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Mingyue Sun, Weiqiang Xiao, Qingxia Xu Department of Clinical Laboratory, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, Henan, People’s Republic of ChinaCorrespondence: Qingxia Xu, Department of Clinical Laboratory, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Dongming Road No. 127, Zhengzhou, Henan Province, People’s Republic of China, Tel +860371-65587147, Email qxiaxu@126.comObjective: Klebsiella michiganensis is an emerging pathogen. In this context, we characterised a strain fxq isolated from a cerebrospinal fluid specimen of a patient with tentorial meningioma, and the K. michiganensis isolate produced carbapenemases of KPC and NDM types.Methods: The Phoenix 100 Automated Microbiology System, MALDI-TOF and whole-genome sequencing were used to identify the species. Anti-microbial susceptibility testing was also conducted with the Phoenix 100. The plasmid locations of the blaKPC-2 and blaNDM-1 genes were determined by S1-nuclease pulsed-field gel electrophoresis and Southern blot. The transfer capacity of plasmids carrying blaKPC-2 and blaNDM-1 was investigated by conjugation experiments, and the resistance plasmid stability was evaluated by culture and subculture. K. michiganensis subtypes were identified by multi-locus sequence typing. We performed whole-genome sequencing to confirm species, characterise plasmids and analyse core genes.Results: fxq was originally identified as Klebsiella oxytoca and showed resistance to imipenem and meropenem, but whole-genome sequencing identified it to be K. michiganensis. The strain fxq belonged to the novel sequence type 202 (ST202) and carried the blaKPC-2 and blaNDM-1 genes located on the pB_KPC InFIA and pE_NDM IncU plasmids, respectively. The blaKPC-2-carrying plasmid was successfully transferred to Escherichia coli EC600 by conjugation, whereas the blaNDM-1 gene on the pE_NDM plasmid was not. The pB_KPC and pE_NDM plasmids demonstrated high stability.Conclusion: This work is the first report on a carbapenem-resistant clinical isolate K. michiganensis ST202 harbouring the blaKPC-2 and blaNDM-1 genes encoded by the IncFIA and IncU plasmids, respectively.Keywords: Klebsiella michiganensis, IncU plasmid, carbapenemase gene, NDM, KPC

Wei Xiao,1 Yanqiong Liu,2 Hua Tang,3 Qin Xie,2 Yanlan Luo,2 Tao Mei1 1Department of Neurosurgical Care Unit, Changde Hospital, Xiangya School of Medicine, Central South University, Changde, 415003, People’s Republic of China; 2Cardiovascular Medicine Department, Changde Hospital, Xiangya School of Medicine, Central South University, Changde, 415003, People’s Republic of China; 3Neurosurgery Department, Changde Hospital, Xiangya School of Medicine, Central South University, Changde, 415003, People’s Republic of ChinaCorrespondence: Tao Mei, Email yilan1008@sina.comBackground: Intracerebral hemorrhage (ICH) affects up to 1% of chronic oral anticoagulation (OAC) users per year. This study explored the knowledge, attitude and practice (KAP) towards ICH prevention among patients taking OACs.Methods: This multicenter cross-sectional survey was conducted at 4 hospitals from February to May 2023, and a self-administered questionnaire was developed to assess KAP toward ICH prevention among patients taking OACs. Structural equation modeling was used to assess the relationship between KAP.Results: A total of 536 valid questionnaires (67.25%) were analyzed, from 43.8% participants on Warfarin, 40.5% on Rivaroxaban and 15.7% on Dabigatran. The average knowledge, attitudes and practice scores were 9.22, 24.11, and 28.01 out of 16, 35 and 40, respectively. Participants who received Rivaroxaban had lower knowledge scores but higher attitude and practice store compared to those who received Warfarin or Dabigatran (all p < 0.001). According to Structure Equation Modeling, attitude had direct positive effect on practice (β = 0.694 [0.603– 0.804], p = 0.012), while knowledge had direct negative effect on attitude (β = − 2.077 [− 2.507– 1.651], p = 0.013), as well as negative effect on practice, both direct (β = − 0.450[− 0.689– 2.03], p=0.012), and indirect (β = − 1.441 [− 1.928– 1.192], p = 0.004).Conclusion: Patients taking OACs showed insufficient knowledge, negative attitude and proactive practice regarding ICH; practice scores were affected by age, type of anticoagulation medication, and attitude rather than knowledge.Keywords: cerebral hemorrhage, anticoagulants, warfarin, dabigatran, rivaroxaban, knowledge, attitude, practice

