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Yulong Xiong,1,2,* Zhenhao Zhang,1,2,* Shangyu Liu,1,2 Lishui Shen,1,2 Lihui Zheng,1,2 Ligang Ding,1,2 Limin Liu,1 Lingmin Wu,1 Zhicheng Hu,1 Le Li,1 Zhao Hu,1 Zhuxin Zhang,1 Likun Zhou,1 Mengtong Xu,1 Yan Yao1,2 1Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 2State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yan Yao, Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, 167A Beilishi Road, Xi Cheng District, Beijing, 100037, People’s Republic of China, Email ianyao@263.net.cnIntroduction: Nanomedicine coated with cell membranes has attracted increasing attention for its enhanced targeting capability and biocompatibility. Based on previous research, we identified interferon regulatory factor 1 (IRF1)-mediated macrophage pyroptosis as a potential therapeutic target for myocarditis. Herein, we fabricated an innovative immune cell membrane-coated zeolitic imidazolate framework-8 (ZIF-8) nano-delivery platform and explored its effects on myocarditis.Methods: ZIF-8 nanoparticles loaded with siRNA targeting IRF1 (siIRF1) were coated with a T lymphocyte-macrophage hybrid membrane (siIRF1@ZIF@HM NPs) via sonication and extrusion. The morphological and biological characteristics of the nanoparticles were evaluated using transmission electron microscopy (TEM) and dynamic light scattering (DLS). Cellular cytotoxicity was assessed by a cell counting kit-8 assay. Cellular uptake and endo-lysosomal escape in M1-differentiated macrophages were visualized via fluorescence microscopy. The targeting specificity and anti-myocarditis effects were evaluated in an experimental autoimmune myocarditis (EAM) mouse model. The anti-pyroptosis effects were assessed by Western blot analysis both in vivo and in vitro.Results: Transcriptional sequencing identified T lymphocytes and macrophages as suitable membrane sources. The ZIF-8 nanoparticles exhibited high siRNA loading capacity and pH responsiveness, enabling an efficient release of siIRF1 from endo-lysosomes to the cytoplasm in macrophages. The hybrid membrane coating enabled specific targeting of M1 macrophages both in vivo and in vitro. Furthermore, delivery of siIRF1 effectively suppressed IRF1 expression and inhibited pyroptosis in IFN-γ-stimulated macrophages. Intravenous injection of siIRF1@ZIF@HM NPs significantly alleviated myocarditis progression without evident side effects.Conclusion: The siIRF1 nanotherapeutic approach shows potential for attenuating myocardial inflammation and mitigating myocarditis progression. Our study highlights the promise of this customized biomimetic nano-delivery system for treating inflammatory diseases. Keywords: hybrid membrane, myocarditis, macrophage, pyroptosis, small interfering RNA, immunotherapy

Xiaoying Cheng,1,2,* Jianhua Wan,1,2,* Denglong Sun,1,2 Yang Zhan,1,2 Jingting Yu,1,2 Yingmeng Li,1,2 Yanxia Xiong,1,2 Wenjun Liu1,2 1State Key Laboratory for the Modernization of Classical and Famous Prescriptions of Chinese Medicine, Nanchang, 330096, People’s Republic of China; 2Research and Development Department, Jiangzhong Pharmaceutical Co., Ltd., Nanchang, 330103, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wenjun Liu, Email crjzliuwenjun@163.comBackground: Jianweixiaoshi tablets (JWXS) is widely used in traditional Chinese medicine for treating functional dyspepsia with spleen deficiency (SD-FD) in China. However, the molecular mechanisms underlying the therapeutic effects of JWXS remain incompletely understood.Methods: Functional dyspepsia was induced in rats with spleen deficiency by iodoacetamide in combination with the modified multiple platform method. The SD-FD rats were administered JWXS at both low and high doses, as well as domperidone. We conducted a comprehensive evaluation of the treatment effects of JWXS, including body weight, gastrointestinal motility, immune organ index, biochemical analysis, gastrointestinal hormones, and hematological studies. Quantitative proteomic analysis based on data-independent acquisition (DIA) was used to determine the changes in protein profiles of gastric and duodenal tissues in SD-FD rats and JWXS intervention rats.Results: The results showed that JWXS effectively alleviated gastrointestinal motility disorders in SD-FD rats, as indicated by accelerated gastric emptying and intestinal propulsion, increased levels of gastrin, motilin, and ghrelin, and reduced levels of cholecystokinin-octapeptide, vasoactive intestinal peptide, and somatostatin. Additionally, JWXS increased the spleen and thymus index, increased %lymphocyte in blood, reduced white blood cell count and %neutrophil, and improved immune function. Through quantitative proteomic analysis of gastric tissues, we identified 333 differentially expressed proteins in the JWXS treatment group and the model group. Notably, the mechanism by which JWXS accelerated gastric emptying may be related to PLC-γ and SERCA2 in the calcium signaling pathway. Furthermore, JWXS treatment altered the expression of 732 proteins in rat duodenal samples. The differentially expressed proteins were enriched in immune-related functions and pathways, including antigen processing and presentation, as well as the intestinal immune network for IgA production.Conclusion: In conclusion, JWXS exhibits a multi-faceted impact on various pathways, demonstrating its efficacy in treating SD-FD. These findings provide a foundation for the clinical application of JWXS in managing SD-FD.Keywords: Jianweixiaoshi tablets, functional dyspepsia, spleen deficiency, traditional Chinese medicine, proteomic

Jimei Li,* Yulin Xiong,* Shengyan Li, Qiong Ye, Yan Han, Xiuxin Zhang, Tongxiu Zhao, Yuan Yang, Xiaoshan Cui, Yinglan Li General Medicine Department, Qinghai Provincial People’s Hospital, Xining, Qinghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yinglan Li, General Medicine Department, Qinghai Provincial People’s Hospital, Gonghe Road 2, Xining, Qinghai, People’s Republic of China, Tel +8613997233103, Email qhlyl@126.comPurpose: This study aimed to establish the prevalence of pulmonary embolism (PE) in chronic obstructive pulmonary disease (COPD) patients with secondary polycythemia (SP) and explore the risk factors for PE in COPD patients with SP.Patients and Methods: We analyzed the prevalence of PE among COPD patients with SP who were hospitalized at Qinghai Provincial People’s Hospital between January 2015 and December 2020. From January 2021 to January 2024, we enrolled patients into three groups (COPD+SP+PE, COPD+SP, and control) and performed laboratory measurements, biomarkers, echocardiography, and pulmonary function tests. Patients in the COPD+SP group received clinical treatment, and biomarkers were measured again seven days after treatment.Results: The prevalence of PE in patients with COPD SP was 5.21%. We found that COPD+SP+PE group had significantly higher levels of erythrocyte distribution width (RDW), platelet volume distribution width (PDW), mean platelet volume (MPV), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), monocyte to large platelet ratio (MLPR), 5-hydroxytryptamine (5-HT), activated protein C (APC), urokinase-type plasminogen activator (u-PA), thrombomodulin (TM), interleukin-38 (IL-38), tissue factor (TF), and fractalkine (FKN) in contrast to COPD+SP group. Biomarkers, such as FKN, β-thromboglobulin (β-TG), APC, u-PA, TM, TF, and IL-38, were risk factors for COPD patients with SP who are complicated by PE. Clinical treatment significantly reduced the levels of β-TG, IL-38, APC, endothelin-1 (ET-1), u-PA, FKN, TM, 5-HT, and neutrophil extracellular traps (NETs) in patients with COPD+SP.Conclusion: PE incidence was significantly higher in patients with COPD and SP. In COPD patients with SP, routine joint detection of blood and cardiac markers, blood gas analysis, and pulmonary function tests can help to identify patients with PE. APC, u-PA, TF, FKN, TM, and IL-38 are risk factors for PE in patients with COPD and SP, and clinical treatment can effectively reduce this risk.Keywords: chronic obstructive pulmonary diseases, secondary polycythemia, pulmonary embolism, biomarker, risk factors

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

Xiuxin Tang,1,* Zhiyun Liu,2,* Danni Li,3 Yan Xiong,3 Kang Liao,1 Yili Chen1 1Department of Laboratory Medicine, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, People’s Republic of China; 2Department of Clinical Laboratory, Huizhou Central People ‘s Hospital, Huizhou, Guangdong, 516001, People’s Republic of China; 3Department of Emergency Medicine, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yili Chen, Department of Laboratory Medicine, The First Affiliated Hospital of Sun Yat-sen University, No. 58 Zhongshan Er Road Guangzhou, Guangzhou, Guangdong Province, 510080, People’s Republic of China, Tel +8620-87330808-8461, Fax +8620-87330808, Email chenyli3@mail.sysu.edu.cnBackground: Elizabethkingia anophelis, an opportunistic pathogen that can cause infections in multiple parts of the human body, has multiple drug resistance and a high mortality rate. However, there have been few reports of infective endocarditis (IE) caused by Elizabethkingia anophelis, which means that diagnosis and treatment face challenges that cannot be ignored. Rapid and accurate identification and drug sensitivity results are needed to make timely treatment adjustments.Case Presentation: An 81-year-old man presented with recurrent fever and increased infection index for more than a month. Based on his clinical symptoms, infection index, reduplicative blood cultures, and results of transesophageal echocardiography, he was ultimately diagnosed with infective endocarditis caused by Elizabethkingia anophelis. The patient had a favorable outcome with a 6-week course of intravenous antibiotic therapy.Conclusion: This is a rare and successfully cured case of IE caused by the pathogen of Elizabethkingia anophelis, which is difficult not only in diagnosis but also in treatment. This case provides a certain referential significance to the treatment of Elizabethkingia anophelis-caused IE in clinical practice.Keywords: Elizabethkingia anophelis, infective endocarditis, drug resistance, treatment

Bohao Dai,1,&ast; Xiaorong Peng,1,&ast; Jia Sun,1 Xueling Zhu,1 Xiang Liu,1 Ye Xiong,1 Zhikai Wan,1 Dairong Xiang,1 Jiangjin Hui,1 Chenxi Ying,2 Huiting Liu,1 Biao Zhu1,&ast; 1The Department of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China; 2Cardivascular Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Biao Zhu, The Department of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qing Chun Road, Hangzhou, 310006, People’s Republic of China, Email zhubiao1207@zju.edu.cnBackground: HIV-1 CRF01_AE is becoming the predominant HIV-1 subtype among patients in China. The distribution and characteristics of transmission clusters of HIV-1 CRF01_AE in Zhejiang, Eastern China remains unclear. This study analyzed the epidemiologic characteristics and transmission clusters of HIV-1 CRF01_AE in Zhejiang.Methods: Plasma samples obtained from 152 patients of HIV-1 CRF01_AE not undergoing ART were used to amplify HIV-1 pol and env gene. CRF01_AE drug resistance mutations (DRM) prevalence was analysed using Stanford University’s HIV Drug Resistance Database. A phylogenetic tree was constructed using FastTree (version 2.1.11) based on the GTR nucleotide substitution model and visualized using Figtree (version 1.4.4) and The Interactive Tree of Life; the Chinese HIV Gene Sequence Data Platform was used to construct genetic transmission networks.Results: Majority samples could be grouped into CRF01_AE transmission Clusters 1 (11.2%), 4 (64.5%), and 5 (7.2%). The CD4+ T-cell counts in Cluster 1, 4a, 4b are lower than 5 were 15, 38, 30, and 248 cells/mm3, respectively (P < 0.05). The high X4 tropism rates were 13.2%, 11.8%, 20.0%, and 0.0% in Clusters 1, 4a, 4b, and 5, respectively. DRM rates in Clusters 4a and 4b were 17.6%, and 25.45% respectively (P < 0.05), whereas they were 17.6% and 18.2% in Clusters 1 and 5, respectively. In total, 24 transmission genetic networks, comprising 72 sequences and 61 links, were discovered; of them, 61.2%, 11.7%, and 18.2% were from Clusters 4, 1, and 5, respectively (P < 0.05).Conclusion: In Zhejiang, different CRF01_AE clusters displayed unique clinic features. Cluster 4, particularly Cluster 4b, was considered a high-risk transmission cluster. The surveillance of epidemiology of HIV-1 should be enhanced to minimize its transmission.Keywords: HIV-1 CRF01_AE, drug resistance mutation, transmission cluster

Jie Jin,1 Jie Lu,1 Xinyang Su,2 Yinhuan Xiong,3 Shasha Ma,4 Yang Kong,5 Hongmei Xu1 1School of Nursing, Binzhou Medical University, Binzhou, People’s Republic of China; 2Department of Spine Surgery, Binzhou Medical University Hospital, Binzhou, People’s Republic of China; 3Department of Nursing, Binzhou People’s Hospital, Binzhou, People’s Republic of China; 4Department of Neurosurgery, Binzhou Medical University Hospital, Binzhou, People’s Republic of China; 5School of Health Management, Binzhou Medical University, Yantai, People’s Republic of ChinaCorrespondence: Hongmei Xu, School of Nursing, Binzhou Medical University, No. 525 Huanghe 3rd Road, Binzhou, 256600, People’s Republic of China, Tel +86-13754689536, Email hmx58@163.com Yang Kong, School of Health Management, Binzhou Medical University, No. 346 Guanhai Road, Yantai, 264003, People’s Republic of China, Tel +86-13773576163, Email kongyang@bzmc.edu.cnPurpose: The purpose of this study was to establish and validate machine learning-based models for predicting the risk of venous thromboembolism (VTE) in intensive care unit (ICU) patients.Patients and Methods: The clinical data of 1494 ICU patients who underwent Doppler ultrasonography or venography between December 2020 and March 2023 were extracted from three tertiary hospitals. The Boruta algorithm was used to screen the essential variables associated with VTE. Five machine learning algorithms were employed: Random Forest (RF), eXtreme Gradient Boosting (XGBoost), Support Vector Machine (SVM), Gradient Boosting Decision Tree (GBDT), and Logistic Regression (LR). Hyperparameter optimization was conducted on the predictive model of the training dataset. The performance in the validation dataset was measured using indicators, including the area under curve (AUC) of the receiver operating characteristic (ROC) curve, specificity, and F1 score. Finally, the optimal model was interpreted using the SHapley Additive exPlanation (SHAP) package.Results: The incidence of VTE among the ICU patients in this study was 26.04%. We screened 19 crucial features for the risk prediction model development. Among the five models, the RF model performed best, with an AUC of 0.788 (95% CI: 0.738– 0.838), an accuracy of 0.759 (95% CI: 0.709– 0.809), a sensitivity of 0.633, and a Brier score of 0.166.Conclusion: A machine learning-based model for prediction of VTE in ICU patients were successfully developed, which could assist clinical medical staff in identifying high-risk populations for VTE in the early stages so that prevention measures can be implemented to reduce the burden on the ICU patients.Keywords: venous thromboembolism, machine learning, algorithm, prediction model, intensive care unit

