Search

Panpan Xu,1,* Di Zhang,2,* Wanqing Zhuo,3 Lin Zhou,4 Yue Du,2 Peipei Zhang,1 Lijuan Ma,4 Yajuan Wang2 1Children’s Hospital Capital Institute of Pediatrics, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 2Department of Neonatology, Children’s Hospital, Capital Institute of Pediatrics, Beijing, People’s Republic of China; 3School of Life Sciences, Peking University, Beijing, People’s Republic of China; 4Department of Clinical Laboratory, Children’s Hospital Affiliated to Capital Institute of Pediatrics, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lijuan Ma; Yajuan Wang, Children’s Hospital Affiliated to Capital Institute of Pediatrics, 2 Yabao Road, Chaoyang District, Beijing, 100020, People’s Republic of China, Email malijuan@shouer.com.cn; cxswyj@vip.sina.comPurpose: Klebsiella michiganensis is an opportunistic pathogen that causes an increasing number of serious infections. This study aimed to investigate the etiology of the severe clinical symptoms of sepsis in preterm infants and the characterization of K. michiganensis isolates.Patients and Methods: Whole-genome sequencing (WGS) was performed on three strains isolated from an infected preterm infant. Additionally, the genomic sequences of 534 K. michiganensis strains were obtained from the NCBI database. To gain deeper insights into these strains, we utilized the Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Clusters of Orthologous Groups (COG), and Pathogen Host Interactions (PHI) database annotation tools for comprehensive gene function analyses. Moreover, the multilocus sequence typing (MLST), EasyCGtree, and virulence factor database (VFDB) were employed to determine the sequence types (STs), construct phylogenetic trees, and identify potential virulence factors.Results: Sequence analysis found that the three isolated strains had identical sequence characteristics and did not correspond to any of the known ST types. Virulence factor analysis revealed that the three strains harbored mrkABCDFHIJ, fimABCDEFGHIK, entABCDEFS, fepABCD, and capsule genes. These virulence factors are likely to play crucial roles in enhancing adhesion and metabolic capabilities, resisting phagocytosis (inducing immune cell damage), and ultimately contributing to prolonged bacteremia. The phylogenetic tree and comparative genomics of virulence factors showed the genetic and virulence factor diversity of the currently reported K. michiganensis strains.Conclusion: We identified a novel strain of K. michiganensis that exhibits high virulence and leads to severe septicemia phenotypes in preterm infants. Furthermore, comparative genomic analysis of previously reported K. michiganensis strains revealed the existence of three clades. This comprehensive analysis provides novel insights into the genetic relationships and virulence factor profiles of diverse strains of K. michiganensis. In future, it will be necessary to investigate the concept of the high virulence of K. michiganensis to determine the treatment method.Keywords: Klebsiella michiganensis, whole-genome sequencing, preterm infant, sepsis

Song Wen,1,&ast; Dongxiang Xu,1,&ast; Yue Yuan,1,&ast; Zhimin Xu,1 Yanyan Li,1 Min Gong,1 Xinlu Yuan,1 Ligang Zhou1,2 1Department of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai, 201399, People’s Republic of China; 2Shanghai Key Laboratory of Vascular Lesions Regulation and Remodeling, Shanghai Pudong Hospital, Shanghai, 201399, People’s Republic of China&ast;These authors contributed equally in this workCorrespondence: Ligang Zhou, Department of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai, 201399, People’s Republic of China, Tel +008613611927616, Email zhouligang1n1@163.comObjective: Serum tumor markers have been discovered to be elevated in individuals with diabetes mellitus (DM); however, their significance in diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemia (HHS) is unknown. We evaluated these indicators in the patients with DKA and HHS.Materials and Methods: We retrospectively collected the laboratory data of 565 diabetic patients from Shanghai Pudong Hospital between Jan, 2019 and May, 2023, including 300 patients with type 2 diabetes mellitus (T2DM), 206 with DKA, and 59 with HHS. Serum tumor biomarkers and further clinical laboratory tests were compared among the three groups. Patients with conspicuous tumor evidence were excluded from the study.Results: We found significantly higher levels of carbohydrate antigen 199 (CA199) in DKA (p< 0.01), carcinoembryonic antigen (CEA), complex prostate specific antigen (CPSA) (p< 0.01), prostate specific antigen (PSA) (p< 0.05) in HHS, as well as the plasma lipid profile, iron, and electrolytes, in addition to decreased thyroid function, hepatic and renal function, and cardiac function (p< 0.05). A Spearman correlational study revealed that osmolar levels were significantly positively correlated with myoglobin (MYO) and cardiac troponin I (cTNI), whereas serum iron concentration (r=0.520) was positively correlated with CEA levels in HHS. pH was negatively correlated with CA199 (r=− 0.195), while HbA1c (r=0.22), globin (r=0.341), and total cholesterol (TC) (r=0.191) were positively correlated with elevated CA199 levels. Moreover, the multilinear regression investigation identified osmolarity as a significant determinant for CEA, as well as other parameters, and all proved to be proper predictors for CEA in HHS via ROC curve establishment.Conclusion: Elevated CA199 levels in DKA were associated with acidosis, whereas HHS with elevated CEA levels may be related to iron homeostasis and could be predicted via the osmolar degree and other predictors.Keywords: diabetes mellitus, diabetic ketoacidosis, hyperosmolar hyperglycemic state, tumor markers, osmolar, iron homeostasis

Lihong Zhou,1 Yan Yong,1 Hao Li,2 Qin Hu1 1Zhejiang Tuberculosis Diagnosis and Treatment Center, Zhejiang Chinese and Western Medicine Integrated Hospital, Hangzhou, Zhejiang, People’s Republic of China; 2Tuberculosis Laboratory, Zhejiang Chinese and Western Medicine Integrated Hospital, Hangzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Qin Hu, Zhejiang Tuberculosis Diagnosis and Treatment Center, Zhejiang Chinese and Western Medicine Integrated Hospital, Hangzhou, Zhejiang, People’s Republic of China, Tel +86-13968146922, Fax +86-571-56109821, Email qinhu19832023@163.comPurpose: The diagnosis of tuberculosis located in the peripheral zone remains challenging and requires ultrasound bronchoscopy-guided maneuvers. We assessed the precision of CapitalBioTM Mycobacterium nucleic acid detection test (CapitalBio MTB test) and Mycobacterium tuberculosis isothermal RNA amplification test (MTB-RNA) using endobronchial ultrasonography with a guide sheath (EBUS-GS) for peripheral pulmonary tuberculosis (PTB) and compared it with those of acid-fast bacilli (AFB) smear and MTB culture tests.Patients and Methods: This retrospective analysis included 287 patients suspected of peripheral pulmonary tuberculosis who underwent EBUS-GS examinations, medical examination results of AFB smears, MTB culture, CapitalBio MTB test, and MTB-RNA were analyzed. We evaluated the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the receiver operating characteristic curve (AUC), and its diagnostic accuracy for peripheral PTB was evaluated in comparison with the final clinical diagnosis.Results: The overall sensitivity, specificity, PPV, NPV, and AUC of CapitalBio MTB test were 44.83%, 100.00%, 100.00%, 54.07%, and 0.72, respectively; those of MTB-RNA were 22.99%, 100.00%, 100.00%, 45.75%, and 0.61, respectively, and those for parallel test (CapitalBio MTB test or MTB-RNA) were 46.55%, 100.00%, 100.00%, 54.85%, and 0.73, respectively. These values for AFB smear were 9.2%, 97.35%, 84.21%, 41.04%, and 0.53, respectively, and those of MTB culture were 31.03%, 100.00%, 100.00%, 48.50%, and 0.69, respectively.Conclusion: The CapitalBio MTB test showed the best diagnostic performance compared with AFB smear, MTB culture, and MTB-RNA assays and was similar to the parallel test (CapitalBio MTB test or MTB-RNA). The CapitalBio MTB test combined with EBUS-GS had satisfactory diagnostic accuracy for diagnosing peripheral PTB.Keywords: sensitivity, specificity, receiver operating characteristic curve, endobronchial ultrasonography, polymerase chain reaction, nucleic acid molecular testing

Chaoying Jin,1,2,&ast; Ruolin Zhao,3,4,&ast; Weihang Hu,5 Xiaolong Wu,4 Li Zhou,6 Letian Shan,4,6 Huiling Wu1,2 1Department of Plastic and Aesthetic Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310003, People’s Republic of China; 2School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310020, People’s Republic of China; 3Yichen Biotechnology Co., Ltd, Hangzhou, Zhejiang, 311200, People’s Republic of China; 4Fuyang Academy, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 311403, People’s Republic of China; 5Department of Critical Care Medicine, Zhejiang Hospital, Hangzhou, Zhejiang, 310013, People’s Republic of China; 6The First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310060, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Letian Shan; Huiling Wu, Email letian.shan@zcmu.edu.cn; zywhl@zju.edu.cnBackground: Pressure ulcer is common in the bedridden elderly with high mortality and lack of effective treatment. In this study, human-adipose-derived-stem-cells-hyaluronic acid gel (hADSCs-HA gel) was developed and applied topically to treat pressure ulcers, of which efficacy and paracrine mechanisms were investigated through in vivo and in vitro experiments.Methods: Pressure ulcers were established on the backs of C57BL/6 mice and treated topically with hADSCs-HA gel, hADSCs, hyaluronic acid, and normal saline respectively. The rate of wound closure was observed continuously during the following 14 days and the wound samples were obtained for Western blot, histopathology, immunohistochemistry, and proteomic analysis. Human dermal fibroblasts (HDFs) and human venous endothelial cells (HUVECs) under normal or hypoxic conditions were treated with conditioned medium of human ADSCs (ADSC-CM), then CCK-8, scratch test, tube formation, and Western blot were conducted to evaluate the paracrine effects of hADSCs and to explore the underlying mechanism.Results: The in vivo data demonstrated that hADSCs-HA gel significantly accelerated the healing of pressure ulcers by enhancing collagen expression, angiogenesis, and skin proliferation. The in vitro data revealed that hADSCs strengthened the proliferation and wound healing capabilities of HDFs and HUVECs, meanwhile promoted collagen secretion and tube formation through paracrine mode. ADSC-CM was also proved to exert protective effects on hypoxic HDFs and HUVECs. Besides, the results of proteomic analysis and Western blot elucidated that lipid metabolism and PPARβ/δ pathway mediated the healing effect of hADSCs-HA gel on pressure ulcers.Conclusion: Our research showed that topical application of hADSCs-HA gel played an important role in dermal regeneration and angiogenesis. Therefore, hADSCs-HA gel exhibited the potential as a novel stem-cell-based therapeutic strategy of treating pressure ulcers in clinical practices. Keywords: pressure ulcer, wound healing, human adipose derived stem cell, hydrogel, PPARβ/δ, lipid metabolism, skin regeneration

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

Jianzhong Li,1,&ast; Yan Xiong,2,&ast; Mingyu Chen,1,&ast; Deyu Xu,1 Ling Zhou,1 Lei Shen,1 Guoyuan Lu1 1Department of Nephrology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215006, People’s Republic of China; 2Department of Nephrology, Kunshan First People’s Hospital Affiliated to Jiangsu University, Kunshan, Jiangsu, 215300, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianzhong Li; Guoyuan Lu, Department of Nephrology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215006, People’s Republic of China, Email lijianzhong1511@suda.edu.cn; sdfyylgy@163.comPurpose: A major limitation of long-term peritoneal dialysis (PD) is peritoneal membrane dysfunction characterized by faster peritoneal solute-transport rate (PSTR). This study aimed to identify efficient complement factors in peritoneal effluents of continuous ambulatory peritoneal dialysis (CAPD) patients that can predict the PSTR.Methods: A multiplex suspension protein array was used to screened related complement pathways in overnight peritoneal effluents among 58 CAPD patients. Then the related complement factors in lectin and classical pathways in effluents were analyzed using ELISA kits among another cohort of 129 CAPD patients. Logistic regression modeling was fitted to predict the PSTR of PD patients.Results: The multiplex suspension protein array showed complement factors including C2, C4b, C5, C5a, Factor D, Factor I, and MBL were detected in effluents of CAPD patients, and the effluent C2 Appearance rate (Ar) and C4b Ar levels were significantly correlated with D/P Cr and D/D0 glucose. The levels of effluents MASP-1 Ar, M-Ficolin Ar, C2 Ar and C4b Ar, which belong to the lectin pathway were also positively correlated with D/P Cr according the ELISA results and these parameters were expressed higher in the high and high-average (H/HA) groups according to the PET results. Moreover, effluent Masp-1 was independently associated with increased PSTR and adverse events related peritoneal transport function failure.Conclusion: This study suggested that the lectin pathway may be involved in local complement activation and peritoneal injury of PD patients, intraperitoneal level of Masp-1 was an independent predictor of increased PSTR in PD patients.Keywords: peritoneal dialysis, complement, lectin pathway, Masp-1, peritoneal solute-transport rate

