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Yu Liu,1,* Enyi Zhu,1,* Yan Lei,1,* Ailing Luo,2 Yaping Yan,2 Mansi Cai,2 Shanshan Liu,2 Yan Huang,3 Hui Guan,1 Ming Zhong,1 Weinian Li,4 Lian Lin,1 Michael Hultstöm,5,6 Enyin Lai,7 Zhihua Zheng,1 Xiaoping Liu,2 Chun Tang1 1Department of Nephrology, Center of Kidney and Urology, the Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518107, People’s Republic of China; 2Department of Hematology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou, 510623, People’s Republic of China; 3The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, 421001, People’s Republic of China; 4Department of Rheumatology, Guangzhou First People’s Hospital, South China University of Technology, Guangzhou, 510623, People’s Republic of China; 5Department of Surgical Sciences, Anesthesiology and Intensive Care, Uppsala University, Uppsala, Sweden; 6Department of Medical Cell Biology, Unit for Integrative Physiology, Uppsala University, Uppsala, Sweden; 7Department of Physiology, School of Basic Medical Sciences, Zhejiang University School of Medicine, Hangzhou, 310058, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chun Tang; Xiaoping Liu, Email tangch28@mail.sysu.edu.cn; liu_xiaoping@gwcmc.orgPurpose: Methyltransferase like 1 (METTL1) regulates epitranscriptomes via the m7G modification in mammalian mRNA and microRNA. Systemic lupus erythematosus (SLE) is caused by abnormal immune reactivity and has diverse clinical manifestations. RNA methylation as a mechanism to regulate gene expression is widely implicated in immune regulation. However, the role of m7G in immune response of SLE has not been extensively studied.Patients and Methods: Expression of METTL1 was identified in the public dataset GSE122459 and validated in an independent cohort of SLE patients. We investigated the association between METTL1-expression and clinical manifestations of SLE. Subsequently, differentially expressed genes (DEG) that were correlated with METTL1-expression in GSE122459 were used for functional enrichment analysis. The correlation between infiltrating immune cells and METTL1, as well as candidate biomarkers identified to be correlated with either METTL1 or immune cell infiltration were assessed by single-sample GSEA. Potential mechanisms were explored with Gene ontology and KEGG pathway enrichment. Diagnostic performances of candidate biomarkers in SLE were analyzed.Results: The mRNA and protein expression of METTL1 in SLE patients were significantly decreased in both datasets. METTL1-coexpressed DEGs were enriched in several key immune-related pathways. Activated CD8 T cells, activated CD4 T cells, memory B cells and type 2 helper T cells were different between patients with high and low METTL1 expression. Further, activated CD8 T-cells, activated CD4 T-cells, memory B-cells were correlated with METTL1. The genes of LAMP3, CD83, PDCD1LG2, IGKVD3D-20, IGKV5-2, IGKV2D-30, IGLV3-19 and IGLV4-60 were identified as candidate targets that were correlated with immune cell proportion. Moreover, LAMP3, CD83, and PDCD1LG2 expression were of diagnostic value in SLE as indicated by ROC analysis.Conclusion: Our findings suggested that METTL1 and its candidate targets LAMP3, CD83, PDCD1LG2 may be used for diagnosing SLE and could be explored for developing targeted molecular therapy for SLE.Keywords: methyltransferase like 1, systemic lupus erythematosus, immunity, single sample gene set enrichment analysis, biomarker

Fan Zhang,* Wei Li,* Yingying Zhang, Dong Wang, Jing Li, Chengpeng Li, Liqun He Department of Cardiology, Intervention Cardiology Center, Wuhan No.1 Hospital, Wuhan, 430022, People’s Republic of China*These authors contributed equally to this workCorrespondence: Liqun He, Department of Cardiology, Intervention Cardiology Center, Wuhan No.1 Hospital, No. 215, Zhongshan Avenue, Qiaokou District, Wuhan, 430022, People’s Republic of China, Tel/Fax +86-027-85332105, Email heliqundr@163.comPurpose: Acute coronary syndrome (ACS) is a common acute myocardial ischemia syndrome and is one of the death-related causes of cardiovascular diseases. Identifying biomarkers to indicate disease severity and predict the occurrence of major adverse cardiovascular events (MACE) would benefit the clinical prognosis of ACS. This study estimated the expression and significance of lncRNA TPRG1-AS1 in the onset and development of ACS, aiming to explore a novel biomarker for the diagnosis and prognosis of ACS.Patients and Methods: A total of 109 ACS patients and 66 patients who received coronary angiography and excluded ACS were enrolled in this study. TPRG1-AS1 in the serum of study subjects was analyzed by PCR. The significance of TPRG1-AS1 in screening ACS was evaluated by ROC analysis. The association of TPRG1-AS1 with the disease severity of ACS was assessed by Pearson correlation analysis with patients’ clinicopathological features. The potential of TPRG1-AS1 in predicting the occurrence of MACE was assessed by logistic regression analysis.Results: Significant upregulation of TPRG1-AS1 was observed in ACS patients, which served as a risk factor for ACS and distinguish between ACS patients and the normal group. TPRG1-AS1 was positively correlated with Gensini score, cys-C, cTnI, and NT-proBNP levels of ACS patients, which indicate severe development of ACS. Additionally, increasing serum TPRG1-AS1 was associated with the high incidence of MACE during patients’ hospitalization and was identified as a risk factor for MACE in ACS patients.Conclusion: Upregulated TPRG1-AS1 in ACS served as a diagnostic biomarker and predicted the severe development of patients.Keywords: cardiovascular disease, lncRNA, onset, inpatient MACE, severity

Huamei Wei,1,* Lizheng Huang,2,* Qi Lu,2,* Zheng Huang,2 Yanyan Huang,2 Zuoming Xu,3 Wenchuan Li,3 Jian Pu3,4 1Department of Pathology, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, People’s Republic of China; 2Graduate College of Youjiang Medical University for Nationalities, Baise, People’s Republic of China; 3Department of Hepatobiliary Surgery, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, People’s Republic of China; 4Guangxi Clinical Medical Research Center of Hepatobiliary Disease, Baise, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jian Pu, Department of Hepatobiliary Surgery, Affiliated Hospital of Youjiang Medical University for Nationalities, No. 18 Zhongshan Two Road, Baise, 533000, People’s Republic of China, Email jian_pu@126.comPurpose: N6-methyladenosine (m6A) modification plays an important role in regulating RNA maturation, stability, and translation. Thus, m6A modification is involved in various pathophysiological processes including hepatocellular carcinoma (HCC). However, the direct contribution of m6A modifications to RNA function in HCC remains unclear. Here, we identified LEAWBIH (long non-coding RNA epigenetically activating Wnt/β-catenin signalling in HCC) as an m6A-modified long non-coding RNA (lncRNA) and investigated the effects of m6A on the function of LEAWBIH in HCC.Methods: Quantitative polymerase chain reaction was performed to measure the gene expression in tissues and cells. The level of m6A modification was detected using a methylated RNA immunoprecipitation assay and single-base elongation- and ligation-based qPCR amplification method. Cell proliferation was evaluated using the Glo cell viability and CCK-8 assays. Cell migration and invasion were evaluated using Transwell migration and invasion assays. The mechanisms of m6A modified LEAWBIH were investigated using chromatin isolation by RNA purification, chromatin immunoprecipitation, and dual-luciferase reporter assays.Results: LEAWBIH was highly expressed and correlated with poor survival in HCC patients. LEAWBIH was identified as a m6A-modified transcript. m6A modification increased LEAWBIH transcript stability. The m6A modification level of LEAWBIH was increased in HCC, and a high m6A modification level of LEAWBIH predicted poor survival. LEAWBIH promotes HCC cell proliferation, migration, and invasion in an m6A modification-dependent manner. Mechanistic investigations revealed that m6A-modified LEAWBIH activated Wnt/β-catenin signaling. m6A-modified LEAWBIH binds to the m6A reader YTHDC1, which further interacts with and recruits H3K9me2 demethylase KDM3B to CTNNB1 promoter, leading to H3K9me2 demethylation and CTNNB1 transcription activation. Functional rescue assays showed that blocking Wnt/β-catenin signaling abolished the role of LEAWBIH in HCC.Conclusion: m6A-modified LEAWBIH exerts oncogenic effects in HCC by epigenetically activating Wnt/β-catenin signaling, highlighting m6A-modified LEAWBIH as a promising therapeutic target for HCC.Keywords: hepatocellular carcinoma, N6-methyladenosine, histone methylation, Wnt/β-catenin signaling

Yinghua Zhu,1,* Haiyan He,2,* Hang Qiu,1 Xudong Zhang,1 Linsheng Wang,1 Wenhua Li1,3 1Institute of Cardiovascular Diseases, Xuzhou Medical University, Xuzhou, People’s Republic of China; 2Department of Cardiology, Xuzhou Municipal Hospital Affiliated to Xuzhou Medical University, Xuzhou, People’s Republic of China; 3Department of Cardiology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wenhua Li, Department of Cardiology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, People’s Republic of China, Tel +86 18052268293, Email xzwenhua0202@163.comObjective: Our objective was to develop and validate a nomogram model aiming at predicting the risk of contrast-induced acute kidney injury (CI-AKI) following percutaneous coronary intervention (PCI) in patients suffering from type 2 diabetes mellitus (T2DM) and also diagnosed with acute coronary syndrome (ACS).Methods: The study gathered data from 722 T2DM patients with ACS who received PCI treatment at the Affiliated Hospital of Xuzhou Medical University between February 2019 and December 2022, serving as the training set. Considering the validation set, the study included 217 patients who received PCI at the East Affiliated Hospital of Xuzhou Medical University. The patients were classified into CI-AKI and non-CI-AKI groups. The study employed univariate and multivariate logistic analysis for identifying independent risk factors for CI-AKI, followed by developing a predictive nomogram model for CI-AKI risk using R software. The predictive performance and clinical utility of the nomogram were assessed through internal and external validation, utilizing the areas under the receiver operating characteristic curve (AUC-ROC), the Hosmer-Lemeshow test and calibration correction curve, and decision curve analysis (DCA).Results: The nomogram comprised four variables: age, estimated glomerular filtration rate (eGFR), triglyceride-glucose (TyG) index, and prognostic nutritional index (PNI). The AUC-ROC were 0.785 (95% confidence interval (CI) 0.729– 0.841) and 0.802 (95% CI 0.699– 0.905) for the training and validation cohorts, respectively, indicating a high discriminative ability of the nomogram. The calibration assessment and decision curve analysis have substantiated the strong concordance and clinical usefulness of the aforementioned.Conclusion: The nomogram exhibits favorable discrimination and accuracy, enabling it to visually and individually identify pre-procedure high-risk patients, and possesses a predictive capacity regarding CI-AKI incidence after PCI in patients diagnosed with both T2DM and ACS.Keywords: triglyceride-glucose index, prognostic nutritional index, acute coronary syndrome, nomogram, percutaneous coronary intervention, contrast-induced acute kidney injury

Wanting Li,1,* Feng Cheng,1,* Jun Zhang,1 Caihong Li,2 Daijing Yu,1 Halimureti Simayijiang,1 Haiyan Liu,2 Sijin Li,2 Jiangwei Yan1 1Shanxi Key Laboratory of Forensic Medicine, Shanxi Medical University, Jinzhong, People’s Republic of China; 2Department of Nuclear Medicine, First Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jiangwei Yan; Sijin Li, Tel +86 03513985386 ; +86 03514639352, Email yanjw@sxmu.edu.cn; lisjnm123@163.comPurpose: Radioactive iodine therapy is administered through oral route, which is accumulated and absorbed in the intestine. However, its effects on the intestine remain unclear. In this study, we investigated the changes in the gut microbiota and metabolites following radioactive iodine therapy.Patients and Methods: A total of 76 stool samples from the same 38 patients were collected at the start of radioactive iodine therapy and three days following the therapy. Stool microbiota and metabolites were detected using 16S rRNA gene sequencing and liquid chromatography-mass spectrometry.Results: Enterobacteriales, Enterobacteriaceae and Escherichia-Shigella were elevated in most patients (27/38) following the therapy. The levels of 2-hydroxyundec-7-enoylcarnitine were significantly lower, whereas those of 5-dehydroavenasterol, butylisopropylamine, and salsoline-1-carboxylate were higher following the therapy. The relative abundance of Escherichia-Shigella was negatively correlated with 2-hydroxyundec-7-enoylcarnitine level (r2 = − 0.661, P = 0.009). Functional pathways were predicted to be involved in amino acid and lipid metabolism following the therapy. Particularly, phenylalanine, linoleic acid, sphingolipid, purine, and alpha-linolenic acid metabolism were the main metabolic pathways.Conclusion: Gut microbiota was disturbed following radioactive iodine therapy, with increased Escherichia-Shigella. Processes associated with energy production seems to be impacted following the therapy, with significantly decreased 2-hydroxyundec-7-enoylcarnitine level. Meanwhile, some metabolites and functional pathways may have a positive effect on intestinal homeostasis, and may be related to the repair and promotion of gut recovery following the therapy. This study provides a basic foundation to explore how radioactive iodine affects gut microbiota and metabolites, and how gut function is regulated in response to radioactive iodine therapy.Keywords: radioactive iodine, gut microbiota, Escherichia-Shigella, metabolism, thyroid carcinoma