Yan Yu,1,&ast; Ti-wei Miao,1,&ast; Wei Xiao,1 Bing Mao,1 Long-yi Du,1 Yan Wang,2 Juan-juan Fu1 1Division of Pulmonary Medicine, Department of Internal Medicine, Institute of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of China; 2Research Core Facility, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Juan-juan Fu, Division of Pulmonary Medicine, Department of Internal Medicine, Institute of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, 37 Guoxue Street, Chengdu, Sichuan, 610041, People’s Republic of China, Tel +86-18980606822, Email fu.juanjuan@scu.edu.cnPurpose: The aim of this study is to uncover the anti-inflammatory propertity of andrographolide (AGP) in acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and the underlying mechanisms related to the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome pathway.Methods: An in vivo experiment was conducted on murine model of AECOPD through endotracheal atomization of elastase and lipopolysaccharide (LPS). Intraperitoneal AGP was administered four times. NLRP3 inflammasome pathway molecules were examined using real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis. By using enzyme-linked immunosorbent assay (ELISA), we tested interleukin (IL)-1β levels in bronchoalveolar lavage fluid. An in vitro study was conducted to determine how AGP impacts the NLRP3 inflammasome in THP-1 derived macrophages. The levels of molecules involved in the pathway were measured. Furthermore, molecular docking analyses were carried out to investigate the interactions between AGP and pathway targets.Results: In the in vivo study, NLRP3 inflammasome activation was observed in mice experiencing AECOPD. The administration of high-dose AGP demonstrated a mitigating effect on inflammatory cells infiltration in the lungs. Moreover, AGP administration effectively suppressed the expression of NLRP3, apoptosis associated speck-like protein that contains a CARD (PYCARD), cysteinyl aspartate-specific protease-1 (Caspase-1), IL-1β, and IL-18 at both the genetic and protein levels. In the in vitro experiment, IL-1β levels were significantly elevated in THP-1 derived macrophages with activated inflammasome compared to the control group. Furthermore, the downregulation of NLRP3, CASP1, and IL1B genes was observed upon the inhibition of NLRP3 expression through small interfering RNA (siRNA). AGP demonstrated inhibitory effects on the gene expression and protein levels of NLRP3, Caspase-1, and IL-1β. Additionally, molecular docking analysis confirmed that AGP exhibited a favorable binding affinity with all five targets of the pathway.Conclusion: AGP effectively inhibited NLRP3 inflammasome activation and mitigated the inflammatory reaction of AECOPD both in animal models and in vitro experiments, highlighting the potential of AGP as a treatment for AECOPD with anti-inflammatory properties.Keywords: andrographolide, NLRP3 inflammasome, IL-1β, chronic obstructive pulmonary disease

Shi-Hua Yan,1,2 Yong Chen,3 Zhi-Qian Huang,1 Wen-Xi Zhong,1 Xiao-Tian Wang,1 Yang-Can Tang,1 Xu-Yi Zhao,1 Yu-Shan Wu,1 Chun Zhou,4 Wei Zhu,5 Wei Xiao,1,6 Xuan Li,2 Dong-Shu Zhang1,2 1School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, People’s Republic of China; 2Department of Traditional Chinese Medicine, The Tenth affiliated Hospital, Southern Medical University (Dongguan People’s Hospital), Dongguan, Guangdong, 523058, People’s Republic of China; 3Department of Rheumatology and Immunology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, 563000, People’s Republic of China; 4School of Pharmaceutical Sciences; Guangdong Provincial Key Laboratory of Shock and Microcirculation, Southern Medical University, Guangzhou, Guangdong, 510515, People’s Republic of China; 5Guangzhou Center for Disease Control and Prevention, Guangzhou, 510440, People’s Republic of China; 6Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education, Guangdong Pharmaceutical University, Guangzhou, Guangdong, 510006, People’s Republic of ChinaCorrespondence: Dong-Shu Zhang, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, People’s Republic of China, Email nyzds@sina.com Wei Xiao, Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education, Guangdong Pharmaceutical University, Guangzhou, Guangdong, 510006, People’s Republic of China, Email xw7688@smu.edu.cnPurpose: Acupoint autohemotherapy (A-AHT) has been proposed as an alternative and complementary treatment for atopic dermatitis (AD), yet the exact role of its blood component in terms of therapeutic efficacy and mechanism of action is still largely unknown.Methods: This study aimed to evaluate the therapeutic efficacies and action mechanisms of intramuscular injections of autologous whole blood (AWB) and mouse immunoglobulin G (IgG) (autologous or heterologous) at acupoints on 2,4-dinitrochlorobenzene (DNCB)-induced AD mouse models. Serum levels of total immunoglobulin E (IgE), IgG, interleukin-10 (IL-10), and interferon-gamma (IFN-γ) were measured, as well as mRNA expression levels of Forkhead box P3 (FoxP3), IL-10 and IFN-γ in dorsal skin lesions, and IL-10+, IFN-γ+ and FoxP3+CD4+T cells in murine spleen.Results: It showed that repeated acupoint injection of AWB, autologous total IgG (purified from autologous blood in AD mice) or heterologous total IgG (purified from healthy blood in normal mice) effectively reduced the severity of AD symptoms and decreased epidermal and dermal thickness as well as mast cells in skin lesions. Additionally, AWB acupoint injection was found to upregulate FoxP3+, IL-10+ and IFN-γ+ CD4+T cells in murine spleen, suppressing the production of IgE antibodies and increasing that of IgG antibodies in the serum. Furthermore, both AWB and autologous total IgG administrations significantly elevated FoxP3 expression, mRNA levels of IL-10 and IFN-γ in dorsal skin lesions. However, acupoint injection of heterologous total IgG had no effect on regulatory T (Treg) and Th1 cells modulation.Conclusion: These findings suggest that the therapeutic effects of A-AHT on AD are mediated by IgG-induced activation of Treg cells.Keywords: autologous whole blood, acupoint injection, atopic dermatitis, anti-idiotypic immunomodulation, Tregs