Chenglin Xu,1,&ast; Song Wen,1,2,&ast; Zhimin Xu,1,&ast; Meiyuan Dong,1,3 Yue Yuan,1 Yanyan Li,1 Ligang Zhou1– 4 1Department of Endocrinology, Shanghai Pudong Hospital, Fudan University, Pudong Medical Center, Shanghai 201399, People’s Republic of China; 2Fudan Zhangjiang Institute, Fudan University, Shanghai 201203, People’s Republic of China; 3Hebei Medical University, Shijiazhuang 050013, People’s Republic of China; 4Shanghai Key Laboratory of Vascular Lesions Regulation and Remodeling, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, People’s Republic of China&ast;These authors contributed equally to this paperCorrespondence: Ligang Zhou, Department of Endocrinology, Shanghai Pudong Hospital, Fudan University, Pudong Medical Center, Shanghai, 201399, People’s Republic of China, Tel +8613611927616, Email zhouligang1n1@163.comObjectives: To investigate the variation in bone turnover biomarkers among patients with type 2 diabetes (T2D) and low triiodothyronine levels (Low T3 syndrome).Materials and Methods: This retrospective analytic study included 418 inpatient records from Shanghai Pudong Hospital covering the years 2021 to 2023. Laboratory data related to metabolic and bone turnover biomarkers in patients were analyzed with T2D and the low T3 syndrome.Results: The results indicated that patients with reduced serum T3 levels exhibited statistically significant variations in thyroid function, age, fasting plasma glucose (FPG), glycated hemoglobin A1c (HbA1c), and the proportion of medication history associated with diabetes in comparison to euthyroid patients. In addition to parathyroid hormones, bone turnover biomarkers including N-terminal middle molecular fragment of osteocalcin (NMID), plasma calcium (Ca2+), β C-terminal cross-linking telopeptide of type 1 collagen (β-CTX), and 25-hydroxyvitamin D3 (25 OH VitD3) exhibited significant changes in patients with decreased T3 levels. Evident irregularities were observed in patients with a decreased T3 level, including elevated serum creatinine (SCr), decreased concentrations of albumin and total protein, and a decreased estimated glomerular filtration rate (eGFR), as assessed through hepatic and renal testing, respectively. Significant associations between bone turnover biomarkers and the subsequent variables (gender, adiposity, hepatic, renal, and thyroid function) were revealed through the correlational analysis. Further investigation utilized multivariate linear regression to determine that, in addition to thyroid function, several other factors such as age, gender, bodyweight, pancreatic, hepatic, and renal function, affected the variability in bone turnover biomarkers among patients demonstrating a low serum T3 level.Conclusions: This comparative study demonstrated that despite age, gender, bodyweight, hepatic, renal function, thyroid hormone and pancreatic function were significant factors associated with bone metabolism in patients with T2D and Low T3 syndrome, which may increase the risk of osteoporosis.Keywords: type 2 diabetes, low T3, bone turnover biomarker, NMID, β-CTX

Lining Zhou,1,&ast; Hong Hong,2,&ast; Fuying Chu,1 Xiang Chen,1 Chenlu Wang1 1Department of Clinical Laboratory, The Second Affiliated Hospital of Nantong University and Nantong City No.1 People’s Hospital, Nantong, People’s Republic of China; 2Department of Clinical Laboratory, Nantong Traditional Chinese Medicine Hospital, Nantong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chenlu Wang; Xiang Chen, Email wangchenlu0101@163.com; ntchenx0520@163.comBackground: Recurrence is the main factor for poor prognosis in ovarian cancer, but few prognostic biomarkers were reported. In this study, we used machine learning methods based on multiple biomarkers to develop a specific prediction model for the recurrence of ovarian cancer.Methods: A total of 277 ovarian cancer patients were enrolled in this study and randomly classified into training and testing cohorts. The prediction information was obtained through 47 clinical parameters using six supervised clustering machine learning algorithms, including K-Nearest Neighbor (K-NN), Decision Tree (DT), Random Forest (RF), Adaptive Boosting (AdaBoost), Gradient Boosting Machine (GBM), and Extreme Gradient Boosting (XGBoost).Results: In predicting the recurrence of ovarian cancer, machine learning algorithm was superior to conventional logistic regression analysis. In this study, XGBoost showed the best performance in predicting the recurrence of ovarian cancer, with an accuracy of 0.95. In addition, neoadjuvant chemotherapy, Monocyte ratio (MONO%), Hematocrit (HCT), Prealbumin (PAB), Aspartate aminotransferase (AST), and carbohydrate antigen 125 (CA125) are the most important biomarkers to predict the recurrence of ovarian cancer.Conclusion: The machine learning techniques can achieve a more accurate assessment of the recurrence of ovarian cancer, which can help clinicians make decisions, and develop personalized treatment strategies.Keywords: ovarian cancer, recurrence, machine learning, biomarkers, predictive modeling

Haiyan Zhang,1,&ast; Chaoying Jin,2,&ast; Jiaqing Hua,3,&ast; Zuxiang Chen,4 Wenxin Gao,4 Wenting Xu,4 Li Zhou,4 Letian Shan1 1The Second Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 2School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China; 3College of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 4The First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Letian Shan; Li Zhou, Email letian.shan@zcmu.edu.cn; zhouli@zcmu.edu.cnAbstract: Osteoarthritis (OA) induced microenvironmental alterations are a common and unavoidable phenomenon that greatly exacerbate the pathologic process of OA. Imbalances in the synthesis and degradation of cartilage extracellular matrix (ECM) have been reported to be associated with an adverse microenvironment. Stem cell therapy is a promising treatment for OA, and mesenchymal stem cells (MSCs) are the main cell sources for this therapy. With multispectral differentiation and immunomodulation, MSCs can effectively regulate the microenvironment of articular cartilage, ameliorate inflammation, promote regeneration of damaged cartilage, and ultimately alleviate OA symptoms. However, the efficacy of MSCs in the treatment of OA is greatly influenced by articular cavity microenvironments. This article reviews the five microenvironments of OA articular cavity, including inflammatory microenvironment, senescence microenvironment, hypoxic microenvironment, high glucose microenvironment and high lipid environment, focus on the positive and negative effects of OA microenvironments on the fate of MSCs. In this regard, we emphasize the mechanisms of the current use of MSCs in OA treatment, as well as its limitations and challenges.Keywords: microenvironment, mesenchymal stem cells, osteoarthritis

Xiang Zhang,1,&ast; Yu Zhou,2,3,&ast; Lu Fu,4,&ast; Lu Zhou,5 Xiangjun Cheng,6 Wei Zhang,2,3 Zhongming Tan5 1Department of Infection Management, The First Affiliated Hospital with Nanjing Medical University, Jiangsu Province Hospital, Nanjing, Jiangsu Province, People’s Republic of China; 2Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, Jiangsu Province, People’s Republic of China; 3Sanya Institute of Nanjing Agricultural University, Sanya, Hainan Province, People’s Republic of China; 4Department of Nosocomial Infection Management, Affiliated Maternity and Child Health Care Hospital of Nantong University, Nantong, Jiangsu Province, People’s Republic of China; 5NHC Key Laboratory of Enteric Pathogenic Microbiology, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, Jiangsu Province, People’s Republic of China; 6Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, Jiangsu Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhongming Tan, NHC Key Laboratory of Enteric Pathogenic Microbiology, Jiangsu Provincial Center for Disease Control and Prevention, No. 172 Jiangsu Road, Gulou District, Nanjing, Jiangsu Province, 210009, People’s Republic of China, Tel +862583759339, Email jstzm@jscdc.cn Wei Zhang, Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Nanjing Agricultural University, No. 1 Tongwei Road, Nanjing, Jiangsu Province, 210095, People’s Republic of China, Tel +862584396517, Email vszw@njau.edu.cnPurpose: Staphylococcus warneri is an opportunistic pathogen responsible for hospital-acquired infections (HAIs). The aim of this study was to describe an outbreak caused by S. warneri infection in a neonatal intensive care unit (NICU) and provide investigation, prevention and control strategies for this outbreak.Methods: We conducted an epidemiological investigation of the NICU S. warneri outbreak, involving seven neonates, staff, and environmental screening, to identify the source of infection. WGS analyses were performed on S. warneri isolates, including species identification, core genome single-nucleotide polymorphism (cgSNP) analysis, pan-genome analysis, and genetic characterization assessment of the prevalence of specific antibiotic resistance and virulence genes.Results: Eight S. warneri strains were isolated from this outbreak, with seven from neonates and one from environment. Six clinical cases within three days in 2021 were linked to one strain isolated from environmental samples; isolates varied by 0– 69 SNPs and were confirmed to be from an outbreak through WGS. Multiple infection prevention measures were implemented, including comprehensive environmental disinfection and stringent protocols, and all affected neonates were transferred to the isolation wards. Following these interventions, no further cases of S. warneri infections were observed. Furthermore, pan-genome analysis results suggested that in human S. warneri may exhibit host specificity.Conclusion: The investigation has revealed that the outbreak was linked to the milk preparation workbench by the WGS. It is recommended that there be a stronger focus on environmental disinfection management in order to raise awareness, improve identification, and prevention of healthcare-associated infections that are associated with the hospital environment.Keywords: Staphylococcus warneri, neonatal intensive care unit, whole-genome sequencing, pan-genome

Mengyi Shen,1,&ast; Leyu Zhou,1,&ast; Xiaoli Fan,1 Ruiqi Wu,1 Shuyun Liu,2 Qiaoyu Deng,1 Yanyi Zheng,1 Jingping Liu,2 Li Yang1 1Department of Gastroenterology and Hepatology and Laboratory of Gastrointestinal Cancer and Liver Disease, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 2NHC Key Laboratory of Transplant Engineering and Immunology, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li Yang; Jingping Liu, Email yangli_hx@scu.edu.cn; liujingping@scu.edu.cnBackground: Autoimmune hepatitis (AIH) is a serious liver disease characterized by immune disorders, particularly effector T-cell overactivation. This study aimed to explore the therapeutic effect and underlying mechanism of mesenchymal stem cell-derived extracellular vesicle (MSC-EV) treatment on CD4+ T-cell overactivation and liver injury in AIH.Methods: The metabolic changes of CD4+ T cells were assayed in human AIH and mouse hepatitis models. The liver protective effect of MSC-EVs was evaluated by transaminase levels, liver histopathology and inflammation. The effect of MSC-EVs on the metabolic state of CD4+ T cells was also explored.Results: Enhanced glycolysis (eg, ~1.5-fold increase in hexokinase 2 levels) was detected in the CD4+ T cells of AIH patient samples and mouse hepatitis models, whereas the inhibition of glycolysis decreased CD4+ T-cell activation (~1.8-fold decrease in CD69 levels) and AIH liver injury (~6-fold decrease in aminotransferase levels). MSC-EV treatment reduced CD4+ T-cell activation (~1.5-fold decrease in CD69 levels) and cytokine release (~5-fold decrease in IFN-γ levels) by reducing glycolysis (~3-fold decrease) while enhancing mitochondrial oxidative phosphorylation (~2-fold increase in maximal respiration) in such cells. The degree of liver damage in AIH mice was ameliorated after MSC-EV treatment (~5-fold decrease in aminotransferase levels). MSC-EVs carried abundant mitochondrial proteins and might transfer them to metabolically reprogram CD4+ T cells, whereas disrupting mitochondrial transfer impaired the therapeutic potency of MSC-EVs in activated CD4+ T cells.Conclusion: Disordered glucose metabolism promotes CD4+ T-cell activation and associated inflammatory liver injury in AIH models, which can be reversed by MSC-EV therapy, and this effect is at least partially dependent on EV-mediated mitochondrial protein transfer between cells. This study highlights that MSC-EV therapy may represent a new avenue for treating autoimmune diseases such as AIH.Keywords: autoimmune hepatitis, extracellular vesicles, metabolic reprogramming, mitochondria, inflammation

Huiqin Sun,1,* Lu Zhou,2,* Yihan Lu,2 Yingchuan Li,3 Yan Huo,4 Weifeng Huang5 1Department of Anesthesiology, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Epidemiology, Ministry of Education Key Laboratory of Public Health Safety, School of Public Health, Fudan University, Shanghai, People’s Republic of China; 3Department of Critical Care Medicine, Tongji University Affiliated Shanghai Tenth People’s Hospital, Shanghai, People’s Republic of China; 4Department of Pharmacy, Yangpu Hospital, School of Medicine, Tongji University, Shanghai, 200090 People’s Republic of China; 5Department of Critical Care Medicine, Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, Fudan University, Fudan, 200031, People’s Republic of China*These authors contributed equally to this workCorrespondence: Weifeng Huang, Department of Critical Care Medicine, Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, Fudan University, 366 NorthLongchuan Rd, Xuhui District, Shanghai, 200031, People’s Republic of China, Email breeze-huang@hotmail.com Yan Huo, Department of Pharmacy, Yangpu Hospital, School of Medicine, Tongji University, Shanghai, 200090, People’s Republic of China, Email huoyan@sjtu.edu.cnIntroduction: Pulmonary embolism (PE), the most serious presentation of venous thromboembolism (VTE), is associated with a high rate of mortality and expense. Clinical studies on pregnant women with PE are scarce. The aim of this study was to analyze the clinical impact of fibrinolytic enzyme activation inhibitor-1 (PAI-1) 4G/5G genetic polymorphisms, methylenetetrahydrofolate reductase (MTHFR) rs1801131 (A1298C) and rs1801133 (C677T) genetic polymorphisms, and establish a predictive model for pregnant women.Material and Methods: Between September 2022 and August 2023, 53 pregnant women with PE were enrolled. Using the propensity score matching method, 106 consecutive pregnant women without VTE were 1:2 matched. The relevant patient data were collected, and the susceptibility genes for PE were detected to determine genetic polymorphisms, and PE susceptibility in pregnant women, as well as to develop predictive models.Results: Our study showed that 4G/4G homozygous mutations increased the risk of pregnant PE fourfold (OR = 4.46, 95% CI = 1.59– 12.50, P = 0.004), whereas the 4G allele mutation increased the risk twofold (OR = 2.33, 95% CI = 1.35– 4.04, P = 0.002). A nomogram was established to predict the risk of pregnant women with PE by four predictive features including PAI-1 genetic polymorphisms, international normalized ratio (INR), antithrombin-III (AT-III) activity, and platelet count (PLT). The area under the curve (AUC) of the nomogram was 0.821 (0.744– 0.898). The AUC of the internal validation group was 0.822 (0.674– 0.971). Decision curve analysis revealed that the nomogram has a higher net benefit in the following threshold: probability interval of ≥ 15%.Conclusion: The PAI-1 4G/4G genotype is an independent risk factor for pregnant women with PE; furthermore, the presence of the 4G allele can increase the risk of PE. The study established a nomogram to predict the risk of PE in pregnant women.Keywords: pulmonary embolism, pregnant women, genetic polymorphisms, PAI-1, nomogram model

