Search

Guanxiang Huang,1– 3,&ast; Wenyu Lin,1– 3,&ast; Hangjing Gao,1– 3 Yuan Ren,1– 3 Jun Shen,4 Shuxia Xu,5 Dabin Liu,6 Yuanjun Cai,6 Chengbin Lin,6 Xite Lin,1– 3 Tingting Jiang,1– 3 Binhua Dong,1– 3 Pengming Sun1– 3 1College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, Fujian, 350001, People’s Republic of China; 2Fujian Key Laboratory of Women and Children’s Critical Diseases Research, Fujian Maternity and Child Health Hospital (Fujian Women and Children’s Hospital), Fuzhou, Fujian, 350001, People’s Republic of China; 3Fujian Clinical Research Center for Gynecological Oncology, Fujian Maternity and Child Health Hospital (Fujian Obstetrics and Gynecology Hospital), Fuzhou, Fujian, 350001, People’s Republic of China; 4Fujian Provincial Cervical Disease Diagnosis and Treatment Health Center, Fujian Maternity and Child Health Hospital, Fuzhou, Fujian, 350001, People’s Republic of China; 5Department of Pathology, Fujian Maternity and Child Health Hospital, Fuzhou, Fujian, 350001, People’s Republic of China; 6Department of Gynecology, Fujian Maternity and Child Health Hospital, Fuzhou, Fujian, 350001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Pengming Sun; Binhua Dong, Laboratory of Gynecologic Oncology, Department of Gynecology, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, Fujian, 350001, People’s Republic of China, Tel +86-591-87558732 ; +86-13599071900, Fax +86-591-87551247, Email fmsun1975@fjmu.edu.cn, sunfemy@hotmail.com; dongbinhua86@fjmu.edu.cn, dbh18-jy@126.comBackground: There are currently few prognostic models for conization in patients with high-grade squamous intraepithelial lesion (HSIL) because it is a rapid procedure that typically collects less case information. The present study aimed to establish a rapid/accurate postoperative prognostic assessment model for these patients.Methods: This study included 631 nonpregnant participants with HSIL confirmed by histopathology from January 2015 to January 2018. The recurrent/residual cervical intraepithelial neoplasia (CIN) were divided into residual CIN, simple recurrent CIN and recurrent CIN accompanied with CIN progression. The recurrence/residual-free survival (RFS) time was defined as the time span from the time of surgery (baseline) until the first lesion of CIN was detected or the 1-/3-/5-year follow-up endpoint was reached.Results: After LASSO regression selection, the higher platelet-to-lymphocyte ratio (PLR) (OR = 1.006, p = 0.002), positive margin status (OR = 2.451, p = 0.021), HPV-16 (OR = 4.414, p < 0.001), − 18 (OR = 3.040, p = 0.009), − 56 (OR = 10.715, p=0.021), and non-HR-HPV (OR = 2.487, p = 0.028) infection showed significant difference in the Logistic model. And HPV-16 infection (OR = 6.159, p = 0.001) could promote recurrent CIN accompanied with CIN progression. In multivariate Cox regression models, the higher PLR (HR = 1.005/1.005/1.005, p = 0.020/0.002/0.003) and HPV-16 infection (HR = 2.758/2.836/2.674, p < 0.001) showed statistical difference during 1-/3-/5-year follow-up. While gland invasion (p = 0.081), margin status (p = 0.075) and HPV infection genotype (p = 0.150) did not showed statistical difference in multivariate Cox regression models based on LASSO regression. And gland invasion (p = 0.251/0.686) and HPV-58 infection (p = 0.148/0.813) also showed no statistical difference in optimized Logistic regression models.Conclusion: HPV-16, − 18, − 56 and non-HR-HPV infection status can be considered as indicators for recurrent CIN during the 5-year follow-up, especially for HPV-16 infection, which also lead to a CIN recurrence accompanied with disease progression. And the preoperative PLR level, gland invasion, positive margin may be predictors for recurrent/residual CIN during 1-, 3- and 5-year follow-up.Keywords: cervical intraepithelial neoplasia, higher platelet-to-lymphocyte ratio, human papillomavirus, conization, prognosis

Na Zhang,1,&ast; Yiran Xu,1,2,&ast; Beibei Liang,1 Jinru Zeng,1 Rui Wang,1 Yun Cai1 1Center of Medicine Clinical Research, Department of Pharmacy, Medical Supplies Center, PLA General Hospital, Beijing, People’s Republic of China; 2Department of Pharmacy, The Second Naval Hospital of Southern Theater Command of PLA, Sanya, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yun Cai, Center of Medicine Clinical Research, Department of Pharmacy, Medical Supplies Center, PLA General Hospital, Beijing, People’s Republic of China, Tel +86-10-6693-7166, Email caicai_hh@126.comAbstract: Colistin is the last-line option for the treatment of multidrug-resistant gram-negative bacterial infections with narrow therapeutic window. It is essential to ensure its efficacy and safety by therapeutic drug monitoring (TDM). Quantitative determination of colistin is difficult due to its complex ingredients. Previous determination methods demand intricate sample pre-treatment which are not only time-consuming but also costly, and is difficult to apply in clinical practice. Therefore, in order to carry out quantitative determination of colistin accurately and quickly, we establish a rapid high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) with simple sample pre-treatment process. The sample was purified by acetonitrile to remove the plasma protein. Then purified colistin was effectively separated from terfenadine, an internal standard (IS) using Phenomenex Kinetex C18 column (50.0× 2.1mm, 5μm) with acetonitrile and water mobile phase at a flow rate of 0.5 mL/min and 40°C column temperature. Colistin and IS were monitored in positive ion mode. Our method expressed good linearity in 50.0~6000 ng/mL of colistin B and 28.31~3397.51 ng/mL of colistin A in plasma. Methodology validations, including selectivity, precision, accuracy, recovery, stability, matrix effect, and dilution integrity met acceptance criteria of Bioanalytical Method Validation (M10) of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH).Keywords: colistin, HPLC-MS/MS, human plasma, protein precipitation, rapid and simple detection

Youni Lin, Min Yang, Qifeng Liu, Yufu Cai, Zhouhua Zhang, Chongfei Xu, Ming Luo Center for Cardiovascular Diseases, Meizhou People’s Hospital, Meizhou, People’s Republic of ChinaCorrespondence: Youni Lin, Center for Cardiovascular Diseases, Meizhou People’s Hospital, Meizhou, People’s Republic of China, Email linyn2024@126.comBackground: Atherosclerosis is a systemic disease that can involve multiple vascular beds. The risk factors for atherosclerosis in multiple vascular beds remain unclear. Apolipoprotein E (APOE) is involved in inflammation and lipid deposition in the process of atherosclerosis. The objective of this study was to investigate whether APOE polymorphisms are associated with atherosclerosis in multiple vascular beds.Methods: A total of 416 patients with atherosclerosis in single vascular bed and 658 patients with atherosclerosis in multiple vascular beds were included. APOE genotypes were detected and the differences of APOE genotypes between the groups were compared. Logistic regression analysis was performed to analyze the relationship between APOE genotypes and atherosclerosis in multiple vascular beds.Results: APOE E3/E4 genotype frequency was lower in the patients with atherosclerosis in multiple vascular beds than that of patients with atherosclerosis in single vascular bed (11.4% vs 17.8%, P=0.004). There was no significant difference in age and gender distribution, proportion of history of smoking, alcohol consumption, hypertension, and diabetes mellitus between the two groups (all P> 0.05), and among patients with different APOE alleles (all P> 0.05). Logistic regression analysis indicated that APOE E3/E4 genotype (E3/E4 vs E3/E3: odds ratio (OR) 0.598, 95% confidence interval (CI): 0.419– 0.854, P=0.005), and APOE &epsiv;4 allele (&epsiv;4 vs &epsiv;3: OR 0.630, 95% CI: 0.444– 0.895, P=0.010) associated with atherosclerosis in multiple vascular beds.Conclusion: APOE &epsiv;4 allele is associated with atherosclerosis in multiple vascular beds.Keywords: APOE, polymorphism, atherosclerosis, multiple vascular beds

Lingling Ding,1,&ast; Guowan Zheng,1– 3,&ast; Aoni Zhou,4 Fahuan Song,1– 3 Lei Zhu,5 Yefeng Cai,6 Yehao Guo,1 Tebo Hua,7 Yunye Liu,1 Wenli Ma,1 Yiqun Hu,1– 3 Yawen Guo,1– 3 Chuanming Zheng1– 3 1Otolaryngology & Head and Neck Center, Cancer Center, Department of Head and Neck Surgery, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, 310000, People’s Republic of China; 2Zhejiang Provincial Clinical Research Center for Malignant Tumor, Hangzhou, Zhejiang, 310000, People’s Republic of China; 3Zhejiang Key Laboratory of Precision Medicine Research on Head & Neck Cancer, Hangzhou, Zhejiang, 310000, People’s Republic of China; 4Hangzhou Normal University, Hangzhou, Zhejiang, 311121, People’s Republic of China; 5Department of Thyroid Surgery, The Fifth Hospital Affiliated to Wenzhou Medical University, Lishui Central Hospital, Lishui, Zhejiang, 323000, People’s Republic of China; 6Department of Thyroid Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, People’s Republic of China; 7Department of Thyroid Surgery, Ningbo Medical Centre Lihuili Hospital, Ningbo, Zhejiang, 315000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yawen Guo; Chuanming Zheng, Department of Head and Neck Surgery, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, No. 158, Shangtang Road, Hangzhou, Zhejiang, People’s Republic of China, Email mingdoc@163.com; gyw20072644@126.comBackground: The incidence of papillary thyroid cancer (PTC) has been increasing annually; however, early diagnosis can improve patient outcomes. Pyroptosis is a programmed cell death modality that has received considerable attention recently. However, no studies have reported using pyroptosis-related genes in PTC diagnosis.Methods: Analyzed 33 pyroptosis-related genes in PTC transcriptome data from the Gene Expression Omnibus database. Subsequently, used the Least Absolute Shrinkage and Selection Operator (LASSO) model to construct a PTC molecular diagnostic model. Furthermore, confirmed differences in the expression of five genes between PTC and non-tumor tissues using immunohistochemistry. Collected 338 PTC and control samples to construct a five-gene PTC diagnostic model, which was then validated using a training set and underwent correlation analysis with immune cell infiltration. Additionally, validated the biological functions of the core gene NOD1 in vitro.Results: The five-gene PTC diagnostic model demonstrated good diagnostic value for PTC. Moreover, identified three reliable subtypes of pyroptosis and found that NOD1 is involved in tumor-suppressive microenvironment formation. Notably, patients with high NOD1 expression had lower Progression-Free Survival (PFS). Additionally, NOD1 expression was positively correlated with immune markers such as CD47, CD68, CD3, and CD8. Lastly, inhibiting NOD1 showed significant anti-PTC activity in vitro.Conclusion: Our results suggest that pyroptosis-related genes can be used for PTC diagnosis, and NOD1 could be a promising therapeutic target.Keywords: pyroptosis-related genes, papillary thyroid cancer, PTC, immune cell infiltration, bioinformatic, diagnosis model

Yitong Cai,1 Ming Liu,2 Weixiang Luo,3 Jingping Zhang,1 Chaoran Qu4 1Xiangya School of Nursing, Central South University, Changsha, Hunan, People’s Republic of China; 2Evidence-Based Medicine Center, Lanzhou University, Lanzhou, Gansu, People’s Republic of China; 3Department of Nursing, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University; the First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, Guangdong, People’s Republic of China; 4Department of Operating Room, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, Guangdong, People’s Republic of ChinaCorrespondence: Jingping Zhang, Xiangya School of Nursing, Central South University, No. 172, Tong-Zi-Po Road, Yue Lu District, Changsha, Hunan, People’s Republic of China, Email jpzhang1965@csu.edu.cn Chaoran Qu, Department of Operating Room, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, Guangdong, People’s Republic of China, Email qvchaoran@outlook.comBackground: Nurses frequently experience both direct and indirect trauma, leading to significant psychological challenges. While much research has focused on the negative impacts of such trauma, less attention has been given to vicarious post-traumatic growth (VPTG). Given the high levels of indirect trauma that nurses face, understanding VPTG is crucial for mitigating its adverse effects and enhancing mental health and work efficiency.Objective: To map and synthesize the literature on vicarious post-traumatic growth and identify key knowledge gaps in vicarious post-traumatic growth research.Methods: This scoping review follows the approach proposed by Arksey and O’Malley. We conducted this scoping review using the methodology recommended by the Joanna Briggs Institute, supported by the PAGER framework. We searched 7 databases and gray literature on May 19, 2023 to obtain relevant research.Results: Finally, we included 29 studies from 9 countries. There are currently no reliable data on the incidence of vicarious post-traumatic growth among nurses worldwide. There are multiple instruments available to investigate vicarious post-traumatic growth in nurses, and the vicarious post-traumatic growth inventory is more recommended. Factors affecting nurses’ vicarious post-traumatic growth include coping styles, psychological factors, and social support. Indirect trauma exposure and vicarious post-traumatic growth coexist. There are currently three intervention strategies for vicarious post-traumatic growth, but none have been proven in clinical trials.Conclusion: This is the first scoping review on vicarious post-traumatic growth, there are a lot of research deficiencies and gaps in current research on vicarious post-traumatic growth for nurses. In view of the impact of secondary traumatic events on nurses, future research should pay more attention to nurses’ vicarious post-traumatic growth and promote the development of vicarious post-traumatic growth.Plain Language Summary: What is already known about the topic?Nurses are exposed to secondary traumatic events as part of their every-day work.Nurses experiencing these different secondary trauma exposures experience both positive and negative outcomes, but there has been less research on vicarious post-traumatic growth.The influencing factors of nurses’ vicarious post-traumatic growth and its related survey tools are not clear yet.What this paper addsGender, trauma type, and nurses’ core beliefs, self-efficacy, coping styles, and social support are influencing factors of vicarious post-traumatic growth.Currently, vicarious post-traumatic growth -related survey tools are roughly divided into three types, among which secondary posttraumatic growth inventory and vicarious post-traumatic growth inventory tools are specific survey tools.There are various relationships between indirect exposure to trauma and vicarious post-traumatic growth, and there are differences between different types of indirect trauma exposure. However, there is basically a consensus that indirect exposure to trauma and vicarious post-traumatic growth coexist. There are currently no targeted, scalable, and repeatable interventions for vicarious post-traumatic growth.Keywords: nurse, vicarious post-traumatic growth, secondary traumatic, scoping review

