, each group were establish a chronic cervical muscle injury model (CCMI). Meloxicam (0.79 mg/kg) was administered by gavage, and in the Tuina group, pressure was applied to the Fengchi acupoint on the affected side once a day. Morphological changes of cervical muscle tissues were detected by ultrasonic diagnostic instrument and HE staining, electrophysiological recordings of electromyographic changes, apoptosis rate was detected by TUNEL staining, and positive expression of Bax, Bcl-2, IGF-1, MyoD, and Pax-7 were detected by Immunohistochemistry and Western blot.Results: In CCMI model rats, we observed that the cervical muscle fibers were disorganized, with irregular morphology, and the amplitude of electromyography was significantly weakened, while Tuina could significantly improve these symptoms and effectively promote the repair of chronic cervical muscle injury. Meanwhile, compared with the model group, Tuina could significantly increase the expression levels of IGF-1 (P< 0.01) and MyoD (P< 0.05) and decrease the expression level of Pax7 (P< 0.05). In addition, we found that the number of apoptotic cells in cervical myocytes was reduced after Tuina intervention (P< 0.05), and Tuina inhibited the expression of pro-apoptotic factor Bax (P< 0.01) and promoted the expression of anti-apoptotic factor Bcl-2 (P< 0.05).Conclusion: Tuina can promote the proliferation and differentiation of satellite cells to repair chronic cervical muscle injury by regulating the expression of Pax7, MyoD, and IGF-1, as well as inhibiting the expression of Bax and promoting the expression of Bcl-2 to ameliorate the apoptosis of cervical myocytes in CCMI model rats.Keywords: Tuina, cervical spondylosis, neck pain, satellite cell

Yu-Yan Qin,1,&ast; Hui Yu,1,2,&ast; Yong Huang,1,&ast; Xiaoyi Yang,1 Songpei Li,1 Ao Shen,1 Yinshan Lin,1 Mei Zhang,1 Qiulian Zhu,1 Jingwei Zhang,1 Lingmin Zhang,1 Xi-Yong Yu1 1Key Laboratory of Molecular Target & Clinical Pharmacology and the State & NMPA Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences & the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, 511436, People’s Republic of China; 2Hutchison Whampoa Guangzhou Baiyunshan Chinese Medicine Co., Ltd, Guangzhou, Guangdong, 510515, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xi-Yong Yu; Lingmin Zhang, School of Pharmaceutical Sciences, Guangzhou Medical University, Xinzao Road, Panyu District, Guangzhou, 511436, People’s Republic of China, Email yuxycn@gzhmu.edu.cn; zhanglm@gzhmu.edu.cnBackground: Acute lung injury (ALI) leads to diffuse pulmonary interstitial and alveolar edema, further developing into acute respiratory distress syndrome (ARDS). The present therapeutic approaches showed limited effects with poor clinical efficacy or severe side effects. This study aims to develop novel pharmaceutical agents to reduce lung damage with acceptable side effects for ALI.Methods: Naked gene delivery system based on epigallocatechin 3-gallate (EGCG) was synthesized to deliver plasmid expressing DNA damage regulated autophagy modulator 1 (DRAM1), designated as EGCG/DRAM1 (ED). ED was characterized by dynamic light scattering analysis and transmission electron microscope. The biodistribution of ED in mice was measured by an in vivo small animal imaging system. The therapeutic potentials of ED were evaluated in MLE12 cells and LPS-induced ALI mice.Results: Our results showed that ED was nearly spherical with a diameter of ~100 nm and increased the stability of DRAM1 plasmid that encapsulated. The synthesized ED showed negligible toxicity at the selected experimental concentration in MLE12 cells. ED could be taken up by MLE12 cells with high efficiency and escape from the lysosome. In ALI mice, ED facilitated the accumulation and retention of DRAM1 plasmid in lung, and attenuated pulmonary edema and pulmonary vascular permeability. The therapeutic effects of ED on ALI were associated with increased autophagy and reduced oxidative stress in lung.Conclusion: In summary, ED attenuated pulmonary edema and pulmonary vascular permeability, and improved pulmonary dysfunction in ALI mice. This naked gene delivery system for autophagy enhancement may serve as a potential therapeutic strategy to attenuate ALI. Keywords: acute lung injury, EGCG, DRAM1, autophagy, oxidative stress

Chunlei Tan,1 Jinling Xu,2 Shiyuan Zhang,1 Shuqiang Liu,1 Xiaotian Yang,1 Danping Wu,1 Boqian Yu,1 Yuanxi Huang1 1Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, 150081, People’s Republic of China; 2Endoscope Department, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, 150081, People’s Republic of ChinaCorrespondence: Yuanxi Huang, Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, 150081, People’s Republic of China, Tel/Fax +86-0451-86298053, Email rxwk@163.comPurpose: The current investigation is to assess FOXP3 expression in breast cancer patients and evaluate the predictive significance of FOXP3.Patients and Methods: A cohort of 313 cases between January 2015 and November 2015 were enrolled this research. Immunohistochemistry (IHC) assay was utilized to detect the expression levels of FOXP3 in primary breast carcinoma specimens. These patients were separated into two groups by semiquantitative scoring approach. Chi-square test and Fisher’s exact test were conducted to investigate the correlations between FOXP3 expression in tumors and clinicopathological variables. Kaplan–Meier method and Log rank test were utilized to generate survival curves for disease-free survival (DFS) and overall survival (OS). The independent factors were examined using Cox regression analysis. Nomogram models were created for assessing DFS and OS rates.Results: Depending on the levels of FOXP3 expression in tumors, these patients were categorized into two groups: low FOXP3 expression (174 cases) and high FOXP3 expression (139 cases). The patients exhibiting low levels of FOXP3 expression in tumors demonstrated a longer survival duration contrasted with those with high expression (DFS: 88.75 vs 65.87 months, χ2=36.1100, P< 0.0001; OS: 89.70 vs 78.37 months, χ2=32.4900, P< 0.0001). Multivariate analysis revealed that FOXP3 was a significant prognostic factor [DFS: hazard ratio (HR): 2.822, 95% CI: 1.595– 4.992, P< 0.0001; OS: HR: 3.232, 95% CI: 1.812– 5.763, P< 0.0001]. The good predictive clinical utility of FOXP3-based nomograms within the threshold probability range for different survival rates was demonstrated by calibration curve and decision curve analyses.Conclusion: FOXP3 expression serves as a crucial prognostic indicator in breast cancer patients, and may aid preoperative evaluation in clinical practice.Keywords: breast cancer, FOXP3, chemotherapy, radiotherapy, survival

Yujia Huang,1,2,&ast; Yinan Li,2,&ast; Tong Su,3 Hao Wang,2 Shuyu Xu,2 Jingzhou Xu,2 Siqi Zheng,4 Jing Du,2 Yajing Wang,2 Ruike Zhang,2 Yao Meng,2 Xin Guo,2 Lei Xiao,2 Yunxiang Tang3 1Psychology Department, The Second Naval Hospital of Southern Theater Command, Sanya, People’s Republic of China; 2Department of Medical Psychology, Faculty of Psychology, Naval Medical University, Shanghai, People’s Republic of China; 3Faculty of Psychology, Naval Medical University, Shanghai, People’s Republic of China; 4Department of Psychology, TongJi University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lei Xiao; Yunxiang Tang, Email xiaolei0237@163.com; tangyun7633@sina.comObjective: To investigate the effects of sleep quality, sleep deprivation, and napping on facial emotion recognition (FER) accuracy and speed.Methods: This research included a cross-sectional study (102 qualified participants) and a randomized controlled study (26 in the napping group and 24 in the control group). The stimuli for the FER task were obtained from the Chinese Facial Affective Picture System (CFAPS). Four facial expressions (fearful, disgusted, sad, and angry) were used. The Pittsburgh Sleep Quality Index (PSQI), Self-Rating Anxiety Scale, and Self-Rating Depression Scale were used to measure participants’ sleep quality and psychological conditions. In Study 1, FER ability was compared between good and poor sleepers. In Study 2, all participants were sleep-deprived for one night, and completed the FER task before and after sleep deprivation. After different interventions (ie, napping for one hour, or walking around for ten minutes), the participants completed the third FER task.Results: Study 1: Poor sleepers were able to recognize sad expressions more accurately compared with good sleepers. Study 2: 30-h sleep deprivation had no significant effect on the accuracy (ACC). Napping after sleep deprivation improved the FER ACC of upper-face expressions and marginally significantly improved the FER ACC of disgusted expressions.Conclusion: Better sleep quality was linked to lower FER accuracy, particularly in recognizing sad expressions, while no significant differences in recognition speed were observed. Additionally, 30 hours of sleep deprivation did not affect FER accuracy, but napping after sleep deprivation improved accuracy for upper-face and marginally for disgusted expressions.Keywords: facial emotion recognition, sleep quality, facial features, facial emotion, sleep deprivation, sleep loss

Yali Liang,1,&ast; Yunxin Zhang,1,&ast; Yong Feng,2 Yuying Huang,2 Cuiling Zhang1 1Nursing Department, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 2College of Nursing, Shanxi University of Chinese Medicine, Taiyuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Cuiling Zhang, Nursing Department, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, NO. 99, Longcheng Street, Xiaodian District, Taiyuan, 030032, People’s Republic of China, Tel +86-13753482546, Email sxbqezcl@163.comPurpose: To assess abusive supervision and organizational silence among nurses and investigate the mediating influence of psychological capital and fear.Background: Since the end of 2019, China’s National Development and Reform Commission (NDRC) department has decided to start the construction of regional medical centers in Shanxi, reducing cross-provincial and cross-regional medical care. In order to improve the overall standard of care in a hospital in a short period of time, health care leadership decision makers may adopt various effective leadership management practices to achieve the set goals and have high work pressure at the same time. In this case, abusive management may occur.Methods: A cross-sectional survey design was employed. In January -March 2024, a convenience sampling method was used to collect data from 470 nurses in a total of 5 hospitals in Shanxi province they were required to complete the questionnaires online anonymously. The chain mediation model was tested using the PROCESS macro program in the SPSS software and multiple linear regression model was used to verify the mediating effect.Results: Psychological capital and fear mediate the relationship between abusive supervision and nurses’ organizational silence, playing indirect mediating roles. Abusive supervision was positively associated with nurses’ organizational silence. Additionally, psychological capital plays a negative mediating role, accounting for 48.48% of the indirect effect, and fear plays a positive mediating role, accounting for 45.83% of the indirect effect. They form a chain intermediary, accounting for 5.69% of the indirect effect.Conclusion: Psychological capital and fear mediate the impact of abusive supervision on nurses’ organizational silence. Positive leadership training should be conducted to help reducing the level of head nurses’ abusive supervision behaviors, while also fostering actions that elevate nurses’ psychological capital levels.Keywords: Abusive supervision, Nurses’ organizational silence, psychological capital, fear, mediating effect

Shuiying Zeng, Hui Liu, Xiaozhen Wen, Yujing Huang Department of Neurosurgery, Ganzhou People’s Hospital, Ganzhou, Jiangxi, 341000, People’s Republic of ChinaCorrespondence: Yujing Huang, Ganzhou People’s Hospital, No. 17 hongqi Avenue, Zhanggong District, Ganzhou City, Jiangxi Province, 341000, People’s Republic of China, Tel +86-0797-8083557, Email huangzhang202202@163.comObjective: This study aims to understand and address the health education needs of family caregivers of people living with epilepsy, irrespective of the patient’s age. It seeks to construct and implement a targeted health education program informed by empowerment education theory and evaluate its effectiveness.Methods: Through semi-structured interviews, we explored the diverse health education needs of family caregivers of people with epilepsy, identifying key themes and constructing a responsive health education plan. The program’s effectiveness was assessed through a quasi-experimental study. The control group received routine health education, while the intervention group participated in an empowerment-based education program in addition to the standard protocol. We evaluated changes in caregivers’ disease management capabilities, knowledge about epilepsy, and quality of life at baseline, one month, and three months post-intervention using appropriate statistical analyses to confirm significance.Results: Sixty-five family caregivers participated, with 32 in the intervention group and 33 in the control group. Guided by phenomenological research, four main themes were identified. Significant improvements in disease management, epilepsy knowledge, and quality of life were observed in the intervention group, exceeding those in the control group at both follow-up intervals (p< 0.05).Conclusion: An empowerment-based health education program significantly enhances caregivers’ competencies across age groups in managing epilepsy, underscoring its effectiveness as an intervention model.Keywords: epilepsy, caregiver, health education, empowered theory