Shanshan Chen,1,2,* Youjia Duan,2,* Yongchao Zhang,2 Long Cheng,2 Liang Cai,2 Xiaopu Hou,2 Wei Li1,2 1Cancer Center, Beijing Tongren Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Cancer Center, Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei Li, Cancer Center, Beijing Tongren Hospital, Capital Medical University, 2 West Ring South Road, Daxing District, Beijing, 100176, People’s Republic of China, Tel +86 15811029005, Email weili8989@ccmu.edu.cnPurpose: Tumor capsule is an independent prognostic factor for patients with hepatocellular carcinoma (HCC) and used increasingly to guide clinical decision-making. Considering the genetic complexity for capsule formation and its potential association with hypoxia, the significance of the polymorphisms of hypoxia-related genes in capsule formation and HCC prognosis remains to be elucidated.Patients and Methods: Peripheral blood samples from HCC patients were collected in this study. Single nucleotide polymorphism (SNP) genotyping was conducted by the iPLEX chemistry on a matrix-assisted laser desorption/ionization time-of-flight mass spectrometer (Sequenom, Inc.). The demographic and clinical data for the patients were obtained through medical chart review and/or consultation with the treating physicians. SPSS 25.0, R 4.1.1, and PLINK toolset were used to perform statistical analysis.Results: A total of 183 patients were enrolled, including 88 patients assigned to the capsule group and 95 to the non-capsule group. SLC2A1 rs841858 T allele, SLC2A1 rs2297977 T allele, STAT1 rs1547550 C allele, and STAT1 rs34997637 G allele were associated with significantly increased risk of capsule formation. The genotypes of SLC2A1 rs841858, SLC2A1 rs2297977, STAT1 rs34997637, and STAT1 rs1914408 were significantly associated with the formation of HCC capsule. The polymorphisms of STAT1 rs2066802, STAT1 rs12693591, and HIF1A rs2057482 showed close relationship with the prognosis of HCC patients in the capsule group, while the genotype distributions of CTNNB1 rs4135385, IFNG rs1861494, and SERPINE1 rs2227631 were closely related to the survival of patients in the non-capsule group. Further haplotype analysis suggested that SLC2A1 block 1 and STAT1 block 2 were related to the susceptibility of HCC capsule.Conclusion: The polymorphisms of the hypoxia-related genes (HIF1A, SERPINE1, IFNG, STAT1, CTNNB1, and SLC2A1) were correlated with the formation of HCC capsule. Several SNPs in these genes also showed association with HCC prognosis except SLC2A1. Further functional studies are warranted to explore the underlying mechanisms.Keywords: single nucleotide polymorphism, hypoxia, capsule formation, hepatocellular carcinoma

Renhou Zhi, Pengfei Hao, Weibin Li, Haoliang Zhao Department of General Surgery, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, 030032, People’s Republic of ChinaCorrespondence: Haoliang Zhao, Department of General Surgery, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, No. 99 Longcheng Street, Xiaodian District, Taiyuan, 030032, People’s Republic of China, Tel +86 138 0340 0588, Email haoliangzhao@hotmail.comPurpose: Cyclin-dependent kinase regulatory subunit 2 (CKS2) has an important function in regulating cancer progression and cell cycle. This research aims to ascertain how CKS2 plays its part through multi-omics analyses, to reveal its relationship with the immune microenvironment in hepatocellular carcinoma (HCC).Material and Methods: Multiple databases were used to determine the transcriptional data of CKS2, epigenetic changes, and effects thereof upon the prognosis of HCC patients. The biological functions of CKS2 in HCC were expounded by functional enrichment analysis. TIMER, GSEA, TIP, and online single-cell sequencing databases were adopted for revealing correlations of CKS2 expression with infiltration of immune cells, immunomodulators, immunity cycle, and immune markers in the immune microenvironment of HCC. In addition, qRT-PCR and Western blot were used to validate gene expression in tissues from HCC patients.Results: Open database analysis confirmed that CKS2 is highly expressed in HCC and that it is related to poor prognosis in HCC patients. Aberrant methylation levels of the two methylation sites of CKS2 in HCC contributed to its high expression and were correlated significantly with survival. The CKS2 expression was positively correlated with most immunomodulators and infiltration levels for B and CD8+T cells, dendritic cells, and macrophages, especially exhausted CD8+T cells. Besides, the CKS2 expression was also found to have significant correlations with immunity cycle steps and diverse immune markers in HCC. The high CKS2 expression was confirmed in HCC at both mRNA and protein levels, showing a significant increase compared to normal tissue.Conclusion: CKS2 is a potential prognostic biomarker of HCC and can promote the progression of HCC via its influences on the immune environment. Additionally, a positive correlation between CKS2 and immune markers was observed, highlighting its potential as an immunotherapeutic target.Keywords: hepatocellular carcinoma, CKS2, tumor immune microenvironment, immune cycle, immune markers, immunomodulators

Zhiwei Jia,1 Shunxin Zhang,2 Wei Li3 1Department of Orthopedics, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 101100, People’s Republic of China; 2Department of Ultrasound, 2nd Medical Center of PLA General Hospital, Beijing, 100853, People’s Republic of China; 3Department of Sports Medicine, Fourth Medical Center of PLA General Hospital, Beijing, 100048, People’s Republic of ChinaCorrespondence: Wei Li, Department of Sports Medicine, Fourth Medical Center of PLA General Hospital, Beijing, 100048, People’s Republic of China, Email weilichn@126.com Shunxin Zhang, Department of Ultrasound, 2nd Medical Center of PLA General Hospital, Beijing, 100853, People’s Republic of China, Email zhangshunxin301@163.comAbstract: Degenerative bone disorders such as intervertebral disc degeneration (IVDD), osteoarthritis (OA), and osteoporosis (OP) pose significant health challenges for aging populations and lack effective treatment options. The field of regenerative medicine holds promise in addressing these disorders, with a focus on utilizing extracellular vesicles (EVs) derived from stem cells as an innovative therapeutic approach. EVs have shown great potential in stimulating biological responses, making them an attractive candidate for rejuvenating degenerative bone disorders. However, a comprehensive review summarizing the current state of this field and providing a clear assessment of EV-based therapies in degenerative bone disorders is currently deficient. In this review, we aim to fill the existing gap by outlining the current knowledge on the role of EVs derived from different types of stem cells, such as mesenchymal stem cells, embryonic stem cells, and induced pluripotent stem cells, in bone regeneration. Furthermore, we discuss the therapeutic potential of EV-based treatments for IVDD, OA, and OP. By substantiating the use of stem cell-derived EVs, we highlight their promising potential as a cell-free strategy to improve degenerative bone disorders.Keywords: nanomedicine, extracellular vesicles, stem cells, regeneration, therapy

Xiangjun Chen,* Wenting Li,* Xueling Li, Keke Li, Guilong Zhang, Wei Hong School of Pharmacy, Shandong New Drug Loading & Release Technology and Preparation Engineering Laboratory, Binzhou Medical University, Yantai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei Hong; Guilong Zhang, Tel/Fax +86-0535-6908191 ; Tel/Fax +86-0535- 6913719, Email hongwei_sy@bzmc.edu.cn; glzhang@bzmc.edu.cnIntroduction: As we enter the post-antibiotic era, the rise of antibiotic-resistant pathogenic bacteria is becoming a serious threat to public health. This problem is further complicated by antibiotic-resistant biofilms, for which current treatment options are limited.Methods: To tackle this challenge, we propose a novel approach that involves the use of photodynamic cationic pH-sensitive liposomes loaded with ultra-small copper oxide (Ce6@Lipo/UCONs) to effectively eliminate drug-resistant bacteria and eradicate biofilms while minimizing safety concerns and the risk of resistance development.Results: Our study demonstrates that Ce6@Lipo/UCONs have minimal toxicity to mammalian cells and can significantly enhance the association affinity with methicillin-resistant Staphylococcus aureus (MRSA) as confirmed by fluorescent microscope and flow cytometry, thereby greatly improving the bactericidal effect against planktonic MRSA. The cationic nature of Ce6@Lipo/UCONs also enables them to penetrate MRSA biofilms and respond to the acidic microenvironment within the biofilm, effectively releasing the loaded UCONs. Our results indicate that Ce6@Lipo/UCONs could effectively eliminate biofilms under light irradiation conditions, as evidenced by both biomass analysis and scanning electron microscopy observations. In addition, significant antibacterial effects and abscess healing were observed in MRSA-infected mice treated with Ce6@Lipo/UCONs upon light irradiation, while good biocompatibility was achieved in vivo.Conclusion: Taken together, our findings suggest that photodynamic cationic ultrasmall copper oxide nanoparticles-loaded liposomes are a highly promising nano platform for combating antibiotic-resistant microbial pathogens and biofilms. The effective biofilm penetration and synergistic effect between photodynamic inactivation and metal sterilization make them a valuable tool for overcoming the challenges posed by antibiotic resistance.Keywords: biofilm, antibiotic resistance, synergistic potential, photodynamic inactivation, metal sterilization

Wei Li, Jun Zhao, Ruiping Hao, Shujuan Wang, Ming Chen, Huijun Liu, Le Qi, Zaijun Hao Department of Anaesthesiology, Ordos Central Hospital, Ordos, Inner Mongolia Autonomous Region, People’s Republic of ChinaCorrespondence: Zaijun Hao, Department of Anesthesiology, Ordos Central Hospital, Ordos, Inner Mongolia Autonomous Region, 017000, People’s Republic of China, Tel/Fax +8615204778880, Email dengdairy@126.comPurpose: Evaluate the efficacy and safety of remimazolam besylate combined with esketamine for outpatient colonoscopy.Patients and methods: A total of 150 outpatients undergoing colonoscopy were randomized into two groups. A MOAA/S score ≤ 3 was maintained. The primary outcome was the rate of successful colonoscopy completion. Time indicators, hemodynamic parameters, the consumption of lidocaine, esketamine, propofol and remimazolam besylate, MOAA/S scores and bispectral index (BIS) values, the lowest SpO2, body movement, the use of rescue medication, endoscopist and patient satisfaction, recall of the procedure, mini-mental state examination (MMSE), fatigue level and adverse events were recorded.Results: Procedure completion was equivalent between groups (P > 0.05). Both induction and awakening times were significantly shorter in the P group (P < 0.05). There were no significant differences in colonoscopy time and discharge time (P > 0.05). The lowest SpO2 was significantly lower in the P group, while the level of fatigue was higher (P < 0.05). Patient satisfaction was significantly higher in the R group (P < 0.05). Endoscopist satisfaction was significantly higher in the P group (P < 0.05). There were no significant differences in both systolic and diastolic blood pressure between groups except at T5 and T6 (P > 0.05). Both HR and RR were significantly lower in the P group from T3 to T5 (P < 0.05). BIS values were significantly lower in the P group from T3 to T5, while MOAA/S was significantly lower in the P group at T3 and T4 (P < 0.05). Pain on injection was significantly higher in the P group (P < 0.05).Conclusion: Remimazolam besylate has a similar efficacy to propofol when combined with subanesthetic doses of esketamine during outpatient colonoscopy. Remimazolam besylate combined with esketamine resulted in less injection pain and more stable hemodynamics, although it prolonged induction and awakening time.Keywords: remimazolam besylate, propofol, esketamine, colonoscopy

Haoxin Guo,1,&ast; Wenbo Li,1,&ast; Kuan Wang,1,2 Zetong Nie,1 Xiang Zhang,1 Siqiong Bai,1 Naxin Duan,1 Xiaorong Li,1 Bojie Hu1 1Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin University Eye Hospital, Tianjin, People’s Republic of China; 2Cangzhou Eye Hospital, Cangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bojie Hu, Email bhu07@tmu.edu.cnPurpose: We aimed to investigate the risk factors associated with revitrectomy in eyes with diabetic vitreous hemorrhage and to determine the prognosis of these patients at least one year postoperatively.Patients and Methods: This retrospective case-control study had a minimum follow-up period of one year. Patients were divided into single vitrectomy group (control group, n=202) and revitrectomy group (case group, n=36) for analysis. The indications, number, and timing of revitrectomies were documented. And the revitrectomy group was further divided into two vitrectomies group (n=30) and three or more vitrectomies group (n=6). The best-corrected visual acuity (BCVA) at the last follow-up and the occurrence of neovascular glaucoma (NVG) were compared among the single vitrectomy, two vitrectomies and three or more vitrectomies groups. We conducted a thorough collection of patient data and used univariate and binary logistic regression analyses to identify the risk factors associated with revitrectomy.Results: A total of 197 patients (238 eyes) were included. Thirty-six eyes (15.1%) required revitrectomy with six eyes (2.5%) undergoing three or more vitrectomies during the follow-up period. The median duration of the second vitrectomy was 3 (2– 6) months. The indications for a second vitrectomy included 28 eyes (77.8%) of postoperative vitreous hemorrhage and 7 eyes (22.2%) combined with tractional retinal detachment. Patients undergoing three or more vitrectomies had significantly worse postoperative BCVA and a higher incidence of NVG (P< 0.01). Fibrinogen> 4 g/L (P< 0.001) and preoperative anti-vascular endothelial growth factor intravitreal injection (P=0.015) were independent risk factors for revitrectomy, and glycated hemoglobin A1c (HbA1c)> 10% (P=0.049) showed significant difference only in univariate analysis.Conclusion: Patients requiring revitrectomy tended to have higher fibrinogen levels, tightly adhered fibrovascular membranes, higher HbA1c levels, and worse prognoses.Keywords: proliferative diabetic retinopathy, vitreous hemorrhage, revitrectomy, fibrinogen, retinal ischemia

Jiaxin Yu,1,2 Wei Zuo,1,2 Hongwei Fan,1,3 Jiayu Wu,1,2 Luyao Qiao,1,2,4 Benyu Yang,1,2,5 Wenxi Li,1,2,5 Yang Yang,1,2,&ast; Bo Zhang1,2,&ast; 1Department of Pharmacy, Peking Union Medical College Hospital, Beijing, People’s Republic of China; 2State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Beijing, People’s Republic of China; 3Department of Infectious Medicine, Peking Union Medical College Hospital, Beijing, People’s Republic of China; 4Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 5School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yang Yang; Bo Zhang, Department of pharmacy, Peking Union Medical College Hospital, Dongdan Campus, No. 1 Shuaifuyuan Wangfujing Dongcheng, District, Beijing, 100730, People’s Republic of China, Tel/Fax +86 10 69156527, Email yangyangsdu2010@126.com; zhangbopumch@163.comPurpose: Ceftazidime-avibactam (C-A) is a treatment option for carbapenem-resistant gram-negative bacterial (CR-GNB) infections, but little is known regarding its suitability for the intensive care unit (ICU). The current study aimed to analyze use of C-A for critically ill patients, determine independent predictors of clinical outcome and mortality and explore routine dosages for patients in continuous renal replacement therapy (CRRT).Patients and Methods: A single-center, retrospective and observational study was conducted in critically ill patients receiving different C-A-based therapies for CR-GNB infections in a tertiary teaching hospital in Beijing, China. Demographic data, severity of infection, clinical outcomes and mortality were assessed. The primary and secondary outcome of this study was 90-day all-cause mortality and 14-day clinical response, respectively.Results: A total of 43 patients with CR-GNB infection were enrolled, including 14 (32.6%) patients received C-A monotherapy. C-A monotherapy and combination with other agents did not affect 14-day clinical response or 90-day survival. All-cause mortality at 90-days was 39.5% (17/43). Multivariate Cox analysis showed that concomitant with bloodstream infection was independent risk factors for 90-day mortality and that the time to initiation of C-A and Acute Physiology and Chronic Health Evaluation (APACHE) score was independent predictors of 14-day clinical response. Five CRRT patients who received high-dose C-A therapy (> 3.75 g/d) had prolonged survival compared with 5 who received low-dose C-A (< 3.75 g/d, p = 0.03).Conclusion: C-A was an effective therapy for severe CR-GNB infections and clinical response correlated with the time of C-A initiation. A dosage > 3.75g/d C-A was associated with prolonged survival of CRRT patients. Randomized controlled trials or multicenter studies are needed to confirm these findings.Keywords: ceftazidime-avibactam, renal replacement therapy, infections, intensive care unit, carbapenem-resistant gram-negative bacteria