Decai Zeng, Linyan Li, Shuai Chang, Xiaofeng Zhang, Yanfen Zhong, Yongzhi Cai, Tongtong Huang, Ji Wu Department of Ultrasonic Medicine, the First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of ChinaCorrespondence: Ji Wu, Department of Ultrasonic Medicine, the First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China, Email gxnnwuji@163.comBackground: Despite the efficacy of catheter ablation (CA) as a treatment for non-valvular atrial fibrillation (NVAF), many patients still experience atrial fibrillation (AF) recurrence after CA. This study aimed to evaluate the predictive value of speckle tracking echocardiographic (STE) parameters for AF recurrence post-ablation.Methods: A total of 380 NVAF patients treated with CA at the First Affiliated Hospital of Guangxi Medical University from January 2020 to March 2023 were prospectively recruited. The mean age was 59.4 ± 10.8 years, and 72.1% were male, including 150 patients (39.5%) with persistent AF and 230 patients (60.5%) with paroxysmal AF. STE was used to evaluate baseline left atrial (LA) function before CA within 48h. Over a median follow-up of 9 (interquartile range, 4– 17) months, AF recurrence occurred in 132 patients (34.7%).Results: The recurrence group showed lower left ventricular ejection fraction, LA reservoir strain (LASr), and conduit strain (LAScd), but higher LA stiffness than non- recurrence group (all P < 0.05). Multivariable Cox regression identified LA stiffness and LASr as independent risk factors. Time-dependent ROC analysis showed that LA stiffness (AUC 0.768, 95% CI 0.705– 0.831) and LASr (AUC 0.755, 95% CI 0.691– 0.820) were better at predicting 1-year AF recurrence than other risk factors. For 2-year AF recurrence post-catheter ablation, LA stiffness (AUC 0.866, 95% CI 0.804– 0.928) and LASr (AUC 0.860, 95% CI 0.800– 0.920) also demonstrated superior predictive performance. Kaplan-Meier curves showed a significant difference in AF recurrence rate for patients with LA stiffness > 0.55 and LASr ≤ 24.3% (Log rank P < 0.01).Conclusion: Evaluation of LA function using STE assists in stratifying the risk of AF recurrence in NVAF patients and guiding follow-up management. LASr and LA stiffness are independent predictors of AF recurrence following CA in NVAF patients, and potentially outperforming other morphological parameters.Keywords: non-valvular atrial fibrillation, catheter ablation, speckle tracking echocardiography, atrial fibrillation recurrence

Shuai Chang,1 Xiaofeng Zhang,1 Chenliang Ge,2 Yanfen Zhong,1 Decai Zeng,1 Yongzhi Cai,1 Tongtong Huang,1 Ji Wu1 1Department of Ultrasonic Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China; 2Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of ChinaCorrespondence: Ji Wu, Department of Ultrasonic Medicine, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road Qingxiu District, Nanning, Guangxi Zhuang Autonomous Region, 530021, People’s Republic of China, Tel +86 15773435752, Email gxnnwuji@163.comPurpose: Left atrial low-voltage areas (LA-LVAs) identified by 3D-electroanatomical mapping are crucial for determining treatment strategies and prognosis in patients with atrial fibrillation (AF). However, convenient and accurate prediction of LA-LVAs remains challenging. This study aimed to assess the viability of utilizing automatically obtained echocardiographic parameters to predict the presence of LA-LVAs in patients with non-valvular atrial fibrillation (NVAF).Patients and Methods: This retrospective study included 190 NVAF patients who underwent initial catheter ablation. Before ablation, echocardiographic data were obtained, left atrial volume and strain were automatically calculated using advanced software (Dynamic-HeartModel and AutoStrain). Electroanatomic mapping (EAM) was also performed. Results were compared between patients with LA-LVAs ≥ 5% (LVAs group) and < 5% (non-LVAs group).Results: LA-LVAs were observed in 81 patients (42.6%), with a significantly higher incidence in those with persistent AF than paroxysmal AF (55.6% vs 19.3%, P

Linan Ren,1,2 Feng Ju,3 Siyuan Liu,1,2 Yunjia Cai,1,2 Xiaokun Gang,1 Guixia Wang1 1Department of Endocrinology and Metabolism, First Hospital of Jilin University, Changchun, Jilin, 130021, People’s Republic of China; 2Institute of Translational Medicine, First Hospital of Jilin University, Changchun, Jilin, 130021, People’s Republic of China; 3Department of Orthopedics, Yuci District People’s Hospital, Yuci, Shanxi, 030600, People’s Republic of ChinaCorrespondence: Xiaokun Gang; Guixia Wang, Department of Endocrinology and Metabolism, The First Hospital of Jilin University, Changchun, Jilin Province, 130021, People’s Republic of China, Email gangxk@jlu.edu.cn; gwang168@jlu.edu.cnAbstract: Obesity represents a substantial risk factor for a multitude of metabolic disorders, which seriously threatens human life and health. As the global obesity epidemic intensifies, obesity-related nephropathy (ORN) has attracted great attention. ORN arises from both physical/mechanical and non-physical insults to the glomerular and tubular structures precipitated by obesity, culminating in structural impairments and functional aberrations within the kidneys. Physical injury factors include changes in renal hemodynamics, renal compression, and mechanical stretching of podocytes. Non-physical injury factors include overactivation of the RAAS system, insulin resistance, lipotoxicity, inflammation, and dysregulation of bile acid metabolism. Exploring molecules that target modulation of physical or nonphysical injury factors is a potential approach to ORN treatment. ORN is characterized clinically by microproteinuria and pathologically by glomerulomegaly, which is atypical and makes early diagnosis difficult. Investigating early diagnostic markers for ORN thus emerges as a critical direction for future research. Additionally, there is no specific drug for ORN in clinical treatment, which mainly focuses on weight reduction, mitigating proteinuria, and preserving renal function. In our review, we delineate a progressive therapeutic approach involving enhancements in lifestyle, pharmacotherapy, and bariatric surgery. Our emphasis underscores glucagon-like peptide-1 receptor agonists (GLP-1 RAs) as poised to emerge as pivotal therapeutic modalities for ORN in forthcoming clinical avenues. Keywords: Obesity-related nephropathy, pathophysiology, diagnostics, therapeutics

Chuanjiang Dong,1,&ast; Yueqing Wang,2,3,&ast; Yi Cai,4,&ast; Yuhuang Wu,2,3 Wei Chen,2,3 Lu Wang,2,3 Xiaowen Liu,2 Lili Zou,2,3 Jun Wang5 1Department of Urology, The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan, Guangdong province, 523718, People’s Republic of China; 2Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, College of Basic Medical Science, China Three Gorges University, Yichang, Hubei Province, 443002, People’s Republic of China; 3Yichang Key Laboratory of Infection and Inflammation, College of Basic Medical Science, China Three Gorges University, Yichang, Hubei Province, 443002, People’s Republic of China; 4Department of Laboratory Medicine, Xiaogan Central Hospital, Xiaogan, Hubei Province, 432099, People’s Republic of China; 5The Second People’s Hospital of China Three Gorges University, Yichang, Hubei Province, 443002, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lili Zou; Jun Wang, Email zoulili@ctgu.edu.cn; wangjfox@ctgu.edu.cnPurpose: Tuberculosis (TB) remains a major health threat worldwide, and the spread of drug-resistant (DR) TB impedes the reduction of the global disease burden. Ebselen (EbSe) targets bacterial thioredoxin reductase (bTrxR) and causes an imbalance in the redox status of bacteria. Previous work has shown that the synergistic action of bTrxR and sensitization to common antibiotics by EbSe is a promising strategy for the treatment of DR pathogens. Thus, we aimed to evaluate whether EbSe could enhance anti-TB drugs against Mycobacterium marinum (M. marinum) which is genetically related to Mycobacterium tuberculosis (Mtb) and resistant to many antituberculosis drugs.Methods: Minimum inhibitory concentrations (MIC) of isoniazid (INH), rifampicin (RFP), and streptomycin (SM) against M. marinum were determined by microdilution. The Bliss Independence Model was used to determine the adjuvant effects of EbSe over the anti-TB drugs. Thioredoxin reductase activity was measured using the DTNB assay, and its effects on bacterial redox homeostasis were verified by the elevation of intracellular ROS levels and intracellular GSH levels. The adjuvant efficacy of EbSe as an anti-TB drug was further evaluated in a mouse model of M. marinum infection. Cytotoxicity was observed in the macrophage cells Raw264.7 and mice model.Results: The results reveal that EbSe acts as an antibiotic adjuvant over SM on M. marinum. EbSe + SM disrupted the intracellular redox microenvironment of M. marinum by inhibiting bTrxR activity, which could rescue mice from the high bacterial load, and accelerated recovery from tail injury with low mammalian toxicity.Conclusion: The above studies suggest that EbSe significantly enhanced the anti-Mtb effect of SM, and its synergistic combination showed low mammalian toxicity in vitro and in vivo. Further efforts are required to study the underlying mechanisms of EbSe as an antibiotic adjuvant in combination with anti-TB drug MS.Keywords: Ebselen, antibiotic adjuvant, thioredoxin reductase, reactive oxygen species

Siyuan Chen,1,2 Jia Liu,1,2 Zhili Feng,1,2 Liubo Zhou,1,2 Yuexiang Cai,1,2 Qiancheng Jing1,2 1Department of Otolaryngology Head and Neck Surgery, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha, Hunan, People’s Republic of China; 2Institute of Otolaryngology Head and Neck Surgery, Hengyang Medical School, University of South China, Changsha, Hunan, People’s Republic of ChinaCorrespondence: Qiancheng Jing, Department of Otolaryngology Head and Neck Surgery, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha, Hunan, People’s Republic of China, Email 2022050001@usc.edu.cnBackground: Exosomes carry various types of transcripts and serve as promising biomarkers for inflammatory diseases. However, the role of serum exosomal microRNAs (miRNAs) in chronic rhinosinusitis with nasal polyps (CRSwNP) is poorly clarified.Methods: A prospective exploratory cohort of 10 CRSwNP patients was conducted, and the serum exosome samples were subjected to miRNA sequencing. Two independent prospective cohorts, consisting of 40 and 54 patients respectively, were recruited from different medical centers for validation. These cohorts were monitored for over two years, with postoperative recurrence serving as the primary outcome measure. The top 3 differentially exosomal miRNAs were validated in the serum samples, and their predictive values for recurrence were assessed.Results: Eight CRSwNP patients completed the follow-up, comprising 4 non-recurrent cases and 4 recurrent cases. Distinctive profiles of serum exosomal miRNAs were identified between the two groups. In the first validation cohort, reverse transcription-polymerase chain reaction results indicated elevated serum exosomal miR-3174 and miR-6750-5p expressions, along with reduced miR-192-3p levels in the recurrence group compared to the non-recurrence group. Receiver operating characteristic (ROC) curves and Kaplan-Meier survival analysis demonstrated significant correlations between expressions of exosomal miR-3174 and miR-192-3p and the risk of postoperative recurrence. These findings were further validated in the second cohort, confirming the elevation of both miRNAs in the recurrence group and their associations with recurrence risk. Additionally, serum exosomal miR-3174 levels increased in recurrent cases compared to their baseline levels.Conclusion: Circulating exosomal microRNA signatures may influence the risk of postoperative recurrence in CRSwNP patients. Serum exosomal elevated exosomal miR-3174 and decreased miR-192-3p were correlated with CRSwNP recurrence risk.Keywords: exosome, chronic rhinosinusitis with nasal polyps, biomarker, recurrence

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

Mengjie Xie,1,&ast; Fansu Meng,2,&ast; Panpan Wang,3,&ast; Alicia Marcelina Díaz-García,4 Marina Parkhats,5 Ralph Santos-Oliveira,6 Mulazim Hussain Asim,7 Nazish Bostan,8 Honghui Gu,9 Lina Yang,9 Qi Li,9 Zhenjiang Yang,9 Haibiao Lai,2 Yu Cai1 1State Key Laboratory of Bioactive Molecules and Druggability Assessment, Jinan University International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Ministry of Education (MOE) of China / Guangdong Key Laboratory of Traditional Chinese Medicine Informatization / International Science and Technology Cooperation Base of Guangdong Province/School of Pharmacy, Jinan University, Guangzhou, Guangdong, 510632, People’s Republic of China; 2Zhongshan Hospital of Traditional Chinese Medicine Affiliated to Guangzhou University of Traditional Chinese Medicine, Zhongshan, Guangdong, 528400, People’s Republic of China; 3The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, 510632, People’s Republic of China; 4Bioinorganic Laboratory, Faculty of Chemistry, University of Havana, Havana, 1400, Cuba; 5B. I. Stepanov Institute of Physics, National Academy of Sciences of Belarus, Minsk, 220072, Belarus; 6Brazilian Nuclear Energy Commission, Nuclear Engineering Institute, Laboratory of Nanoradiopharmacy and Synthesis of New Radiopharmaceuticals, Rio de Janeiro, RJ, 21941906, Brazil; 7College of Pharmacy, University of Sargodha, Punjab, 40100, Pakistan; 8Department of Pharmaceutics, Faculty of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur, 63100, Pakistan; 9Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, Guangdong, 518033, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yu Cai; Haibiao Lai, Email caiyu8@sohu.com; lhb8829@163.comAbstract: Data published in 2020 by the International Agency for Research on Cancer (IARC) of the World Health Organization show that breast cancer (BC) has become the most common cancer globally, affecting more than 2 million women each year. The complex tumor microenvironment, drug resistance, metastasis, and poor prognosis constitute the primary challenges in the current diagnosis and treatment of BC. Magnetic iron oxide nanoparticles (MIONPs) have emerged as a promising nanoplatform for diagnostic tumor imaging as well as therapeutic drug-targeted delivery due to their unique physicochemical properties. The extensive surface engineering has given rise to multifunctionalized MIONPs. In this review, the latest advancements in surface modification strategies of MIONPs over the past five years are summarized and categorized as constrast agents and drug delivery platforms. Additionally, the remaining challenges and future prospects of MIONPs-based targeted delivery are discussed. Keywords: Nanopreparations, Organic Nanomaterials, Inorganic Nanomaterials, Surface Engineering, Targeted Delivery