Yiming Huang,1,&ast; Xinran Wang,1,&ast; Wenjing Li,1,&ast; Feng Yue,1,2 Miao Wang,1 Feifan Zhou1,2 1State Key Laboratory of Digital Medical Engineering, School of Biomedical Engineering, Hainan University, Sanya, People’s Republic of China; 2One Health Institute, Hainan University, Haikou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Miao Wang; Feifan Zhou, Email wangm@hainanu.edu.cn; zhouff@hainanu.edu.cnPurpose: To avoid the biotoxicity and poor bioavailability of deferoxamine mesylate (DFO), an iron chelation for the treatment of Parkinson’s disease (PD), a self-oriented DFO nanoparticle functionalized with Exendin-4 was developed, which can be targeted delivered into the lesion brain area to achieve synergistic effects against PD by iron chelation and inflammatory suppression.Methods: The self-oriented DFO nanoparticles (Ex-4@DFO NPs) were synthesized by double emulsion technique, and characterized in terms of the particle size, morphology and DFO encapsulation efficiency. The cellular internalization, biocompatibility and cytoprotection of NPs were assessed on BV-2 and SH-SY5Y cells. The brain targeting and therapeutic effect of NPs were investigated in MPTP-induced PD mice by near-infrared II fluorescence imaging and immunofluorescence staining, as well as mobility behavioral tests.Results: Ex-4@DFO NPs with a particle size of about 100 nm, showed great biocompatibility and cytoprotection in vitro, which inhibited the decrease of mitochondrial membrane potential of SH-SY5Y cells and the release of inflammatory factors of BV-2 cells. In MPTP-induced PD mice, Ex-4@DFO NPs could penetrate the BBB into brain, and significantly mitigate the loss of dopaminergic neurons and inflammation in the substantia nigra, finally alleviate the mobility deficits.Conclusion: This self-oriented nanosystem not only improved the biocompatibility of DFO, but also enhanced therapeutic effects synergistically by ameliorating neuronal damage and neuroinflammation, showing a potential therapeutic strategy for PD. Keywords: Parkinson’s disease, deferoxamine mesylate, Exendin-4, nanoparticle system, brain targeting

Yanling Huang,1,&ast; Bing Li,1,&ast; Suibin Feng,2,&ast; Sifen Jiang,1 Kun Zeng1,3 1School of Nursing, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of China; 2Pediatric Urology Department, Dongguan Eighth People’s Hospital (Dongguan Children’s Hospital), Dongguan, People’s Republic of China; 3Science and Education Section, Dongguan Eighth People’s Hospital (Dongguan Children’s Hospital), Dongguan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Kun Zeng, School of Nursing, Guangdong Pharmaceutical University, No. 283, Jianghai Avenue, Haizhu District, Guangzhou City, Guangdong Province, 510310, People’s Republic of China, Tel +86 13790300213, Email zengkun660524@163.comPurpose: This study aimed to investigate the current state of empathy for pain among clinical nurses, analyze the relationship between resilience and empathy for pain, and explore the mediating effects of coping styles.Methods: This was a multicenter cross-sectional study conducted among 1601 clinical nurses in Guangdong Province, China. The convenience sampling method was used to collect data from Sociodemographic information, the 14-Item Resilience Scale, the Simplified Coping Style Questionnaire, and the Chinese version of the Empathy for Pain Scale from June to September 2023. To analyze the relationship between resilience, coping styles, and empathy for pain among clinical nurses with descriptive statistics, Spearman correlation analysis, and mediation analysis.Results: The empathy for pain score among Chinese clinical nurses was 2.92 ± 0.79, with the empathy reactions dimension at 3.56 ± 0.74, and the body and mind discomfort reactions dimension at 2.70 ± 0.89. Clinical nurses’ resilience was positively related to the coping styles and the empathy reactions dimension, whereas negatively associated with the body and mind discomfort reactions dimension. Coping styles were negatively related to the empathy for pain and the body and mind discomfort reactions dimension, whereas positive with the empathy reactions dimension. Coping styles partially mediated between resilience and empathy reactions dimension (β=0.127, 95% CI: 0.070~0.183), accounting for 56.19% of the total effect. There were suppressing effects of coping styles between resilience and empathy for pain (β=− 0.157, 95% CI: − 0.189~-0.126), the body and mind discomfort reactions dimension (β=− 0.172, 95% CI: − 0.203~-0.142).Conclusion: The effects of resilience on clinical nurses’ empathy for pain were partially mediated and suppressed by coping styles. During clinical pain management, nursing administrators should focus on developing clinical nurses’ resilience and positive coping strategies to improve nurses’ physical and mental health, optimize pain management, and foster a heightened sense of empathy for pain.Keywords: resilience, coping styles, empathy for pain, mediating effect, suppressing effect

Chenrui Zhao,1,2,&ast; Yuanyuan Ding,2,&ast; Yihan Huang,2 Chao Wang,2 Bin Guo,1 Tao Zhang2 1Department of Anesthesiology, Xi’an Honghui Hospital, Xi’an Jiaotong University, Xi’an, 710054, People’s Republic of China; 2College of Pharmacy, Xi’an Jiaotong University, Xi’an, 710061, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bin Guo, Department of Anesthesiology, Xi’an Honghui Hospital, Xi’an Jiaotong University, Xi’an, 710054, People’s Republic of China, Email xuan_310755@sina.comBackground: CMRF35-like molecule-1 (CLM-1) is a receptor of the CD300 family that inhibits MRGPRX2-mediated mast cell degranulation. Understanding the role and mechanism of CLM-1 agonist has significant implications for the treatment of allergic disease. Quercetin is a natural small molecule compound derived from plants and vegetables that has been shown to prevent histamine release by immune cells.Objective: This study aims to examine the inhibitory effects of quercetin on MRGPRX2-mediated mast cell degranulation via CLM-1.Results: We found that C48/80 stimulation resulted in significantly increased release of β-hexosaminidase, histamine and Ca2+ in CLM-1-knockdown LAD2 cells than in NC-LAD2 cells. Surface plasmon resonance (SPR) and molecular docking analyses revealed high-affinity binding between quercetin and CLM-1 (KD = 2.962× 10− 5 mol/L) mediated by the formation of hydrogen bonds. In addition, quercetin can selectively bind to CLM-1 on mast cells, leading to SHP-1 phosphorylation and subsequent inhibition of downstream MyD88/IKK/NF-κB signaling. Furthermore, activation of CLM-1 modulated the surface expression of MRGPRX2 by inhibiting F-actin, leading to internalization of the MRGPRX2 receptor via the PI3K/AKT/ Rac1/Cdc42 pathway.Conclusion: Quercetin is a promising treatment for allergic diseases by acting as a CLM-1 agonist that inhibits MRGPRX2-mediated mast cell degranulation. Keywords: quercetin, CLM-1, inhibition, MRGPRX2, mast cell degranulation

Yong Huang,&ast; Chunmei Yin,&ast; Jue Wang, Maijian Wang, Xingbin Zheng, Ming Xie, Jiwei Wang Department of General Surgery, Digestive Disease Hospital, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiwei Wang, Department of General Surgery, Digestive Disease Hospital, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Huichuan District, Zunyi, Guizhou, People’s Republic of China, Tel +86-13017410630, Email wjw@smail.nju.edu.cnPurpose: This study investigated the effects of parenteral glutamine (Gln) supplement immunonutrition versus conventional nutritional support on postoperative Clavien–Dindo classification complications and recovery, perioperative nutritional status, and immune, inflammation, and safety indicators in patients with colorectal cancer (CRC).Patients and Methods: Clinical data were collected for a retrospective cohort study of 178 patients (58 and 120 patients in the observation and control groups, respectively) who underwent radical resection of CRC from January 2019 to December 2021. The incidence of postoperative complications was calculated. Postoperative recovery, nutritional indicators, inflammatory factors indicator, and the safety indicators before operation and at 1, 3, and 7 days after operation were compared. SPSS 29.0 statistical software was used for statistical analysis.Results: The incidence of postoperative overall complications in the control group and the observation group was 22.50% (27/120) and 17.24% (10/58), respectively, and there was no significant difference between the two groups (P=0.42). The incidence of postoperative complications of Clavien-Dindo grade ≥III in the control group and the observation group was 14.17% (17/120) and 3.45% (2/58), respectively, and the difference between the two groups was statistically significant (P=0.03). Secondary outcomes (first exhaust, defecation, and liquid diet intake times) were significantly recovered earlier in the observation group than those in the control group (P< 0.05), while the postoperative hospital stay was significantly shorter(P=0.04). The perioperative nutritional status did not significantly differ between the groups before and after surgery(P> 0.05), although significant differences were observed in several inflammatory and safety indicators(P< 0.05).Conclusion: Unlike conventional nutritional support, postoperative parenteral Gln supplementation reduced the incidence of postoperative Clavien–Dindo complications grade ≥III in patients with CRC while increasing intestinal and immune functions, decreasing inflammation, and reducing the length of hospital stay.Keywords: glutamine, parenteral nutrition, colorectal cancer, clavien–dindo complication

Fengsong Chen,1,&ast; Yanhua Huang,1,&ast; Yongxia Liu,2 Yanwen Zhuang,3 Xiaowei Cao,3 Xiaogang Qin2 1Department of Gastroenterology, Nantong Haimen People’s Hospital, Nantong, Jiangsu, 226100, People’s Republic of China; 2Department of gastroenterology, Traditional Chinese Medicine Hospital of Tongzhou District, Nantong, Jiangsu, 226300, People’s Republic of China; 3Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, Jiangsu, 225001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaogang Qin, Email tzqinxiaogang@163.comBackground: Colorectal cancer (CRC) has become a significant global public health challenge, demanding immediate attention due to its high incidence and mortality rates. Regular CRC screening is essential for the early detection of precancerous lesions and CRC.Methods: : We developed a novel surface-enhanced Raman scattering (SERS) analysis platform that employs high-throughput microarray chips as carriers and Au/SnO2 nanoring arrays (Au/SnO2 NRAs) as substrates. This platform utilizes an aptamer recognition-release strategy to achieve efficient and sensitive detection of protein tumor markers. In the detection process, the strong affinity and high specificity between the aptamer and the target protein result in competitive replacement of the SERS nanoprobes originally bound to the substrate surface. As a result, the SERS nanoprobes carrying Raman reporter genes are dislodged, leading to a reduction in the SERS signal intensity.Results: The platform demonstrated excellent detection performance, with rapid detection completed within 15 minutes and limits of detection (LOD) as low as 6.2× 10− 12 g/mL for hnRNP A1 and 6.51× 10− 12 g/mL for S100P. Clinical samples analyzed using the SERS platform showed high consistency with enzyme-linked immunosorbent assay (ELISA) results.Conclusion: This platform offers strong support for the early detection, risk assessment, and treatment monitoring of colorectal cancer precancerous lesions, with broad potential for clinical applications.Keywords: colorectal cancer, precancerous lesions, surface enhanced raman scattering, aptamer, microarray chip

Xiaoyan Hong,1 Yangrong Huang,1 Wei Lin,1 Yi Zhang,1 Jianyun Lin,1 Shengguo Zhang,2 Fengquan Cai,1 Jie Chen1 1Department of Emergency, Third Affiliated Hospital of Wenzhou Medical University (Rui’an People’s Hospital), Wenzhou, Zhejiang, People’s Republic of China; 2Department of Infection, Third Affiliated Hospital of Wenzhou Medical University (Rui’an People’s Hospital), Wenzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Fengquan Cai; Jie Chen, Department of Emergency, Third Affiliated Hospital of Wenzhou Medical University (Rui’an People’s Hospital), 108 Wansong Road, Wenzhou, 325200, Zhejiang, People’s Republic of China, Tel +86-13967723666 ; +86-13587409966, Email cfqruiyi@163.com; woshichenjie@wmu.edu.cnAbstract: Staphylococcus aureus (S. aureus) infection is readily disseminated, yet the multiple septic arthritis and extensive migratory skin and soft tissue infections it causes are uncommon and challenging to treat. The infection can be life-threatening, with a mortality rate of 15– 31%. Early, targeted antibiotic therapy is critical to improve prognosis. However, routine cultures are time-consuming and have low positivity rates, which may lead to errors in antibiotic regimen selection, depriving patients of optimal treatment. Genetic testing technologies, such as macrogenomic next-generation sequencing (mNGS) and digital polymerase chain reaction (dPCR), are now emerging as powerful tools for early pathogen diagnosis as well as pathogen diagnosis of target detectors with low microbial loads. In this study, we report a 53-year-old man who was admitted to the ICU for treatment of septic shock. The causative agent was targeted earlier as S. aureus by mNGS, and the shock was corrected more quickly with targeted antibiotic medication. However, he later developed multiple septic arthritis and an extensive migratory skin soft tissue infection with persistent fever, and at one point a gram-negative bacterial infection was suspected, and the antibiotic regimen was incorrectly changed. Blood dPCR suggested that the causative organism was still methicillin-sensitive S. aureus (MSSA), with no drug resistance gene detected, and the anti-infective regimen was readjusted, and the patient eventually recovered and was discharged from the hospital. We present this rare case and review related studies to validate the superiority of genetic testing technology in pathogen diagnosis, which deserves further application.Keywords: disseminated Staphylococcus aureus disease, multiple suppurative arthritis, extensive migratory skin and soft tissue infections, digital polymerase chain reaction, next-generation sequencing