Bin Gao,1,2,&ast; Yuanyuan Liu,3,&ast; Quanwei Shen,4 Changqing Fu,3 Weiyi Li,5 Xu Li4 1Research Institute for International and Comparative Education, Shanghai Normal University, Shanghai, 200234, People’s Republic of China; 2Lab for Educational Big Data and Policymaking, Shanghai Normal University, Shanghai, 200234, People’s Republic of China; 3Mental Health Center, Hubei University of Medicine, Shiyan, 442000, People’s Republic of China; 4School of Education, Shanghai Normal University, Shanghai, 200234, People’s Republic of China; 5School of Business Administration, Jimei University, Xiamen, 361021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Quanwei Shen, School of Education, Shanghai Normal University, 100 Guilin Road, Xuhui District, Shanghai, 200234, People’s Republic of China, Tel +86 13429962432, Email psywe@qq.comBackground: With the popularity of smartphone and their increasingly rich functions, people’s attachment to their phones is increasing. While people enjoy the convenience that smartphone bring (eg, accessing information and socializing), it also leads to problematic smartphone use (eg, phubbing). Previous research has shown that boredom proneness can trigger phubbing. However, the underlying psychological mechanisms are not yet clear.Methods: To address this research gap, we surveyed 556 Chinese college students (Mage = 18.89 years, SD = 1.18) during the COVID-19 pandemic and all participants completed a self-report questionnaire. Drawing the Interaction of Person-Affect-Cognition-Execution model (I-PACE) for addictive behaviors, this study developed and examined a multiple mediation model incorporating boredom proneness, loneliness, fear of missing out (FoMO), and phubbing.Results: (1) Boredom proneness could positively predict phubbing; (2) loneliness and FoMO mediated the relationship between boredom proneness and phubbing, respectively; and (3) loneliness and FoMO sequentially mediated the relationship between boredom proneness and phubbing.Conclusion: These findings are not only valuable for understanding the underlying mechanisms linking boredom proneness and phubbing, but also suggest that three types of interventions could be effectively used to decrease the risk of phubbing among college students, namely, reducing boredom proneness, relieving loneliness, and decreasing FoMO.Keywords: boredom proneness, loneliness, FoMO, phubbing, multiple mediation model, college students

Yan Yang,1 Yaofeng Xue,1 Wenjing Li,1 Fang Yang,1 Xiaohe Guo,1 Zhongyin Zhou2 1Department of Gastroenterology, The First Affiliated Hospital of Xinxiang Medical University, Weihui, People’s Republic of China; 2Department of Gastroenterology, Renmin Hospital of Wuhan University, Hubei Key Laboratory of Digestive System Disease, Wuhan, People’s Republic of ChinaCorrespondence: Zhongyin Zhou, Department of Gastroenterology, Renmin Hospital of Wuhan University, Hubei Key Laboratory of Digestive System Disease, No. 238, Jiefang Road, No. 99, Zhangzhidong Road, Wuchang District, Wuhan, 430060, People’s Republic of China, Tel +86-13871029766, Fax +86 027-88043958, Email wuyangwu712@163.comPurpose: Patients with gastrointestinal bleeding (GIB) and acute myocardial infarction (AMI) have higher mortality than that with either GIB or AMI alone. The aims of this study were to determine the incidence and risk factors of AMI in patients with GIB.Patients and Methods: From January 2015 to January 2018, we retrospectively studied 1287 patients with GIB in Renmin Hospital of Wuhan University. Various demographic, laboratory and outcome data were reviewed by charts.Results: Thirty-seven patients had AMI and were placed in AMI group and the rest 1250 patients were in non-AMI group. Patients with AMI were more likely to be older than 70 years, have hypertension, coronary heart disease, chronic kidney disease, and have the recent history of taking aspirin before admission. The ROC curve of hemoglobin (HB) on admission showed area under curve was 0.762, the optimal cut-off value is 76.5g/L. Logistic regression analysis showed that age ≥ 70 years old, coronary heart disease and HB < 76.5g/L on admission were independent risk factors of AMI in patients with GIB. The mortality of patients during hospitalization in AMI group and in non-AMI group were 45.95% and 5.48%, respectively. Patients who displayed a history of liver disease and HB < 76.5g/L on admission had a higher death rate.Conclusion: GIB increased the risk of subsequent AMI, especially in patients over 70 years old, with history of coronary heart disease and HB < 76.5g/L on admission. Patients with GIB and AMI who had history of liver disease and HB < 76.5g/L on admission had a higher mortality rate. Clinicians should identify the high-risk patients of AMI among the GIB population early and prevent AMI.Keywords: cardiovascular, evaluation, gastrointestinal hemorrhages, prognosis

Weiling Zhou,1 Qian Gao,1 Lianjing Wang,2 Weijing Li,2 Cuiying He,2 Yanting Li,3 Lei Feng,1 Wei Liu,2 Lihong Liu,2 Yuan Wang1 1Department of Endocrine and Metabolic Diseases, The Fourth Hospital of Hebei Medical University, Shijiazhuang, HeBei Province, 050000, People’s Republic of China; 2Department of Hematology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, HeBei Province, 050000, People’s Republic of China; 3Department of Glandular Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang, HeBei Province, 050000, People’s Republic of ChinaCorrespondence: Lihong Liu, Department of Hematology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, HeBei Province, 050000, People’s Republic of China, Email liulihong111222@163.com Yuan Wang, Department of Endocrine and Metabolic Diseases, The Fourth Hospital of Hebei Medical University, Shijiazhuang, HeBei Province, 050000, People’s Republic of China, Email wyuan1111122222@163.comBackground: Diffuse large B-cell lymphoma (DLBCL) involving the breast, spleen, and bone in a male patient with hepatitis B virus (HBV) infection is extremely rare in clinical practice.Case Presentation: We report a case of DLBCL involving the breast, spleen, and bone (triple expression of Bcl-2+, Bcl-6+, and 70% positive C-mcy) in a male patient with HBV admitted to our hospital. The patient was treated with EPOCH× 4, lenalidomide+EPOCH× 2 chemotherapy, intermittent methotrexate intrathecal injections to prevent central invasion, and autologous stem cell transplantation (ASCT). The patient is currently in complete remission, and the follow-up time was 43 months.Conclusion: A patient with DLBCL involving the breast, spleen, and bone can be treated with a combination of multiple regimens. If the patient’s economic conditions permit it, ASCT can be considered.Keywords: breast, viral hepatitis B, diffuse large B-cell lymphoma, triple expression, autologous stem cell transplantation

Rui Yuan,1,&ast; Yuwen Zhang,1,&ast; Liqiong Liao,2 Yige Ge,1 Weichang Li,1 Qinghui Zhi1 1Hospital of Stomatology, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong, 510030, People’s Republic of China; 2Biomaterials Research Center, School of Biomedical Engineering, Southern Medical University, Guangzhou, Guangdong, 510515, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qinghui Zhi, Hospital of Stomatology, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-Sen University, Guangzhou, Guangdong, 510055, People’s Republic of China, Email zhiqingh@mail.sysu.edu.cn Weichang Li, Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-Sen University, Guangzhou, Guangdong, 510055, People’s Republic of China, Email liwch57@mail.sysu.edu.cnBackground: Dentin caries remains a significant public concern, with no clinically viable material that effectively combines remineralization and antimicrobial properties. To address this issue, this study focused on the development of a bio-inspired multifunctional nanogel with both antibacterial and biomineralization properties.Methods: First, p(NIPAm-co-DMC) (PNPDC) copolymers were synthesized from N-isopropylacrylamide (NIPAm) and 2-methacryloyloxyethyl-trimethyl ammonium chloride (DMC). Subsequently, PNPDC was combined with γ-polyglutamic acid (γ-PGA) through physical cross-linking to form nanogels. These nanogels served as templates for the mineralization of calcium phosphate (Cap), resulting in Cap-loaded PNPDC/PGA nanogels. The nanogels were characterized using various techniques, including TEM, particle tracking analysis, XRD, and FTIR. The release properties of ions were also assessed. In addition, the antibacterial properties of the Cap-loaded PNPDC/PGA nanogels were evaluated using the broth microdilution method and a biofilm formation assay. The remineralization effects were examined on both demineralized dentin and type I collagen in vitro.Results: PNPDC/PGA nanogels were successfully synthesized and loaded with Cap. The diameter of the Cap-loaded PNPDC/PGA nanogels was measured as 196.5 nm at 25°C and 162.3 nm at 37°C. These Cap-loaded nanogels released Ca2+ and PO43- ions quickly, effectively blocking dental tubules with a depth of 10 μm and promoting the remineralization of demineralized dentin within 7 days. Additionally, they facilitated the heavy intrafibrillar mineralization of type I collagen within 3 days. Moreover, the Cap-loaded nanogels exhibited MIC50 and MIC90 values of 12.5 and 50 mg/mL against Streptococcus mutans, respectively, with an MBC value of 100 mg/mL. At a concentration of 50 mg/mL, the Cap-loaded nanogels also demonstrated potent inhibitory effects on biofilm formation by Streptococcus mutans while maintaining good biocompatibility.Conclusion: Cap-loaded PNPDC/PGA nanogels are a multifunctional biomimetic system with antibacterial and dentin remineralization effects. This strategy of using antibacterial nanogels as mineral feedstock carriers offered fresh insight into the clinical management of caries.Graphical Abstract: Keywords: nanomaterial, mineralization, antibacterial materials, dentinal tubule occlusion, caries

Wenjian Li Department of Urology, Changzhou Third People’s Hospital, Changzhou Medical Center, Nanjing Medical University, Changzhou, Jiangsu, People’s Republic of ChinaCorrespondence: Wenjian Li, Department of Urology, Changzhou Third People’s Hospital, Changzhou Medical Center, Nanjing Medical University, 300 Lanling North Road, Changzhou, Jiangsu, 213001, People’s Republic of China, Tel +86-0519-82009011, Email bolite@163.com

Danni Xue,1,&ast; Binghai Sun,1,&ast; Weijian Li,1 Hui Zhou,2 Fujun Ding,1 Weilong Xiao1,3 1School of Psychology, Zhejiang Normal University, Jinhua, 321004, People’s Republic of China; 2Jinhua Advanced Research Institute, Jinhua, Zhejiang, 321004, People’s Republic of China; 3Research Unit Occupational & Organizational Psychology and Professional Learning, KU Leuven, Leuven, 3000, Belgium&ast;These authors contributed equally to this workCorrespondence: Fujun Ding, School of Psychology, Zhejiang Normal University, 688 Yingbin Road, Jinhua, 321004, People’s Republic of China, Email dfj201810100017@163.comBackground: Teacher burnout is characterized by emotional and physical exhaustion resulting from excessive work-related stress. Previous research based on traditional latent variable theory has revealed a significant negative relationship between TB and psychological capital (PsyCap). This study explored the complex symptoms of TB and the contact points of PsyCap in reducing TB using psychometric network analysis.Methods: A total of 3991 teachers completed the burnout subscale of the Professional Quality of Life and Psychological Capital Scale.Results: The results showed that: (a) In the TB network, the core symptoms displayed by teachers due to burnout are difficulty feeling “I am a very caring person”, “I am happy”, and “I am the person I always wanted to be”; (b) The TB-PsyCap network was closely connected, and the symptoms affected each other. PsyCap affected the TB network through “I feel optimistic and happy almost every day” and “I often feel that there is a future as a teacher”; (c) PsyCap’s bridge symptoms had a negative impact on TB, and PsyCap may reduce TB primarily through optimistic, hopeful dimensions.Conclusion and Implications: Psychometric network analysis helps us understand the complex symptoms of TB and the contact points of PsyCap in reducing TB. This study offers valuable insights into the prevention of, and intervention in, burnout within the teaching community.Keywords: teacher burnout, psychological capital, network analysis, network comparison

Zhiping Liu, Wensha Zhang, Zhiwei Zhao, Wenhao Li, Jinhua Zhang Department of Gastroenterology, Hankou Hospital of Wuhan, Wuhan, Hubei, People’s Republic of ChinaCorrespondence: Jinhua Zhang, Department of Gastroenterology, Hankou Hospital of Wuhan, No. 7, Erqice Road, Jiangan District, Wuhan, Hubei, 430012, People’s Republic of China, Tel +86 27 8228 3181, Email jinhuazh2000@outlook.comPurpose: Vitamin D deficiency was thought to be associated with insulin resistance and metabolic-associated fatty liver disease (MAFLD). The aim of this study was to investigate the relationship between the triglyceride-glucose (TyG) index, a useful surrogate biomarker of insulin resistance, and vitamin D status in patients with MAFLD.Patients and Methods: A total of 566 patients with MAFLD were included in this retrospective cross-sectional study. Clinical characteristics were compared between participants with and without vitamin D deficiency. The association between the TyG index and serum 25-hydroxyvitamin D [25(OH)D] levels was determined by Spearman correlation analysis and logistic regression analysis. The receiver operating characteristic curve (ROC) was used to assess the diagnostic efficacy of TyG index for vitamin D deficiency in MAFLD patients.Results: The TyG index levels were higher in the vitamin D deficient group than in the non-vitamin D deficient group, and serum 25(OH)D was negatively correlated with the TyG index. The TyG index was an independent risk factor for vitamin D deficiency in patients with MAFLD. The area under the curve (AUC) of the TyG index for the identification of vitamin D deficiency in MAFLD patients was 0.744 (95% CI: 0.701– 0.787, p< 0.001).Conclusion: The TyG index is negatively associated with vitamin D status in patients with MAFLD. In patients with MAFLD, a higher TyG index may be an indication of a higher prevalence of vitamin D deficiency.Keywords: triglyceride-glucose index, 25-hydroxyvitamin D, metabolic-associated fatty liver disease, insulin resistance