Yanyan Li,1 Xia Deng,2 Xunan Wu,2 Ligang Zhou,1 Guoyue Yuan2 1Department of Endocrinology, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Pudong, Shanghai, 201399 People’s Republic of China; 2Department of Endocrinology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu Province, 210031, People’s Republic of ChinaCorrespondence: Guoyue Yuan, Department of Endocrinology, Affiliated Hospital of Jiangsu University, No. 438 Jiefang Road, Zhenjiang City, Jiangsu Province, 210031, People’s Republic of China, Email yuanguoyue@ujs.edu.cn Ligang Zhou, Department of Endocrinology, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, 2800 Gongwei Road, Pudong, Shanghai, 201399, People’s Republic of China, Email zhouligang@yahoo.comObjective: Tsukushi is a newly identified hepatokine. Recent studies have shown that it relates to diabetes, lipid metabolism and fibrosis, but there is currently no investigation about whether Tsukushi is associated with diabetic kidney disease. Therefore, this study aimed to investigate the relationship between Tsukushi and diabetic kidney disease by characterizing Tsukushi levels in healthy subjects and type 2 diabetes with urinary albumin-creatinine ratio.Methods: Serum Tsukushi level was quantified by enzyme-linked immunosorbent assay in 167 normoalbuminuria, 80 microalbuminuria, and 31 macroalbuminuria patients with type 2 diabetes as compared with 53 healthy subjects. The correlation analysis was used to investigate the relationship between urinary albumin-creatinine ratio or Tsukushi level and other metabolic parameters. Multiple linear regression and logistic regression analysis were used to analyze the independent factors for urinary albumin-creatinine ratio and estimated glomerular filtration rate.Results: The Tsukushi level in the macroalbuminuria group was significantly higher than that in the normoalbuminuria or the microalbuminuria group. Multiple linear regression showed that the significantly independent factors for UACR included high Tsukushi quartile, systolic blood pressure, creatinine, homeostasis model assessment of insulin resistance, low 2-h post-oral glucose tolerance test c-peptide and female. Logistic regression demonstrated that the odds ratio of Tsukushi for glomerular filtration rate ≤ 90(mL/min/1.73m2) was 1.636 (95% CI 1.091– 2.452, P=0.017).Conclusion: The circulating Tsukushi increased in type 2 diabetes patients with albuminuria and was associated with urinary albumin-creatinine ratio, implying that Tsukushi may be involved in the pathogenesis of diabetic kidney disease, which deserves future studies.Keywords: type 2 diabetes, urinary albumin-creatinine ratio, hepatokine, Tsukushi

Hanzhi Chen,1,&ast; Leting Zhou,1,&ast; Meilin Yan,1,&ast; Cheng Li,1 Bin Liu,1 Xiaobin Liu,1 Weiwei Shan,1 Ya Guo,2 Zhijian Zhang,1 Liang Wang1 1Department of Nephrology, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, Jiangsu, 214000, People’s Republic of China; 2Key Laboratory of Advanced Process Control for Light Industry (Ministry of Education), Jiangnan University, Wuxi, Jiangsu, 214122, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhijian Zhang, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical University, 299 Qingyang Road, Wuxi, Jiangsu, 214000, People’s Republic of China, Email zzjwxyy@163.com Liang Wang, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, 299 Qingyang Road, Wuxi, Jiangsu, 214000, People’s Republic of China, Email wangliang_wuxi@126.comBackground: End-stage kidney disease (ESKD) patients often face complications like anemia, malnutrition, and cardiovascular issues. Serological tests, which are uncomfortable and not frequently conducted, assist in medical assessments. A non-invasive, convenient method for determining these test results would be beneficial for monitoring patient health.Objective: This study develops machine learning models to estimate key serological test results using non-invasive cellular bioelectrical impedance measurements, a routine procedure for ESKD patients.Methods: The study employs two machine learning models, Support Vector Machine (SVM) and Random Forest (RF), to determine key serological tests by classifying cell bioelectrical indicators. Data from 688 patients, comprising 3,872 biochemical–bioelectrical records, were used for model validation.Results: Both SVM and RF models effectively categorized key serological results (albumin, phosphorus, parathyroid hormone) into low, normal, and high. RF generally outperformed SVM, except in classifying calcium levels in women.Conclusion: The machine learning models effectively classified serological test results for maintenance hemodialysis patients using cellular bioelectrical indicators, therefore can help in making judgments about physicochemical indicators using electrical signals, thereby reducing the frequency of serological tests.Keywords: serological test results, cellular bioelectrical indicators, machine learning, End-stage kidney disease

Yun Zhong,1– 3 Yufei Zhao,4 Xin Meng,2 Fan Wang,2 Lei Zhou1 1Department of Dermatology, the Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of China; 2Department of Dermatology, Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 3Department of Dermatology, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 4Department of Gastrointestinal Surgery, Laboratory of Surgery, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of ChinaCorrespondence: Lei Zhou, Department of Dermatology, the Third Affiliated Hospital, Sun Yat-sen University, 600 Tianhe Road, Tianhe District, Guangzhou, Guangdong, 510630, People’s Republic of China, Tel +020-85253333, Fax +020-85253336, Email zhoulei53@mail.sysu.edu.cnBackground: Rosacea, a recurring dermatological disorder, demands effective therapeutic approaches. Traditional Chinese medicine, particularly Liangxue Siwu Decoction (LXSWD), has shown promise in managing inflammatory skin diseases, such as rosacea. This study focuses on uncovering LXSWD’s specific effects on the inflammatory symptoms of rosacea.Objective: Our research investigates LXSWD’s therapeutic effectiveness in rosacea treatment and delves into its underlying mechanisms.Methods: Network pharmacology was utilized to identify LXSWD’s key components and their targets in rosacea management, which were then validated by molecular docking. An in vivo rosacea-like model in LL-37-induced mice was developed, subdividing them into control, model, and LXSWD groups. The LXSWD group received oral administration (25.0 g/kg/day) for six days before model induction. Post-treatment evaluations included skin tissue analyses to verify our network pharmacology predictions.Results: Key active ingredients in LXSWD, such as quercetin, kaempferol, and luteolin, were identified alongside central target proteins like TNF and MMPs. Our molecular docking study confirmed the interactions between these ingredients and targets. Analyses through GO and KEGG pathways indicated LXSWD’s role in mitigating inflammation, particularly influencing the TNF and IL-17 pathways. LXSWD treatment in vivo markedly alleviated LL-37-induced symptoms in mice, showing a marked reduction in inflammatory cytokines (p < 0.05) and modulation of crucial genes (p < 0.05). These results, supported by immunofluorescence analysis and Western blot, underline the modulatory effects of LXSWD on MMPs, offering significant protection against rosacea’s inflammation alterations (p < 0.05).Conclusion: Integrating network pharmacology, molecular docking, and in vivo experiments, this study elucidates LXSWD’s potential mechanisms in rosacea treatment. It offers a novel theoretical framework for its clinical use in managing rosacea.Keywords: Liangxue siwu decoction, molecular docking, network pharmacology, rosacea, skin inflammation

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

David A Zarrin,1 Li Zhou2 1David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA; 2Department of Medicine, University of California, Los Angeles, CA, 90095, USACorrespondence: David A Zarrin, University of California Los Angeles, 10833 Le Conte Avenue, Los Angeles, CA, 90095, USA, Tel +408-438-8127, Email dzarrin@mednet.ucla.eduBackground: There is growing need for physician-innovators to address the mounting challenges within the US healthcare system. Despite this, there remains a significant gap in understanding of the efficacy of innovation programs for US MD candidates. We present initial program outcomes of a novel, clinically immersive medical innovation program offered to MD candidates at the David Geffen School of Medicine (DGSOM) at UCLA.Methods: A novel clinically immersive medical innovation curriculum was developed based on existing and reputable medical innovation frameworks and tailored for medical students. Curricular topics broadly included clinical ethnography, interviewing techniques, mind mapping, needs formulation and prioritization, quality improvement, intellectual property, reimbursement pathways, solution landscaping and prioritization, regulatory processes. The program was trialed during an unscheduled summer with voluntary enrollees from DGSOM Class of 2024. The traditional four-level Kirkpatrick model was employed to assess program outcomes.Results: Program outcomes were positive on all four Kirkpatrick levels. Students rated enjoyment at 9.5/10 for lectures and 9.1/10 for clinical immersion. Student-perceived confidence in key skills increased by 43%, and 75% of faculty directly perceived improvement in ethnographic skills. Students were highly engaged in both didactics and clinical immersion, discovering on average 2.6 faculty-verified needs per week. Faculty largely felt their students discovered important unmet clinical needs and added value to their clinical practice.Conclusion: We developed and trialed a novel clinically immersive medical innovation curriculum tailored for medical students. This program achieved positive outcomes on all four levels of the Kirkpatrick model. Our findings have driven the local adoption of this program into our institution’s medical school curriculum. We hope that the program efficacy demonstrated herein catalyzes more institutions to trial similar medical innovation programs.Plain Language Summary: We conducted this investigation after recent literature identified a significant gap in our understanding of the role of innovation and entrepreneurship (I&E) programs in the United States (US) medical education. I&E programs are meant to teach the skills necessary to identify and assess ongoing challenges in health care and subsequently formulate a solution for such challenges. The rate of adoption of I&E programs into US medical education has been unexplainably slow, despite a strong reported interest among medical students in learning the associated topics. We sought to answer the question: how effectively can an I&E curriculum be integrated into the traditional US medical doctorate (M.D). curriculum? We designed a novel medical innovation program tailored for medical students and offered this six-week program to 16 M.D. candidates at UCLA during an unscheduled summer. By describing the curriculum in detail and presenting our holistic assessment of program outcomes including learners’ feeling, learnings, transference of knowledge, and the program’s real-world impact, we demonstrate methods by which medical innovation can effectively be taught to medical students and the impact this may have on our future physician workforce. Our implementation of a quality improvement conceptual framework examining multiple process measures enabled iterative and real-time improvement of the program throughout its offering. Our surveys were administered at regular intervals through the course, thereby allowing iterative feedback from enrolled students to drive course improvement, similar to how quality improvement frameworks incrementally improve outcomes through closed-loop feedback in health care settings. We posit that analogous medical innovation curricula should be increasingly integrated into MD curricula more broadly.Keywords: medical education, medical innovation, ethnography, clinical needs, Kirkpatrick model

Tong Chen,1– 4 Yu Liu,2,3 Shiquan Wu,2 Siyu Long,2 Ling Feng,4,5 Wenqian Lu,6 Wenya Chen,2 Guoai Hong,2 Li Zhou,2 Fang Wang,2 Yuechan Luo,2 Hequn Zou,2,4,6 Weihua Liu7 1Department of Nephrology, Chongqing Key Laboratory of Prevention and Treatment of Kidney Disease, Chongqing Clinical Research Center of Kidney and Urology Diseases, Xinqiao Hospital, Army Medical University (Third Military Medical University), Chongqing, 400037, People’s Republic of China; 2South China Hospital of Shenzhen University, Shenzhen, 518116, People’s Republic of China; 3Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, National Regional Key Technology Engineering Laboratory for Medical Ultrasound School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen, 518060, People’s Republic of China; 4Department of Nephrology, The Third Affiliated Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 5Department of Nephrology, Shenzhen Hospital, Southern Medical University, Shenzhen, People’s Republic of China; 6School of Medicine, The Chinese University of Hong Kong, Shenzhen, People’s Republic of China; 7Department Nephrology of Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fujian, 350001, People’s Republic of ChinaCorrespondence: Weihua Liu, Department Nephrology of Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fujian, 350001, People’s Republic of China, Email lwh10280465@163.com Hequn Zou, School of Medicine, The Chinese University of Hong Kong, Shenzhen, People’s Republic of China, Email zouhequn@cuhk.edu.cnBackground: Obesity and insulin resistance (IR) are positively associated with chronic kidney disease (CKD). Previous studies have identified triglyceride-glucose index (TyG) as a valuable surrogate of insulin resistance. Recently, new indicators combining TyG and simple anthropometric indices have emerged, The objective of this study was to assess the diagnostic accuracy of TyG and newly TyG related indicators in detecting CKD and explore which indices were superior in associating with CKD in Chinese population.Methods: Correlation test, logistic regression analysis, and receiver operating characteristic (ROC) analyses were used to evaluate the optimal cut-off and value of TyG, TyG-body mass index (TyG-BMI), TyG-waist circumference (TyG-WC), TyG-waist to height ratio (TyG-WHtR) for predicting CKD.Results: TyG-WHtR, TyG-WC, and TyG-BMI correlated with several risk factors for CKD. After adjusting for confounders, TyG-WHtR and TyG-WC remained significantly associated with CKD, while TyG-BMI did not. The highest quartiles of TyG-WHtR and TyG-WC had 1.95- and 1.91-fold increased risk of CKD than the lowest quartiles (P< 0.05). TyG-WHtR had the largest AUC (0.687) for CKD detection, followed by TyG-WC (0.669), TyG (0.652), and TyG-BMI (0.648). A united model that involved TyG-WHtR and other risk variables had higher predictive performance (AUC=0.791) than a single TyG related indicator. However, TyG had the highest OR (2.713, 95% CI, 1.446– 5.090) for reduced eGFR in the fully adjusted model. A united model that involved TyG and WHtR separately had stronger predictive ability (AUC: 0.794) than the model that involved TyG-WHtR individually (AUC:0.791).Conclusion: This study found that TyG-WHtR had a better diagnostic value in the diagnosis of CKD, compared to other TyG related indicators, but none of the TyG related indicators showed a stronger association with CKD than TyG. Further research and more refined algorithms are needed to verify these new indicators.Keywords: chronic kidney disease, insulin resistance, obesity, TyG related indicators