Song Chang,1,2 Yaohua Zhang,1,2 Chunxu Wang,1 Fan Xu,1 Yunyun Huang,1,2 Sufei Xin1,2 1College of Education, Ludong University, Yantai, Shandong, People’s Republic of China; 2Collaborative Innovation Center for the Mental Health of Youth from the Era of Conversion of New and Old Kinetic Energy along the Yellow River Basin, Yantai, Shandong, People’s Republic of ChinaCorrespondence: Sufei Xin, College of Education, Ludong University; Collaborative Innovation Center for the Mental Health of Youth from the Era of Conversion of New and Old Kinetic Energy along the Yellow River Basin, No. 186, Hongqi Middle Road, Yantai, Shandong, People’s Republic of China, Email xinsufei2016@ldu.edu.cnPurpose: The alleviating effects of a growth mindset on depression are promising. However, whether a growth mindset can attenuate the effect of low family socioeconomic status (SES) on depressive symptoms among adolescents remains unknown. Based on the Family Stress Model, the current study explores whether a growth mindset could moderate the associations between family SES, interparental conflict, and adolescent depressive symptoms.Methods: The participants were 1572 Chinese adolescents (Mage = 13.35 years, SD = 1.16, 51.84% female). They completed the family SES questionnaire, Children’s Perceptions of Interparental Conflict scale, Growth Mindset scale, and Center for Epidemiologic Studies Depression scale. We tested the moderation, mediation, and moderated mediation models using the SPSS macro program PROCESS.Results: A growth mindset moderated the association between family SES and depressive symptoms. Family SES was significantly related to depressive symptoms in adolescents with a lower growth mindset, but not in those with a higher growth mindset. After incorporating the mediating effect of interparental conflict, the growth mindset did not exert a significant moderating influence on the direct path; however, it significantly moderated the mediating effect of interparental conflict on depressive symptoms. Specifically, while a lower growth mindset in adolescents was associated with an increased risk of depressive symptoms due to interparental conflict, those with a higher growth mindset showed a less pronounced effect.Conclusion: A growth mindset attenuates the link between family SES and depressive symptoms among adolescents. These findings highlight the benefits of a growth mindset on mental health, especially for low-SES adolescents.Keywords: growth mindset, socioeconomic status, depression, adolescent, interparental conflict

Wen Chen,1,2 Yun Li,2 Haitham Jahrami,3,4 Weiyan Wang,5 Wei Zheng,2 Yuxia Huang,1 Nicola Luigi Bragazzi,6,7 Weijia Gao1 1Department of Child Psychology, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children’s Regional Medical Center, Hangzhou, People’s Republic of China; 2Department of Psychiatry, Xiamen Xianyue Hospital, Xiamen, People’s Republic of China; 3College of Medicine and Medical Sciences, Arabian Gulf University, Manama, Bahrain; 4Ministry of Health, Manama, Bahrain; 5Affiliated Mental Health Center & Hangzhou Seventh People’s Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 6Laboratory for Industrial and Applied Mathematics, Department of Mathematics and Statistics, York University, Toronto, Canada; 7Human Nutrition Unit (HNU), Department of Food and Drugs, Medical School, University of Parma, Parma, ItalyCorrespondence: Weijia Gao, Department of Child Psychology, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children’s Regional Medical Center, Hangzhou, Zhejiang Province, People’s Republic of China, Email 6314017@zju.edu.cn Nicola Luigi Bragazzi Human Nutrition Unit (HNU), Department of Food and Drugs, Medical School, University of Parma, Parma, Italy, Email robertobragazzi@gmail.comPurpose: This study focused on the validation of the Three-Factor Reflective Functioning Questionnaire for Youth(RFQY) within a sample of Chinese adolescents.Patients and Methods: All the items of the RFQY were translated into Chinese language through the process of translation and back translation. A total of 532 adolescents aged between 12– 20 years completed the Chinese version of RFQY, McLean Screening Instrument for Borderline Personality Disorder (MSI-BPD), Basic Empathy Scale (BES), and the 20-item Toronto Alexithymia Scale (TAS-20).Results: Twenty items meeting psychometric standards were retained in the Chinese version of the RFQY. The indices for confirmatory factor analysis, including χ 2/df (2.354), SRMR (0.053), GFI (0.930), CFI (0.921), TLI (0.910), and RMSEA (0.050), all conformed to the requirements of psychometrics. The Cronbach’s alpha coefficients for the three factors, “uncertainty/confusion”, “interest/curiosity”, and “excessive certainty”, were 0.820, 0.673, and 0.839, respectively, with test-retest reliability scores of 0.751, 0.643, and 0.764. A significant positive correlation was found between uncertainty/confusion and symptoms of borderline personality disorder (BPD), particularly in adolescents with high BPD traits. Excessive certainty was positively correlated with unstable interpersonal relationships, while the interest/curiosity factor shows no significant correlation with BPD symptoms. The uncertainty/confusion factor demonstrates a complex relationship with empathy, correlating positively with affective empathy but negatively with cognitive empathy. The uncertainty/confusion factor shows a significant positive correlation with alexithymia, while the factor of excessive certainty demonstrates the opposite effect. Additionally, a significant negative correlation exists between the interest/curiosity factor and the externally oriented thinking.Conclusion: This study validates the Chinese version of the Reflective Functioning Questionnaire for Youth (RFQY), demonstrating its reliability and validity in assessing reflective functioning among Chinese adolescents. This enhances the understanding of reflective functioning and its role in adolescent mental health.Keywords: mentalizing, adolescence, psychometric validation, borderline personality disorder

Na Chen,1,2 Xuben Yu,3 Lu Li,1 Ping Yang,1 Rong Dong,1,4 Yizhen Huang,1,5 Xiao Ling,1,6 Qiaoqiao Shentu,1,7 Wenqiao Yu,8 Saiping Jiang1 1Department of Clinical Pharmaceutical, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 2Zhejiang Provincial Key Laboratory for Drug Evaluation and Clinical Research, Hangzhou, People’s Republic of China; 3Department of Pharmacy, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China; 4Department of Clinical Pharmacy, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 5Department of Pharmacy, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, People’s Republic of China; 6Department of Pharmacy, The People’s Hospital of Yuhuan, Taizhou, People’s Republic of China; 7Department of Pharmacy, Dongyang Red Cross Hospital, Jinhua, People’s Republic of China; 8Department of Hepatobiliary and Pancreatic Surgery and Intensive Care Unit, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, People’s Republic of ChinaCorrespondence: Saiping Jiang; Wenqiao Yu, Email j5145@zju.edu.cn; yuwenqiao1980@zju.edu.cnBackground: The population pharmacokinetics of nirmatrelvir/ritonavir (NIR/RIT) has not yet been described for critically ill adult patient.Purpose: This was a prospective observational population pharmacokinetic study of nirmatrelvir/ritonavir (NIR/RIT) in critically ill adult patients and identify optimal dosing regimens.Patients and Methods: The prescription of NIR/RIT is determined by the attending physician and ranges from 150mg/100mg to 300mg/100mg twice a day. Two to three serial blood samples were collected for each patient after the second doses. We developed and validated PK model for plasma NIR and plasma RIT. Monte Carlo dosing simulations were performed to assess target attainment.Results: We analyzed 89 plasma samples from 31 adult patients. The data were best described by a one-compartment model. Among the covariates tested on pharmacokinetic parameters, creatinine clearance (CrCL) and area under curve (AUC) of RIT had a significant effect on apparent clearance (CL/F) of NIR. Mean (SD) parameters estimates for the absorption rate constant (Ka), apparent distribution (V/F) and CL/F were 0.42 (0.10) h− 1. 36.5 (8.5) L, 3.6 (0.26) L/h, respectively. Dosing simulations showed that the target in vitro 90% effective concentration (EC90) was more likely to be achieved twice a day than once a day at the same daily dose of NIR. High CrCL, low AUC of RIT were associated with a reduced likelihood of NIR reaching the target EC90.Conclusion: Based on our dosing simulations, the initial dosage of NIR/RIT was 300mg/100mg twice a day in critically ill patients with CrCL> 45 mL/min; When CrCL in critically ill patients is between 15 and 45 mL/min, NIR/RIT is 150mg/100mg twice a day. The maintenance dose is adjusted according to CrCL and AUC of RIT, with the dosages varying between 75mg/100mg and 300mg/100mg.Keywords: nirmatrelvir, ritonavir, pharmacokinetics, critically ill, creatinine clearance

Mengfan Yang,1,&ast; Youqun Huang,1,&ast; Anqi Tang,1 Yu Zhang,2 Yu Liu,3 Zhenliang Fan,4 Mingquan Li1 1Department of Nephrology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, People’s Republic of China; 2Department of Nephrology, Shaanxi Provincial Hospital of Traditional Chinese Medicine, Xi’an, Shaanxi Provincial, People’s Republic of China; 3Department of Nephrology, South China Hospital, Health Science Center, Shenzhen University, Shenzhen, People’s Republic of China; 4Department of Nephrology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mingquan Li, Department of Nephrology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, People’s Republic of China, Email limingquan@cdutcm.edu.cnPurpose: Acute kidney injury (AKI) is a common clinical critical condition that has become a significant healthcare burden. In recent years, the relationship between AKI and mitochondria has attracted increasing attention. Protecting mitochondria or restoring their function has emerged as a novel therapeutic strategy for alleviating AKI. This study aims to analyze and summarize the current status, research trends, and hotspots in this field, providing references and directions for future research.Methods: AKI and mitochondria-related literature from the Web of Science core collection were retrieved and collected. Bibliometric and visualization analyses were conducted using Microsoft Excel 2021, bibliometric tools (VosViewer, Citespace 6.3.R1, and the bibliometrix R package), R 4.3.2, and SCImagoGraphica software.Results: A total of 2433 publications were included in this study. The number of annual publications in this field has increased year by year. China and the United States are the two most productive countries. Central South University is the most influential research institution in terms of research output, and Parikh SM, Schnellmann RG, and Dong Z are the most influential authors in this field. KIDNEY INTERNATIONAL, JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, and AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY are the most influential journals. Initially, the research focused on keywords such as oxidative stress, ischemia-reperfusion injury, apoptosis, inflammation, and autophagy. In recent years, new research hotspots have emerged, including ferroptosis, aging, mitochondrial quality control, messenger RNA, mitochondrial-targeted antioxidants, extracellular vesicles, and nanodrug delivery.Conclusion: Research on the relationship between mitochondria and AKI has broad developing prospects, and targeting mitochondrial regulation will become a focus of future AKI prevention and treatment research.Keywords: acute kidney injury, mitochondria, bibliometric analysis, visualization, VOSviewer, citespace

Fengsong Chen,1 Yanhua Huang,1 Yayun Qian,2 Ya Zhao,2 Chiwen Bu,3 Dong Zhang3 1Department of Gastroenterology, Haimen People’s Hospital, Nantong, 226000, People’s Republic of China; 2Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, 225001, People’s Republic of China; 3Institute of Surgery, Guanyun People’s Hospital, Guanyun, 222200, People’s Republic of ChinaCorrespondence: Dong Zhang; Chiwen Bu, Email gyxrmyykjk@163.com; gyxrmyybcw@163.comBackground: Gastric lesions pose significant clinical challenges due to their varying degrees of malignancy and difficulty in early diagnosis. Early and accurate detection of these lesions is crucial for effective treatment and improved patient outcomes.Methods: This paper proposed a label-free and highly sensitive classification method for serum of patients with different degrees of gastric lesions by combining surface-enhanced Raman scattering (SERS) and machine learning analysis. Specifically, we prepared Au lotus-shaped (AuLS) nanoarrays substrates using seed-mediated and liquid–liquid interface self-assembly method for measuring SERS spectra of serum, and then the collected spectra were processed by principal component analysis (PCA) - multi-local means based nearest neighbor (MLMNN) model to achieve differentiation.Results: By employing this pattern analysis, AuLS nanoarray substrates can achieve fast, sensitive, and label-free serum spectral detection. The classification accuracy can reach 97.5%, the sensitivity is higher than 96.7%, and the specificity is higher than 95.0%. Moreover, by analyzing the PCs loading plots, the most critical spectral features distinguishing different degrees of gastric lesions were successfully captured.Conclusion: This discovery lays the foundation for combining SERS with machine learning for real-time diagnosis and recognition of gastric lesions.Keywords: surface-enhanced Raman scattering, gastric lesions, Au lotus-shaped nanoarrays, principal component analysis, multi-local means based nearest neighbor