Luyao Liu,1 Wang Xiao,2 Chaojie Zhang,1 Peizhi Fan,1 Jie Zeng,1 Jianing Yi1 1Department of Breast and Thyroid Surgery, Hunan Provincial People’s Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, People’s Republic of China; 2Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha, People’s Republic of ChinaCorrespondence: Jianing Yi; Jie Zeng, Department of Breast and Thyroid Surgery, Hunan Provincial People’s Hospital, The First Affiliated Hospital of Hunan Normal University, 61 Jiefang West Road, Changsha, Hunan, 410005, People’s Republic of China, Tel +8613007436234 ; +8613974837749, Email yijianing@hunnu.edu.cn; zengjie227@hunnu.edu.cnBackground: Breast cancer (BC) continues to pose a substantial challenge to global health, necessitating an enhanced understanding of its fundamental mechanisms. Among its various pathological classifications, breast invasive carcinoma (BRCA) is the most prevalent. The role of the transcription factor forkhead box P3 (FOXP3), associated with regulatory T cells, in BRCA’s diagnosis and prognosis remains insufficiently explored, despite its recognized importance.Methods: We examined the mRNA expression profile of FOXP3 in BRCA patients, assessing its correlation with disease detection, patient survival, immune checkpoint alterations, and response to anticancer drugs.Results: Our analysis revealed significantly elevated FOXP3 mRNA levels in BRCA patients, with a 95.7% accuracy for BRCA detection based on the area under the curve. High FOXP3 mRNA levels were positively correlated with overall survival and showed significant associations with CTLA4, CD274, PDCD1, TMB, and immune cell infiltration status. Furthermore, FOXP3 mRNA expression was linked to the efficacy of anticancer drugs and the tumor inflammation signature.Discussion: These findings suggest that FOXP3 serves as a promising biomarker for BRCA, offering valuable insights into its diagnosis and prognosis. The correlation between FOXP3 expression and immune checkpoint alterations, along with its predictive value for treatment response, underscores its potential in guiding therapeutic strategies.Conclusion: FOXP3 stands out as an influential factor in BRCA, highlighting its diagnostic accuracy and prognostic value. Its association with immune responses and treatment efficacy opens new avenues for research and clinical applications, positioning FOXP3 as a vital target for further investigation in BRCA management.Keywords: breast cancer, FOXP3, regulatory T cells, immune checkpoint alterations, anticancer drugs response, immune cell infiltration

Yubin Zhu,1 Yilu Zhuang,2 Yawen Yu,2 Jinyue Wang,2 Yongtai Liu,3 Zhi Ruan,2,4 Wei Xiao,5 Yingying Kong2,4 1Department of Gastroenterology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 2Department of Clinical Laboratory, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 3The First Division Hospital of XinJiang Production and Construction Group, XinJiang, People’s Republic of China; 4Key Laboratory of Precision Medicine in Diagnosis and Monitoring Research of Zhejiang Province, Hangzhou, People’s Republic of China; 5Department of Emergency Medicine, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of ChinaCorrespondence: Yingying Kong; Wei Xiao, Email kongyy@zju.edu.cn; Xiaowei 2022@zju.edu.cnAbstract: Raoultella planticola is an emerging bacterial pathogen responsible for causing infections in both humans and animals. Unfortunately, sporadic reports of carbapenem-resistant R. planticola (CRRP) have been documented worldwide. Here we first reported the complete genome sequence of a CRRP isolate RP_3045 co-carrying blaIMP-4 and blaSHV-12, recovered from a patient in China, and its genetic relatedness to 82 R. planticola strains deposited in the NCBI GenBank database, sourced from humans, animals, and the environment. Whole-genome sequencing was performed using the Illumina NovaSeq 6000 and Oxford Nanopore MinION platforms. Phylogenetic analysis was also performed and visualized using a single nucleotide polymorphism (SNP)-based strategy. The complete genome of R. planticola strain RP_3045 was determined to be 6,312,961 bp in length, comprising five contigs that included one chromosome and four plasmids. RP_3045 was found to be multidrug-resistant and harbored several antimicrobial resistance genes, including both blaIMP-4 and blaSHV-12 genes located on a single plasmid. The most closely related strain was hkcpe63, recovered from humans in Hong Kong, China, in 2014, with 506 SNP differences. R. planticola strains were distributed globally and exhibited strong associations among isolates obtained from different sectors. This study provides evidence for the potential of R. planticola to disseminate carbapenem resistance across different sectors, highlighting the critical need for active and continuous surveillance of CRRP.Keywords: Raoultella planticola, blaIMP-4, blaSHV-12, antimicrobial resistance