Jianping Cheng,1 Chanjuan Fan,1 Zhen Li,1 Zhaojing Dong,2 Xiaolin Zhao,1 Yong Cai,1 Haiou Ding,3 Yan Dou,4 Xiaomei Zhang4 1Department of Gastroenterology and Oncology, Civil Aviation General Hospital, Beijing, People’s Republic of China; 2Department of Medical Record, Civil Aviation General Hospital, Beijing, People’s Republic of China; 3Department of Pharmacy, Civil Aviation General Hospital, Beijing, People’s Republic of China; 4Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing, People’s Republic of ChinaCorrespondence: Jianping Cheng, Department of Gastroenterology and Oncology, Civil Aviation General Hospital, Beijing, 100123, People’s Republic of China, Tel +86 10 85762244, Email cjpczy2004@163.com Xiaomei Zhang, Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing, 100112, People’s Republic of China, Email zhangxiaomeinew@163.comBackground and Objectives: The success rate of Helicobacter pylori (H. pylori) eradication in China is declining. The aim of this study was to evaluate eradication outcomes in clinical practice and identifies factors contributing to treatment failure.Methods: A retrospective review was conducted on patients treated for H. pylori infection with 14-day bismuth-containing quadruple therapy at a Beijing medical center from January 2020 to December 2023. We analyzed demographic and clinical data, eradication rates across regimens, and performed multivariate analysis to pinpoint predictors of failure.Results: Out of 3340 participants, 2273 (68.1%) achieved eradication. Amoxicillin-based combinations (69.2%) outperformed other antibiotic regimens (58.9%, p < 0.001), with amoxicillin plus doxycycline reaching a 71.4% success rate. Esomeprazole-based regimens were more effective (73.6%) than other PPI regimens (65.2%, p = 0.001), notably, a rabeprazole, amoxicillin, doxycycline, and bismuth combination had an 80.0% success rate. Age, gender, and smoking and drinking were significant eradication failure predictors.Conclusion: In real-world settings, 14-day amoxicillin and esomeprazole-based quadruple regimens have been demonstrated to be more effective than other regimens. Age, gender, and lifestyle habits are identified as independent risk factors for eradication failure.Registration: This study was registered in the Chinese Clinical Trial Registry on 08/01/2024 (clinical trial registration number: ChiCTR2400079647).Keywords: Helicobacter pylori, quadruple therapy, antibiotics, proton pump inhibitor, retrospective study

Ming Li,&ast; Xinrui Zhang,&ast; Yujie Zhou, Yuteng Chu, Jie Shen, Yue Cai, Xuanrong Sun Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou, 310014, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xuanrong Sun, Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou, 310014, People’s Republic of China, Email sunxr@zjut.edu.cnIntroduction: Glioblastoma multiforme (GBM), a highly invasive and prognostically challenging brain cancer, poses a significant hurdle for current treatments due to the existence of the blood-brain barrier (BBB) and the difficulty to maintain an effective drug accumulation in deep GBM lesions.Methods: We present a biomimetic nanoplatform with angiopep-2-modified macrophage membrane, loaded with indocyanine green (ICG) templated self-assembly of SN38 (AM-NP), facilitating active tumor targeting and effective blood-brain barrier penetration through specific ligand-receptor interaction.Results: Upon accumulation at tumor sites, these nanoparticles achieved high drug concentrations. Subsequent combination of laser irradiation and release of chemotherapy agent SN38 induced a synergistic chemo-photothermal therapy. Compared to bare nanoparticles (NPs) lacking cell membrane encapsulation, AM-NPs significantly suppressed tumor growth, markedly enhanced survival rates, and exhibited excellent biocompatibility with minimal side effects.Conclusion: This NIR-activatable biomimetic camouflaging macrophage membrane-based nanoparticles enhanced drug delivery targeting ability through modifications of macrophage membranes and specific ligands. It simultaneously achieved synergistic chemo-photothermal therapy, enhancing treatment effectiveness. Compared to traditional treatment modalities, it provided a precise, efficient, and synergistic method that might have contributed to advancements in glioblastoma therapy.Keywords: biomimetic macrophage membrane, drug delivery, synergistic treatment, glioma inhibition, near infrared-activatable

Yingzi Zhang,1 Xiajuan Yao,1 Yaoquan Zhang,1 Zhuyun Chen,1 Zhongke Qin,1 Ying Cai,2 Wenkai Xia,1 Hong Hu1 1Department of Nephrology, Jiangyin People’s Hospital Affiliated to Nantong University, Jiangyin, Jiangsu, 214400, People’s Republic of China; 2Department of Hematology, Jiangyin People’s Hospital Affiliated to Nantong University, Jiangyin, Jiangsu, 214400, People’s Republic of ChinaCorrespondence: Wenkai Xia; Hong Hu, Department of Nephrology, Jiangyin People’s Hospital Affiliated to Nantong University, 3 Yingrui Road, Jiangyin, Jiangsu, 214400, People’s Republic of China, Email xiawenkai.xia@gmail.com; huhong1523@163.comBackground: The albumin-to-globulin ratio (AGR) and neutrophil-to-lymphocyte ratio (NLR) have been recently regarded as promising prognostic factors in various malignancies. The present study investigated the prognostic value of combining the AGR and NLR (ANS) for risk assessments in multiple myeloma (MM) with renal impairment (RI).Methods: From 2011 to 2018, 79 patients with MM and RI were enrolled in this study. Receiver operating curves (ROCs) were constructed to determine optimal AGR and NLR thresholds for predicting overall survival (OS) and progression-free survival (PFS) during follow up. The prognostic values of AGR, NLR, and ANS were evaluated with Cox regression and Kaplan-Meier methods. We also created a predictive nomogram for prognostic evaluations of OS and PFS, and the predictive accuracy was assessed with a concordance index (c-index).Results: The ROC curves analyses showed that the optimal cut-off levels were 2.27 for NLR and 1.57 for AGR. A high NLR and a high ANS were significantly associated with worse OS and PFS. However, a high NLR combined with a low AGR was associated with worse OS. Multivariate analyses demonstrated that both the NLR and ANS were independent predictors for both OS and PFS and that a low AGR was an independent predictor of a reduced OS. The nomogram accurately predicted OS (c-index: 0.785) and PFS (c-index: 0.786) in patients with MM and RI.Conclusion: ANS may serve as a potential prognostic biomarker in patients with MM and RI. The proposed nomograms may facilitate prognostic predictions for patients with MM and RI.Keywords: multiple myeloma, renal impairment, neutrophil–lymphocyte ratio, albumin-to-globulin ratio, prognosis

Jingping Sun,1,2,&ast; Jun Zhang,3,&ast; Bailong Xin,1 Zekang Ye,1,2 Yaozhuo Cai,2 Ke Lu,2 Yuzhen Wang,2 Xueyao Lei,2 Chanjuan Zheng,2 Xueli Cai3 1Department of Neurology, the Municipal Central Hospital of Lishui, Fifth Affiliated Hospital of Wenzhou Medical College, Lishui, Zhejiang, People’s Republic of China; 2Lishui Clinical Research Center for Neurological Diseases, Lishui, Zhejiang, People’s Republic of China; 3Zhejiang University, School of Medicine, Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xueli Cai, Department of Neurology, the Municipal Central Hospital of Lishui, Fifth Affiliated Hospital of Wenzhou Medical College, Lishui, Zhejiang, People’s Republic of China, Email xueli_cai_official@126.comPurpose: Lipid-lowering therapy is integral in acute ischemic stroke (AIS), yet the connection between lipid parameters and parenchymal hemorrhage (PH) after endovascular treatment (EVT) for AIS is not well-defined. This research aims to assess the association between various lipid parameters and the PH risk following EVT.Patients and Methods: We examined a database of patients who underwent EVT for AIS between September 2021 and May 2023 retrospectively. Traditional and non-traditional lipid parameters were documented. PH was identified on dual energy computed tomography images within 48 h. We employed logistic regression analysis and restricted cubic splines to examine the association between various lipid parameters and the risk of PH. The predictive capacity of the lipid parameters for PH was evaluated by comparing the area under the curve.Results: The study included 384 patients, 65 of whom (17.7%) developed PH. After adjusting for potential confounders, only triglyceride was associated with PH among the traditional lipid parameters, while all non-traditional lipid parameters were related to PH. Based on ROC curve, the ratio of remnant cholesterol to high-density lipoprotein cholesterol (RC/HDL-C) exhibited the highest predictive capability for PH. Furthermore, our analysis revealed a significant nonlinear correlation between triglyceride, non-high-density lipoprotein cholesterol, RC, RC/HDL-C and PH risk.Conclusion: In assessing the risk of PH after EVT, non-traditional lipid parameters are often superior to traditional lipid parameters. It is recommended that routine evaluation of non-traditional lipid parameters could also be conducted in clinical practice as well.Keywords: endovascular treatment, hemorrhagic transformation, serum lipids

Wenjuan Wang,1 Juanjuan Liang,1 Rong Fan,2 Yuanqing Cai,3 Baisong Yin,1 Yangyi Hu1 1School of Government, Central University of Finance and Economics, Beijing, 100081, People’s Republic of China; 2Peking University Cancer Hospital & Institute, Beijing, 100142, People’s Republic of China; 3Chinese Academy of Social Sciences Evaluation Studies, Beijing, 100732, People’s Republic of ChinaCorrespondence: Yangyi Hu, School of Government, Central University of Finance and Economics, 39 South College Road, Beijing, 100081, People’s Republic of China, Email yangyi.hu@outlook.comPurpose: The medical–pharmaceutical separation (MPS) reform is a healthcare reform that focuses on reducing the proportion of drug expenditure. This study aims to analyze the impact of the MPS reform on hospitalization expenditure and its structure in tertiary public hospitals.Methods: Using propensity score matching and multi-period difference-in-difference methods to analyze the impact of the MPS reform on hospitalization expenditure and its structure, a difference-in-difference-in-difference model was established to analyze the heterogeneity of whether the tertiary public hospital was a diagnosis-related-group (DRG) payment hospital. Of 22 municipal public hospitals offering tertiary care in Beijing, monthly panel data of 18 hospitals from July 2011 to March 2017, totaling 1242 items, were included in this study.Results: After the MPS reform, the average drug expenditure, average Western drug expenditure, and average Chinese drug expenditures per hospitalization decreased by 24.5%, 24.6%, and 24.1%, respectively (P < 0.001). The proportions of drug expenditure decreased by 4.5% (P < 0.001), and the proportion of medical consumables expenditure increased significantly by 2.7% (P < 0.001).Conclusion: The MPS reform may significantly optimize the hospitalization expenditure structure and control irrational increases in expenditure. DRG payment can control the tendency to increase the proportions of medical consumables expenditure after the reform and optimize the effect of the reform. There is a need to strengthen the management of medical consumables in the future, promote the MPS reform and DRG payment linkage, and improve supporting measures to ensure the long-term effect of the reform.Keywords: diagnosis-related-group, provider payment reforms, healthcare expenditure, propensity-score-matching, difference-in-difference-in-difference, China

Yaping Jiang,1,&ast; Yuying Cai,1,&ast; Xin Zhang,1 Li Chen,1 Xingtao Zhou,2 Yihui Chen1 1Department of Ophthalmology, Yangpu Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China; 2Eye Institute and Department of Ophthalmology, Institute for Medical and Engineering Innovation, Eye & ENT Hospital, Fudan University; NHC Key Laboratory of Myopia (Fudan University), Key Laboratory of Myopia, Chinese Academy of Medical Sciences, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xingtao Zhou, Eye Institute and Department of Ophthalmology, Institute for Medical and Engineering Innovation, Eye & ENT Hospital, Fudan University; NHC Key Laboratory of Myopia (Fudan University), Key Laboratory of Myopia, Chinese Academy of Medical Sciences, No. 19 Baoqing Road, Xuhui District, Shanghai, 200031, People’s Republic of China, Email doctzhouxingtao@163.com Yihui Chen, Department of Ophthalmology, Yangpu Hospital, School of Medicine, Tongji University, 450 Tengyue Road, Shanghai, 200090, People’s Republic of China, Email 1300089@tongji.edu.cnBackground: Laser therapy has been proven as an effective technique for managing ophthalmological disorders. To guide future research, we conducted a bibliometric analysis of laser applications in eye diseases from 1990 to 2022, aiming to identify key themes and trends.Methods: We retrieved 3027 publications from the Web of Science Core Collection (WoSCC). Bibliometrix was used for science mapping of the literature, while VOSviewer and CiteSpace were applied to visualize co-authorship, co-citation, co-occurrence, and bibliographic coupling networks.Results: From a co-citation reference network, we identified 52 distinct clusters. Our analysis uncovered three main research trends. The first trend revolves around the potential evolution of corneal laser surgery techniques, shifting from the treatment of refractive errors to broader applications in biomedical optics. The second trend illustrates the advancement of laser applications in treating a range of disorders, from retinal and ocular surface diseases to glaucoma. The third trend focuses on the innovative uses of established technologies.Conclusion: This study offers significant insights into the evolution of laser applications in ophthalmology over the past 30 years, which will undoubtedly assist scientists in directing further research in this promising field.Keywords: laser, bibliometric, research trend, systematic review, CiteSpace

Ping Zhang, Yanan Cai, Fei Ge, Zunmin Zhu, Kai Sun Department of Hematology, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, Zhengzhou, People’s Republic of ChinaCorrespondence: Kai Sun, Department of Hematology, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, &num;7 Weiwu Road, Zhengzhou, People’s Republic of China, Email sunkai900@163.comIntroduction: This study aims to investigate the incidence, clinical characteristics, and prognosis of thrombosis in Chinese patients with immune thrombocytopenia (ITP).Methods: This was a single-center, retrospective study of adult patients with ITP at the Henan Provincial People’s Hospital from January 2018 to June 2023.Results: A total of 3216 adult patients with primary ITP were included in the study period, with 25 (0.93%) having thrombotic events. The average age of 25 patients with thrombosis is 62.76± 12.79 years, including 11 males and 14 females. In addition, among the 25 thrombotic events, 19 cases were arterial thrombosis (AT), and 6 cases were venous thrombosis (VT). The incidence of AT is higher than that of VT (P=0.009). There was no obvious difference in clinical characteristics between the two groups. The median platelet count at the time of thrombosis in 25 patients was 35 (23, 52) × 109/L. At the onset of thrombosis, 23 patients (92.0%) had a low PLT (< 100× 109/L). One patient with ischemic stroke died in the hospital due to severe infection.Conclusion: ITP may be considered a bleeding disorder with a high risk of thrombosis, and AT is more common than VT in the Chinese population.Keywords: immune thrombocytopenia, arterial thrombosis, venous thrombosis, platelet, hemorrhagic disease