Chunjiao Lu,&ast; Xuewei Wu,&ast; Xin Meng,&ast; Yi Liu, Ting Yang, Yan Zeng, Yang Chen, Yishan Huang, Zhou Fang, Xiaojun Yang, Juanjuan Luo Engineering Research Center of Key Technique for Biotherapy of Guangdong Province, Shantou University Medical College, Shantou, 515041, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaojun Yang; Juanjuan Luo, Shantou University Medical College, 22 Xinling Road, Shantou, 515041, People’s Republic of China, Email yangx@stu.edu.cn; 15jjluo1@stu.edu.cnIntroduction: The potential toxic effects of wastewater discharges containing silver nanoparticles (AgNPs) and their release into aquatic ecosystems on aquatic organisms are becoming a major concern for environmental and human health. However, the potential risks of AgNPs to aquatic organisms, especially for cardiac development by Focal adhesion pathway, are still poorly understood.Methods: The cardiac development of various concentrations of AgNPs in zebrafish were examined using stereoscopic microscope. The expression levels of cardiac development-related genes were analyzed by qRT-PCR and Whole-mount in situ hybridization (WISH). In addition, Illumina high-throughput global transcriptome analysis was performed to explore the potential signaling pathway involved in the treatment of zebrafish embryos by AgNPs after 72 h.Results: We systematically investigated the cardiac developing toxicity of AgNPs on the embryos of zebrafish. The results demonstrated that 2 or 4 mg/L AgNPs exposure induces cardiac developmental malformations, such as the appearance of pericardial edema phenotype. In addition, after 72 h of exposure, the mRNA levels of cardiac development-related genes, such as myh7, myh6, tpm1, nppa, tbx5, tbx20, myl7 and cmlc1, were significantly lower in AgNPs-treated zebrafish embryos than in control zebrafish embryos. Moreover, RNA sequencing, KEGG (Kyoto Encyclopedia of Genes) and Genomes and GSEA (gene set enrichment analysis) of the DEGs (differentially expressed genes) between the AgNPs-exposed and control groups indicated that the downregulated DEGs were mainly enriched in focal adhesion pathways. Further investigations demonstrated that the mRNA levels of focal adhesion pathway-related genes, such as igf1ra, shc3, grb2b, ptk2aa, akt1, itga4, parvaa, akt3b and vcla, were significantly decreased after AgNPs treatment in zebrafish.Conclusion: Thus, our findings illustrated that AgNPs could impair cardiac development by regulating the focal adhesion pathway in zebrafish.Keywords: AgNPs, focal adhesion, cardiac development, zebrafish

Yanan Huang,1,&ast; Yunfeng Wang,2,&ast; Tianyu Zheng,1,&ast; Shuang Nie,1 Yanli Wang,3 Hui Shen,1 Fengfeng Mo1 1Department of Naval Nutrition and Food Hygiene, Faculty of Navy Medicine, Naval Medical University, Shanghai, People’s Republic of China; 2Department of Gastroenterology, Changhai Hospital, Shanghai, People’s Republic of China; 3International Joint Research Center of Human-Machine Intelligent Collaborative for Tumor Precision Diagnosis and Treatment of Hainan Province, Hainan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yanli Wang; Fengfeng Mo, Email hyyaoxueyuan2022@163.com; mofengfeng@smmu.edu.cnPurpose: Erythrocytes and fibroblasts in the pancreatic cancer tumor microenvironment promote tumor cell growth and invasion by providing nutrients and promoting immunosuppression. Additionally, they form a barrier against the penetration of chemotherapeutic drugs. Therefore, the search for diversified tumor-targeting materials plays an essential role in solving the above problems.Methods: Physicochemical characterization of Graphene fluorescent nanoparticles (GFNPs) and nanomedicines were analyzed by transmission electron microscopy (TEM), elemental analyzers and ultraviolet fluorescence (UV/FL) spectrophotometer. Localization of GFNPs in cell and tissue sections imaged with laser confocal microscope, fluorescence scanner and small animal in vivo imager. Qualitative detection and quantitative detection of GFNPs and GFNPs-GEM were performed using High performance liquid chromatography (HPLC).Results: Based on the 3 nm average dimensions, GFNPs penetrate vascular endothelial cells and smooth muscle cells, achieve up to label 30% tumor cells and 60% cancer-associated fibroblasts (CAFs) cells, and accurately label mature red blood cells in the tumor microenvironment. In orthotopic transplanted pancreatic cancer models, the fluorescence intensity of GFNPs in tumors showed a positive correlation with the cycle size of tumor development. The differential spatial distribution of GFNPs in three typical clinical pancreatic cancer samples demonstrated their diagnostic potential. To mediate the excellent targeting properties of GFNPs, we synthesized a series of nanomedicines using popular chemotherapeutic drugs, in which complex of GFNPs and gemcitabine (GFNPs-GEM) possessed stability in vivo and exhibited effective reduction of tumor volume and fewer side effects.Conclusion: GFNPs with multiple targeting tumor microenvironments in pancreatic cancer possess diagnostic efficiency and therapeutic potential. Keywords: graphene fluorescent nanoparticles, cancer-associated fibroblasts, pancreatic cancer cells, dual-targeting, chemo-target therapy

Zhi-Jun Shen, Miao Liu, Jun-Xia Zhang, Yu Huang, Ying Kong, Shi-Guo Liu Department of Clinical Laboratory, Hubei Third People´s Hospital Affiliated to Jianghan University, Wuhan, 430033, People’s Republic of ChinaCorrespondence: Shi-Guo Liu, Department of Clinical Laboratory, Hubei Third People´s Hospital Affiliated to Jianghan University, No. 26, Zhongshan Road, Wuhan, Qiaokou District, People’s Republic of China, Email llsgg518@163.comBackground: Although observational studies have reported a correlation between vitamin D deficiency and type 2 diabetes mellitus (T2DM), epidemiological evidence on the risk of obese subjects suffering T2DM due to a vitamin D deficiency is limited. Therefore, we investigated the correlation between T2DM and serum vitamin D, lipids, blood pressure, insulin indexes in an obese population.Methods: A total of 1440 participants including 450 healthy controls and 990 obese subjects, 470 without T2DM and 520 with T2DM. Serum vitamin D levels were measured, and the association between low levels and T2DM in obese subjects was examined using multinomial and linear regression analyses.Results: Of the participants, 35% had deficient or insufficient vitamin D levels (ie, < 20 ng/mL). Compared with healthy controls, obese subjects, particularly those with T2DM had lower vitamin D levels. Multinomial logistic regression analysis showed that obese subjects with T2DM had a gradually increasing risk for desirable (RO = 1.41, 95% CI 1.06– 1.93, P = 0.027), insufficient (RO = 1.83, 95% CI 1.27– 2.84, P < 0.001), or deficient ((RO = 2.14, 95% CI 1.15– 3.75, P = 0.014) vitamin D levels. In obese subjects with T2DM, vitamin D levels correlated inversely with the risk indicators for diabetes, such as the levels of HbA1c (β = − 0.16, P = 0.002), fasting insulin (Fins; β = − 0.31, P = 0.008), and HOMA-IR (β = − 0.19, P < 0.001). In obese subjects without T2DM, vitamin D was associated negatively with the risk of having T2DM at five-year follow-up (relative risk = 0.93, 95% CI 0.79– 0.97, P = 0.037).Conclusion: This study demonstrates that low vitamin D levels correlate with the presence of T2DM in the obese population. This finding indicates that hypovitaminosis D may be a potential biological vulnerability factor for the development of T2DM in obese subjects.Keywords: vitamins, T2DM, obesity, biomarker

Juan Li,1,&ast; Shu Wang,2,&ast; Chaoping Ma,1,&ast; Ning Ning,3,&ast; Yingying Huang,1,4,&ast; Min Jiao,1 Jiyuan Zhang,1 Wenwu Sun,3 Jiaoyan Li,3 Bing Zhao,3 Enqiang Mao,3 Zaiqian Che,3 Chengjin Gao1 1Department of Emergency, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China; 2Department of Intensive Care Medicine, Chongqing University Central Hospital, Chongqing Emergency Medical Center, Chongqing, 400016, People’s Republic of China; 3Departments of Emergency, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200025, People’s Republic of China; 4Dementia Research Center, Macquarie University, Sydney, Australia&ast;These authors contributed equally to this workCorrespondence: Chengjin Gao, Department of Emergency, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, 1665 Kongjiang Road, Shanghai, People’s Republic of China, Email gaochengjin@xinhuamed.com.cn Zaiqian Che, Departments of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China, Email chezaiqian@163.comPurpose: New-onset atrial fibrillation (NOAF) and sepsis-induced coagulopathy (SIC) are severe complications in septic patients. However, the relationship between NOAF and SIC score has not been clearly defined. This study aims to investigate the association between SIC score and NOAF, as well as their effect on mortality in sepsis.Patients and Methods: This study was a two-center retrospective analysis. Medical data were collected from patients diagnosed with sepsis. The patients were divided into NOAF and non-NOAF groups, and the SIC score was calculated for each group. Univariable and multivariable logistic regression analyses were performed to explore the relationship between the SIC score and NOAF, as well as their effects on mortality. The Kaplan-Meier curve was used to assess the survival rate.Results: A total of 2,280 septic patients were included, with 132 (5.7%) suffering from NOAF. Multivariable logistic regression analyses indicated that age, gender, the Acute Physiology and Chronic Health Evaluation II score (APACHE II), heart rate, renal failure, stroke, chronic obstructive pulmonary disease (COPD), and the SIC score were independent risk factors for NOAF in sepsis. Moreover, NOAF was associated with an increased risk of in-hospital mortality, 28-day mortality, and 90-day mortality. These results were consistent across subgroup analyses.Conclusion: The SIC score was an independent risk factor for NOAF in septic patients, and NOAF was an independent risk factor for predicting mortality.Keywords: sepsis, sepsis-induced coagulopathy, new-onset atrial fibrillation, association, mortality

Shaoyan Shi, Leiming Hu, Dong Hu, Xuehai Ou, Yansheng Huang Department of Hand Surgery, Honghui Hospital, Xi’an Jiaotong University, Xi’an, 710000, People’s Republic of ChinaCorrespondence: Yansheng Huang, Department of Hand Surgery, Honghui Hospital, Xi’an Jiaotong University, Xi’an, 710000, People’s Republic of China, Email yshg1991@163.comAbstract: Diabetic wounds pose a significant challenge in modern healthcare due to their chronic and complex nature, often resulting in delayed healing, infections, and, in severe cases, amputations. In recent years, nanotherapeutic approaches have emerged as promising strategies to address the unique pathophysiological characteristics of diabetic wounds. This review paper provides a comprehensive overview of the latest advancements in nanotherapeutics for diabetic wound treatment. We discuss various nanomaterials and delivery systems employed in these emerging therapies. Furthermore, we explore the integration of biomaterials to enhance the efficacy of nanotherapeutic interventions. By examining the current state-of-the-art research, challenges, and prospects, this review aims to offer valuable insights for researchers, clinicians, and healthcare professionals working in the field of diabetic wound care.Keywords: diabetic wounds, nanoparticle, biomaterials, DELIVERY system

Yiwen Zhou,1,&ast; Yuyan Huang,1,&ast; Yingwen Wang,2 Xiaofeng Xu,1 Zhuowen Yu,1 Ying Gu3 1Department of Gastroenterology, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai, 201102, People’s Republic of China; 2Centre for Clinical Practice Guideline Production and Evaluation, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai, 201102, People’s Republic of China; 3Nursing Department, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai, 201102, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ying Gu, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai, 201102, People’s Republic of China, Email guying0128@aliyun.com Zhuowen Yu, Department of Gastroenterology, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai, 201102, People’s Republic of China, Email yzw100@126.comBackground: The Theoretical Domains Framework (TDF) is among the most extensively utilised foundational frameworks in implementation science. It was developed from 33 psychological theories, with the latest version identifying 14 domains encompassing 84 theoretical constructs. These domains and constructs capture the complexity of factors that affect behaviours, making the framework a valuable tool for designing and implementing interventions within health and social care settings.Objective: To summarise the development, hot topics, and future trends in TDF-related research and provide implementation practitioners with more information on the application of TDF.Methods: We used TDF as the topic and searched the ISI Web of Science Core Collection, identifying 1382 relevant publications. We used analytical tools such as Excel, Tableau, VOSviewer, and Citespace to conduct a bibliometric analysis of the relevant publication.Results: We identified the United Kingdom as the primary contributor, with University College London as the key institution. Susan Michie ranked highest in total citations. The analysis highlighted cancer and stroke as primary clinic medicine-related topics using TDF. Emerging themes encompass abuse, violence, maternal health, antenatal care, patient involvement, and trauma-informed care et al. “Nurse” and “qualitative research” emerged as recent and enduring hotspots, possibly indicating future research trends.Conclusion: This article represents the first attempt to summarise the TDF using bibliometric analysis. We suggest this method can be used to analyse other theoretical frameworks in scientific implementation of its objectivity and quantifiability. Overall, the application scope of TDF is shifting from public health towards more specialised clinical directions, although its application in the field of public health is continuously expanding. In the future, the number of users of TDF is also expected to expand from implementation scientists to professional technical personnel.Keywords: theoretical domains framework, bibliometric analysis, visualization, implementation science

