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Ruiming Deng,1,2,* Hang Yang,1,* Weibo Zhong,2 Juan Zhou,3 Guiming Huang,2 Kai Zeng1 1Department of Anesthesiology, The First Affiliated Hospital of Fujian Medical University, Fuzhou City, Fujian Province, 350004, People’s Republic of China; 2Department of Anesthesiology, Ganzhou People’s Hospital, Ganzhou City, Jiangxi Province, 341000, People’s Republic of China; 3Department of Thyroid and Breast Surgery, Ganzhou People’s Hospital, Ganzhou City, Jiangxi Province, 341000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Kai Zeng, Department of Anesthesiology, The First Affiliated Hospital of Fujian Medical University, Fuzhou City, Fujian Province, 350004, People’s Republic of China, Email fymzk6822@163.com Guiming Huang, Department of Anesthesiology, Ganzhou People’s Hospital, Ganzhou City, Jiangxi Province, 341000, People’s Republic of China, Email huangguiming@mail.gzsrmyy.comBackground: Sepsis-associated acute kidney injury (S-AKI) is a prevalent and severe clinical complication in intensive care units (ICUs) and is associated with high mortality and poor prognosis. The dysfunction of renal tubular epithelial cells (TECs), particularly through their metabolic reprogramming, plays a critical role in the onset and progression of S-AKI. CITED2 is shown to regulate a variety of cellular processes, but its specific impact on TECs metabolism and S-AKI pathogenesis remains unclear. The aim of this study was to investigate the role of CITED2 in the metabolic reprogramming of TECs and its effects on inflammation and kidney injury in S-AKI.Material and Methods: The C57BL/6 mouse model of S-AKI was established using cecal ligation and puncture (CLP). We assessed the inflammatory responses, glucose metabolism and CITED2 expression in the kidneys of septic mice. Additionally, the effect of CITED2 on TECs metabolism and inflammation was evaluated using in vivo and in vitro models. CITED2 silencing and overexpression were employed to elucidate its regulatory role, focusing on the AKT signaling pathway.Results: S-AKI causes structural and functional kidney damage, aggravated inflammatory responses, and dysregulated glucose metabolism, accompanied by increased expression of CITED2. CITED2 silencing attenuated TECs metabolic dysfunction and reduced inflammation, thereby protecting the kidney from injury. Conversely, CITED2 overexpression exacerbated TECs metabolic dysfunction, promoted inflammatory responses, and worsened kidney injury. Mechanistically, CITED2 regulates TEC metabolism through the AKT signaling pathway, promoting S-AKI-related inflammation and contributing to kidney injury.Conclusion: CITED2 drives the metabolic reprogramming of TECs through the AKT signaling pathway, thereby aggravating the inflammatory response and leading to kidney injury, highlighting its critical role in S-AKI. Targeting CITED2 inhibition may represent a novel therapeutic approach for managing S-AKI.Keywords: CITED2, Sepsis, Acute kidney injury, Metabolic reprogramming, TECs

Zizhang Cheng,1,* Xiaoli Li,2,* Shu Wang,1 Weijin Sun,1 Junhong Pan,1 Xiongfei Wang,1 Jian Zhou,1 Tianfu Li,3– 5 Guoming Luan,1,4,5 Yuguang Guan1,4,5 1Department of Neurosurgery, SanBo Brain Hospital, Capital Medical University, Beijing, 100093, People’s Republic of China; 2Department of Neurology, Affiliated Zhong Da Hospital, Southeast University, Nanjing, People’s Republic of China; 3Department of Neurology, Sanbo Brain Hospital, Capital Medical University, Beijing, People’s Republic of China; 4Beijing Key Laboratory of Epilepsy, Beijing, 100093, People’s Republic of China; 5Center of Epilepsy, Beijing Institute of Brain Disorders, Collaborative Innovation Center for Brain Disorders, Laboratory for Clinical Medicine, Capital Medical University, Beijing, 100093, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yuguang Guan; Guoming Luan, Department of Neurosurgery, SanBo Brain Hospital Capital Medical University, Beijing, 100093, People’s Republic of China, Email guanyg2020@ccmu.edu.cn; luangm@ccmu.edu.cnPurpose: Sturge-Weber syndrome (SWS), a rare congenital neurological and skin disorder, is frequently associated with drug-resistant epilepsy. Translocation of high mobility group box 1 (HMGB1) protein from the nucleus to the cytoplasm or extracellular milieu has been implicated in neuroinflammatory processes contributing to the development of epileptogenesis. This study aimed to explore the expression and distribution of HMGB1 in brain tissue from SWS patients with drug-resistant epilepsy, with the goal of elucidating its potential involvement in the pathogenesis of epilepsy.Patients and Methods: The study enrolled eight patients with drug-resistant epilepsy who underwent hemispherectomy. Brain tissue specimens were obtained and analyzed using immunofluorescence staining to detect HMGB1 distribution in microglia, astrocytes, or different neuronal subtypes. Correlation analyses were performed to investigate the potential relationship between HMGB1 translocation within cells and the clinical characteristics of SWS patients.Results: In lesional tissues of SWS patients, we observed significantly higher cytoplasmic HMGB1 levels. Meanwhile, HMGB1 was widely distributed in the cytoplasm of microglia and neurons, while in astrocytes, it was primarily localized in the nucleus. This translocation occurred across many neuronal subtypes, including excitatory glutamatergic, inhibitory GABAergic, and cholinergic neurons. The lower proportion of HMGB1-translocated cholinergic neurons was seen compared to the other two neuronal subtypes. Furthermore, no correlation was found between cytoplasmic HMGB1 levels and clinical characteristics of SWS patients.Conclusion: The results suggest the involvement of HMGB1 in the pathogenesis of drug-resistant epilepsy in SWS patients. Additional research is required to elucidate the precise mechanisms and potential therapeutic targets associated with HMGB1 that underlie the epilepsy linked to SWS.Keywords: high mobility group box 1, translocation, Sturge Weber syndrome, drug-resistant epilepsy, cell subtype

Pilong Shi,1,* Yuetong Sha,1,* Xinran Wang,1,* Tao Yang,1 Jiawei Wu,1 Jiajun Zhou,1 Kai Liu,1 Xue Guan,2 Song Wang,1 Yongsheng Liu,1 Jingquan Gao,3 Hongli Sun,1 Tao Ban,1 Yonggang Cao1 1Department of Pharmacology, Harbin Medical University, Heilongjiang, 163319, People’s Republic of China; 2Morphological Experiment Center, Harbin Medical University, Heilongjiang, 163319, People’s Republic of China; 3Department of Nursing, School of Medicine, Lishui University, Lishui, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yonggang Cao; Hongli Sun, Email 437343482@qq.com; sunhongli@hmudq.edu.cnPurpose: Myocardial ischemia-reperfusion injury (MI/RI) is associated with increased oxidative damage and mitochondrial dysfunction, resulting in an elevated risk of mortality. MI/RI may be alleviated by protecting cardiomyocytes from oxidative stress. Lutein, which belongs to a class of carotenoids, has proven to be effective in cardiovascular disease treatment due to its remarkable antioxidant properties, but its application is limited due to its poor stability and low bioavailability in vivo.Methods: In this study, a delivery system was developed based on distearoyl phosphatidyl ethanolamine (DSPE)-thiol-ketone (TK)-PEG2K (polyethylene glycol 2000) (abbreviated as DTP) and PCM-SH (CWLSEAGPVVTVRALRGTGSW) to deliver lutein (abbreviated as lutein@DTPP) to damaged myocardium. First, lutein, lutein@DTP, or lutein@DTPP were injected through the tail vein once a day for 3 days and then MI/RI model rats were established by exposing rats to ischemia for 45 min and reperfusion for 6 h. We employed a range of experimental techniques including qRT-PCR, Western blotting, transmission electron microscopy, immunohistochemistry, immunofluorescence, flow cytometry, immunoprecipitation, molecular docking, and molecular dynamics simulations.Results: Lutein@DTPP exhibited good myocardial targeting and ROS-responsive release. Our data suggested that lutein@DTPP effectively suppresses ferroptosis in cardiomyocytes. Mechanistically, we observed an upregulation of mouse double minute-2 (MDM2) in the hearts of MI/RI models and cardiomyocytes exposed to hypoxia/reoxygenation (H/R) conditions. In addition, NADH-ubiquinone oxidoreductase 75 kDa Fe-S protein 1 (NDUFS1) translocation from the cytosol to the mitochondria was inhibited by MDM2 upregulation. Notably, no significant variation in the total NDUFS1 expression was observed in H/R-exposed cardiomyocytes following treatment with siMDM2. Further study indicated that lutein facilitates the translocation of NDUFS1 from the cytosol to mitochondria by directly binding and sequestering MDM2, thereby improving mitochondrial function and inhibiting ferroptosis.Conclusion: Lutein@DTPP promoted the mitochondrial translocation of NDUFS1 to restore mitochondrial function and inhibited the ferroptosis of cardiomyocytes by directly binding and sequestering MDM2. Keywords: myocardial ischemia-reperfusion injury, lutein, ROS, MDM2, NDUFS1, ferroptosis

Shuang Dai, Lan Gao, Chao Zou, Minghui Ge, Junwei Zhou, Yinghua Yun Department of Neurology, Jilin University First Hospital, Changchun, Jilin, 130061, People’s Republic of ChinaCorrespondence: Yinghua Yun, Department of Neurology, Jilin University First Hospital, No. 71 Xinmin Street, Chaoyang District, Changchun, Jilin, 130061, People’s Republic of China, Tel +86 0431-85612995, Email yuanyinghua542y@163.comObjective: This study aimed to investigate the gratitude experience of young and middle-aged patients with spinal muscular atrophy (SMA) during hospitalisation to provide a theoretical basis for medical professionals to develop gratitude intervention programs.Methods: Patients with SMA who were treated with nusinersen in the Department of Neurology of the First Hospital of Jilin University between April 20 and May 20, 2024 were selected using the purposive sampling method, and semi-structured interviews were conducted. The interview data were analysed using Colaizzi’s 7-step analysis method.Results: Four themes were extracted: gratitude stimulated positive emotions; gratitude enhanced life motivation; gratitude reflected the level of social support; and gratitude promoted life restructuring planning.Conclusion: Patients with SMA have gratitude experience and their own perception of life. Strengthened feelings of gratitude could be helpful to the psychological resilience of patients, influence their view of life in a grateful way of thinking and help them actively plan all aspects of their lives, from daily living to social re-integration.Keywords: young and middle-aged, spinal muscular atrophy, gratitude, social support, positive psychology

Jingxin Zhou,1,&ast; Can Cao,1,&ast; Tonghua Liu,2 Lili Wu,2 Juan Miao1 1Department of Nephrology and Endocrinology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 101121, People’s Republic of China; 2Key Laboratory of Health Cultivation of the Ministry of Education, Beijing University of Chinese Medicine, Beijing, 100029, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lili Wu; Juan Miao, Email qingniao_566@163.com; 77915183@qq.comBackground: Thyroid dysfunction is more common in other endocrine disorders such as diabetes mellitus (DM). Carcinoembryonic antigen (CEA), a common tumor biomarker, is found elevated in patients with thyroid dysfunction. However, the relationship between thyroid hormone levels and CEA levels remains unclear.Methods: In total, 663 patients with type 2 diabetes at the Tongzhou Branch of Dongzhimen Hospital were enrolled in this retrospective study. Data were collected from inpatient electronic files between December 2011 and December 2019. Laboratory indices were statistically analyzed using logistic regression and Spearman correlation analyses.Results: In our study, total triiodothyronine (TT3), free triiodothyronine (FT3), serum albumin(ALB), total protein (TP), and triglyceride (TG) levels were significantly higher in the T2DM patients with normal values of CEA than T2DM patients who had abnormal values of CEA, whereas alkaline phosphatase (ALP), Glucose (GLU), and HbA1c levels were significantly increased in the T2DM patients with abnormal CEA level. Binary logistic regression analysis demonstrated that FT3, GLU, HbA1c, and TG levels remained as independent risk factors for CEA in patients with T2DM (β=− 0.907, P =0.004; β =− 1.009, P=0.004; β =0.090, P = 0001; β= 0.336, P < 0.001; β= − 0.293, P =0.009, resp). Spearman correlation analysis showed that CEA level was significantly positively correlated with HbA1c and GLU (rs value: 0.265, P < 0.001; rs value: 0.270, P < 0.001, resp.) and negatively correlated with FT3 and TG levels (rs value: − 0.139, P < 0.001; rs value: − 0.103 P =0.008, resp). Furthermore, multivariate logistic regression analysis indicated that the FT3 quartiles were significantly associated with CEA levels before and after adjusting for confounding factors.Conclusion: Our study determined that FT3 remained an independent risk factor for CEA in patients with T2DM and was significantly negatively correlated with CEA levels.Keywords: retrospective study, free triiodothyronine, carcinoembryonic antigen, thyroid function, type 2 diabetes mellitus

Jun Zhou,1,2,&ast; Liu Shi,1,2,&ast; Chuwei Tian,1,2 Yucheng Gao,1,2 Jinyu Wang,2,3 Jin Mao,2,4 Yan Li,2,4 Wenbin Fan,1,2 Xiangxu Chen,1,2 Cheng Zhang,1,2 Tian Xie,1,2 Yunfeng Rui1,2,&ast; 1Department of Orthopaedics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, People’s Republic of China; 2Multidisciplinary Team for Geriatric Hip Fracture Comprehensive Management, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, People’s Republic of China; 3Department of Rehabilitation, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, People’s Republic of China; 4Department of Emergency, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yunfeng Rui, Department of Orthopaedics, Zhongda Hospital, School of Medicine, Southeast University, NO. 87 Ding Jia Qiao, Nanjing, Jiangsu, 210009, People’s Republic of China, Tel +86 13705182577, Email ruiyunfeng@126.comIntroduction: This study aims to assess the impacts of the Fast Access to Surgery in Emergency (FASE) strategy on (1) the workflow of multidisciplinary team (MDT) during hospitalization; (2) the clinical outcomes of geriatric femoral neck fracture (FNF) patients.Methods: A retrospective study was conducted in a single trauma center to evaluate the clinical data of geriatric FNF patients admitted through emergency from July 2017 to June 2022. The FASE strategy was implemented since Jan 1st 2020, and patients were categorized into the FASE group or the control group according to the time of admission (before/after the initiation timepoint of FASE strategy). Propensity score matching (PSM) was utilized to limit confounding bias between the two groups.Results: Finally, 344 patients were included after a one-to-one matching. The FASE strategy resulted in a slightly prolonged duration in emergency (6.02± 5.99 h vs 2.72± 4.22 h, p< 0.001) but was meanwhile associated with significant decreases in time to surgery (61.16± 38.74 h vs 92.02± 82.80 h, p< 0.001), actual surgery delay (67.18± 39.04 h vs. 94.25± 84.41 h, p< 0.001) and total length of hospital stay (10.57± 4.93 h vs 12.50± 4.73 h, p < 0.001). Besides, despite the consistency of transfusion rate between the two groups, improved blood management was achieved in the FASE group, as evidenced by a smaller drop in hemoglobin levels (− 20.49± 17.02 g/L vs − 25.28± 16.33 g/L, p = 0.013) in patients without preoperative or intraoperative transfusion. However, no significant differences were observed regarding the overall clinical outcomes such as mortality or postoperative complications.Conclusion: The Fast Access to Surgery in Emergency (FASE) for geriatric FNF patients effectively optimized the preoperative evaluation workflow, which significantly shortened time to surgery and length of hospital stay, and reduced perioperative blood loss. FASE strategy improved the surgical workflows and turnover efficiency of geriatric FNF patients, therefore could play an important role in the optimal MDT co-management for geriatric FNF patients. Keywords: femoral neck fracture, geriatric, emergency optimization, multidisciplinary management, early surgery