Shaoqiu Zhang,1,&ast; Qun Zhang,2,&ast; Jian Wang,1,3,&ast; Yifan Pan,4 Zhiyi Zhang,5 Yu Geng,1 Bei Jia,1 Bing Tian,2 Yali Xiong,1 Xiaomin Yan,1 Jie Li,1,3– 5 Huali Wang,6 Rui Huang,1,3– 5 Chao Wu1,3– 5 1Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, People’s Republic of China; 2Department of Infectious Diseases, Affiliated Zhongda Hospital of Southeast University, Nanjing, Jiangsu, People’s Republic of China; 3Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, Jiangsu, People’s Republic of China; 4Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 5Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China; 6Department of General Practice, Nanjing Second Hospital, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chao Wu; Rui Huang, Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, No. 321 Zhongshan Road, Nanjing, Jiangsu, 210008, People’s Republic of China, Tel +86-25-83105890, Fax +86-25-83307115, Email dr.wu@nju.edu.cn; doctor_hr@126.comBackground: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging epidemic infectious disease with high mortality rate. This study aimed to investigate the association of red blood cell distribution width (RDW) and mortality risk in hospitalized SFTS patients.Methods: Clinical data of SFTS patients was retrospectively collected from three hospitals between October 2010 and August 2022. Cox proportional hazards model was used to identity the risk factors for fatal outcome. The predictive value of RDW for fatal outcome was evaluated by the receiver operating characteristic (ROC) analysis and Kaplan–Meier methods.Results: Of 292 patients, the median age was 61.5 years. Non-survivors showed higher RDW value than survivors (13.6% vs.13.0%, P < 0.001). The mortality rate was 44.8% in patients with elevated RDW compared to 18.4% of patients with normal RDW, with a relative risk (RR) of 2.439. Elevated RDW was an independent risk factor of mortality (hazards ratio: 1.167, P = 0.019). Patients with elevated RDW had a higher cumulative mortality than patients with normal RDW. The area under the ROC curve (AUC) of RDW for the prediction of mortality was 0.690 (P < 0.001).Conclusion: Elevated RDW was associated with higher mortality risk for patients hospitalized for SFTS. RDW may be helpful for risk stratification in SFTS patients.Keywords: severe fever with thrombocytopenia syndrome, red blood cell distribution width, prognosis, survival

Yiqi Xiong,1,&ast; Wenying Qiao,2,3,&ast; Tingting Mei,1,&ast; Kang Li,4 Ronghua Jin,2,3 Yonghong Zhang1 1Interventional Therapy Center for Oncology, Beijing You’an Hospital, Capital Medical University, Beijing, 100069, People’s Republic of China; 2National Center for Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, People’s Republic of China; 3Changping Laboratory, Beijing, 102206, People’s Republic of China; 4Research center for biomedical Resources, Beijing You’an Hospital, Capital Medical University, Beijing, 100069, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yonghong Zhang, Interventional therapy center for oncology; Beijing You’an Hospital, Capital Medical University, 8 Xitoutiao, Youanmenwai Street, Fengtai District, Beijing, Tel +86-13810108505, Email zhangyh@ccmu.edu.cn Ronghua Jin, National center for infectious diseases, Beijing Ditan Hospital, Capital Medical University, 8 Jingshundong Street, Chaoyang District, Beijing, Tel +86-13811611118, Email ronghuajin@ccmu.edu.cnPurpose: The aim of our study was to investigate the relationship between albumin-bilirubin (ALBI) grade and recurrence in patients who underwent TACE sequential ablation. We developed and validated a nomogram to predict low levels of ALBI patients’ recurrence.Patients and Methods: A total of 880 patients undergoing TACE combined ablation at Beijing Youan Hospital from January 2014 to December 2021 were retrospectively enrolled, including 415 patients with L-ALBI (≤-2.6) and 465 patients with high levels (>-2.6) of ALBI (H-ALBI). L-ALBI patients were randomized in a 7:3 ratio into the training cohort (N=289) and validation cohort (N=126). Multivariate Cox regression followed by random survival forest was carried out to identify independent risk factors for prediction nomogram construction. An examination of nomogram accuracy was performed using the C-index, receiver operating characteristic (ROC), calibration curves, and decision curve analysis (DCA) curves. According to the nomogram, the patients were divided into low-risk, intermediate-risk, and high-risk groups. Kaplan-Meier (KM) curves were applied to compare the difference in recurrence-free survival (RFS) among the three groups.Results: The median RFS in L-ALBI patients was significantly longer than the H-ALBI patients (40.8m vs 20.1m, HR:1.71, 95% CI:1.44– 2.04, P< 0.0001). The nomogram was composed of five variables, such as age, Barcelona Clinic Liver Cancer (BCLC) stage, globulin, gamma-glutamyl transferase to lymphocyte ratio (GLR), and international normalized ratio (INR). The C-index (0.722 and 0.731) and 1-, 3-, and 5-year AUCs (0.725, 0.803, 0.870, and 0.764, 0.816, 0.798) of the training and validation cohorts proved the good predictive performance of the nomogram. Calibration curves and DCA curves demonstrated good consistency and good clinical utility. There were significant differences in RFS between the low-risk, intermediate-risk, and high-risk groups (P< 0.0001).Conclusion: L-ALBI Patients who underwent TACE combined ablation had better recurrence-free survival than patients with H-ALBI. The nomogram developed and validated in our study had good predictive ability in recurrence for L-ALBI patients.Keywords: hepatocellular carcinoma, HCC, ablation, nomogram, recurrence, albumin-bilirubin, ALBI

Kangping Hui,1,&ast; Chengying Hong,2,&ast; Yihan Xiong,3 Jinquan Xia,4 Wei Huang,5 Andi Xia,2 Shunyao Xu,2 Yuting Chen,2 Zhongwei Zhang,6 Huaisheng Chen2 1The Second Clinical Medical College, Jinan University, Shenzhen, Guangdong Province, People’s Republic of China; 2Department of Critical Care Medicine, Shenzhen People’s Hospital, Second Clinical Medical College of Jinan University, First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, Guangdong Province, People’s Republic of China; 3Neurology Department, Shenzhen People’s Hospital, Second Clinical Medical College of Jinan University, First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, Guangdong Province, People’s Republic of China; 4Department of Clinical Medical Research Center, the Second Clinical Medical College, Jinan University (Shenzhen People’s Hospital), the First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, Guangdong Province, People’s Republic of China; 5Department of Clinical Microbiology, Shenzhen People’s Hospital, Second Clinical Medical College of Jinan University, First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, Guangdong Province, People’s Republic of China; 6Department of Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Huaisheng Chen, Department of Critical Care Medicine, Shenzhen People’s Hospital, Second Clinical Medical College of Jinan University, First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, Guangdong Province, People’s Republic of China, Email sunshinic@hotmail.com Zhongwei Zhang, Department of Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China, Email 2422708196@qq.comIntroduction: This study aims to establish a comprehensive, multi-level approach for tackling tropical diseases by proactively anticipating and managing Persistent Inflammation, Immunosuppression, and Catabolism Syndrome (PICS) within the initial 14 days of Intensive Care Unit (ICU) admission. The primary objective is to amalgamate a diverse array of indicators and pathogenic microbial data to pinpoint pivotal predictive variables, enabling effective intervention specifically tailored to the context of tropical diseases.Methods: A focused analysis was conducted on 1733 patients admitted to the ICU between December 2016 and July 2019. Utilizing the Least Absolute Shrinkage and Selection Operator (LASSO) regression, disease severity and laboratory indices were scrutinized. The identified variables served as the foundation for constructing a predictive model designed to forecast the occurrence of PICS.Results: Among the subjects, 13.79% met the diagnostic criteria for PICS, correlating with a mortality rate of 38.08%. Key variables, including red-cell distribution width coefficient of variation (RDW-CV), hemofiltration (HF), mechanical ventilation (MV), Norepinephrine (NE), lactic acidosis, and multiple-drug resistant bacteria (MDR) infection, were identified through LASSO regression. The resulting predictive model exhibited a robust performance with an Area Under the Curve (AUC) of 0.828, an accuracy of 0.862, and a specificity of 0.977. Subsequent validation in an independent cohort yielded an AUC of 0.848.Discussion: The acquisition of RDW-CV, HF requirement, MV requirement, NE requirement, lactic acidosis, and MDR upon ICU admission emerges as a pivotal factor for prognosticating PICS onset in the context of tropical diseases. This study highlights the potential for significant improvements in clinical outcomes through the implementation of timely and targeted interventions tailored specifically to the challenges posed by tropical diseases.Keywords: sepsis, persistent inflammation immunosuppression catabolism syndrome, LASSO regression, mortality, predictive model

Hui Liu,1,2 Xuan Xu,3 Ji Li,3 Zheyu Liu,1 Yuwen Xiong,1 Mengli Yue,4 Pi Liu1 1Department of Gastroenterology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, People’s Republic of China; 2Gastroenterology Institute of Jiangxi Province, Nanchang, People’s Republic of China; 3Department of Gastroenterology, The People’s Hospital of Longhua, Shenzhen, People’s Republic of China; 4Affiliated Longhua People’s Hospital, The Third School of Clinical Medicine, Southern Medical University, Shenzhen, People’s Republic of ChinaCorrespondence: Pi Liu, Department of Gastroenterology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, People’s Republic of China, Tel +86-13507913736, Email liupi126@sina.comPurpose: Capillary leak syndrome (CLS) is an intermediary phase between severe acute pancreatitis (SAP) and multiple organ failure. As a result, CLS is of clinical importance for enhancing the prognosis of SAP. Plakophilin2 (PKP2), an essential constituent of desmosomes, plays a critical role in promoting connections between epithelial cells. However, the function and mechanism of PKP2 in CLS in SAP are not clear at present.Methods: We detected the expression of PKP2 in mice pancreatic tissue by transcriptome sequencing and bioinformatics analysis. PKP2 was overexpressed and knocked down to assess its influence on cell permeability, the cytoskeleton, tight junction molecules, cell adhesion junction molecules, and associated pathways.Results: PKP2 expression was increased in the pancreatic tissues of SAP mice and human umbilical vein endothelial cells (HUVECs) after lipopolysaccharide (LPS) stimulation. PKP2 overexpression not only reduced endothelial cell permeability but also improved cytoskeleton relaxation in response to acute inflammatory stimulation. PKP2 overexpression increased levels of ZO-1, occludin, claudin1, β-catenin, and connexin43. The overexpression of PKP2 in LPS-induced HUVECs counteracted the inhibitory effect of SB203580 (a p38/MAPK signaling pathway inhibitor) on the p38/MAPK signaling pathway, thereby restoring the levels of ZO-1, β-catenin, and claudin1. Additionally, PKP2 suppression eliminated the enhanced levels of ZO-1, β-catenin, occludin, and claudin1 induced by dehydrocorydaline. We predicted that the upstream transcription factor PPARγregulates PKP2 expression, and our findings demonstrate that the PPARγactivator rosiglitazone significantly upregulates PKP2, whereas its antagonist GW9662 down-regulates PKP2. Administration of rosiglitazone significantly reduced the increase in HUVECs permeability stimulated by LPS. Conversely, PKP2 overexpression counteracted the GW9662-induced reduction in ZO-1, phosphorylated p38/p38, and claudin1.Conclusion: The activation of the p38/MAPK signaling pathway by PKP2 mitigates CLS in SAP. PPARγactivator rosiglitazone can up-regulate PKP2. Overall, directing efforts toward PKP2 could prove to be a feasible treatment approach for effectively managing CLS in SAP. Keywords: severe acute pancreatitis, plakophilin2, capillary leak syndrome, tight junction, p38/MAPK signaling pathway

Wenying Qiao,1– 3,&ast; Yiqi Xiong,1,&ast; Kang Li,4 Ronghua Jin,2,3 Yonghong Zhang1,5 1Interventional Therapy Center for Oncology, Beijing You’an Hospital, Capital Medical University, Beijing, 100069, People’s Republic of China; 2National Center for Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, People’s Republic of China; 3Changping Laboratory, Beijing, 102206, People’s Republic of China; 4Research Center for Biomedical Resources, Beijing You’an Hospital, Capital Medical University, Beijing, 100069, People’s Republic of China; 5Beijing Research Center for Respiratory Infectious Diseases, Beijing, 100006, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yonghong Zhang, Interventional Therapy Center for Oncology, Beijing You’an Hospital, Capital Medical University, 8 Xitoutiao, Youanmenwai Street, Fengtai District, Beijing, People’s Republic of China, Tel +86-13810108505, Email zhangyh@ccmu.edu.cn Ronghua Jin, National Center for Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, 8 Jingshundong Street, Chaoyang District, Beijing, People’s Republic of China, Tel +86-13811611118, Email ronghuajin@ccmu.edu.cnPurpose: We explored the role of tumor size and number in the prognosis of HCC patients who underwent ablation and created a nomogram based on machine learning to predict the recurrence.Patients and Methods: A total of 990 HCC patients who underwent transcatheter arterial chemoembolization (TACE) combined ablation at Beijing Youan Hospital from January 2014 to December 2021 were prospectively enrolled, including 478 patients with single small HCC (S-S), 209 patients with single large (≥ 30mm) HCC (S-L), 182 patients with multiple small HCC (M-S), and 121 patients with multiple large HCC (M-L). S-S patients were randomized in a 7:3 ratio into the training cohort (N=334) and the validation cohort (N=144). Lasso-Cox regression analysis was carried out to identify independent risk factors, which were used to construct a nomogram. The performance of the nomogram was evaluated by C-index, receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) curves. Patients in the training and validation cohorts were divided into low-risk, intermediate-risk, and high-risk groups based on the risk scores of the nomogram.Results: The median recurrence-free survival (mRFS) in S-S patients was significantly longer than the S-L, M-S, and S-L patients (P< 0.0001). The content of the nomogram includes age, monocyte-to-lymphocyte (MLR), gamma-glutamyl transferase-to-lymphocyte (GLR), International normalized ratio (INR), and Erythrocyte (RBC). The C-index (0.704 and 0.71) and 1-, 3-, and 5-year AUCs (0.726, 0.800, 0.780, and 0.752, 0.761, 0.760) of the training and validation cohorts proved the excellent predictive performance of the nomogram. Calibration curves the DCA curves showed that the nomogram had good consistency and clinical utility. There were apparent variances in RFS between the low-risk, intermediate-risk, and high-risk groups (P< 0.0001).Conclusion: S-S patients who underwent ablation had the best prognosis. The nomogram developed and validated in the study had good predictive ability for S-S patients.Keywords: hepatocellular carcinoma, HCC, transcatheter arterial chemoembolization, TACE, ablation, nomogram, recurrence