Fujie Jiang,1,&ast; Shuling Liu,1,&ast; Lu Wang,1 Huifang Chen,1 Yao Huang,2 Ying Cao,2 Xiaoxia Wang,1 Meng Lin,1 Jiuquan Zhang1 1Department of Radiology, Chongqing University Cancer Hospital, Chongqing Key Laboratory for Intelligent Oncology in Breast Cancer (iCQBC), Chongqing, 400030, People’s Republic of China; 2School of Medicine, Chongqing University, Chongqing, 400030, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiuquan Zhang; Meng Lin, Department of Radiology Chongqing University Cancer Hospital, No. 181 Hanyu Road, Shapingba District, Chongqing, 400030, People’s Republic of China, Tel/Fax +86-23-65079339, Email zhangjq_radiol@foxmail.com; 15823113338@139.comPurpose: Chemotherapy mediated by Reactive oxygen species (ROS)-responsive drug delivery systems can potentially mitigate the toxic side effects of chemotherapeutic drugs and significantly enhance their therapeutic efficacy. However, achieving precise targeted drug delivery and real-time control of ROS-responsive drug release at tumor sites remains a formidable challenge. Therefore, this study aimed to describe a ROS-responsive drug delivery system with specific tumor targeting capabilities for mitigating chemotherapy-induced toxicity while enhancing therapeutic efficacy under guidance of Fluorescence (FL) and Magnetic resonance (MR) bimodal imaging.Methods: Indocyanine green (ICG), Doxorubicin (DOX) prodrug pB-DOX and Superparamagnetic iron oxide (SPIO, Fe3O4) were encapsulated in poly(lactic-co-glycolic acid) (PLGA) by double emulsification method to prepare ICG/ pB-DOX/ Fe3O4/ PLGA nanoparticles (IBFP NPs). The surface of IBFP NPs was functionalized with mammaglobin antibodies (mAbs) by carbodiimide method to construct the breast cancer-targeting mAbs/ IBFP NPs (MIBFP NPs). Thereafter, FL and MR bimodal imaging ability of MIBFP NPs was evaluated in vitro and in vivo. Finally, the combined photodynamic therapy (PDT) and chemotherapy efficacy evaluation based on MIBFP NPs was studied.Results: The multifunctional MIBFP NPs exhibited significant targeting efficacy for breast cancer. FL and MR bimodal imaging clearly displayed the distribution of the targeting MIBFP NPs in vivo. Upon near-infrared laser irradiation, the MIBFP NPs loaded with ICG effectively generated ROS for PDT, enabling precise tumor ablation. Simultaneously, it triggered activation of the pB-DOX by cleaving its sensitive moiety, thereby restoring DOX activity and achieving ROS-responsive targeted chemotherapy. Furthermore, the MIBFP NPs combined PDT and chemotherapy to enhance the efficiency of tumor ablation under guidance of bimodal imaging.Conclusion: MIBFP NPs constitute a novel dual-modality imaging-guided drug delivery system for targeted breast cancer therapy and offer precise and controlled combined treatment options.Keywords: targeted drug delivery, photodynamic therapy, ROS-responsive chemotherapy, bimodal imaging

Xinyue Chen,1 Xue Zhang,2 Ruijia Gao,2 Yu Huang,3 Shimeng Mao,2 Bing Wang,4 Jiying Feng4 1Department of Anesthesiology, Jinzhou Medical University, Jinzhou, Liaoning, People’s Republic of China; 2Department of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of China; 3Department of Anesthesiology, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 4Department of anesthesiology, the Affiliated Lianyungang Hospital of Xuzhou Medical University, the First People’s Hospital of Lianyungang, Lianyungang, Jiangsu, People’s Republic of ChinaCorrespondence: Jiying Feng, No. 6 East Zhenhua Road, The Affiliated Lianyungang Hospital of Xuzhou Medical University, Lianyungang, Jiangsu, People’s Republic of China, Email fengjymz@163.comPurpose: Anxiety and depression can affect the physiology of the gastrointestinal tract through the brain-gut axis, causing gastrointestinal dysfunction, which is mainly manifested as indigestion, diarrhoea, constipation, or abdominal pain. Preoperative anxiety arises in children due to separation from parents, fear of unfamiliar surroundings and anaesthesia and surgical procedures.To discuss the effect of alleviating preoperative anxiety on postoperative recovery of gastrointestinal function in children with indirect inguinal hernia after laparoscopic high ligation of the hernia sac.Patients and Methods: 90 children with laparoscopic high ligation of the herniated sac in oblique inguinal hernia were randomly divided into control group (Group C) and experimental group (Group M). The Group M was given midazolam oral solution 0.5mg/kg (maximum dose 20mg), and The Group C was given 5% glucose solution with the same dose.Primary outcome was the time to first postoperative defecation and I-FEED scores.The secondary outcomes included mYPAS-SF scores; child sedation scores; child-parent separation scores; parental STAI scores;PHBQ scores;FLACC scores, operative time, and fluid input and surgeon job satisfaction.Results: Compared with Group C, there was a shorter time to first postoperative defecation (P < 0.05), and lower I-FEED scores on postoperative day 1 (P < 0.05). The mYPAS-SF scores, which were significantly different in Group M at T1, T2, and T3 (P < 0.05), parental STAI scores at S1, child sedation scores and child-parent separation scores in T1, and surgeon job satisfaction between the two groups were significantly different (P < 0.05). There were no statistically significant differences in I-FEED scores on days 2 and 3, PHBQ scores, FLACC scores, operative time, and fluid input between the two groups of children (P > 0.05).Conclusion: Preoperative application of midazolam oral solution to relieve preoperative anxiety helps to promote the recovery of postoperative gastrointestinal function in children with indirect inguinal hernia and increases the surgeon job satisfaction.Keywords: preoperative anxiety, gastrointestinal function, midazolam:pediatric surgery

Ying Zhu,1 Tao Zeng,1 Hongbo Huai,2 Tong Zhu,3 Ying Huang,3 Jing Li,3 Jian Lin3 1Department of Pain Medicine, Kunshan Integrated TCM and Western Medicine Hospital, Kunshan, 215332, People’s Republic of China; 2Rehabilitation Department, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, People’s Republic of China; 3Department of Pain Medicine, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, People’s Republic of ChinaCorrespondence: Hongbo Huai; Tong Zhu, Email Huaihongbo@njglyy.com; 1911033561@qq.comPurpose: This retrospective study was to investigate the efficacy of Gasserian ganglion pulsed radiofrequency therapy (PRF) combined with low-dose morphine injection in the treatment of refractory ophthalmic herpetic neuralgia.Patients and methods: A total of 40 intractable ophthalmic herpetic neuralgia patients who received Gasserian ganglion PRF therapy in Pain Department of Nanjing Drum Tower Hospital were retrospectively analysed, with an average age of 70.2 ± 8.5 years and an average disease course of 30 (30, 60) days. According to different interventions, they were divided into two groups: Group A, 19 patients who received Gasserian ganglion PRF therapy combined with 0.2 mg morphine injection via puncture needle; Group B, 21 patients who received only Gasserian ganglion PRF therapy. Data related to the length of hospital stay and associated costs, numerical rating scale scores (NRS), intravenous morphine and oral oxycodone doses during hospitalization, Short form McGill pain questionnaire and Pittsburgh sleep quality index (PSI), and conditions of opioid use and postherpetic neuralgia after discharge were collected in the two groups. SPSS 25.0 was used to perform statistical analysis on data.Results: The hospital stay, hospitalization costs, and oxycodone dosages for Group A were lower than those for Group B (p = 0.02, p = 0.015 and p = 0.023, respectively). The proportion of patients in group A still taking oral opioids 1 month after discharge and experiencing postherpetic neuralgia 6 months after the onset was lower than that in group B (p = 0.004 and p = 0.049). The NRS upon discharge, as well as the McGill and PSQI scores at the time of discharge and at 1, 3, 6 and 12 months post-discharge, were all significantly reduced compared to those measured upon admission in two groups (p = 0.000).Conclusion: Gasserian ganglion PRF therapy combined with low-dose morphine injection offers an alternative option for managing intractable herpetic neuralgia and prevention of postherpetic neuralgia in ocular branches.Clinical Trial Registration: ChiCTR2300073281.Keywords: ophthalmic, herpetic neuralgia, pulsed radiofrequency, Gasserian ganglion, opioids

Yu Huang,&ast; Ying Huang,&ast; Chaoyong Xiao, Qingling Huang, Xue Chai Department of Radiology, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, 210029, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xue Chai, Department of Radiology, Brain Hospital Affiliated to Nanjing Medical University, Nanjing, 210029, People’s Republic of China, Email 20600412@163.comObjective: This study aims to evaluate the effectiveness of Magnetic Resonance Virtual Endoscopy combined with 3D-FIESTA-c and 3D-TOF-MRA in preoperative assessment of MVD for PTN, with a focus on accurately detecting neuromuscular contact.Methods: We retrospectively analyzed clinical and imaging data from 240 patients with unilateral primary trigeminal neuralgia undergoing MVD surgery between April 2016 and July 2023. Preoperative scans with 3D-FIESTA-c and 3D-TOF-MRA were performed, and MRVE images were obtained to analyze the relationship between the trigeminal nerve and adjacent vessels. Using the findings during microvascular decompression (MVD) surgery as the gold standard, the diagnostic results of 3D-TOF-MRA + 3D-FIESTA-c were considered as group I, while the combined use of MRVE, 3D-TOF-MRA + 3D-FIESTA-c was considered as group II.Results: In 240 cases, group I had a positive rate of 96.25% and an accuracy rate of 86.25% for identifying responsible blood vessels, while group II had a positive rate of 98.3% and an accuracy rate of 94.17%. There were no statistically significant differences in positive rates between group I and group II, group I and MVD, or group II and MVD (P > 0.05). However, there were statistically significant differences in accuracy rates (P < 0.05). The accuracy for single and multiple arteries with group I was 99.38% and 80.0%, respectively, while with group II, it was 100% and 95.0%. No statistically significant difference was found in accuracy for single or multiple arteries (P> 0.05). The accuracy of evaluating responsibility veins with or without other vessels was 52.73% and 80.0%, respectively, with a statistically significant difference (P< 0.05).Conclusion: MRVE combined with 3D-TOF-MRA + 3D-FIESTA-c significantly improves the accuracy of identifying responsibility vessels, especially veins, in preoperative assessment for MVD. This has important clinical implications for preoperative decision-making and surgical planning. Keywords: primary trigeminal neuralgia, magnetic resonance imaging, magnetic resonance virtual endoscopy, microvascular decompression

Hailing Yu,1,&ast; Yongquan Huang,2,&ast; Zhisheng Nong,3,&ast; Xi Lin,1 Kexin Tang,1 Zeyu Cai,1 Kaichen Huang,4 Ting Yu,1 Huimin Lan,1 Qianqian Zhang,1 Qiang Wang,5 Lei Yang,6 Jingchuan Zhu,7 Lili Wu,8 Hui Luo1 1Guangdong Provincial Engineering Research Center of Molecular Imaging, Guangdong-Hong Kong-Macao University Joint Laboratory of Interventional Medicine, The Fifth Affiliated Hospital, Sun Yat-Sen University, Zhuhai, Guangdong, People’s Republic of China; 2Department of Ultrasound, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong, People’s Republic of China; 3School of Materials Science and Engineering, Shenyang Aerospace University, Shenyang, Liaoning, People’s Republic of China; 4Department of Clinical laboratory, The Third People’s Hospital of Zhuhai, Zhuhai, Guangdong, People’s Republic of China; 5The Green Aerotechnics Research Institute of Chongqing Jiaotong University, Chongqing, People’s Republic of China; 6Center for Composite Materials and Structures, Harbin Institute of Technology, Harbin, Heilongjiang, People’s Republic of China; 7School of Materials Science and Engineering, Harbin Institute of Technology, Harbin, Heilongjiang, People’s Republic of China; 8Key Laboratory for Photonic and Electronic Bandgap Materials, Ministry of Education, School of Physics and Electronic Engineering, Harbin Normal University, Harbin, Heilongjiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hui Luo; Lili Wu, Email luoh53@mail.sysu.edu.cn; wll790107@hotmail.comIntroduction: Traditional cancer treatment strategies often have severe toxic side effects and poor therapeutic efficacy. To address the long-standing problems related to overcoming the complexity of tumors, we develop a novel nanozyme based on the in situ oxidation of 2D Ti3C2 structure to perform simultaneous phototherapy and sonodynamic therapy on tumors. Ti3C2 nanozymes exhibit multi-enzyme activity, including intrinsic peroxidase (POD) activities, which can react with H2O2 in the tumor microenvironment. This new material can construct Ti3C2/TiO2 heterostructures in vivo.Methods: Photothermal (PTT), sonodynamic (SDT) effects, and photoacoustic (PA) image-guided synergy therapy can be achieved. Finally, anticancer immune responses occur with this nanozyme. In vivo experiments revealed that the Ti3C2/TiO2 heterostructure inhibited tumor growth.Results: Complementarily, our results showed that the Ti3C2/TiO2 heterostructure enhanced the immunogenic activity of tumors by recruiting cytotoxic T cells, thereby enhancing the tumor ablation effect. Mechanistic studies consistently indicated that Reactive Oxygen Species (ROS) regulates apoptosis of HCC cells by modulating NRF2/OSGIN1 signaling both in vitro and in vivo. As a result, Ti3C2 nanozyme effectively inhibited tumor through its synergistic ability to modulate ROS and enhance immune infiltration of cytotoxic T cells in the tumor microenvironment.Discussion: These findings open up new avenues for enhancing 2D Ti3C2 nanosheets and suggest a new way to develop more effective sonosensitizers for the treatment of cancer.Keywords: nanozyme, sonodynamic therapy, Ti3C2/TiO2, ROS