Jia Zhou,1,&ast; Wenwen Wang,1,&ast; Qiyu Zhang,1,&ast; Hanlin Zhang,1 Keyun Tang,1 Chenhui Mao,2 Mingli Li,3 Jun Li1 1Department of Dermatology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases, Beijing, People’s Republic of China; 2Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 3Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jun Li, Department of Dermatology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Disease, No. 1 Shuaifuyuan Wangfujing Dongcheng District, Beijing, 100730, People’s Republic of China, Tel +86-010-69151500, Fax +86-010-69151502, Email lijun35@hotmail.comPurpose: Syphilis, caused by Treponema pallidum, presents a diagnostic challenge due to its diverse clinical manifestations. Neurosyphilis has seen a resurgence in recent years, particularly among men who have sex with men and those living with HIV. Diagnosis of neurosyphilis in emergency settings is challenging due to its varied neurological presentations. This study aims to serve as a reference for dermatologists and neurologists in diagnosing and treating neurosyphilis.Patients and Methods: This retrospective study analyzed patients who presented with neuropsychiatric symptoms and were ultimately diagnosed with neurosyphilis. These patients were collected from the emergency department in Peking Union Medical College Hospital between January 2018 and November 2023. The medical history, clinical symptoms, laboratory examinations, cranial MRI characteristics, and treatment regimens of these patients were investigated.Results: Among the included 12 neurosyphilis patients, memory deterioration was observed in 8 out of the 12 neurosyphilis patients. Diagnosis often resulted in delays, with misdiagnoses mainly including Alzheimer’s disease, stroke, and epilepsy. Neuroimaging revealed various abnormalities, predominantly affecting ventricular and temporal regions. Treatment with penicillin-based regimens varied in compliance, with only a minority of patients adhering to guidelines. Treatment outcomes were inconsistent, with some patients experiencing irreversible neurological damage and fluctuating serum rapid plasma reagin (RPR) titers.Conclusion: Diagnosis of neurosyphilis in the emergency department remains challenging, necessitating awareness of its varied neurological presentations. Enhanced diagnostic strategies are imperative to accelerate treatment initiation and improve outcomes for affected individuals.Keywords: neurosyphilis, emergency department, neuropsychiatric symptoms, cerebrospinal fluid, serologic tests

Runing Fu,1,&ast; Wenping Lian,1,&ast; Bohao Zhang,2,&ast; Gang Liu,3 Xinyu Feng,1 Yingjie Zhu,1 Jiuan Zhou,1 Xinyu Zhang,4 Shukai Wang,1 Huijuan Huo,1 Daxin Wang,1 Cui Liu,1 Saisai Gao,1 Yajie Ma,4 Mengle Peng1,&ast; 1Department of Clinical Laboratory, The Third People’s Hospital of Henan Province, Zhengzhou, Henan, 450006, People’s Republic of China; 2Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450000, People’s Republic of China; 3The Center of Meige Syndrome, The Third People’s Hospital of Henan Province, Zhengzhou, Henan, 450006, People’s Republic of China; 4Department of Medical Affair, the Third People’s Hospital of Henan Province, Zhengzhou, Henan, 450006, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mengle Peng; Yajie Ma, Email pengmengle1990@126.com; szsyywk@sina.comPurpose: Inflammatory markers are known to be associated with many diseases, but their role in Meige syndrome (MS) remains unclear. This study aimed to develop and validate a nomogram for the risk prediction of MS based on inflammatory markers.Patient Data and Methods: Data from 448 consecutive patients with MS at the Third People’s Hospital of Henan Province between January 2022 and December 2023 were retrospectively reviewed. The MS cohort was randomly divided into separate training and validation sets. A nomogram was constructed using a multivariate logistic regression model based on data from the training set. The model’s performance was validated through cross-validation, receiver operating characteristic (ROC) curve analysis, calibration curve analysis and decision curve analysis (DCA).Results: A total of five predictors, including red blood cell distribution width (RDW), hemoglobin (HGB), high-density lipoprotein cholesterol (HDL-C), the lymphocyte-to-monocyte ratio (LMR), and the systemic immune‐inflammation index (SII), were identified using multivariate logistic regression from a total of 11 variables. The cross-validation results indicated the stability of the model constructed with the above five predictors. The model showed moderate predictive ability, with an area under the ROC curve of 0.767 in the training set and 0.735 in the validation set. The calibration curve and DCA results indicate that the model has strong consistency and significant potential for clinical application.Conclusion: We constructed a nomogram based on five risk predictors, RDW, HGB, HDL-C, the LMR and the SII, to predict MS and enhance the predictive accuracy for identifying MS risk.Keywords: Meige syndrome, inflammatory marker, nomogram, LMR, SII

Rongce Zhao,1,&ast; Jing Zhou,2,&ast; Zehao Zheng,1,&ast; Xinhao Xiong,1 Qiaoxuan Wang,3 Shaohua Li,1 Wei Wei,1 Rongping Guo1 1Department of Liver Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China; 2Department of Pathology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China; 3Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Rongping Guo; Wei Wei, Department of Liver Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China, Email guorp@sysucc.org.cn; weiwei@sysucc.org.cnBackground: For patients with large unresectable hepatocellular carcinoma (HCC), the effectiveness of conventional transarterial chemoembolization (TACE) remains suboptimal, which necessitates the administration of substantial volumes of chemotherapy drugs and lipiodol, thereby increasing the risk of liver failure and other chemotherapy-related complications. Therefore, we devised a strategy of initial hepatic arterial infusion chemotherapy (HAIC) followed by sequential drug-eluting bead TACE (DEB-TACE). In our treatment design, a lower tumor burden after HAIC facilitated complete embolization of tumor vasculature, and the use of less amount of embolic agents reduced the incidence of liver failure and embolization syndromes.Methods: This retrospective study evaluated consecutive patients with unresectable large HCC with a maximum tumor diameter of ≥ 7 cm who received FOLFOX-HAIC combined with sequential DEB-TACE from April 2019 to February 2024. Efficacy was evaluated using the objective response rate (ORR), overall survival (OS), and progression-free survival (PFS); and safety was assessed using the frequency of key adverse events (AEs).Results: Among the 76 patients included, the median maximum tumor diameter was 12.4 cm (range, 7.0– 23.4 cm). The overall ORRs based on mRECIST and RECIST 1.1 criteria were 94.1% and 51.5%, respectively. The median OS was 28.1 months (95% CI, 22.7– 33.4), and the median PFS was 11.7 months (95% CI, 7.7– 15.8). All patients experienced AEs, but only 18.4% experienced grade 3 or 4 AEs, there was no treatment-related mortality.Conclusion: In this single-center, retrospective study, our results suggested that FOLFOX-HAIC with sequential DEB-TACE demonstrated promising efficacy and safety for patients with unresectable HCC with a maximum tumor diameter of ≥ 7 cm.Keywords: large unresectable hepatocellular carcinoma, hepatic arterial infusion chemotherapy, drug-eluting bead transarterial chemoembolization, sequential

Jiayue Zhou,1,2 Yingxiang Wu,1,2 Zhiyan Lu,1,2 Yan Wang1,2 1Yunnan Provincial Key Laboratory of Entomological Biopharmaceutical R&D, Dali University, Dali, Yunnan Province, 671000, People’s Republic of China; 2National-Local Joint Engineering Research Center of Entomoceutics, Dali University, Dali, Yunnan Province, 671000, People’s Republic of ChinaCorrespondence: Yan Wang, Yunnan Provincial Key Laboratory of Entomological Biopharmaceutical R&D, Dali University, Dali, Yunnan Province, 671000, People’s Republic of China, Tel +86 0872-2257401, Email jessica9428@sina.comPurpose: Rodgersia sambucifolia Hemsl (also known as Yantuo) is a traditional Chinese medicine commonly utilized as a medicinal herb with its rhizomes, mainly used to regulate the immune function of the human body. However, relatively few studies have investigated its active components and potential mechanisms of action in vivo.Methods: First, the chemical composition in vitro was identified and analyzed using the UPLC-Q-TOF MS/MS technique. Cyclophosphamide (CTX) was then administered intraperitoneally to rats to establish an immunosuppression model. Physiological and biochemical parameters, organ indices, and histopathological findings were evaluated for efficacy. Subsequently, potential biomarkers in rat serum were identified using multivariate statistical analysis and enriched and topologized using online platforms such as MetaboAnalyst and KEGG to reveal the critical metabolic pathways and their roles in the immunomodulatory network. Finally, the integrated analysis of components in vivo and in vitro, along with metabolic pathways, was performed using network pharmacology and molecular docking technology to elucidate the mechanisms of their roles in organismal immunity.Results: A total of 28 chemical components in vitro were identified, while pharmacodynamic experiments confirmed the immunomodulatory effects of Yantuo, especially in the high-dose administration group. Metabolomics analysis showed that 37 potential immune-related biomarkers were identified in positive and negative ion modes, involving 16 metabolic pathways such as arginine biosynthesis, pyrimidine metabolism, and riboflavin metabolism. The results of network pharmacology and molecular docking indicated that Yantuo may affect 7-O-galloyl-catechin, Cynaroside, Quercetin-7-O-beta-D-glucopyranoside, and 1.6-bis-O-galloyl-beta-D-glucose through interactions with the immune system, with significant pathways of action including galactose metabolism, glycolysis/gluconeogenesis, pyrimidine metabolism, and riboflavin metabolism.Conclusion: In our experiments, we confirmed the organismal modulatory effect of Yantuo on immunocompromised rats, clarified the key components, target proteins, and pathways of its possible action, and provided possibilities for follow-up studies. Keywords: immunosuppression, Yantuo, metabolomics, network pharmacology, molecular docking

Wenyi Li,1,2 Zhenguo Liu,1 Min Song,1 Zhenpeng Shi,1 Jihang Zhang,3 Junyu Zhou,1 Yidan Liu,1 Yun Qiao,4 Deshan Liu4 1First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, People’s Republic of China; 2Research Center for Basic Medical Sciences, Qilu Hospital of Shandong University, Jinan, People’s Republic of China; 3Traditional Chinese Medicine College, Shandong University of Traditional Chinese Medicine, Jinan, People’s Republic of China; 4Department of Traditional Chinese Medicine, Qilu Hospital of Shandong University, Jinan, People’s Republic of ChinaCorrespondence: Deshan Liu, Department of Traditional Chinese Medicine, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, People’s Republic of China, Tel +86 18560087381, Email liudeshan@sdu.edu.cnContext: Diabetic nephropathy (DN) and cognitive dysfunction (CD) are common complications of diabetes. Yi-Qi-Bu-Shen Recipe (YQBS) can effectively reduce blood glucose, improve insulin resistance, and delay the progression of diabetic complications. The underlying mechanisms of its effects need to be further studied.Objective: This study elucidates the mechanism of YQBS in DN with CD through network pharmacology and experimental validation.Materials and Methods: Protein-protein interaction, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed. Male Sprague-Dawley (SD) rats were divided into 6 groups: model, YQBS (2, 4, 8 g/kg), positive control (metformin, 200 mg/kg), and control; the DN model was established by high sugar and high fat diet combined with intraperitoneal streptozotocin injection. After the DN model was established, the rats were gavaged for 10 weeks. Serum, kidneys, and hippocampus tissues were collected to measure the expression levels of TLR4, NF-κB, TNF-α, and IL-6.Results: The network pharmacology analysis showed that quercetin and kaempferol were the main active components of YQBS. TNF and IL-6 were the key targets, and TLR4/NF-κB pathway was crucial to YQBS in treating DN complicated with CD. Experimental validation showed that the intervention of YQBS can reduce TNF-α and IL-6 in serum, and also significantly decreases the protein expression of TLR4 and NF-κB.Conclusion: YQBS exerts anti-inflammatory effects on DN with CD through TLR4/NF-κB pathway. This study provides a biological basis for the scientific usage of YQBS in inflammation diseases and supplies experimental evidence for future traditional Chinese medicine development.Keywords: Yiqi Bushen Recipe, diabetes nephropathy, cognitive dysfunction, network pharmacology, inflammation

Jinlei Zhou,1,&ast; Shanggao Xie,1,&ast; Sen Xu,1,&ast; Yuan Zhang,2 Yanlei Li,1 Qice Sun,2 Jun Zhang,1,3 Tingxiao Zhao1 1Center for Plastic & Reconstructive Surgery, Department of Orthopedics, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, People’s Republic of China; 2Department of Rheumatology, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 3Department of Orthopedics, Zhejiang Provincial People’s Hospital Bijie Hospital, Bijie, 551700, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tingxiao Zhao, Center for Plastic & Reconstructive Surgery, Department of Orthopedics, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Shangtang Road 158&num;, Hangzhou, Zhejiang, People’s Republic of China, Email spinezhaotingxiao@163.com Jun Zhang, Department of Orthopedics, Zhejiang Provincial People’s Hospital Bijie hospital, Guanghui Road 112&num;, Bijie, Guizhou, People’s Republic of China, Email spinecarezhangjun@163.comObjective: Comprehensive analyses of the burden of musculoskeletal disorders (MSDs) are crucial for deepening our understanding of their impact on population health and for evaluating progress toward achieving international health goals.Study Design: A comprehensive analysis was performed using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021.Methods: We gathered data on the number of prevalent cases, incidences, deaths, and disability-adjusted life years (DALYs) for MSDs from 1990 to 2021. Subsequently, crude indicators, age-standardized rates (ASRs) and estimated annual percentage change (EAPC) were calculated for MSDs from 1990 to 2021 at the global, regional, national, age and gender levels. Finally, decomposition analysis, frontier analysis, and EAPC cluster analysis were employed to examine changes in the indicators and the factors influencing them.Results: In 2021, there were 367,193,430 incident cases and 1,686,561,517 prevalent cases of MSDs globally. Between 1990 and 2021, the age-standardized incidence rates (ASIR) declined marginally from 4641.5 to 4351.79 cases per 100,000 population [EAPC: − 0.16 (− 0.19 to − 0.13)], while the age-standardized DALY rates (ASDR) increased from 1886.2 to 1908.87 per 100,000 population [EAPC: 0.09 (0.07 to 0.11)]. The ASRs were markedly elevated in the high SDI regions in comparison to the remaining SDI regions. The EAPC and its phase clustering analyses indicated a notable upward trajectory in the burden of MSDs in the low and middle SDI regions, particularly in Central Asia. The prevalence of MSDs is highest among individuals aged 50– 59 years and among women. At the global level, the burden of MSDs is 1.43 to 2.30 times higher for women than for men.Conclusion: From 1990 to 2021, the burden of MSDs has been concentrated in high SDI regions, with a gradual shift towards low and middle SDI regions.Keywords: musculoskeletal disease, global burden of disease, prevalence, incidence, DALYs, epidemiology