Ruonan Zhang, Yiying Xiong, Linyi Zhang, Lin Liu Department of Hematology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Lin Liu, Email liulin@cqmu.edu.cnPurpose: To investigate the clinical characteristics, etiology, and risk factors of bacterial bloodstream infection (BSI) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. This study also aimed to provide a clinical basis for early identification of high-risk patients and optimization of empirical antimicrobial treatment.Patients and Methods: This is a retrospective study of clinical data during agranulocytosis from 331 patients with hematological malignancies who underwent allo-HSCT at our institute between January 2016 and December 2022. The incidence, distribution and drug resistance patterns, and the risk factors of BSI were analyzed.Results: Among the 331 HSCT patients, 250 had febrile neutropenia and 45 cases were found to have BSI. The incidence of BSI in patients with agranulocytosis fever was 18% (45/250). A total of 48 pathogens were isolated during BSI episodes, gram-negative bacteria (GNB) accounted for 70.8% (34/48), gram-positive bacteria (GPB) for 29.2% (14/48). Multivariate analysis revealed that ≥grade 2 acute graft-versus-host disease (aGVHD) and previous BSI within 6 months before HSCT were independently associated with an increased occurrence of BSI. Coagulase-negative staphylococci (CoNS) and Escherichia coli were the most commonly isolated GPB and GNB, respectively. A total of 32 GNB were tested for drug susceptibility, the detection rate of carbapenem-resistant Enterobacteriaceae (CRE) was 12.5% (4/32), and extended-spectrum β-lactamase (ESBL) accounted for 56.3% (18/32).Conclusion: BSIs are still a common and severe complication after allo-HSCT. In our center, BSIs in allo-HSCT patients are dominated by gram-negative bacteria and the resistance rate to carbapenem drugs is high. Risk factors for BSI during agranulocytosis were previous BSI within 6 months before HSCT and ≥grade 2 aGVHD.Keywords: allogeneic hematopoietic stem cell transplantation, bloodstream infection, pathogenic bacteria, antibiotic resistance patterns, risk factors

Xusheng Gao, Caihong Ding, Dan Xie, Qing Wang, Peipei Jiang, Yuyu Wang, Yu Xiong Department of Tuberculosis, Shandong Public Health Clinical Center, Shandong University, Jinan, Shandong, People’s Republic of ChinaCorrespondence: Yu Xiong, Department of Tuberculosis, Shandong Public Health Clinical Center, Shandong University, No. 11, Lieshishan East Road, Licheng District, Jinan, Shandong, People’s Republic of China, Tel +8615589995880, Email yiyiruguo1@163.comBackground: In recent decades, there has been a substantial surge in the incidence of non-tuberculous Mycobacteria (NTM) infections. However, the diagnosis and management of NTM globally present significant challenges, particularly in cases involving Mycobacterium abscessus complex (MABC) infection where effective therapeutic options are limited.Case Presentation: We reported a 38-year-old female patient who was infected with MABC of skin due to “beauty needle” at a beauty salon, with mass on both cheeks, accompanied by redness, and pain, and some of them was ulcered and effused. Puncture pumping pus from bilateral cheek mass for many times, rinsed with “metronidazole”, and oral “cephalosporin” treatment did not work. Therefore, she came to our hospital. MABC was detected in abscess paracentesis pus by nucleic acid mass spectrometry, and was proved by the cultured result of the pus. Thus, the patient was diagnosed as skin MABC infection, and anti-NTM treatment was taken. However, adverse reactions such as tinnitus, hepatotoxicity and neurovirulence occurred during the initial treatment. After adjusting to the contezolid-containing regimen, these adverse reactions improved. After nearly 6 months of treatment, the cheek mass was gradually reduced and the skin ruptures were gradually healed. Follow-up for 10 months showed that the patient’s facial symptoms were significantly improved, and no drug-related adverse reactions happened.Conclusion: This was the first successful case of multiple drug resistance MABC infection of skin treated with contezolid-containing antibiotic management strategies, which exhibited remarkable efficacy and good safety in this intractable disease.Keywords: Mycobacterium abscessus complex, antibiotic therapy, contezolid, Case report

Yuan Ma,1,2 Li Li,1 Li Yu,1 Wei He,1 Ling Yi,1 Yuxin Tang,1 Jijie Li,1 Zhigang Zhong,3 Meixian Wang,4 Shiyao Huang,5,6 Yiquan Xiong,5,6 Pei Xiao,7 Yuxiang Huang1 1Department of Medical Record Management, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 2Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, Sichuan, People’s Republic of China; 3Department of Prevention, Office of Cancer Prevention and Treatment, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Cancer Hospital Affiliate to University of Electronic Science and Technology of China, Chengdu, Sichuan, People’s Republic of China; 4National Center for Birth Defects Monitoring, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 5Chinese Evidence-Based Medicine Center, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 6NMPA Key Laboratory for Real World Data Research and Evaluation in Hainan, Chengdu, Sichuan, People’s Republic of China; 7Medical Insurance Office, West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of ChinaCorrespondence: Yuxiang Huang, Email 3593213104@qq.comBackground: Uterine leiomyoma (UL) is one of the most common benign tumors in women, and its incidence is gradually increasing in China. The clinical complications of UL have a negative impact on women’s health, and the cost of treatment poses a significant burden on patients. Diagnosis-related groups (DRG) are internationally recognized as advanced healthcare payment management methods that can effectively reduce costs. However, there are variations in the design and grouping rules of DRG policies across different regions. Therefore, this study aims to analyze the factors influencing the hospitalization costs of patients with UL and optimize the design of DRG grouping schemes to provide insights for the development of localized DRG grouping policies.Methods: The Mann–Whitney U-test or the Kruskal–Wallis H-test was employed for univariate analysis, and multiple stepwise linear regression analysis was utilized to identify the primary influencing factors of hospitalization costs for UL. Case combination classification was conducted using the exhaustive chi-square automatic interactive detection (E-CHAID) algorithm within a decision tree framework.Results: Age, occupation, number of hospitalizations, type of medical insurance, Transfer to other departments, length of stay (LOS), type of UL, admission condition, comorbidities and complications, type of primary procedure, other types of surgical procedures, and discharge method had a significant impact on hospitalization costs (P< 0.05). Among them, the type of primary procedure, other types of surgical procedures, and LOS were the main factors influencing hospitalization costs. By incorporating the type of primary procedure, other types of surgical procedures, and LOS into the decision tree model, patients were divided into 11 DRG combinations.Conclusion: Hospitalization costs for UL are mainly related to the type of primary procedure, other types of surgical procedures, and LOS. The DRG case combinations of UL based on E-CHAID algorithm are scientific and reasonable.Keywords: uterine leiomyoma, diagnosis-related groups, decision tree

Yuzhu Qu,1– 3,&ast; Ying Peng,4,&ast; Yan Xiong,5 Xiaohui Dong,3 Peihong Ma,6 Shirui Cheng2,3 1Post-Doctoral Scientific Research Workstation of Affiliated Sport Hospital, Chengdu Sport University, Chengdu, Sichuan, People’s Republic of China; 2Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, People’s Republic of China; 3Acupuncture and Brain Science Research Center, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, People’s Republic of China; 4Medical Aesthetics Department, Affiliated Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, People’s Republic of China; 5Department of Osteoporosis, West China Fourth Hospital Sichuan University, Chengdu, Sichuan, People’s Republic of China; 6Medical Technology School, Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shirui Cheng, Chengdu University of Traditional Chinese Medicine, 1166 &num; Liutai Avenue, Chengdu, Sichuan, 611137, People’s Republic of China, Email csr1190@163.com Peihong Ma, Tianjin University of Traditional Chinese Medicine, 10 &num; Poyanghu Road, Tuanpo Xincheng West District, Jinghai District, Tianjin, 301617, People’s Republic of China, Email acu_madai@163.comAbstract: Acupuncture has been widely applied for treating knee osteoarthritis (KOA). Numerous studies have found that acupuncture can effectively alleviate KOA symptoms. With the advancement of neuroimaging techniques, integrating neuroimaging with in-depth investigations of acupuncture mechanisms has emerged as a hot topic in traditional Chinese medical neuroscience research. This review aimed to analyze the study design and main findings from neuroimaging studies of acupuncture-related therapy for KOA to provide a reference for future research. Original studies were sourced from English databases (PubMed, Embase, and Cochrane Library) and Chinese databases (Chinese National Knowledge Infrastructure, Chinese Biomedical Literature Database, the Chongqing VIP database, and Wanfang database). As a result, thirteen articles were ultimately included in this review. Functional magnetic resonance imaging was the most frequently used neuroimaging technique to explore cerebral responses to acupuncture-related therapy for KOA. Findings suggested that acupuncture-related therapy could regulate some brain regions in patients with KOA. Specifically, for acupuncture, it showed that the medial pain pathway and the limbic system were involved in the regulation of KOA. Meanwhile, moxibustion induced a wide range of functional activity throughout the entire brain.Keywords: acupuncture-related therapy, knee osteoarthritis, cerebral response, neuroimaging study

Chengying Hong,1 Yihan Xiong,2 Jinquan Xia,3 Wei Huang,4 Andi Xia,1 Shunyao Xu,1 Yuting Chen,1 Zhikun Xu,1 Huaisheng Chen,1 Zhongwei Zhang5 1Department of Critical Care Medicine, Shenzhen People’s Hospital, Second Clinical Medical College of Jinan University, First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, Guangdong, 518020, People’s Republic of China; 2Neurology Department, Shenzhen People’s Hospital, Second Clinical Medical College of Jinan University, First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, Guangdong, 518020, People’s Republic of China; 3Department of Clinical Medical Research Center, The Second Clinical Medical College, Jinan University (Shenzhen People’s Hospital), The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, Guangdong, 518020, People’s Republic of China; 4Department of Clinical Microbiology, Shenzhen People’s Hospital, Second Clinical Medical College of Jinan University, First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, Guangdong, 518020, People’s Republic of China; 5Department of Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of ChinaCorrespondence: Huaisheng Chen, Department of Critical Care Medicine, Shenzhen People’s Hospital, Second Clinical Medical College of Jinan University, First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, Guangdong, 518020, People’s Republic of China, Email sunshinic@hotmail.com Zhongwei Zhang, Department of Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of China, Email 716461751@qq.comObjective: The objective of this study was to utilize LASSO regression (Least Absolute Shrinkage and Selection Operator Regression) to identify key variables in septic patients and develop a predictive model for intensive care unit (ICU) mortality.Methods: We conducted a cohort consisting of septic patients admitted to the ICU between December 2016 and July 2019. The disease severity and laboratory index were analyzed using LASSO regression. The selected variables were then used to develop a model for predicting ICU mortality. AUCs of ROCs were applied to assess the prediction model, and the accuracy, sensitivity and specificity were calculated. Calibration were also used to assess the actual and predicted values of the predictive model.Results: A total of 1733 septic patients were included, among of whom 382 (22%) died during ICU stay. Ten variables, namely mechanical ventilation (MV) requirement, hemofiltration (HF) requirement, norepinephrine (NE) requirement, septicemia, multiple drug-resistance infection (MDR), thrombocytopenia, hematocrit, red-cell deviation width coefficient of variation (RDW-CV), C-reactive protein (CRP), and antithrombin (AT) III, showed the strongest association with sepsis-related mortality according to LASSO regression. When these variables were combined into a predictive model, the area under the curve (AUC) was found to be 0.801. The AUC of the validation group was 0.791. The specificity of the model was as high as 0.953. Within the probability range of 0.25 to 0.90, the predictive performance of the model surpassed that of individual predictors within the cohort.Conclusion: Our findings suggest that a predictive model incorporating the variables of MV requirement, HF requirement, NE requirement, septicemia, MDR, thrombocytopenia, HCT, RDW-CV, CRP, and AT III exhibiting an 80% likelihood of predicting ICU mortality in sepsis and demonstrates high accuracy.Keywords: sepsis, mortality, LASSO regression, predictive model, ICU

Youli Jiang, Yao Xiong, Yue Chi, Fu Lin, Qingshi Zhao, Yanfeng Li Department of Neurology, People’s Hospital of Longhua, Shenzhen, 518109, People’s Republic of ChinaCorrespondence: Qingshi Zhao; Yanfeng Li, Email 66327285@qq.com; 308114251@qq.comPurpose: Timely medical attention is crucial for patients with Acute Ischemic Stroke (AIS), as delays can significantly impact therapeutic outcomes. These delays are influenced by a combination of socio-cultural, educational, and clinical factors.Patients and Methods: An in-depth analysis was conducted to assess the prevalence and median duration of healthcare-seeking delays in AIS patients. The study specifically investigated the independent impacts of sociocultural and clinical determinants on these delays, with a focus on immigrant status, gender disparities, and educational levels. Multivariate regression analysis was employed to identify these independent effects while controlling for potential confounding factors.Results: Among 1419 AIS patients, 82.52% (n = 1171) experienced delays exceeding 2 hours from symptom onset of symptoms to hospital arrival. The median delay was 12.3 hours. Immigrant populations encountering longer delays compared to native groups. Younger males (< 45 years) and elderly females were more prone to delay in healthcare-seeking. Identified independent risk factors for delay included male gender (OR = 1.65 [95% CI:1.14− 2.48]), self-acknowledged diabetes (OR = 2.50 [95% CI:1.21– 5.17]), small vessel (OR = 2.07 [95% CI:1.27– 3.36]), and wake stroke (OR = 7.04 [95% CI:3.69– 13.44]). Educational background (high school and above), GCS score with 3– 8 points (OR = 0.52 [95% CI:0.09– 0.69]), understanding stroke-related knowledge (OR = 0.26 [95% CI:0.09– 0.44]), conscious disturbance (OR = 0.25 [95% CI:0.10– 0.62]) and limb weakness (OR=0.21[95% CI:0.21– 0.49]) are protective factors for timely treatment.Conclusion: Immigrant populations experienced longer delays from symptom onset to hospital arrival. The crucial roles of education and knowledge about stroke underscore the need for enhanced health literacy campaigns and public awareness, with a targeted focus on younger males and elderly females.Keywords: healthcare-seeking behavior, immigrant population, educational disparity, pre-hospital delay, AIS