Hui Tang,1,&ast; Xiaoxia Ding,2,3,&ast; Youming Huang,2 Danfeng Xu,2 Yibin Fan1,2 1Graduate School of Clinical Medicine, Bengbu Medical College, Bengbu, 233030, People’s Republic of China; 2Center for Plastic & Reconstructive Surgery, Department of Dermatology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital of Hangzhou Medical College, Hangzhou, 310014, People’s Republic of China; 3Department of Dermatology and Venereology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yibin Fan, Graduate School of Clinical Medicine, Bengbu Medical College, Bengbu, 233030, People’s Republic of China, Tel +86 18806538451, Email fanyibin@hmc.edu.cnIntroduction: Vitiligo is an acquired skin pigmentation disorder, the cause of which is poorly understood. Researchers in this field are dedicated to exploring novel treatments for achieving re-pigmentation.Methods: Mice were randomly selected and divided into control, model, and model+laser groups. Evaluate the impact of different levels of carbon dioxide laser irradiation on tyrosinase activity, melanocyte viability, and melanin content.Results: In this study, it was found that the cell viability and melanin content were significantly enhanced in human melanocytes after treatment with different energy densities of fractional carbon dioxide laser. In addition, laser-treated vitiligo mouse models showed mild pathological changes.Discussion: Therefore, we believe that fractional carbon dioxide laser may be a potential adjunctive modality for treating vitiligo.Keywords: vitiligo, fractional carbon dioxide laser, melanocytes, melanogenesis, vitiligo mouse models

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

Zheng Zhang,1,&ast; Yan Li,1,&ast; Siyuan Wang,2 Jizhi Wang,1 Ying Huang,1 Xiaoping Wang,1 Huijuan Guo,1 Jiansong Zhou1 1Department of Psychiatry, National Clinical Research Center for Mental Disorders, and National Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, Hunan, 410011, People’s Republic of China; 2Pingtang Compulsory Isolation Detoxification Institute in Hunan Province, Changsha, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Huijuan Guo; Jiansong Zhou, Department of Psychiatry, National Clinical Research Center for Mental Disorders, and National Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of China, 410011, Email guohuijuan2023@csu.edu.cn; zhoujs2003@csu.edu.cnBackground: Correctional officers face widespread workplace violence and the resulting overwork that can profoundly damage their physical and mental health.Purpose: This study aims to investigate the mediating role of overwork in the relationship between workplace violence and the manifestation of physical and mental health issues among correctional officers.Methods: This study enlisted 472 eligible participants. Cross-sectional data were obtained using the Chinese version of the Workplace Violence Scale (WVS), while the physical and mental health of correctional officers was evaluated through relevant scales. Analysis involved descriptive statistics, correlation analyses, and tests for mediation models.Results: The study found significant correlations between workplace violence, overwork, and various mental health variables (depression, anxiety, stress, suicidal ideation, and insomnia), with correlations ranging from 0.135 to 0.822 (p < 0.01). Mediation analysis revealed that workplace violence directly impacts correctional officers’ physical and mental health (p < 0.001) and also has an indirect effect through overwork (p < 0.023). These findings underscore the substantial impact of workplace violence on the health of correctional officers, both directly and indirectly.Conclusion: Workplace violence and overwork significantly contribute to the physical and mental health challenges faced by correctional officers. Overwork acts as a mediator in the relationship between workplace violence and these health issues. The study suggests addressing workplace violence and mental health issues among correctional officers by increasing their numbers, improving the work environment, and implementing enhanced welfare policies.Keywords: correctional officers, workplace violence, overwork, physical and mental health

Wenbin Wang,1 Lin Liu,2 Weida Qiu,1 Chaolei Chen,1 Yuqing Huang,1 Anping Cai,1 Zhiqiang Nie,1 Yanqiu Ou,1 Yicheng Zhu,1 Yingqing Feng1 1Department of Cardiology, Hypertension Research Laboratory, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, People’s Republic of China; 2Department of Medicine, The University of Hong Kong, Hong Kong, ChinaCorrespondence: Yingqing Feng; Yicheng Zhu, Department of Cardiology, Hypertension Research Laboratory, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, No. 106, Zhongshan 2nd Road, Yuexiu District, Guangzhou, 510080, People’s Republic of China, Email fengyingqing@gdph.org.cn; zhuyicheng@gdph.org.cnIntroduction: Traditional clinical risk factors are insufficient to estimate the residual risk of large-vessel ischemic stroke. Non-targeted lipidomic techniques provide an opportunity to evaluate these risks.Methods: Plasma samples were collected from 113 hypertensive individuals, including 55 individuals at high risk of ischemic stroke and 58 matched individuals, in a prospective nested case-control cohort. To identify dysregulated lipid metabolites, we conducted multivariate and univariate analyses. A classifier based on a cross-validated procedure was employed to select the optimal combination of lipid species and their ratios.Results: We identified 23 dysregulated lipid species in patients with and without ischemic stroke, including 16 (69.6%) up-regulated and 7 (30.4%) down-regulated lipid species. Through internal cross-validation, the optimal combination of two lipid features (phosphatidylcholine 34:2 and triglyceride 18:1/18:1/22:1 / phosphatidylcholine 34:2, referred to as ischemic stroke-related 2 lipid features - IS2LP) was selected, leading to a more precise prediction probability for ischemic stroke within 3.9 years. In the comparison of different risk factors, the traditional risk score, the IS2LP risk score, and the combination of the traditional risk score with IS2LP yield AUC values of 0.613(95% CI:0.509– 0.717), 0.833(95% CI:0.755– 0.911), and 0.843(95% CI:0.777– 0.916), respectively. The combination of the traditional risk score and IS2LP exhibited significantly improved discriminative performance, with an integrated discrimination improvement (IDI) of 0.31 (p< 0.001) and a continuous net reclassification improvement (NRI) of 1.06 (p < 0.001) compared to the traditional risk score.Conclusion: We identified new lipidomic biomarkers associated with the futural event of large-vessel ischemic stroke. These lipid species could serve as potential blood biomarkers for assessing the residual risk of ischemic stroke in hypertensive individuals.Keywords: hypertension, lipidomics, ischemic stroke, risk factors

Yuan Huang,1,&ast; Hong Yang,2,&ast; Rui Ding,1,&ast; Li Wang,3 Ji Li,2 Wenbo Li,4 Xuzhen Qin,1 Yingchun Xu,1 Jiaming Qian2 1Department of Laboratory Medicine, Peking Union Medical College Hospital & Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 2Department of Gastroenterology, Peking Union Medical College Hospital & Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 3Department of Epidemiology and Health Statistics, Institute of Basic Medicine, Peking Union Medical College, Beijing, People’s Republic of China; 4Department of Ultrasound, Peking Union Medical College Hospital & Chinese Academy of Medical Sciences, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xuzhen Qin; Jiaming Qian, Email qxz_01@163.com; qianjiaming1957@126.comObjective: Serum pepsinogen (PG) is a good indicator of atrophic changes in the gastric mucosa. Gastric mucosal atrophy is a high-risk factor for gastric cancer. Serological testing for PG combined with endoscopy can help to improve gastric cancer screening. In this study, we established the reference ranges of serum PG-I, PG-II, and the PG-I/II ratio (PGR) in the Chinese population by chemiluminescence immunoassay (CLIA) and enzyme-linked immunosorbent assay (ELISA). Besides, in the real world, doctors are often confused by the results of different testing platforms. Thus, a comparison of methods CLIA and ELISA was performed.Methods: 2904 individuals were enrolled from six regions in China as part of the Chinese Adult Digestive Diseases Surveillance (2016) program. The individuals completed questionnaires and volunteered to undergo examinations, including gastroscopy, urea breath test, abdominal ultrasound examination and routine serologic tests. Serum was collected to measure PGs (including PG-I, PG-II and PGR) by CLIA and ELISA. Participants who were found obvious abnormalities or absent from the examinations were excluded. Ultimately, 747 healthy individuals were enrolled in this study. The Kolmogorov–Smirnov test was used to assess the distribution of variables. The Kruskal–Wallis H or Mann–Whitney U-tests were used to compare different sex, age, and geographical groups. The 95% reference ranges of PGs obtained by the two methods were established according to document CLSI-EP28-A3, with covariates of sex, age, and region. Spearman correlation analysis, linear regression analysis and allowable total error (ATE) zone analysis were utilized for comparing the two methods.Results: On overall, the 95% reference ranges of PG-I, PG-II, and PGR measured by CLIA were 23.00– 110.64 ng/mL, 2.50– 19.13 ng/mL, and 3.87– 13.30, respectively. Meanwhile, the reference ranges of PG-I, PG-II, and PGR measured by ELISA were 36.93– 205.06 ng/mL, 1.65– 17.96 ng/mL, and 7.50– 33.60, respectively. Both PG-I and PG-II levels measured by the two platforms were found to be influenced by sex and age. PGR measured by CLIA was influenced by age but not by sex, while PGR measured by ELISA was not affected by either age or sex. Regional factors did not significantly impact the PG results, except for PG-I detected by ELISA. Ultimately, reference ranges for PGs were established based on age and sex stratification. Additionally, the Spearman correlation analysis revealed that the correlation coefficients for PG-I, PG-II, and PGR detected by the two methods were 0.899, 0.887, and 0.777, respectively, indicating a strong correlation between the two methods. The regression equation for the PG levels detected by two methods was obtained through linear regression analysis. The ATE analysis provided a visual depiction of the consistency between the two methods, clearly indicating the poor agreement between them.Conclusion: This study established the reference ranges of PGs by strict and intact enrollment standard. In addition, the results indicated a strong linear relationship between the two methods, yet with a clear bias, which was valuable for laboratory interpretation.Keywords: pepsinogen, reference range, gastric cancer

Yongpeng Huang, Hui Tang, Xiangyan Meng, Dongxin Liu, Yanli Liu, Bo Chen, Zhiyun Zou State Key Laboratory of NBC Protection for Civilian, Beijing, People’s Republic of ChinaCorrespondence: Bo Chen; Zhiyun Zou, Email NBC_BoChen@163.com; zouzhiyun65@163.comIntroduction: Nanoparticles have the advantages of improving the solubility of poorly water-soluble drugs, facilitating the drug across biological barriers, and reducing macrophage phagocytosis in pulmonary drug delivery. However, nanoparticles have a small aerodynamic particle size, which makes it difficult to achieve optimal deposition when delivered directly to the lungs. Therefore, delivering nanoparticles to the lungs effectively has become a popular research topic.Methods: Nanoaggregate microparticles were used as a pulmonary drug delivery strategy for the improvement of the bioavailability of cyclosporine A (CsA). The nanoaggregate microparticles were prepared with polyvinyl pyrrolidone (PVP) as the excipient by combining the anti-solvent method and spray drying process. The physicochemical properties, aerodynamic properties, in vivo pharmacokinetics and inhalation toxicity of nanoaggregate microparticles were systematically evaluated.Results: The optimal nanoparticles exhibited mainly spherical shapes with the particle size and zeta potential of 180.52 nm and − 19.8 mV. The nanoaggregate microparticles exhibited irregular shapes with the particle sizes of less than 1.6 μm and drug loading (DL) values higher than 70%. Formulation NM-2 as the optimal nanoaggregate microparticles was suitable for pulmonary drug delivery and probably deposited in the bronchiole and alveolar region, with FPF and MMAD values of 89.62% and 1.74 μm. In addition, inhaled NM-2 had Cmax and AUC0-∞ values approximately 1.7-fold and 1.8-fold higher than oral cyclosporine soft capsules (Neoral®). The inhalation toxicity study suggested that pulmonary delivery of NM-2 did not result in lung function damage, inflammatory responses, or tissue lesions.Conclusion: The novel nanoaggregate microparticles for pulmonary drug delivery could effectively enhance the relative bioavailability of CsA and had great potential for clinical application. Keywords: pulmonary drug delivery, dry powder inhalers, nanoaggregate microparticles, aerosol performance, pharmacodynamic study, inhalation toxicity