Li Zhou,1,&ast; Youlin Wu,1,2,&ast; Jiani Wang,1 Haiyun Wu,1 Yongjun Tan,1 Xia Chen,1,3 Xiaosong Song,1,4 Yu Ren,1 Qin Yang1 1Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Department of Neurology, Chongzhou People’s Hospital, Sichuan, People’s Republic of China; 3Department of Neurology, the Seventh People’s Hospital of Chongqing, Chongqing, People’s Republic of China; 4Department of Neurology, the Ninth People’s Hospital of Chongqing, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qin Yang, Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong District, Chongqing, 400016, People’s Republic of China, Tel +86-023-89012008, Fax +86-023-68811487, Email xyqh200@126.comBackground and Purpose: Ischemic stroke is a leading cause of mortality and disability globally, necessitating accurate prediction of intra-hospital mortality (IHM) for improved patient care. This study aimed to develop a practical nomogram for personalized IHM risk prediction in ischemic stroke patients.Methods: A retrospective study of 422 ischemic stroke patients (April 2020 - December 2021) from Chongqing Medical University’s First Affiliated Hospital was conducted, with patients divided into training (n=295) and validation (n=127) groups. Data on demographics, comorbidities, stroke risk factors, and lab results were collected. Stroke severity was assessed using NIHSS, and stroke types were classified by TOAST criteria. Least absolute shrinkage and selection operator (LASSO) regression was employed for predictor selection and nomogram construction, with evaluation through ROC curves, calibration curves, and decision curve analysis.Results: LASSO regression and multivariate logistic regression identified four independent IHM predictors: age, admission NIHSS score, chronic obstructive pulmonary disease (COPD) diagnosis, and white blood cell count (WBC). A highly accurate nomogram based on these variables exhibited excellent predictive performance, with AUCs of 0.958 (training) and 0.962 (validation), sensitivities of 93.2% and 95.7%, and specificities of 93.1% and 90.9%, respectively. Calibration curves and decision curve analysis validated its clinical applicability.Conclusion: Age, admission NIHSS score, COPD history, and WBC were identified as independent IHM predictors in ischemic stroke patients. The developed nomogram demonstrated high predictive accuracy and practical utility for mortality risk estimation. External validation and prospective studies are warranted for further confirmation of its clinical efficacy.Keywords: ischemic stroke, nomogram, predictors, lasso, intra-hospital mortality

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

Shengfeng Wang,1,&ast; Ruxue Fang,1,&ast; Lei Huang,1,&ast; Liping Zhou,1,2 Haibo Liu,3 Meiling Cai,4 Abubakar Sha’aban,5 Chunxiang Yu,1 Mohammed Ahmed Akkaif3 1Rehabilitation Department of Chinese Medicine, The Fourth People’s Hospital of Kunshan, Kunshan City, Jiangsu Province, People’s Republic of China; 2Department of Community Health, Advanced Medical and Dental Institute, Universiti Sains Malaysia, Bertam, Pulau Pinang, Malaysia; 3Department of Cardiology, QingPu Branch of Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 4Department of Obstetrics and Gynecology, Qingpu Branch, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 5Health and Care Research Wales Evidence Centre, Cardiff University, Heath Park, Cardiff, UK&ast;These authors contributed equally to this workCorrespondence: Mohammed Ahmed Akkaif, Department of Cardiology, QingPu Branch of Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China, Email akkaif@fudan.edu.cn Chunxiang Yu, Rehabilitation Department of Chinese medicine, The Fourth People’s Hospital of Kunshan, Kunshan City, Jiangsu Province, People’s Republic of China, Email yuchunxiang868@gmail.comAbstract: Cardiovascular diseases (CVDs) are increasingly prevalent in clinical settings. With the continuous improvement of people’s living standards, the gradual acceleration of the pace of life, and the deterioration of the living environment in recent years, the incidence of CVDs is increasing annually. The prevalence of CVDs among individuals aged 50 and above is notably elevated, posing a significant risk to patients’ well-being and lives. At this juncture, numerous clinical treatment choices are available for managing CVDs, with traditional Chinese medicine (TCM) therapy standing out as a practical, safe, and reliable option. Over the recent years, there has been growing acknowledgement among both medical professionals and patients. With the expanding integration of TCM in the treatment of various clinical conditions, the use of TCM in managing CVDs has gained significant attention within the medical community, potentially emerging as an efficacious approach for addressing cardiovascular diseases. This article conducts a comprehensive review of the TCM approach, particularly acupuncture, as a supplementary treatment for CVDs, highlighting its ability to effectively lower blood pressure, decrease coronary artery events, mitigate arrhythmias, and enhance cardiac function when used alongside conventional medication. The review underscores the promise of acupuncture in enhancing cardiovascular health, although variations in research methodologies necessitate standardized applications.Keywords: cardiovascular diseases, traditional Chinese medicine, acupuncture, clinical treatment

Lingling Wang,1 Huiguo Liu,1 Ling Zhou,1 Pengdou Zheng,1 Hai Li,2,3 Huojun Zhang,4,&ast; Wei Liu2,3,&ast; 1Department of Respiratory and Critical Care Medicine, Key Laboratory of Pulmonary Diseases of Health Ministry, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 3Key Laboratory of Vascular Aging, Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 4Department of Respiratory and Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Huojun Zhang, Email hjzhang@whu.edu.cn; Wei Liu, Email 404793938@tjh.tjmu.edu.cnAbstract: Obstructive sleep apnea (OSA), a common sleep-disordered breathing condition, is characterized by intermittent hypoxia (IH) and sleep fragmentation and has been implicated in the pathogenesis and severity of nonalcoholic fatty liver disease (NAFLD). Abnormal molecular changes mediated by IH, such as high expression of hypoxia-inducible factors, are reportedly involved in abnormal pathophysiological states, including insulin resistance, abnormal lipid metabolism, cell death, and inflammation, which mediate the development of NAFLD. However, the relationship between IH and NAFLD remains to be fully elucidated. In this review, we discuss the clinical correlation between OSA and NAFLD, focusing on the molecular mechanisms of IH in NAFLD progression. We meticulously summarize clinical studies evaluating the therapeutic efficacy of continuous positive airway pressure treatment for NAFLD in OSA. Additionally, we compile potential molecular biomarkers for the co-occurrence of OSA and NAFLD. Finally, we discuss the current research progress and challenges in the field of OSA and NAFLD and propose future directions and prospects.Keywords: intermittent hypoxia, hypoxia-inducible factor 1 alpha, nonalcoholic fatty liver disease, oxidative stress, dyslipidemia, leptin resistance

Chenglin Xu,1,&ast; Song Wen,1,2,&ast; Min Gong,1,&ast; Meiyuan Dong,1,3,&ast; Yue Yuan,1 Yanyan Li,1 Mingyue Zhou,4 Ligang Zhou1,3,5 1Department of Endocrinology, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, 201399, People’s Republic of China; 2Fudan Zhangjiang Institute, Fudan University, Shanghai, 201203, People’s Republic of China; 3Hebei Medical University, Shijiazhuang, 050013, People’s Republic of China; 4Clinical Research OB/GYN REI Division, University of California, San Francisco, CA, USA; 5Shanghai Key Laboratory of Vascular Lesions Regulation and Remodeling, Shanghai Pudong Hospital, Shanghai, 201399, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ligang Zhou, Department of Endocrinology, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, 201399, People’s Republic of China, Tel +8613611927616, Email zhouligang1n1@163.comObjective: To investigate the implications of elevated myoglobin (MYO) in acute diabetic conditions of diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS).Materials and methods: This study integrates in-patient data from Shanghai Pudong Hospital from 2019 to 2023. Laboratory data were compared between stable T2D patients (without acute diabetic complications), DKA, and HHS patients. The multilinear regression explored variables relevant to the elevated MYO in DKA and HHS. The dynamics of MYO, the survival rate, and associated risk factors in HHS were determined.Results: Except for triglyceride, procalcitonin, low-density lipoprotein, islet cell autoimmune antibodies, N-terminal Pro-brain natriuretic peptide (NT-ProBNP), and brain natriuretic peptide (BNP), there were significant differences in age, gender distribution, duration of diabetes, type of diabetes, and other referred laboratory data (p< 0.05). The age, gender, creatine kinase (CK), estimated glomerular filtration rate (eGFR), and free triiodothyronine (FT3) in DKA, whereas osmolar, uric acid (UA), and cardiac troponin I (cTNI) in the HHS, were significant determinants of elevated MYO, respectively (p< 0.05). The dynamic of MYO in HHS was in line with the survival trend, where the percentage of death was 29.73%, and aging with higher procalcitonin levels was a key risk factor. Besides, the cumulative survival rates between patients with or without bone fracture or muscle injury were substantially different.Conclusion: This real-world study demonstrated DKA and HHS potentially have unique causes for increased MYO. By utilizing the appropriate regression parameters, we could forecast the progression of increased MYO in groups of DKA and HHS, while based on risk factors of aging, severity of infection, and different MYO sources, we could predict the prognosis of HHS.Keywords: diabetes mellitus, diabetic ketoacidosis, hyperosmolar hyperglycemic state, myoglobin, survival

Zhaoting Wu,1,2 Lihua Tang,1 Yaozhen Lai,1 Muyuan Liu,3 Li Zhou1 1Department of Gynecologic Oncology, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, People’s Republic of China; 2Department of Gynecology, the First People’s Hospital of Chenzhou, Chenzhou, Hunan, People’s Republic of China; 3Head and Neck Surgery Department, Cancer Hospital of Shantou University, Medical College, Shantou, Guangdong, People’s Republic of ChinaCorrespondence: Li Zhou, Email zlyyzl@126.com Muyuan Liu, Email muyuan-1981@163.comPurpose: Struma ovarii is a highly specialized teratoma consisting primarily of mature thyroid tissue. However, malignant struma ovarii coexisting with thyroid carcinoma, not to mention autoimmune disease, is uncommon. Malignant struma ovarii complicated with papillary thyroid carcinoma, Hashimoto’s thyroiditis and polycystic ovarian syndrome has never been reported in literature.Patients and Methods: A 32-year-old female was admitted to our hospital due to a history of abdominal distension and menolipsis over the past half a year. Physical examination touched a 6 × 6 cm mass with a clear boundary, normal movement, and no pressing pain in the right adnexal area, Imaging revealed a cystic solid mass of 6 × 7 cm in the right ovary and the level of tumor markers including CA125, CA199, CA153, CEA, AFP were normal, but with low TSH and increased TPOAb, TGAb, TRAb. Laparoscopic right ovary tumor resection was performed, followed by comprehensive staging surgery, as well as thyroidectomy after pathologic diagnosis. The patient was diagnosed with a combination of follicular thyroid cancer from struma ovarii, papillary thyroid carcinoma and Hashimoto’s thyroiditis, along with polycystic ovarian syndrome. Immunohistochemical staining showed positivity for Ag, CK-pan, CK7, PAX8 and TTF-1 in the right ovarian mass, and the left thyroid was positive for the BRAF V600E mutation.Results: The patient underwent thyroxine suppression therapy and radioactive iodine 131I therapy after operation. Serum thyroglobulin was undetectable, and no signs of recurrence or metastasis were detected in the imaging examination at the 2-year follow-up.Conclusion: Malignant struma ovarii coexisting with thyroid carcinoma is rare. No report has been identified in literature review on the rare malignant struma ovarii coexisting with thyroid carcinoma, Hashimoto’s thyroiditis and polycystic ovarian syndrome. Our case can offer experience of diagnosis and treatment to some extent for such rare case. Therefore, it is essential to consider the association between ovarian tumors and the endocrine system. This case is valuable in understanding the diagnosis and management of such an unusual complicated disease.Keywords: struma ovarii, follicular thyroid carcinoma, case report, gynaecological tumor

Juan Bu,1 Yeledan Mahan,1 Yanmin Zhang,2 Shengnan Zhang,1 Xuanxia Wu,1 Xiaoling Zhang,1 Ling Zhou1 1Medical and Translational Research Center, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, People’s Republic of China; 2Scientific Research and Education Center, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, People’s Republic of ChinaCorrespondence: Ling Zhou, Medical and Translational Research Center, People’s Hospital of Xinjiang Uygur Autonomous Region, 91 Tianchi Road, Tianshan District, Urumqi, Xinjiang, 830001, People’s Republic of China, Tel +86 991 8562 317, Email zlrmyy@sina.comBackground: Acacetin is a natural flavonoid known for its anti-tumor, antioxidant, and anti-inflammatory properties. Our previous studies have shown its protective effects against cerebral ischemia-reperfusion injury (IRI), but the underlying molecular mechanisms remain unclear.Purpose: The study delves into acacetin’s mechanism in mitigating cerebral IRI, with a focus on transcriptomic insights.Methods: We established the oxygen-glucose deprivation/re-oxygenation (OGD/R) model in BV2 microglia, treating them with 10μM acacetin. Then we assessed cell proliferation using CCK-8 and measured Lactate Dehydrogenase (LDH) release. High-throughput RNA sequencing (RNA-seq) underpinned the analysis of differentially expressed genes (DEGs) and long non-coding RNAs (lncRNAs), functional enrichment, and alternative splicing events (ASEs), validated by reverse transcription–quantitative polymerase chain reaction (RT-qPCR).Results: OGD/R injury significantly impaired cell proliferation and increased LDH release, effects mitigated by acacetin. RNA-seq identified 2148 upregulated and 2135 downregulated DEGs post-OGD/R. In contrast, the acacetin-treated group showed 248 upregulated and 240 downregulated DEGs compared to the OGD/R group. All DEGs were enriched in both Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Overlapping analysis indicated that acacetin treatment reversed the expression of 203 genes affected by OGD/R, including inflammation-related genes such as Isg15, Fcgr1, Il1b, and Parp12. Moreover, the oxidative stress-related gene, Mt2, was downregulated post-OGD/R but upregulated following acacetin treatment. We further found that OGD/R and acacetin treatment could modulate gene splicing events, impacting cell apoptosis or inflammatory responses, such as the A3SS splicing event in the Trim47 gene. RNA-seq also highlighted differential expression of numerous lncRNAs, particularly the upregulation of lncRNA Rmrp and Terc post-OGD/R and their subsequent downregulation post-acacetin treatment. These lncRNAs might regulate cell proliferation through mediating target gene expressions. RT-qPCR validation confirmed these findings.Conclusion: Significant upregulation of genes and ASEs linked to oxidative stress and inflammatory response is observed in cerebral IRI. Acacetin intervention reverses these effects, highlighting its mechanism in alleviating the injury by modulating gene expression and splicing events.Keywords: acacetin, ischemic stroke, inflammation, genome-wide analysis, differentially expressed genes, alternative splicing, long non-coding RNA, RNA sequencing