Zheyu Liu,1 Huajing Ke,1 Yuwen Xiong,1 Hui Liu,1 Mengli Yue,2 Pi Liu3 1Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 2Affiliated Longhua People’s Hospital, The Third School of Clinical Medicine, Southern Medical University, Shenzhen, People’s Republic of China; 3Department of Gastroenterology, Affiliated Longhua People’s Hospital, Southern Medical University, Shenzhen, People’s Republic of ChinaCorrespondence: Pi Liu, Department of Gastroenterology, Affiliated Longhua People’s Hospital, Southern Medical University, Shenzhen, People’s Republic of China, Tel +86- 13507913736, Email liupi126@sina.comPurpose: Necrotizing pancreatitis (NP) complicated by gastrointestinal fistula is challenging and understudied. As the treatment of necrotizing pancreatitis changed to a step-up strategy, we attempted to evaluate the incidence, risk factors, clinical outcomes and treatment of gastrointestinal fistulas in patients receiving a step-up approach.Methods: Clinical data from 1274 patients with NP from 2014– 2022 were retrospectively analyzed. Multivariable logistic regression analysis was conducted to identify risk factors and propensity score matching (PSM) to explore clinical outcomes in patients with gastrointestinal fistulas.Results: Gastrointestinal fistulas occurred in 8.01% (102/1274) of patients. Of these, 10 were gastric fistulas, 52 were duodenal fistulas, 14 were jejunal or ileal fistulas and 41 were colonic fistulas. Low albumin on admission (OR, 0.936), higher CTSI (OR, 1.143) and invasive intervention prior to diagnosis of gastrointestinal fistula (OR, 5.84) were independent risk factors for the occurrence of gastrointestinal fistula, and early enteral nutrition (OR, 0.191) was a protective factor. Patients who developed a gastrointestinal fistula were in a worse condition on admission and had a poorer clinical outcome (p< 0.05). After PSM, both groups of patients had similar baseline information and clinical characteristics at admission. The development of gastrointestinal fistulas resulted in new-onset persistent organ failure, increased open surgery, prolonged parenteral nutrition and hospitalization, but not increased mortality. The majority of patients received only conservative treatment and minimally invasive interventions, with 7 patients (11.3%) receiving surgery for upper gastrointestinal fistulas and 11 patients (26.9%) for colonic fistulas.Conclusion: Gastrointestinal fistulas occurred in 8.01% of NP patients. Independent risk factors were low albumin, high CTSI and early intervention, while early enteral nutrition was a protective factor. After PSM, gastrointestinal fistulas resulted in an increased proportion of NP patients receiving open surgery and prolonged hospitalization. The majority of patients with gastrointestinal fistulas treated with step-up therapy could avoid surgery.Keywords: necrotizing pancreatitis, a step-up approach, gastrointestinal fistula, minimally invasive step-up intervention

Yu Hu,1– 3 Hui Guo,1– 3 Shuai Cheng,1– 3 Junpeng Sun,2,4 Jiaqun Du,2,4 Xiaobang Liu,2,4 Ying Xiong,5 Liqing Chen,6 Chang Liu,3,6 Chao Wu,2,4 He Tian1– 3 1School of Basic Medicine, Jinzhou Medical University, Jinzhou, Liaoning, 121001, People’s Republic of China; 2Liaoning Provincial Collaborative Innovation Center for Medical Testing and Drug Research, Jinzhou Medical University, Jinzhou, Liaoning, 121001, People’s Republic of China; 3Key Laboratory of Medical Tissue Engineering of Liaoning Province, Jinzhou Medical University, Jinzhou, Liaoning, 121001, People’s Republic of China; 4Pharmacy School, Jinzhou Medical University, Jinzhou, Liaoning, 121001, People’s Republic of China; 5Laboratoire Catalyse et Spectrochimie (LCS), Normandie Université, ENSICAEN, UNICAEN, CNRS, Caen, 14050, France; 6Department of Endocrinology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, 121000, People’s Republic of ChinaCorrespondence: He Tian; Chao Wu, Email tianhe@jzmu.edu.cn; wuchao@jzmu.edu.cnBackground: Oxidative stress induced reactive oxygen species (ROS) and aggregation of amyloid β (Aβ) in the nervous system are significant contributors to Alzheimer’s disease (AD). Cerium dioxide and manganese oxide are known as to be effective and recyclable ROS scavengers with high efficiency in neuroprotection.Methods: A hollow-structured manganese-doped cerium dioxide nanoparticle (LMC) was synthesized for loading Resveratrol (LMC-RES). The LMC-RES were characterized by TEM, DLS, Zeta potential, and X-ray energy spectrum analysis. We also tested the biocompatibility of LMC-RES and the ability of LMC-RES to cross the blood-brain barrier (BBB). The antioxidant effects of LMC-RES were detected by SH-SY5Y cells. Small animal live imaging was used to detect the distribution of LMC-RES in the brain tissue of AD mice. The cognitive abilities of mice were tested by water maze and nesting experiments. The effects of LMC-RES in reducing oxidative stress and protecting neurons was also explored by histological analysis.Results: The results showed that LMC-RES had good sustained release effect and biocompatibility. The drug release rate of LMC-RES at 24 hours was 80.9 ± 2.25%. Meanwhile, LMC-RES could cross the BBB and enrich in neurons to exert antioxidant effects. In Aβ-induced SH-SY5Y cells, LMC-RES could inhibits oxidative stress through the Nrf-2/HO-1 signaling pathway. In AD model mice, LMC-RES was able to reduce ROS levels, inhibit Aβ-induced neurotoxicity, and protect neurons and significantly improve cognitive deficits of AD mice after drug administration.Conclusion: LMC-RES can effectively across the BBB, reduce oxidative stress, inhibit Aβ aggregation, and promote the recovery of neurological function.Keywords: cerium dioxide nanoparticles, manganese, oxidative stress, resveratrol, Alzheimer’s disease

Yujun Xiong,1,&ast; Haoqi Yan,2,&ast; Lang Qu,3 Shuqi Wang,4 Xiangda Meng,5 Xingyun Zhu,6 Pan Zhang,1 Su Yuan,2 Jihua Shi1 1Department of Gastroenterology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 2Department of Anesthesiology, Fuwai Hospital, National Center of Cardiovascular Diseases, Chinese Academy of Medical Sciences; Peking Union Medical College, Beijing, 100037, People’s Republic of China; 3Department of Anesthesiology, Shanghai General Hospital, Shanghai, People’s Republic of China; 4Department of Otolaryngology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, People’s Republic of China; 5Department of Neurosurgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, People’s Republic of China; 6Department of Endocrinology, Beijing Jishuitan Hospital, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Su Yuan, Department of Anesthesiology, Fuwai Hospital, Chinese Academy of Medical Sciences; Peking Union Medical College, Xicheng District, Beijing, People’s Republic of China, Email fuwaiys@126.com Jihua Shi, Department of Gastroenterology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, 100370, People’s Republic of China, Email shijihua1981@sina.comBackground: Gastrointestinal (GI) endoscopy becomes more and more common now in order to diagnose and treat GI diseases, and anesthesia/sedation plays an important role. We aim to discuss the developmental trends and evaluate the research hotspots using bibliometric methods for GI endoscopy anesthesia/sedation in the past two decades.Methods: The original and review articles published from 2001 to December 2022 related to GI endoscopy anesthesia/sedation were extracted from the Web of Science database. Four different softwares (CiteSpace, VOSviewer, and Bibliometrix, Online Analysis Platform of Literature Metrology (Bibliometric)) were used for this comprehensive analysis.Results: According to our retrieval strategy, we found a total of 3154 related literatures. Original research articles were 2855, and reviews were 299. There has been a substantial increase in the research on GI endoscopy anesthesia/sedation in recent 22 years. These publications have been cited 66,418 times, with a mean of 21.04 citations per publication. The US maintained a leading position in global research, with the largest number of publications (29.94%), and China ranked second (19.92%). Keyword burst and concurrence showed that conscious sedation, colonoscopy and midazolam were the most frequently occurring keywords.Conclusion: Our research found that GI endoscopy anesthesia/sedation was in a period of rapid development and demonstrated the improvement of medical instruments and surgical options that had significantly contributed to the field of GI endoscopy anesthesia/sedation. The US dominates this field, and the selection and dosage of sedative regimens have always been the foci of disease research to improve comfort and safety, while adverse events and risks arouse attention gradually. In the past 20 years, hotspots mainly focus on upper gastrointestinal endoscopy, gastroscopy, and esophagogastroduodenoscopy. These data would provide future directions for clinicians and researchers regarding GI endoscopy anesthesia/sedation.Keywords: gastrointestinal endoscopy anesthesia, sedation, bibliometric analysis, CiteSpace, VOSviewer

Chenxi Liao,1,&ast; Siyu Tao,1,&ast; Yan Xiong,2,&ast; Jingyang Dai,3 Yu Bai,4 Xue Wang,1 Yuan Li,5 Ping Wu1 1Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 2Department of Osteoporosis, Huaxi Fourth Hospital, Sichuan University, Chengdu, People’s Republic of China; 3Department of Traditional Chinese Medicine, Chengdu Fifth People’s Hospital, Chengdu, People’s Republic of China; 4Department of Traditional Chinese Medicine, Chengdu Second People’s Hospital, Chengdu, People’s Republic of China; 5Department of Rheumatology, The Affiliated Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ping Wu, Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, People’s Republic of China, Email wuping_33@163.comPurpose: To investigate the effects of moxibustion in relieving pain, and other clinical symptoms for patients with rheumatoid arthritis (RA), and explore the potential mechanism of moxibustion treatment for RA.Patients and Methods: Seventy qualified RA patients were randomly assigned in a 1:1 ratio to the moxibustion group or the routine group. The routine group only took oral methotrexate tablets and folic acid tablets. The moxibustion group was treated with moxibustion based on oral pharmaceutical. Moxibustion was performed two times weekly for 8 weeks, a total of 16 sessions. Patients scored their pain on a visual analog scale (VAS). The American College of Rheumatology improvement criteria of 20%, 50% and 70% (ACR20, ACR50 and ACR70) after treatment were investigated. Clinical symptoms, a disease activity score using 28 joint counts (DAS28), simplified disease activity index (SDAI), clinical disease activity index (CDAI), health assessment questionnaire (HAQ), interleukin 1β (IL-1β), tumor necrosis factor-alpha (TNF-α), and vascular endothelial growth factor (VEGF) of RA patients were analyzed before and after treatment.Results: After treatment, the VAS scores, tender and swollen joint counts, morning stiffness scores, disease activity scores (DAS28, SDAI, CDAI), HAQ scores in the two groups were both improved, and the effects of moxibustion group were more obvious (P < 0.05). The ACR20 and ACR50 of the moxibustion group were greater than that of the routine group (P < 0.05), no significant difference of the ACR70 existed between the two groups (P > 0.05). In addition, the decreases of IL-1β, TNF-α, VEGF of the moxibustion group were better than that of the routine group (P < 0.05).Conclusion: Moxibustion could effectively relieve pain, ameliorate the clinical symptoms, and decrease the disease activity of RA. The potential mechanism may be the decrease in the level of serum inflammatory factors.Keywords: moxibustion, rheumatoid arthritis, pain, inflammatory factor

Xiang Zhao,1 Junfang Huang,1 Lina Wang,1 Cuiyan Guo,1 JiTing Di,2 Yan Xiong,2 Weiming Huang,3 Jing Ma,1 Guangfa Wang1 1Department of Respiratory and Critical Care Medicine, Peking University First Hospital, Beijing, People’s Republic of China; 2Department of Pathology, Peking University First Hospital, Beijing, People’s Republic of China; 3Department of Thoracic Surgery, Peking University First Hospital, Beijing, People’s Republic of ChinaCorrespondence: Junfang Huang, Department of Respiratory and Critical Care Medicine, Peking University First Hospital, Beijing, 100034, People’s Republic of China, Tel +86 13466716682, Email fang198608@126.comAbstract: Pulmonary actinomycosis (PA) is an uncommon, asymptomatic, and frequently misdiagnosed pulmonary infectious illness. Our patient remained undiagnosed despite extensive regular and invasive testing, significant intermittent hemoptysis, and repeated bronchial artery embolization. Ultimately, a left lower lobectomy was performed via video-assisted thoracoscopic surgery, and a histopathological examination revealed an actinomycete infection.Keywords: actinomycosis, hemoptysis, bronchoscopy

Wenlong Jiang, Yunzhi Xiong, Fangzhou Cheng Cardiovascular, Shenzhen Yantian District People’s Hospital, Shenzhen, People’s Republic of ChinaCorrespondence: Wenlong Jiang, Cardiovascular, Shenzhen Yantian District People’s Hospital, Wutong Road 2010 Yantian District, Shenzhen, 518081, People’s Republic of China, Tel +86 0755-25215050, Email 776508319@qq.comAbstract: Hysteroscopic local endometrial resection and curettage are common surgical procedures. Postoperative arterial thromboembolism is rare. However, coronary and renal embolism after the procedure has never been reported in the literature, so far. We report a 50-year-old woman who developed arterial thromboembolism 4 hours after local endometrial resection and curettage. Thrombus disappeared after anticoagulant therapy was started as soon as possible. How do strange clots form and by what route do they occur in the arterial system?Keywords: embolism, uterine curettage, coronary artery, renal artery