Huishan Zhang,1,2,&ast; Jing Lin,3,4,&ast; Yufang Huang,3,4 Yu Chen3,4 1Department of Phase I Clinical Trial Ward, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, Fujian, 350014, People’s Republic of China; 2Department of Radiation Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, Fujian, 350014, People’s Republic of China; 3Department of Medical Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, Fujian, 350014, People’s Republic of China; 4Cancer Bio-Immunotherapy Center, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, Fujian, 350014, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yu Chen, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, 420 Fuma Road, Fuzhou, Fujian, 350014, People’s Republic of China, Tel +86-62752224 Ext 0596, Email chenyu1980@fjmu.edu.cnPurpose: Patients with locally advanced esophageal squamous cell carcinoma (ESCC) scheduled for neoadjuvant radiotherapy still have a poor prognosis. This study was to explore the prognostic value of the pretreatment systemic immune-inflammation index (SII) in patients with locally advanced ESCC after neoadjuvant radiotherapy (NRT).Materials and Methods: Eighty-two consecutive patients with ESCC scheduled for neoadjuvant radiotherapy between 2011 and 2017 were enrolled in this study. SII values (SII = platelet × neutrophil/lymphocyte), prognostic nutritional index values (PNI = albumin concentration (g/L) + 5 × total lymphocyte count (109/L)), platelet–lymphocyte ratio (PLR), and neutrophil–lymphocyte ratio (NLR) were retrospectively collected and calculated before treatment. The Cut-off Finder application was applied to find out the cut-off points of the SII, NLR, PNI and PLR. A regression model was used to examine prognostic factors for overall survival (OS) rates.Results: The median follow-up was 44 months (3 to 83). Sixty patients (73.17%) underwent surgery as scheduled. This study found that factors improving OS were a lower SII (≤ 916.6 × 109/L) (P=0.040) and neoadjuvant chemoradiotherapy (NCRT) (P=0.034). The patients with a lower SII and NCRT had a better OS (P< 0.001). Moreover, additionally, a higher SII was associated with a lower resectability rate (P=0.035).Conclusion: The SII can predict resectability in ESCC patients following neoadjuvant radiotherapy. Both the SII and neoadjuvant chemoradiotherapy appear to influence OS.Keywords: ESCC, NCRT, SII, resectable

Qingran Sun, Yi Wang, Pei Wang, Yuankai Huang, Xiaoyu Xi National Medical Products Administration Key Laboratory for Drug Regulatory Innovation and Evaluation, China Pharmaceutical University, Nanjing, Jiangsu Province, People’s Republic of ChinaCorrespondence: Xiaoyu Xi, Email xixy@cpu.edu.cnPurpose: This study aimed to survey and analyze the preferences for pharmacist-managed clinic among urban residents in China.Materials and Methods: A discrete choice experiment was conducted in Nanjing, China. A D-efficient fractional factorial design was used to generate the questionnaire. Three models were used to investigate each patient’s strength of preference and preference heterogeneity. The relative importance for each treatment attribute was also determined.Results: 156 usable questionnaires (of 228 questionnaires sent out) were received. Respondents preferred pharmacist-managed clinics with the following characteristics: good pharmacists’ knowledge and clinical medication practice competency, lower consultation fees, a dedicated consultation room, physician-pharmacist joint clinic, with pharmacists’ knowledge competency receiving the highest priority. Latent class analysis revealed three classes (Experiential Type, Content Type and Economic Type) were identified based on respondents’ preferences for pharmacist-managed clinics.Conclusion: The respondents were willing to choose a PMC relative to the current situation. When deciding on a pharmacist-managed clinic, residents are driven by pharmacists’ competency, consultation fee, availability of consultation rooms and collaborative care or independent pharmacist service. Differences in patients’ preferences identified in the study provide information on pharmacist-managed clinics that meet residents’ expectations.Keywords: conjoint analysis, discrete choice experiment, pharmacist-managed clinic, preference study, patients

Shanshan Li,1,2 Le Zhang,3 Boyi Yang,3 Yi Huang,3 Yuqi Guan,3 Nanbo Huang,1 Yingnan Wu,1 Wenshuo Wang,1 Qing Wang,1 Haochen Cai,1 Yong Sun,1 Zijun Xu,1 Qin Wu1,2 1Medical College, Jiangsu Vocational College of Medicine, Yancheng, People’s Republic of China; 2Jiangsu Engineering Research Centers for Cardiovascular and Cerebrovascular Disease and Cancer Prevention and Control, Jiangsu Vocational College of Medicine, Yancheng, People’s Republic of China; 3Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of ChinaCorrespondence: Qin Wu, Medical College, Jiangsu Vocational College of Medicine, No. 283, South Jiefang Road, Yancheng, 224005, People’s Republic of China, Tel +86-515-88159750, Email hhwuq@163.comBackground: In elderly diabetic patients, depression is often overlooked because professional evaluation requires psychiatrists, but such specialists are lacking in the community. Therefore, we aimed to create a simple depression screening model that allows earlier detection of depressive disorders in elderly diabetic patients by community health workers.Methods: The prediction model was developed in a primary cohort that consisted of 210 patients with diabetes, and data were gathered from December 2022 to February 2023. The independent validation cohort included 99 consecutive patients from February 2023 to March 2023. Multivariable logistic regression analysis was used to develop the predictive model. We incorporated common demographic characteristics, diabetes–specific factors, family structure characteristics, the self–perceived burden scale (SPBS) score, and the family APGAR (adaptation, partnership, growth, affection, resolution) score. The performance of the nomogram was assessed with respect to its calibration (calibration curve, the Hosmer–Lemeshow test), discrimination (the area under the curve (AUC)), and clinical usefulness (Decision curve analysis (DCA)).Results: The prediction nomogram incorporated 5 crucial factors such as glucose monitoring status, exercise status, monthly income, sleep disorder status, and the SPBS score. The model demonstrated strong discrimination in the primary cohort, with an AUC of 0.839 (95% CI, 0.781– 0.897). This discriminative ability was further validated in the validation cohort, with an AUC of 0.857 (95% CI, 0.779– 0.935). Moreover, the nomogram exhibited satisfactory calibration. DCA suggested that the prediction of depression in elderly patients with diabetes mellitus was of great clinical value.Conclusion: The prediction model provides precise and user–friendly guidance for community health workers in preliminary screenings for depression among elderly patients with diabetes.Keywords: prediction model, depression, elderly, diabetes, community–based

Xiamin Pu,1 Houqiang Huang,2 Xiaolei Zhao,3 Feng Liu,1 Yebo Leng,4 Ya Deng,5 Lingyi Huang,5 Xingchen Zhou,5 Fen Xu,1 Yongli Huang,6 Shengmin Guo2 1Department of Cardiovascular Medicine, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, People’s Republic of China; 2Department of Nursing, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, People’s Republic of China; 3Department of Hematology, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, People’s Republic of China; 4Department of Orthopedics, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, People’s Republic of China; 5School of Nursing, Southwest Medical University, Luzhou, 646000, People’s Republic of China; 6Department of Outpatient, The Affiliated Hospital, Southwest Medical University, Luzhou, People’s Republic of ChinaCorrespondence: Shengmin Guo, Department of Nursing, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, People’s Republic of China, Tel +86-13980255653, Email 2930773281@qq.comBackground: A global public health problem, frailty is closely associated with poor prognosis after percutaneous coronary intervention (PCI) in older patients with acute myocardial infarction (AMI). Although exercise intervention is the most commonly used method to reverse and alleviate frailty, its application is restricted in patients with acute myocardial infarction following PCI due to cardiovascular instability and autonomic imbalance. Consequently, there is a need for a new practical intervention to address frailty syndrome in these patients.Purpose: This study aimed to investigate the effect of neuromuscular electrical stimulation in frail older AMI patients post-PCI.Patients and Methods: A single-blind, randomized controlled trial was carried out in the Department of Cardiovascular Medicine from March to October 2023. A total of 100 eligible participants were randomly divided into two groups: experimental (n = 50) and control (n = 50) groups, respectively. Both groups received usual care. The experimental group underwent neuromuscular electrical stimulation (NMES) on bilateral quadriceps and gastrocnemius muscles for 30 minutes daily from day 1 to day 7 after surgery. The primary outcomes measured included the frailty score, lower limb muscle strength, and lower limb muscle quality. Secondary outcomes included the activities of daily living score, inflammatory markers, and length of hospital stay. All participants were included in an intention-to-treat analysis after the study ended.Results: The frailty scores of the two groups exhibited a gradual decrease over time, and the scores of the experimental group were lower than those of the control group at 4 and 7 days after surgery (P< 0.001). Concurrently, the lower limb muscle strength showed an increasing trend over the time in the experimental group and a decreasing trend in the control group, and the scores of the experimental group surpassed those of the control group (p< 0.001). Moreover, a statistical difference was observed in the lower limb muscle mass across the groups after 7 days postoperatively compared with baseline on both sides (p< 0.05).Conclusion: Neuromuscular electrical stimulation has the potential to enhance lower limb function and alleviate frailty in elderly patients with acute myocardial infarction after PCI. These findings introduce a novel intervention approach for frailty management in the elderly population.Keywords: acute myocardial infarction, older, frailty, neuromuscular electrical stimulation, PCI

Haiping Xie,1,&ast; Xuexin Zhong,1,&ast; Junlin Chen,2 Shuang Wang,1 Yuefang Huang,2 Niansheng Yang1 1Department of Rheumatology and Clinical Immunology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, People’s Republic of China; 2Department of Pediatrics, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Niansheng Yang, Department of Rheumatology and Clinical Immunology, The First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan Second Road, Guangzhou, 510080, People’s Republic of China, Tel +86-20-87755766 ext 8150, Email yangnsh@mail.sysu.edu.cnBackground: Interstitial lung disease (ILD), characterized by pulmonary fibrosis (PF), represents the end-stage of various ILDs. The immune system plays an important role in the pathogenesis of PF. V-domain immunoglobulin suppressor of T-cell activation (VISTA) is an immune checkpoint with immune suppressive functions. However, its specific role in the development of PF and the underlying mechanisms remain to be elucidated.Methods: We assessed the expression of VISTA in CD4 T cells from patients with connective tissue disease-related interstitial lung disease (CTD-ILD). Spleen cells from wild-type (WT) or Vsir−/− mice were isolated and induced for cell differentiation in vitro. Additionally, primary lung fibroblasts were isolated and treated with interleukin-17A (IL-17A). Mice were challenged with bleomycin (BLM) following VISTA blockade or Vsir knockout. Moreover, WT or Vsir−/− CD4 T cells were transferred into Rag1−/− mice, which were then challenged with BLM.Results: VISTA expression was decreased in CD4 T cells from patients with CTD-ILD. Vsir deficiency augmented T-helper 17 (Th17) cell differentiation in vitro. Furthermore, IL-17A enhanced the production of inflammatory cytokines, as well as the differentiation and migration of lung fibroblasts. Both VISTA blockade and knockout of Vsir increased the percentage of IL-17A-producing Th17 cells and promoted BLM-induced PF. In addition, mice receiving Vsir−/− CD4 T cells exhibited a higher percentage of Th17 cells and more severe PF compared to those receiving WT CD4 T cells.Conclusion: These findings demonstrate the significant role of VISTA in modulating the development of PF by controlling Th17 cell differentiation. These insights suggest that targeting VISTA could be a promising therapeutic strategy for PF. Keywords: VISTA, lung fibrosis, Th17 cells, IL-17A, fibroblast

Xiaodong Zhu,1 Ya Huang,2 Jia Ding,1 Jianguo Liu,1 Changmeng Cui,1 Guangkui Han1 1Department of Neurosurgery, Affiliated Hospital of Jining Medical University, Jining, 272000, People’s Republic of China; 2College of Traditional Chinese Medicine, Shandong Polytechnic College, Jining, 272000, People’s Republic of ChinaCorrespondence: Guangkui Han, Department of Neurosurgery, Affiliated Hospital of Jining Medical University, 89 Guhuai Road, Jining, Shandong, 272000, People’s Republic of China, Tel +8618266808351, Email hanguangkui1997@163.comPurpose: SN-38 (7-ethyl-10-hydroxycamptothecin), the active metabolite of irinotecan, has been extensively studied in drug delivery systems. However, its impact on neural metabolism remains unclear. This study aims to investigate the toxic effects of SN-38 on mouse brain metabolism.Methods: Male mice were divided into an SN-38 group and a control group. The SN-38 group received SN-38 (20 mg/kg/day) via intraperitoneal injection, while the control group was given an equal volume of a blank solvent mixture (DMSO and saline, ratio 1:9). Gas chromatography-mass spectrometry (GC-MS) was employed to analyze differential metabolites in the cortical and hippocampal regions of the SN-38-treated mice.Results: SN-38 induced metabolic disturbances in the central nervous system. Eighteen differential metabolites were identified in the hippocampus and twenty-four in the cortex, with six common to both regions. KEGG pathway enrichment analysis revealed statistically significant alterations in six metabolic pathways in the hippocampus and ten in the cortex (P< 0.05).Conclusion: This study is the first to demonstrate the neurotoxicity of SN-38 in male mice through metabolomics. Differential metabolites in the hippocampal and cortical regions were closely linked to purine metabolism, pyrimidine metabolism, amino acid metabolism, and glyceride metabolism, indicating disruptions in the blood-brain barrier, energy metabolism, and central signaling pathways.Keywords: SN-38 (7-ethyl-10-hydroxycamptothecin), biomarker, gas chromatography mass spectrometry, metabolomics, toxicity mechanism