Cunzi Li,1 Lan Zhou,2,3 Hongyan Sun,2 Ming Ming Yang2 1The Second Clinical Medical College of Jinan University (Shenzhen People’s Hospital), Shenzhen, 518020, People’s Republic of China; 2Department of Ophthalmology, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, 518020, People’s Republic of China; 3Post-Doctoral Scientific Research Station of Basic Medicine, Jinan University, Guangzhou, 510632, People’s Republic of ChinaCorrespondence: Ming Ming Yang, Department of Ophthalmology, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), No. 1017 Dongmen North Road, Luohu District, Shenzhen, 518020, People’s Republic of China, Tel +86 22944163, Email ming4622@163.comAbstract: Age-related macular degeneration (AMD) is a degenerative ocular disease primarily affecting central vision in the elderly. Its pathogenesis is complex, involving cellular senescence and immune homeostasis dysregulation. This review investigates the interaction between these two critical biological processes in AMD pathogenesis and their impact on disease progression. Initially, cellular senescence is analyzed, with particular emphasis on retinal damage induced by senescent retinal pigment epithelial cells. Subsequently, the occurrence of immune homeostasis dysregulation within the retina and its mechanistic role in AMD areis explored. Furthermore, the paper also discusses in detail the interplay between cellular senescence and immune responses, forming a vicious cycle that exacerbates retinal damage and may influence treatment outcomes. In summary, a deeper understanding of the interrelation between cellular senescence and immune dysregulation is vital for the developing innovative therapeutic strategies for AMD.Keywords: age-related macular degeneration, cellular senescence, immune homeostasis dysregulation

Jiaqian Wang,1 Yuan Xue,2 Liang Zhou3 1Department of Orthopaedic, Zhongshan Hospital, Fudan University, Shanghai, 200032, People’s Republic of China; 2Department of Orthopaedic, Wuxi Ninth People’s Hospital of Soochow University, Wuxi, 214000, People’s Republic of China; 3Department of Orthopaedic, Lianshui County People’s Hospital, Huai‘an, People’s Republic of ChinaCorrespondence: Jiaqian Wang, Email 1580443814@qq.comBackground: Rheumatoid arthritis (RA) is a chronic systemic immune disease characterized by joint synovitis, but there are differences in clinical manifestations and serum test results among different patients.Methods: This is a bioinformatics study. We first obtained the gene expression profile of RA and normal synovium from the database, and screened the differentially expressed immune related genes for enrichment analysis. Subsequently, we classified RA into three subtypes by unsupervised clustering of serum gene expression profiles based on immune enrichment scores. Then, the enrichment and clinical characteristics of different subtypes were analyzed. Finally, according to the infiltration of different subtypes of immune cells, diagnostic markers were screened and verified by qRT-PCR.Results: C1 subtype is related to the increase of neutrophils, C-reactive protein and erythrocyte sedimentation rate, and joint pain is more significant in patients. C2 subtype is related to the expression of CD8+T cells and Tregs, and patients have mild joint pain symptoms. The RF value of C3 subtype is higher, and the expression of various immune cells is increased. CD4 T cells, NK cells activated, macrophages M1 and neutrophils are immune cells significantly infiltrated in synovium and serum of RA patients. IFNGR1, TRAC, IFITM1 can be used as diagnostic markers of different subtypes.Conclusion: In this study, RA patients were divided into different immune molecular subtypes based on gene expression profile, and immune diagnostic markers were screened, which provided a new idea for the diagnosis and treatment of RA.Keywords: rheumatoid arthritis, molecular subtype, immune cells, immunodiagnostic markers

Runting Ma, Lianhong Zhou, Wenping Li, Yuanjin Li, Diewenjie Hu, Yi Lu, Cancan Zhang, Beixi Yi Department of Ophthalmology, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of ChinaCorrespondence: Lianhong Zhou, Department of Ophthalmology, Renmin Hospital of Wuhan University, No. 238 Jiefang Road, Wuhan, 430060, People’s Republic of China, Tel +86 027-88041911-81219, Email zlh681102@aliyun.comPurpose: This study aimed to analyze myopia distribution in Hubei and the impact of regional Sunshine Duration on myopia in children and adolescents.Patients and Methods: The Cross-sectional study included students (kindergarten to grade 12) through multistage cluster stratified sampling in 17 cities (103 areas) of Hubei, China, who underwent ophthalmic examinations from September 2021 to November 2021. The association of sunshine duration with the prevalence and distribution of myopia was analyzed. Using Moran’s index to quantify the distribution relationship, a spatial analysis was constructed.Results: A total of 435,996 students (53.33% male; mean age, 12.16± 3.74 years) were included in the study. A negative association was identified between myopia prevalence and sunshine duration in the region, especially in population of primary students (r=− 0.316, p< 0.001). Each 1-unit increment in the sunshine duration was associated with a decreased risk of myopia prevalence (OR=0.996; 95% CI, 0.995– 0.998; P < 0.001). Regression showed a linear relationship between sunshine duration and myopia rates of primary school students [Prevalence%= (− 0.1331&ast;sunshine duration+47.73)%, p = 0.02]. Sunshine duration influenced the distribution of myopia rates among primary (Moran’s I=− 0.206, p< 0.001) and junior high school (Moran’s I=− 0.183, p=0.002). Local spatial analysis showed that areas with low sunshine duration had high myopia prevalence concentration.Conclusion: This study revealed sunshine duration associations with myopia prevalence at the regional and population levels. The results may emphasize the significance of promptly implementing myopia control in regions with poor sunshine. The effect of sunshine on myopia is pronounced in the early years of education, especially in primary students.Keywords: myopia, sunshine duration, children, Spatial Analysis, Moran’s Index, epidemiology

Juanjuan Liu,1 Minqin Xu,1 Ling Zhou,1 Li Yang,1 Hong Li,2 Xue Li1 1Department of Obstetrics and Gynecology, Second Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 2Department of Radiology, Second Affiliated Hospital of Soochow University, Suzhou, People’s Republic of ChinaCorrespondence: Xue Li, Department of Obstetrics and Gynecology, Second Affiliated Hospital of Soochow University, 1055 San Xiang Road, Suzhou, 215004, People’s Republic of China, Tel +8613584834618, Email zlanling@163.comObjective: To investigate the magnetic resonance imaging (MRI) features of women with prior second-trimester pregnancy loss, and to establish a nomogram prediction model for subsequent miscarriage.Methods: A retrospective cohort study of women with prior second-trimester pregnancy loss from January 2018 to December 2021 in Second Affiliated Hospital of Soochow University was performed. A total of 245 patients were included. Data from January 2018 to December 2019 were used to construct the model, and data from January 2020 to December 2021 were used to evaluate the model. Data on maternal demographic characteristics, MRI cervical measurements were extracted. The prediction model was constructed with independent variables determined by multivariate logistic regression analyses. Through receiver-operating characteristic (ROC) curve analysis, the predictive ability of the model for subsequent second trimester pregnancy loss in women was evaluated, and internal validation was performed through validation data.Results: Thin cervix was observed in 77 (31.42%) women with prior second-trimester pregnancy loss, the mean longitudinal diameter of cervical canal on MRI was 11.76± 2.75mm. The model reached a sensitivity of 80%, specificity of 75.90%, positive predictive value (PPV) of 55.80% and negative predictive value of 90.90%; ROC characteristics proved that the model was superior to any single parameter with an AUC of 0.826.Conclusion: Our observations showed that thin cervix and longitudinal diameter of cervical canal reliably predicted second trimester pregnancy loss. We developed and validated a nomogram model to predict the individual probability of second trimester pregnancy loss in the next pregnancy and hopefully improve the prediction and indication of interventions.Keywords: cervical insufficiency, MRI, nomogram, magnetic resonance imaging, CI

Qiong Wu,1,&ast; Shiying An,1,&ast; RueyJyh Lee,1 Dongwen Gao,2 Yinyifan Zhou,1 Longping Peng,1 Chunrui Hu,1 Lei Yao,3 Chang Zhou,4 Li Zhou,5 Junjie Gao,6 Min Cao,1 Meijiao Mao,1 Guanghao Li,1 Bing Deng,1 Yingjia Xu,4 Youhua Wang1 1Department of Cardiology, Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Department of Ultrasound, Longhua Hospital affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 3Department of Cardiology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 4Department of Cardiology, Shanghai Fifth People’s Hospital Affiliated to Fudan University, Shanghai, People’s Republic of China; 5Department of Cardiology, Shanghai Jiading Nanxiang Hospital, Shanghai, People’s Republic of China; 6Department of Cardiology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yingjia Xu, Shanghai Fifth People’s Hospital, Fudan University, Minhang District, 128 Ruili Road, Shanghai, 200240, People’s Republic of China, Tel +862164308151, Email xuyingjia@5thhospital.com Youhua Wang, Department of cardiology, Longhua Hospital affiliated to Shanghai University of Traditional Chinese Medicine, Xunhui, 725 South Wan-Ping Road, Shanghai, 200032, People’s Republic of China, Tel +862164385700, Email doctorwyh@163.comBackground: Dilated cardiomyopathy (DCM) is a severe heterogeneous cardiomyopathy characterized by cardiac enlargement and declining heart function, often leading to refractory heart failure and life-threatening outcomes, particularly prevalent in China. The challenge lies in the scarcity of targeted therapies with substantial efficacy for DCM. Additionally, traditional anti-heart failure drugs are constrained due to hypotension propensity or limited symptom improvement. Kuoxin Formula (KXF), internally endorsed at Longhua Hospital, demonstrates clear biological evidence for enhancing cardiac function and myocardial remodeling. Previous clinical studies suggest its potential to enhance patients’ quality of life. This trial aims to further evaluate KXF’s safety and efficacy in managing DCM-related heart failure.Methods: This prospective, randomized, double-blind, placebo-controlled, multicenter trial aims to recruit 230 DCM patients from five centers. Participants will be randomly assigned to either KXF or placebo for 12 weeks, with careful monitoring of key indicators and adverse events. The primary outcome measures the proportion of patients with NT-proBNP reduction exceeding 30%. Secondary outcomes include New York Heart Association functional classification, Traditional Chinese Medicine syndrome scores, 6-minute walk test, Lee’s heart failure score, and Minnesota Heart Failure Quality of Life Scale score. Ventricular remodeling will be assessed using cardiac ultrasound and ELISA. Safety metrics and adverse events will be meticulously recorded.Discussion: This study will be the first multicentered research conducted in China that utilizes a randomized, double-blind, placebo-controlled design to investigate the use of TCM in the treatment of DCM. It seeks to develop new theoretical frameworks and provide solid clinical data to support the integration of TCM and modern medicine in treating heart failure in DCM patients.Trial Registration: China Clinical Trial Registry, ChiCTR2300068937. Registered on March 1, 2023. https://www.chictr.org.cn/bin/project/edit?pid=190926.Keywords: dilated cardiomyopathy, heart failure, Kuoxin Formula, traditional Chinese medicine, clinical trials

Lihua Zhou,1,&ast; Kun Zhang,2,3,&ast; Juanjuan Guo,4 Jianbo Liu,5 Suhong Wang,6 Jingbo Gong7 1College of Education Science, Hengyang Normal University, Hengyang, People’s Republic of China; 2Suzhou Guangji Hospital, Suzhou, People’s Republic of China; 3Affiliated Guangji Hospital of Soochow University, Suzhou, People’s Republic of China; 4School of Education, Hunan University of Science and Technology, Xiangtan, Hunan, People’s Republic of China; 5Department of Child Psychiatry of Shenzhen Kangning Hospital, Shenzhen Mental Health Center, School of Mental Health, Shenzhen University, Shenzhen, People’s Republic of China; 6Department of Clinical Psychology, The Third Affiliated Hospital, Soochow University, Changzhou, People’s Republic of China; 7Shanghai Changning Mental Health Centre, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jingbo Gong, Shanghai Changning Mental Health Center, Shanghai, 200335, People’s Republic of China, Email yefenhua@126.com Suhong Wang, Department of Clinical Psychology, The Third Affiliated Hospital, Soochow University, Changzhou, People’s Republic of China, Email yarmine@gmail.comBackground: The present study aimed to investigate the potential role of perceived stress, impulsivity trait, executive dysfunction in non-suicidal self-injury (NSSI) thoughts among college students, as well as the gender differences.Methods: A sample of 890 university students completed self-report measures of NSSI thoughts in the past month, the level of perceived stress, impulsivity traits, and executive dysfunction.Results: Compared to those with low level of perceived stress, participants with high level of perceived stress reported significant higher levels of impulsivity trait and executive dysfunction, and higher frequency of NSSI thoughts, and there were no gender differences. Male participants with NSSI thoughts, compared to males without NSSI thoughts, reported significant higher levels of perceived stress and executive dysfunction. Female participants with NSSI thoughts, compared to females without NSSI thoughts, reported significant higher levels of perceived stress, impulsivity trait, and executive dysfunction. Hierarchical regression analysis revealed only executive dysfunction was associated with NSSI thoughts in males, while only perceived stress was associated with NSSI thoughts in females.Conclusion: This study revealed different influence factors for NSSI thoughts in male and female college students. NSSI thoughts in males were more likely associated with executive dysfunction while in females were due to recently perceived stress.Keywords: perceived stress, impulsivity, executive dysfunction, non-suicidal self-injury, gender difference