Yi Xiong,1,2,&ast; Yani Luo,2,&ast; Ting Yuwen,2,&ast; Jiana Li,2 Rongchang Chen,3 Fei Shi1 1Emergency Department, Shenzhen People’s Hospital, Shenzhen, Guangdong Province, People’s Republic of China; 2Biomedical Research Institute, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, Guangdong Province, People’s Republic of China; 3Key Laboratory of Shenzhen Respiratory Diseases, Institute of Shenzhen Respiratory Diseases, Shenzhen People’s Hospital, Shenzhen, Guangdong Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Rongchang Chen, Email chenrc@vip.163.com Fei Shi, Email shi.fei@szhospital.comPurpose: Airway remodeling is a significant pathological change of asthma. This study aimed to detect differentially expressed microRNAs in the serum of asthma patients and airway smooth muscle cells (ASMCs) of asthmatic mice, exploring their role in the airway remodeling of asthma.Methods: The differentially expressed microRNAs in the serum of mild and moderate-severe asthma patients compared to healthy subjects were revealed using the “limma” package. Gene Ontology (GO) analysis was used to annotate the functions of microRNA target genes. The relative expressions of miR-107 (miR-107-3p in mice sharing the same sequence) in the primary airway smooth muscle cells (ASMCs) of the asthma mice model were tested by RT-qPCR. Cyclin-dependent kinases 6 (Cdk6), a target gene of miR-107, was predicted by algorithms and validated by dual-luciferase reporter assay and Western blot. The roles of miR-107, Cdk6, and protein Retinoblastoma (Rb) in ASMCs were examined by transwell assay and EDU KIT in vitro.Results: The expression of miR-107 was down-regulated in both mild and moderate-severe asthma patients. Intriguingly, the level of miR-107 was also decreased in ASMCs of the asthma mice model. Up-regulating miR-107 suppressed ASMCs’ proliferation by targeting Cdk6 and the phosphorylation level of Rb. Increasing the expression of Cdk6 or suppressing Rb activity abrogated the proliferation inhibition effect of ASMCs induced by miR-107. In addition, miR-107 also inhibits ASMC migration by targeting Cdk6.Conclusion: The expression of miR-107 is down-regulated in serums of asthma patients and ASMCs of asthmatic mice. It plays a critical role in regulating the proliferation and migration of ASMCs via targeting Cdk6.Keywords: asthma, microRNA microarray, airway smooth muscle cells, miR-107, Cdk6

Yiting Du,1,2 Limin Zuo,2 Ying Xiong,1 Xuedong Wang,3 Jun Zou,2 Hong Xu1 1Department of Pediatrics, Key Laboratory of Birth Defects and Related Diseases of Women and Children, West China Second University Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 2Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 611731, People’s Republic of China; 3Key Laboratory of Birth Defects and Related Diseases of Women and Children, West China Second University Hospital, Sichuan University, Chengdu, 610041, People’s Republic of ChinaCorrespondence: Ying Xiong, Department of Pediatrics, Key Laboratory of Birth Defects and Related Diseases of Women and Children, West China Second University Hospital, Sichuan University, Sec. 3 No. 17, South Renmin Road, Chengdu, 610041, People’s Republic of China, Email xiongying20006@163.comBackground: Bronchopulmonary dysplasia (BPD) refers to a chronic lung disease which is commonly observed in preterm infants. It can usually be caused by several pathological processes that endanger the long-term lung development, such as inflammation and immune dysfunction.Methods: In this study, a bioinformatics approach was applied to identify the differentially expressed immune-related genes (DEIRGs). We downloaded the transcriptional profiles (GSE32472 dataset) from the Gene Expression Omnibus (GEO) database and performed gene set enrichment analysis (GSEA). Cell type Identification By Estimating Relative Subsets of RNA Transcripts (CIBERSORT), microenvironment cell populations counter (MCPcounter), and Estimation of STromal and Immune cells in Malignant Tumor tissues using Expression data (ESTIMATE) were used for the analysis of the immune cell infiltration landscape of BPD. A weighted co-expression network was subsequently constructed using weighted gene co-expression network analysis (WGCNA) to screen candidate differentially expressed immune related genes (DEIRGs).Results: GSEA results indicated that immune-related pathways were mainly involved in BPD. Ten significantly different immune cell types were observed between BPD and normal groups. A total of 228 DEGs in the turquoise module were identified, and 31 DEIRGs were further identified. Cluster of the differentiation 8 alpha (CD8A) expression was down-regulated in BPD, and its expression was validated by the GSE25286, GSE25293, GSE99633 datasets and qRT-PCR. In addition, CD8A expression was closely associated with immune cells infiltration, especially T cells CD8 and neutrophil.Conclusion: A distinct immune cell infiltration landscape was found between BPD and normal group. CD8A can be a novel candidate biomarker for BPD, which plays an essential role in the onset and progress of hyperoxia-related BPD via the disruption of immune cell functions.Keywords: bronchopulmonary dysplasia, CD8A, preterm infants, immunocytes infiltrate, hyperoxia

Yongai Xiong,1,2 Tingting Chen,1,2 Lei Chen,1,2 Rongshan Cai1,2 1Key Laboratory of Basic Pharmacology of Guizhou Province and School of Pharmacy, Zunyi Medical University, Zunyi, Guizhou, 563000, People’s Republic of China; 2Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, Guizhou, 563000, People’s Republic of ChinaCorrespondence: Yongai Xiong, Email yaxiong@zmu.edu.cnIntroduction: Radiotherapy and chemotherapy are the fundamental causes of myelosuppression in cancer patients, which usually induce a serious hematopoietic system toxicity, causing the hemocytes and immunity decline of patients. Ziyuglycoside I (ZgI), an active ingredient isolated from traditional Chinese medicine Sanguisorba officinalis L, has been demonstrated to increase the leucocytes and protect hematopoietic stem cells, which is related to its promotion of autophagy in hematopoietic stem cells.Methods: In the present study, we formulated the SH-PEG-NH2-coated gold nanoparticles loading ZgI (ZgI-AuNPs) with a enhanced autophagy promotion in hematopoietic stem cells. ZgI-AuNPs were prepared by HAuCl4-sodium citrate reduction method, and the synthesis of ZgI-AuNPs was validated by XRD, FT-IR, DSC, and TEM findings. Furthermore, the drug loading rate and the release of ZgI were evaluated, and the ZgI-AuNPs’ effects on autophagy and immunofluorescence staining for LC3B were tested. Finally, the effect of ZgI-AuNPs on the autophagy and hematopoietic ability of HSCs in vivo was also carried out.Results: The prepared ZgI-AuNPs have an irregular cubic crystal structure by TEM observation, and the average particle size was 340 ± 16.5 nm determined by DLS. The XRD, FT-IR and DSC detection showed that the ZgI had been well loaded in AuNPs, and the AuNPs can load the ZgI at a content of 160.63 ± 1.35 μg·mg− 1. Meanwhile, the AuNPs can reduce the drug release rate of ZgI. Importantly, the ZgI-AuNPs enhanced autophagy of HSCs both in vitro and in vivo. At the same time, the gold nanoparticles enhance the hematopoietic effect of ZgI on mice HSCs.Conclusion: Our research suggests that SH-PEG-NH2-coated gold nanoparticles loading ZgI has potential application in myelosuppression therapy.Graphical Abstract: Keywords: myelosuppression, HSCS, autophagy, gold nanoparticles, Ziyuglycoside I

Shaozeng Li,1,* Yu Shi,1,* Yulin Xiong,1 Yali Liu2 1Department of Clinical Laboratory, the Fourth Medical Center of PLA General Hospital, Beijing, 100037, People’s Republic of China; 2Department of Clinical Laboratory, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100730, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yali Liu, Email liuyluijk@aliyun.comAbstract: Nocardia is an aerobic actinomycete that causes serious opportunistic infections in immunocompromised individuals. Gene sequencing is the gold standard for pathogenic bacteria diagnosis. This study uses 16S rRNA gene sequencing to diagnose three cases of bone infections caused by Nocardia, including one rare case (N. cyriacigeorgica), and the clinial features, etiological characteristics, treatment, and prognosis of the patients.Keywords: Nocardia, 16S rRNA gene sequencing, bone infection, clinical features

Ping Luo,1 Ying Fan,2 Yusha Xiong,2 Chunlin Zhang,1 Zhiping Yang,1 Fenglan Sun,1 Bing Mei1 1Department of Laboratory Medicine, Jingzhou Hospital Affiliated to Yangtze University, Jingzhou, People’s Republic of China; 2Gongan County Maternal and Child Health Care Hospital, Jingzhou, People’s Republic of ChinaCorrespondence: Bing Mei, Department of Laboratory Medicine, Jingzhou Hospital Affiliated to Yangtze University, Jingzhou, People’s Republic of China, Email meibing008@163.comObjective: To describe the metabolic characteristics of gestational diabetes mellitus (GDM) and assess their effects on perinatal outcomes.Methods: A two-center nested case‒control study was designed, including 192 pregnant women with GDM and 191 pregnant women with normal glucose tolerance (NGT). Serum glucose and insulin concentrations based upon the 75 g oral glucose tolerance test (OGTT) were measured. Several indices were calculated to describe the metabolic characteristics of the subjects. The relationship between glucose metabolism parameters and pregnancy outcomes was evaluated using stepwise linear regression and binary logistic regression.Results: Compared with the NGT group, the GDM group showed significantly higher fasting and postprandial glucose parameters but significantly lower fasting and postprandial insulin responses. Meanwhile, the GDM group had significantly lower HOMA-β, DI and ISIMatsuda but comparable HOMA-IR. The IFG subgroup showed significantly lower FINS/FPG only, while the IGT and IFSG subgroups showed deficiency in both fasting and postprandial insulin response. The IFSG subgroup had the highest glucose parameters and the lowest insulin parameters, as well as significantly lower ISIMatsuda and HOMA-β than the NGT group. FPG had a significant effect on infants’ birth weight, and 1hPG and FINS/FPG had a significant effect on delivery gestational age. AUC-INS, IGI60 and DI were related to premature delivery risk after adjusting for confounders. The IFG subgroup of GDM was 2.319 times more likely to be subject to cesarean section than the NGT group. FPG, FINS/FPG, AUC-GLU, AUC-INS/AUC-GLU and HOMA-β were related to macrosomia risk.Conclusion: Beta cell dysfunction rather than insulin resistance determines the occurrence of GDM in the central Chinese population. Women with predominant insulin secretion defects had a similar risk of adverse perinatal outcomes to women with NGT. Our study provided a basis for the selection of glucose metabolism monitoring indicators useful for the prevention of adverse perinatal outcomes.Keywords: insulin resistance, insulin sensitivity, glucose metabolism, perinatal outcomes, type 2 diabetes mellitus

Jing Li,&ast; Hong Gao,&ast; Yue Xiong,&ast; Ling Wang, Haojie Zhang, Fumei He, Jingxin Zhao, Shuna Liu, Liqian Gao, Ying Guo, Wenbin Deng School of Pharmaceutical Sciences (Shenzhen), Shenzhen Campus of Sun Yat-Sen University, Shenzhen, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ying Guo; Wenbin Deng, Email guoying1226@hotmail.com; dengwb5@mail.sysu.edu.cnBackground: Wound healing of skin is a complicated process. Cutaneous innervation and neurotrophic factors could participate in multiple stages of wound healing. Neurotrophic factors are mainly produced and released by neurons and neural stem cells (NSCs) which could be obtained in large quantities from human-induced pluripotent stem cells (iPSCs) in vitro. However, the potential wound healing effects of NSC secretions, such as exosomes, are unexplored yet.Methods: NSCs-derived exosomes (NSC-exo) and iPSCs-derived exosomes (iPSC-exo) were isolated from the cell culture supernatants by centrifugation, and then quantified and characterized. The effects of these exosomes on the migration of human dermal fibroblasts (HDF) cells and the tube formation of human umbilical vein endothelial cells (HUVECs) were investigated in vitro. And the in vivo wound healing effect of these exosomes were tested on the mouse skin trauma model. Therefore, a dipeptide/hyaluronic acid (Nap-FF/HA) composite hydrogel was used to encapsulate the exosomes as a sustained release carrier. Histological observations were performed to evaluate the wound healing effect of exosomes. Furthermore, the non-labeling proteomic analysis was performed to explore the possible mechanisms of NSC-exo on wound healing.Results: We obtained extracellular vesicles in a bowl-like structure with membranes which meet the general standards of exosomes. NSC-exo showed promotion effect on the migration of HDF cells and the tube formation of HUVECs in vitro. In a mouse skin injury model, NSC-exo enhanced the wound healing and the Nap-FF/HA hydrogel that contained exosomes did so with less drug frequency by sustaining release of exosomes. Further proteomic analysis demonstrated that the carried neurotrophic factors and immunity-related proteins in NSC-exo may play a functional role in wound healing.Conclusion: NSC-exo may enhance wound healing via neurotrophic factors and immunomodulation.Graphical Abstract: Keywords: wound healing, neural stem cells, exosomes, proteomic analysis

Guangshuo Li,1 Chuanying Wang,1 Shang Wang,1,2 Yahui Hao,2 Yunyun Xiong,1– 3,&ast; Xingquan Zhao1,&ast; 1Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2China National Clinical Research Center for Neurological Diseases, Beijing, People’s Republic of China; 3Chinese Institute for Brain Research, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xingquan Zhao, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, No. 119 Nansihuanxilu, Fengtai District, Beijing, 100070, People’s Republic of China, Tel +86– 10– 59975549, Email zxq@vip.163.com Yunyun Xiong, National Clinical Research Center for Neurological Diseases, Beijing, People’s Republic of China, Email xiongyunyun@bjtth.orgObjective: The clinical significance of different glycemic parameters has been rarely investigated in ischemic stroke patients treated with intravenous tissue plasminogen activator (IV tPA). This study was aimed to investigate the association between different glycemic parameters and favorable functional outcome in patients treated with IV tPA.Methods: Patients with ischemic stroke who received IV tPA therapy at our stroke center were retrospectively enrolled. Four glycemic parameters were collected including admission glucose, HbA1c, stress hyperglycemia ratio (SHR) and glycemic gap (GG). Additional information was also recorded including demographics, medical history, stroke severity, imaging measures and mRS score at discharge. We used 5 machine learning models to investigate the predictive value of glycemic parameters.Results: Our study included 294 patients treated with IV tPA. SHR and GG were independently associated with favorable functional outcome (adjusted OR for SHR 0.03, 95% CI 0.01– 0.72, P = 0.03; adjusted OR for GG 1.024, 95% CI 1.00– 1.05, P = 0.04).Conclusion: SHR and GG were associated with functional outcomes in acute ischemic stroke patients with intravenous thrombolysis.Keywords: stroke, thrombolysis, tissue plasminogen activator, glucose, hyperglycemia