Shaohua Tan,1,&ast; Xiangchen Li,2,&ast; Bing Lu,1,3 Yibin Lin,3 Yunxiang Cai,1 Jie He,4 Sisi Chen,2 Junli Gao,2 Junshun Gao,2 Xinhua Qiang1 1Department of Clinical Laboratory, The First People’s Hospital of Huzhou, Huzhou, Zhejiang, 313000, People’s Republic of China; 2Key Laboratory of Precision Medicine in Diagnosis and Monitoring Research of Zhejiang Province, Hangzhou, Zhejiang, 310020, People’s Republic of China; 3School of Medicine, Huzhou University, Huzhou, Zhejiang, 313000, People’s Republic of China; 4Department of Infectious Diseases, The First People’s Hospital of Huzhou, Huzhou, Zhejiang, 313000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xinhua Qiang, Department of Clinical Laboratory, The First People’s Hospital of Huzhou, No. 158 Back Square Road, Wuxing District, Huzhou, Zhejiang, 313000, People’s Republic of China, Email qiangxinhua@zjhu.edu.cnAbstract: Carbapenem-resistant Salmonella enterica (S. enterica) pose a significant threat to public health, causing gastroenteritis and invasive infections. We report the first emergence of a carbapenem-resistant S. enterica serovar London strain, A132, carrying the blaNDM-5 gene in China. Whole-genome sequencing and bioinformatics analysis assigned A132 to be ST155, a multidrug-resistant clone frequently reported in China. The strain A132 exhibited resistance to multiple antibiotics, with 20 acquired antibiotic resistance genes (ARGs) identified, predominantly located on the IncFIB plasmid (pA132-1-NDM). Notably, the blaNDM-5 gene was located within an IS 26 flanked-class 1 integron-ISCR1 complex, comprising two genetic cassettes. One cassette is the class 1 integron, which may facilitate the transmission of the entire complex, while the other is the blaNDM-5-containing ISCR1-IS 26-flanked cassette, carrying multiple other ARGs. Genbank database search based on the blaNDM-5-carrying cassette identified a similar genetic context found in transmissible IncFIA plasmids from Escherichia coli (p91) and Enterobacter hormaechei (p388) with a shared host range, suggesting the potential for cross-species transmission of blaNDM-5. To our knowledge, this is the first reported case of Salmonella serovar London ST155 harboring blaNDM-5 gene. Phylogenetic analysis indicated a close relationship between A132 and eight S. London ST155 strains isolated from the same province. However, A132 differed by carrying the blaNDM-5 gene and four unique ARGs. Given the high transmissibility of the F-type plasmid harboring blaNDM-5 and 18 other ARGs, it is imperative to implement vigilant surveillance and adopt appropriate infection control measures to mitigate the threat to public health.Keywords: blaNDM-5, Salmonella London, ST155, carbapenem resistance, IncFIB, integron

Beiying Deng,1,2,&ast; Ying Chen,1,2,&ast; Pengzhan He,1,2,&ast; Yinghui Liu,3 Yangbo Li,1,2 Yuli Cai,4 Weiguo Dong1 1Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China; 2Central Laboratory, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China; 3Department of Geriatric, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China; 4Department of Endocrinology, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Weiguo Dong, Department of Gastroenterology, Renmin Hospital of Wuhan University, No. 99 Zhangzhidong Road, Wuhan, Hubei Province, 430060, People’s Republic of China, Email dongweiguo@whu.edu.cnBackground: This study aims to elucidate the role of mitochondrial autophagy in metabolic dysfunction-associated steatohepatitis (MASH) by identifying and validating key mitophagy-related genes and diagnostic models with diagnostic potential.Methods: The gene expression profiles and clinical information of MASH patients and healthy controls were obtained from the Gene Expression Omnibus database (GEO). Limma and functional enrichment analysis were used to identify the mitophagy-related differentially expressed genes (mito-DEGs) in MASH patients. Machine learning models were used to select key mito-DEGs and evaluate their efficacy in the early diagnosis of MASH. The expression levels of the key mito-DEGs were validated using datasets and cell models. A nomogram was constructed to assess the risk of MASH progression based on the expression of the key mito-DEGs. The mitophagy-related molecular subtypes of MASH were evaluated.Results: Four mito-DEGs, namely MRAS, RAB7B, RETREG1, and TIGAR were identified. Among the machine learning models employed, the Support Vector Machine demonstrated the highest AUC value of 0.935, while the Light Gradient Boosting model exhibited the highest accuracy (0.9189), kappa (0.7204), and F1-score (0.9508) values. Based on these models, MRAS, RAB7B, and RETREG1 were selected for further analysis. The logistic regression model based on these genes could accurately predict MASH diagnosis. The nomogram model based on these DEGs exhibited excellent prediction performance. The expression levels of the three mito-DEGs were validated in the independent datasets and cell models, and the results were found to be consistent with the findings obtained through bioinformatics analysis. Furthermore, our findings revealed significant differences in gene expression patterns, immune characteristics, biological functions, and enrichment pathways between the mitophagy-related molecular subtypes of MASH. Subtype-specific small-molecule drugs were identified using the CMap database.Conclusion: Our research provides novel insights into the role of mitophagy in MASH and uncovers novel targets for predictive and personalized MASH treatments.Keywords: metabolic dysfunction-associated steatohepatitis, mitophagy, biomarkers, diagnostic model, machine learning

Yuhang Wang,1,&ast; Chunsun Li,2,&ast; Huan Zhang,1 Yulong Chi,1 Yun Cai1 1Center of Medicine Clinical Research, Department of Pharmacy, Medical Supplies Center of PLA General Hospital, Beijing, People’s Republic of China; 2Laboratory of Department of Pulmonary and Critical Care Medicine, PLA General Hospital, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yun Cai, Center of Medicine Clinical Research, Department of Pharmacy, Medical Supplies center of PLA General Hospital, Postal Address: 28 Fu Xing Road, Beijing, 100853, People’s Republic of China, Tel +86-10-6693-7166, Fax +86-10-8821-4425, Email caicai_hh@126.comObjective: Pseudomonas aeruginosa (PA) often displays drug resistance and biofilm-mediated adaptability. Here, we aimed to evaluate the antibiofilm efficacy of azithromycin-based combination regimens.Methods: Minimum inhibitory concentrations (MICs), minimal biofilm eradication concentrations (MBECs), and MBEC-combination of azithromycin, colistin, amikacin, and levofloxacin to bioluminescent strain PAO1 and carbapenem-resistant PAO1 (CRPAO1) were assessed. An animal biofilm infection model was established and detected using a live animal bio-photonic imaging system.Results: In vitro, PAO1 and CRPAO1 were susceptible to colistin, amikacin, and levofloxacin, while they were unsusceptible to azithromycin. The combinations based on azithromycin have no synergistic effect on biofilm in vitro. In vivo, azithromycin plus colistin or levofloxacin could shorten the PAO1 biofilm eradication time, which totally eradicates the biofilm in all mice on the 8th or 6th day, while monotherapy only eradicate biofilm in 70% or 80% mice on the 8th day. For CRPAO1 biofilm, only azithromycin–colistin combination and colistin monotherapy eradicated the bacteria in 60% and 40% of mice at the 6th day.Conclusion: Azithromycin-based combinations containing levofloxacin or colistin had no synergistic effect in vitro, and they are promising for clinical applications due to the good synergistic activity against PAO1 biofilms in vivo.Keywords: Pseudomonas aeruginosa, biofilm, azithromycin, combinations

Xiaohong Chen,1,&ast; Shiqi Zhou,2,&ast; Lin Yang,1 Qianqian Zhong,1 Hongguang Liu,3 Yongjian Zhang,1 Hanyi Yu,2 Yongjiang Cai1 1Center of Health Management, Peking University Shenzhen Hospital, Shenzhen, People’s Republic of China; 2School of Future Technology, South China University of Technology, Guangzhou, People’s Republic of China; 3Center of Health Management, Huazhong University of Science and Technology Union Hospital (Nanshan Hospital), Shenzhen, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yongjiang Cai, Center of Health Management, Peking University Shenzhen Hospital, Shenzhen, 518036, People’s Republic of China, Email caiyj2000@sina.cn Hanyi Yu, School of Future Technology, South China University of Technology, Guangzhou, People’s Republic of China, Email yuhanyi@scut.edu.cnPurpose: The purpose of this study is to explore the independent-influencing factors from normal people to prediabetes and from prediabetes to diabetes and use different prediction models to build diabetes prediction models.Methods: The original data in this retrospective study are collected from the participants who took physical examinations in the Health Management Center of Peking University Shenzhen Hospital. Regression analysis is individually applied between the populations of normal and prediabetes, as well as the populations of prediabetes and diabetes, for feature selection. Afterward,the independent influencing factors mentioned above are used as predictive factors to construct a prediction model.Results: Selecting physical examination indicators for training different ML models through univariate and multivariate logistic regression, the study finds Age, PRO, TP, and ALT are four independent risk factors for normal people to develop prediabetes, and GLB and HDL.C are two independent protective factors, while logistic regression performs best on the testing set (Acc: 0.76, F-measure: 0.74, AUC: 0.78). We also find Age, Gender, BMI, SBP, U.GLU, PRO, ALT, and TG are independent risk factors for prediabetes people to diabetes, and AST is an independent protective factor, while logistic regression performs best on the testing set (Acc: 0.86, F-measure: 0.84, AUC: 0.74).Conclusion: The discussion of the clinical relationships between these indicators and diabetes supports the interpretability of our feature selection. Among four prediction models, the logistic regression model achieved the best performance on the testing set.Keywords: prediabetes, prediction model, physical examination, machine learning, regression analysis

Lin Feng,1 Jiachen Li,1 Zhenbei Qian,2 Chenglong Li,3,4 Darui Gao,3,4 Yongqian Wang,3,4 Wuxiang Xie,3,4 Yutong Cai,5 Zhaohui Tong,2 Lirong Liang1 1Department of Clinical Epidemiology, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Heart and Vascular Health Research Center, Peking University Clinical Research Institute, Peking University First Hospital, Beijing, People’s Republic of China; 4Key Laboratory of Epidemiology of Major Diseases (Peking University), Ministry of Education, Beijing, People’s Republic of China; 5Centre for Environmental Health and Sustainability, Department of Health Sciences, University of Leicester, Leicester, UKCorrespondence: Lirong Liang, Department of Clinical Epidemiology, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China, Email llrcruie@163.comPurpose: Patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) exhibit heterogeneous responses to corticosteroid treatment. We aimed to determine whether combining eosinophil levels with other routine clinical indicators can enhance the predictability of corticosteroid treatment outcomes and to come up with a scoring system.Patients and Methods: Consecutive patients admitted with AECOPD receiving corticosteroid treatment between July 2013 and March 2022 at Beijing Chao-Yang Hospital were retrospectively analyzed. Data on patients’ demographics, smoking status, hospitalization for AECOPD in the previous year, comorbidities, blood laboratory tests, in-hospital treatment and clinical outcomes were collected. Least absolute shrinkage and selection operator (LASSO) regression and backward logistic regression were used for predictor selection, and predictive nomograms were developed. The discrimination and calibration of the nomograms were assessed using the area under the receiver operating curve (AUC) and calibration plots. Internal validation was performed using the 500-bootstrap method, and clinical utility was evaluated using decision curve analysis (DCA).Results: Among the 3254 patients included, 804 (24.7%) had treatment failure. A nomogram of eosinophils, platelets, C-reactive protein (CRP), low density lipoprotein cholesterol, prognostic nutritional index (PNI), hospitalization for AECOPD in the previous year, ischemic heart diseases and chronic hepatic disease was developed to predict treatment failure for patients with a smoking history. For patients without a smoking history, a nomogram of CRP, PNI, ischemic heart diseases and chronic hepatic disease was developed. Although the AUCs of these two nomograms were only 0.644 and 0.647 respectively, they were significantly superior to predictions based solely on blood eosinophil levels.Conclusion: We developed easy-to-use comprehensive nomograms utilizing readily available clinical biomarkers related to inflammation, nutrition and immunity, offering modestly enhanced predictive value for treatment outcomes in corticosteroid-treated patients with AECOPD. Further investigations into novel biomarkers and additional patient data are imperative to optimize the predictive performance.Keywords: chronic obstructive pulmonary disease, glucocorticoids, prediction model, least absolute shrinkage and selection operator

Liang Fu,1,2,&ast; Wenfei Wang,2,3,&ast; Juan Xiong,4,&ast; Peize Zhang,2 Hui Li,2 Xilin Zhang,5 Hancheng Liang,6 Qianting Yang,2 Zhaoqin Wang,2 Xinchun Chen,3 Guofang Deng,2 Yi Cai,3 Shenjie Tang1 1Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumour Research Institute, Beijing, People’s Republic of China; 2Shenzhen Third People’s Hospital, National Clinical Research Center for Infectious Disease (Shenzhen), Shenzhen Clinical Research Center for Tuberculosis, Southern University of Science and Technology, Shenzhen, Guangdong, People’s Republic of China; 3Department of Pathogen Biology, Guangdong Key Laboratory of Regional Immunity and Diseases, Shenzhen University School of Medicine, Shenzhen, Guangdong, People’s Republic of China; 4Health Science Center, Shenzhen University, Shenzhen, Guangdong, People’s Republic of China; 5Tuberculosis Prevention and Control Department, the Fourth People’s Hospital of Foshan, Foshan, Guangdong, People’s Republic of China; 6Division Two of Tuberculosis Diseases Department, the Sixth People’s Hospital of Dongguan, Dongguan, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shenjie Tang; Yi Cai, Email tangsj1106@hotmail.com; caiyi0113@szu.edu.cnBackground: The rising prevalence and limited efficacy of treatments for pre-extensively drug-resistant tuberculosis (pre-XDR-TB) underscore an immediate need for innovative therapeutic options. A combination of host-directed therapy (HDT) and anti-TB treatment presents a viable alternative for pre-XDR-TB management. Sulfasalazine (SASP), by targeting the amino acid transport system xc (xCT), potentially reduces the intracellular Mycobacterium tuberculosis load and mitigates lung pathology, positioning it as a promising TB HDT agent. This study aims to assess the efficacy of SASP as a supplementary therapy for pre-XDR-TB.Methods: A pilot study examined the safety and effectiveness of two 9-month short-course, all-oral regimens for pre-XDR-TB treatment: Bdq-regimen (consisting of Bdq, linezolid, cycloserine, clofazimine, and pyrazinamide) and SASP-regimen (comprising SASP, linezolid, cycloserine, clofazimine, and pyrazinamide). The primary endpoint was the incidence of unfavorable outcomes 12 months post-treatment.Results: Of the 44 participants enrolled, 43 were assessable 12 months post-treatment. Culture conversion rates stood at 73.2% by Month 2 and escalated to 95.1% by Month 6. Overall, 88.4% (38/43) of the participants exhibited favorable outcomes, 85.2% (19/23) for the Bdq-regimen and 93.8% (14/15) for the SASP-regimen. The SASP-regimen group recorded no deaths or treatment failures.Conclusion: Both 9-month short-course, all-oral regimens manifested commendable primary efficacy in treating pre-XDR-TB patients. The SASP-regimen emerged as effective, safe, well-tolerated, and cost-effective.Plain language summary: This study explored a new way to treat a hard-to-treat type of tuberculosis (TB) using a medicine called Sulfasalazine, alongside usual TB treatments. Over 9 months, two groups of patients were given different sets of medicines, one including Sulfasalazine. The results, checked 12 months after treatment, showed that most patients improved, especially those given Sulfasalazine. No one in the Sulfasalazine group died or had their treatment fail, suggesting that Sulfasalazine could be a promising addition to current treatments for this tough-to-treat TB.Keywords: Sulfasalazine, host-directed therapy, pre-extensive drug-resistant tuberculosis, short-course, treatment