Jiaxing Zhang,1,2,&ast; Liwei Gu,3,&ast; Yumao Jiang,4,&ast; Yun Ma,5,&ast; Ziyue Zhang,3 Shengnan Shen,3 Shuo Shen,3 Qing Peng,6 Wei Xiao2,7 1Institute of Digestive Disease, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People’s Hospital, Qingyuan, Guang Dong, People’s Republic of China; 2School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guang Dong, People’s Republic of China; 3Artemisinin Research Center and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China; 4Gannan Medical University, Ganzhou, Jiang Xi, People’s Republic of China; 5Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou, Guang Dong, People’s Republic of China; 6Institute of Basic Medical Sciences, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China; 7Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qing Peng; Wei Xiao, Email pengqing85@163.com; xw7688@smu.edu.cnBackground: Acute kidney injury (AKI) is a syndrome, posing a substantial healthcare burden. The pathological basis of AKI is associated with inflammation and oxidative stress which cause additional damage to mitochondria. Artesunate (ATS) is a derivative of artemisinin isolated from Artemisia annua L. that is an effective treatment for malaria and favored for the prevention and treatment of kidney diseases. However, there are still challenges related to its efficacy, including poor water solubility, limited oral bioavailability and short half-life. Liposome-based nanoparticles are used for drug delivery due to their ideal biocompatibility and their ability to improve the bioavailability of specific drugs and enhance drug efficacy.Methods: In this study, a novel TPP-based natural ATS-nanoliposome, namely T-A-Ls, was applied for the treatment of AKI. ATS was encapsulated with or without triphenylphosphonium (TPP)-modified nanoliposomes. AKI was induced by cisplatin in C57BL/6J mice and a cisplatin-induced injury model was generated in HK-2 cells in vitro. Blood urea nitrogen (BUN), serum creatinine (Scr) measurements and section staining were utilized to assess renal protective effect of T-A-Ls. Inflammatory-related factors and proteins were quantified via Elisa, Immunofluorescence and Western Blot (WB). The anti-mitochondrial oxidative stress effect of T-A-Ls was determined by ROS, JC-1 and oxygen consumption rate (OCR) kits. Immunohistochemistry and WB were conducted to measure associated protein expressions. In vivo biodistribution and the concentration of T-A-Ls in kidney were also explored.Results: T-A-Ls exhibited good oxidative resistance, preferential renal uptake, mitochondrial targeting, and it ameliorated kidney injury in cisplatin-induced AKI mice. Mitochondrial dysfunction, ATP production and respiratory capacity were improved in damaged HK-2 cells; ROS content decreased while mitochondrial membrane potential recovered. T-A-Ls exerted renal protection by inhibiting inflammation and reducing oxidative stress; these effects were mediated by a downregulation in the expression of RAGE and iNOS and an upregulation in both Nrf2 and HO-1.Conclusion: T-A-Ls could improve the delivery of ATS to the kidney, offering a promising avenue to treat AKI. Keywords: artesunate, liposomes, AKI, cisplatin, oxidative stress, inflammation

Na Li,1 Xiaochun Jiang,2 Wanju Zhang,1 Wenping Xiao,1 Zhaona Wu,1 Huirong Wang,1 Feng He1 1Li Shizhen College of Traditional Chinese Medicine, Huanggang Normal University, Huanggang, 438000, People’s Republic of China; 2Hubei Key Laboratory for Processing and Application of Catalytic Materials, College of Chemistry and Chemical Engineering, Huanggang Normal University, Huanggang, 438000, People’s Republic of ChinaCorrespondence: Na Li; Feng He, Email ln19860622@126.com; hfeng@hust.edu.cnIntroduction: Combined multimodal therapy for breast cancer is a promising therapeutic approach to increase treatment efficacy and reduce systemic toxicity. The present study aimed to develop a novel multifunctional drug release nanoplatform based on RGD-conjugated hyaluronic acid (HA)-functionalized copper sulfide (CuS) for activatable dual-targeted synergetic therapy against cancer.Methods: The pH and NIR-responsive dual-targeting nanoplatform CuS:Ce6@HA:DOX@RGD was prepared, characterized, and evaluated for its stability and photodynamic and photothermal properties. The loading and release of the drug were measured at different pH values with or without laser radiation using the dialysis method. The cellular uptake of the platform specifically by the tumor cells treated with different formulations was investigated through fluorescence imaging. The in vitro and in vivo biosafety levels were assessed systematically. Finally, the antitumor efficiencies against breast cancer were assessed via in vitro and in vivo experiments.Results: The spheroid CuS:Ce6@HA:DOX@RGD exhibited remarkable stability and monodispersity in solution. The photosensitive CuS and Ce6 could simultaneously absorb the near-infrared light efficiently to convert NIR light to fatal heat and to generate reactive oxygen species. The CuS:Ce6@HA:DOX@RGD dissociated under an acid environment, causing the release of DOX into the tumor to accelerate upon laser irradiation. The CuS:Ce6@HA:DOX@RGD exhibited target-specific and strong binding ability via a synergic CD44/αvβ3 receptor-mediated bimodal targeting, which led to improved therapeutic efficacy. The tumor growth was effectively inhibited using synergetic photodynamic/photothermal/chemo therapy. No evident systemic toxicity was noted during treatment.Conclusion: The newly prepared CuS:Ce6@HA:DOX@RGD has great potential as an activatable theranostic nanoplatform for efficient dual-targeted synergistic therapy against breast cancer. Keywords: responsive nanoplatform, targeting, drug delivery, synergistic therapy, breast cancer