Fuxun Zhang1,2 &ast;, Yang Xiong1,2 &ast;, Feng Qin,1 Jiuhong Yuan1,2 1Andrology Laboratory, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 2Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiuhong Yuan, Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, People’s Republic of China, Email jiuhongyuan2107@163.comAbstract: The meaning of sleep has puzzled people for millennia. In modern society, short sleep duration is becoming a global problem. It has been established that short sleep duration can increase the risk of several diseases, such as cardiovascular and metabolic diseases. Currently, a growing body of research has revealed a possible link between sleep disorders and erectile dysfunction (ED). However, the mechanisms linking short sleep duration and ED are largely unknown. Thus, we provide a review of clinical trials and animal studies. In this review, we propose putative pathways connecting short sleep duration and ED, including neuroendocrine pathways and molecular mechanisms, aiming to pave the way for future research. Meanwhile, the assessment and improvement of sleep quality should be recommended in the diagnosis and treatment of ED patients.Keywords: erectile dysfunction, molecular mechanisms, sleep disorder, short sleep duration, signaling pathway

Haibo Li,1,2,&ast; Yuan Fang,1,2,&ast; Xu Li,2,&ast; Jingting Chen,1 Yao Xiong,1 Yongzhou Shi,3 Shengli Li,1 Lincai Ye,4 Shoubao Wang,1,&ast; Jianda Zhou2,&ast; 1Department of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Plastic Surgery, The Third Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 3Department of Neurosurgery, Neihuang Chinese Medicine Hospital, Anyang, People’s Republic of China; 4Department of Thoracic and Cardiovascular Surgery, Shanghai Children’s Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shoubao Wang; Jianda Zhou, Email wxldragon198418@163.com; zhoujianda@csu.edu.comAim: The development of microsurgery has greatly advanced vascularized composite allotransplantation (VCA). However, like organ transplantation, VCA is also limited by acute rejection, and concerns regarding long-term survival and function of the transplanted graft. Therefore, it is necessary to elucidate the molecular mechanisms underlying acute rejection caused by VCA, in order to improve patient survival.Methods: Firstly, we used Brown Norway rats and Lewis rats to construct animal model of VCA. Regularly record the appearance changes of all subjects. Specimens were collected for histological examination, microRNAs (miRNAs) sequencing and RT-qPCR verification when acute immune rejection occurred. Then, bioinformatics analysis was employed to predict miRNA related molecules and pathway information. Finally, differentially expressed miRNAs were tested and verified.Results: MiRNAs are small non coding RNA transcripts that regulate gene expression at the post-transcriptional level. Studies have shown that miRNAs are involved in immune regulation and several miRNAs have been identified that are potential diagnostic and prognostic biomarkers of acute rejection. In this study, we found that the expression levels of rno-miR-21-5p, rno-miR-340-5p, rno-miR-1-3p and rno-miR-195-5p are significantly associated with acute rejection following VCA.Conclusion: This miRNA signature can potentially an auxiliary diagnostic indicator of rejection, which can help clinicians adjust the immunosuppressive program in time during acute rejection.Keywords: vascularized composite tissue allograft1, VCA2, miRNAs4, acute rejection5

Guangshuo Li,1 Yahui Hao,2 Chuanying Wang,1 Shang Wang,1,2 Yunyun Xiong1– 3&ast;, Xingquan Zhao1 &#x002A1Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2China National Clinical Research Center for Neurological Diseases, Beijing, People’s Republic of China; 3Chinese Institute of Brain Research, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yunyun Xiong, China National Clinical Research Center for Neurological Diseases, Beijing, People’s Republic of China, Email xiongyunyun@bjtth.org Xingquan Zhao, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, No. 119 Nansihuanxilu, Fengtai District, Beijing, 100070, People’s Republic of China, Email zxq@vip.163.comObjective: Investigations on neutrophil-to-lymphocyte ratio (NLR) and lymphocyte-to-monocyte ratio (LMR) in patients with ischemic stroke are insufficient. We aimed to investigate the relationship of NLR and LMR with in-hospital clinical outcomes at different time points in ischemic stroke patients treated with intravenous tissues plasminogen activator (IV tPA).Methods: We retrospectively enrolled patients who received IV tPA therapy within 4.5 hours from symptoms onset. Demographics, clinical characteristics, imaging measures, and the in-hospital clinical outcomes including early neurological improvement (ENI, defined as NIHSS score reduction within 24 hours ≥ 4 points or decreased to the baseline) and favorable functional outcome (defined as modified Rankin scale 0– 1) were collected. Multivariable logistic regression analyses were performed to test whether NLR or LMR was an independent predictor for the in-hospital clinical outcomes.Results: One hundred and two patients treated with IV tPA were included. NLR at 24 hours proved to be an independent predictor of ENI (adjusted OR=0.85, 95% CI=0.75– 0.95, P=0.04). NLR at 48 hours and LMR at 48 hours proved to be independent predictors of mRS 0– 1 at discharge (NLR at 48 hours: adjusted OR=0.64, 95% CI=0.49– 0.83, P=0.01; LMR at 48 hours: adjusted OR=1.50, 95% CI=1.08– 2.09, P=0.02). The AUC of NLR at 48 hours to predict favorable functional outcome at discharge was 0.79 (95% CI=0.70– 0.88, P< 0.001) and the optimal cut-off was 5.69 (sensitivity=0.52, specificity=0.63).Conclusion: In our study, NLR at 24 hours was correlated with ENI. Both NLR and LMR at 48 hours were closely associated with favorable functional outcomes at discharge.Keywords: stroke, thrombolysis, tissue plasminogen activator, neutrophil, inflammation

Bing Xu,1,&ast; Jian Liang,1,&ast; Hecun Zou,2,&ast; Jingwen Wang,2 Yubo Xiong,1,3 Jiao Pei1 1Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, Hubei, 441021, People’s Republic of China; 2Institute of Life Sciences, Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 3Department of Neurosurgery, General Hospital of the Yangtze River Shipping, Wuhan Brain Hospital, Wuhan, Hubei, 430010, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiao Pei; Yubo Xiong, Email Ajiao2012@outlook.com; fengshu525@163.comPurpose: tsRNA is a type of small non-coding RNA derived from tRNA. Diffuse gliomas are the most common brain tumors. This investigation focused on tsRNA identification and characterization within gliomas.Methods: The sequences of human tRNA and tsRNAs were taken from GtRNAdb, tRFdb and tRFexplorer databases. Data processing and bioinformatic analysis were performed with R or Python software. The expression of tsRNAs in glioma tissues was analyzed by qRT-PCR assay.Results: With computational approaches, we identified hundreds of tsRNAs with available expression abundance in the glioma datasets, most of them derived from the 3′ end or 5′ end of mature tRNA. Among the tsRNAs derived from tRNA-Leu-CAA, ts-26, tRFdb-3012a, and tRFdb-3012b (tRFdb-3012a/b) were significantly decreased in diffuse gliomas. The clinical survivals of glioma patients with low tsRNA (ts-26, tRFdb-3012a, and tRFdb-3012b) expression were remarkably worse than that of those with high expression. Expression of tRFdb-3012a/b was correlated with IDH mutant status and MGMT promoter mutation in gliomas, and tRFdb-3012a/b and ts-23 tended to be highly expressed in patients with the IDH mutant. The enrichment analysis showed that some tRFdb-3012a/b-related genes were enriched in RNA splicing and processing, the spliceosome pathway and astrocyte molecular signatures. Moreover, the 3′ untranslated region of the RBM43 gene was predicted to contain putative binding sites of tRFdb-3012a/b, ts-26 may directly bind to the 3′ untranslated region of the HOXA13 gene, and the expressions of both RBM43 and HOXA13 were up-regulated in diffuse gliomas. High RBM43 and HOXA13 expressions were significantly associated with poor survival outcome of glioma patients.Conclusion: These results suggest that tRNA-Leu-CAA-derived tsRNAs (ts-26, tRFdb-3012a, and tRFdb-3012b) could be explored as diagnostic and prognostic biomarkers for diffuse gliomas, and tRFdb-3012a/b and ts-26 may play an important role in the progression of gliomas, through binding RBM43 and HOXA13, respectively.Keywords: tRNA-Leu-CAA, tRFdb-3012a/b, ts-26, diffuse gliomas, RBM43

Nan Wang,1 Yuanting Gu,1 Lin Li,1 Jiangrui Chi,1 Xinwei Liu,1 Youyi Xiong,1 Chaochao Zhong2 1Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China; 2Department of Plastic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of ChinaCorrespondence: Nan Wang, Email fccwangn2@zzu.edu.cnBackground: The changes of lipid metabolism have been implicated in the development of many tumors, but its role in breast invasive carcinoma (BRCA) remains to be fully established. Here, we attempted to ascertain the prognostic value of lipid metabolism-related genes in BRCA.Methods: We obtained RNA expression data and clinical information for BRCA and normal samples from public databases and downloaded a lipid metabolism-related gene set. Ingenuity Pathway Analysis (IPA) was applied to identify the potential pathways and functions of Differentially Expressed Genes (DEGs) related to lipid metabolism. Subsequently, univariate and multivariate Cox regression analyses were utilized to construct the prognostic gene signature. Functional enrichment analysis of prognostic genes was achieved by the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Kaplan-Meier analysis, Receiver Operating Characteristic (ROC) curves, clinical follow-up results were employed to assess the prognostic potency. Potential compounds targeting prognostic genes were screened by Connectivity Map (CMap) database and a prognostic gene-drug interaction network was constructed using Comparative Toxicogenomics Database (CTD). Furthermore, we separately validated the selected marker genes in BRCA samples and human breast cancer cell lines (MCF-7, MDA-MB-231).Results: IPA and functional enrichment analysis demonstrated that the 162 lipid metabolism-related DEGs we obtained were involved in many lipid metabolism and BRCA pathological signatures. The prognostic classifier we constructed comprising SDC1 and SORBS1 can serve as an independent prognostic marker for BRCA. CMap filtered 37 potential compounds against prognostic genes, of which 16 compounds could target both two prognostic genes were identified by CTD. The functions of the two prognostic genes in breast cancer cells were verified by cell function experiments.Conclusion: Within this study, we identified a novel prognostic classifier based on two lipid metabolism-related genes: SDC1 and SORBS1. This result highlighted a new perspective on the metabolic exploration of BRCA.Keywords: lipid metabolism, breast invasive carcinoma, BRCA, prognostic classifier, SDC1, SORBS1

Yan Li,1,&ast; Cuiyu Li,1,&ast; Yuhua Xiong,1 Bin Fang,1 Xing Lin,1 Quanfang Huang2 1Life Sciences Institute, Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of China; 2The Pharmaceutical Department, Guangxi University of Chinese Medicine First Affiliated Hospital, Nanning, Guangxi, 530023, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xing Lin, Guangxi Medical University Life Sciences Institute, Nanning, Guangxi, 530021, People’s Republic of China, Email gluck4668@sina.com Quanfang Huang, The Pharmaceutical Department, Guangxi University of Chinese Medicine First Affiliated Hospital, Nanning, 530023, People’s Republic of China, Email g723m6@sina.comIntroduction: Origanum vulgare L. is a traditional Chinese herb, having a strong hepatoprotective effect. In our previous experiments, we have isolated an ingredient from this herb and identified it as didymin. This study aimed to investigate the effects and underlying mechanisms of didymin on liver injury and fibrosis, elucidating whether it was the pharmacodynamic material basis of Origanum vulgare L.Methods: Mice were injected with CCl4 for 10 weeks to induce liver fibrosis, followed by didymin treatment for 6 weeks. Then, biochemical analysis and histopathological examinations were conducted to evaluate the therapeutic effects of didymin in alleviating fibrosis. Next, the possible mechanisms of didymin were predicted by transcriptomics and then verified by the multiple relevant examinations.Results: The pharmacodynamic experiments indicated that didymin significantly attenuated CCl4-induced hepatic injury and fibrogenesis, as evidenced by the ameliorative pathological tissue, low transaminase activity, and decreased collagen accumulation. Interestingly, the transcriptome analysis predicted that the potential targets were likely to be endoplasmic reticulum stress (ERS), inflammation, apoptosis, and metabolic pathways. And the predictions were then verified by the following examinations: (1) didymin significantly inhibited ERS by regulating the ATF6, IRE1α, and PERK pathways; (2) didymin markedly alleviated hepatocyte apoptosis by restoring the expression of Bcl-2 and caspase families, as well as the mitochondrial dysfunction; (3) didymin significantly decreased the production of the pro-inflammatory cytokines (IL-1β and IL-6); (4) didymin inhibited the glycerophospholipid metabolism pathway by decreasing the synthesis of phosphatidylethanolamines and phosphatidylcholines.Conclusion: Our findings demonstrate that didymin can ameliorate liver fibrosis, which is mainly attributed to the inhibition of ERS, inflammation, and glycerophospholipid metabolism.Keywords: didymin, transcriptomics, metabolomics, liver fibrosis, endoplasmic reticulum stress, ERS

Guangshuo Li,1 Chuanying Wang,1 Shang Wang,1,2 Yunyun Xiong,1– 3,&ast; Xingquan Zhao1,2,&ast; 1Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2China National Clinical Research Center for Neurological Diseases, Beijing, People’s Republic of China; 3Chinese Institute of Brain Research, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xingquan Zhao, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, West Nansihuan Road 119, Beijing, People’s Republic of China, Email zxq@vip.163.com Yunyun Xiong, China National Clinical Research Center for Neurological Diseases, Beijing, People’s Republic of China, Email xiongyunyun@bjtth.orgPurpose of Review: Intravenous thrombolysis is the first-line therapy for ischemic stroke, and alteplase has been used as an intravenous thrombolysis drug for over 20 years. However, considering its low rate of recanalization and risk of intracerebral hemorrhage, alteplase may not be the optimal thrombolytic drug of choice for ischemic stroke. Tenecteplase (TNK) is a genetically engineered, mutant, tissue plasminogen activator that is a potential substitute to alteplase in ischemic stroke. The pharmacokinetic advantages of TNK include greater fibrin selectivity than alteplase and prolonged half-life time. In this review, we have summarized the clinical trials of TNK in ischemic stroke.Recent Findings: Clinical trials showed a higher recanalization rate of TNK over alteplase without increasing the rate of intracerebral hemorrhage. However, not all clinical trials showed superiority of TNK over alteplase in functional outcomes and early neurological improvement. TNK was superior to alteplase in terms of recanalization in patients who fulfilled the imaging mismatch criteria and in those planning to undergo mechanical thrombectomy.Summary: TNK has the potential to substitute alteplase for ischemic stroke therapy. Future TNK clinical trials that target functional outcomes are warranted.Keywords: stroke, thrombolysis, TNK-tissue plasminogen activator, tenecteplase, clinical trial