Zhen Cheng,&ast; Chunyu Hu,&ast; Yalan Zhang, Jie Zhou, Jiayang Shi, Li Sun, Zongtao Chen Health Management Centre, First Affiliated Hospital of Army Medical University, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zongtao Chen; Li Sun, Health Management Centre, First Affiliated Hospital of Army Medical University, No. 30, Gaotanyan Street, Shapingba District, Chongqing, People’s Republic of China, Tel +86 2368765191 ; +86 2368765228, Email zongtaochen@126.com; 51088031@qq.comPurpose: The aim of this study was to comprehensively compare the predictive effect of 10 body fat indexes on MAFLD in different sex, age and BMI subgroups.Patients and Methods: A total of 5403 physical examination data were included and divided into the MAFLD group (N=2632) and non-MAFLD group (N=2771). The differences and correlation of 10 promising indicators between the two groups were compared, including fatty liver index (FLI), hepatic steatosis index (HSI), lipid accumulation product (LAP), visceral fat index (VAI), cardiometabolic index (CMI), body adiposity index (BAI), and triglyceride-glucose index (TyG), waist circumference index (WC), body mass index (BMI), waist to height ratio (WHtR). Logistic regression was used to analyze the risk of MAFLD under different adjustment conditions. The operating characteristic curve of different genders, BMI levels and age subgroups was plotted.Results: Male gender, smoking, alcohol drinking, and higher age are risk factors for MAFLD. In addition to BAI, the other 9 indicators had a high correlation with MAFLD, the area under the curve (AUC) value was > 0.7, and the prediction effect was better in females, BMI< 24 kg/m2, age < 35 years subgroup, among which FLI (AUC: 0.912, 95% CI: 0.905– 0.920), LAP (AUC: 0.894, 95% CI: 0.8866– 0.903), and HSI (AUC: 0.881, 95% CI: 0.872– 0.890) have better prediction effects.Conclusion: Our study confirmed the accuracy of body fat-related indexes in predicting MAFLD in people of different sexes, ages, and BMI levels. Among them, FLI, LAP and HSI have high predictive value and can be utilized as simple and cost-effective tools for screening MAFLD in clinical settings.Keywords: metabolic dysfunction-associated fatty liver disease, body fat index, metabolic index, cross-sectional study

Lin Zhang,&ast; Yuanhang Zhang,&ast; Jin Zhou, Xiaoshuai Zhang, Lei Gao School of Health Management, Harbin Medical University, Harbin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lei Gao, School of Health Management, Harbin Medical University, Harbin, People’s Republic of China, Tel +86130-9171-9592, Email hydgaolei@163.comPurpose: The primary aim of this study is to investigate the mediating role of school adaptation in the impact of adolescent bullying victimization on mental health, as well as the gender differences therein. These findings offer a novel perspective for parents and educators, aiding bullied adolescents in managing and addressing mental health concerns.Methods: The primary data source for this study was the 2020/2021 Adolescent Health Theme Database from the China Population Health Data Center (PHDA). The research sample consisted of high school students from 16 cities in Shandong Province. Descriptive statistics, reliability and validity testing, structural equation modeling, as well as mediation analysis and multiple group analysis were conducted using SPSS 26.0 and AMOS 26.0.Results: School adaptation serves as a mediating variable between adolescent bullying and mental health. The model fit indices are as follows: GFI=0.946, AGFI=0.922, RMSEA=0.070, NFI=0.978, IFI=0.979, CFI=0.97. Even when considering gender, the model still demonstrates good fit. School bullying has significant negative effects on the mental health of both male and female victims (p< 0.05). For female victims, the mitigating effect of school adaptation on mental health is slightly lower than that for males (− 2.256). Regarding cyberbullying, male victims face a greater threat to mental health (− 3.234), with a impact of − 0.109 from cyberbullying on male mental health and − 0.065 from school bullying on female mental health.Conclusion: The school is found to mediate between school bullying, cyberbullying, and mental health. Schools may play a greater role in improving female mental health than male mental health. The impact of campus bullying on female mental health is greater than that of cyberbullying, whereas the opposite is true for males. Enhancing adolescents’ school adaptation levels helps mitigate the adverse effects of school and cyberbullying on adolescent mental health.Keywords: adolescents, bullying, school adjustment, mental health

Xilong Tang,1,2 Jianjin Xue,1,2 Jie Zhang,2 Jiajia Zhou1,2 1Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, People’s Republic of China; 2Department of Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, People’s Republic of ChinaCorrespondence: Jiajia Zhou, Department of Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, People’s Republic of China, Email zhoujj29@mail.sysu.edu.cnBackground: Hepatocellular carcinoma (HCC) is a prevalent malignancy within the digestive system, known for its poor prognosis. Gluconeogenesis, a critical metabolic pathway, is responsible for the synthesis of glucose in the normal liver. This study aimed to examine the role of gluconeogenesis-related genes (GRGs) in HCC and evaluate their impact on the tumor microenvironment infiltration and drug sensitivity in HCC.Methods: We retrieved gene expression and clinical pathological data of HCC from The Cancer Genome Atlas (TCGA) database. This dataset was utilized to develop a prognosis model. The data from The International Cancer Genome Consortium (ICGC) served as an independent validation cohort. A least absolute shrinkage and selection operator (LASSO) regression analysis was applied to a curated panel of GRGs to construct and validate the predictive model. Furthermore, unsupervised consensus clustering, based on the expression levels of GRGs, categorized HCC patients into distinct subgroups.Results: A four-gene prognostic model, referred to as GRGs, has been successfully developed with high accuracy and stability for the prediction of HCC patient prognosis. This model enables the stratification of patients into high or low risk groups based on individual risk scores, revealing significant differences in immune infiltration patterns and anti-tumor drug responses. Unsupervised consensus clustering analysis delineated four distinct subgroups of patients, each characterized by a unique prognosis and tumor immune microenvironment (TIME).Conclusion: This study is the first to develop a prognostic model incorporating 4-GRGs that effectively predicts the prognosis, tumor microenvironment infiltration, and drug sensitivity in HCC patients. The model based on 4 GRGs may contribute to predict the prognosis, immunotherapy and chemotherapy response of HCC patients.Keywords: hepatocellular carcinoma, gluconeogenesis metabolism, prognostic model, tumor microenvironment infiltration, drug sensitivity

Jiahua Wu, Xihua Lin, Xueyao Yin, Zhiye Xu, Nan Wu, Ziyi Zhang, Jiaqiang Zhou,&ast; Hong Li&ast; Department of Endocrinology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hong Li; Jiaqiang Zhou, Department of Endocrinology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 3 East Qingchun Road, Hangzhou, 310016, People’s Republic of China, Email srrshnfm@zju.edu.cn; zjq8866@zju.edu.cnPurpose: Metabolic syndrome (MetS) is an increasingly prevalent issue in China’s public health landscape. Few studies have investigated the metabolic syndrome (MetS) in overweight people. We proposed to analyze and contrast the occurrence of MetS in normal-weight and overweight individuals and identify potential indicators for forecasting MetS in adults in Zhejiang Province.Methods: This cohort study included 359 adults aged 40– 65 years and followed up for five years in Zhejiang Province. The study assessed the predictive capabilities of five indicators linked to obesity and lipid levels, namely body mass index (BMI), waist-to-height ratio (WHtR), triglyceride-glucose index (TyGi), and their combined indices (TyG-BMI, TyG-WHtR). The evaluation was done employing the area under the Receiver Operating Characteristic (ROC) Curve (AUC). DeLong test was applied to compare area under different ROC curves.We evaluated the relationships between five variables and MetS using multivariate logistic regression.Results: In normal-weight individuals, the five-year cumulative incidence of MetS was 21.85%, but in overweight people, it was 60.33%. After adjusting for confounding factors, BMI, WHtR, TyGi, TyG-BMI, and TyG-WHtR were independently linked to MetS in normal-weight individuals, while BMI, TyGi, TyG-BMI, and TyG-WHtR were independently linked to MetS in overweight individuals. In normal-weight individuals, the WHtR (AUC=0.738 and optimal threshold value =0.469) and TyG-WHtR (AUC=0.731 and optimal threshold value =4.121) had the larger AUC, which was significantly greater than that of the different three indicators. The TyG-BMI (AUC=0.769 and optimal threshold value = 211.099) was the best predictor of MetS in overweight individuals.Conclusion: The five-year cumulative incidence of MetS in overweight people was approximately triple that of normal-weight people in Zhejiang Province. In the overweight population, the TyG-BMI performed better than the other indices in predicting MetS. WHtR and TyG-WHtR outperformed BMI, TyGi, and TyG-BMI in anticipating MetS in a normal-weight population.Keywords: metabolic syndrome, normal weight, overweight, WHtR, BMI, TyG

Jiajun Zhou,1,2,&ast; Yandong Luo,1,2,&ast; Ping Chang,1,2 Liping Li1 1School of Public Health, Shantou University, Shantou, People’s Republic of China; 2Injury Prevention Research Center, Shantou University Medical College, Shantou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Liping Li, School of Public Health, Shantou University, Shantou, People’s Republic of China, Email lpli@stu.edu.cnBackground: Poly-victimization involves more than just counting incidents; it varies in severity and type among adolescents and can change over time.Objective: The aim is to identify latent classes of poly-victimization among children in early adolescence, investigate transition probabilities between these latent categories, and examine the influencing factors.Methods: We used stratified cluster random sampling to select 2275 junior high students from five rural middle schools in Shantou and Jieyang, China, and surveyed them in two waves. Latent Class Analysis (LCA) and Latent Transition Analysis (LTA) identified latent classes of poly-victimization, and multi-factor logistic regression examined factors influencing the probability of students transitioning between these latent classes.Results: LCA identified three categories of poly-victimization: low poly-victimization, group, and high child maltreatment and peer and sibling victimization. The probabilities of remaining in the high child maltreatment and peer and sibling victimization group, transitioning to the transition group, or shifting to the low poly-victimization group were 37.00%, 29.20%, and 33.80%, respectively. Most transition group members remained in the same group, with a conversion probability of 77.10%, followed by transitioning to the low poly-victimization group with a probability of 15.80%. Physically healthy children, compared to those with disabilities or illnesses, were less likely to switch from the low poly-victimization group to the transition group (OR=0.034) or the high child maltreatment and peer and sibling victimization group (OR=0.14). Non-left-behind children, compared to left-behind children, have a higher probability of switching from the high child maltreatment and peer and sibling victimization group to the low poly-victimization group (OR=6.905).Conclusion: The high child maltreatment and peer and sibling victimization group had similar probabilities of transitioning into other categories. Physical illness or disability, as well as being left behind, are significant risk factors for children transitioning from the low-harm group to the high-harm group.Keywords: poly-victimization, latent class analysis, latent transition analysis, left-behind children, child maltreatment, peer and sibling victimization

Fei Chen,1,2 Rujun Chen,3,&ast; Jiangfeng Zhou,1,2,&ast; Weiyi Xu,1,2,&ast; Jiahui Zhou,1,4 Xianxian Chen,1,5 Xiaohua Gong,1 Zimiao Chen1 1Department of Endocrinology and Metabology, The First Affiliated Hospital of Wenzhou Medical University, Zhejiang, People’s Republic of China; 2Wenzhou Medical University, Zhejiang, People’s Republic of China; 3Department of Burn, 906 Hospital of the Joint Logistics Team, PLA, Wenzhou, People’s Republic of China; 4Department of Internal Medicine, The First People’s Hospital of Longwan District, Wenzhou, People’s Republic of China; 5Department of Internal Medicine, The People’s hospital of Pingyang, Wenzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaohua Gong; Zimiao Chen, Department of Endocrinology and Metabology, The First Affiliated Hospital of Wenzhou Medical University, Zhejiang, People’s Republic of China, Email gxh1204@163.com; zimiaochen@163.comBackground: Thyroid hormone levels are associated with the distribution of body components in humans.Objective: This study aimed to investigate the associations between thyroid hormone (TH) levels, central sensitivity to THs, and body composition in overweight and obese patients with euthyroid type 2 diabetes mellitus (T2DM).Methods: This cross-sectional study included 1215 euthyroid T2DM patients (721 men and 494 women) aged 20– 80 years. The thyroid hormone sensitivity indices included the thyroid feedback quartile-based index (TFQI), thyrotroph T3 resistance index (TT3RI), thyrotroph T4 resistance index (TT4RI), and thyroid-stimulating hormone index (TSHI). The appendicular fat ratio, trunk fat ratio, android fat ratio, gynoid fat ratio, and appendicular skeletal muscle mass (ASM) were measured via dual-energy X-ray absorptiometry.Results: The data revealed a greater proportion of subjects with impaired central sensitivity to THs in the obese group. TFQIFT4 and TFQIFT3 levels were positively correlated with the upper limb fat ratio, lower limb fat ratio, gynoid fat ratio, and total fat ratio. TSHI was positively correlated with body mass index (BMI), upper limb fat ratio, lower limb fat ratio, trunk fat ratio, android fat ratio, gynoid fat ratio, total fat ratio, and appendicular skeletal muscle mass index (ASMI) in women. In men, TSHI was only positively correlated with upper limb fat ratio, lower limb fat ratio, and total fat ratio. Logistic regression analysis indicated that TT3RI and TFQIFT3 were independently and positively associated with central obesity and low muscle mass in overweight and obese men. No significant differences were found among the women.Conclusion: THs central sensitivity is related to the body composition of euthyroid T2DM patients. Specifically, high levels of TT3RI and TFQIFT3 are associated with central obesity and low muscle mass in T2DM men with overweight and obesity.Keywords: thyroid hormones central sensitivity, euthyroid, body components, muscle mass, fat ratio, obese