Xiaolan Zhou,1 Rumeng Chen,2 Yichen Cai,1 Qiu Chen1 1Department of Endocrinology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 2School of Life Sciences, Beijing University of Chinese Medicine, Beijing, People’s Republic of ChinaCorrespondence: Qiu Chen, Department of Endocrinology, Hospital of Chengdu University of Traditional Chinese Medicine, No. 39, Shierqiao Road, Chengdu, Sichuan, People’s Republic of China, Tel +86 18981885702, Fax +86 28-87765517, Email chenqiu1005@cdutcm.edu.cnPurpose of Review: The aim of this review is to summarize the role of gastrointestinal microbiome (GM) in the development of type 2 diabetes mellitus (T2DM). Besides, we discuss the feasibility of applying FMT in the treatment of T2DM and propose a series of processes to refine the use of FMT in the treatment of T2DM.Recent Findings: T2DM is a metabolic disease which is connected with the GM. According to many researches, GM can produce a variety of metabolites such as bile acid, short chain fatty acids, lipopolysaccharides and trimethylamine oxide which play an important role in metabolism. FMT is a method to regulate GM and has been observed to be effective in the treatment of metabolic diseases such as T2DM in some mouse models and people. However, there is still a lack of direct evidence for the use of FMT in the treatment of T2DM, and the process of FMT is not standardized.Summary: Dysregulation of GM is closely related to the development of T2DM. Promoting the conversion of GM in T2DM patients to normal population through FMT can reduce insulin resistance and lower their blood glucose level, which is an optional treatment for T2DM patients in the future. At present, the feasibility and limitations of applying FMT to the treatment of T2DM need to be further studied.Keywords: fecal microbiota transplantation, type 2 diabetes mellitus, gastrointestinal microbiome, treatment

Jiemei Ye,1,2,&ast; Xiaoying Huang,3,4,&ast; Weiling Qin,1,2,&ast; Pan Liang,3,4 Jun Zhao,4 Yinxin Ye,1,2 Huojin Ji,1,2 Xinyun Peng,1,2 Yushan Liang,3,4 Yonglin Cai1,5 1Guangxi Health Commission Key Laboratory of Molecular Epidemiology of Nasopharyngeal Carcinoma, Wuzhou Red Cross Hospital, Wuzhou, Guangxi, People’s Republic of China; 2Department of Clinical Laboratory, Wuzhou Red Cross Hospital, Wuzhou, Guangxi, People’s Republic of China; 3Department of Otolaryngology-Head and Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 4Guangxi Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 5Department of Preventive Medicine, Wuzhou Cancer Center, Wuzhou, Guangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yonglin Cai, Guangxi Health Commission Key Laboratory of Molecular Epidemiology of Nasopharyngeal Carcinoma, Wuzhou Red Cross Hospital, Wuzhou, Guangxi, 543002, People’s Republic of China, Email cylzen@163.com Yushan Liang, Department of Otolaryngology-Head and Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of China, Email yushanliang33@outlook.comPurpose: Paired Box 5 (PAX5) is a transcription factor that is widely associated with carcinogenesis. PAX5 can maintain Epstein-Barr virus (EBV) latency in B cells, while a close association exists between EBV infection and nasopharyngeal carcinoma (NPC). However, there are very few reports on the correlation between PAX5 and NPC development. The aim of this study was to investigate the role of PAX5 in NPC.Patients and Methods: The clinical value and prognostic significance of PAX5 in NPC and the association with PAX5 expression and immune cell infiltration were analyzed by multiple GEO datasets. In vivo and in vitro experiments including real-time PCR, Western blot, CCK-8 assay, and methylation sequencing were used to validate the results of bioinformatics analysis.Results: The expression of PAX5 was significantly reduced in NPC tissues, with the low expression being correlated with advanced clinical stage, low tumor mutation burden and immune activation, high relative expression of EBV, poor survival for NPC patients. PAX5 exhibited excellent diagnostic performance and had potential as a predictive factor for response to the immune checkpoint inhibitors therapy. Enrichment analysis suggested that the low expression of PAX5 was associated with the dysregulation of Hippo and Wnt signaling pathways. The promoter of PAX5 gene was hypermethylated in NPC tissues. Furthermore, the in vitro and in vivo experiments revealed that NPC tissue and cell lines had low mRNA expression levels of PAX5, the PAX5 promoter was hypermethylated in NPC cell lines, and PAX5 overexpression inhibited NPC cell proliferation and tumor growth in nude mice.Conclusion: PAX5 may be a tumor suppressor and serve as a novel potential diagnostic and prognostic marker for NPC.Keywords: nasopharyngeal carcinoma, transcription factor, PAX5, prognosis, immunity, Epstein-Barr virus

Na Yan,1 Tong Zhou,1 Mingming Hu,1 Yuxuan Cai,1 Ling Qi,1 Blen Dereje Shiferaw,1 Wei Wang,1– 3 Chunxia Miao4 1School of Public Health, Xuzhou Medical University, Xuzhou, 221004, People’s Republic of China; 2Research Center for Mental Crisis Prevention and Intervention of College Students in Jiangsu Province, Xuzhou Medical University, Xuzhou, 221004, People’s Republic of China; 3Jiangsu Engineering Research Center of Biological Data Mining and Healthcare Transformation, Xuzhou Medical University, Xuzhou, 221004, People’s Republic of China; 4School of Management, Xuzhou Medical University, Xuzhou, 221004, People’s Republic of ChinaCorrespondence: Wei Wang, School of Public Health, Xuzhou Medical University, 209 Tong Shan Road, Xuzhou, Jiangsu, 221004, People’s Republic of China, Email weiwang90@163.com Chunxia Miao, School of management, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, Jiangsu, 221004, People’s Republic of China, Email miaochunxia1978@163.comBackground: Previous findings indicate that stress has a profound influence on suicide behavior, but the potential mediating and moderating mechanisms are unknown between uncertainty stress and suicide behavior. The present study, therefore, examined the relationship between uncertainty stress and suicide behavior, the mediating effect of depressive symptoms, and the moderating effect of family relationship in a sample of university students in China.Methods: 1828 university students were assessed anonymously by using the Uncertainty Stress Scale, Center for Epidemiologic Studies Depression Scale, Brief Suicidal Scale, and Family Relationship Scale between May to June in 2021. SPSS 26.0 was used for descriptive statistics and Spearman correlation analysis. PROCESS 3.5 was used to calculate the significance of the mediating and moderating effects of the variables.Results: Moderated mediation model analyses showed that: (a) depressive symptoms partially mediated the link between uncertainty stress and suicide behavior (indirect effect = 0.14, 95%bootstrap CI = 0.10, 0.19). The indirect effect of the depressive symptoms accounted for 67.12% of the total variance in suicide behavior. (b) The indirect association between uncertainty stress and suicide behavior was moderated by family relationship. Specifically, the paths from uncertainty stress to depressive symptoms (interact effect = − 0.06, P< 0.001) and depressive symptoms to suicide behavior (interact effect = − 0.08, P< 0.01) were weakened in the context of higher family relationship.Conclusion: Depressive symptoms play a crucial role in bridging uncertainty stress and suicide behavior, while the family relationship can buffer the mediation impact of depressive symptoms. These findings significantly contribute to the prevention and intervention of suicide in Chinese university students.Keywords: uncertainty stress, depressive symptoms, suicide behavior, family relationship, university students

Zheng Wang,1,&ast; Dahai Yu,1,2,&ast; Uchechukwu Levi Osuagwu,3,4 Karen Pickering,5 John Baker,5,6 Richard Cutfield,5,7 Yamei Cai,1 Brandon J Orr-Walker,5,6 Gerhard Sundborn,8 Zhanzheng Zhao,1 David Simmons1,4 1Department of Nephrology, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, 450052, People’s Republic of China; 2Primary Care Centre Versus Arthritis, School of Medicine, Keele University, Keele, ST5 5BG, UK; 3Translational Health Research Institute (THRI), Western Sydney University, Campbelltown, Sydney NSW, 2560, Australia; 4School of Medicine, Western Sydney University, Campbelltown, Sydney NSW, 2751, Australia; 5Diabetes Foundation Aotearoa, Otara, New Zealand; 6Department of Diabetes and Endocrinology, Counties Manukau Health, Auckland, New Zealand; 7Department of Diabetes and Endocrinology, Waitemata District Health Board, Auckland, New Zealand; 8Section of Pacific Health, The University of Auckland, Auckland, New Zealand&ast;These authors contributed equally to this workCorrespondence: David Simmons; Zhanzheng Zhao, Department of Nephrology, The First Affiliated Hospital Zhengzhou University, Zhengzhou, 450052, People’s Republic of China, Tel +6124620 3899 ; +86 13938525666, Fax +6124620 3890 ; +863716698 8753, Email Da.Simmons@westernsydney.edu.au; zhanzhengzhao@zzu.edu.cnPurpose: We aimed to examine socioeconomic inequality (SI) in cause-specific outcomes among adults with impaired glucose tolerance (IGT) and/or Impaired fasting glucose (IFG) in New Zealand (NZ) over 25 years.Patients and Methods: A population-based open cohort was derived from Diabetes Care Support Service in NZ with national databases linkage. Patients aged ≥ 18 years with IGT and/or IFG were enrolled between 01/01/1994 and 31/07/2018 and followed up until death or 31/12/2018. Incident outcomes (all-cause, premature, cardiovascular, and cancer death; cardiovascular, myocardial infarction, stroke, heart failure, and end-stage kidney disease hospitalization) by demographic, anthropometric, socioeconomic status, clinical measurements, enrol-time-periods, and IGT/IFG were evaluated. Adjusted incidence rate ratios, absolute risk difference, and SI measurements (slope and relative index of inequality) were estimated using Age-Period-Cohort models.Results: 29,894 patients (58.5 (SD 14.3) years mean age; 52.2% female) were enrolled with 5.6 (IQR: 4.4– 7.4) years of median follow-up. Mortality rates decreased, whereas hospitalization (except myocardial infarction) rates increased. SI was significant for each outcome. Higher mortality and hospitalization rates and worsened SI were common in men, older, the most deprived, and M&amacr;ori patients, as well as patients with obesity, current smoking, with both IFG and IGT, and greater metabolic derangement (higher systolic blood pressure, lipids, and HbA1c, and lower level of mean arterial pressure).Conclusion: Enhanced management strategies are necessary for people with IGT and/or IFG to address persisting SI, especially for men, older people, current smokers, NZ European and M&amacr;ori patients, patients with obesity, or with any abnormal metabolic measurements.Keywords: impaired glucose tolerance, impaired fasting glucose, New Zealand, M&amacr;ori, ethnic disparity, socioeconomic inequality, mortality, cardiovascular diseases, heart failure, cancer, end-stage renal disease

Haishi Zheng,1,2 Yirixiati Aihaiti,2 Yongsong Cai,2 Qiling Yuan,2 Mingyi Yang,2 Zheng Li,2 Ke Xu,2 Peng Xu1,2 1Department of Orthopedics, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China; 2Department of Joint Surgery, HongHui Hospital, Xi’an Jiaotong University, Xi’an, People’s Republic of ChinaCorrespondence: Peng Xu, Department of Orthopedics, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China, Tel +86 13772090019, Email xupeng369@mail.xjtu.edu.cnPurpose: The goal of this study was to explore the expression characteristics of RNA modification-related genes, reveal immune landscapes and identify novel potential diagnostic biomarkers in osteoarthritis (OA) and rheumatoid arthritis (RA) patients.Patients and Methods: RNA microarray and single-cell sequencing (scRNA-seq) data were downloaded from gene expression omnibus (GEO) database. Differentially expressed RNA modification-related genes were identified and then functionally annotated. Univariate logistic regression and lasso regression analysis were used to identify primary disease genes for OA and RA. Validation was done using scRNA-seq analysis and immunohistochemistry (IHC) in human knee synovial tissues and a murine destabilization of the medial meniscus (DMM) model. Through WGCNA analysis, genes associated with cell pyroptosis or autophagy in OA and RA were identified, which were then combined with differentially expressed RNA modification-related genes to construct a PPI interaction network. Furthermore, hub genes were selected for ceRNA interaction network analysis, correlation analysis with OA and RA molecular subtypes, as well as correlation analysis with 22 immune cells.Results: Six RNA modification-related genes (ADAMDEC1, IGHM, OGN, TNFRSF11B, SCARA3 and PTN) were identified as potential OA and RA pathogenesis biomarkers. Their expression was validated in human knee synovial tissues and a murine DMM model. Functional enrichment of differentially expressed RNA modification-related genes between RA and OA was analyzed using GO, KEGG, GSEA, and GSVA. Based on WGCNA and PPI analysis, the six hub genes related to pyroptosis and RNA modification (CXCL10, CXCL9, CCR7, CCL5, CXCL1, and CCR2) were identified as central nodes for ceRNA interaction, correlation with OA and RA molecular subtypes, and association with 22 immune cells.Conclusion: Our research revealed the significance of RNA modification-related genes in the development of OA and RA pathogenesis, thereby providing a novel research direction for understanding the mechanisms, diagnosis, and treatment of OA and RA.Keywords: m6A, m5C, m1A, osteoarthritis, rheumatoid arthritis, single-cell sequencing

Mei Fan, Fangyi Deng, Rui Tang, Yixian Cai, Xiaotao Zhang, Hongyao Li, Ting Xiang, Jiyang Pan Department of Psychiatry, Sleep Medicine Centre, The First Affiliated Hospital, Jinan University, Guangzhou, People’s Republic of ChinaCorrespondence: Jiyang Pan, Department of Psychiatry, Sleep Medicine Centre, The First Affiliated Hospital, Jinan University, 613, West Huangpu Avenue, Guangzhou, 510630, People’s Republic of China, Tel +86 2038688651, Email jiypan@vip.163.comPurpose: This research aimed to investigate serum Zonula occludens-1 (ZO-1) and Claudin-5 (CLDN5) levels to show whether or not their eventual changes in patients with insomnia disorder could have etiopathogenetic importance. There was no research investigating serum ZO-1 and CLDN5 concentrations in insomnia disorder.Patients and Methods: This study included 60 insomnia disorder patients and 45 normal controls. None of the patients received drugs for insomnia. The patients completed Insomnia Severity Index (ISI) and Pittsburgh Sleep Quality Index (PSQI), and Polysomnography (PSG) to score the insomnia disorder symptoms. Venous blood samples were collected, and serum ZO-1 and claudin-5 levels were analyzed by enzyme-linked immunosorbent assay (ELISA).Results: Serum ZO-1 level was significantly higher without a significant difference between age, sex, and body mass index, whereas the difference in serum claudin-5 level between the two groups was not statistically significant. In addition, ZO-1 levels were positively correlated with ISI and PSQI and negatively with N1 and N1_perc. We also demonstrated a positive correlation between the levels of CLDN5 and HAMA, and a negative correlation with total sleep time (TST), N1 and N1_perc.Conclusion: Our findings suggest an association between these intestinal and brain endothelial permeability markers and insomnia disorders. However, these remain modest and preliminary and need more extensive studies, including long-term follow-up populations and involving gut microbes, to further validate and explore the mechanisms involved.Keywords: insomnia disorder, blood-brain barrier, intestinal permeability, claudin-5, zonula occludens-1, biomarker