Yi Xiong,1 Ye He,2 Yan Peng,3 Yun Geng4 1Department of Orthopaedic, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Hubei, People’s Republic of China; 2Department of Preventive Treatment of Diseases,Shaanxi Meixian Hospital of Traditional Chinese Medicine, Shaanxi, People’s Republic of China; 3Department of Medical Examination, Yili Kazak Autonomous Prefecture Hospital of Traditional Chinese Medicine, Xinjiang, People’s Republic of China; 4Department of Pharmacology, Shandong First Medical University and Shandong Academy of Medical Sciences, Shandong, People’s Republic of ChinaCorrespondence: Yun Geng, Tel/Fax +86-531-59556066, Email gengyunsd@163.comPurpose: Osteoporotic vertebral compression fracture (OVCF) is a common disease in the elderly, and genetic factors play a key role in its occurrence. The present study was conducted to investigate the association between interleukin-6 (IL-6) and the transforming growth factor (TGF-β) gene polymorphisms and the occurrence of thoracolumbar OVCF.Patients and Methods: This case–control study recruited 146 patients with OVCF and 144 osteoporosis patients as the control group. Genotypes of the IL-6 rs1800796 and TGF-β rs1982073 were analyzed by sequencing. Genotype distribution and allelic frequencies were investigated by the χ2 test. Odds ratios (OR) and 95% confidence intervals (CI) evaluated the relationship of IL-6 or TGF-β polymorphism and OVCF susceptibility.Results: Allele G and genotype GG of IL-6 rs1800796 was more frequent in patients with OVCF (40.07% vs.28.47%; 19.18% vs.7.64%) compared with controls. GG genotype (OR=3.394, 95% CI=1.560– 7.385, P < 0.001) and G allele (OR=1.680, 95% CI=1.187– 2.376, P < 0.001) of IL-6 rs1800796 was significantly associated with increased risk of OVCF. What is more, CT and TT genotypes (41.78 vs.51.39; 19.86 vs.26.39) and allele T (40.75 vs 52.08) of TGF-β rs1982073 were less frequent in OVCFs, more common in controls and protective against OVCF risk (OR=0.436, 95% CI=0.228– 0.835, P = 0.012; OR=0.615, 95% CI=0.443– 0.855, P = 0.004).Conclusion: Our results suggest that the G allele and GG genotype of IL-6 rs1800796 may contribute to increased susceptibility to OVCF in elderly Chinese. In contrast, CT and TT genotypes and the T allele of TGF-β rs1982073 may contribute to lower susceptibility of OVCF.Keywords: OVCF, IL-6, TGF-β, gene polymorphisms

Yurong Xiong,1,2,&ast; Yun Yu,1,2,&ast; Jianduan Cheng,3 Wei Zhou,2,4 Huihui Bao,1,2,4 Xiaoshu Cheng1,2,4 1Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 2Jiangxi Provincial Cardiovascular Disease Clinical Medical Research Center, Nanchang, Jiangxi, People’s Republic of China; 3Wuyuan Chinese Medicine Hospital, Shangrao, Jiangxi, People’s Republic of China; 4Center for Prevention and Treatment of Cardiovascular Diseases, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Huihui Bao; Xiaoshu Cheng, Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang University, No. 1 Minde Road, Nanchang, Jiangxi, 330006, People’s Republic of China, Tel +8613870092915 ; +8613607089128, Fax +86-0791-86262262, Email huihui_bao77@126.com; xiaoshumenfan126@163.comObjective: This study aimed to assess the associations of sleep duration, midday napping and the risk of atrial fibrillation (AF) in patients with hypertension.Methods: We conducted a cross-sectional study enrolling 11,524 hypertensive participates from the Chinese Hypertension Registry Study. Information on sleep duration and midday napping were obtained by a self-administered questionnaire. Multivariate logistic regression analyses were performed to estimate odds ratio (OR) and 95% confidence intervals (CIs) for the risk of AF.Results: Compared with sleeping 6 to ≤ 8 hours/night, those reporting shorter sleep duration (≤ 5 hours/night) had a greater risk of AF (OR 1.95; 95% CI 1.28– 2.95) in the fully adjusted model, while longer sleep (≥ 9 hours/night) was not significantly associated with the risk of AF. Compared with nonhabitual nappers, nappers had a higher risk of AF (OR 1.28; 95% CI 1.03– 1.60) in the fully adjusted model. Moreover, we observed significant joint effects of sleeping ≤ 5 hours/night and nap (OR 2.13; 95% CI 1.09– 4.14) on the risk of AF after adjusting for confounding factors.Conclusion: Short sleep duration and midday napping were independently and jointly associated with higher risks of AF in patients with hypertension.Keywords: sleep medicine, midday napping, atrial fibrillation, hypertension

Yongjie Xiong,1 Yi Qu,1 Zhe Min,1 Jun Wu,2 Suming Zhang,1 Zheng Xue1 1Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, People’s Republic of China; 2Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450000, People’s Republic Of ChinaCorrespondence: Zheng Xue, Department of Neurology, Tongji Hospital, Tongji College of Medicine, Huazhong University of Science and Technology, Wuhan, 430000, People’s Republic of China, Tel +86 1 404 234 5433, Email xuezheng@hust.edu.cnPurpose: Magnetic resonance imaging (MRI) is a promising technique for detecting amyloid beta (Aβ) deposits in Alzheimer’s disease (AD). Contrast agents can reduce the scanning time and provide specific images to identify various structures. This study aimed to develop an ultrasmall superparamagnetic iron oxide (USPIO) nanoparticle coupled with a functional protein as a targeted MRI contrast agent to detect Aβ deposits.Methods: The targeted MRI contrast agent USPIO nanoparticle was coupled with Aβ(16– 20) (KLVFF) and HIV-1 trans-activating transcriptor-protein transduction domain (Tat-PTD) to produce the Tat-PTD-USPIO-Aβ(16– 20) structure to better penetrate the blood–brain barrier (BBB). In vitro studies were conducted to measure the coupling efficiency, including bicinchoninic acid protein assays, potassium ferrocyanide staining of cardiac microvascular endothelial cells, 1.5T MRI, and toxicity assessments. The contrast agent was injected into five transgenic mice and five age-matched wild-type mice for MRI and histological studies. The targeted agent was diluted, and all mice were scanned with a 7.0 Tesla MRI-scanner. The brain tissues were processed as frozen sections for Thioflavin-S staining to detect Aβ.Results: The coupling efficiency reached 97.75%. The developed MRI contrast agent successfully passed through biological membranes, bound to Aβ deposits, and decreased the MRI signal of tissue in vitro and in vivo. Compared with Aβ(16– 20) or Aβ(1– 40) alone, there was no significant toxicity of Tat-PTD or Aβ(16– 20) when coupled with USPIO nanoparticles.Conclusion: Our novel MRI contrast agent USPIO nanoparticle coupled with functional protein can pass through biological membranes in vitro and visualize Aβ deposits in AD animal models by MRI.Keywords: Alzheimer’s disease, transgenic mice, contrast agent, magnetic resonance imaging, nanomolecular imaging

Kai Dai,1,&ast; Zhibing Li,2,&ast; Yafei Luo,1,&ast; Qianhui Xiong,1,&ast; Yao Xiong,3,&ast; Zhifang Song,1,&ast; Wenjun Xiong1 1Department of Cardiovascular Medicine, The First Affiliated Hospital of Nanchang University, Medical Department of Nanchang University, Nanchang, 330006, Jiangxi, People’s Republic of China; 2Department of Intensive Care Unit, The First Affiliated Hospital of Nanchang University, Medical Department of Nanchang University, Nanchang, 330006, Jiangxi, People’s Republic of China; 3Department of Cardiovascular Medicine, Jiangxi Provincial People’s Hospital Affiliated to Nanchang University, Medical Department of Nanchang University, Nanchang, 330006, Jiangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wenjun XiongDepartment of Cardiovascular Medicine, The First Affiliated Hospital of Nanchang University, Medical Department of Nanchang University, No. 461 Bayi Avenue, Nanchang, 330006, Jiangxi, People’s Republic of China, Tel +8613767970074, Email xiongwenjunnc@foxmail.comBackground: Cardiac rupture (CR) is a serious complication of acute myocardial infarction (AMI). We aimed to explore the predictive value of blood cell parameters for identifying CR in patients with AMI using the introduction of propensity score matching (PSM).Methods: This retrospective study enrolled patients who were diagnosed with AMI from January 2013 to May 2020. A total of 109 patients with CR were included, and 327 hospitalized non-CR patients were randomly selected at a 1:3 ratio. Based on the 1:1 nearest neighbour matching method by using SPSS, the covariances of the two groups were balanced. After PSM, the independent risk factors for CR were selected by using multivariate logistic regression analysis, and receiver operating characteristic (ROC) curve analysis was applied to evaluate the predictive value of blood cell parameters for CR. Ninety cases were matched successfully in each of the two groups.Results: Among the 180 patients with AMI after PSM, the results of multivariate logistic regression analysis showed that the monocyte-to-lymphocyte ratio (MLR) (OR = 3.57, 95% CI: 1.28– 9.97, P = 0.015) and monocyte-to-haematocrit ratio (MHR) (OR = 1.80, 95% CI: 1.02– 3.20, P = 0.043) were independently related to the risk of CR. Additionally, the MLR (area under the curve (AUC): 0.74) and MHR (AUC: 0.73) were useful for distinguishing CR patients after PSM. To differentiate CR patients from the control subjects, the optimal cut-offs of the MLR and MHR were 0.61 (63% sensitivity and 80% specificity) and 2.06 (57% sensitivity and 81% specificity), respectively.Conclusion: The blood cell parameters MLR and MHR were independently correlated with CR. Additional, the MLR and MHR were useful to predict CR in patients with AMI.Keywords: cardiac rupture, acute myocardial infarction, blood cell parameters, monocyte-to-lymphocyte ratio, inflammatory, monocyte-to-haematocrit ratio

Jun Zhang,1– 3,&ast; Chun-Lin Mai,1,&ast; Ying Xiong,1 Zhen-Jia Lin,1 Ying-Tao Jie,1 Jie-Zhen Mai,1 Chong Liu,1 Man-Xiu Xie,4 Xin Zhou,2,3 Xian-Guo Liu1,5,6 1Department of Physiology and Pain Research Center, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, People’s Republic of China; 2Department of Anesthesiology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, People’s Republic of China; 3Guangdong Cardiovascular Institute, Guangzhou, 510080, People’s Republic of China; 4Department of Anesthesiology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, People’s Republic of China; 5Department of Anesthesiology, Guangdong Second Provincial Central Hospital, Guangzhou, 510317, People’s Republic of China; 6Guangdong Province Key Laboratory of Brain Function and Disease, Guangzhou, 510080, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xian-Guo Liu; Xin Zhou Email liuxg@mail.sysu.edu.cn; zhoux89@mail2.sysu.edu.cnPurpose: Postmenopausal women often suffer from chronic pain, memory decline and mood depression. The mechanisms underlying the neuronal disorders are not fully understood, and effective treatment is still lacking.Methods: Oral administration of magnesium-L-threonate was tested to treat the neuronal disorders in ovariectomized and aged female mice. The pain hypersensitivity, memory function and depression-like behaviors were measured with a set of behavioral tests. Western blots, immunochemistry and in situ hybridization were used to assess molecular changes.Results: Chronic oral administration of magnesium-L-threonate substantially prevented or reversed the chronic pain and memory/emotional deficits in both ovariectomized and aged female mice. We found that phospho-p65, an active form of nuclear factor-kappaB, tumor necrosis factor-alpha and interleukin-1 beta were significantly upregulated in the neurons of dorsal root ganglion, spinal dorsal horn and hippocampus in ovariectomized and aged mice. The microglia and astrocytes were activated in spinal dorsal horn and hippocampus. Calcitonin gene–related peptide, a marker for peptidergic C-fibers, was upregulated in dorsal horn, which is associated with potentiation of C-fiber-mediated synaptic transmission in the model mice. In parallel with neuroinflammation and synaptic potentiation, free Mg2+ levels in plasma, cerebrospinal fluid and in dorsal root ganglion neurons were significantly reduced. Oral magnesium-L-threonate normalized the neuroinflammation, synaptic potentiation and Mg2+ deficiency, but did not affect the estrogen decline in ovariectomized and aged mice. Furthermore, in cultured dorsal root ganglion neurons, estrogen at physiological concentration elevated intracellular Mg2+, and downregulated phospho-p65, tumor necrosis factor-alpha and interleukin-1 beta exclusively in the presence of extracellular Mg2+.Conclusion: Estrogen decline in menopause may cause neuroinflammation by reducing intracellular Mg2+ in neurons, leading to chronic pain, memory/emotional deficits. Supplement Mg2+ by oral magnesium-L-threonate may be a novel approach for treating menopause-related neuronal disorders.Keywords: magnesium-L-threonate, postmenopause, neuroinflammation, chronic pain, memory, depression