Zheng Wang,1,&ast; Hui Xu,1,2,&ast; Hang Zhou,1 Wanyu Li,1 Tao Yang,1 Yunfeng Zhou1 1Henan University of Chinese Medicine, Zhengzhou, 450046, People’s Republic of China; 2Tuina Department, the Third Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, 450046, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yunfeng Zhou, College of Acupuncture and Massage, Henan University of Chinese Medicine, No. 156, Jinshui East Road, Zhengzhou, Henan Province, People’s Republic of China, Tel +8615639717497, Fax +86037165962633, Email zyf5680198@126.comPurpose: Tuina is a nonpharmacological modality for pain relief that has found applications in the treatment of several pain disorders. Tuina analgesia has been increasingly studied; however, few studies have focused on the previous publication trends, prevalent research areas, collaborations, and other factors. This study aimed to systematically analyze research trends and hot topics in the field of tuina analgesia over the past 30 years, using bibliometric analysis, to inform future research.Methods: The web of science database was searched for literature on tuina analgesia from 1992– 2023. VOSviewer and CiteSpace were used to analyze annual publication volumes, countries, institutions, journals and CO-cited journals, authorship, articles, and keywords and their relevance, and to perform co-occurrence and clustering analyses.Results: A total of 621 literature elements were included in the analysis. The annual volume of publications has increased steadily in recent years. The top three high-yielding countries were the United States, China, and Canada, respectively. The top three institutional outputs were from Shanghai University of Chinese medicine, Beijing University of Chinese medicine, and McMaster University, respectively. Notably, there was an imbalance between national outputs and centrality, with higher centrality in the United States (0.35) and lower in China (0.01). Cochrane Database of Systematic Reviews was the journal with the most publications (22), and PAIN was the most influential co-cited journals (publications=306). Moreover, current research in this field was dominated by studies on Tuina for relieving postoperative pain, the effectiveness of Tuina analgesia, and Tuina treatment for pain accompanied by anxiety.Conclusion: This study employed bibliometrics to analyze the literature on Tuina for pain treatment over a 30-year period, identifying potential collaborators, institutions, hot topics, and future research trends that will inform potential future directions.Keywords: analgesia, tuina, bibliometric analysis, VOSviewer, CiteSpace

Shaoxing Zhang,1 Yuxin Zhang,1 Ruijie Liu,1 Shuying Yuan,2 Yanwen Chen,1 Wenjie Li,1 Xinrong Lu,3 Yongliang Tong,3 Linlin Hou,4 Li Chen,3 Guiqin Sun1 1School of Medical Technology and Information Engineering, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 2Clinical Laboratory Department, Jiaxing Maternity and Child Health Care Hospital, Jiaxing, Zhejiang, People’s Republic of China; 3Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Fudan University, Shanghai, People’s Republic of China; 4College of Veterinary Medicine, Qingdao Agricultural University, Qingdao, Shandong, People’s Republic of ChinaCorrespondence: Guiqin Sun, School of Medical Technology and Information Engineering, Zhejiang Chinese Medical University, 548 Binwen Road, Binjiang District, Hangzhou, Zhejiang, People’s Republic of China, Tel +86 13868118601, Fax +86 571-86633307, Email sunguiqin2001@163.com Li Chen, Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Fudan University, 131 Dongan Road, Xuhui District, Shanghai, People’s Republic of China, Tel +86 15821138980, Fax +86 21-54237381, Email lichen_bk@fudan.edu.cnPurpose: Elizabethkingia meningoseptica (EM) is a multi-drug-resistant bacterium of global concern for its role in nosocomial infection and is generally resistant to aminoglycoside antibiotics. In the whole genome of an EM strain (FMS-007), an aminoglycoside-6-adenyl transferase gene (ant(6)FMS-007) was predicted. This study aimed to characterize the biochemical function of ANT(6)FMS-007 and analyze the relationship between genotype and phenotype of ant(6) in clinical EM isolates, so as to provide evidence for clinical precision drug use. This study could establish a method for the verification of known or unknown functionally resistant genes.Methods: A total of 42 EM clinical isolates were collected from clinical departments during 2015– 2023. The phenotype of aminoglycoside antibiotics was analyzed by broth microdilution (BMD) and Kirby-Bauer (K-B) methods. The whole-length ant(6) from EM clinical isolates was analyzed by polymerase chain reaction (PCR) and sequencing. The biochemical function of predictive ANT(6)FMS-007 from the FMS-007 whole genome was identified by 3D plate experiment and mass spectrometry analysis. Candidate active sites were predicted by multi-species sequence alignment and molecular docking, and other important sites were identified in the comparison of ant(6) genotypes and phenotypes of EM clinical isolates. Drug susceptibility test was used to verify the function of these sites.Results: The predictive ANT(6)FMS-007 protein could inactivate STR by modifying STR with ATP to form STR-AMP. Four active sites (Asp-38, Asp-42, Lys-95, and Lys-213) of ANT(6)FMS-007 were identified. Thirty-one EM clinical isolates (74%) carried the ant(6) gene. Eight EM clinical isolates containing the ant(6) gene had MIC values (

Xuehe Zhang,1,&ast; Jixin Zhang,1,&ast; Fen Liu,2 Wenling Li,1 Tong Zhang,1 Binbin Fang,2 Zhiyang Zhang,1 Qian Xie,1 Yining Yang,3 Xiaomei Li1 1Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, People’s Republic of China; 2State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Clinical Medical Research Institute, the First Affiliated Hospital of Xinjiang Medical University, Urumqi, People’s Republic of China; 3Department of Cardiology, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yining Yang, Department of Cardiology, People’s Hospital of Xinjiang Uygur Autonomous Region, 91 Tianchi Road, Urumqi, 830054, People’s Republic of China, Tel +86-991-4361690, Email yangyn5126@163.com Xiaomei Li, Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, 137 Liyushan South Road, Urumqi, 830054, People’s Republic of China, Tel +86-991-4362611, Email lixm505@163.comPurpose: There is a lack of research on nutritional status and poor prognosis in patients with metabolic syndrome and heart failure. This study evaluated the relationship between nutritional status as defined by the PNI and adverse outcomes in patients with metabolic syndrome and heart failure.Methods: A total of 1048 heart failure patients with metabolic syndrome admitted to the Heart Center of the First Affiliated Hospital of Xinjiang Medical University from January 2015 to December 2019 were consecutively. PNI was used to assess their nutritional status.Results: A total of 51.0% of the patients were in the nonmalnutrition group (PNI≥ 45), 27.9% were in the mild malnutrition group (40≤PNI< 45), and 21.1% of patients were in the malnutrition group (PNI< 40). At 36 months of follow-up, after adjusting for other confounding factors, malnutrition (PNI< 40) was independently associated with all-cause death (HR: 1.787, 95% CI: 1.451– 2.201, P< 0.001) and cardiovascular death (HR: 1.837, 95% CI: 1.467– 2.301, P< 0.001). PNI showed additional prognostic predictive value when included in the established risk factor model, both for all-cause death (AUC: 0.620, 95% CI: 0.579– 0.661, P< 0.001) and cardiovascular death (AUC: 0.596, 95% CI: 0.555– 0.636, P< 0.001).Conclusion: In patients with metabolic syndrome and heart failure, malnutrition assessed by PNI is an independent predictor for all-cause death and cardiovascular death, and PNI is negatively correlated with the occurrence of adverse outcomes.Keywords: prognostic nutritional index, metabolic syndrome, heart failure, malnutrition, prognosis

Guiyun Zhang,1 Yufeng Lu,2 Bin Liu,3 Yanmei Wang,4 Wenyi Li,1 Yangchun Xu1 1Department of Dermatology, The Second Hospital of Jilin University, Changchun, 130041, People’s Republic of China; 2Department of Thoracic Surgery, China-Japan Union Hospital of Jilin University, Changchun, 130000, People’s Republic of China; 3Department of Breast Surgery, The Second Hospital of Jilin University, Changchun, 130041, People’s Republic of China; 4Department of Clinical Nutrition, Jilin Province People’s Hospital, Changchun, 130021, People’s Republic of ChinaCorrespondence: Yangchun Xu, Department of Dermatology, The Second Hospital of Jilin University, No. 218 Ziqiang Street, Nanguan District, Changchun, 130041, People’s Republic of China, Tel +86-431-8113-6244, Email xuyc@jlu.edu.cnIntroduction: Bowen’s disease (BD) commonly occurs in sites of chronic sunlight exposure such as head, neck and extremities. It rarely distributes on the nipple and areola.Case Presentation: A 59-year-old female presented with crusted plaque on the right breast for over 1 month. Physical examination found an asymptomatic plaque (5 cm × 5 cm) with irregular shape on the right breast. Histopathological examination suggested irregularly acanthotic epidermis and atypical epidermal cells. Dermis showed inflammatory cell infiltration. Immunohistochemical staining showed negative staining for cytokeratin 7 and cytokeratin 20, and positive staining for Ki67 (60%). The mass was excised and no recurrence occurred in the follow-up. Additionally, we reviewed the literature about BD of the breast and summarized the clinical manifestations, histological features, and treatment options.Conclusion: We reported a rare BD case involving nipple and areola. Wide local excision and complete nipple excision are effective for patients with BD of the nipple and areola.Keywords: Bowen’s disease, breast, nipple, case report

Qinglin Ye,&ast; Guiling Xu,&ast; Haizhen Huang,&ast; Shuting Pang, Boji Xie, Bingmei Feng, Peng Liang, Yijie Qin, Siji Li, Yin Luo, Chao Xue, Wei Li Department of Nephrology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Li; Chao Xue, Department of Nephrology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of China, Email liwei030514@126.com; xccqh@126.comPurpose: Chronic kidney disease (CKD) progression is complex. There are not standardized methods for predicting the prognosis of CKD. Nicotinamide N-methyltransferase (NNMT) has been shown to be associated with renal fibrosis. This study aimed to validate NNMT as a prognostic biomarker of progressive CKD.Patients and Methods: We explored the relationship between NNMT expression and CKD-related outcome variables using the NephroseqV5 and GEO databases. Additionally, a validation set of 37 CKD patients was enrolled to measure the correlation between NNMT expression levels and CKD outcomes. Furthermore, single-cell RNA sequencing data and the Human Protein Atlas were reanalyzed to investigate the expression specificity of NNMT in the kidney. Finally, to detect the status of NNMT expression with tubular fibrosis in vivo, we constructed a unilateral ureteral obstruction (UUO) mouse treated with an NNMT inhibitor.Results: Analyzing the datasets showed that NNMT was expressed mainly in proximal tubule compartments. And patients with high NNMT expression levels had a significantly lower overall survival rate compared to those with low NNMT expression levels (P = 0.013). NNMT was independent of prognosis factors in the multivariate Cox regression model, and the AUCs for CKD progression at 1, 3, and 5 years were 0.849, 0.775, and 0.877, respectively. Pathway enrichment analysis indicated that NNMT regulates the biological processes of tubulointerstitial fibrosis (TIF). In the validation group, NNMT levels were significantly higher in the CKD group combined with interstitial fibrosis. In vivo, NNMT was a high expression in the UUO group, peaking at postoperative day 21. Treatment with an NNMT inhibitor improved renal tubular interstitial fibrosis, and expression levels of FN, α-SMA, VIM, and TGF-β 1 were decreased compared with UUO (P < 0.05).Conclusion: NNMT was expressed mainly in tubular renal compartments, and associated with CKD prognosis. It holds potential as a diagnostic biomarker for tubular fibrosis in CKD.Graphical Abstract: Keywords: nicotinamide N-methyl transferase, tubular fibrosis, chronic kidney disease, biomarker diagnosis

Hai-bo Liu,1,&ast; Min Yang,2,&ast; Wan Li,2 Ting Luo,2 Yang Wu,2 Xiang-yu Huang,2 Yao-lei Zhang,3 Tao Liu,2 Yong Luo2,&ast; 1Department of Biomedical Engineer, General Hospital of Western Theater Command, Chengdu, Sichuan, People’s Republic of China; 2Department of Traditional Chinese Medicine, General Hospital of Western Theater Command, Chengdu, Sichuan, People’s Republic of China; 3Basic Medical Laboratory, General Hospital of Western Theater Command, Chengdu, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yong Luo, Department of Traditional Chinese Medicine, General Hospital of Western Theater Command, Chengdu, Sichuan, 610083, People’s Republic of China, Tel +86 28-86571619, Email yongl019@sina.comPurpose: Dispelling dampness, relieving turbidity and dredging collaterals decoction (DED), is a traditional Chinese medicine used in the treatment of hyperuricemia. We aimed to explore the effect and mechanism of DED in the treatment of hyperuricemia.Methods: The effects of DED (9.48, 4.74, and 2.37 g/kg/d) on potassium oxonate (750 mg/kg/d)-induced hyperuricemia in rats were evaluated by serum uric acid (UA), creatinine (CRE), blood urea nitrogen (BUN), and renal pathological changes. Network pharmacology was used to identify the effective components and targets of DED, and the key targets and signaling pathways for its effects on hyperuricemia were screened. Molecular docking was used to predict the action of DED. H&E, immunohistochemistry, WB, and PCR were used to validate the network pharmacology results.Results: DED can effectively alleviate hyperuricemia, inhibit UA, CRE, BUN, and xanthine oxidase (XOD) activity, and reduce renal inflammatory cell infiltration and glomerular atrophy. The experiment identified 27 potential targets of DED for hyperuricemia, involving 9 components: wogonin, stigmasterol 3-O-beta-D-glucopyranoside, 3β-acetoxyatractylone, beta-sitosterol, stigmasterol, diosgenin, naringenin, astilbin, and quercetin. DED can relieve hyperuricemia mainly by inhibiting RAGE, HMGB1, IL17R, and phospho-TAK1, and by regulating the AGE-RAGE and IL-17 signaling pathways.Conclusion: DED can alleviate hyperuricemia by inhibiting XOD activity and suppressing renal cell apoptosis and inflammation via the AGE-RAGE signaling pathway and IL-17 signaling pathway. This study provides a theoretical basis for the clinical application of DED.Graphical Abstract: Keywords: dispelling dampness, relieving turbidity, dredging collaterals, hyperuricemia, network pharmacology