Xili Wen,1 Yujun Cai,1 Kai Li,1 Zisu Wang,1 Weiyi Zhang,1 Man Qin2 1School of Physical Education, Shanghai University of Sport, Shanghai, People’s Republic of China; 2Shanghai Lixin University of Accounting and Finance, Shanghai, People’s Republic of ChinaCorrespondence: Man Qin, Shanghai Lixin University of Accounting and Finance, Shanghai, People’s Republic of China, Email hnqinman@126.comPurpose: The study aims to explore the relationship and potential mechanisms between screen time and anxiety and have a clear understanding of the role of negative emotions and emotion regulation, thus providing guidance for Chinese college students to improve mental health.Methods: We conducted a questionnaire survey by selecting 1721 academic college students from 6 colleges and universities in 5 provinces in China, and the data were analyzed through the Process program of SPSS for mediating effect and moderating effect.Results: There is a significant positive relationship between screen time and anxiety, negative emotions play a mediating role between the two (indirect effect = 0.32, p < 0.001), mediating effect accounts for 59.88% of the total effect, and emotion regulation regulates the direct relationship between screen time and anxiety (interaction effect = 0.027, p < 0.001).Conclusion: This study sheds light on the potential mechanisms by which screen time affects anxiety in academic college students, providing a fresh perspective on anxiety reduction. Screen time positively affects anxiety levels, where negative emotions have a mediating role and emotion regulation has a moderating role. In the future, we can control screen ++time, increase physical activities, reduce negative emotions, and improve the emotional regulation ability to relieve anxiety, so as to improve the mental health of academic college students, and expect to have a positive impact on future learning, life, and planning.Keywords: college students, sedentary behavior, anxiety, negative emotions, emotion regulation

Zisu Wang,1 Kai Li,1 Shuangshuang Guo,2 Xili Wen,1 Ziyi He,1 Yujun Cai1 1School of Physical Education, Shanghai University of Sport, Shanghai, People’s Republic of China; 2Physical education Group, High school Attached to Shanghai Normal University Minhang Campus, Shanghai, People’s Republic of ChinaCorrespondence: Yujun Cai, School of Physical Education, Shanghai University of Sport, Shanghai, People’s Republic of China, Email caiyujun@sus.edu.cnPurpose: The purpose of this study was to examine the relationships between academic engagement and moderate-to-vigorous physical activity (MVPA), muscle-strengthening exercise (MSE) and sedentary behavior (SB) among adolescents, so as to provide evidence from the perspective of exercising for students to learn efficiently, teachers to improve classroom teaching, and schools to improve educational quality.Methods: A questionnaire survey was conducted in 12 junior high schools in Shanghai, China, which were selected by a multi-stage stratified cluster sampling method. Then, with the valid data of 2078 students collected from the survey. A data analysis was performed using SPSS Statistics 26.0. Multiple linear regression models were adopted to analyze the factors affecting adolescent academic engagement and to determine whether MVPA, MSE, and SB play roles in it.Results: (1) The differences in academic engagement depended on the exercise adherence to the recommended amount of MVPA, MSE, and screen-based SB. (2) In terms of the three independent variables of total time, MSE (β = 0.206) and MVPA (β = 0.175) showed a significant positive correlation with academic engagement, while SB (β = − 0.155) was negatively correlated with academic engagement. (3) From the linear regression model of eight combination groups divided by the exercise adherence to the recommended amount of MVPA, MSE and SB, the group that met none of the recommendations (β = − 0.235) showed a significant negative effect on academic engagement, while the groups that met any two or all three of the recommendations demonstrated strong positive correlations with academic engagement (P < 0.001).Conclusion: Increasing adolescents’ muscle-strengthening exercise and moderate-to-vigorous physical activity and reducing sedentary behavior can effectively promote academic engagement. Therefore, adolescents are suggested to reach the recommended amounts of physical activity, muscle-strengthening exercise, and sedentary behavior so as to improve academic engagement more effectively.Keywords: moderate-to-vigorous physical activity, muscle-strengthening exercise, academic engagement, sedentary behaviors

Ya Wang,1,&ast; Jiajia Zhang,2,&ast; Xiaoyan Chen,1,&ast; Min Sun,3 Yanqing Li,4 Yanan Wang,5 Yan Gu,6 Yinyin Cai1 1Neurosurgical Intensive Care Unit, Department of Neurosurgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu, People’s Republic of China; 2Neurosurgery Section Two, Department of Neurosurgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu, People’s Republic of China; 3Department of Geriatrics Section Three, Affiliated Hospital of Nantong University, Nantong, Jiangsu, People’s Republic of China; 4Department of Neurosurgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu, People’s Republic of China; 5Respiratory and Critical Care Medicine Intensive Care Unit, Affiliated Hospital of Nantong University, Nantong, Jiangsu, People’s Republic of China; 6Infection Management Office, Affiliated Hospital of Nantong University, Nantong, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoyan Chen, Email CXYtdfy@126.comObjective: To develop a predictive model for assessing the risk of multidrug-resistant organisms (MDROs) infection and validate its effectiveness.We conducted a study on a total of 2516 patients admitted to the neurosurgery intensive care unit (NICU) of a Grade-III hospital in Nantong City, Jiangsu Province, China, between January 2014 and February 2022. Patients meeting the inclusion criteria were selected using convenience sampling. The patients were randomly divided into modeling and validation groups in a 7:3 ratio. To address the category imbalance, we employed the Synthetic Minority Over-sampling Technique (SMOTE) to adjust the MDROs infection ratio from 203:1558 to 812:609 in the training set. Univariate analysis and logistic regression analysis were performed to identify risk factors associated with MDROs infection in the NICU. A risk prediction model was developed, and a nomogram was created. Receiver operating characteristic (ROC) analysis was used to assess the predictive performance of the model.Patients and Methods: Results: Logistic regression analysis revealed that sex, hospitalization time, febrile time, invasive operations, postoperative prophylactic use of antibiotics, mechanical ventilator time, central venous catheter indwelling time, urethral catheter indwelling time, ALB, PLT, WBC, and L% were independent predictors of MDROs infection in the NICU. The area under the ROC curve for the training set and validation set were 0.880 (95% CI: 0.857– 0.904) and 0.831 (95% CI: 0.786– 0.876), respectively. The model’s prediction curve closely matched the ideal curve, indicating excellent predictive performance.Conclusion: The prediction model developed in this study demonstrates good accuracy in assessing the risk of MDROs infection. It serves as a valuable tool for neurosurgical intensive care practitioners, providing an objective means to effectively evaluate and target the risk of MDROs infection.Keywords: multidrug-resistant, infection, neurosurgical intensive care unit, nomogram

Kaiyang Wang,1,&ast; Huhai Zhang,2,&ast; Lie Yuan,3,4 Xiaoli Li,3,4 Yongqing Cai1 1Department of Pharmacy, Daping Hospital, Army Medical University, Chongqing, People’s Republic of China; 2Department of Nephrology, Southwest Hospital, Army Medical University, Chongqing, People’s Republic of China; 3Department of Pharmacology, College of Pharmacy, Chongqing Medical University, Chongqing, People’s Republic of China; 4Chongqing Key Research Laboratory for Drug Metabolism, College of Pharmacy, Chongqing Medical University, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yongqing Cai, Department of Pharmacy, Daping Hospital, Army Medical University, No. 10 Changjiang Branch Road, Yuzhong District, Chongqing, 400042, People’s Republic of China, Tel +86 023 68746950, Email cy0721@163.com Xiaoli Li, Department of Pharmacology, College of Pharmacy, Chongqing Medical University, No. 1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, People’s Republic of China, Tel +86 023 63657050, Email lixiaoli@cqmu.edu.cnAbstract: Hyperoside is a flavonol glycoside mainly found in plants of the genera Hypericum and Crataegus, and also detected in many plant species such as Abelmoschus manihot, Ribes nigrum, Rosa rugosa, Agrostis stolonifera, Apocynum venetum and Nelumbo nucifera. This compound exhibits a multitude of biological functions including anti-inflammatory, antidepressant, antioxidative, vascular protective effects and neuroprotective effects, etc. This review summarizes the quantification, original plant, chemical structure and property, structure–activity relationship, pharmacologic effect, pharmacokinetics, toxicity and clinical application of hyperoside, which will be significant for the exploitation for new drug and full utilization of this compound.Keywords: hyperoside, original plant, chemical structure, pharmacology, pharmacokinetics, toxicity

Xiaofeng Zhang,1,&ast; Jiaqi Zhang,1,&ast; Yongzhi Cai,1 Yue Li,1 Shiyun Qin,1 Jingtao Li,1 Decai Zeng,1 Tongtong Huang,1 Liu Liu Huang,2 Yanfen Zhong,1 Lihui Wei,1 Ji Wu1 1Department of Ultrasonic Medicine, the First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China; 2Department of Cardiothoracic Surgery, the First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ji Wu, Email gxnnwuji@163.comBackground: Rheumatic mitral stenosis(RMS) may leads to left ventricular remodeling (LVR), which can persist even after valve surgery. Identifying markers for early structure and function in patients with rheumatic heart disease who are at risk for adverse LVR after surgery can help determine the optimal timing of intervention. This study aimed to investigate whether preoperative parameters of global left ventricular long-axis strain (LVGLS) and mechanical discretization (MD) could predict postoperative adverse LVR.Methods: A total of 109 adult patients with RMS and 50 healthy controls were enrolled in this study. Baseline clinical features, conventional echocardiography results, LVGLS, and MD were compared between the two groups. Pre- and post-surgery echocardiography measurements were collected, and adverse LVR was defined as a> 15% increase in left ventricular end-diastolic volume or > 10% decrease in left ventricular ejection fraction. Binary regression analysis was used to determine independent predictors of poor left ventricular remodeling.Results: The variables associated with adverse LVR in this study were LVGLS (P< 0.001, odds ratio: 1.996, 95% CI: 1.394– 2.856) and MD (P=0.011, odds ratio: 1.031, 95% CI: 1.007– 1.055). The poorly reconstructed group had lower absolute values of LVGLS and higher MD than the healthy control group and the non-poorly reconstructed group. A LVGLS cutoff of − 15.0% was the best predictor for patients with poorly reconstructed LVR (sensitivity: 75.7%; specificity: 100.0%; AUC: 0.93), and a MD cutoff of 63.8ms was the best predictor (sensitivity: 63.8%; specificity: 98.6%; AUC: 0.88).Conclusion: Speckle tracking echocardiography has potential value for predicting the progression of adverse LVR and for identifying non-responders among patients with RMS undergoing surgery.Keywords: rheumatic mitral stenosis, left ventricular remodeling, left ventricular global longitudinal strain, mechanical dispersion, speckle tracking echocardiography

Jinrong Ning,1,&ast; Guodong Zheng,1,&ast; Yi Cai,1,&ast; Yunguang Hu,2,&ast; Yiqi Liu,1 Enping Lai,1 Baizhong Chen,3 Yujie Liu,1 Ziqi Liang,1 Jijun Fu,1 Minyan Wei1 1Key Laboratory of Molecular Target & Clinical Pharmacology and the State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences & The Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, 511436, People’s Republic of China; 2Medical Department, Guangdong Yifang Pharmaceutical Co., Ltd, Foshan, Guangdong, 528200, People’s Republic of China; 3Guangdong Xinbaotang Biological Technology Co., Ltd, Jiangmen, Guangdong, 529000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Minyan Wei; Jijun Fu, Guangzhou Medical University, Guangzhou, 511436, People’s Republic of China, Tel +86-20-37103268, Email weiminyan@163.com; fujj@gzhmu.edu.cnPurpose: APAP-induced liver injury (AILI) is a common cause of acute liver failure (ALF). Nobiletin (NOB) is a potential hepatoprotective agent for the treatment of APAP-induced liver injury. However, the poor solubility and low bioavailability of NOB hinders its application. In this study, a novel self-assembly nano-drug delivery system of nobiletin (solid dispersion of NOB, termed as NOB/SD) was developed based on solid dispersion technology to improve the bioavailability and hepatoprotective ability of NOB for APAP-induced liver injury therapy.Methods: The optimized NOB/SD system was constructed using the amphiphilic copolymers of Soluplus and PVP/VA 64 via hot melt extrusion technology (HME). NOB/SD was characterized by solubility, physical interaction, drug release behavior, and stability. The bioavailability and hepatoprotective effects of NOB/SD were evaluated in vitro and in vivo.Results: NOB/SD maintained NOB in matrix carriers in a stable amorphous state, and self-assembled NOB-loaded nanomicelles in water. Nanostructures based on solid dispersion technology exhibited enhanced solubility, improved release behavior, and promoted cellular uptake and anti-apoptosis in vitro. NOB/SD displayed significantly improved bioavailability in healthy Sprague Dawley (SD) rats in vivo. Furthermore, NOB/SD alleviated the APAP-induced liver injury by improving anti-oxidative stress with reactive oxygen species (ROS) scavenging and nuclear factor erythroid 2-related factor 2 (Nrf2) activation.Conclusion: These results suggested that NOB/SD could be considered as a promising hepatoprotective nano-drug delivery system for attenuating APAP-induced acute liver injury with superior bioavailability and efficient hepatoprotection, which might provide an effective strategy for APAP-induced acute liver injury prevention and treatment.Graphical Abstract: Keywords: nobiletin, self-assembly micelles, solid dispersion technology, hot melt extrusion, acetaminophen-induced liver injury