Shandong Jiang,1,2 Libin Hu,1,2 Hang Zhou,1,2 Jianan Wu,1,2 Jiayin Zhou,1,2 Xian Yu,1,2 Gao Chen1,2 1Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310016, People’s Republic of China; 2Key Laboratory of Precise Treatment and Clinical Translational Research of Neurological Diseases, Hangzhou, 310016, People’s Republic of ChinaCorrespondence: Gao Chen, Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Clinical Research Center for Neurological Diseases of Zhejiang Province, Hangzhou, 310009, People’s Republic of China, Email d-chengao@zju.edu.cnAbstract: Intracerebral hemorrhage (ICH) is a primary, non-traumatic cerebral event associated with substantial mortality and disability. Despite advancements in understanding its etiology and refining diagnostic techniques, a validated treatment to significantly improve ICH prognosis remains elusive. Exosomes, a subtype of extracellular vesicles, encapsulate bioactive components, predominantly microRNAs (miRNAs), facilitating and regulating intercellular communication. Currently, exosomes have garnered considerable interests in clinical transformation for their nanostructure, minimal immunogenicity, low toxicity, inherent stability, and the ability to traverse the blood-brain barrier. A wealth of studies has demonstrated that exosomes can improve the prognosis of ICH through anti-apoptosis, neurogenesis, angiogenesis, anti-inflammation, immunomodulation, and autophagy, primarily via the transportation or overexpression of selected miRNAs. More importantly, exosomes can be easily customized with specific miRNAs or bioactive compounds to establish delivery systems, broadening their potential applications. This review focuses on the therapeutic potential of exosomes in ICH, reviewing the mechanisms of molecular biology mediated by certain miRNAs, discussing the benefits, challenges, and future prospects in ICH treatment. We hope comprehensive understanding of exosomes based on miRNAs will provide new insights into the treatment of ICH and guide the translation of exosome’s research from laboratory to clinical practice. Keywords: intracerebral hemorrhage, exosomes, extracellular vesicles, microRNAs, stem cells

Tong Guo,1,2 Yuan Feng,1,2 Jingjing Zhou,1,2 Linghui Meng,1,2 Xuequan Zhu,1,2 Xu Chen,1,2 Le Xiao,1,2 Lei Feng,1,2 Ling Zhang,1,2 Yu-Tao Xiang,3,4 Yan-Jie Zhao,1,2 Gang Wang1,2 1Beijing Key Laboratory of Mental Disorders, National Clinical Research Center for Mental Disorders & National Center for Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, People’s Republic of China; 3Unit of Psychiatry, Department of Public Health and Medicinal Administration, Faculty of Health Sciences, Institute of Translational Medicine, University of Macau, Taipa, Macao SAR, People’s Republic of China; 4Centre for Cognitive and Brain Sciences, University of Macau, Taipa Macao SAR, People’s Republic of ChinaCorrespondence: Yan-Jie Zhao; Gang Wang, Email yzhao118@126.com; gangwangdoc@ccmu.edu.cnBackground: Understanding the dynamic relationship between depressive symptoms and quality of life (QOL) is essential in improving long-term outcomes for patients with Major Depressive Disorder (MDD). While previous studies often relied on cross-sectional data, there is a pressing need for stronger evidence based on longitudinal data to better inform the development of effective clinical interventions. By focusing on key depressive symptoms, such interventions have the potential to ultimately enhance QOL in individuals with MDD.Methods: This multi-center prospective study, conducted between 2016 and 2020, enrolled outpatients and inpatients diagnosed with MDD across twelve psychiatric hospitals in China. Longitudinal data on Patient Health Questionnaire – 9 (PHQ-9) and Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF) was analyzed using an Extended Bayesian Information Criterion (EBIC) graphical least absolute shrinkage and selection operator (gLASSO) network model to explore the connections between depressive symptom changes and QOL changes. Flow network was applied to investigate relationships between individual symptom changes and overall QOL score change, as well as daily functional independence.Results: This study included 818 participants with complete data after 8-week antidepressant treatment. Apart from the overlapping items from PHQ-9 and Q-LES-Q-SF, the three edges between “mood” (delta-QLES2) and “anhedonia” (delta-DEP1), between “physical health” (delta-QLES1) and “sleep problems” (delta-DEP3), and between “physical health” (delta-QLES1) and “sad mood” (delta-DEP2) were the most strong bridges between the cluster of depressive symptoms alleviation and the cluster of QOL change. “Anhedonia” (delta-DEP1), “sad mood” (delta-DEP2) and “loss of energy” (delta-DEP4) had the highest bridge strength between the alleviations of depressive symptoms and the total score change of Q-LES-Q-SF. Anhedonia had the greatest connection with participants’ satisfaction with function in daily life.Conclusion: This study highlighted the potential for developing highly effective interventions by targeting on central symptoms, thereby to ultimately improve QOL for patients with MDD.Keywords: network analysis, patients with MDD, acute phase treatment, depressive symptoms, quality of life

Xia Gu,1,2,&ast; Hui Zhou,1,&ast; Mengyue Miao,1 Daifeng Hu,1 Xinyue Wang,3 Jing Zhou,4 Alexander Tobias Teichmann,1 Youzhe Yang,1,5 Chunyan Wang1 1Sichuan Provincial Center for Gynaecology and Breast Diseases, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of China; 2Department of Gynaecology and Obstetrics, Leshan People’s Hospital, Leshan, 614003, People’s Republic of China; 3The Basic Medical College, Army Medical University, Chongqing, 400038, People’s Republic of China; 4Department of Endocrinology, Chengdu Third People’s Hospital, Chengdu, 610014, People’s Republic of China; 5Academician (Expert) Workstation of Sichuan Province, Luzhou, 646000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Youzhe Yang; Chunyan Wang, The Affiliated Hospital of Southwest Medical University, NO. 25 Taiping Street, Jiangyang District, Luzhou, 646000, People’s Republic of China, Email yangyouzhe@swmu.edu.cn; wangchunyan6813@swmu.edu.cnAbstract: Endometriosis (EMS) is defined as the appearance, growth, infiltration, and repeated bleeding of endometrioid tissue (glands and stroma) outside the uterus cavity, which can form nodules and masses. Endometriosis is a chronic inflammatory estrogen-dependent disease and occurs in women of reproductive age. This disorder may significantly affect the quality of life of patients. The pathogenic processes involved in the development and maintenance of endometriosis remain unclear. Current treatment options for endometriosis mainly include drug therapy and surgery. Drug therapy mainly ties to the use of non-steroidal anti-inflammatory drugs (NSAIDs) and hormonal drugs. However, these drugs may produce adverse effects when used for long-term treatment of endometriosis, such as nausea, vomiting gastrointestinal reactions, abnormal liver and kidney function, gastric ulcers, and thrombosis. Although endometriosis lesions can be surgically removed, the disease has a high recurrence rate after surgical resection, with a recurrence rate of 21.5% within 2 years and 40% to 50% within 5 years. Thus, there is an urgent need to develop alternative or additional therapies for the treatment of endometriosis. In this review, we give a systematic summary of therapeutic multiple component prescriptions (including traditional Chinese medicine and so on), bioactive crude extracts of plants/herbs and purified compounds and their newly found mechanisms reported in literature in recent years against endometriosis.Keywords: endometriosis, treatment, multiple component prescriptions, extracts of plants/herbs, purified compounds, mechanisms

Xiao-Dong Huang,1,&ast; Jia-Bao Chen,2,&ast; Xiao-Yun Dong,1 Wei-Long Wang,1 Jin Zhou,1 Zhen-Feng Zhou1 1Department of Anesthesiology, Hangzhou Women’s Hospital (Hangzhou Maternity and Child Health Care Hospital, Hangzhou First People’s Hospital Qianjiang New City Campus, Zhejiang Chinese Medical University), Hangzhou, People’s Republic of China; 2Department of Anesthesiology, Zhejiang Provincial People’s Hospital (People’s Hospital of Hangzhou Medicine College), Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhen-Feng Zhou, Department of Anesthesiology, Hangzhou Women’s Hospital (Hangzhou Maternity and Child Health Care Hospital, Hangzhou First People’s Hospital Qianjiang New City Campus, Zhejiang Chinese Medical University), Hangzhou, 310008, People’s Republic of China, Tel +86-571-56005077, Email zhenfeng9853@163.comPurpose: This study aimed to investigate the influence of fentanyl on the effective dose of remimazolam-induced sedation in elderly female patients undergoing general anesthesia.Patients and Methods: Sixty female patients aged 65– 80 years undergoing selective general anesthesia were randomized into two groups: Group R+F received an initial dose of remimazolam (7.5 mg) with fentanyl (1 μg/kg), while Group R received remimazolam alone. Dosing adjustments (± 2.5 mg) were made based on the response of the preceding patient using the up-and-down allocation technique. The ED50 and ED95 were calculated using a sequential formula and probit regression. Probit regression was also used to assess the relative potency of remimazolam between groups. Sedation levels were evaluated using the Modified Observer’s Assessment of Alertness/Sedation (MOAA/S) scale.Results: The ED50 for remimazolam was significantly lower in Group R+F compared to Group R (p= 0.007). Probit regression estimated the ED50 and ED95 values for Group R+F at 4.878 mg (95% CI, 3.845– 5.859) and 8.184 mg (95% CI, 6.636– 13.546), respectively. In contrast, Group R demonstrated ED50 and ED95 values of 6.733 mg (95% CI, 5.533– 8.068) and 11.298 mg (95% CI, 9.101– 19.617), respectively.Conclusion: This study provides compelling evidence that the administration of 1 μg/kg of fentanyl significantly reduces the required sedative dose of remimazolam by approximately 30% during induction in elderly patients. Importantly, the concomitant use of 1 μg/kg of fentanyl does not increase the risk of adverse effects such as hypotension, respiratory depression.Keywords: remimazolam, fentanyl, effective dose, elderly

Jing Ren,1,&ast; Jiahua Zhou,2,&ast; Qinhui Wang,1,&ast; Linna Liu,1 Wei Liu,3 Shan Wang,4 Yao Zheng,1 Li Luo,1 Qi Yang1 1Department of Pharmacy, The Second Affiliated Hospital of Air Force Medical University, Xi’an, Shaanxi, People’s Republic of China; 2Department of Neurosurgery, The Second Affiliated Hospital of Air Force Medical University, Xi’an, Shaanxi, People’s Republic of China; 3Department of Orthopedics, The Second Affiliated Hospital of Air Force Medical University, Xi’an, Shaanxi, People’s Republic of China; 4Department of Pharmacy, New York University Langone Hospital – Long Island, Mineola, NY, USA&ast;These authors contributed equally to this workCorrespondence: Qi Yang; Li Luo, Department of Pharmacy, The Second Affiliated Hospital of Air Force Medical University, Xi’an, Shaanxi, 710038, People’s Republic of China, Tel +86 15829673096, Fax +86 029-84777154, Email 376230719@qq.com; luolixueshu@163.comAbstract: Aseptic abscess (AA) syndrome is a rare inflammatory disorder often associated with inflammatory bowel disease (IBD). Cases of IBD-associated AA have been reported in Japan, India, and Canada, but rarely in China. Herein, we present the case of a Chinese patient with IBD-associated AAs and review the literature on AA with underlying IBD. We report the case of a 48-year-old male patient with multiple AAs on his left hand and lungs who was successfully treated with prednisone. He had undergone cutaneous abscess incision and drainage twice in the previous 2 years. The patient presented to our hospital with ulcerative colitis and pain in the dorsum of the left hand. Pus from his hand and blood cultures revealed sterile cutaneous abscesses. Chest computed tomography examination during hospitalization revealed a lung abscess. The AA was unresponsive to cefotiam or cefoperazone-sulbactam. The patient’s left hand and lung conditions did not improve until prednisone was administered. The patient was followed up as an outpatient for 3 months and recovered without any clinical symptoms. We retrieved 17 cases of IBD-associated AA from the literature. None of the patients showed evidence of infection and failed antibiotic treatment, and all improved with corticosteroid use. AA may be an extra-intestinal manifestation of IBD. Effective medications include corticosteroids and immunosuppressive agents. This case may increase the awareness of AA and aid in early identification.Keywords: aseptic abscess, inflammatory bowel disease, ulcerative colitis, extra-intestinal manifestation

Dongdong Li,1 Lijun Bian,1 Lili Cui,2 Jingying Zhou,1 Gaotian Li,1 Xiaoyan Zhao,1 Liao Xing,1 Jiaxing Cui,1 Bo Sun,1 Chunlai Jiang,1,3,4 Wei Kong,1,3,4 Yong Zhang,1,3,4 Yan Chen1,3,4 1National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, People’s Republic of China; 2Beijing Institute of Drug Metabolism, Beijing, People’s Republic of China; 3Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun, People’s Republic of China; 4NMPA Key Laboratory of Humanized Animal Models for Evaluation of Vaccines and Cell Therapy Products, Jilin University, Changchun, People’s Republic of ChinaCorrespondence: Yan Chen; Yong Zhang, National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, 130012, People’s Republic of China, Tel +86-431-85167751, Fax +86-431-85167674, Email chen_yan0417@126.com; zhypharm@jlu.edu.cnPurpose: Heterologous immunization using different vaccine platforms has been demonstrated as an efficient strategy to enhance antigen-specific immune responses. In this study, we performed a head-to-head comparison of both humoral and cellular immune response induced by different prime-boost immunization regimens of mRNA vaccine and adjuvanted protein subunit vaccine against varicella-zoster virus (VZV) in middle-aged mice, aiming to get a better understanding of the influence of vaccination schedule on immune response.Methods: VZV glycoprotein (gE) mRNA was synthesized and encapsulated into SM-102-based lipid nanoparticles (LNPs). VZV-primed middle-aged C57BL/6 mice were then subjected to homologous and heterologous prime-boost immunization strategies using VZV gE mRNA vaccine (RNA-gE) and protein subunit vaccine (PS-gE). The antigen-specific antibodies were evaluated using enzyme-linked immunosorbent assay (ELISA) analysis. Additionally, cell-mediated immunity (CMI) was detected using ELISPOT assay and flow cytometry. Besides, in vivo safety profiles were also evaluated and compared.Results: The mRNA-loaded lipid nanoparticles had a hydrodynamic diameter of approximately 130 nm and a polydispersity index of 0.156. Total IgG antibody levels exhibited no significant differences among different immunization strategies. However, mice received 2×RNA-gE or RNA-gE>PS-gE showed a lower IgG1/IgG2c ratio than those received 2×PS-gE and PS-gE> RNA-gE. The CMI response induced by 2×RNA-gE or RNA-gE>PS-gE was significantly stronger than that induced by 2×PS-gE and PS-gE> RNA-gE. The safety evaluation indicated that both mRNA vaccine and protein vaccine induced a transient body weight loss in mice. Furthermore, the protein vaccine produced a notable inflammatory response at the injection sites, while the mRNA vaccine showed no observable inflammation.Conclusion: The heterologous prime-boost strategy has demonstrated that an mRNA-primed immunization regimen can induce a better cell-mediated immune response than a protein subunit-primed regimen in middle-aged mice. These findings provide valuable insights into the design and optimization of VZV vaccines with the potentials to broaden varicella vaccination strategies in the future.Keywords: varicella-zoster Virus, mRNA vaccine, glycoprotein E, lipid nanoparticles, heterologous prime-boost, cell-mediated immunity