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

Fangfang Yuan,1 Weiqiang Xiao,2 Xiaokun Wang,2 Yuewen Fu,1 Xudong Wei1 1Department of Hematology, The Affiliated Cancer Hospital of Zhengzhou University& Henan Cancer Hospital, Zhengzhou, People’s Republic of China; 2Department of Laboratory Science, The Affiliated Cancer Hospital of Zhengzhou University& Henan Cancer Hospital, Zhengzhou, People’s Republic of China;Correspondence: Xudong Wei; Yuewen Fu, Department of Hematology, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, People’s Republic of China, Tel +86-371-65587218 ; +86-371-65587027, Email xudongwei@zzu.edu.cn; zlyyfuyuewen1480@zzu.edu.cnObjective: To analyze the clinical characteristics and prognostic risk factors of carbapenem-resistant Pseudomonas aeruginosa (CRPA) bloodstream infections in patients with hematologic malignancies.Methods: Medical records and drug susceptibility data of patients with hematologic malignancies complicated by CRPA bloodstream infections admitted to the Cancer Hospital of Zhengzhou University between January 1, 2018, and December 31, 2022, were retrospectively analyzed.Results: A total of 64 patients were included in the study, with a mortality rate of 37.5% (24/64) at 28 days after the occurrence of CRPA bloodstream infection. In Cox regression analysis, an absolute neutrophil count < 0.5× 109/L at discharge (HR 0.039, 95% CI 0.006 ~ 0.258, p=0.001), admission to the intensive care unit (HR 7.546, 95% CI 1.345 ~ 42.338, p= 0.022), and a higher Pitt bacteremia score (HR 0.207, 95% CI 0.046 ~ 0.939, p = 0.041) were independent risk factors associated with 28-day mortality. Survival analysis showed that patients receiving ceftazidime-avibactam-based (HR 0.368, 95% CI 0.107~ 1.268, p = 0.023) or polymyxin B (HR 2.561, 95% CI 0.721 ~ 9.101, p = 0.015) therapy had a higher survival rate.Conclusion: Patients with hematologic neoplasms had high mortality from CRPA bloodstream infections, and admission to the intensive care unit, higher Pitt bacteremia score (PBS) scores, granulocyte deficiency, and granulocyte deficiency at discharge were independently associated with higher mortality. Early anti-infective treatment with ceftazidime-avibactam or polymyxin B may improve the clinical prognosis of patients.Keywords: Pseudomonas aeruginosa, carbapenem resistance, bloodstream infection, hematologic neoplasm, risk factors

Yubo Li,1,2,&ast; Chengming Li,1,2,&ast; Tao Luo,3,&ast; Tian Yue,4 Wenjing Xiao,5 Ling Yang,1,2 Zaiyuan Zhang,6 Fei Han,3,&ast; Pan Long,3 Yonghe Hu6 1School of Clinical Medicine, Chengdu University of TCM, Chengdu, People’s Republic of China; 2Basic Medical Laboratory, The General Hospital of Western Theater Command, Chengdu, People’s Republic of China; 3Department of Ophthalmology, The General Hospital of Western Theater Command, Chengdu, People’s Republic of China; 4School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, People’s Republic of China; 5Department of Pharmacy, The General Hospital of Western Theater Command, Chengdu, People’s Republic of China; 6College of Medicine, Southwest Jiaotong University, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Pan Long, Department of Ophthalmology, The General Hospital of Western Theater Command, Rongdu Avenue &num;270, Chengdu, People’s Republic of China, Tel +86-181-9125-6132, Email longpan1005@qq.com Yonghe Hu, College of Medicine, Southwest Jiaotong University, No. 111, North First section of the Second Ring Road, Chengdu, People’s Republic of China, Tel +86-138-8059-6789, Email huyonghezyy@163.comAbstract: With the increasing of altitude activities from low-altitude people, the study of high altitude cerebral edema (HACE) has been revived. HACE is a severe acute mountain sickness associated with exposure to hypobaric hypoxia at high altitude, often characterized by disturbance of consciousness and ataxia. As for the pathogenesis of HACE, previous studies suggested that it might be related to the disorder of cerebral blood flow, the destruction of blood-brain barrier and the injury of brain parenchyma cells caused by inflammatory factors. In recent years, studies have confirmed that the imbalance of REDOX homeostasis is also involved in the pathogenesis of HACE, which mainly leads to abnormal activation of microglia and destruction of tight junction of vascular endothelial cells through the excessive production of mitochondrial-related reactive oxygen species. Therefore, this review summarizes the role of REDOX homeostasis and the potential of the treatment of REDOX homeostasis in HACE, which is of great significance to expand the understanding of the pathogenesis of HACE. Moreover, it will also be helpful to further study the possible therapy of HACE related to the key link of REDOX homeostasis.Keywords: high altitude cerebral edema, hypobaric hypoxia, REDOX homeostasis, mitochondria dysfunction, microglia