Runqi Cheng,1 Tiansheng Wang,1 Yuankun Cai,1 Songshan Chai,1 Lei Shen,1 Dongyuan Xu,1 Jingyi Yang,1 Chuqiao Yue,1 Jianzhang Pu,2 Nanxiang Xiong1 1Department of Neurosurgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei Province, People’s Republic of China; 2Department of Neurosurgery, Beijing Shunyi District Hospital, Shunyi Teaching Hospital of Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Nanxiang Xiong, Email mozhuoxiong@163.comObjective: To predict the volume and shape of the balloon before PBC by reconstructing the Meckel’s cave (MC) and establishing a volumetric measurement model, supporting preoperative preparation and intraoperative decisions.Methods: The clinical data of 31 patients with good therapeutic effects who underwent PBC are retrospectively collected, including preoperative MRI, the volume of contrast agent injected into the balloon, and intraoperative lateral X-ray images. The MC on the affected side of the 31 patients is reconstructed based on MRI using 3D Slicer, while the volume of the MC is calculated to compare with the volume of contrast agent. The width (W) and length (L) of the model of the MC in lateral view are measured and used to classify the shape of the MC based on W/L. The consistency between the W/L of the model of the MC and the W/L of the intraoperative balloon is evaluated.Results: For volume, the mean value of the models of the MC (V1) in 31 patients is 399.77± 155.13 mm³, while the mean value of the contrast agent injected during PBC (V2) is 539.03± 111.93 mm³. The formula obtained by linear regression is V2= 392.1 + 0.3676×V1. Based on the value of W/L, the shape of the MC is classified into thin “pear” in 5 patients (16.13%), standard “pear” in 22 patients (70.97%), and square “pear” in 4 patients (12.90%). There is no significant difference in W/L between the models of the MC and the intraoperative balloons in 31 patients (P=0.221).Conclusion: In 31 patients with good efficacy, it is verified that the prediction of the MC before PBC by 3D Slicer is consistent with the actual situation of the intraoperative balloon. This method can provide certain basis for preoperative preparation and intraoperative judgment.Keywords: trigeminal neuralgia, percutaneous balloon compression, Meckel’s cave, 3D Slicer, reconstruction

Xiaochong Li,1,&ast; Bowen Hu,1,&ast; Jiachen Zheng,2,3 Zhiyong Pan,1 Yuxiang Cai,4 Mingjuan Zhao,1 Xiaoqing Jin,2 Zhi-Qiang Li1 1Department of Neurosurgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, 430071, People’s Republic of China; 2Emergency Center, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, 430071, People’s Republic of China; 3The Second Clinical School, Wuhan University, Wuhan, Hubei, 430071, People’s Republic of China; 4Department of Pathology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, 430071, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoqing Jin; Zhi-Qiang Li, Email redjin@whu.edu.cn; lizhiqiang@whu.edu.cnIntroduction: Temozolomide (TMZ) induces intestinal mucosa injury that cannot be fully counteracted by supportive treatment. Probiotics regulate gut microbial composition and the host immune system and may alleviate this side effect. We aimed to investigate the potential and mechanism of Lactobacillus rhamnosus GG (LGG) in relieving intestinal mucosal injury induced by TMZ.Methods: Glioblastoma mice were divided into four groups: CON (control), LGG (109 CFU/mL, treated for 7 days), TMZ (50 mg/kg·d, treated for 5 days), LGG+TMZ (LGG for 7 days and TMZ subsequently for 5 days). Body weight, food intake, and fecal pH were recorded. Intestinal tissue samples were collected 1 day after the end of TMZ treatment. Degree of damage to intestine, expression of IL1β, IL6, TNFα, and IL10 in jejunum were determined. Levels of tight-junction proteins (ZO1, occludin), TLR4, IKKβ, IκBα, and P65 with their phosphorylation in jejunum were measured.Results: Decreases in body weight, food intake, spleen index in the TMZ group were mitigated in the LGG+TMZ group, and the degree of intestinal shortening and damage to jejunum villus were also alleviated. The expression of tight-junction proteins in the LGG+TMZ group was significantly greater than that in the TMZ group. IκBα in intestinal tissue significantly decreased in the TMZ group, phos–IKKβ and phos-P65 increased compared to the CON group, and LGG reversed such changes in IκBα and phos-P65 in the LGG+TMZ group. Intestinal inflammatory cytokines were significantly increased in the TMZ group, but lower in the LGG+TMZ group. Moreover, expression of TLR4 in LGG group was significantly lower than that in the CON group. LGG inhibited the rise of TLR4 after TMZ in the LGG+TMZ group compared to the TMZ group.Conclusion: LGG inhibits the activation of the TLR4–NFκB pathway and alleviates intestinal mucosal inflammation induced by TMZ, thereby protect the jejunum villi and mucosal physical barrier.Keywords: Lactobacillus rhamnosus GG, temozolomide, intestinal mucosal injury, TLR4, NFκB

Ru Wen,1– 3,&ast; Peng Xu,3,&ast; Yimin Cai,1,&ast; Fang Wang,3 Mengfei Li,3 Xianchun Zeng,2 Chen Liu3 1Medical College, Guizhou University, Guizhou, 550000, People’s Republic of China; 2Department of Medical Imaging, Guizhou Provincial People Hospital, Guiyang City, Guizhou Province, 550000, People’s Republic of China; 3Department of Radiology, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, 400038, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chen Liu, Department of Radiology, Southwest Hospital, Army Medical University (Third Military Medical University), 30 Gao Tan Yan St, Chongqing, 400038, People’s Republic of China, Tel +8613108968808, Email liuchen@aifmri.com Xianchun Zeng, Department of Medical Imaging, Guizhou Provincial People Hospital, No. 83, East Zhongshan Road, Nanming District, Guiyang City, Guizhou Province, 550000, People’s Republic of China, Tel +8615286061024, Email zengxianchun04@foxmail.comPurpose: This study aimed to develop a deep learning model based on chest radiography (CXR) images and clinical data to accurately classify gram-positive and gram-negative bacterial pneumonia in children to guide the use of antibiotics.Methods: We retrospectively collected CXR images along with clinical information for gram-positive (n=447) and gram-negative (n=395) bacterial pneumonia in children from January 1, 2016, to June 30, 2021. Four types of machine learning models based on clinical data and six types of deep learning algorithm models based on image data were constructed, and multi-modal decision fusion was performed.Results: In the machine learning models, CatBoost, which only used clinical data, had the best performance; its area under the receiver operating characteristic curve (AUC) was significantly higher than that of the other models (P< 0.05). The incorporation of clinical information improved the performance of deep learning models that relied solely on image-based classification. Consequently, AUC and F1 increased by 5.6% and 10.2% on average, respectively. The best quality was achieved with ResNet101 (model accuracy: 0.75, recall rate: 0.84, AUC: 0.803, F1: 0.782).Conclusion: Our study established a pediatric bacterial pneumonia model that utilizes CXR and clinical data to accurately classify cases of gram-negative and gram-positive bacterial pneumonia. The results confirmed that the addition of image data to the convolutional neural network model significantly improved its performance. While the CatBoost-based classifier had greater advantages owing to a smaller dataset, the quality of the Resnet101 model trained using multi-modal data was comparable to that of the CatBoost model, even with a limited number of samples.Keywords: pediatrics, antibiotics, clinical data, X-ray, multi-modal data

Dahai Yu,1,2 Uchechukwu Levi Osuagwu,3,4 Karen Pickering,5 John Baker,5,6 Richard Cutfield,5,7 Zheng Wang,1 Yamei Cai,1,&ast; Brandon J Orr-Walker,5,6 Gerhard Sundborn,8 Zhanzheng Zhao,1,&ast; David Simmons1,3,4,&ast; 1Department of Nephrology, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, 450052, People’s Republic of China; 2Primary Care Centre Versus Arthritis, School of Medicine, Keele University, Keele, UK; 3Translational Health Research Institute (THRI), Western Sydney University, Sydney, NSW, Australia; 4School of Medicine, Western Sydney University, Sydney, NSW, Australia; 5Diabetes Foundation Aotearoa, Auckland, New Zealand; 6Department of Diabetes and Endocrinology, Counties Manukau Health, Auckland, New Zealand; 7Department of Diabetes and Endocrinology, Waitemata District Health Board, Auckland, New Zealand; 8Section of Pacific Health, The University of Auckland, Auckland, New Zealand&ast;These authors contributed equally to this workCorrespondence: David Simmons; Zhanzheng Zhao, Department of Nephrology, The First Affiliated Hospital Zhengzhou University, Zhengzhou, 450052, People’s Republic of China, Tel +61 2 4620 3899 ; +86 139 3852 5666, Fax +61 2 4620 3890 ; +86 371 6698 8753, Email Da.Simmons@westernsydney.edu.au; zhanzhengzhao@zzu.edu.cnPurpose: The study aimed to examine the separate population-level contributions of the ethnic and socioeconomic disparities among people with type 2 diabetes mellitus (T2DM) and residence in New Zealand (NZ).Patients and Methods: A prospective cohort enrolled T2DM patients from 01/01/1994 into the Diabetes Care Support Service, a primary care audit program in Auckland, NZ. The cohort was linked to national registry databases (socioeconomic status, pharmaceutical claim, hospitalization, and death registration). Each cohort member was followed up till death or the study end time (31/12/2019), whichever came first. Incident clinical events (stroke, myocardial infarction (MI), heart failure (HF), end-stage renal disease (ESRD), and premature mortality (PM)) were used as outcomes. The attributable fractions (AFs) were estimated for the whole population and for specific population with NZ Europeans (NZE) and/or least deprived population as reference, both unadjusted and with adjustment for covariables by Cox Regression models.Results: Among 36,267 patients, adjusted population AFs indicated 6.6(− 30.8– 33.3)% of PM, 17.1(5.8– 27.0)% of MI, 35.3(22.6– 46.0)% of stroke, 14.3(3.2– 24.2)% of HF, and 15.9(6.7– 24.2)% of ESRD could be attributed to deprivation; while 14.3(3.3– 25.4)% of PM, − 3.3(− 8.3– 1.5)% of MI, − 0.5(− 6.7– 5.3)% of stroke, 4.7(0.3– 8.8)% of HF, 13.3(9.9– 16.6)% of ESRD could be attributed to ethnicity. Deprivation contributed a significant AF to stroke, while ethnicity was important for ESRD. Gradient of AF for deprivation indicated NZE and Asians were most affected by deprivation across outcomes. Conversely, M&amacr;ori, with the highest AFs for ethnicity of PM and ESRD, were unaffected by deprivation. At same deprivations, the AFs of MI and stroke were greatest among NZE compared with other ethnic groups; the AF of ESRD was greatest among M&amacr;ori and Pasifika.Conclusion: Both socioeconomic deprivation and ethnicity are strongly associated with outcomes in patients with T2DM in NZ, although the extent of the deprivation gradient is greatest among NZE and Asians, and least among M&amacr;ori.Keywords: stroke, myocardial infarction, heart failure, end-stage renal disease, premature mortality, M&amacr;ori

Meng Li, Tingting Yan, Miaozhou Wang, Yanqiu Cai, Yingyuan Wei Graduate School of Qinghai University, Qinghai University, Xining, Qinghai Province, People’s Republic of ChinaCorrespondence: Miaozhou Wang, Email wangmiaozhou@163.comAbstract: Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer and is mainly treated with chemotherapy-based combination therapy. In recent years, with the increasing development of global precision medicine, single-cell sequencing (SCS) has become one of the most promising technologies in the field of biotechnology. Moreover, the related application of this technology in TNBC has been applied and developed. By using SCS to study the heterogeneity of TNBC tumor cells, metastasis, drug resistance mechanisms, mutations, and cloning; it can further guide clinical chemotherapy, targeted therapy, and immunotherapy. To further reflect the importance of SCS in TNBC, this paper elaborated on and summarized the research and application progress of SCS in TNBC.Keywords: TNBC, SCS, heterogeneity, drug resistance, metastasis

Qianting Yang, Jiao Xie, Yan Cai, Na Wang, Yan Wang, Li Zhang, Youjia Li, Jingjie Yu, Ya Li, Haitao Wang, Kanghuai Zhang Department of Pharmacy, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of ChinaCorrespondence: Kanghuai Zhang, Department of Pharmacy, The Second Affiliated Hospital of Xi’an Jiaotong University, No. 157 Xiwu Road, Xi’an, 710004, People’s Republic of China, Tel +86-29-87679282, Email zhangkanghuai12@163.comPurpose: To determine whether combinations of antifungal drugs are effective and safe for patients in intensive-care units.Methods: This study compared the efficacy and safety of caspofungin (CAS), voriconazole (VOR), amphotericin B liposome (L-AmB), CAS+VOR, and CAS+L-AmB as empirical, preemptive, and targeted therapies for invasive fungal infection (IFI).Results: Comparing the CAS, VOR, and CAS+VOR groups revealed that there were no differences in response rates between all therapy types, IFI-associated death within 90 days was less common in the CAS+VOR group (1.8%) than the VOR group (14.3%), and there were more adverse events in the VOR group than in the CAS group (P < 0.05). For empirical or preemptive therapy, the CAS group had a better response rate (80.0%) than the CAS+VOR group (47.1%), and there were more adverse events in the VOR group than in the CAS group (P < 0.05). For targeted therapy, no differences were found for efficacy and safety. There were no differences among the CAS, L-AmB, and CAS+L-AmB groups in efficacy and safety.Conclusion: Patients who received CAS monotherapy as an empirical or preemptive therapy could achieve good outcomes. Patients who received CAS+VOR or CAS+L-AmB achieved almost the same outcomes when compared with those who received CAS, VOR, and L-AmB monotherapy as targeted therapies, but those who received CAS+VOR had a lower IFI mortality rate than did those who received VOR monotherapy.Keywords: caspofungin, voriconazole, amphotericin B liposome, combination therapy, invasive fungal infection, intensive-care units

Ting Sun,1 Yijie Liu,2 Ying Cai,3 Tianshu Zhai,3 Yun Zhou,4 Bin Yang,5 Xiaojing Wu,3,&ast; Qingyuan Zhan1,3,&ast; 1Capital Medical University China-Japan Friendship School of Clinical Medicine, Beijing, People’s Republic of China; 2Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 3Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, National Center for Respiratory Medicine, China-Japan Friendship Hospital, Beijing, People’s Republic of China; 4Laboratory Medicine, China-Japan Friendship Hospital, Beijing, People’s Republic of China; 5Vision Medicals Center for Infection Diseases, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qingyuan Zhan, Capital Medical University China-Japan Friendship School of Clinical Medicine, No. 2 Yinghua East Road, Chaoyang District, Beijing, People’s Republic of China, Tel +86 13911785957, Fax +86 010-64217749, Email drzhanqy@163.com Xiaojing Wu, Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, National Center for Respiratory Medicine, China-Japan Friendship Hospital, No. 2 Yinghua East Road, Chaoyang District, Beijing, 100029, People’s Republic of China, Tel +86 13811743537, Fax +86 010-64217749, Email xpwxj@163.comPurpose: Plasma metagenomic next-generation sequencing (mNGS) has emerged as an attractive and minimally invasive technique for pathogen detection. However, few studies have demonstrated the need for simultaneous plasma and bronchoalveolar lavage fluid (BALF) mNGS in patients with severe pneumonia.Patients and Methods: This study retrospectively performed a paired comparison of BALF and plasma mNGS in critically ill patients with suspected severe pneumonia from April 2019 to December 2020. The diagnostic performance of BALF and plasma mNGS was compared using the clinical composite diagnosis as the reference standard.Results: In total, 57 patients were included in this study. Patients with positive plasma mNGS had shorter hospital stay days at the time of specimen acquisition (4.5 vs 11, P = 0.028) and a higher positivity rate of BALF culture (50% vs 22.9%, P = 0.033) than patients with negative plasma mNGS. Fifty-three patients (93%) were finally diagnosed with severe pneumonia. Significant differences were observed in the sensitivity of BALF and plasma mNGS (100% vs 42%, P < 0.001), and the diagnostic accuracy was 96% and 46%, respectively. The proportion of virus in positive plasma mNGS results was higher than that in BALF mNGS (23% vs 11%, P = 0.173) without significant difference. Although plasma mNGS detected additional microorganisms in 11/53 patients, the beneficial effect was observed in only 5/53 (9%) patients.Conclusion: In this study, the clinical effect of simultaneously conducting mNGS of BALF and plasma samples was found to be limited. For patients with the suspected virus infection, plasma mNGS may be a supplementary test. Further studies are needed to identify the optimal indications for plasma mNGS.Keywords: mNGS, infection, cell-free DNA, diagnosis, pathogen