Zhipeng Liu,1,&ast; Xinyu Yuan,2,&ast; Yan Huang,3 Zihan Gu,4 Lu Xue,5 Shanshan Xue,6 Jun Wang2 1Information Department, The Affiliated Taizhou People’s Hospital of Nanjing Medical University, Taizhou School of Clinical Medicine, Nanjing Medical University, Taizhou, Jiangsu Province, 225300, People’s Republic of China; 2Emergency Department, The Affiliated Taizhou People’s Hospital of Nanjing Medical University, Taizhou School of Clinical Medicine, Nanjing Medical University, Taizhou, Jiangsu Province, 225300, People’s Republic of China; 3Medical College, Yangzhou University, Yangzhou, 225009, People’s Republic of China; 4Nanjing University of Finance & Economics, Nanjing, 210023, People’s Republic of China; 5Department of Critical Care Medicine, The Affiliated Taizhou People’s Hospital of Nanjing Medical University, Taizhou School of Clinical Medicine, Nanjing Medical University, Taizhou, Jiangsu Province, 225300, People’s Republic of China; 6Institute of Clinical Laboratory, The Affiliated Taizhou People’s Hospital of Nanjing Medical University, Taizhou School of Clinical Medicine, Nanjing Medical University, Taizhou, Jiangsu Province, 225300, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jun Wang; Shanshan Xue, Email 15061008998@163.com; 245116999@qq.comBackground: Sepsis refers to a life-threatening organ dysfunction which can be resulted from the infection-induced dysregulated host response. A large number of inflammatory cytokines are released to act on the liver, making the liver one of the common target organs for the development of multiple organ dysfunction syndrome (MODS) in patients with sepsis. Sepsis-induced acute liver injury (SALI) can aggravate systemic disease. As a result, it is of great clinical significance to comprehend the molecular biological mechanism of SALI and to identify the markers for evaluating SALI. Interferon-induced proteins with tetratricopeptide repeats 1 and 2 (IFIT1, IFIT2) have been recognized as the anti-inflammatory factors that are widely expressed in various organs. The present study was aimed at clarifying the roles of IFIT1 and IFIT2 in the development of SALI.Methods: A two-sample Mendelian randomization (MR) analysis was employed. Summary statistics datas were obtained from GWAS for inflammatory factors [tumor necrosis factor (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6)], IFIT2, and sepsis as well as liver injury. Independent SNPs were selected as instrumental variables (IVs). Inverse variance weighted (IVW) in the MR analysis was adopted as the primary method for estimating the causal associations of inflammatory factors and IFIT2 with two diseases, and the associations of inflammatory factors with IFIT2. Additionally, weighted median method, MR-Egger and sensitivity analyses were applied in assessing the robustness of the results and ensure the result reliability. Subsequently, 119 healthy volunteers, 116 patients with sepsis and 116 SALI patients were recruited. The ELISA method was employed to quantify the expression levels of TNF-α, IL-1β, and IL-6. Additionally, qRT-PCR was conducted to measure the expression of IFIT1 and IFIT2. Furthermore, the correlations of IFIT1 and IFIT2 with inflammatory factors, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were explored.Results: As shown by the MR analysis, the genetically predisposed sepsis was significantly associated with the risk of IL-1β, with an odds ratio (OR) of 1.069 (95% confidence interval (CI), 1.015– 1.127, p = 0.0119), and negatively associated with the risk of IL-6, with an OR of 0.880 (95% CI: 0.792– 0.979, p= 0.0184). Meanwhile, there were positive causal effects of IL-6 (OR = 1.269, 95% CI: 1.032– 1.561, p= 0.0238), IL-1β (OR = 1.106, 95% CI: 1.010– 1.211, p = 0.0299) and IFIT2 (OR = 1.191, 95% CI: 1.045– 1.359, p = 0.0090) on liver injury. Additionally, there was a positive causal effect of IFIT2 (OR = 1.164, 95% CI: 1.035– 1.309, p= 0.0110) on IL-1β. Upon sensitivity analyses, there was weak evidence of such effects, indicating that the findings of this study were robust and reliable. Our results revealed the elevated levels of TNF-α, IL-1β, and IL-6 in the blood samples of sepsis and SALI patients (p < 0.0001). Conversely, IFIT1 and IFIT2 demonstrated the significantly decreased levels in peripheral blood mononuclear cells (PBMCs) of SALI patients (p < 0.0001). Furthermore, the expression levels of IFIT1 and IFIT2 were both negatively correlated with ALT activity (r = − 0.3426, p = 0.0002; r = − 0.3069, p = 0.0008) and AST activity (r = − 0.2483, p = 0.0072; r = − 0.3261, p = 0.0004), respectively. Moreover, the expression of IFIT1 and IFIT2 was both negatively related to the levels of TNF-α (r = − 0.5027, p < 0.0001; r = − 0.4218, p < 0.0001), IL-1β (r = − 0.3349, p = 0.0002; r = − 0.4070, p < 0.0001) and IL-6 (r = − 0.2734, p = 0.0030; r = − 0.3536, p < 0.0001), respectively.Conclusion: IFIT1 and IFIT2 can serve as the diagnostic markers for sepsis-related liver injury, and IFIT1 and IFIT2 may participate in the pathological process of sepsis-related liver injury by regulating inflammation and liver function.Keywords: acute liver injury, sepsis, IFIT1, IFIT2, inflammation, Mendelian randomization

Xin Tang,1,&ast; Qifu Li,1,&ast; Gaoyangzi Huang,1 Ziwen Chen,2 Ya Huang,1 Xianmei Pei,1 Siwen Zhao,1 Zili Liu,1 Taipin Guo,1 Fanrong Liang2 1School of Second Clinical Medicine/The Second Affiliated Hospital, Yunnan University of Chinese Medicine, Kunming, People’s Republic of China; 2College of Acupuncture and Tuina, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Taipin Guo, School of Second Clinical Medicine/The Second Affiliated Hospital, Kunming, People’s Republic of China, Email gtphncs@126.com Fanrong Liang, College of Acupuncture and Tuina, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, People’s Republic of China, Email acuresearch@126.comPurpose: Acute lumbar sprain (ALS) is a common clinical disease characterized by persistent intolerable low back pain and limitation of movement, and quick pain relief and restoration of mobility in a short time are the main needs of patients when they visit the clinic. This study aims to evaluate the immediate efficacy of contralateral acupuncture (CAT) on SI3 combined with active exercise in treating ALS.Methods and Analysis: This study is a randomized controlled trial which will recruit 118 eligible participants aged 18 to 55 years with ALS at the Second Affiliated Hospital of Yunnan University of Chinese Medicine between March 2024 and December 2026. Participants will be randomly assigned to the acupuncture group or the sham-acupuncture group in a 1:1 ratio. The acupuncture group will receive a 10-minute acupuncture treatment combined with active exercise, while the sham-acupuncture group will receive a 10-minute sham acupuncture treatment combined with active exercise. Randomization will use a computer-generated sequence with allocation concealed in opaque envelopes. The primary outcome will be the pain visual analogue scale (VAS) scores after 10 minutes of treatment. Secondary outcomes will include the pain VAS scores at other time points (2, 4, 6, and 8 minutes post-treatment), the lumbar range of motion (ROM) scores at various time points, blinded assessment, the treatment effect expectancy scale, and the rescue analgesia rate. The analysis will follow the intention-to-treat principle. The primary outcome will be analyzed using ANCOVA, and secondary outcomes with repeated measures ANOVA. The rescue analgesia rate will be assessed using either the χ2 test or Fisher’s exact test.Discussion: This study is the first randomized controlled trial to assess the immediate efficacy of CAT in combination with active exercise for ALS. This study will provide a simple, rapid, and effective treatment for the clinical management of ALS.Keywords: acute lumbar sprain, immediate efficacy, contralateral acupuncture, active exercise, randomized controlled trial

Yanlei Li,1,&ast; Meng Ge,2,&ast; Jinlong Tian,1,&ast; Jinlei Zhou,1,3 Yao Kang,1 Chen Xia,1 Haiyu Shao,1 Yongguang Wang,4 Yazeng Huang,1 Tingxiao Zhao1 1Center for Plastic & Reconstructive Surgery, Department of Orthopedics, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, People’s Republic of China; 2Department of Orthopedics, Hospital of Traditional Chinese Medicine of Xiaoshan District, Hangzhou, Zhejiang, People’s Republic of China; 3Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 4Department of Orthopedics, Linping Hospital of Integrated Traditional Chinese and Western Medicine, Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tingxiao Zhao; Yazeng Huang, Center for Plastic & Reconstructive Surgery, Department of Orthopedics, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Shangtang Road 158&num;, Hangzhou, Zhejiang, People’s Republic of China, Email spinezhaotingxiao@163.com; huangyazeng2007@163.comPurpose: Percutaneous endoscopic transforaminal lumbar interbody fusion (PE-TLIF) has become one of the most popular minimally invasive surgeries today. However, the issue of hidden blood loss (HBL) in this surgery has received little attention. This study aims to examine the HBL in PE-TLIF surgery and the effect of tranexamic acid (TXA) on blood loss.Methods: In our research, We conducted a retrospective analysis of 300 patients who underwent PE-TLIF from September 2019 to August 2023. They were divided into 2 groups based on whether they received intravenous TXA injection before surgery. The variables compared included: demographic data, pre-and postoperative hemoglobin (HB), hematocrit (HCT), platelets (PLT), red blood cells (RBC), total blood loss (TBL), visible blood loss (VBL), HBL, operation time, postoperative hospital stay, inflammatory markers, coagulation parameters, and adverse events.Results: Regarding demographic characteristics, besides the operation time, no significant differences were observed between the two groups. Compared with the control group, the TXA group showed a significant reduction trend in TBL, HBL, and VBL (P < 0.05). On the first day after surgery, there were significant differences in prothrombin (PT), activated partial thromboplastin time (APTT), and D-dimer (D-D) levels between the two groups. Similarly, HCT also found similar results on the third day after surgery. No adverse events occurred in either group.Conclusion: Research has found that there is a significant amount of HBL in patients undergoing PE-TLIF. Intravenous injection of TXA can safely and effectively reduce perioperative HBL and VBL. Additionally, compared to the control group, the TXA group shows a significant reduction in operation time.Keywords: percutaneous endoscopic transforaminal lumbar interbody fusion, tranexamic acid, total blood loss, visible blood loss, hidden blood loss

Zhiyuan Wang,1,&ast; Ruilin Wang,1,&ast; Xiaoyu Li,1,&ast; Lin Bai,1 Pingan Fan,1 Yuanyuan Tang,2 Xin Li,3 Yangmu Huang,4 Xiaoyan Nie,1,5 Sheng Han,1,5 Luwen Shi,1,5 Jing Chen1,5 1Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmaceutical Sciences, Peking University, Beijing, People’s Republic of China; 2Bidding Management Office, Suqian First Hospital, Suqian, Jiangsu, People’s Republic of China; 3Department of Clinical Pharmacy, School of Pharmacy, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 4School of Public Health, Peking University, Beijing, People’s Republic of China; 5International Research Center for Medicinal Administration, Peking University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jing Chen, Email jingchen@bjmu.edu.cnBackground: Although affordable generics could probably contribute to the solution of rapidly increasing pharmaceutical expenditure, those drugs are prescribed at a lower rate in China. Physicians’ perception and knowledge of generics have a great influence on their prescribing behavior.Objective: This study aimed to identify factors that affect physicians’ generic prescribing behavior based on the theory of planned behaviors (TPB).Methods: Data were collected by both electronic and paper-based surveys from 1297 Chinese physicians, and 1047 surveys were retained. The structural equation model (SEM) was employed to investigate the relationship between four behavioral constructs, namely, attitudes, subjective norms, perceived control of behaviors, and intentions.Results: About 50% of Chinese physicians had a positive attitude towards generic drugs that had passed the “Consistency Evaluation of Quality and Efficacy of Generic Drugs” (high-quality generic drugs), but their knowledge of generic drugs was relatively inadequate. The path coefficients for the effect of attitudes, subjective norms, and perceived behavioral control on behavioral intention were 0.285, 0.366, and 0.322 respectively. The path coefficients for the effect of behavioral intention and perceived behavioral control on prescribing behavior were 0.009 and 0.410 respectively.Conclusion: Physicians’ attitudes, subjective norms, and perceived behavioral control were significant positive correlation predictors of behavioral intention. Subjective norms and perceived behavior control had a greater impact than attitude on physicians’ prescribing intention. However, the generic prescribing behavior is not under the volitional control of Chinese physicians. Physicians’ prescribing practice is likely affected by perceived strong control over prescribing generic drugs.Keywords: generic prescribing behavior, perception, structural equation model, theory of planned behaviors