Weijia Wang,1– 3 Xiaojing Kang,1– 3 Yuan Ding,1– 3 Lidan Mao,1– 3 Abudureyimu Dilinuer,1– 3 Wenzheng Li1– 3 1Department of Dermatology and Venereology, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, People’s Republic of China; 2Xinjiang Clinical Research Center for Dermatologic Diseases, Urumqi, People’s Republic of China; 3Xinjiang Key Laboratory of Dermatology Research (XJYS1707), Urumqi, People’s Republic of ChinaCorrespondence: Xiaojing Kang, Department of Dermatology and Venereology, People’s Hospital of Xinjiang Uygur Autonomous Region, No. 91 Tianchi Road, Tianshan District, Urumqi, People’s Republic of China, Email drkangxj666@163.comBackground: IgG4-related disease (IgG4-RD) is a rare fibroinflammatory disease that has a high tendency to misdiagnosis in clinics.Case Presentation: A 48-year-old man developed a rash with progressive itching 3 years ago after hormone therapy for an ocular “inflammatory pseudotumor”. The disease condition of this patient involved multiple organs which involved the skin. The patient was misdiagnosed with other diseases during the period of hospitalization, leading to poor therapeutic effects and repeated skin lesions. The dermatopathological report indicated plasma cell proliferative disorder, with IgG4/IgG exceeding 40% and abnormally elevated serum IgG4 levels. After the patient was diagnosed with IgG4-RD, a series of treatments improved skin lesions, relieved other symptoms, and decreased serum IgG4 levels.Conclusion: IgG4-RD is a highly misdiagnosed disease that deserves the attention of physicians. The patient we reported could be considered a representative case of IgG4-RD that presents with skin lesions. For patients with suspected IgG4-RD, serum IgG4 testing should be performed, and further imaging, serological tests, and pathology examinations are needed to exclude malignancy, infection, and autoimmune diseases.Keywords: IgG4-RD, fibro-inflammatory, dermatopathological, misdiagnosis, diagnosis, treatment

Chen Li,1,&ast; Jun Hao,2,&ast; Chuangshi Wang,2 Jie Yang,1 Yitian Zheng,1 Kuo Zhang,3 Wen Hui,4 Xiangbin Meng,1 Jun Gao,1 Wei Li,2 Yi-Da Tang1,5 1Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, People’s Republic of China; 2Medical Research and Biometrics Center, National Clinical Research Center for Cardiovascular Diseases, Fuwai Hospital, National Center for Cardiovascular Diseases, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 3Department of Cardiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 4Department of Science and Technology, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 5Research Unit of Medical Science Research Management/Basic and Clinical Research of Metabolic Cardiovascular Diseases, Chinese Academy of Medical Sciences, Beijing People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Li; Yi-Da Tang, Email liwei@mrbc-nccd.com; tangyida@bjmu.edu.cnObjective: The incidence rate of thyroid diseases increased worldwide. This study aims to overview the changing landscape of drug clinical trials on thyroid disease during 2009– 2022.Methods: The detailed information of thyroid disease drug trials registered on the National Medical Products Administration (NMPA) Registration and Information Disclosure Platform for Drug Clinical Studies was searched and collected. The thyroid drug clinical trials were analyzed by the characteristics, time trends, indications, and geographical distribution.Results: Sixty-five thyroid disease drug clinical trials were launched from 2009 to 2022 in China, which included 21 trials in nontumorous thyroid disease and 44 trials in thyroid carcinoma. The number of registered trials of thyroid diseases including thyroid carcinoma and nontumorous thyroid disease increased steadily from 2009 to 2020. Bioequivalence studies accounted for the largest proportion (32[49.2%]), while phase I and Phase II studies both only accounted for 18.5% (12/65). A significant difference was observed in the trials phase, and randomization between thyroid carcinoma and nontumorous thyroid disease. In terms of clinical indications and drug mechanisms, the number of trials in multi-target tyrosine kinase inhibitors for thyroid carcinoma (n=35) ranked first, followed by thyroid hormone for hypothyroidism (n=7), thyrotropin for thyroid carcinoma (n=6). Sixty-five trials were led by 36 principal investigator (PI) units, and more than 30% of PI-leading units were located in Shanghai (n=7) and Beijing (n=4).Conclusion: During the past 13 years, the development of thyroid diseases drugs trials has achieved certain progress in thyroid carcinoma, especially the molecular targeted therapy, yet the development of drug trials on nontumorous thyroid disease was very slow.Keywords: thyroid disease, thyroid carcinoma, nontumorous thyroid disease, China, drug clinical trial

Fan Zhang,1,2 Yan Han,1,2 Liming Zheng,3 Jianhong Liu,4 Yunfei Wu,4 Zuowei Bao,5 Longgen Liu,6 Wenjian Li7 1Department of Endocrinology, Changzhou Third People’s Hospital, Changzhou Medical Center, Nanjing Medical University, Changzhou, Jiangsu, People’s Republic of China; 2Department of Clinical Nutrition, Changzhou Third People’s Hospital, Changzhou Medical Center, Nanjing Medical University, Changzhou, Jiangsu, People’s Republic of China; 3Clinical Laboratory, Changzhou Third People’s Hospital, Changzhou Medical Center, Nanjing Medical University, Changzhou, Jiangsu, People’s Republic of China; 4Department of Pathology, Changzhou Third People’s Hospital, Changzhou Medical Center, Nanjing Medical University, Changzhou, Jiangsu, People’s Republic of China; 5Department of Ultrasonography, Changzhou Third People’s Hospital, Changzhou Medical Center, Nanjing Medical University, Changzhou, Jiangsu, People’s Republic of China; 6Department of Liver Diseases, Changzhou Third People’s Hospital, Changzhou Medical Center, Nanjing Medical University, Changzhou, Jiangsu, People’s Republic of China; 7Department of Urology, Changzhou Third People’s Hospital, Changzhou Medical Center, Nanjing Medical University, Changzhou, Jiangsu, People’s Republic of ChinaCorrespondence: Longgen Liu, Department of Liver Diseases, Changzhou Third People’s Hospital, Changzhou Medical Center, Nanjing Medical University, 300 Lanling North Road, Changzhou, Jiangsu, 213001, People’s Republic of China, Tel +86-0519-82009057, Email ssewllg@163.com Wenjian Li, Department of Urology, Changzhou Third People’s Hospital, Changzhou Medical Center, Nanjing Medical University, 300 Lanling North Road, Changzhou, Jiangsu, 213001, People’s Republic of China, Tel +86-0519-82009011, Email bolite@163.comPurpose: The identification of significant fibrosis is critical for predicting the prognosis of non-alcoholic fatty liver disease (NAFLD). This study aimed to compare the predictive value of chitinase-3-like protein 1 (CHl3L1) and other non-invasive biomarkers, as well as to establish a novel non-invasive diagnostic model for assessing the risk of significant fibrosis in NAFLD.Patients and Methods: A total of 71 patients with confirmed NAFLD based on liver biopsy were included in this study. Serum CHI3L1 levels and other non-invasive fibrosis assessment measures were determined. The aspartate aminotransferase-to-platelet ratio index (APRI) and Fibrosis-4 Index (FIB-4) were calculated to assess the diagnostic superiority of serum CHI3L1 compared to other non-invasive fibrosis assessment measures. Multivariate logistic regression analysis was conducted to identify relevant variables for constructing a diagnostic model. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic accuracy of each index, including the area under ROC curve (AUC), sensitivity, and specificity. A nomogram was established based on the logistic regression model.Results: Serum CHI3LI levels were found to be higher in NAFLD patients with significant fibrosis compared to those without significant fibrosis. Multivariate logistic regression analysis revealed that aspartate aminotransferase (AST), type IV collagen (IV-C), CHI3L1, and liver stiffness measurement (LSM) were identified as potential independent risk factors associated with significant fibrosis in patients. The AUC of CHI3L1 for diagnosing significant liver fibrosis was 0.716 (0.596,0.836), with the optimal cut-off point of 125.315. The nomogram incorporating CHI3LI, AST, IV-C, and LSM further improved the potential predictive value, with an AUC for diagnosing significant fibrosis of 0.864 (0.766,0.962). This was superior to IV-C, CHI3L1, LSM, and APRI (all p < 0.05).Conclusion: The diagnostic model constructed by CHI3L1 combined with the existing non-invasive markers AST, IV-C, and LSM can help assess the risk of significant liver fibrosis in NAFLD.Keywords: nonalcoholic fatty liver disease, fibrosis, chitinase 3-like protein 1, liver biopsy, nomogram

Fan Zhang,1,&ast; Hao Peng,1,&ast; Chuanyi Fu,1 Yidong Deng,1 Mao Zhang,1 Wenan Li,1 Jian Zhong,1 Qing Zhou,1 Li Huang,1 Shuli Xiao,1 Jiannong Zhao2 1Department of Cerebrovascular Disease, Hainan Affiliated Hospital of Hainan Medical University, Hainan General Hospital, Haikou, Hainan, 570311, People’s Republic of China; 2Department of Neurosurgery, Hainan Medical University, Hainan Affiliated Hospital of Hainan Medical University, Hainan General Hospital, Haikou, Hainan, 571199, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiannong Zhao, Department of Neurosurgery, Hainan Medical University, Hainan Affiliated Hospital of Hainan Medical University, Hainan General Hospital, Haikou, 571199, Hainan, People’s Republic of China, Tel/Fax +86-13876673888, Email jiannong_zhao@163.comBackground: Stroke has a high disability rate, and 30% of stroke cases have an unknown cause. Accurate diagnosis and treatment of stroke requires consideration of several rare heritable and non-heritable factors.Objective: This study aimed to evaluate the impacts of three genetic polymorphisms (rs369149111 in HTRA1, rs1803628 in GAS6 and rs9808753 in IFNGR2) on stroke susceptibility among the Chinese Han population.Methods: Three single nucleotide polymorphisms (SNPs) from 623 stroke cases and 572 healthy controls were genotyped by the Agena MassARRAY platform. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by logistic regression analysis to evaluate the associations of three SNPs with stroke susceptibility. Additionally, SNP-SNP interactions were analyzed by multifactor dimensionality reduction (MDR).Results: As demonstrated by the overall analysis, rs9808753 in IFNGR2 (allele: OR = 1.25, 95% CI = 1.06– 1.47, p = 0.007; homozygous: OR = 1.59, 95% CI = 1.14– 2.23, p = 0.007; dominant: OR = 1.31, 95% CI = 1.02– 1.67, p = 0.032; recessive: OR = 1.42, 95% CI = 1.05– 1.91, p = 0.022; additive: OR = 1.26, 95% CI = 1.07– 1.48, p = 0.007) was associated with an increased susceptibility to stroke. Besides, stratification analysis suggested that rs9808753 was associated with an increased risk of stroke in subgroup aged ≤ 64 years, males and drinkers (p < 0.05). And rs1803628 in GAS6 was significantly associated with an increased susceptibility to stroke in non-smokers (p < 0.05).Conclusion: A risk-increasing effect of IFNGR2 rs980875 on stroke was detected in this study, which further broadens the understanding of the relationship between genetic polymorphisms and stroke susceptibility.Keywords: IFNGR2, polymorphisms, stroke, susceptibility, case-control

Xingyu Mu,1,&ast; Wen Li,2,&ast; Ming Zhang,2 Changxiao Yang,2 Xianxu Yang,2 Dan Li,2 Yan Ding3 1The First Clinical College of Hainan Medical University, Haikou, Hainan, People’s Republic of China; 2Department of Dermatology, The Fifth People’s Hospital of Hainan Province, Haikou, Hainan, People’s Republic of China; 3Department of Dermatology, Affiliated Dermatology Hospital of Hainan Medical University, The Fifth People’s Hospital of Hainan Province, Haikou, Hainan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dan Li, Department of Dermatology, The Fifth People’s Hospital of Hainan Province, No. 8 Longhua Road, Longhua District, Haikou, Hainan, People’s Republic of China, Tel +8613807656023, Email hn1380765@163.com Yan Ding, Department of Dermatology, Affiliated Dermatology Hospital of Hainan Medical University, The Fifth People’s Hospital of Hainan Province, No. 8 Longhua Road, Longhua District, Haikou, Hainan, People’s Republic of China, Tel +8618689980361, Email annymilk@126.comAbstract: Eruptive pruritic papular porokeratosis (EPPP) is a rare subtype of porokeratosis that presents as an acute exacerbation of an annular papule with a distinct peripheral hyperkeratotic ridge border and severe pruritus. EPPP is mainly reported in elderly East Asian men. Its etiology and pathogenesis are unknown. We hereby present a case report of EPPP in a 68-year-old Chinese male with persistent circumscribed papules on the extremities, accompanied by severe pruritus for one year. After the patient was given conventional medication, a new rash appeared on the patient’s extremities and he felt intense itching in the area of the rash. The patient was switched to oral tofacitinib treatment. The patient felt that the pruritus had largely disappeared after one month of oral dosing, leaving only brown pigmentation on the erythema of the extremities. The patient has been off the drug for 2 months. There was no pruritus or new rash during the follow-up period.Keywords: eruptive pruritic papular porokeratosis, porokeratosis, tofacitinib