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

Jin Chen,1,&ast; Guoping Zhu,2,&ast; Wenbo Xiao,3 Xiaosong Huang,4 Kewu Wang,2 Yi Zong2 1Department of Hematology, Yiwu Central Hospital, Yiwu, People’s Republic of China; 2Department of Radiology, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, People’s Republic of China; 3Department of Radiology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 4Department of Pharmacy, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Kewu Wang; Yi Zong, Department of Radiology, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, No. N1, Shangcheng Avenue, Yiwu, Zhejiang, People’s Republic of China, Email 8016070@zju.edu.cn; zong@zju.edu.cnBackground: The main propanaxatriol-type saponin found in ginseng (Panax ginseng C. A. Mey), ginsenoside Rg1 (G-Rg1), has bioactivities that include anti-inflammatory, antioxidant, and anti-diabetic properties. This study aimed to investigate the effects of G-Rg1 on streptozotocin (STZ)-induced Type 1 Diabetes mellitus (T1DM) mice and the insulin-secreting cell line in RIN-m5F cells with high-glucose (HG) treatment.Methods: The STZ-induced DM mice model was treated with G-Rg1 alone or combined with 3-Methyladenine (3-MA, an autophagy inhibitor)/rapamycin (RAPA, an autophagy activator) for 8 weeks, and levels of glucose and lipid metabolism, histopathological changes, as well as autophagy and apoptosis of relevant markers were estimated. In vitro, the HG-induced RIN-m5F cells were treated with G-Rg1, 3-MA, and Compound C (CC), an AMPK inhibitor, or their combinations to estimate the influences on cell apoptosis, autophagy, and AMPK/mTOR pathway-associated target gene levels.Results: G-Rg1 treatment attenuated glucose and lipid metabolism disorder and pancreatic fibrosis in diabetic mice. In addition, subdued autophagy and p-AMPK protein expression, and enhanced p-mTOR protein expression and apoptosis levels in TIDM mice and HG-induced RIN-m5F cells were ameliorated by G-Rg1 treatment. Furthermore, these anti-apoptosis effects of G-Rg1 were partially abolished by 3-MA and CC.Conclusion: Our findings revealed that G-Rg1 exhibits strong anti-apoptosis ability in pancreatic tissues of type 1 diabetic mice and HG-induced RIN-m5F cells, and the mechanisms involved in activating AMPK and inhibiting mTOR-mediated autophagy, indicating that G-Rg1 may have the therapeutic and preventive potential for treating pancreatic injury in diabetic patients.Keywords: diabetes mellitus, ginsenoside Rg1, autophagy, apoptosis, AMPK

Xiachuan Qin,1,2 Xiaomin Hu,2 Weihan Xiao,2 Chao Zhu,3 Qianqin Ma,1 Chaoxue Zhang1 1Department of Ultrasound, The First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China; 2Department of Ultrasound, Nanchong Central Hospital, The Second Clinical Medical College, North Sichuan Medical College (University), Nan Chong, People’s Republic of China; 3Department of Radiology, The First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of ChinaCorrespondence: Chaoxue Zhang, Department of Ultrasound, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230022, People’s Republic of China, Tel +86-13955158023, Email zcxay@163.comObjective: Distinguishing the degree of differentiation, hepatocellular carcinoma (HCC) has important clinical significance in the therapeutic decision-making and patient prognosis evaluation.Methods: We developed a deep-learning radiomics (DLR) model based on contrast-enhanced ultrasound (CEUS) to evaluate the differentiation of HCC noninvasive. We retrospectively analyzed HCC patients who had undergone resection and CEUS one week preoperatively between November 2015 and August 2022. Enrolled patients were randomly divided into training (n=190) and testing (n=82) cohorts in a 7:3 ratio. The depth of learning and radiological characteristics reflecting the differentiation degree of HCC were extracted, and the least absolute shrinkage and selection operator(LASSO) was used for feature selection to obtain the most valuable features and then build a DLR model based on the useful features.Results: The deep-learning Radiomics model could accurately predict the degree of differentiation of HCC; the area under the curve of the DLR model in the training and testing cohorts was 0.969 and 0.932, respectively. The accuracy, sensitivity, and specificity of the CEUS-based DLR model for predicting the differentiation of HCC were 0.915, 0.938, and 0.900, respectively, in the testing cohort. The decision curve analysis confirmed that the combined model predicted good overall net income for differentiation.Conclusion: The CEUS-based DLR model provides an easy-to-use, visual, and personalized tool for predicting the differentiation of HCC and can help doctors formulate more favorable treatment plans for patients.Keywords: hepatocellular carcinoma, differentiated, contrast-enhanced ultrasound, deep-learning, radiomics

Xiachuan Qin,1,2,&ast; Linlin Xia,1,&ast; Chao Zhu,3 Xiaomin Hu,2 Weihan Xiao,2 Xisheng Xie,4 Chaoxue Zhang1 1Department of Ultrasound, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of China; 2Department of Ultrasound, Nanchong Central Hospital, The Second Clinical Medical College, North Sichuan Medical College (University), Nan Chong, Sichuan, People’s Republic of China; 3Department of Radiology, The First Affiliated Hospital of Anhui Medical university, Hefei, Anhui, People’s Republic of China; 4Department of Nephrology, Nanchong Central Hospital, The Second Clinical Medical College, North Sichuan Medical College (University), Nan Chong, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chaoxue Zhang, Department of Ultrasound, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of China, Email zcxay@163.com Xisheng Xie, Department of Nephrology, Nanchong Central Hospital, The Second Clinical Medical College, North Sichuan Medical College (University), Nan Chong, Sichuan, People’s Republic of China, Email xishengx@163.comIntroduction: To explore whether ultrasonic radiomics extracted by machine learning method can noninvasively evaluate lupus nephritis (LN) activity.Materials and Methods: This retrospective study included 149 patients with LN diagnosed by renal biopsy. They were divided into a training cohort (n=104) and a test cohort (n=45). Ultrasonic radiomics features were extracted from the ultrasound images, and the radiomics features were constructed. Furthermore, five machine learning algorithms were compared to evaluate LN activity. The performance of the binary classification model was evaluated by the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV).Results: The average AUC of the five machine learning models was 79.4, of which the MLP model was the best. The AUC of the training group was 89.1, with an accuracy of 81.7%, a sensitivity of 83%, a specificity of 80.7%, a negative predictive value of 85.2%, and a positive predictive value of 78%. The AUC of the test group was 82.2, the accuracy was 73.3%, the sensitivity was 78.9%, the specificity was 69.2%, the negative predictive value was 81.8%, and the positive predictive value was 65.2%.Conclusion: Machine learning classifier based on ultrasonic radiomics has high accuracy for LN activity. The model can be used to noninvasively detect the activity of LN and can be an effective tool to assist the clinical decision-making process.Keywords: systemic lupus erythematosus, lupus nephritis, activity, ultrasound, machine learning