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

Zhaohua Xiao,1,&ast; Jiangfeng Zhao,1,&ast; Guanhong Ji,1 Xiangqing Song,1 Xia Xue,2 Wenhao Zhang,1 Guomeng Sha,1 Yongjia Zhou,1 Jie Zhou,1 Zhongxian Tian,1,3 Xiaogang Zhao,1,3 Ning Jiang1 1Department of Thoracic Surgery, the Second Hospital of Shandong University, Jinan, 250033, People’s Republic of China; 2Department of Pharmacy, the Second Hospital of Shandong University, Jinan, People’s Republic of China; 3Key Laboratory of Chest Cancer, Shandong University, the Second Hospital of Shandong University, Jinan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ning Jiang, Department of Thoracic Surgery, the Second Hospital of Shandong University, Jinan, 250033, People’s Republic of China, Tel +86-17660081908, Email sdujiangning@163.comBackground: Exosomal microRNAs (miRNAs) in the tumor microenvironment play crucial roles in tumorigenesis and tumor progression by participating in intercellular cross-talk. However, the functions of exosomal miRNAs and the mechanisms by which they regulate esophageal squamous cell carcinoma (ESCC) progression are unclear.Methods: RNA sequencing and GEO analysis were conducted to identify candidate exosomal miRNAs involved in ESCC development. Receiver operating characteristic curve analysis was performed to assess the diagnostic value of plasma exosomal miR-493-5p. EdU, tube formation and Transwell assays were used to investigate the effects of exosomal miR-493-5p on human umbilical vein endothelial cells (HUVECs). A subcutaneous xenograft model was used to evaluate the antitumor effects of miR-493-5p and decitabine (a DNA methyltransferase inhibitor). The relationship between miR-493-5p and SP1/SP3 was revealed via a dual-luciferase reporter assay. A series of rescue assays were subsequently performed to investigate whether SP1/SP3 participate in exosomal miR-493-5p-mediated ESCC angiogenesis.Results: We found that miR-493-5p expression was notably reduced in the plasma exosomes of ESCC patients, which showed the high potential value in early ESCC diagnosis. Additionally, miR-493-5p, as a candidate tumor suppressor, inhibited the proliferation, migration and tube formation of HUVECs by suppressing the expression of VEGFA and exerted its angiostatic effect via exosomes. Moreover, we found that SP1/SP3 are direct targets of miR-493-5p and that re-expression of SP1/SP3 could reverse the inhibitory effects of miR-493-5p. Further investigation revealed that miR-493-5p expression could be regulated by DNA methyltransferase 3A (DNMT3A) and DNMT3B, and either miR-493-5p overexpression or restoration of miR-493-5p expression with decitabine increased the antitumor effects of bevacizumab.Conclusion: Exosomal miR-493-5p is a highly valuable ESCC diagnosis marker and inhibits ESCC-associated angiogenesis. miR-493-5p can be silenced via DNA methylation, and restoration of miR-493-5p expression with decitabine increases the antitumor effects of bevacizumab, suggesting its potential as a therapeutic target for ESCC treatment.Keywords: esophageal squamous cell carcinoma, exosomes, miR-493-5p, VEGFA, angiogenesis

Jiamei Chen,1 Jin Wang,1 Ziwei Deng,2 Yongzhong Li,1 Jianliang Zhou3 1Department of Infectious Diseases, Hunan Medical College General Hospital, Huaihua, Hunan Province, People’s Republic of China; 2Department of Clinical Pharmacy Group, Hunan Medical College General Hospital, Huaihua, Hunan Province, People’s Republic of China; 3Department of Intensive Care Medicine, Hunan Medical College General Hospital, Huaihua, Hunan Province, People’s Republic of ChinaCorrespondence: Jianliang Zhou, Email 82125817@qq.comBackground: We aimed to describe the difference between Chlamydia psittaci pneumonia group and non C. psittaci bacterial pneumonia group in community acquired pneumonia in this single-center clinical study.Methods: We collected the data of 35 patients with C. psittaci pneumonia cases and 46 patients with non C. psittaci bacterial pneumonia cases diagnosed with metagenomic next-generation sequencing assays from February 2019 to December 2021 in Huaihua First People’s Hospital in China.Results: In the C. psittaci pneumonia group, 35 patients (100%) had a chance of exposure to poultry or birds, and their body temperature was greater than or equal to 39.0°C. The other common symptoms were a slow pulse (68.6%), cough (65.7%), expectoration (54.3%), chills (51.4%) and a shortness of breath (37.1%). Laboratory tests showed that > 90% of the cases had markedly elevated infection indicators, and 97.1% of the cases had markedly declined calcium. The most common imaging finding was patchy shadows (94.3%), pleural effusion (68.6%), bilateral in 54.3% (n = 19) and unilateral in 45.7% (n = 16) participants, and 51.4% (n = 18) of cases met the criteria for severe pneumonia. In the non C. psittaci bacterial pneumonia group, 18 patients (39.1%) had a chance of exposure to poultry or birds, and 11 patients (23.9%) body temperature was greater than or equal to 39.0°C. Laboratory tests showed that > 67% of cases had a mildly elevated infection indicators, and mildly declined serum albumin.Conclusion: The following characteristics are more likely to help distinguish C. psittaci pneumonia from non C. psittaci bacterial pneumonia. Including had a chance of exposure to poultry or birds, high fever, exhibit chills, expectoration, relatively slow pulse, and progress into severe pneumonia. Percentage of neutrophils, C-reactive protein, procalcitonin, lactate dehydrogenase, and myoglobin levels are higher. Blood calcium and corrected calcium are lower. Chest CT showed pleural effusion, pericardial effusion, and mediastinal lymphadenopathy.Keywords: Chlamydia psittaci pneumonia, non Chlamydia psittaci bacterial pneumonia, clinical features

Xia Cao,1 Yusheng Tian,2 Hui Chen,2 Sihong Li,2 Jiansong Zhou2 1Health Management Center, The Third Xiangya Hospital of Central South University, Changsha, People’s Republic of China; 2National Clinical Research Center for Mental Disorders, and Department of Psychiatry, The Second Xiangya Hospital of Central South University, Changsha, People’s Republic of ChinaCorrespondence: Jiansong Zhou, National Clinical Research Center for Mental Disorders, and Department of Psychiatry, The Second Xiangya Hospital of Central South University, Renmin Road 139, Changsha, Hunan Province, People’s Republic of China, Tel +86-073185295888, Fax +86-073188618573, Email jasonzhou75@163.comObjective: The concept of intrinsic capacity (IC) revolves around healthy aging and active aging. Since the Introduction of the concept by the World Health Organization in 2015, a series of studies have been conducted by scholars from multiple fields. However, no bibliometric analysis has systematically investigated this issue. We aim to identify the current landscape and frontier trends of scientific achievements on IC in older adults through bibliometric approaches.Methods: Quantitative analysis of publications relating to IC in older adults from 2015 to 2023 was interpreted and graphed through the Web of Science Core Collection database on December 5, 2023. A variety of quantitative variables was analyzed, including publication and citation counts, H-index, and journal citation reports. Co-authorship, citation, co-citation, and co-occurrence analyses were performed for countries/regions, institutions, authors, and keywords using the VOSviewer and CiteSpace.Results: A total of 952 original and review articles in English were identified. The European countries possessed an absolute advantage in this field. The most contributive institution was the University of São Paulo. The most productive author is Cesari Matteo from France, followed by Qaisar Rizwan from the United Arab Emirates. However, a relatively low level of research cooperation existed between institutions and authors. Important topics mainly include the connotations, theoretical framework models, evaluation, screening tools, and application scenarios of IC. Among the promising hotspots, “biological aging”, “ICOPE”, “Covid-19”, “prevention”, “inflammation”, “caf22”, “prevalence”, and “randomized controlled trial” displayed relatively latest average appearing year.Conclusion: Global trends indicate a growing scientific output on IC in older adults, and developed countries are leading the way. There is still room for improvement in research team collaboration. The focus gradually shifts from theoretical research to empirical research. It is recommended to pay attention to the latest hot spots, such as “biological aging”, “ICOPE implementation”, “post-COVID-19 syndrome”, and “biomarkers”.Keywords: intrinsic capacity, old adults, bibliometrics, research frontier, visualization

Jingru Zhou,1 Yanjun Liu,2 Fang Yang,1 Meiling Jing,3 Xiaoli Zhong,1 Yanfen Wang,1 Yan Liu,1 Wenwen Ming,1 Huangyan Li,1 Tianxia Zhao,1 Lin He1 1Department of Nursing, Deyang People’s Hospital, Deyang, Sichuan, 618200, People’s Republic of China; 2Department of Infection, Mianzhu People’s Hospital, Mianzhu, Sichuan, 618000, People’s Republic of China; 3Department of Nursing, West China Hospital, Sichuan University, Chengdu, Sichuan, 610000, People’s Republic of ChinaCorrespondence: Lin He; Xiaoli Zhong, Email 2507148852@qq.com; 20943794@qq.comObjective: Sarcopenia is a common complication of COPD associated with an age-related reduction in skeletal muscle mass associated with decreased muscle strength and / or reduced mobility. The incidence of sarcopenia in patients with COPD is twice that of non-COPD patients and is associated with poor prognosis, this study aimed to investigate the influencing factors of sarcopenia in COPD patients.Methods: Selected studies from PubMed, Embase, Web of Science, Cochrane Library, Wanfang, Wanfang, CNKI, CBM, and Wanfang databases as of November 12023. Patients aged 18 were selected; data were then independently extracted by two reviewers using a standard data collection form.Results: In total, 17 articles reporting on 5408 patients were included. Age (OR = 1.083; 95% CI, 1.024– 1.145), ALB (OR = 0.752; 95% CI, 0.724– 0.780), BMI(OR = 0.701; 95% CI, 0.586– 0.838), smoking (OR = 1.859; 95% CI, 1.037– 3.334), diabetes (OR = 1.361; 95% CI, 1.095– 1.692), qi deficiency (OR = 9.883; 95% CI, 2.052, 47.593), GOLD C (OR =2.232; 95% CI, 1.866, 2.670) and GOLD D (OR = 2.195; 95% CI, 1.826– 2.637) were factors affecting muscle loss in COPD patients.Conclusion: Sarcopenia is more prevalent in patients with COPD. Age, body mass index, smoking, diabetes mellitus, qi deficiency, ALB, and GOLD grade were the contributing factors for sarcopenia in patients with chronic obstructive pulmonary disease. In the future, medical staff should not only pay attention to the early screening of sarcopenia in high-risk groups, but also provide relevant prevention information.Keywords: sarcopenia, chronic obstructive pulmonary disease, prevalence, risk factors, meta-analysis

Jinxian Xu, Yang Zhang, Lujian Zhu, Shiyue Tang, Hanglu Xu, Dehe Zhang, Haijun Chen, Jing Zhou Department of Infectious Diseases, Zhejiang University Medical College Affiliated Jinhua Hospital, Jinhua, People’s Republic of ChinaCorrespondence: Jing Zhou, Department of Infectious Diseases, Zhejiang University Medical College Affiliated Jinhua Hospital, Jinhua, People’s Republic of China, Email zhoujing001011@sina.comBackground: Chronic hepatitis B (CHB) presents a global health challenge due to its potential to cause severe liver conditions such as hepatocellular carcinoma (HCC) and cirrhosis. Prior research has established a correlation between CHB infection with low-level viremia (LLV) and liver disease progression, such as increased HCC incidence. This study aims to investigate whether LLV during treatment with nucleos(t)ide analogs (NAs) contributes to the accelerated progression of liver fibrosis (LF).Methods: This retrospective cohort study at Jinhua Central Hospital focused on CHB patients undergone NA monotherapy for over 96 weeks. Patients were categorized into maintained virological response (MVR) and LLV groups based on hepatitis B virus (HBV) DNA levels. The study assessed LF using various markers and methods, including chitinase 3-like 1 protein (CHI3L1), aspartate aminotransferase-to-platelet ratio index (APRI), fibrosis-4 (FIB-4) score, and transient elastography.Results: Analysis was conducted on 92 CHB patients, categorized into LLV (n=42) and MVR (n=50) groups, following the exclusion of 101 patients for various reasons. Significant findings included lower baseline HBV DNA in MVR (< 20 IU/mL) compared to LLV (67.8 IU/mL, P< 0.001) and different AST/ALT ratios (LLV: 1.1, MVR: 1.36, P=0.011). LF was assessed using CHI3L1, FIB-4, and APRI, with LLV showing a higher baseline CHI3L1 (LLV:83.3 ng/mL vs MVR: 54.5 ng/mL, P=0.016) and scores compared to MVR, indicative of fibrosis. CHI3L1 levels in LLV were higher at baseline and weeks 48, 72, and 96 than MVR, with significance at baseline (P=0.038) and week 48 (P=0.034). Liver stiffness measurement (LSM) showed a time-dependent decline in both groups but no significant intergroup differences.Conclusion: Non-invasive monitoring of CHB patients who have received treatment indicates that LLV contributes to the progression of LF, necessitating proactive adjustment of antiviral treatment strategies.Keywords: chronic hepatitis B, low-level viremia, liver fibrosis, non-invasive methods, treatment strategies

Mengwen Feng,1 Min Huang,2 Yuanyuan Fan,1 Genyan Liu,3 Suming Zhou,2 Jing Zhou2 1Department of Critical Care Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China; 2Department of Geriatric Intensive Care Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China; 3Department of Laboratory Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of ChinaCorrespondence: Jing Zhou, Department of Geriatric Intensive Care Medicine, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu Province, 210029, People’s Republic of China, Email zhoujing1364@jsph.org.cnPurpose: Elizabethkingia spp. infections have recently increased, and they are difficult to treat because of intrinsic antimicrobial resistance. This study aimed to investigate the clinical characteristics of patients with pulmonary infection with Elizabethkingia spp. and reveal the risk factors for infection and death.Patients and Methods: In this retrospective case–control study, patients were divided into infection and control groups based on the bacterial identification results. Patients in the infection group were further divided into survival and death groups according to their hospital outcomes. Clinical characteristics between different groups were compared. We further analyzed antimicrobial susceptibility testing results of the isolated strains.Results: A total of the 316 patients were divided into infection (n = 79), 23 of whom died, and control (n = 237) groups. Multivariate logistic regression analysis showed that glucocorticoid consumption (OR: 2.35; 95% CI: 1.14– 4.81; P = 0.02), endotracheal intubation (OR: 3.74; 95% CI: 1.62– 8.64; P = 0.002), and colistin exposure (OR: 2.50; 95% CI: 1.01– 6.29; P = 0.046) were significantly associated with pulmonary infection with Elizabethkingia spp. Advanced age (OR: 1.07, 95% CI: 1.00– 1.15; P = 0.046), high acute physiology and chronic health evaluation (APACHE) II score (OR: 1.21; 95% CI: 1.01– 1.45; P = 0.037), and low albumin level (OR: 0.73, 95% CI: 0.56– 0.96; P = 0.025) were significantly associated with in-hospital mortality of infected patients. Elizabethkingia spp. was highly resistant to cephalosporins, carbapenems, macrolides, and aminoglycoside, and was sensitive to fluoroquinolones, minocycline, and co-trimoxazole in vitro.Conclusion: Glucocorticoid consumption, tracheal intubation, and colistin exposure were associated with pulmonary infection with Elizabethkingia spp. for critically ill patients. Patients with advanced age, high APACHE II score, and low albumin level had higher risk of death from infection.Keywords: Elizabethkingia spp, intensive care unit, infection, mortality, antimicrobial susceptibility testing