Haoyuan Xu,&ast; Wanpeng Li,&ast; Huankang Zhang, Huan Wang, Li Hu, Xicai Sun, Dehui Wang Department of Otolaryngology - Head and Neck Surgery, Affiliated Eye, Ear, Nose, and Throat Hospital, Fudan University, Shanghai, 200031, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xicai Sun; Dehui Wang, Department of Otolaryngology - Head and Neck Surgery, Affiliated Eye, Ear, Nose, and Throat Hospital, Fudan University, 83 Fen Yang Road, Shanghai, People’s Republic of China, Email laryngeal@163.com; wangdehuient@sina.comObjective: To investigate the effects of endoscopic endonasal surgery (EES) on longitudinal quality of life (QoL) in patients with malignant tumors of the anterior skull base.Methods: Eligible patients prospectively completed the Anterior Skull Base Surgery Questionnaire (ASBQ) and the 22-item Sino-Nasal Outcome Test (SNOT-22) questionnaires in referring to 3 different periods throughout their treatment and recovery.Results: Forty patients were included. The median volume coronal maximum length of the tumor was 3.6 cm (95% CI 2.7– 4.1cm). Overall QoL significantly worsened at 1 month postoperatively but returned to baseline after 1 year. Unrelieved symptoms in specific domains prompted further evaluation of individual items. Transient worsening of taste (p=0.011) and olfaction (p=0.004) lasted for 1 month but gradually relieved within the first postoperative year, but vision consistently worsened over the course of the treatment (p=0.126). Age> 50 years (p< 0.001), comorbidities (p< 0.001), tumor necrosis (p< 0.001) and recurrence (p=0.001) were associated with worse preoperative QoL. Poor long-term QoL was noted in those undergoing adjuvant therapy (p=0.032). Overall ASBQ scores (p=0.024), subdomain scores in specific symptoms (p=0.016), and vision scores (p=0.009) were worse only in patients with the greater coronal maximum diameter at 1-month postoperatively. Greater coronal maximum diameter was related to worse preoperative subdomain scores regarding specific symptoms (p=0.030) and decreased postoperative long-term decreased vision scores (p=0.014).Conclusion: Long-term site-specific and sinonasal QoL eventually stabilized after EES. Greater coronal maximum diameter was significantly associated with worsened vision function. Temporarily worse olfactory, vision, and taste function may be tied to decreased short-term QoL.Keywords: quality of life, endoscopic endonasal surgery, anterior skull base, malignant tumors, prospective study

Zhichao Gong, Yi Guo, Xiaowei Liu, Kun Ai, Wu Li, Jiangshan Li College of Acupuncture, Massage and Rehabilitation, Hunan University of Chinese Medicine, Changsha, Hunan, People’s Republic of ChinaCorrespondence: Jiangshan Li, College of Acupuncture, Massage and Rehabilitation, Hunan University of Chinese Medicine, No. 300, Xueshi Road, Yuelu District, Changsha, Hunan Province, 410208, People’s Republic of China, Tel +86 13707315642, Fax +8673188458187, Email 292463008@qq.com; Wu Li, College of Acupuncture, Massage and Rehabilitation, Hunan University of Chinese Medicine, No. 300, Xueshi Road, Yuelu District, Changsha, Hunan Province, 410208, People’s Republic of China, Tel +86 13707315642, Fax +8673188458187, Email 272434694@qq.comAbstract: Tuina is an effective treatment for neck pain (NP). However, there has been no bibliometric analysis of the global application and emerging trends of tuina performed for NP. Therefore, this study aimed to provide an overview of the current state and future trends in the field. Articles about tuina for NP, published from January 1, 2013, to January 1, 2023, were searched in the Web of Science Core Collection database. CiteSpace (6.1.R6) and VOSviewer (1.6.18) software were used to analyze annual trends in literature posts, countries, institutions, authors, cited references, and knowledge graphs of keyword co-occurrence, clustering, and burst using standard bibliometric indicators. The final analysis comprised 505 valid documents. The results demonstrate that the number of articles in the field of tuina therapy for NP has gradually increased over the years, showing the most active countries, institutions, journals, and authors. There were 323 keywords in the field, 322 research authors, and 292 research institutions, with the USA having the most publications (n = 140). The most published institution is Vrije University Amsterdam, and the most published journal is the Cochrane Database of Systematic Reviews. Peter R Blanpied is the most influential and most-cited author. Interventions (dry needling, massage therapy, and muscle energy techniques), common treatment sites for NP (upper trapezius), and complications (cervicogenic headache) are the top three frontiers mentioned in the field of tuina research for NP. The bibliometric study showed the current status and trends in clinical research on treating patients with NP using tuina, which may help researchers identify topics of interest and scope for future research in this field.Keywords: tuina, neck pain, CiteSpace, VOSviewer, knowledge graph analysis

Weiqiang Xiao,1,&ast; Xiaokun Wang,1,&ast; Yuanye Qu,1 Mingyue Sun,1 Yanmin Chang,1 Wenjiao Li,1 Yong Shen,1,2 Xiufang Shi,3 Min Jing,1 Qingxia Xu1,4 1Department of Clinical Laboratory, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China; 2Institute of Biophysics, Chinese Academy of Sciences, Foshan, People’s Republic of China; 3School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, People’s Republic of China; 4Zhengzhou Key Laboratory for Diagnosis of Digestive System Tumor Markers, Zhengzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qingxia Xu; Xiufang Shi, Email zlyyxuqingxia0575@zzu.edu.cn; xfshi@zzu.edu.cnBackground: Emergence of blaKPC and blaNDM co-harboring Klebsiella pneumoniae has escalated the threat of Carbapenem-resistant Klebsiella pneumoniae (CRKP) to healthcare. It remains unknown the prevalence and molecular characteristics of CRKP co-producing KPC and NDMs carbapenemases in Henan.Methods and Results: Twenty-seven CRKP strains isolated from different times were selected randomly in affiliated cancer hospital of Zhengzhou University from January 2019 to January 2021, among which one KPC-2 and NDM-5 positive CRKP named K9 was isolated from an abdominal pus sample of a 63-year-old male patient with leukemia. Sequencing of K9 determined that K9 belonged to ST11-KL47, which is resistant to antibiotics such as meropenem, ceftazidime-avibactam and tetracycline. K9 carried two different plasmids that contained blaNDM− 5 and blaKPC− 2. Both plasmids were shown to be novel hybrid plasmids and IS 26 played an important role in generation of two plasmids. Gene blaKPC-2 was flanked by the NTEKPC-Ib-like genetic structure (IS 26-ΔTn 3-ISKpn8-blaKPC-2-ISKpn6-IS 26) and was located on a conjugative IncFII/R/N type hybrid plasmid.Conclusion: The resistance gene blaNDM− 5 located on a region organized as IS 26-blaNDM– 5-ble-trpF-dsbD-ISCR1-sul1-aadA2-dfrA12-IntI1-IS 26 was carried by a phage-plasmid. We described a clinical CRKP co-producing KPC-2 and NDM-5 and emphasized an urgent need to control their further spread.Keywords: carbapenem-resistant Klebsiella pneumoniae, KPC-2, NDM-5, beta-lactamases, hybrid plasmid, IS 26

Qianqing Ma,1,&ast; Chunyun Shen,2,&ast; Yankun Gao,3,&ast; Yayang Duan,1 Wanyan Li,4 Gensheng Lu,5 Xiachuan Qin,1 Chaoxue Zhang,1 Junli Wang2 1Department of Ultrasound, the First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China; 2Department of Ultrasound, Wuhu No. 2 People’s Hospital, Wuhu, People’s Republic of China; 3Department of Radiology, the First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China; 4Department of Ultrasound, Linquan Country People’s Hospital, Fuyang, People’s Republic of China; 5Department of Pathology, Wuhu No. 2 People’s Hospital, Wuhu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Junli Wang, Department of Ultrasound, Wuhu No. 2 People’s Hospital, No. 259 Jiuhuashan Road, Jinghu District, Wuhu, Anhui, 241001, People’s Republic of China, Tel +86 18055317022, Email wjl980134@163.com Chaoxue Zhang, Department of Ultrasound, the First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Shushan District, Hefei, Anhui, 230022, People’s Republic of China, Tel +86 13955158023, Email zcxay@163.comBackground: Breast cancer is the most common tumor globally. Automated Breast Volume Scanner (ABVS) and strain elastography (SE) can provide more useful breast information. The use of radiomics combined with ABVS and SE images to predict breast cancer has become a new focus. Therefore, this study developed and validated a radiomics analysis of breast lesions in combination with coronal plane of ABVS and SE to improve the differential diagnosis of benign and malignant breast diseases.Patients and Methods: 620 pathologically confirmed breast lesions from January 2017 to August 2021 were retrospectively analyzed and randomly divided into a training set (n=434) and a validation set (n=186). Radiomic features of the lesions were extracted from ABVS, B-ultrasound, and strain elastography (SE) images, respectively. These were then filtered by Gradient Boosted Decision Tree (GBDT) and multiple logistic regression. The ABVS model is based on coronal plane features for the breast, B+SE model is based on features of B-ultrasound and SE, and the multimodal model is based on features of three examinations. The evaluation of the predicted performance of the three models used the receiver operating characteristic (ROC) and decision curve analysis (DCA).Results: The area under the curve, accuracy, specificity, and sensitivity of the multimodal model in the training set are 0.975 (95% CI:0.959– 0.991),93.78%, 92.02%, and 96.49%, respectively, and 0.946 (95% CI:0.913 − 0.978), 87.63%, 83.93%, and 93.24% in the validation set, respectively. The multimodal model outperformed the ABVS model and B+SE model in both the training (P < 0.001, P = 0.002, respectively) and validation sets (P < 0.001, P = 0.034, respectively).Conclusion: Radiomics from the coronal plane of the breast lesion provide valuable information for identification. A multimodal model combination with radiomics from ABVS, B-ultrasound, and SE could improve the diagnostic efficacy of breast masses.Keywords: radiomics, automated breast volume scanner, strain elastography, ultrasound, breast cancer

Haoyuan Xu,&ast; Wanpeng Li,&ast; Xiaole Song,&ast; Huankang Zhang, Huan Wang, Jingjing Wang, Li Hu, Houyong Li, Xicai Sun,&ast; Dehui Wang&ast; Department of Otolaryngology-Head and Neck Surgery, Affiliated Eye Ear Nose and Throat Hospital, Fudan University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dehui Wang; Xicai Sun, Department of Otolaryngology-Head and Neck Surgery, Affiliated Eye Ear Nose and Throat Hospital, Fudan University, 83 Fen Yang Road, Shanghai, People’s Republic of China, Email wangdehuient@sina.com; laryngeal@163.comBackground: As a cancer stem cells (CSCs) surface marker, Lgr5 plays an important role in the signal transduction of cancer cells and is a potential biomarker for cancer diagnosis and prognosis. However, the expression and prognostic value of Lgr5 in recurrent nasopharyngeal carcinoma (rNPC) remains ambiguous.Materials: We used RNA sequencing to screen differentially expressed mRNAs in eleven specimens of rNPC tissues and five fresh adjacent normal tissue samples and the CSC marker, Lgr5, was identified. The expression level of Lgr5 in rNPC samples was also detected by immunohistochemistry and Western blot assay. The chi-square test was used to analyze the relationship between the clinicopathological variables and the immunostaining of Lgr5. The Log-rank method was used for prognosis analysis. The Cox regression model was used for univariate and multivariate analysis.Results: Significantly elevated expression of Lgr5 in the rNPC tissues was observed compared to the normal tissues using RNA sequencing, Western blot and immunohistochemistry. The expression of Lgr5 was significantly correlated with the T stage (P=0.014). High Lgr5 expression (P=0.007), tumor necrosis (P=0.013) and WHO type II (P=0.043) in rNPC patients exhibited worse overall survival (OS). Lgr5 expression was proved to be an independent risk factor for OS (P=0.035) in multivariate analyses, and had promising predictive value for survival and recurrence in rNPC patients (area under the ROC curve: 0.711 and 0.665, P=0.017 and 0.028, respectively).Conclusion: Lgr5 as a CSC marker is a promising therapeutic target and could be employed to predict the survival prognosis of rNPC patients.Keywords: recurrent nasopharyngeal carcinoma, cancer stem cell, Lgr5, survival

Yuan Li,1,2,&ast; Wanni Li,1,&ast; Ming Zhang,1 Xianxu Yang,1 Changxiao Yang,1 Dan Li1 1Dermatology Department, The Fifth People’s Hospital of Hainan Province, Haikou, Hainan, People’s Republic of China; 2Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Changxiao Yang; Dan Li, Dermatology Department, The Fifth People’s Hospital of Hainan Province, No. 8 Longhua Road, Longhua District, Haikou, Hainan, 570100, People’s Republic of China, Email 13648641216@163.com; hn1380765@163.comAbstract: Our report concerns a 72-year-old female patient who presented with nodular ulcers on her right lower extremity and foot for a duration of 5 months. Based on the results of a dermatological examination, histopathological examination of the lesions, and immunohistochemical findings, we were able to diagnose the patient with Mari-type pseudocaposi sarcoma. Further research allowed us to clarify the distinction between this type of sarcoma and Kaposi’s sarcoma, which will be crucial in devising an effective treatment plan for the patient as we continue to monitor her progress during clinical supervision.Keywords: pseudo-Kaposi’s sarcoma, Kaposi’s sarcoma, immunohistochemistry, CD34

Jiayi Li,1,2 Jiao Zhang,2 Xu Wang,2 Xumin Zheng,2 Hongmei Gao,2 Shimin Jiang,2 Wenge Li1,2 1Department of Nephrology, Peking University China-Japan Friendship School of Clinical Medicine, Beijing, People’s Republic of China; 2Department of Nephrology, China-Japan Friendship Hospital, Beijing, People’s Republic of ChinaCorrespondence: Wenge Li, Department of Nephrology, China-Japan Friendship Hospital, No. 2, Yinghua Dong Street, Chaoyang District, Beijing, 100029, People’s Republic of China, Email wenge_lee2002@126.comIntroduction: Complement activation is highly involved in membranous nephropathy. Identifying the mechanism of the complement activation pathway carries crucial therapeutic implications yet remains controversial. This study explored lectin complement pathway activation in PLA2R-associated membranous nephropathy (MN).Methods: One hundred and seventy-six patients with biopsy-proven PLA2R-associated MN were enrolled in the retrospective study and divided into the remission group (24-hour urine protein < 0.75g and serum albumin > 35 g/L) and the nephrotic syndrome group. The clinical manifestation and C3, C4d, C1q, MBL, and B factor in renal biopsy tissues and C3, C4, and immunoglobulins in serum were evaluated.Results: Deposition of glomerular C3, C4d, and mannose-binding lectin (MBL) was significantly higher in the activated state than in the remission state in PLA2R-associated MN. MBL deposition was the risk factor for no remission. During follow-up, the persistent non-remission patients have significantly lower serum C3 levels.Conclusion: Activation of the lectin complement pathway in PLA2R-associated MN may contribute to proteinuria progression and disease activity.Keywords: membranous nephropathy, anti-PLA2R antibody, complement, lectin pathway