Lihua Zhu,1,&ast; Lingling Zhou,2,3,&ast; Liang Wang,4,&ast; Cunte Chen,2 Jie Qiao,1 Xinran Huang,1 Xiaoyan Su,1 Shaohua Chen,2 Bo Li,2 Xiuli Wu,2 Yangqiu Li2 1Department of Rheumatology and Immunology, First Affiliated Hospital, Jinan University, Guangzhou, 510632, People’s Republic of China; 2Institute of Hematology, School of Medicine, Key Laboratory for Regenerative Medicine of Ministry of Education, Jinan University, Guangzhou, 510632, People’s Republic of China; 3Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, 510632, People’s Republic of China; 4Department of Oncology, First Affiliated Hospital, Jinan University, Guangzhou, 510632, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yangqiu Li, Institute of Hematology, School of Medicine, Key Laboratory for Regenerative Medicine of Ministry of Education, Jinan University, Guangzhou, 510632, People’s Republic of China, Tel +86 20 85226877, Fax +86 20 85226877, Email yangqiuli@hotmail.com Lihua Zhu, Department of Rheumatology and Immunology, First Affiliated Hospital, Jinan University, Guangzhou, 510632, People’s Republic of China, Email zhulihua20121113@163.comBackground: There have been several studies regarding the susceptibility of A20 gene SNPs (rs2230926 and rs5029937) in rheumatoid arthritis (RA). However, little is known about the association between polymorphisms in the A20 promoter and RA. The aim of this study was to investigate the characteristics of A20 promoter polymorphisms and the association between these polymorphisms and clinical significance in Chinese RA patients.Methods: PCR and sequencing were used to identify A20 gene polymorphisms in peripheral blood mononuclear cells (PBMCs) from 123 RA cases and 31 healthy individuals.Results: Only one SNP (rs5029924) in the A20 gene promoter was identified in RA patients and healthy individuals. 6 patients who carried heterozygous rs5029924 (3918C>T) together with heterozygous rs5029937 (11,571 G>T) and rs2230926 (12,486 T>G, Phe127Cys) suffered from joints deformity or refractory RA.Conclusion: We reported the A20 promoter polymorphism rs5029924 in RA patients for the first time. rs5029924 concomitant with rs2230926 and rs5029937 may be a prognostic predictor for joint deformity or refractory RA.Keywords: A20, promoter, polymorphism, RA, deformity, refractory, predictor

Dingbin Yang,1,2 Yu Mao,3 Lu Peng,2 Shuqiong Huang,2 Lijun Zhou,2 Changqiang Li1 1Department of Dermatology, the Affiliated Hospital, Southwest Medical University, Luzhou, 646000, People’s Republic of China; 2Department of Dermatology, People’s Hospital of Leshan, Leshan, 614000, People’s Republic of China; 3Department of Pathology, People’s Hospital of Leshan, Leshan, 614000, People’s Republic of ChinaCorrespondence: Changqiang Li, Department of Dermatology, the Affiliated Hospital, Southwest Medical University, Luzhou, 646000, People’s Republic of China, Email lcq-1973@163.comAbstract: Keratoacanthoma (KA) is a papule, plaque, or nodule in an exposed area, with a crater-like horn plug in the center. Multiple KAs are rare disorders, especially when the lesions are agglomerated together. Herein, we report a case of 65-year-old man who presented with four red nodules of different sizes on the right side of the chest. The lesions were clustered, with central keratotic cores, similar in appearance to a four-leaf clover. The nodules were completely removed by excisional surgery and the diagnosis of Agglomerate KAs was made based on clinical and pathological results. A 6-year follow-up found no recurrence.Keywords: agglomerate keratoacanthomas, four-leaf clover

Jiachen Lu, Xiaofeng Dou, Yaohui Yi, Yingying Yu, Ling Zhou School of Public Health, Dalian Medical University, Dalian, People’s Republic of ChinaCorrespondence: Ling Zhou, Email zhouling0609@163.comPurpose: To assess the anxiety and depression and their predictors among healthcare workers in Liaoning Province, China.Methods: In order to explore the influencing factors and prevalence of anxiety and depression among healthcare workers, a cross-sectional research design was used to survey 500 healthcare workers using the 14-item Hospital Anxiety Depression Scale (HADS), the Rosenberg Self-Esteem Scale (RSES), the Multidimensional Scale of Perceived Social Support (MSPSS), and the Survey of Perceived Organizational Support (SPOS).Results: About 47.12% of the healthcare workers suffered from anxiety and 71.63% suffered from depression. In our study, we found that the health status (OR: 0.540, 95% CI: 0.298– 0.976), self-esteem (OR: 0.395, 95% CI: 0.251– 0.619), PSS (OR: 0.621, 95% CI: 0.388– 0.994), organizational support (OR: 0.533, 95% CI. 0.333– 0.854) were protective factors for healthcare workers suffering from anxiety, and resistance to COVID-19 (OR: 1.703, 95% CI: 1.082– 2.681) was a risk factor for healthcare workers suffering from anxiety, while good quality of life (OR: 0.385, 95% CI: 0.206– 0.719) self-esteem (OR: 0.187, 95% CI: 0.110– 0.317), and PSS (OR: 0.475, 95% CI: 0.267– 0.847) were protective factors for healthcare workers suffering from depression, and at the age of 35– 40 years (OR: 2.475, 95% CI: 1.140– 5.369) and resistance to COVID-19 (OR: 2.219, 95% CI: 1.313– 3.751) were risk factors for healthcare workers suffering from depression.Conclusion: The anxiety and depression status of healthcare workers in China is poor, and hospital administrators should take positive measures to support healthcare workers and give positive expectations to alleviate negative emotions such as anxiety and depression.Keywords: anxiety, depression, cross-sectional study, healthcare workers

Longjiang Zhou,1,&ast; Haitao Xiang,2,&ast; Susu Liu,3 Honglin Chen,4 Yuanwei Yang,4 Jianyong Zhang,4 Wei Cai4 1Department of Neurology, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, 225012, People’s Republic of China; 2Suzhou Kowloon Hospital, Shanghai Jiao Tong University School of Medicine, Suzhou, 215028, People’s Republic of China; 3School of Life Science and Technology, Xidian University and Engineering Research Center of Molecular and Neuro Imaging, Ministry of Education, Xi’an, 710126, People’s Republic of China; 4Department of Neurosurgery, Suqian First Hospital, Suqian, 223800, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Cai; Jianyong Zhang, Department of Neurosurgery, Suqian First Hospital, No. 120, Suzhi Road, Sucheng District, Suqian, Jiangsu Province, People’s Republic of China, Tel +86 15162908957 ; +86 15261296169, Fax +86 527 80766363 ; +86 527 80766155, Email doccaiwei@126.com; 935349804@qq.comPurpose: Hypoxia is often associated with glioma chemoresistance, and alleviating hypoxia is also crucial for improving treatment efficacy. However, although there are already some methods that can improve efficacy by alleviating hypoxia, real-time monitoring that can truly achieve hypoxia relief and efficacy feedback still needs to be explored.Methods: AQ4N/Gd@PDA-FA nanoparticles (AGPF NPs) were synthesized using a one-pot method and were characterized. The effects of AGPF NPs on cell viability, cellular uptake, and apoptosis were investigated using the U87 cell line. Moreover, the effectiveness of AGPF NPs in alleviating hypoxia was explored in tumor-bearing mice through photoacoustic imaging. In addition, the diagnosis and treatment effect of AGPF NPs were evaluated by magnetic resonance imaging (MRI) and bioluminescent imaging (BLI) on orthotopic glioma mice respectively.Results: In vitro experiments showed that AGPF NPs had good dispersion, stability, and controlled release. AGPF NPs were internalized by cells through endocytosis, and could significantly reduce the survival rate of U87 cells and increase apoptosis under irradiation. In addition, we monitored blood oxygen saturation at the tumor site in real-time through photoacoustic imaging (PAI), and the results showed that synergistic mild-photothermal therapy/chemotherapy effectively alleviated tumor hypoxia. Finally, in vivo anti-tumor experiments have shown that synergistic therapy can effectively alleviate hypoxia and inhibit the growth of orthotopic gliomas.Conclusion: This work not only provides an effective means for real-time monitoring of the dynamic feedback between tumor hypoxia relief and therapeutic efficacy, but also offers a potential approach for the clinical treatment of gliomas.Keywords: gliomas, hypoxia relief, photothermal therapy, real-time monitoring, photoacoustic imaging

Zhili Cui,1 Liyuan Zhou,1 Xin An,2 Wenli Liu,1 Jingxia Li,1 Yueping Zhang,3 Wei Zhang4 1Department of Gynecology, Affiliated Hospital of Hebei University of Engineering, Handan, Hebei, 056002, People’s Republic of China; 2Department of Pathology, Handan First Hospital, Handan, Hebei, 056000, People’s Republic of China; 3Shexian Maternal and Child Health Hospital, Shexian, Hebei, 056004, People’s Republic of China; 4Department of Gynecology, Handan Traditional Chinese Medicine Hospital, Handan, Hebei, 056001, People’s Republic of ChinaCorrespondence: Zhili Cui, Department of Gynecology, Affiliated Hospital of Hebei University of Engineering, No. 81 Congtai Road, Congtai District, Handan, Hebei, 056002, People’s Republic of China, Tel + 86-3103962266, Email cuizhili72@yeah.netBackground: Circular RNAs (circRNAs) exhibit unique patterns of expression and high levels of stability in patient plasma samples such that they represent ideal non-invasive biomarkers that can be leveraged to detect a wide array of diseases including endometrial cancer (EC). This study was designed to identify circRNAs with potential diagnostic utility in serum samples from EC patients while also evaluating the utility of macrophage migration inhibitory factor (MIF) as a biomarker when screening for this form of cancer in the clinic.Methods: Levels of circEPSTI1 and MIF were assessed in the plasma of EC patients and healthy subjects (n=186 each) through qPCR and ELISAs. The diagnostic utility of these biomarkers was assessed with receiver operating characteristic curve (ROC) analyses.Results: Relative to healthy subjects, EC patient serum contained significantly elevated circEPSTI1 and MIF. An association was noted between circEPSTI1 expression in stages, histologic grade, and residual tumor. ROC curves confirmed that serum circEPSTI1 levels distinguished between controls and patients with EC with an Area of 0.835 and serum MIF levels distinguished between controls and patients with EC with an Area of 0.6646. When instead diagnosing patients based on the combination of MIF and circEPSTI1, the Area further rose to 0.8604.Conclusion: Assessing the combination of circEPSTI1 and MIF may be a viable approach to reliably diagnosing EC.Keywords: circEPSTI1, MIF, diagnostic biomarker, endometrial cancer

Yaohui Yi, Meng Sun, Jiachen Lu, Xiaofeng Dou, Yingying Yu, Ling Zhou School of Public Health, Dalian Medical University, Dalian City, Liaoning Province, People’s Republic of ChinaCorrespondence: Ling Zhou, School of Public Health, Dalian Medical University, Dalian City, Liaoning Province, People’s Republic of China, Tel +86-411-8611-0368, Email zhouling0609@163.comBackground: As future health workers, medical students’ attitudes towards tuberculosis (TB) patients can impact TB control. However, in China, there is a lack of well-quantified assessment regarding the stigma among medical students towards TB patients. Therefore, this study aimed to validate the Chinese version of the Tuberculosis related-Stigma Scale (TSS) in medical students and to apply the scale to measure stigma and its determinants.Methods: A total of 1035 eligible medical students participated in the cross-sectional questionnaire. Exploratory factor analyses (EFA) and confirmatory factor analyses (CFA) were first conducted to test Chinese version of the TSS construct validity, and then internal consistency was assessed using Cronbach’s α. Finally, multiple linear regression analyses were conducted to identify predictors of stigma.Results: EFA extracted two factors (“Social distance” and “Exclusionary sentiments”). The CFA further confirmed the two-factor construct. The internal consistency, convergent and divergent validity of the adapted Chinese version of the TSS was acceptable. Furthermore, Whether one has received TB health education and whether know a person with TB are associated with all dimensions of TB stigma, while differences in sex and place of residence play different roles in influencing the different dimensions of stigma.Conclusion: The adapted Chinese version of the TSS can be used to assess the level of stigma among medical students in China towards tuberculosis patients. When implementing future interventions to reduce stigma associated with TB, special attention should be given to medical students from urban areas, of male gender, who have not received TB health education, and no know a person with TB. However, these two dimensions (“Social distance” and “Exclusionary sentiments”) are impacted by different determinants and should therefore be addressed separately when designing, implementing, and evaluating measures to reduce stigma.Keywords: tuberculosis related-stigma scale, medical student, psychometrics, determinants