Wenwu Xiao,1 Huaichun Yang,1 Zhuangfu Wang,2 Haian Mao,1 Hongjiang Wang,1 Zengming Hao,1 Yao Zu,1 Chuhuai Wang1 1Department of Rehabilitation Medicine, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of China; 2Faculty of Population Health Sciences, Institute of Child Health I, University College London, London, UKCorrespondence: Chuhuai Wang, Department of Rehabilitation Medicine, the First Affiliated Hospital, Sun Yat-Sen University, No. 58 Zhongshan Er Road, Guangzhou, 510080, People’s Republic of China, Tel +86 13316191023, Email wangchuh@mail.sysu.edu.cnAbstract: Low back pain is a major global public health problem, but the current intervention effect is not ideal. A large body of previous literature suggests that patients with chronic low back pain may have abnormal postural control, which is more evident in the dual task situation. In recent years, research on postural control in patients with low back pain under dual-task conditions has gradually become a hot topic. However, the results obtained from these studies were not entirely consistent. In this review, we summarized relevant studies on the performance of postural control in patients with low back pain under dual-task conditions, analyze it from the perspective of the theoretical model of dual-task interaction, the specific research paradigm of dual task, the performance of postural control, and the related factors affecting postural control performance, etc. It was reasonable to assume that patients with low back pain might have a certain degree of abnormal postural control, and this abnormality was affected by comprehensive factors such as age, cognitive resource capacity, attention needs, complex sensorimotor integration, external environment, etc. Furthermore, postural control performance in low back pain patients under dual-task conditions was further influenced by the nature and complexity of the different tasks. In general, the more attention resources were needed, the external environmental conditions were worse, and the age-related functions were degenerate, etc., the weaker posture control ability was. In short, a deeper understanding of postural control in patients with low back pain under dual-task conditions may shed light on more references for the rehabilitation and management of low back pain, as well as some new ideas for scientific research on cognition and postural control.Keywords: postural control, low back pain, dual-task, cognitive, motor

Xuegang Wang,1,&ast; Weiquan Li,2,&ast; Ning Lou,3,&ast; Weiwei Han,3 Bo Hai,2 Wen Xiao,2 Xiaoping Zhang2 1Department of Urology, The First Affiliated Hospital, School of Medicine, Xiamen University, Xiamen, Fujian, People’s Republic of China; 2Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 3Department of Urology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wen Xiao; Bo, Hai, Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, Hubei Province, 430022, People’s Republic of China, Tel +86-17088353610, Fax +86 85776343, Email xiaowenx11@163.com; Haibo2022@hust.edu.cnBackground: Invasion and metastasis led to poor prognosis and death of clear cell renal cell carcinoma (ccRCC) patients. The deoxynucleotidyl transferase terminal interacting protein 1 (DNTTIP1) was reported to promote multiple tumor progression. However, there is no research about DNTTIP1 in ccRCC.Methods: Kaplan–Meier survival analysis, multivariate analysis demonstrated the prognostic indicator in overall survival (OS) and disease-free survival (DFS) of ccRCC with DNTTIP1 expression in the Cancer Genome Atlas Kidney Clear Cell Carcinoma (TCGA-KIRC). Receiver operator characteristic (ROC) curve analyzed diagnostic ability of DNTTIP1 in TCGA-KIRC and validation dataset. The quantitative real-time polymerase chain reaction (qRT-PCR) detected the DNTTIP1 expression in renal cancer tissues, and the Office of Cancer Clinical Proteomics Research (CPTAC) verified the protein expression of DNTTIP1. Moreover, nomogram predicted the role of DNTTIP1 in ccRCC patient. Single-sample Gene Set Enrichment Analysis (SsGSEA) and GSEA evaluated the pathogenesis role of DNTTIP1 in TCGA-KIRC.Results: DNTTIP1 expression was higher in ccRCC tumor tissues. High expression of DNTTIP1 was associated with poor OS (HR = 1.618, P < 0.0001), and poor DFS (HR = 1.789, P < 0.0001). SsGSEA and GSEA showed DNTTIP1 was associated with hypoxia, epithelial-mesenchymal transition (EMT), angiogenesis, G2M checkpoint. DNTTIP1 had a positive correlation with EMT biomarkers in ccRCC, and might be an effective target for ccRCC.Conclusion: This study provided that higher expression of DNTTIP1 predicted poor prognosis in ccRCC, and DNTTIP1 might be a novel detection biomarker and therapeutic target of tumor malignant in the future.Keywords: DNTTIP1, ccRCC, gene therapy, prognostic indicator