Huamei Cai,1,2,&ast; Xiaowen Liu,1,&ast; Dingyi Wang,3,4 Weixia Li,1 Hongli Ma,1,2 Jing Zhao1,2 1Department of Anesthesiology, China-Japan Friendship Hospital, Beijing, People’s Republic of China; 2Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 3National Center for Respiratory Medicine & National Clinical Research Center for Respiratory Diseases, Institute of Respiratory Medicine & Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 4Department of Clinical Research and Data Management Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jing Zhao, Department of Anesthesiology, China- Japan Friendship Hospital, No. 2 Yinghua East Road, Beijing, 100029, People’s Republic of China, Tel +86 010 8420 5876, Email zhaojing1009@aliyun.comPurpose: Perioperative anaphylaxis (POA) is an acute severe systemic hypersensitivity reaction characterized by life-threatening respiratory and circulatory collapse. In our previous study, we reported the epidemiology of suspected POA in China. In the present study, we aimed to elucidate the management and outcomes of these cases and further verify the risk factors for near-fatal and fatal outcomes.Patients and Methods: This was a retrospective study of 447 cases of suspected life-threatening POA encountered at 112 tertiary hospitals in mainland China between September 2018 and August 2019. Patient characteristics, symptoms, duration of hypotension, treatments, and clinical outcomes were documented. Bivariate logistic regression was used to identify risk factors for near-fatal and fatal outcomes.Results: Most cases of suspected POA (89.9%) were recognized and treated within 5 min. Epinephrine was administered as the initial treatment in 232 (51.9%) cases. Corticosteroids (26.6%), other vasoactive drugs (18.3%), and bronchodilators (1.6%) were also administered as the initial treatment instead of epinephrine. The initial dosage of epinephrine (median, 35 μg) was insufficient according to the anaphylaxis guidelines. On multivariable analysis, age ≥ 65 years (odds ratio [OR] 7.48; 95% confidence interval [CI]: 1.33– 41.87, P=0.022), ASA physical status IV (OR 17.68; 95% CI: 4.53-68.94; P< 0.001), and hypotension duration ≥ 15 min (OR 3.63; 95% CI: 1.11– 11.87; P=0.033) were risk factors for fatal and near-fatal outcomes.Conclusion: Most cases in this study were managed in a timely manner, but the epinephrine application should be optimized according to the guidelines. Age ≥ 65 years, ASA physical status IV, and long-term hypotension were risk factors for near-fatal and fatal outcomes.Keywords: perioperative anaphylaxis, epinephrine, risk factors, perioperative outcomes

Xuehe Zhang,1 Fen Liu,1 Wenling Li,1 Jixin Zhang,1 Tong Zhang,1 Xiaolin Yu,2 Junyi Luo,1 Qian Zhao,1 Jinyu Zhang,1 Binbin Fang,1 Yining Yang,2 Xiaomei Li1 1Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, People’s Republic of China; 2Department of Cardiology, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, People’s Republic of ChinaCorrespondence: Yining Yang, Department of Cardiology, People’s Hospital of Xinjiang Uygur Autonomous Region, 91 Tianchi Road, Urumqi, 830054, People’s Republic of China, Tel +86-991-4361690, Email yangyn5126@163.com Xiaomei Li, Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, 137 Liyushan South Road, Urumqi, 830054, People’s Republic of China, Tel +86-991-4362611, Email lixm505@163.comPurpose: This study aimed to evaluate the association between metabolic score for insulin resistance (METS-IR) and adverse cardiovascular events in patients with ischemic cardiomyopathy (ICM) and type 2 diabetes mellitus (T2DM).Methods: METS-IR was calculated using the following formula: ln[(2 × fasting plasma glucose (mg/dL) + fasting triglyceride (mg/dL)] × body mass index (kg/m2)/(ln[high-density lipoprotein cholesterol (mg/dL)]). Major adverse cardiovascular events (MACEs) were defined as the composite outcome of nonfatal myocardial infarction, cardiac death, and rehospitalization for heart failure. Cox proportional hazards regression analysis was used to evaluate the association between METS-IR and adverse outcomes. The predictive value of METS-IR was evaluated by the area under the curve (AUC), continuous net reclassification improvement (NRI), and integrated discrimination improvement (IDI).Results: The incidence of MACEs increased with METS-IR tertiles at a 3‑year follow‑up. Kaplan‒Meier curves showed a significant difference in event-free survival probability between METS-IR tertiles (P< 0.05). Multivariate Cox hazard regression analysis adjusting for multiple confounding factors showed that when comparing the highest and lowest METS-IR tertiles, the hazard ratio was 1.886 (95% CI:1.613– 2.204; P< 0.001). Adding METS-IR to the established risk model had an incremental effect on the predicted value of MACEs (AUC=0.637, 95% CI:0.605– 0.670, P< 0.001; NRI=0.191, P< 0.001; IDI=0.028, P< 0.001).Conclusion: METS-IR, a simple score of insulin resistance, predicts the occurrence of MACEs in patients with ICM and T2DM, independent of known cardiovascular risk factors. These results suggest that METS-IR may be a useful marker for risk stratification and prognosis in patients with ICM and T2DM.Keywords: metabolic score for insulin resistance, ischemic cardiomyopathy, type 2 diabetes mellitus, major adverse cardiac events, prognosis

Qing Xia,&ast; Yue Tang,&ast; Wang Li, Tingting Liang, Yue Zhou, Jun Liu, Feila Liu School of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Feila Liu, School of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing, People’s Republic of China, Tel +86-15123002638, Fax +86 2362563190, Email liufeila@cqut.edu.cnIntroduction: The immunosuppressive tumor microenvironment (TME) of solid tumors inhibits most drug delivery system-based nanomaterials from achieving deep penetration in tumor tissue and interferes with T cell activity in terms of differentiation and exhaustion, which is becoming a critical therapy hurdle for solid tumors. Therefore, developing a therapeutic strategy with abilities of rapid establishment of tumor-targeted cells, elimination of immune obstacles, and enhanced active immunization is very important, while is still a big challenge.Methods: A new strategy was explored to enhance immune therapy via the conjugation of microRNA155 (miR) to the surface of therapeutic monocyte with graphene quantum dots (GQDs).Results: TME was reversed using surface-engineered monocyte immunotherapy via reprogramming pro-tumoral M2 TAMs into antitumor M1, and thus tumor elimination was dramatically enhanced.Conclusion: Such a surface-engineered monocyte immunotherapy has been demonstrated to be well tolerated to intravenous administration and bio-compatible, showing the potential to be extended for the solid tumor treatment.Graphical Abstract: Keywords: solid tumor, surface-engineered monocyte, GQDs, miR155, immunotherapy

Wenting Li, Wei Sha Department of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University, Shanghai, People’s Republic of ChinaCorrespondence: Wei Sha, Shanghai Pulmonary Hospital, Tongji University, Number 507 Zhengmin Road, Shanghai, 200433, People’s Republic of China, Tel +86 21 6511 5006 (ext 2013), Fax +86 2155662767, Email feikeshawei2020@163.comIntroduction: Minimally invasive diagnosis of chest wall tuberculosis remains a challenge. Fine needle aspiration (FNA) is a simple and safe method of sampling. However, previous studies have shown that conventional tuberculosis tests had poor diagnostic performance in the needle aspirates. With the popularization of molecular detection application, the value of FNA in the diagnosis of chest wall tuberculosis needs to be reevaluated.Methods: We retrospectively studied patients with suspected chest wall tuberculosis at admission who underwent FNA for diagnosis and reported the diagnostic efficacy of acid-fast bacilli smear, mycobacterial culture, cytology and Xpert MTB/RIF (GeneXpert) when testing FNA specimens. A composite reference standard (CRS) was used as the diagnostic gold standard for this study.Results: Among 89 included FNA specimens, acid-fast bacilli smear, mycobacterial culture, and GeneXpert were positive in 15 (16.85%), 23 (25.8%), and 61 (68.5%), respectively. Thirty-nine (43.8%) had cytologic features suggestive of tuberculosis. According to CRS, 75 (84.3%) cases were categorized as chest wall tuberculosis, 14 (15.7%) were not diagnosed with tuberculosis. Using CRS as the gold standard, acid-fast bacilli smear, mycobacterial culture, cytology and GeneXpert exhibited sensitivity of 20%, 30.7%, 52% and 81.3%, respectively. Specificity in these four tests was found to be 100%. Sensitivity of GeneXpert was significantly higher than that of smear, culture and cytology, X2=66.3, p< 0.001.Conclusion: GeneXpert achieved higher sensitivity as compared to cytology and conventional TB tests in the chest wall FNA specimens. The implementation of GeneXpert may increase the diagnostic efficacy of FNA in the diagnosis of chest wall TB.Keywords: chest wall tuberculosis, fine needle aspiration, Xpert MTB/RIF, cytology, culture

Minli Zhu,1 Leying Wang,1 Zhangming Zhuge,1 Wei Li,1,2 Yihui Zheng,1 Jingyun Mai,1 Zhenlang Lin,1 Jing Lin1,3 1Key Laboratory of Perinatal Medicine of Wenzhou, Department of Neonatology, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, 325027, People’s Republic of China; 2Zhijin People’s Hospital of Guizhou Province, Guizhou, 552100, People’s Republic of China; 3Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USACorrespondence: Jing Lin, Department of Pediatrics, Icahn School of Medicine at Mount Sinai, One Gustave Levy Place, New York, NY, 10029, USA, Tel +1-212-241-6186, Fax +1-212534-5207, Email jing.lin@mssm.edu Zhenlang Lin, Department of Neonatology, the Second Affiliated Hospital and Yuying Children’s Hospital, Wenzhou Medical University, Wenzhou, 325027, People’s Republic of China, Tel +86 13806689800, Email linzhenlang@hotmail.comBackground and Objective: An increasing number of cases of neonatal sepsis due to extended-spectrum beta-lactamase (ESBL)-producing multi-drug resistant (MDR) Escherichia coli (E. coli) have been reported worldwide. The aim of this study was to explore the risk factors associated with ESBL-producing MDR E. coli among neonates with culture-confirmed E. coli sepsis and thereby to help selection of appropriate empirical antibiotics.Patients and Methods: All newborn infants with a confirmed pathogen isolated from blood or cerebrospinal fluid (CSF) from 2016 to 2021 were identified and those with E. coli infection were included in this analysis. We compared a group of neonatal patients with ESBL-producing MDR E. coli sepsis (n=69) to a group with ESBL-negative E. coli (n=70) based on antimicrobial susceptibility reports. We used multivariable regression analysis to determine the risk factors associated with ESBL-producing MDR E. coli strains among the neonates with culture-confirmed E. coli sepsis.Results: ESBL-producing MDR E. coli sepsis was more common in premature infants and newborns with hospital-acquired late-onset sepsis (HALOS). The mortality rate of neonatal sepsis caused by ESBL-producing E. coli was about twice as that of sepsis caused by ESBL-negative E. coli. Antepartum exposure to cephalosporins (OR=25.191, 95% CI: 3.184– 199.326, P< 0.01) and parenteral nutrition for more than 1 week (OR=4.495, 95% CI: 2.009– 10.055, P< 0.01) were independent risk factors for neonatal infection with ESBL-producing stains among infants with E. coli sepsis.Conclusion: E. coli remains the most common Gram-negative bacterial pathogen causing neonatal sepsis. A higher proportion of ESBL-producing MDR E. coli is seen in premature infants and those newborns with HALOS and is associated with higher mortality. Antepartum use of cephalosporins and prolonged use of parenteral nutrition may be important factors to consider in the selection of empirical antibiotics for use in neonatal sepsis caused by gram-negative rods prior to the availability of the results of antimicrobial susceptibility.Keywords: infant, newborn, neonatal sepsis, Escherichia coli, drug resistance, extended-spectrum beta-lactamase

Fanghui Li,1,2,&ast; Dongze Li,1,&ast; Jing Yu,1 Yu Jia,3 Jirui Wen,4 Wentao Li,2 Yao Tong,2 Jiang Wu,4 Zhi Wan,1 Yu Cao,1 Qing Zhang,2 Rui Zeng1,2 1Department of Emergency Medicine, Laboratory of Emergency Medicine, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 2Department of Cardiology, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 3Department of General Practice and National Clinical Research Center for Geriatrics, International Medical Center, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 4Deep Underground Space Medical Center, West China Hospital, Sichuan University, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Rui Zeng; Qing Zhang, Department of Cardiology, West China Hospital, Sichuan University, 37 Guoxue Road, Chengdu, Sichuan, 610041, People’s Republic of China, Tel +86-28-85423248, Fax +86-28-85582944, Email zengrui_0524@126.com; qzhang2000cn@163.comBackground: The plasma lipidome profile is likely to improve risk stratification in patients with acute coronary syndrome (ACS) and predict cardiovascular events for secondary disease prevention. Ceramides are involved in the initiation or acceleration of several key pathophysiological processes in atherosclerosis. This study evaluated whether plasma ceramide levels at admission was associated with one-year mortality in patients with ACS.Methods: In total, 826 patients with ACS from a prospective multicenter study for early evaluation of acute chest pain were enrolled. High-performance liquid chromatography with tandem mass spectrometry (LC/MS) was used to measure the plasma levels of eleven ceramides (C16–C26). The primary outcome was all-cause mortality, and the secondary outcome was cardiac mortality during the one-year follow-up. The relationship between the ceramide levels and mortality was evaluated by Cox regression analysis. The receiver operating characteristic (ROC) curve was established to evaluate discrimination of ceramides.Results: Eighty-eight (10.7%) patients died after a 12-month follow-up. Five ceramides (C16:0, C18:0, C20:0, C24:1 and C24:2) and their ratios to Cer(d18:1/24:0) were independently associated with the risk of all-cause death and cardiac death. Combining the Global Registry of Acute Coronary Events (GRACE) score with ceramides and their ratios to Cer(d18:1/24:0) had areas under ROC curves ranging from 0.778– 0.804 (P< 0.001) for all-cause mortality, which was greater than that of the GRACE score alone.Conclusion: Measurements of long-chain ceramides and very-long-chain ceramides may help in identifying a high risk of mortality beyond traditional assessment tools in patients with ACS.Trial Registration: clinicaltrials.gov, identifier: NCT04122573.Keywords: ceramide, acute coronary syndrome, mortality, high-performance liquid chromatography with tandem mass spectrometry