Xue Zhang,1,&ast; Aili Zhang,2,&ast; Hao Guan,1 Li Zhou,1 Jiao Zhang,3 Wenjie Yin1 1Department of Pharmacy, Kunming Yan’an Hospital, Yan’an Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, 650051, People’s Republic of China; 2Department of Scientific Research, Kunming Yan’an Hospital, Yan’an Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, 650051, People’s Republic of China; 3Department of Basic Medicine, Zhaotong Health Vocational College, Zhaotong, Yunnan, 657000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wenjie Yin; Xue Zhang, Department of Pharmacy, Kunming Yan’an Hospital, Yan’an Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, 650051, People’s Republic of China, Email yinwenjie0606@163.com; zxyougubaihe@163.comObjective: Low back pain is one of the main causes of disability in the world. Although regenerative medicine may represent breakthroughs in the management of low back pain, its use remains controversial. Therefore, we conducted a meta-analysis to evaluate the clinical efficacy of platelet-rich plasma (PRP) injection therapy versus different control groups for chronic low back pain during 4 weeks, 3 months, and 6 months.Methods: Different electronic databases were searched for randomized controlled trials up to August 2023. Mean changes from baseline in pain and Oswestry Disability Index (ODI) scores at 4 weeks, 3 months, and 6 months and standard deviations of outcome were recorded.Results: Four articles with 154 cases were finally included in this meta-analysis. After 4 weeks, corticosteroid (CS) was the optimal treatment option for chronic low back pain in terms of improvement in pain and disability index (surface under the cumulative ranking curve [SUCRA]=71.3%, SUCRA=57.8%, respectively). After 3 months, radiofrequency (RF) emerged as the best therapy in pain (SUCRA=100%) and disability index (SUCRA=98.5%), followed by PRP (SUCRA=62.3%, SUCRA=64.3%, respectively), CS (SUCRA=24.6%, SUCRA=25.9%, respectively) and lidocaine (SUCRA=13.1%, SUCRA=11.3%, respectively). At 6 months, RF was most likely to be the best treatment in pain (SUCRA=94.9%) and disability index (SUCRA=77.3%), followed by PRP (SUCRA=71.2%, SUCRA=79.6%, respectively). However, compared with the last follow-up, there was a slight downward trend in improvement pain and disability index with RF, while PRP was still an upward trend.Conclusion: This study demonstrated better short-term improvement of chronic low back pain with CS after 4 weeks. PRP and RF improvement effects matched, but follow-up of at least 6 months showed that PRP seemed to be more advantageous in improvement in disability indices. Considering the limitations of this study, these conclusions still need to be verified by more comparative RCTs and a longer follow-up period.Keywords: platelet-rich plasma, chronic low back pain, meta-analysis, randomized controlled trial, clinical efficacy

Xiaoyan He,1 Guozhen Zai,1 Lidan Zhou,2 Shengyang Chen,3 Guizhi Wang1 1Department of Pathology, the Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 2Department of Radiology, the Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 3Department of Hepatobiliary Pancreatic Surgery, the Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of ChinaCorrespondence: Guizhi Wang, Email wgz2019@126.comBackground: Research has indicated that VRK1 is essential for the tumor cell cycle. However, its prognostic and immunotherapeutic predictive significance has not been documented in hepatocellular carcinoma (HCC).Methods: The TCGA, ICGC, and GSE14520 datasets were used to investigate VRK1 expression and its predictive significance of survival outcomes. The qRT-PCR and immunohistochemistry (IHC) were used to confirm the findings. The immunotherapeutic response of VRK1 was anticipated by the IMvigor210 cohort. Lastly, the association between immune infiltration, m6A modification, and functional enrichment of differentially expressed genes (DEGs) was investigated in connection to VRK1 expression.Results: VRK1 expression was markedly elevated on both the mRNA and protein levels in HCC. In HCC patients, a high expression of VRK1 was linked to a poor prognosis. Furthermore, there was a substantial positive correlation seen between increased VRK1 expression and the response rate to anti-PD-L1 immunotherapy. Relationships between VRK1 and m6A-related genes as well as different immune cells were shown by correlation studies. Lastly, enrichment analysis revealed a tight relationship between VRK1 and important biological functions, including DNA replication, cell cycle control, and fatty acid metabolism.Conclusion: Our research reveals the potential of VRK1 as a novel biomarker for prognosis and immunotherapy response in HCC patients.Keywords: VRK1, immune infiltration, immunotherapy, m6A, HCC

Chunsheng Duan, Yuan Li, Jiansu Ma, Yanglin Song, Lixia Zhou Department of Pediatric Surgery, Xingtai People’s Hospital, Xingtai, Hebei, 054000, People’s Republic of ChinaCorrespondence: Lixia Zhou, Department of Pediatric Surgery, Xingtai People’s Hospital, 16 Hongxing Street, Xingtai, Hebei, 054000, People’s Republic of China, Tel/Fax +86-0319-3286096, Email zhoulx_xt@163.comPurpose: Surgery impairs immune function and increases postoperative complications. B7H3, a co-stimulatory molecule, plays a crucial role in immune regulation. The present study examined the impact of B7H3 on the postoperative immune response in children with acute suppurative appendicitis (ASA) by comparing preoperative and postoperative B7H3 levels in laparoscopic surgery (LA) and open appendectomy (OA).Patients and Methods: 198 pediatric ASA patients were enrolled. The researcher group performed LA, while the control group performed OA. Perioperative time, recovery time of gastrointestinal function, time to pass gas, length of incision, and length of hospitalization were compared in the perioperative period. Additionally, an ELISA assay was conducted to examine the levels of inflammatory factors and B7H3 and CD28. Short-term postoperative complications were also evaluated.Results: Compared with the control group, the research group had a short operative time, gastrointestinal function recovery time, gas time, and hospitalization time. The short-term complication rate was significantly lower in the research group. More importantly, B7H3 and CD28 were insignificantly different preoperatively, but they were all reduced postoperatively. Moreover, the reduction was more pronounced in the research group. The same results were noted in inflammatory factors and immune markers, which were non-significant different preoperatively and were typically reduced postoperatively, particularly in the research group. Finally, postoperative B7H3 was positively correlated with both inflammatory factors and immune cell levels.Conclusion: B7H3 was reduced in both postoperative periods, and the reduction was more pronounced in the LA group. B7H3 may be involved in postoperative recovery by modulating postoperative inflammation and immune responses.Keywords: ASA, laparoscopic surgery, open appendectomy, B7H3, CD298

Hui Yu,1 Xinyi He,1 Jinmeng Yao,1 Xiaoya Gu,1 Lin Zhou,1 Li Gao,1,2 Jia Wang1 1Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 2Health Science Center, Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of ChinaCorrespondence: Jia Wang; Li Gao, Email wangjia_80@163.com; gaoli23@mail.xjtu.edu.cnBackground: Molybdenum diselenide (MoSe2), as a nano near-infrared absorber, has been widely studied in the field of photothermal therapy of cancer. However, there is little research on its application in the treatment of human choriocarcinoma.Methods and Results: In this paper, a new type of carbon-coated MoSe2 (MEC) nanoparticles was prepared by a one-step hydrothermal method. The chemical characterization including SEM, TEM, EDS, XRD, FT-IR, TGA, Roman, and XPS showed that MEC was successfully synthesized. MEC exhibited a high photothermal conversion efficiency (50.97%) and extraordinary photothermal stability under laser irradiation. The cell experiment results showed that MEC had good biocompatibility on normal cells while significant photothermal effect on human choriocarcinoma (JEG-3) cells, achieving a good anticancer effect. The level of reactive oxygen species (ROS) in JEG-3 cells was significantly increased under the combination of MEC nanoparticles and near-infrared radiation. MEC nanoparticles could induce apoptosis of JEG-3 cells in combination with near-infrared radiation. Finally, transcriptomic analysis verified that MEC combined with laser radiation could inhibit DNA replication and induce apoptosis, thus improving its therapeutic effect on human choriocarcinoma.Conclusion: MEC nanoparticles exert an excellent photothermal effect and may become an important candidate drug for the treatment of human choriocarcinoma.Keywords: MoSe2, carbon-coated, biocompatibility, human choriocarcinoma, photothermal therapy

Debiao Xiang,1– 3 Lili Zhou,4 Rui Yang,1,4 Fang Yuan,1– 3 Yilin Xu,4 Yuan Yang,1,4 Yong Qiao,1– 3 Xin Li1– 3 1Department of Pharmacy, The Third Hospital of Changsha, Changsha, Hunan Province, People’s Republic of China; 2Hunan Provincial Key Laboratory of Anti-Resistance Microbial Drugs, Changsha, Hunan Province, People’s Republic of China; 3The Clinical Application Research Institute of Antibiotics in Changsha, Changsha, Hunan Province, People’s Republic of China; 4College of Pharmacy, Hunan University of Chinese Medicine, Changsha, Hunan Province, People’s Republic of ChinaCorrespondence: Xin Li, 176 Laodong West Road, Tianxin District, Changsha, Hunan Province, People’s Republic of China, Tel +86 0731-85171320, Email xin-li@cssdsyy.comAbstract: Currently, cancer remains one of the most significant threats to human health. Treatment of most cancers remains challenging, despite the implementation of diverse therapies in clinical practice. In recent years, research on the mechanism of ferroptosis has presented novel perspectives for cancer treatment. Ferroptosis is a regulated cell death process caused by lipid peroxidation of membrane unsaturated fatty acids catalyzed by iron ions. The rapid development of bio-nanotechnology has generated considerable interest in exploiting iron-induced cell death as a new therapeutic target against cancer. This article provides a comprehensive overview of recent advancements at the intersection of iron-induced cell death and bionanotechnology. In this respect, the mechanism of iron-induced cell death and its relation to cancer are summarized. Furthermore, the feasibility of a nano-drug delivery system based on iron-induced cell death for cancer treatment is introduced and analyzed. Secondly, strategies for inducing iron-induced cell death using nanodrug delivery technology are discussed, including promoting Fenton reactions, inhibiting glutathione peroxidase 4, reducing low glutathione levels, and inhibiting system Xc−. Additionally, the article explores the potential of combined treatment strategies involving iron-induced cell death and bionanotechnology. Finally, the application prospects and challenges of iron-induced nanoagents for cancer treatment are discussed.Keywords: cancers, ferroptosis, nano-drug delivery system, target

Linqi Zhou,1 Changyuan Qiao,1 Jialing Huang,2 Jian Lin,2 Haisheng Zhang,2 Jian Xie,2 Yonggui Yuan,3 Changchun Hu2 1School of the Fourth Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 2Department of Clinical Psychology, Affiliated Hangzhou First People’s Hospital, Westlake University School of Medicine, Hangzhou, People’s Republic of China; 3Department of Psychosomatics and Psychiatry, Zhong Da Hospital, School of Medicine, Southeast University, Nanjing, People’s Republic of ChinaCorrespondence: Changchun Hu, Department of Clinical Psychology, Affiliated Hangzhou First People’s Hospital, Westlake University School of Medicine, No. 261 Huansha Road, Shangcheng District, Hangzhou, 310002, People’s Republic of China, Tel +86-571-56006902, Email chuntianjs@163.comBackground: Previous studies have demonstrated a strong association between recent stressful life events and non-suicidal self-injury (NSSI) among adolescents. Internalizing symptoms and difficulty in emotion regulation (DER) may mediate this relationship. This study aimed to investigate the relationship between recent stressful life events and NSSI severity in adolescents and the potential moderating role of internalizing symptoms and DER.Methods: A total of 224 adolescent inpatients (78.6% female) participated in the study, with an age range of 12– 18 years old. Data on recent stressful life events, internalizing symptoms, DER, and NSSI behaviors were collected using a clinician-rated questionnaire. A structural equation model was used to test the hypothesized model.Results: The rate of NSSI reporting among adolescents in the past 12 months was 65.18%. Recent stressful life events were found to be directly associated with NSSI severity (β = 0.128, P = 0.023). A chain-mediating effect between recent stressful life events and NSSI was also confirmed (β = 0.034, P = 0.023), with DER and internalizing symptoms playing a chain-mediating role and DER having a significantly indirect association with NSSI through internalizing symptoms.Conclusion: Recent stressful life events appear to play a role in the etiology of NSSI, particularly punishment and interpersonal relationship events that warrant special attention. DER and internalizing symptoms play a chain-mediating role in the relationship between life events and NSSI. Reducing recent stressful life events, screening for internalizing symptoms, and improving emotion regulation may decrease NSSI behavior among adolescents.Keywords: non-suicidal self-injury, adolescents, recent stressful life events, internalizing symptoms, difficulty in emotion regulation, structural equation model

Chenjun Huang,1,&ast; Xiao Xiao,1,&ast; Lin Tong,2,&ast; Zhiyuan Gao,1 Jun Ji,2 Lin Zhou,3 Ya Li,4 Lijuan Liu,5 Huijuan Feng,5 Meng Fang,2 Chunfang Gao1,2 1Department of Clinical Laboratory Medicine Center, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, People’s Republic of China; 2Department of Laboratory Medicine, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, 200438, People’s Republic of China; 3Department of Laboratory Medicine, Shanghai Changzheng Hospital, Shanghai, 200003, People’s Republic of China; 4Department of Laboratory Medicine, The First Affiliated Hospital of Kunming Medical University, Kunming, 650032, People’s Republic of China; 5Department of Laboratory Medicine, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chunfang Gao, Department of Clinical Laboratory Medicine Center, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, People’s Republic of China, Tel +86-21-65161782-1210, Email gaocf1115@163.com; gaocf1115@shutcm.edu.cnPurpose: Early detection of hepatocellular carcinoma (HCC) through surveillance could reduce this cancer-associated mortality. We aimed to develop and validate algorithms using panel serum biomarkers to identify HCC in a real-world multi-center study in China.Patients and Methods: A total of 10,359 eligible subjects, including HCCs and benign liver diseases (BLDs), were recruited from six Chinese medical centers. The three nomograms were built using logistic regression and their sensitivities and specificities were carefully assessed in training and validation cohorts. HCC patients after surgical resection were followed to determine the prognostic values of these algorithms. Prospective surveillance performance was assessed in a cohort of chronic hepatitis B patients during 144 weeks follow-up.Results: Independent risk factors such as alpha-fetoprotein (AFP), lens cuinaris agglutinin-reactive fraction of AFP (AFP-L3), des-gamma-carboxy prothrombin (DCP), albumin (ALB), and total bilirubin (TBIL) obtained from train cohort were used to construct three nomograms (LAD, C-GALAD, and TAGALAD) using logistic regression. In the training and two validation cohorts, their AUCs were all over 0.900, and the higher AUCs appeared in TAGALAD and C-GALAD. Furthermore, the three nomograms could effectively stratify HCC into two groups with different survival and recurrence outcomes in follow-up validation. Notably, TAGALAD could predict HCC up to 48 weeks (AUC: 0.984) and 24 weeks (AUC: 0.900) before clinical diagnosis.Conclusion: The proposed nomograms generated from real-world Chinese populations are effective and easy-to use for HCC surveillance, diagnosis, as well as prognostic evaluation in various clinical scenarios based on data feasibility.Keywords: hepatocellular carcinoma, real-world data, diagnostic, prognosis, algorithm