Yilin Xiong,1,&ast; Yuqiao Han,1,&ast; Zinan Zhao,1,&ast; Wenting Gao,2 Yong Ma,2 Shiyu Jiang,1 Mengyao Wang,1 Qingqing Zhang,3 Yun Zhou,4 Yang Chen1 1Department of Biotechnology, College of Basic Medical Sciences, Dalian Medical University, Dalian, People’s Republic of China; 2Institute of Genome Engineered Animal Models for Human Disease, Dalian Medical University, Dalian, People’s Republic of China; 3Laboratory of Pathogenic Biology, College of Basic Medical Sciences, Dalian Medical University, Dalian, People’s Republic of China; 4Department of Clinical Nutrition, Second Affiliated Hospital of Dalian Medical University, Dalian, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yang ChenDepartment of Biotechnology, College of Basic Medical Sciences, Dalian Medical University, 9 West Section of Lvshun South Road, Dalian, 116044, People’s Republic of ChinaTel/Fax +86 411 86110350Email yangchen@dmu.edu.cnYun ZhouDepartment of Clinical Nutrition, Second Affiliated Hospital of Dalian Medical University, 467 Zhongshan Road, Dalian, 116023, People’s Republic of ChinaTel +86 411 84690722Fax +86 411 84672130Email dmu_yunzhou@yeah.netPurpose: Antibiotic resistance is a growing health crisis that is further complicated by treatment failures caused by bacteria that exhibit heterogeneous susceptibility to antibiotics. The aim of this study was to describe imipenem (IPM)-heteroresistant strains among multidrug-resistant (MDR) ESBL/AmpC-producing Klebsiella pneumoniae clinical isolates, investigate their molecular phenotypic characteristics, and elucidate the outcome of antibiotic treatment in mice infected with the heteroresistant isolates.Materials and Methods: Antimicrobial susceptibility of K. pneumoniae isolates was determined by the disk diffusion and E-test methods. Heteroresistance to IPM was confirmed by population analysis profile (PAP) assays. PCR and sequencing were employed to detect MDR determinants. Molecular differences between the susceptible and resistant subpopulations were evaluated by sequencing and quantitative real-time reverse transcription PCR (qRT-PCR) analysis. The effect of the carbapenem-heteroresistant strains on antibiotic treatment was assessed using a mouse model of peritonitis with heteroresistant K. pneumoniae and subsequent treatment with IPM.Results: In total, 37 MDR ESBL/AmpC-producing clinical isolates of K. pneumoniae were identified between September 2018 and December 2019. These strains were notably resistant to conventional antimicrobials other than carbapenems. Among the isolates, three strains exhibited heteroresistance to IPM and carried several ESBL and/or AmpC genes. Mice infected with a lethal dose of any of the three heteroresistant isolates were unable to survive in the presence of IPM treatment, as the percentage of the IPM-resistant subpopulation of each strain was increased in the peritoneum of these mice at 24 h after infection. The resistant subpopulation of the strains presented pulsed-field gel electrophoresis (PFGE) profiles that were identical to those of the susceptible subpopulation, but ompK36 porin showed a reduction in gene expression (0.09- to 0.50-fold) in the resistant subpopulation.Conclusion: Carbapenem-heteroresistant strains were present among the MDR K. pneumoniae isolates producing ESBL/AmpC β-lactamases, and these heteroresistant strains failed IPM therapy in experimentally infected mice.Keywords: Enterobacteriaceae, imipenem, heterogeneous susceptibility, treatment failure, OmpK porin, in vivo

Xiang He,1,2,&ast; Lei Zhang,1,2,&ast; Lingjuan Hu,1,3,&ast; Shengbin Liu,1,2 Anying Xiong,1,2 Junyi Wang,1,2 Ying Xiong,4 Guoping Li1,2 1Laboratory of Allergy and Precision Medicine, Chengdu Institute of Respiratory Health, The Third People’s Hospital of Chengdu, Affiliated Hospital of Southwest Jiaotong University, Chengdu, 610031, People’s Republic of China; 2Department of Pulmonary and Critical Care Medicine, Chengdu Third People’s Hospital Branch of National Clinical Research Center for Respiratory Disease, Affiliated Hospital of ChongQing Medical University, Chengdu, 610031, People’s Republic of China; 3Department of Respiratory Disease, Renshou County People’s Hospital, Renshou, 620550, People’s Republic of China; 4Department of Pulmonary and Critical Care Medicine, Sichuan Friendship Hospital, Chengdu, 610000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guoping Li; Ying Xiong Email lzlgp@163.com; ly65110@126.comBackground: Exposure to air pollutants cause exacerbation of asthma, but the experimental evidence and the mechanisms still need to be collected and addressed.Methods: Asthma model was constructed by ovalbumin (OVA) combined with or without airborne fine particulate matter 2.5 (PM2.5) exposure. Lung sections were stained by hematoxylin-eosin staining (H&E) and Masson’s trichrome. RNA-seq and gene set enrichment analysis (GSEA) was performed to identify the key pathway. TdT mediated dUTP Nick End Labeling (TUNEL) assay, real-time qPCR, Western blot, immunofluorescence and lentivirus transfection were applied for mechanism discovery.Results: In this study, we found PM2.5 aggravated airway inflammation in OVA-induced asthmatic mice. RNA-seq analysis also showed that epithelial mesenchymal transition (EMT) was enhanced in OVA-induced mice exposed to PM2.5 compared with that in OVA-induced mice. In the meantime, we observed that apoptosis was significantly increased in asthmatic mice exposed to PM2.5 by using GSEA analysis, which was validated by TUNEL assay. By using bioinformatic analysis, Fas associated via death domain (FADD), a new actor in innate immunity and inflammation, was identified to be related to apoptosis, EMT and tight junction. Furthermore, we found that the transcript and protein levels of tight junction markers, E-cadherin, zonula occludens (ZO)-1 and Occludin, were decreased after PM2.5 exposure in vivo and in vitro by using RT-qPCR and immunofluorescence, with the increased expression of FADD. Moreover, down-regulation of FADD attenuated PM2.5-induced apoptosis and tight junction disruption in human airway epithelial cells.Conclusion: Taken together, we demonstrated that PM2.5 aggravated epithelial tight junction disruption through apoptosis mediated by up-regulation of FADD in OVA-induced model.Keywords: asthma, epithelial tight junction disruption, PM2.5, FADD, apoptosis

Huanyu Guo,1,&ast; Wenwei Jiang,2,&ast; Bo Zhao,1 Yanhua Xiong,3 Zhenya Lu1 1Department of FSTC Clinic of The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310009, People’s Republic of China; 2Department of Internal Medicine of Traditional Chinese Medicine, Huzhou Central Hospital, Huzhou, 310003, People’s Republic of China; 3Department of Internal Medicine of Traditional Chinese Medicine, Zhejiang Hospital, Hangzhou, 310007, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhenya LuDepartment of FSTC Clinic of The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310009, People’s Republic of ChinaTel +86 13575458480Email 1199026@zju.edu.cnPurpose: To develop a predictive model for the risk of metabolic syndrome (MetS).Patients and Methods: Totally, 1556 residents without MetS were finally included in 2006 and they were observed for 8 years to check who developed MetS. Univariate and multivariate logistic regression analyses was adopted to explore the risk factors of MetS and develop the predictive model that used the medical examination information of MetS risk after 8 years. The receiver operating characteristic (ROC) curve was drawn to assess the predictive capacity of the model.Results: The risk of MetS in overweight, prehypertension, hypertension subjects were 4.610 [95% confidence interval (CI): 2.415 to 8.800], 2.759 (95% CI: 1.519 to 5.011) and 3.589 (95% CI: 1.672 to 7.706) times higher than that in controls, respectively. The risk of MetS in people with high-density lipoprotein (HDL) < 1.10 mmol/L was 3.716-fold in comparison with HDL ≥ 1.55 mmol/L [odds risk (OR) = 3.716, 95% CI: 1.483 to 9.313]. Individuals with fatty liver had a higher risk of MetS (OR = 2.577, 95% CI: 1.472 to 4.512). The AUC of the predictive model was 0.831 (95% CI: 0.798 to 0.865), with the sensitivity of 0.898 (95% CI: 0.831 to 0.941) and the specificity of 0.676 (95% CI: 0.651 to 0.700).Conclusion: The model performed well predictive power for the risk of MetS, which may provide a reference for clinicians to identify high-risk groups early.Keywords: metabolic syndrome, predictive model, 8-year, Chinese cohort

Yaming Xiong, Hailing Tang Department of Thoracic Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, People’s Republic of ChinaCorrespondence: Yaming Xiong Email xym0214@163.comBackground: EGFR and KRAS are the most frequently mutated genes in lung cancers, occurring in about 60% of all cases. Mutation genes assay has emerged as a promising blood-based biomarker for monitoring cancer dynamics noninvasively. However, detection can be challenging in patients where plasma often contains low levels of tumor-derived DNA fragments.Methods: We have developed a nuclease-based enrichment assay for detecting mutant alleles. The procedure is based on Surveyor endonuclease cleaves mismatched DNA molecules, and these DNA fragments were enriched for mutation screening. We screened lung cancer specimens for mutations in exons 18 and 21 of EGFR, and the majority of activating mutations in lung cancer occur in codons 12 (G12X) and 13 (G13X) of exon 2 of the KRAS gene. The method screened all mutant genes with the same pair primers and three relevant TaqMan probes.Results: The method can effectively remove wild-type sequences and enrich mutation DNA, and the sensitivity detectable mutant allele frequencies (MAF) achieved 0.001%. The method increases the sensitivity and efficiency of mutation DNA for cancers screening. This highlights the importance of complex DNA variation like mutations in exon 21 of EGFR and exon 2 of the KRAS gene detected by the same probe.Conclusion: We developed a simple and sensitive methodology for mutation gene screening. The method is a cost-effective and sensitive method for mutation DNA enrichment and detection.Keywords: liquid biopsy, Surveyor, enrichment, lung cancer

Tingting Song,&ast; Hong Wang,&ast; Yue Liu, Rongshan Cai, Dezhi Yang, Yongai Xiong Department of Pharmacy, Zunyi Medical University, Zunyi City, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yongai Xiong Email yaxiong@zmu.edu.cnBackground: Ziyuglycoside I (ZgI), an active ingredient isolated from traditional Chinese medicine Sanguisorba officinalis L, has been demonstrated to increase the leucocytes and protect hematopoietic stem cells. However, the poor solubility and a short half-life of ZgI limit its bioavailability and efficacy. The D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) has been widely used to increase the solubility, improve the encapsulation rate, and extend the half-life of drugs.Methods: Here, we formulated the TPGS-modified long-circulating liposomes loading ZgI with a sustained drug release and enhanced therapy for myelosuppression. ZgI-TPGS-liposomes were manufactured using a thin-film hydration technique, followed by characterizations of physicochemical properties, including the particle size, zeta potential, TEM, SEM, FTIR, XRD, stability, drug loading (DL), encapsulation efficiency (EE). The in vitro and in vivo delivery efficiency were further evaluated by cellular uptake, in vitro drug release and in vivo pharmacokinetics. Finally, therapeutic effect on myelosuppression was investigated.Results: The ZgI-TPGS-liposomes had an particle size of 97.89 ± 1.42 nm and ZP of − 28.65 ± 0.16 mV. It exhibited DL of 9.06 ± 0.76% and EE of 92.34 ± 3.83%, along with excellent storage stability, cellular uptake and sustained drug release to free ZgI and liposomes without TPGS. Additionally, the TPGS modified liposomes significantly enhanced the therapeutic effect of ZgI on CTX induced myelosuppression, which can be confirmed in the apoptosis inhibition and cell viability promotion of CTX injured HSPC-1 cells. Also, the mice in vivo pharmacodynamics demonstrated that TPGS liposomes promoted ZgI increasing the numbers of leucocytes and neutrophils in myelosuppression mice induced by CTX.Conclusion: Our research suggest that TPGS-modified long-circulating liposomes loading ziyuglycoside I has potential application in myelosuppression therapy.Keywords: myelosuppression, therapy, TPGS, long-circulating liposomes, ziyuglycoside I

Chen Xu,1,&ast; Junli Fan,1,&ast; Yi Luo,1,&ast; Ziwu Zhao,1,&ast; Peng Tang,1,&ast; Gui Yang,1 Yunbao Pan,1 Shuang Guo,1 Yingjuan Liu,1 Yong Xiong,2 Wen Xie,1 Xinghua Long1 1Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China; 2Department of infectious diseases, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xinghua Long; Wen XieDepartment of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of ChinaEmail zhoulongxinghua@qq.com; whxw007@126.comObjective: Patients with rheumatic immune diseases were more likely to develop severe or critical COVID-19. We aimed to determine whether rheumatoid factor antibodies were present in COVID patients and the level and type of rheumatoid factor antibodies produced in COVID-19 patients were related to the degree of the patient’s condition. The study also aimed to determine the prevalence and characteristics of rheumatoid factor antibodies in patients with COVID-19.Methods: Sera collected from 129 patients with COVID-19 were tested for rheumatoid factor antibodies by ELISA. Five patients were tracked for several months to monitor dynamic changes of these antibodies.Results: Rheumatoid-associated autoantibodies were detected in 20.16% of patients (26/129) following infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In addition, IgM-RF was primarily present in critically ill patients, while IgA-RF was mainly present in mild patients. Five patients were able to track for several months to monitor dynamic changes of these antibodies. Rheumatoid factor antibodies peaks in the later phase of the disease and last for longer time. Anti-Jo-1 antibody was found in one of the five patients.Conclusion: This was the case series report that rheumatoid-associated autoantibodies are present in patients with COVID-19. The clinical significance of these antibodies was not fully understood and needed further characterization. These autoantibodies are related to the severity of the patient’s disease and exist for a long time in the patient’s body, while their impact on the patient’s health is unknown.Keywords: rheumatoid factor, IgA-RF, IgG-RF, IgM-RF, anti-Jo-1, COVID-19, SARS-CoV-2

Yugang Hu,* Jia Zhou,* Quan Cao, Hao Wang, Yuanting Yang, Ye Xiong, Qing Zhou Department of Ultrasound Imaging, Renmin Hospital of Wuhan University, Wuhan, 430061, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qing ZhouDepartment of Ultrasound Imaging, Renmin Hospital of Wuhan University, 99 Ziyang Road, Wuhan, 430060, People’s Republic of ChinaTel +86027-88041911Email qingzhou@whu.edu.cnBackground: We aimed to investigate the association between usage of transthoracic echocardiography (TTE) within 24 hours after acute kidney injury (AKI) and the prognosis of patients in intensive care unit (ICU).Methods: The Medical Information Mart for Intensive Care III (MIMIC-III) database was used to identify AKI patients with and without TTE administration. The primary outcome was 28-day mortality. Multivariable regression was used to clarify the association between TTE and clinical outcomes and propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were utilized to validate our findings.Results: Among 23,945 eligible AKI patients, 3361 patients who received TTE and 3361 who did not conduct TTE had similar propensity scores which were included in this study. After matching, the TTE group had a significantly lower 28-day mortality (OR 0.80, 95% CI 0.72– 0.88, P< 0.001). Patients in the TTE group received more fluid on day 1 and day 2 and had a more urine volume on day 1 and day 3, and the reduction in serum creatinine was greater than that in the no TTE group. The mediating effect of creatinine reduction was remarkable for the whole cohort (P=0.02 for the average causal mediation effect).Conclusion: TTE utilization was associated with decreased risk-adjusted 28-day mortality for AKI patients in ICU and was proportionally mediated through creatinine reduction.Keywords: echocardiography, acute kidney injury, medical information mart for intensive care, propensity score matching, mortality