Yimin Cai,1,&ast; Zhoumin Shen,1,&ast; Bifang Zhou,2 Xiali Zheng,3 Yulian Li,2 Yuming Liu,3 Jiayu Yang,3 Nian Xie,4 Hongjiao Chen4 1Department of Nursing, Hunan Provincial People’s Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, 410005, People’s Republic of China; 2Department of Interventional Vascular Surgery, Hunan Provincial People’s Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, Hunan, 410005, People’s Republic of China; 3Department of Pediatrics, Hunan Provincial People’s Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, Hunan, 410005, People’s Republic of China; 4Department of Nursing, Medical School, Medical College of Hunan Normal University, Changsha, Hunan, 410013, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bifang Zhou, Department of Interventional Vascular Surgery, Hunan Provincial People’s Hospital (The First Affiliated Hospital of Hunan Normal University), No. 61 of Jiefang West Road, Furong District, Changsha, 410005, People’s Republic of China, Tel +86-13755027990, Fax +86-0731-82278012, Email yul_2021@21cn.comObjective: To investigate the psychological status of women during their second pregnancy.Methods: A total of 162 women who were pregnant for the second time were selected as the research subjects. The general demographic data and pregnancy-related conditions of the subjects were investigated by a questionnaire developed for this study. The anxiety and depression of the subjects were evaluated with a self-rating anxiety scale (SAS) and a self-rating depression scale (SDS).Results: The subjects scored themselves on the SAS and on the SDS. There was a statistically significant difference when comparing the scores and total scores with the domestic norm. Statistical data analysis was conducted using SPSS 19.0 software. The results of a multi-factor logistics regression analysis showed that four factors, namely a low age, low education level, low monthly household income and foetal sex expectations, were the main influencing factors for the occurrence of anxiety among women during their second pregnancies (p < 0.05). Three factors, namely a low education level, low monthly household income and a poor relationship between the husband and wife, were the main influencing factors for the occurrence of depression among the subjects (p < 0.05).Conclusion: During their second pregnancies, women have different degrees of anxiety and depression. Measures should be taken to intervene and guide women who develop these adverse emotions.Keywords: second child, psychological condition, anxiety, depression, influencing factors

Qingen Da,1,2,&ast; Mingming Ren,2,&ast; Lei Huang,2 Jianhua Qu,1 Qiuhua Yang,3 Jiean Xu,4 Qian Ma,4 Xiaoxiao Mao,4 Yongfeng Cai,4 Dingwei Zhao,4 Junhua Luo,5 Zilong Yan,1 Lu Sun,2 Kunfu Ouyang,2 Xiaowei Zhang,6 Zhen Han,2 Jikui Liu,1 Tao Wang2 1Department of Hepatobiliary Surgery, Peking University Shenzhen Hospital, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, People’s Republic of China; 2Department of Cardiovascular Surgery, Peking University Shenzhen Hospital, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, People’s Republic of China; 3Vascular Biology Center, Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, GA, USA; 4Shenzhen Graduate School, Peking University, Shenzhen, People’s Republic of China; 5Department of Urological Surgery, Peking University Shenzhen Hospital, Shenzhen, People’s Republic of China; 6School of Basic Medical Sciences, Peking University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jikui Liu, Department of Hepatobiliary Surgery, Peking University Shenzhen Hospital, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, People’s Republic of China, Email liu8929@126.com Tao Wang, Department of Cardiovascular Surgery, Peking University Shenzhen Hospital, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, People’s Republic of China, Email szwangtao@126.comObjective: We aimed to explore the prognostic patterns of ferroptosis-related genes in papillary renal cell carcinoma (PRCC) and investigate the relationship between ferroptosis-related genes and PRCC tumor immune microenvironment.Methods: We obtained the mRNA expression and corresponding clinical data of PRCC from the public tumor cancer genome atlas database (TCGA). The PRCC patients were randomly divided into two cohort, training cohort and verification cohort, respectively. Univariate Cox regression, LASSO Cox regression, multivariate Cox regression analysis were utilized to construct ferroptosis signature for PRCC patients. And then, risk prognostic model was established and verified. The correlation of ferroptosis-related signature with survival and immune microenvironment was systematically analyzed.Results: A 4-genes ferroptosis signature (CDKN1A, MIOX, PSAT1, and RRM2) was constructed. Multivariate Cox regression assay indicates that the risk score of ferroptosis signature was an independent prognostic indicator (HR=1.391, p< 0.001). The survival curve shows that the high-risk group has a poorer prognosis than the low-risk group (p< 0.001). The risk prognostic model was established based on prognostic factors of clinical-stage, hemoglobin, and risk score. The time-dependent receiver operating characteristic curve (ROC) analysis proves the predictive capacity of the ferroptosis signature, the 3 years area under the curve (AUC) is 0.890, and the 5 years AUC is 0.733. Further analysis suggested that cell cycle, pentose phosphate pathway, P53 signaling pathway were significantly enriched in the high-risk group. The significantly different fractions of dendritic cells resting, macrophage cells, and T cells follicular helper were observed in risk groups.Conclusion: This study implicates a ferroptosis signature which has a good predict capacity of the prognosis in PRCC patients. Ferroptosis-related genes may have a key role in the process of anti-tumor and serve as therapeutic targets for PRCC.Keywords: papillary renal cell carcinoma, ferroptosis, gene signature, prognosis model, tumor immune microenvironment

Chunting Liang &ast;, Tongtong Huang &ast;, Xiaofeng Zhang, Huaqing Rao, Zhiru Jin, Xiaoxiong Pan, Jingtao Li, Yingying Mo, Yongzhi Cai, Ji Wu Department of Ultrasonic Medicine, The First Hospital Affiliated to Guangxi Medical University, Nanning, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ji Wu, Department of Ultrasonic Medicine, The First Hospital Affiliated to Guangxi Medical University, Nanning, 530021, People’s Republic of China, Email gxnnwuji@126.comPurpose: To study the thrombolytic effect and safety of cRGD urokinase liposomes (cRGD-UK-LIP) in rats with acute pulmonary microthromboembolism (APMTE), and explore the application value of echocardiography (ECHO) in animal models.Patients and Methods: Ninety-six SD rats were randomized into 6 groups (16/group): normal control, sham operation, APMTE, normal saline (NS), free urokinase (UK), cRGD-UK-LIP. Four groups (APMTE, NS, UK, cRGD-UK-LIP) of rats were injected with autologous thrombus to induce APMTE. Samples were injected into 3 groups (NS, UK, cRGD-UK-LIP) of rats after modeling. Echocardiography was used to assess right ventricle (RV) function and morphology in rats. Six rats in each group were randomly selected and pulmonary artery pressure (PAP) of them was measured through ECHO-guided transthoracic puncture. Finally, the rats were killed and their tissues were taken for pathological examination.Results: Compared with normal control or sham operation group, rats in APMTE group had enlarged RV, decreased RV function, increased PAP, and lung tissue of them showed postthromboembolic appearance. There was no significant difference between NS group and APMTE group. RV morphology and function of rats in the UK group and cRGD-UK-LIP group were better and vessels with residual thrombus in these 2 groups were less than APMTE group, especially in the cRGD-UK-LIP group. In terms of PAP, only cRGD-UK-LIP group was significantly lower than APMTE group. No hyperemia, bleeding and swelling were observed in heart, liver and kidney of rats in each group.Conclusion: A rat model of APMTE was successfully established. cRGD-UK-LIP has better thrombolytic effect than free urokinase and it is safe. Echocardiography is not merely an important way to evaluate the morphology and function of RV, transthoracic puncture measurement under the guidance of it can be an effective way to monitor PAP in animal models.Keywords: cRGD urokinase liposomes, acute pulmonary microthromboembolism, targeted thrombolysis, right ventricle, echocardiography, pulmonary artery pressure

Chen Pan,1 Honghong Wang,2 Minzhen Chen,3 Yu Cai,1 Peihuan Li,4 Changgen Xiao,5 Qiuping Tang,1 Deborah Koniak-Griffin6 1Department of Clinical Psychology, The Third Xiangya Hospital of Central South University, Changsha, People’s Republic of China; 2Department of Fundamental Nursing, Xiangya School of Nursing, Central South University, Changsha, People’s Republic of China; 3Department of AIDS, The First Hospital of Changsha, Changsha, People’s Republic of China; 4College of Resources of Environment, Hunan Agricultural University, Changsha, People’s Republic of China; 5Department of Applied Psychology, Hunan University of Chinese Medicine, Changsha, People’s Republic of China; 6School of Nursing, University of California Los Angeles, Los Angeles, CA, USACorrespondence: Qiuping Tang, Department of Clinical Psychology, The Third Xiangya Hospital of Central South University, Changsha, People’s Republic of China, Tel +86 731 88618567, Email tt96@sina.comBackground/Purpose: Nurses engaged in the care of people living with HIV (PLWH) are commonly exposed to workplace stress. This study aimed to explore the stress experiences and coping strategies among nurses taking care of PLWH in China.Methods: Nurses were recruited from the AIDS department of a public, general, third-grade class-A hospital, which has the largest HIV care department in the Hunan Province of China. Thirty-three nurses working in the AIDS Department were recruited in this qualitative study. Eight nurses participated in a focus group and 25 nurses underwent in-depth individual interviews aimed at characterizing the nurse’s feelings and struggles with stress during caregiving for PLWH. The interviews were audio-recorded, transcribed verbatim, anonymized, and imported into NVivo 8.0 software. The data were coded and subjected to thematic analysis.Results: Concerns about occupational exposure, heavy workload, mental health problems and risk behaviors of patients, and discrimination towards nurses caring for PLWH were the four main sources of stress. The negative impact of stress included problems with emotion regulation, somatic health and sleep, and work performance. Some participants also reported a positive impact of work stress on their mental health. Using personality strengths, problem-solving, help-seeking, concealing and avoiding/suppression were common coping strategies employed by nurses caring for PLWH.Conclusion: Our findings help characterize the stress experienced by nurses caring for PLWH in the Chinese cultural context, and may inform specific interventions to help manage stress and promote mental health of nurses.Keywords: HIV, nurses, stress, job burnout, coping

Yajun Mao,1,2 Biyao Xie,2 Baixin Chen,1,2 Yilin Cai,2 Jiahan Wu,2 Jiansheng Zhang,1 Ruifan Shao,1 Yun Li1,2 1Department of Sleep Medicine, Shantou University Mental Health Center, Shantou University Medical College, Shantou, Guangdong Province, People’s Republic of China; 2Sleep Medicine Center, Shantou University Medical College, Shantou, Guangdong Province, People’s Republic of ChinaCorrespondence: Yun Li, Email s_liyun@stu.edu.cnObjective: We aimed to examine the effects of sleep quality on the association between pre-bedtime electronic screen media use for entertainment and academic performance among college students. We hypothesized that sleep quality mediates the association between pre-bedtime electronic screen media entertainment use and academic performance among college students.Methods: This was a cross-sectional survey with 1385 participants (age 19.99 ± 1.4 years [range, 17– 24 years] and 36.82% males) conducted at Shantou University. The levels of academic performance were based on self-reported academic class ranking from average grades of their last final major examinations. Poor sleep quality was defined as a total score of the Pittsburgh Sleep Quality Index > 7. The pre-bedtime prolonged electronic screen media use for entertainment (PESM-E) was defined as the use of electronic screen media for entertainment longer than 60 minutes/night after 10:00 p.m. during the past 6 months.Results: College students with pre-bedtime PESM-E were 1.28-fold more likely to have a poor academic performance than those who used electronic screen media less than 60 minutes (95% confidence interval [CI]: 1.04– 1.57, P=0.020). Furthermore, pre-bedtime PESM-E was significantly associated with poor sleep quality (adjusted odds ratio [AOR]=1.87, 95% CI: 1.27– 2.74, P=0.001) after controlling for confounders. Mediation model showed that poor sleep quality accounted for 53.08% of the effect of pre-bedtime PESM-E on lower levels of academic performance (Sobel Z=2.04, P=0.041).Conclusion: Pre-bedtime PESM-E is associated with poor academic performance in college students, and this association is mediated by poor sleep quality. Our findings highlight the importance of limiting the use of electronic screen media before bedtime in college students.Keywords: poor sleep quality, sleep, academic performance, electronic screen use, college students

Lingling Liu,1 Jin Wang,1 Huan Zhang,1 Mengli Chen,2 Yun Cai1 1Center of Medicine Clinical Research, Department of Pharmacy, Medical Supplies Center, PLA General Hospital, Beijing, People’s Republic of China; 2Department of Pharmacy, Medical Supplies Center, PLA General Hospital, Beijing, People’s Republic of ChinaCorrespondence: Yun CaiCenter of Medicine Clinical Research, Department of Pharmacy, Medical Supplies Center, PLA General Hospital, 28 Fu Xing Road, Beijing, 100853, People’s Republic of ChinaTel +86-10-6693-7166Email caicai_hh@126.comMengli ChenDepartment of Pharmacy, Medical Supplies Center, PLA General Hospital, 28 Fu Xing Road, Beijing, 100853, People’s Republic of ChinaTel +86-10-6693-9610Email helloLily301cn@126.comAbstract: As a heterogeneous and wide inflammation, osteoarticular infection (OAI) shows an increasing incidence in recent years. Staphylococcus aureus is the most important pathogen causing OAI. The antibiotic treatment will affect the outcomes of OAI patients, and the drug selection and dosage regimen highly rely on patients’ variability, pathogen susceptibility, and drug property like bone permeability. Model-informed precision dosing (MIPD) provides options to describe and quantify the pharmacokinetic (PK) variability of the OAI population using different models, such as the population pharmacokinetic (PPK) model and physiological-based pharmacokinetic (PB/PK) model. In the present review, we highlighted that the MIPD of antibiotics played a critical role in OAI and listed the dose regimen recommended by the model. Collectively, our current study provided a valuable reference for the treatment of patients and improved the safety and efficiency of drug use.Keywords: osteoarticular infection, antibiotic, PPK, PBPK, dose