Renzhe Tang,1,&ast; Chong Li,2,&ast; Dongmei Di,1 Lin Zhou,2 Yongxiang Qian,1 Chaohua Qiang,3 Chao Ma,1 Rui Zhou,1 Bin Wang,1 Min Wang1 1Department of Cardiothoracic Surgery, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu Province, 213003, People’s Republic of China; 2Department of Respiratory Medicine, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu Province, 213003, People’s Republic of China; 3Department of Echocardiography, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu Province, 213003, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Min Wang; Bin Wang, Department of Cardiothoracic Surgery, The Third Affiliated Hospital of Soochow University, No. 185 of Juqian Street, Changzhou, Jiangsu Province, 213003, People’s Republic of China, Email wangmin80808@163.com; wangbin1987@suda.edu.cnObjective: Obstructive sleep apnea (OSA) is a disorder characterized by disruption in breathing and hypoventilation. In parallel, metabolic syndrome (MetS) mainly co-occur with OSA, however, their association has not been fully elucidated. Therefore, this study aimed to reveal the relationship between OSA and MetS using data from the National Health And Nutrition Examination Survey (NHANES) database and pooled data from Genome-Wide Association Studies (GWAS).Material and Methods: Data from the National Health and Nutrition Examination Survey and pooled data from genome-wide association analysis (GWAS) were used univariate and multivariate logistic regression analyses were carried out to evaluate the correlation between OSA and MetS, and multivariate logistic regression models were utilized for adjusting for potential confounders. Two-sample Mendelian randomization (MR) was used to assess the causal relationship between OSA and MetS. The variance-weighted inverse method was employed as the main method of analysis.Results: A positive relationship of OSA with Mets was evidenced by multivariate logistic regression analysis, and OSA was associated with higher incidence rates of all-cause and cardiovascular mortality. OSA is strongly associated with abdominal obesity, hypertension, hyperglycemia, high triglycerides, and low HDL. Furthermore, except for hypertriglyceridemia, MR analysis indicated that genetically driven OSA was causally associated with a higher risk of MetS.Conclusion: The positive relationship of OSA with Mets was revealed, and higher incidence rates of all-cause mortality and cardiovascular mortality were noted to be correlated with OSA. MR analysis further confirmed the causal relationship of OSA with MetS and cardiovascular disease.Keywords: obstructive sleep apnea, metabolic syndrome, cardiovascular disease, NHANES, Mendelian randomization

Song Wen,1,&ast; Yufeng Ruan,2,&ast; Zhongyu Shi,3 Shujie Dan,2 Ligang Zhou1– 4 1Department of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai, People’s Republic of China; 2Department of General Practice, Huinan Health Service Center, Shanghai, People’s Republic of China; 3Department of International Medicine, Shanghai Pudong Hospital, Fudan University, Shanghai, People’s Republic of China; 4Shanghai Key Laboratory of Vascular Lesions Regulation and Remodeling, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ligang Zhou, Department of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai, 201399, People’s Republic of China, Tel +8613611927616, Email zhouligang1n1@163.comBackground: Despite the demonstrated benefits of insulin therapy, many general practitioners (GPs) are hesitant to administer it due to challenges such as a lack of knowledge, time constraints, and patient reluctance. The barriers that prevent a GP from initiating insulin therapy may vary in comparison to those encountered by a diabetic patient; this aspect of clinical research in the South Shanghai metropolitan area has received limited attention so far.Objective: This is a 6-months of interventional analytic cohort study. The prime aim is to investigate the barriers general practitioners (GPs) face when initiating insulin therapy for patients with type 2 diabetes (T2D).Materials and Methods: As part of a training program, all 189 registered GPs in Nanhui Health Service Center in Shanghai were given a structured online-multi-choice questionnaire before and after a six-month interval, during which the GPs received sessions of training on insulin therapy either on theoretic classes or clinical practices.Results: Before and after training, via the methods of multiple-response analyses, the results showed that social, GP’s, and patient barriers to initiating insulin therapy were comparable. However, through the crosstabs chi-square test, we found significant changes in the basal insulin initiation following the prescription of the senior endocrinologists, the titration of insulin, and the need for training (p< 0.05). The Spearman analyses discovered significant changes associated with the cause of initial insulin refusal and the factors influencing insulin administration. Finally, the binary logistic regression analysis revealed that distinct causes such as social factors, insurance, GP experience, insulin dosage calculation, follow-up, and patients’ feelings are related to insulin treatment application before and after training.Conclusion: According to this study, training increased general practitioners’ confidence in initiating insulin administration, especially basal insulin. General practitioners require additional education on insulin therapy, with a potential need for increased face-to-face training for insulin initiation.Keywords: diabetes mellitus, insulin initiation barrier, general practitioner, community

Tong Chen,1– 3 Shiquan Wu,1 Ling Feng,4 SiYu Long,1 Yu Liu,1,2 WenQian Lu,5 Wenya Chen,1 Guoai Hong,1 Li Zhou,1 Fang Wang,1 Yuechan Luo,1 Hequn Zou1,3,5 1Department of Nephrology, South China Hospital of Shenzhen University, Shenzhen, People’s Republic of China; 2Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, National Regional Key Technology Engineering Laboratory for Medical Ultrasound School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen, People’s Republic of China; 3Department of Nephrology, The Third Affiliated Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 4Department of Nephrology, Shenzhen Hospital, Southern Medical University, Shenzhen, People’s Republic of China; 5Department of Medicine, The Chinese University of Hong Kong, Shenzhen, People’s Republic of ChinaCorrespondence: Hequn Zou, School of Medicine, The Chinese University of Hong Kong, Shenzhen, People’s Republic of China, Email zouhequn@cuhk.edu.cnBackground: The annual prevalence of metabolic syndrome (MetS) is increasing. Therefore, early screening and recognition of MetS are critical. This study aimed to evaluate the association between high-density lipoprotein (HDL) subclasses and MetS and to examine whether they could serve as early indicators in a Chinese community-based population with normal high-density lipoprotein cholesterol (HDL-C) levels.Methods: We used microfluidic chip technology to measure HDL subclasses in 463 people with normal HDL levels in 2018. We assessed how HDL subclasses correlated with and predicted insulin resistance (IR) and metabolic syndrome (MetS), evaluated by homeostatic model insulin resistance index (HOMA-IR) and the 2009 International Diabetes Federation (IDF), the American Heart Association (AHA), and the National Heart, Lung, and Blood Institute (NHLBI) criteria, respectively. We used correlation tests and ROC curves for the analysis.Results: The results indicate that there was a negative association between HDL2b% and the risk of IR and MetS in both sexes. Subjects in the highest quartile of HDL2b% had a significantly lower prevalence of IR and MetS than those in the lowest quartile (P< 0.01). Correlation analysis between HDL2b% and metabolic risk factors showed that HDL2b% had a stronger association with these factors than HDL-C did in both sexes. ROC curve analysis also showed that HDL2b% had significant diagnostic value for IR and MetS compared to other lipid indicators.Conclusion: This study showed that MetS alters the distribution of HDL subclasses even when HDL-C levels are within the normal range. HDL-2b% has better diagnostic value for IR and MetS than HDL-C alone and may be a useful marker for early screening.Keywords: HDL subclass, insulin resistance, metabolic syndrome, normal HDL-C population

Cheng Peng, Yilin Xu, Jing Wu, Donghai Wu, Lili Zhou, Xinhua Xia School of Pharmacy, Hunan University of Chinese Medicine, Changsha, People’s Republic of ChinaCorrespondence: Xinhua Xia; Lili Zhou, Email xiaxinhua001@hnucm.edu.cn; 004683@hnucm.edu.cnAbstract: The tumor microenvironment (TME) plays an important role in various stages of tumor generation, metastasis, and evasion of immune monitoring and treatment. TME targeted therapy is based on TME components, related pathways or active molecules as therapeutic targets. Therefore, TME targeted therapy based on environmental differences between TME and normal cells has been widely studied. Biomimetic nanocarriers with low clearance, low immunogenicity, and high targeting have enormous potential in tumor treatment. This review introduces the composition and characteristics of TME, including cancer‑associated fibroblasts (CAFs), extracellular matrix (ECM), tumor blood vessels, non-tumor cells, and the latest research progress of biomimetic nanoparticles (NPs) based on TME. It also discusses the opportunities and challenges of clinical transformation of biomimetic nanoparticles.Keywords: nanoparticles, biomimetic delivery system, tumor therapy, cell membrane-coating

Xiaoguang Xu,1,2 Lefei Zhou,3 Zhaohui Tong1 1Department 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; 2Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Jilin Medical University, Jilin, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, Ordos Central Hospital, Ordos School of Clinical Medicine, Inner Mongolia Medical University, Inner Mongolia, People’s Republic of ChinaCorrespondence: Zhaohui Tong, Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, No. 8, Gongti South Road, Chaoyang District, Beijing, 100020, People’s Republic of China, Tel +8613089172570, Fax +8601085231217, Email tongzhaohuicy@sina.comObjective: To identify the relationship between patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and their fractional-exhaled nitric oxide (FeNO) levels.Methods: Patients diagnosed with AECOPD in the respiratory department of Beijing Chaoyang Hospital from June 2017 to August 2019 were recorded. The demographic data, FeNO value, peripheral blood eosinophil count, number of acute exacerbations in the past year, pulmonary function test, use of inhaled glucocorticoids (ICS) and other data were collected and analyzed. FeNO was measured again three months after discharge, the participants were assessed to determine if the stable period criteria were met.Results: A total of 214 patients met the requirements of this study. 25ppb for FeNO was used as the cutoff for further analysis. The proportion of males, number of acute exacerbations in the past year, number of ICS users, leukocyte count and eosinophil count in the high FeNO-level group was significantly higher than that in the low-level group (P < 0.05). The results showed that the number of acute exacerbations in the past year, number of ICS users, and eosinophil count were statistically significant in the model (P < 0.05). The study also showed that the level of FeNO in the acute exacerbation phase was significantly higher than that in the stable phase. The ROC curve that the area under the curve used by FeNO to predict ICS used is 0.631 (95% CI: 0.526– 0.736), and the corresponding P value is 0.022.Conclusion: FeNO is closely related to activated T2 inflammation and eosinophil count in COPD patients. The FeNO levels can be used as an index to evaluate the severity of COPD and predict the recovery of activity after ICS treatment. FeNO can predict the use of ICS and is a beneficial supplement to eosinophils.Keywords: fractional exhaled nitric oxide, chronic obstructive pulmonary disease, acute exacerbation, airway inflammation

Joseph M Coney,1 Jasmyne E McCoy,1 Samriddhi Buxy Sinha,2 Nina Sonbolian,2 Lujia Zhou,3 Thomas P Hull,1 Shawn A Lewis,1 David G Miller,1 Michael A Novak,1 Scott D Pendergast,1 Hang Pham,1 Sean M Platt,1 Llewelyn J Rao,1 Jerome P Schartman,1 Lawrence J Singerman,1 Richard Donkor,1 Margaret Fink,1 Ryan Zubricky,4 Helene Karcher2 1Retina Associates of Cleveland Inc, Beachwood, OH, USA; 2Novartis Pharma AG, Basel, Switzerland; 3KMK Consulting, Morristown, NJ, USA; 4Geisinger Eye Institute, Danville, PA, USACorrespondence: Joseph M Coney, Retina Associates of Cleveland Inc, 24075 Commerce Park, Beachwood, OH, 44122, USA, Tel +1 (216) 831-5700, Email jconey@retina-assoc.comObjective: Retrospective, real-world study to evaluate visual acuity (VA), anti-vascular endothelial growth factor (anti-VEGF) injection intervals, and central macular thickness (CMT) in neovascular age-related macular degeneration (nAMD) eyes switched to brolucizumab only or to brolucizumab alternating with another anti-VEGF.Methods: The overall study population comprised eyes that were given ≥ 1 brolucizumab injection between 1 October 2019 and 30 November 2021. The brolucizumab-only (BRO) cohort consisted of prior anti-VEGF-treated eyes treated exclusively with ≥ 3 brolucizumab injections over ≥ 12 or ≥ 18 months; the alternating brolucizumab (ALT) cohort comprised prior anti-VEGF-treated eyes treated with ≥ 2 brolucizumab injections and ≥ 1 other anti-VEGF over ≥ 12 or ≥ 18 months.Results: A total of 482 eyes received ≥ 1 brolucizumab injection during the study period. Mean VA changes from baseline were − 1.1± 15.1 letters (BRO cohort; n = 174) and 1.3± 13.0 letters (ALT cohort; n = 47) at Month 12, and 0.0± 13.5 letters (BRO cohort; n = 95) and − 7.3± 17.2 letters (ALT cohort; n = 29) at Month 18. Mean changes in injection intervals were +26.9± 48.1 days (BRO cohort) and +11.1± 17.3 days (ALT cohort) at Month 12 and +36.3± 52.3 days (BRO cohort) and +14.0± 19.9 days (ALT cohort) at Month 18. Mean changes in CMT were − 35.2± 108.1 μm (BRO cohort) and − 31.5± 91.2 μm (ALT cohort) at Month 12 and − 38.9± 75.0 μm (BRO cohort) and − 9.0± 59.9 μm (ALT cohort) at Month 18. Intraocular inflammation-related adverse events were recorded in 22/482 (4.6%) eyes.Conclusion: Treatment with either brolucizumab alone or brolucizumab alternating with another anti-VEGF can preserve vision, reduce CMT, and extend anti-VEGF injection intervals in patients with nAMD.Keywords: alternating anti-VEGF treatments, brolucizumab, neovascular age-related macular degeneration, wet age-related macular degeneration, 12-month outcomes, 18-month outcomes