Jiajia Zhou,1,2,&ast; Shuang Song,2,3,&ast; Senlin Xue,2 Yingxing Zhu,3 Boyin Xu,4 Ping Ma,2,3 Yanguan Lv,1 Haiquan Kang2,3 1The Huai’an Maternity and Child Clinical College of Xuzhou Medical University, Huai’an, People’s Republic of China; 2Medical Technology School, Xuzhou Medical University, Xuzhou, People’s Republic of China; 3Department of Clinical Laboratory, Affiliated Hospital of Xuzhou Medical University, Xuzhou, People’s Republic of China; 4Department of Infection Control, Affiliated Hospital of Nantong University, Nantong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haiquan Kang, Department of Clinical Laboratory, Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221000, People’s Republic of China, Tel +86-516 85802759, Email hqk811029@163.com Yanguan Lv, The Huai’an Maternity and Child Clinical College of Xuzhou Medical University, Huai’an, 223001, People’s Republic of China, Tel +86-517 89687770, Email lvyanguan@163.comBackground: The emergence of carbapenem-resistant Klebsiella pneumoniae (CRKP) has garnered international concern due to its significant antibiotic resistance. Notably, children exhibit distinct resistance mechanisms compared to adults, necessitating a differential approach to antibiotic selection. A thorough analysis of CRKP’s epidemiology and drug resistance mechanisms is essential for establishing a robust foundation for clinical anti-infection strategies and precise prevention and control measures.Methods: This study involved the collection of 31 non-repetitive strains from pediatric and adult patients at a tertiary hospital in China, spanning from July 2016 to July 2022, testing for resistance genes, antimicrobial susceptibility, and homology analysis.Results: Infants (0– 1 year) were the largest pediatric CRKP group, with 61.3% of cases. The neonatal intensive care unit (NICU) and pediatrics were the main departments affected. Adults with CRKP had a mean age of 67 years, with the highest prevalence in neurology and emergency ICU. Antimicrobial susceptibility testing revealed that adult CRKP strains exhibited higher resistance to amikacin, ciprofloxacin, cotrimoxazole, and aztreonam compared to pediatric strains. Conversely, pediatric strains showed a higher rate of resistance to ceftazidime/avibactam. The predominant resistance genes identified were blaNDM-5 in children (58.1%) and blaKPC-2 in adults (87.1%), with over 93% of both groups testing positive for extended-spectrum beta-lactamase (ESBL) genes. Multilocus Sequence Typing (MLST) indicated ST2735 and ST11 as the predominant types in children and adults, respectively. Pulsed-field gel electrophoresis (PFGE) identified clonal transmission patterns of ST11 blaKPC-2 and ST15 blaOXA-232 across both age groups. Notably, this study reports the first instance of ST1114-type CRKP co-producing blaNDM-5 and blaOXA-181 in the NICU.Conclusion: This study reveals distinct resistance mechanisms and epidemiology in CRKP from children and adults. The identified clonal transmission patterns emphasize the need for improved infection control to prevent the spread of resistant strains.Keywords: children, adults, Klebsiella pneumoniae, carbapenemases, drug resistance mechanisms

Yanzhao Zhou,1,&ast; Jingzhong Ouyang,2– 4,&ast; Hongcai Yang,5,&ast; Zhengzheng Wang,2,&ast; Yi Yang,3,4,&ast; Qingjun Li,2 Haitao Zhao,6 Jinxue Zhou,2 Qiang Li1 1Department of Hepatobiliary Cancer, Liver Cancer Research Center, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin, People’s Republic of China; 2Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, Henan, People’s Republic of China; 3Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 4Key Laboratory of Gene Editing Screening and Research and Development (R&D) of Digestive System Tumor Drugs, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 5Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 6Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiang Li, Department of Hepatobiliary Cancer, Liver Cancer Research Center, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin, People’s Republic of China, Email liqiang@tjmuch.com Jinxue Zhou, Department of Hepatobiliary and Pancreatic Surgery, Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, Henan, 450008, People’s Republic of China, Email zhoujx888@126.comPurpose: The impact of visceral adiposity on overall survival (OS) in hepatocellular carcinoma (HCC) receiving immunotherapy was unclear. We aimed to determine how visceral adiposity affected OS and explore the interrelationships between visceral adiposity, body mass index (BMI), and other body compositions.Patients and Methods: Data from three centers were retrospectively analyzed. Skeletal muscle index (SMI), skeletal muscle density (SMD), visceral adipose tissue index (VATI), and subcutaneous adipose tissue index (SATI) were used to define each body composition. The BMI subgroups included the underweight, the normal weight, and the obesity. The Log rank test compared survival curves calculated by the Kaplan-Meier method. The relationships between body compositions and BMI with OS were examined using Cox proportional risk regression models.Results: A total of 305 patients who met the criteria were included. Patients with low VATI had significantly worse OS (P = 0.001). The protections of VATI (P = 0.011) on OS were independent of covariates. However, after additional adjustment of SMI, the effect of VATI on OS disappeared (P = 0.146), but the effect of SMD on OS did not (P = 0.021). BMI has a significant U-shaped relationship with OS, and the effect of BMI on OS equally disappeared after additional adjustment by SMI.Conclusion: This study first demonstrated that high VATI and mid-level BMI were protective for the survival of patients with HCC receiving immunotherapy. Skeletal muscle status (including SMI and SMD) may be the better predictor for outcomes of patients with HCC receiving immunotherapy.Keywords: hepatocellular carcinoma, immunotherapy, body mass index, body composition, obesity paradox

Li-Mian Song,1,&ast; Du-Juan Yao,1,&ast; Lin Xia,1 Xu-Ming Wang,2 Tian Liu,2 Qian-Qian Tang,1 Jun Zhou1 1Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2Department of Pathology, Affiliated Hospital of Guilin Medical College, Guilin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jun Zhou, Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China, Email bbfat51740@sina.comPurpose: To explore the effect of DSG2 on the growth of cervical cancer cells and its possible regulatory mechanism.Methods: The expression levels and survival prognosis of DSG2 and ADAM17 in cervical squamous cell carcinoma tissues and adjacent normal tissues were analyzed by bioinformatics. CCK-8 assay, colony formation assay and Transwell assay were used to detect the effects of DSG2 on the proliferative activity, colony formation ability and migration ability of SiHa and Hela cells. The effect of DSG 2 on the level of ADAM17 transcription and translation was detected by qPCR and Western blot experiments. The interaction between DSG2 and c-MYC was detected by immunocoprecipitation. c-MYC inhibitors were used in HeLa cells overexpressing DSG2 to analyze the effects of DSG2 and c-MYC on proliferation, colony formation and migration of Hela cells, as well as the regulation of ADAM17 expression.Results: DSG2 was highly expressed in cervical squamous cell carcinoma compared with normal tissues (P< 0.05), and high DSG2 expression suggested poor overall survival (P< 0.05). After DSG2 knockdown, the proliferative activity, colony formation and migration ability of SiHa and Hela cells were significantly decreased (P< 0.05). Compared with adjacent normal tissues, ADAM17 was highly expressed in cervical squamous cell carcinoma (P< 0.05), and high ADAM17 expression suggested poor overall survival in cervical cancer patients (P< 0.05). The results of immunocoprecipitation showed the interaction between DSG2 and c-MYC. Compared with DSG2 overexpression group, DSG2 overexpression combined with c-MYC inhibition group significantly decreased cell proliferation, migration and ADAM17 expression (P < 0.05).Conclusion: DSG2 is highly expressed in cervical cancer, and inhibition of DSG2 expression can reduce the proliferation and migration ability of cervical cancer cells, which may be related to the regulation of ADAM17 expression through c-MYC interaction.Keywords: cervical cancer, proliferation, migration, DSG2, c-MYC, ADAM17

Bingwei Hu,1,&ast; Xianhui Kang,2,&ast; Cheng Zhou,1 Jie Zhou,1 Weixing Xu,3 Weiguo Ding,3 Zhiying Feng,4 Hongwei Wang1 1Department of Anaesthesiology, Tongde Hospital of Zhejiang Province, Hangzhou, People’s Republic of China; 2Department of Anaesthesiology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 3Department of Spine Surgery, Tongde Hospital of Zhejiang Province, Hangzhou, People’s Republic of China; 4Department of of Pain Department, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongwei Wang; Zhiying Feng, Tongde Hospital of Zhejiang Province, Zhejiang Chinese Medical University, No. 234 Gucui Road, Xihu District, Hangzhou, People’s Republic of China, Email Wanghw1022@163.com; fzy1972@zju.edu.cnIntroduction: Nerve injury is a serious complication of percutaneous endoscopic transforaminal lumbar discectomy due to nerve root contact. The maximum tolerable concentration (MTC) of ropivacaine concentration for epidural anaesthesia, is defined as the concentration that minimises pain while preserving the sensation of the nerve roots. This distinct advantage allows the patient to provide feedback to the surgeon when the nerve roots are contacted.Methods: We used a biased-coin design to determine the MTC, which was estimated by the 10% effective concentration (EC10), ie, the concentration at which 10% of patients lost sensation in the nerve roots. The determinant for positive response was lack of sensory feedback upon contact with the nerve root, and the feedback from occurrence of sensations in the innervation area upon contact with the nerve root was defined as a negative response. Primary outcome was the response from contact nerve root. Secondary outcomes were the type and number of statements of negative response and each patient’s pain score during surgery.Results: Fifty-four patients were included in this study. The EC10 was 0.434% (95% CI: 0.410%, 0.440%) using isotonic regression in comparison with 0.431% (95% CI: 0.399%, 0.444%) using probit regression. Three type statements of negative response were reported including “tactile sensation”, radiculalgia, and numbness.Conclusion: The MTC of ropivacaine used for epidural anaesthesia was 0.434% to avoid nerve injury in percutaneous endoscopic transforaminal lumbar discectomy.Keywords: maximum tolerable concentration, epidural anaesthesia, transforaminal percutaneous endoscopic lumbar discectomy, biased-coin design, isotonic regression

Jieyang Yu,1,2 Yanan Zhang,1 Lijia Cai,1 Qingqing Sun,1 Wanru Li,1 Junfang Zhou,1 Jianmin Liang,2 Zan Wang1 1Sleep Centre, Department of Neurology, The First Hospital of Jilin University, Changchun, Jilin Province, People’s Republic of China; 2Department of Pediatric Neurology, The First Hospital of Jilin University, Changchun, Jilin Province, People’s Republic of ChinaCorrespondence: Jianmin Liang, Department of Pediatric Neurology, The First Hospital of Jilin University, Changchun, Jilin Province, 130021, People’s Republic of China, Email liangjm@jlu.edu.cn Zan Wang, Sleep Centre, Department of Neurology, The First Hospital of Jilin University, Changchun, Jilin Province, 130021, People’s Republic of China, Email wangzan@jlu.edu.cn; wangzanprof@163.comPurpose: This study aimed to evaluate nocturnal sleep structure and anxiety, depression, and fatigue in patients with narcolepsy type 1 (NT1).Methods: Thirty NT1 patients and thirty-five healthy controls were enrolled and evaluated using the Epworth sleepiness scale (ESS), Generalized Anxiety Disorder-7, Patient Health Questionnaire-9, Fatigue Severity Scale (FSS), polysomnography, multiple sleep latency test, and brain function state monitoring. Statistical analyses were performed using SPSS Statistics for Windows, version 23.0. Benjamini-Hochberg correction was performed to control the false discovery rate.Results: Apart from typical clinical manifestations, patients with NT1 are prone to comorbidities such as nocturnal sleep disorders, anxiety, depression, and fatigue. Compared with the control group, patients with NT1 exhibited abnormal sleep structure, including increased total sleep time (Padj=0.007), decreased sleep efficiency (Padj=0.002), shortening of sleep onset latency (Padj< 0.001), elevated wake after sleep onset (Padj=0.002), increased N1% (Padj=0.006), and reduced N2%, N3%, and REM% (Padj=0.007, Padj< 0.001, Padj=0.013). Thirty-seven percent of patients had moderate to severe obstructive sleep apnea-hypopnea syndrome. And sixty percent of patients were complicated with REM sleep without atonia. Patients with NT1 displayed increased anxiety propensity (Padj< 0.001), and increased brain fatigue (Padj=0.020) in brain function state monitoring. FSS scores were positively correlated with brain fatigue (Padj< 0.001) and mean sleep latency was inversely correlated with FSS scores and brain fatigue (Padj=0.013, Padj=0.029). Additionally, ESS scores and brain fatigue decreased after 3 months of therapy (P=0.012, P=0.030).Conclusion: NT1 patients had abnormal nocturnal sleep structures, who showed increased anxiety, depression, and fatigue. Excessive daytime sleepiness and fatigue improved after 3 months of treatment with methylphenidate hydrochloride prolonged-release tablets in combination with venlafaxine.Keywords: narcolepsy, sleep structure, excessive daytime sleepiness, anxiety, depression, fatigue

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

Lingyan Sheng,1,&ast; Wenhong Jiang,1,2,&ast; Yake Yao,1 Jianying Zhou,1 Hua Zhou1 1Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Jiangshan People Hospital, Quzhou, 324110, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hua Zhou, Email zhouhua1@zju.edu.cnBackground: The role of Aspergillus-specific IgG antibody test in the diagnosis of non-neutropenic invasive pulmonary aspergillosis (IPA) is still uncertain, and related studies are also limited.Purpose: This study aims to evaluate the quantitative test value of Aspergillus fumigatus-specific IgG antibody in non-neutropenic IPA, which could provide additional evidence for related clinical diagnosis.Methods: This prospective study collected clinical data of suspected IPA patients from January, 2020 to December, 2022, and patients were divided into two groups, IPA and non-IPA. The study analyzed clinical characteristics and diagnostic value of Aspergillus-specific IgG antibody test, using the receiver operating characteristic (ROC) curve to evaluate diagnostic efficacy.Results: The study enrolled 59 IPA cases and 68 non-IPA cases, the average admission age of IPA group was 63.2± 9.6 (33– 79), and the gender ratio (male:female) of IPA group was 42:17. The proportion of patients with history of smoking and COPD were higher in IPA group (59.3% vs 39.7%, P=0.027; 33.9% vs 14.7%, P =0.011, respectively). The level of Aspergillus fumigatus-specific IgG antibody in IPA group was significantly higher than non-IPA group (202.1± 167.0 vs 62.6± 58.0, P< 0.001). The area under the ROC curve was 0.799 (95%CI: 0.718, 0.865 P< 0.001), and the cut-off with best diagnostic efficacy was 91 AU/mL.Conclusion: Immunological test plays an important role in the diagnosis of pulmonary aspergillosis, and Aspergillus-specific IgG antibody test has the good diagnostic value in non-neutropenic IPA.Keywords: Aspergillus, invasive pulmonary aspergillosis, IgG, non-neutropenic, diagnosis