Jie Wang,&ast; Bin Cao,&ast; Sihao Lin, Yong Wang, Qifa Zhang, Yang Jiang, Wei Li, Yingjian Zhu Department of Urology, Jiading Branch of Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201803, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yingjian Zhu; Wei Li, Department of Urology, Jiading Branch of Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 800 Huangjiahuayuan Road, Shanghai, 201803, People’s Republic of China, Tel +8613764490868 ; +8618117094957, Email zhuyingjian_sjtu@126.com; croma_shh@126.comPurpose: Urologic chronic pelvic pain syndrome has attracted a lot of attention in the new century, and an increasing number of relevant studies have been published. Therefore, we performed a bibliometric analysis of these publications, hoping to show the current research hotspots and future research trends.Methods: The articles on were selected from the Web of Science Core Collection. Countries, authors, references and keywords in the field were visualized and analyzed using CiteSpace and VOSViewer software.Results: A total of 1014 articles on urologic chronic pelvic pain syndrome were identified, with “chronic pelvic pain syndrome” being the most common keyword, with a strong association with “interstitial cystitis” and “chronic prostatitis”. The hotspot of urologic chronic pelvic pain syndrome research has gradually shifted from chronic prostatitis / urologic chronic pelvic pain syndrome to cystitis/bladder pain syndrome over the past few years. Future research tends to focus on urologic chronic pelvic pain syndrome etiology, including oxidative stress and inflammation.Conclusion: Research on urologic chronic pelvic pain syndrome is steadily growing. The United States has made the most prominent contribution in this area, and the share of China’s contribution is expected to grow further. The etiology of urologic chronic pelvic pain syndrome, including inflammation and oxidative stress, have been the focus of current research and developmental trends in the future research.Keywords: bibliometric analysis, chronic pelvic pain syndrome, interstitial cystitis, chronic prostatitis, mechanisms, treatments

Lingyun Tian,1,2 Anhua Wu,3 Wan Li,2 Xun Huang,3 Nan Ren,3 Xinyu Feng,4 Ying Zhang2,3 1Department of Nursing, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, People’s Republic of China; 2Teaching and Research Section of Clinical Nursing, Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 3Infection Control Center, Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 4Xiangya School of Nursing, Central South University, Changsha, People’s Republic of ChinaCorrespondence: Ying Zhang, Tel +8613787263396, Email zhang_ying1013@hotmail.comBackground: Few studies have focused on the work engagement of infection control nurses (ICNs). The perceived organizational support (POS) and psychological capital (PsyCap) might be important factors influencing ICNs’ work engagement. Moreover, PsyCap might play a mediating role in the relationship between POS and work engagement.Objective: This study aims to clarify the relationships among POS, PsyCap and work engagement of Chinese ICNs.Methods: A cross-sectional design was performed to collect data on 7382 ICNs from 20 provinces in China. Data collection was conducted by an online questionnaire, including questions about demographics, the Chinese version of the Utrecht work engagement scale (UWES), the Chinese version of the psychological capital questionnaire (PCQ) and the perceived organizational support scale for medical staff. Univariate analysis, the Spearman correlation method and the mediating effect test were conducted.Results: The work engagement was at a relatively high level, with a total score of 80.87 ± 14.95. The total scores of POS and PsyCap scale were 41.45 ± 7.37 and 89.14 ± 9.06 respectively, both of which were at the upper-middle level. Work engagement was positively associated with both POS and PsyCap (both P< 0.01). Furthermore, the mediating effect of PsyCap on the relationship between POS and work engagement was 0.394, the total effect was 0.443, and the ratio of mediating effect to total effect was 88.94%.Conclusion: The findings suggest that both POS and PsyCap can directly increase the work engagement of the Chinese ICNs. Besides, POS can indirectly improve work engagement, partially through PsyCap. Therefore, enhancing POS and PsyCap could be effective in improving the work engagement of ICNs.Keywords: infection control nurses, mediating effect test, perceived organizational support, psychological capital, work engagement

Mingyang Gao,1,&ast; Yanan Li,1,&ast; Jiaxu Yu,1 Wei Li,1 Shiji Qin,2 Yahui Zhang,3 Lian Zhu,4 Zhiyong Hou,4 Qiujun Wang1 1Department of Anesthesiology, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, People’s Republic of China; 2Department of Foot and Ankle Surgery, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 3Department of Nursing, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 4Department of Orthopaedics, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiujun Wang, Department of Anesthesiology, Third Hospital of Hebei Medical University, No. 139, Ziqiang Road, Shijiazhuang City, Hebei, People’s Republic of China, Tel/Fax +86-311-8860-2072, Email wangqiujunsy@163.comPurpose: A single-injection nerve block provides excellent analgesia in a short time, but rebound pain after the nerve block disappears has attracted researchers’ attention. The aim of this study is to evaluate the effect of intravenous dexamethasone on rebound pain after adductor canal block (ACB) and popliteal sciatic nerve block in patients with ankle fracture.Methods: We recruited 130 patients with ankle fractures scheduled for open reduction and internal fixation (ORIF), each of whom received ACB and popliteal sciatic nerve block. Patients were divided into two groups: C (ropivacaine only) and IV (ropivacaine with intravenous dexamethasone). The primary outcome was the incidence of rebound pain. Secondary outcomes included the following: pain scores at 6 h (T1), 12 h (T2), 18 h (T3), 24 h (T4), and 48 h (T5) after operation; duration of the nerve block; number of presses of the analgesia pump and rescue analgesic consumption in the three-day postoperative period; quality of recovery scale (QoR-15 score); postoperative sleep quality; satisfaction of patients; and levels of serum inflammatory markers (IL-1β, IL-6, and TNF-α) six hours after surgery.Results: Compared with group C, the incidence of rebound pain in group IV was significantly reduced, and the duration of nerve block was extended by approximately nine hours (P< 0.05). Moreover, patients in group IV had significantly lower pain scores at T2-T4, lower levels of serum inflammatory markers (IL-1β, IL-6, and TNF-α), higher QoR-15 score two days after the operation, and satisfactory sleep quality the night after surgery (P< 0.05).Conclusion: Intravenous dexamethasone can reduce the rebound pain after adductor block and sciatic popliteal nerve block in patients with ankle fracture surgery, prolong the duration of nerve block, and improve the quality of early postoperative recovery.Keywords: dexamethasone, nerve block, postoperative analgesia, ankle fracture, rebound pain

Mingwei Ma,1,&ast; Shufeng Wei,2,&ast; Dan Yin,2 Weizhong Li,2 Chen Li2 1School of Clinical Medicine, Peking Union Medical College Hospital (PUMC and CAMS), Beijing, 100730, People’s Republic of China; 2Department of Rheumatology, Fangshan Hospital Beijing University of Chinese Medicine, Beijing, 102401, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chen Li, Department of Rheumatology, Fangshan Hospital, Beijing University of Chinese Medicine, No. 4, Chengguan Health Road, Fangshan District, Beijing, People’s Republic of China, Tel +86 13810988688, Email casio1981@163.comAbstract: SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis) syndrome is a rare disease characterized by osteoarticular and cutaneous manifestations. SAPHO syndrome mostly involves the skin, mainly presented as palmoplantar pustulosis and severe acne. Sweet’s syndrome (SS) is a neutrophilic dermatosis of unknown cause, which may be caused by autoinflammation. So far, SAPHO syndrome complicated with SS has been rarely reported worldwide. Here, we present a rare case diagnosed in our hospital with detailed clinical information. This patient presented pain and swelling in her right leg. Later, she developed red papules on her right lower eyelid and a skin biopsy showed diffuse lymphocytic and neutrophilic infiltration in the superficial dermis. She was diagnosed with SAPHO syndrome and SS according to medical history and examination. These two diseases share parts of autoinflammatory signaling pathways and might be different variations of the spectrum of autoinflammatory diseases. Through this case, we aim to provide a new horizon for the regulation of neutrophils in SAPHO syndrome and skin lesions like SS.Keywords: SAPHO syndrome, Sweet’s syndrome, autoinflammation disease

Lihua Kang,1 Xiangliang Liu,1 Wei Ji,1 Kaiwen Zheng,1 Yuguang Li,2 Yanqiu Song,1 Hua He,1 Xiaomeng Wang,1 Tingting Yang,1 Meng Guan,1 Ge Zhu,1 Yangyang Gao,1 Yanjie Guan,1 Lei Wang,1 Wei Li1 1Cancer Center, The First Hospital of Jilin University, Changchun, Jilin Province, People’s Republic of China; 2College of Instrumentation and Electrical Engineering, Jilin University, Changchun, Jilin Province, People’s Republic of ChinaCorrespondence: Wei Li, Cancer Center, The First Hospital of Jilin University, No. 71 Xinmin Street, Changchun, 130021, People’s Republic of China, Tel +86-13756661267, Email liwei66@jlu.edu.cnAim: Neutrophil-to-lymphocyte ratio (NLR) is an index of systemic inflammation. This study is to clarify the role of NLR in body functional status, nutritional risk and nutritional status in the course of tumor.Methods: A multi-center cross-sectional study of patients with various types of malignant tumors was accrued from the whole country. There were 21,457 patients with completed clinical data, biochemical indicators, physical examination, the Patient-Generated Subjective Global Assessment (PG-SGA) and Nutrition Risk Screening 2002 (NRS2002) survey. Logistic regression analysis was used to figure out the influencing factors of NLR, and four models were established to evaluate the influence of NLR on body functions, nutritional risks and nutritional status.Results: Male patients, TNM stage IV, total bilirubin, hypertension and coronary atherosclerotic heart disease (CAHD) were independent predictors of NLR > 2.5. BMI, digestive systemic tumors and triglyceride negatively affect NLR in multivariable logistic regression. NLR was an independent predictor of Karnofsky Performance Scale (KPS), fat store deficit in all degrees, moderate and severe muscle deficit, mild fluid retention and PG-SGA grade.Conclusion: Male patients and those with hypertension and CAHD are prone to systemic inflammation. Systemic inflammation significantly degrades body function status and nutritional status, increases nutritional risk and influences fat and muscle metabolism in patients with malignant tumor. Improving the intervenable indicators such as elevating albumin and pre-albumin, decreasing total bilirubin and enhancing nutrition support are imperative. Obesity and triglyceride behave like anti-systemic inflammation, which is misleading due to reverse causation in the course of malignancy.Keywords: neutrophil-to-lymphocyte ratio, inflammation, tumor, nutrition, body function

Wei Xu,1,&ast; Qiankun Hu,1,&ast; Chong Chen,2,&ast; Weixia Li,2 Qiang Li,1 Liang Chen1 1Department of Liver Disease, Shanghai Public Health Clinical Center, Fudan University, Shanghai, People’s Republic of China; 2Department of Infectious Disease, Shanghai Public Health Clinical Center, Fudan University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiang Li; Liang Chen, Email liqiang66601@163.com; chenliang@shaphc.orgBackground and Aims: Chronic hepatitis B virus (HBV) infection patients who do not fulfill the typical treatment indications should be followed up. This study aimed to evaluate the risk of liver fibrosis progression (LFP) and assess the role of noninvasive tests (NITs) of liver fibrosis in monitoring LFP in these patients.Methods: A total of 116 patients with active HBV replication, persistently normal or minimally elevated alanine aminotransferase (ALT) levels, and no or mild hepatic necroinflammation or fibrosis based on liver biopsy tests at baseline and followed by a repeated liver biopsy assessment during follow-up. LFP was defined as increase in METAVIR fibrosis score by 1 score or more.Results: Among 116 patients, 40 (34.5%) progressed by at least one fibrosis stage, 16 (13.8%) progressed by at least two fibrosis stages at a median follow-up interval of 27 months (IQR: 12– 36). Multivariate analysis confirmed the significant association of an increase in liver stiffness measurement (LSM) value with LFP on histology (p =0.005). The AUROC of LSM value increase rate is significantly higher than that of serum-based NITs of liver fibrosis for the prediction of LFP (p < 0.05). An increase in LSM by 20% is the optimal cutoff for the prediction of LFP.Conclusion: LFP is non-negligible in patients with active HBV replication, persistently normal or minimally elevated ALT, and initially no or minimal hepatic necroinflammation or fibrosis. Serial LSM tests would be more reliable in identifying LFP than serum-based NITs, and easier to obtain than serial liver biopsy tests.Keywords: liver fibrosis progression, noninvasive tests, transient elastography, liver stiffness measurement, chronic hepatitis B

Hang Qiu,1 Yinghua Zhu,1 Guoqi Shen,1 Zhen Wang,1 Wenhua Li1,2 1Institute of Cardiovascular Diseases, Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of China; 2Department of Cardiology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of ChinaCorrespondence: Wenhua Li, Department of Cardiology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of China, Tel +86 18052268293, Email xzwenhua0202@163.comPurpose: Development and validation of a nomogram model to predict the risk of Contrast-Induced Acute Kidney Injury (CI-AKI) after emergency percutaneous coronary intervention (PCI) in elderly patients with acute ST-segment elevation myocardial infarction (STEMI).Patients and Methods: Retrospective analysis of 542 elderly (≥ 65 years) STEMI patients undergoing emergency PCI in our hospital from January 2019 to June 2022, with all patients randomized to the training cohort (70%; n=380) and the validation cohort (30%; n=162). Univariate analysis, LASSO regression, and multivariate logistic regression analysis were used to determine independent risk factors for developing CI-AKI in elderly STEMI patients. R software is used to generate a nomogram model. The predictive power of the nomogram model was compared with the Mehran score 2. The area under the ROC curve (AUC), calibration curves, and decision curve analysis (DCA) was used to evaluate the prediction model’s discrimination, calibration, and clinical validity, respectively.Results: The nomogram model consisted of five variables: diabetes mellitus (DM), left ventricular ejection fraction (LVEF), Systemic immune-inflammatory index (SII), N-terminal pro-brain natriuretic peptide (NT-proBNP), and highly sensitive C-reactive protein(hsCRP). In the training cohort, the AUC is 0.84 (95% CI: 0.790– 0.890), and in the validation cohort, it is 0.844 (95% CI: 0.762– 0.926). The nomogram model has better predictive ability than Mehran score 2. Based on the calibration curves, the predicted and observed values of the nomogram model were in good agreement between the training and validation cohort. Decision curve analysis (DCA) and clinical impact curve showed that the nomogram prediction model has good clinical utility.Conclusion: The established nomogram model can intuitively and specifically screen high-risk groups with a high degree of discrimination and accuracy and has a specific predictive value for CI-AKI occurrence in elderly STEMI patients after PCI.Keywords: nomogram, elderly, risk prediction model, ST-segment elevation myocardial infarction, percutaneous coronary intervention, contrast-induced acute kidney injury