Lingling Yuan,1 Ting Wang,1 Jinsheng Duan,2 Jing Zhou,1 Na Li,1 Guizhi Li,1 Hong Zhou1 1Department of Endocrinology, the Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050004, People’s Republic of China; 2Department of Cardiology, the Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050004, People’s Republic of ChinaCorrespondence: Hong Zhou, Department of Endocrinology, the Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China, Tel +86-15130119625, Email zhoubs2013@hebmu.edu.cn; zhoubs2013@163.comIntroduction: Cardiac fibrosis is one of the important causes of heart failure and death in diabetic cardiomyopathy (DCM) patients. Circular RNAs (circRNAs) are covalently closed RNA molecules in eukaryotes and have high stability. Their role in myocardial fibrosis with diabetic cardiomyopathy (DCM) remain to be fully elucidated. This study aimed to understand the expression profiles of circRNAs in myocardial fibrosis with DCM, exploring the possible biomarkers and therapeutic targets for DCM.Methods: At 21 weeks of age, db/db mice established the type 2 DCM model measured by echocardiography, and the cardiac tissue was extracted for Hematoxylin–eosin, Masson’s trichrome staining, and transmission electron microscopy. Subsequently, the expression profile of circRNAs in myocardial fibrosis of db/db mice was constructed using microarray hybridization and verified by real‐time quantitative polymerase chain reaction. A circRNA–microRNA–messenger RNA coexpression network was constructed, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were done.Results: Compared with normal control mice, db/db mice had 77 upregulated circRNAs and 135 downregulated circRNAs in their chromosomes (fold change ≥ 1.5, P ≤ 0.05). Moreover, the enrichment analysis of circRNA host genes showed that these differentially expressed circRNAs were mainly involved in mitogen-activated protein kinase signaling pathways. CircPHF20L1, circCLASP1, and circSLC8A1 were the key circRNAs. Moreover, circCLASP1/miR-182-5p/Wnt7a, circSLC8A1/miR-29b-1-5p/Col12a1, and most especially circPHF20L1/miR-29a-3p/Col6a2 might be three novel axes in the development of myocardial fibrosis in DCM.Conclusion: The findings will provide some novel circRNAs and molecular pathways for the prevention or clinical treatment of DCM through intervention with specific circRNAs.Keywords: Circular RNAs, expression profile, diabetic cardiomyopathy, cardiac fibrosis, bioinformatic analysis

Wen-Bin Duan,1 Xiao-Hui Wang,2 Guo-Can Zhang,2 Zhuo He,1 Shao-Qiang Li,3 Jie Zhou1 1Division of Hepatobiliopancreatic Surgery, Department of General Surgery, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University, Guangzhou, 510515, People’s Republic of China; 2Department of Hepatobiliary Surgery, Hunan Provincial People’s Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, 410005, People’s Republic of China; 3Hepatic Pancreatobiliary Surgery Center, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, People’s Republic of ChinaCorrespondence: Xiao-Hui Wang, Department of Hepatobiliary Surgery, Hunan Provincial People’s Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, Hunan Province, 410005, People’s Republic of China, Tel +86-0731-83928052, Email xiaohuiwang21@163.com Jie Zhou, Division of Hepatobiliopancreatic Surgery, Department of General Surgery, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, People’s Republic of China, Tel +86-020-61641701, Email jacky_nfyy@163.comBackground: Lenvatinib or Sorafenib combined with programmed cell death protein-1 (PD-1) inhibitor as recommend treatment of advanced hepatocellular carcinoma (HCC) with extrahepatic metastasis (EHM). We aimed to compared the prognosis of Lenvatinib plus PD-1 inhibitor (Len+PD-1) versus Sorafenib plus PD-1 (Sora+PD-1) as an initial therapy for HCC with EHM.Methods: Incorporating a sum of 229 HCC patients with EHM were encompassed within this study, with 127 in the Sora+PD-1 group and 102 in the Len+PD-1 group. Through propensity score matching (PSM), we compared overall survival (OS), progression-free survival (PFS), and patient safety between these two groups.Results: The median OS were 13.0 months and 14.2 months in the Sora+PD-1 group and Len+PD-1 group. The 6-, 12-, and 24-month OS rates were 92.9%, 58.9% and 5.6% in Sora+PD-1 group and 93.1%, 61.8% and 22.6% in Len+PD-1 group, respectively. The Len+PD-1 group had obviously better OS than the Sora+PD-1 group (P = 0.002). The 3-, 6-, and 12-month PFS rates were 76.4%, 27.6% and 1.6% in Sora+PD-1 group and 86.2%, 50.5% and 12.2% in Len+PD-1 group, respectively. Compared with Sora+PD-1 group, the Len+PD-1 group had obviously better PFS (P < 0.001). Analysis within subgroups showed that OS was significant in patients receiving TACE in Len+PD-1 group than Sora+PD-1 group (p = 0.003).Conclusion: Len+PD-1 group had longer OS and PFS than Sora+PD-1 group for patient with EHM. In addition, OS in patients received TACE was improved with Len+PD-1 treatment. For patients without TACE, there was no significance between Sora+PD-1 and Len+PD-1 groups.Keywords: hepatocellular carcinoma, extrahepatic metastasis, lenvatinib, sorafenib, PD-1 inhibitor

Xiping Liao,1,2,&ast; Ji Liu,3,&ast; Xiaolong Guo,1 Ruiping Meng,1 Wei Zhang,1 Jianyun Zhou,1 Xia Xie,1,2 Hongli Zhou1 1Clinical Medical Research Center, the Second Affiliated Hospital, Army Medical University, Chongqing, People’s Republic of China; 2Department of Gastroenterology, the Second Affiliated Hospital, Army Medical University, Chongqing, People’s Republic of China; 3Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xia Xie, Department of Gastroenterology, the Second Affiliated Hospital, Army Medical University, No. 83 Xinqiao Main Street, Shapingba District, Chongqing, 400037, People’s Republic of China, Email xiexia0128@163.com Hongli Zhou, Clinical Medical Research Center, the Second Affiliated Hospital, Army Medical University, No. 83 Xinqiao Main Street, Shapingba District, Chongqing, 400037, People’s Republic of China, Email zhouhli7@mail2.sysu.edu.cnAbstract: Inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), is a chronic disease resulting from the interaction of various factors such as social elements, autoimmunity, genetics, and gut microbiota. Alarmingly, recent epidemiological data points to a surging incidence of IBD, underscoring an urgent imperative: to delineate the intricate mechanisms driving its onset. Such insights are paramount, not only for enhancing our comprehension of IBD pathogenesis but also for refining diagnostic and therapeutic paradigms. Monocytes, significant immune cells derived from the bone marrow, serve as precursors to macrophages (M&phis;s) and dendritic cells (DCs) in the inflammatory response of IBD. Within the IBD milieu, their role is twofold. On the one hand, monocytes are instrumental in precipitating the disease’s progression. On the other hand, their differentiated offsprings, namely moM&phis;s and moDCs, are conspicuously mobilized at inflammatory foci, manifesting either pro-inflammatory or anti-inflammatory actions. The phenotypic spectrum of these effector cells, intriguingly, is modulated by variables such as host genetics and the subtleties of the prevailing inflammatory microenvironment. Notwithstanding their significance, a palpable dearth exists in the literature concerning the roles and mechanisms of monocytes in IBD pathogenesis. This review endeavors to bridge this knowledge gap. It offers an exhaustive exploration of monocytes’ origin, their developmental trajectory, and their differentiation dynamics during IBD. Furthermore, it delves into the functional ramifications of monocytes and their differentiated progenies throughout IBD’s course. Through this lens, we aspire to furnish novel perspectives into IBD’s etiology and potential therapeutic strategies.Keywords: IBD, monocytes, inflammatory response

Lujian Zhu,1,&ast; Jing Zhou,1,&ast; Chen Yu,2 Lei Gu,3 Qin Wang,1 Hanglu Xu,1 Yin Zhu,4 Maodong Guo,5 Minli Hu,5 Wei Peng,6 Hao Fang,7 Haizhen Wang8 1Department of Infectious Diseases, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 4Department of Infectious Diseases, Taizhou Enze Medical Center (Group), Enze Hospital, Taizhou, People’s Republic of China; 5Department of Gastroenterology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, People’s Republic of China; 6Department of Intensive Care Unit, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, People’s Republic of China; 7Department of Trauma Surgery, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, People’s Republic of China; 8Department of Health Management Center, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haizhen Wang, Department of Health Management Center, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, People’s Republic of China, Email whz002012@sina.comAbstract: Ferroptosis, a type of programmed cell death that relies on iron, is distinct in terms of its morphological, biochemical and genetic features. Unlike other forms of cell death, such as autophagy, apoptosis, necrosis, and pyroptosis, ferroptosis is primarily caused by lipid peroxidation. Cells that die due to iron can potentially trigger an immune response which intensifies inflammation and causes severe inflammatory reactions that eventually lead to multiple organ failure. In recent years, ferroptosis has been identified in an increasing number of medical fields, including neurological pathologies, chronic liver diseases and sepsis. Ferroptosis has the potential to cause an inflammatory tempest, with many of the catalysts and pathological indications of respiratory ailments being linked to inflammatory reactions. The growing investigation into ferroptosis in respiratory disorders has also garnered significant interest to better understand the mechanism of ferroptosis in these diseases. In this review, the recent progress in understanding the molecular control of ferroptosis and its mechanism in different respiratory disorders is examined. In addition, this review discusses current challenges and prospects for understanding the link between respiratory diseases and ferroptosis.Keywords: respiratory system, ferroptosis, iron metabolism, oxidative stress, treatment

Jiaxin Zhao,1 Cheng Wang,1 Liang Zhao,1 Huiying Zhou,1 Rui Wu,1 Tao Zhang,1 Jiawei Ding,1 Junjie Zhou,2 Huilin Zheng,3 Lei Zhang,3 Tianci Kong,3 Jie Zhou,4 Zhenhua Hu1,4 1Department of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Fourth Affiliated Hospital, School of Medicine, Zhejiang University, Yiwu, Zhejiang Province, People’s Republic of China; 2Department of Radiology, Fourth Affiliated Hospital, School of Medicine, Zhejiang University, Yiwu, Zhejiang Province, People’s Republic of China; 3Zhejiang Provincial Collaborative Innovation Center of Agricultural Biological Resource Biochemical Manufacturing, School of Biological and Chemical Engineering, Zhejiang University of Science and Technology, Hangzhou, Zhejiang Province, People’s Republic of China; 4Department of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, People’s Republic of ChinaCorrespondence: Zhenhua Hu, Department of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Fourth Affiliated Hospital, School of Medicine, Zhejiang University, Yiwu, Zhejiang Province, People’s Republic of China, Tel/Fax +86-570-89935878, Email huzhenh@zju.edu.cn Jie Zhou, Department of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, People’s Republic of China, Tel +86-13429661721, Email jzhou329@zju.edu.cnPurpose: Nonsense-mediated RNA decay (NMD), a surveillance pathway for selective degradation of aberrant mRNAs, is associated with cancer progression. Its potential as a predictor for aggressive hepatocellular carcinoma (HCC) is unclear. Here, we present an innovative NMD risk model for predicting HCC prognosis.Methods: The Cancer Genome Atlas (TCGA) data of 374 liver HCC (LIHC) and 50 normal liver samples were extracted. A risk model based on NMD-related genes was developed through least absolute shrinkage and selection operator Cox (LASSO-Cox) regression of the LIHC-TCGA data. Prognostic validation was done using GSE54236, GSE116174, and GSE76427 data. Univariate and multivariate Cox regression analyses were conducted to assess the prognostic value of the model. We also constructed nomograms for survival prediction. Tumor immune infiltration was evaluated using the CIBERSORT algorithm, and the tumor cell phenotype was assessed. Finally, mouse experiments verified UPF3B knockdown effects on HCC tumor characteristics.Results: We developed a risk model based on four NMD-related genes (PABPC1, RPL8, SMG5, and UPF3B) and validated it using GSE54236, GSE116174, and GSE76427 data. The model effectively distinguished high- and low-risk groups corresponding to unfavorable and favorable HCC outcomes. Its prognostic prediction accuracy was confirmed through time-dependent ROC analysis, and clinical-use nomograms with calibration curves were developed. Single-cell RNA sequencing results indicated significantly higher expression of SMG5 and UPF3B in tumor cells. Knockdown of SMG5 and UPF3B inhibited HCC cell proliferation, invasion, and migration, while affecting cell-cycle progression and apoptosis. In vivo, UPF3B knockdown delayed tumor growth and increased immune cell infiltration.Conclusion: Our NMD-related gene-based risk model can help identify therapeutic targets and biomarkers for HCC. Additionally, it assists clinicians in predicting the prognosis of HCC patients.Keywords: nonsense-mediated RNA decay, hepatocellular carcinoma, biomarker, LASSO, survival, tumor immunity

Jiaqing Zhou,1 Huan Xu,2 Wen Du,1 Lijun Peng1 1Department of Respiratory Medicine, West China Fourth Hospital, Sichuan University, Chengdu, People’s Republic of China; 2Department of Scientific Affairs, Vision Medicals for Infectious Diseases, Guangzhou, People’s Republic of ChinaCorrespondence: Lijun Peng, Department of Respiratory Medicine, West China Fourth Hospital, Sichuan University, No. 17, Section 3, Renmin South Road, Wuhou District, Chengdu, 610041, People’s Republic of China, Tel +86 13208119408, Email penglijun711@163.comAbstract: We reported a 51-year-old male electric welder with stage I pneumoconiosis, who had no significant cough, sputum, fever, chest pain, or other discomfort. However, regular physical examination at our hospital revealed bilateral pulmonary nodules with cavity formation. Blood routine, liver or kidney function, and infection-related biomarkers, including interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), and procalcitonin (PCT), were normal. Sputum and alveolar lavage fluid (BALF) acid-fast bacilli (AFB) smears, BALF Mycobacterium tuberculosis (TB) PCR, and T-SPOT.TB were negative. The nucleic acid sequence of Mycobacterium europaeum was detected by BALF metagenomic next-generation sequencing (mNGS), which was confirmed by the subsequent positive culture for NTM. Considering stable conditions, no significant discomfort, and no significant changes in the lung lesion, the patient was diagnosed with inactive nontuberculous mycobacterial pulmonary disease (NTM-PD).Keywords: pneumoconiosis, nontuberculous mycobacterial pulmonary disease, NTM-PD, Mycobacterium europaeum, metagenomic next-generation sequencing, mNGS

Junya Zhou,1 Qingzhu Qin,1 Songge Chen,1 Hongmei Zhang2 1Department of Cardiology, Henan Provincial Key Medicine Laboratory of Nursing, Henan Provincial People’s Hospital; Zhengzhou University People’s Hospital, Zhengzhou, Henan, 450003, People’s Republic of China; 2Department of Nursing, Henan Provincial Key Medicine Laboratory of Nursing, Henan Provincial People’s Hospital; Zhengzhou University People’s Hospital, Zhengzhou, Henan, 450003, People’s Republic of ChinaCorrespondence: Hongmei Zhang, Department of Nursing, Henan Provincial Key Medicine Laboratory of Nursing, Henan Provincial People’s Hospital; Zhengzhou University People’s Hospital, No. 7 Weiwu Road, Zhengzhou, Henan, 450003, People’s Republic of China, Tel +86 15699930876, Email zhang_hongmei2023@yeah.netAbstract: In intensive care units, patients are often restrained to ensure their safety, with physical restraints being the most commonly used method. However, physical restraints compromises the patient’s freedom, health and comfort, and nurses often face moral dilemmas when deciding whether to use physical restraints. This article examines physical restraints through the four universal principles of autonomy, beneficence, non-maleficence and justice. Through these principles, the authors will critically explore whether the physical restraints of patients by nurses is ethical in practice and what moral issues exist. This paper also explores conflicts and moral dilemmas for nurses in this context. Finally, suggestions are made on changes to education and clinical practice.Keywords: physical restraints, ethical dilemmas, ethics

Xiaoxiao Zhao,1 Hanjun Zhao,1 Runzhen Chen,1 Jiannan Li,1 Jinying Zhou,1 Nan Li,1 Shaodi Yan,2 Chen Liu,1 Peng Zhou,1 Yi Chen,1 Li Song,1 Hongbing Yan2 1Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Peking Union Medical College & Chinese Academy of Medical Sciences, BeiJing, People’s Republic of China; 2Department of Cardiology, Fuwai Hospital Chinese Academy of Medical Sciences, ShenZhen, People’s Republic of ChinaCorrespondence: Hanjun Zhao, Department of Cardiology, Fuwai Hospital, Chinese Academy of Medical Sciences, No. 167, Beijing, 100037, People’s Republic of China, Tel +86-15210020808, Email 15210020808@163.com Hongbing Yan, Fuwai Hospital, Chinese Academy of Medical Sciences, 12 Langshan Road, Shenzhen, 518000, People’s Republic of China, Tel +86-1301339287, Email hbyanfuwai2018@163.comBackground and Aim: An elevated triglyceride-glucose (TyG) level is associated with increased risk of mortality in patients with CAD. Trimethylamine N-oxide (TMAO) has mechanistic links to atherosclerotic coronary artery disease (CAD) pathogenesis and is correlated with adverse outcomes. However, the incremental prognostic value of TMAO and TyG in the cohort of optical coherence tomography (OCT)-defined high-risk ST-segment elevation myocardial infarction (STEMI) patients is unknown.Methods: We studied 274 consecutive aged ≥ 18 years patients with evidence of STEMI and detected on pre-intervention OCT imaging of culprit lesions between March 2017 and March 2019.Outcomes: There were 22 (22.68%), 27 (27.84%), 26 (26.80%), and 22 (22.68%) patients in groups A-D, respectively. The baseline characteristics according to the level of TMAO and TyG showed that patients with higher level in both indicators were more likely to have higher triglycerides (p < 0.001), fasting glucose (p < 0.001) and higher incidence of diabetes (p = 0.008). The group with TMAO > median and TyG ≤ median was associated with higher rates of MACEs significantly (p = 0.009) in fully adjusted analyses. During a median follow-up of 2.027 years, 20 (20.6%) patients experienced MACEs. To evaluate the diagnostic value of the TyG index combined with TMAO, the area under the receiver operating characteristic curve for predicting MACEs after full adjustment was 0.815 (95% confidence interval, 0.723– 0.887; sensitivity, 85.00%; specificity, 72.73%; cut-off level, 0.577). Among the group of patients with TMAO > median and TyG ≤ median, there was a significantly higher incidence of MACEs (p= 0.033). A similar tendency was found in the cohort with hyperlipidemia (p= 0.016) and diabetes mellitus (p= 0.036).Conclusion: This study demonstrated the usefulness of combined measures of the TyG index and TMAO in enhancing risk stratification in STEMI patients with OCT-defined high-risk plaque characteristics.Trial Registration: This study was registered at ClinicalTrials.gov as NCT03593928.Keywords: optical coherence tomography, triglyceride glucose index, trimethylamine N-oxide, high risk plaque feature, major adverse cardiovascular events, prospective study

Jian Zhou,1 Ya-Jie Li,2 Xiao-Dong Zhou,3 Li-Juan Wang1 1Department of Cardiology, The Heart Center, Zhe Jiang Hospital, Hangzhou, 310012, People’s Republic of China; 2Psychiatry Department, Fuyang District Third People’s Hospital, Hangzhou, 311400, People’s Republic of China; 3Department of Cardiology, The Heart Center, The First Affiliated Hospital of Wenzhou Medical University, Zhejiang, 325000, People’s Republic of ChinaCorrespondence: Jian Zhou, Department of Cardiology, Zhe Jiang Hospital, 12 Lingyin Road, Xihu Qu, Hangzhou, 310012, People’s Republic of China, Tel +86-517-8798-7373, Email zhoujian202211@163.comBackground: Rate-pressure product (RPP) calculated by multiplying heart rate by systolic blood pressure, is a convenient indicator closely associated with cardiac work or myocardial oxygen consumption. It has been reported to relate strongly to important indices of cardiovascular risk in patients with myocardial ischemia. However, its relationship with short- and long-term mortality in patients with acute coronary syndrome (ACS) undergoing primary PCI/immediate invasive strategy has not been defined.Methods: This study analyzed 1301 consecutive ACS patients who had undergone primary PCI, between January 2018 and September 2021. Patients with systolic BP < 90 mmHg were excluded to avoid the confounding effect of cardiogenic shock. RPP values were collected on admission and were divided into four groups: RPP ≤ 7.4, 7.4 ≤ 8.8, 8.8 < 8.8 < RPP8, and RPP > 10.8. Clinical endpoints were in-hospital cardiac and long-term all-cause mortality. The predictive performance was assessed by C-statistic, multivariate analysis and survival analysis.Results: Multivariate analysis showed that these in the highest vs lowest category of RPP (> 10.8 vs ≤ 7.4) had OR of 4.33 (95% CI=1.10 − 17.01; P = 0.036) in in-hospital cardiac mortality and 3.15 (95% CI=1.24 − 8.00; P = 0.016) in long-term all-cause mortality. In C-statistic analyses, RPP was a strong predictor in ACS, STEMI or UA/NSTEMI group for in-hospital cardiac mortality (AUC = 0.746, 95% CI = 0.722– 0.770, p < 0.001) and long-term all-cause mortality (AUC = 0.701, 95% CI = 0.675– 0.725, p < 0.001). The Kaplan–Meier event rate for long-term survival of RPP > 10.8 was significantly lower than that of RPP ≤ 10.8.Conclusion: RPP showed a positive association with in-hospital cardiac or long-term all-cause mortality in ACS patients undergoing primary PCI/immediate invasive strategy, and RPP > 10.8 can be as an independent predictor.Keywords: rate-pressure product, acute coronary syndrome, short-and long-term mortality

Shan-Shan Hong,1,&ast; Yang Li,2,&ast; Yu-Yi Lin,3 San-Gang Wu,4 Li-Ying Chen,1 Juan Zhou5 1Department of Obstetrics and Gynecology, Quanzhou Women’s and Children’s Hospital, Quanzhou, 362000, People’s Republic of China; 2School of Basic Medical Sciences, Fujian Medical University, Fuzhou, 350122, People’s Republic of China; 3Department of Radiation Oncology, the Second Affiliated Hospital of Xiamen Medical College, Xiamen, 361021, People’s Republic of China; 4Department of Radiation Oncology, Xiamen Cancer Center, Xiamen Key Laboratory of Radiation Oncology, the First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, 361003, People’s Republic of China; 5Department of Obstetrics and Gynecology, the First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, 361003, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li-Ying Chen, Department of Obstetrics and Gynecology, Quanzhou Women’s and Children’s Hospital, Quanzhou, 362000, People’s Republic of China, Email aziliying@163.com Juan Zhou, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, 361003, People’s Republic of China, Email zhoujuan@xmu.edu.cnPurpose: To determine the disparities in survival outcomes between stage IIB-IVA cervical squamous cell carcinoma (SCC) and adenocarcinoma (AC) treated with chemoradiotherapy.Methods: Patients diagnosed between 2004 and 2015 were retrospectively included from the Surveillance, Epidemiology, and End Results databases. Propensity score matching (PSM) was used in this study. The primary endpoints were cervical cancer-specific survival (CCSS) and overall survival (OS).Results: A total of 2752 patients were identified, including 87.5% (n=2408) were SCC and 12.5% (n=344) were AC. Patients with AC had inferior 5-year CCSS (67.5% vs 54.8%, P< 0.001) and OS (58.4% vs 47.2%, P< 0.001) compared to those with the SCC subtype. The hazard curve of cervical cancer-related death in AC peaked at 2 years (19%) and still small peaks in the 7 and 11 years of follow-up. Regarding SCC, cervical cancer-related deaths peaked at 2 years (15%) and the hazard rate was 2.0% during the six years of follow-up. The multivariate Cox regression analyses indicated that histology was an independent prognostic factor associated with survival outcomes. Patients with AC had significantly poor CCSS (P< 0.001) and OS (P< 0.001). Similar results were found after PSM.Conclusion: Our study demonstrates a significantly better prognosis for cervical SCC patients compared to those with cervical AC undergoing chemoradiotherapy. These results highlight the importance of histological subtyping in predicting treatment outcomes and tailoring therapeutic strategies.Keywords: cervical cancer, squamous cell carcinoma, adenocarcinoma, chemotherapy, radiotherapy, hazard curve

Jingjing Zhou,1,2 Dongfeng Li,2 Youmin Wang1 1Department of Endocrinology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230001, People’s Republic of China; 2Department of Endocrinology, The Second People’s Hospital of Lu’an, Affiliated Hospital of West Anhui Health Vocational College, Lu’an, Anhui, 237000, People’s Republic of ChinaCorrespondence: Youmin Wang, Email 971359183@qq.comObjective: Vitamin D deficiency is associated with patients with diabetic peripheral neuropathy (DPN), and low levels of vitamin D are common in patients with depression. Depression is common in DPN patients and the definite pathogenesis remains unclear. This study aimed to determine vitamin D deficiency in the onset of depression in DPN and evaluate the effect of vitamin D supplementation on depression.Methods: A total of 192 patients with DPN were enrolled in this study. Clinical and laboratory information was collected. Chemiluminescent immunoassay was used to measure the level of 25(OH)D. Enzyme-linked immunosorbent assay was employed to measure the concentrations of interleukin (IL)-1β, tumor necrosis factor-α (TNF-α), and IL-17A. Subjects with low 25(OH)D received 5000IU vitamin D daily for 12 weeks. Depression scores and levels of 25(OH)D, IL-1β, TNF-α, and IL-17A were re-evaluated after supplementation.Results: The incidence of vitamin D deficiency and depression was high in DPN patients. Compared with vitamin D sufficient participants, Hamilton Depression Rating Scale (HAMD) scores and the levels of inflammatory markers IL-1β, TNF-α, and IL-17A were significantly higher in insufficient group (all p< 0.05). HAMD score, IL-1β, TNF-α, and IL-17A were negatively correlated with 25(OH)D (all p< 0.05). A linear relationship existed among IL-1β, TNF-α, IL-17A, and 25(OH)D (p< 0.05). HAMD scores, IL-1β, TNF-α, and IL-17A were all reduced significantly after supplementation of vitamin D (p< 0.05). Binary logistic analysis revealed that vitamin D insufficiency was an independent risk factor for depression in patients with DPN. Receiver operating characteristic (ROC) curve analysis showed a high sensitivity (87.20%) of 25(OH)D in discriminating DPN patients with depression.Conclusion: Vitamin D deficiency participated in occurrence of depression in DPN patients and could be mediated, at least in part, by upregulation of pro-inflammatory cytokines. Vitamin D supplementation may be effective in improving depressive symptoms in DPN patients.Keywords: vitamin D, depression, diabetic peripheral neuropathy, interleukin-1 beta, tumor necrosis factor-alpha, interleukin-17A

Wenwei Feng,&ast; Jiancong Zhou,&ast; Zhubin Lun, Dianhua Zhou, Peiwen Li, Jianfeng Ye Department of Cardiology, Dongguan Hospital of Guangzhou University of Chinese Medicine, Dongguan, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianfeng Ye, Department of Cardiology, Dongguan Hospital of Guangzhou University of Chinese Medicine, Dongguan, Guangdong, People’s Republic of China, Email yipjf@hotmail.comBackground: Contrast-associated acute kidney injury (CA-AKI) is a prevalent complication following coronary angiography (CAG). However, there is ongoing controversy surrounding its precise definition. Although previous studies have demonstrated the successful application of appropriate definitions in managing high-risk CA-AKI patients, there remains limited research on the association between different definitions and prognosis specifically in patients with chronic kidney disease (CKD).Methods: A total of 4197 CKD patients undergoing coronary angiography (CAG) were included in this study. Two definitions of contrast-associated acute kidney injury (CA-AKI) were used: CA-AKIA, which was defined as an increase of ≥ 0.5 mg/dL or > 25% in serum creatinine (SCr) from baseline within 72 hours after CAG, and CA-AKIB, which was defined as an increase of ≥ 0.3 mg/dL or > 50% in SCr from baseline within 48 hours after CAG. Cox regression analysis was employed to assess the association between these two definitions and long-term mortality. Additionally, population attributable risks (PARs) were calculated to evaluate the impact of CA-AKI definitions on long-term prognosis.Results: During the median follow-up period of 4.70 (2.50– 7.78) years, the overall long-term mortality was 23.6%, and the long-term mortality in patients with CA-AKI according to both CA-AKIA and CA-AKIB criteria were 33.5% and 33.8%, respectively. We found that CA-AKIA (HR: 1.45, 95% CI: 1.23– 1.70, p< 0.001) and CA-AKIB (HR: 1.44, 95% CI: 1.23– 1.69, p< 0.001) were associated with long-term mortality. The PARs were the highest for CA-AKIA (5.87%), followed by CA-AKIB (5.70%).Conclusion: Contrast-associated acute kidney injury (CA-AKI) is a frequently observed complication in CKD patients undergoing coronary angiography (CAG), and both definitions of CA-AKI are significantly correlated with a poor long-term prognosis. Consequently, in the clinical management of CKD patients, it is crucial to prioritize CA-AKI, irrespective of the specific CA-AKI definition used.Keywords: contrast-associated acute kidney injury, chronic kidney disease, definitions, long-term mortality, population attributable risks