The porous carbon blacks rationally designed by a facile yet efficient NH3 thermal etching route have been investigated as anode materials in an ether-based electrolyte for sodium-ion batteries. The as-synthesized CBN35 carbon black with a 35% weight loss after NH3 thermal etching exhibited a large specific charge capacity of 352 mAh g−1 at 50 mA g−1 and a superior rate capability of 101 mAh g−1 at 16000 mA g−1, due to its highest microporosity, an appropriate surface area, a desirable microstructure, and a promising hybrid intercalation mechanism. Impressively, even cycled at 1600 mA g−1 over 3200 cycles, an outstanding reversible capacity of 103 mAh g−1 with a negligible 0.0162% capacity loss per cycle can still be achieved. Based on the multimodal characterizations including the structural probes of phase evolution for carbon materials, the electrochemical techniques, and the surface-sensitive XAS measurements, the exceptional electrochemical properties should stem from several merits of modified carbon black system. While the particular microporous structure provides relatively more accessible sodium storage sites, a novel hybrid intercalation mechanism in ether-based electrolyte would incorporate the sodium ion insertion into the disordered structure with the solvated sodium ion species co-intercalation into the graphitic phase. In addition to the diffusion-controlled redox reactions, the noticeable surface-induced pseudocapacitive reactions also significantly contribute to the charge storage upon sodiation and guarantee the rapid migrations of sodium ions/solvated compounds. This system further features a controlled emergence of a robust but thin solid electrolyte interphase layer, which could suppress the side reactions of active electrode with reactive electrolyte, maintain the fragile porous structure upon cycling, and facilitate the migrations of sodium ions and solvated sodium ion compounds.

Abstract The space environment includes unique hazards like radiation and microgravity which can adversely affect biological systems. We assessed a multi-omics NASA GeneLab dataset where mice were hindlimb unloaded and/or gamma irradiated for 21 days followed by retinal analysis at 7 days, 1 month or 4 months post-exposure. We compared time-matched epigenomic and transcriptomic retinal profiles resulting in a total of 4178 differentially methylated loci or regions, and 457 differentially expressed genes. Highest correlation in methylation difference was seen across different conditions at the same time point. Nucleotide metabolism biological processes were enriched in all groups with activation at 1 month and suppression at 7 days and 4 months. Genes and processes related to Notch and Wnt signaling showed alterations 4 months post-exposure. A total of 23 genes showed significant changes in methylation and expression compared to unexposed controls, including genes involved in retinal function and inflammatory response. This multi-omics analysis interrogates the epigenomic and transcriptomic impacts of radiation and hindlimb unloading on the retina in isolation and in combination and highlights important molecular mechanisms at different post-exposure stages.

Junwei Gao,1 Ziyun Li,1 Jing Li,2 Ping Song,3 Jinsheng Yang,1 Wei Xiao,4 Ning Li,1 Ruodan Xu1 1Department of Biomedical Engineering and Technology, Institute of Basic Theory for Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China; 2Department of Nephropathy, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 3Department of Dermatology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China; 4Key Laboratory of New-Tech for Chinese Medicine Pharmaceutical Process, Jiangsu Kanion Pharmaceutical Co. Ltd., Lianyungang, People’s Republic of ChinaCorrespondence: Ruodan Xu; Ning Li, Email ruodanxu@gmail.com; lili.li.ning@gmail.comPurpose: Peptide-based high-density lipoprotein (pHDL) structurally and functionally resembles the natural HDL as anti-atherosclerosis (AS) therapies. Since pHDL contains a large hydrophobic core, this study aims to evaluate the potentials of pHDL as a hydrophobic drug carrier and the efficiency of drug-loaded pHDL in the control of AS.Methods: The pHDL encapsulation of hydrophobic components from natural plants, including curcumin (Cur) and tanshinone IIA (TanIIA), was achieved using one-step microfluidics. Then, morphological features and loading efficiencies of pHDL-Cur and pHDL-TanIIA were determined by TEM and high-performance liquid chromatography (HPLC), respectively. Taking the fluorescence advantage of Cur, localizations of loaded Cur in pHDL were investigated by fluorescence quenchers, and recruitments of Cur to AS plaques were assessed with ex vivo imaging. Based on anti-inflammatory properties of TanIIA, pHDL-TanIIA was accordingly developed to evaluate the anti-AS effects through examinations of plasma lipid parameters and pathological alterations of plaque-associated regions.Results: Both lipophilic Cur and TanIIA can be efficiently loaded into pHDL carriers. The resultant pHDL-Cur and pHDL-TanIIA inherit the homogeneous nano-disk structure of pHDL. By using pHDL-Cur, the encapsulated hydrophobics are tracked in the core of pHDL, and incorporations of Cur with pHDL vehicles greatly improve the bioavailability and association of Cur with AS plaques. Moreover, when loaded with TanIIA, which has established its role in anti-AS as an anti-inflammatory candidate, synergistic effects in reducing AS lesions and improving pathological alterations of main organs related to AS were achieved.Conclusion: The pHDL system could potentially be applied for both imaging and therapy in animal models of AS. Benefits of pHDL-based drug delivery will potentially extend the application scenarios of bioactive chemicals from natural plants which are underutilized due to features like low bioavailability and facilitate the clinical translation of synthetic HDL therapies in HDL-associated disorders, including but not limited to AS.Graphical Abstract: Keywords: HDL, peptide-based HDL, atherosclerosis, drug delivery, natural plants, antiatherogenic therapy

Xiaoning Zhao, Xiaoqian Li, Ying Wang, Weijie Xiao, Baihui Zhang, Xin Meng, Xijia Sun The Department of Anesthesiology, The First Affiliated Hospital of China Medical University, Shenyang, People’s Republic of ChinaCorrespondence: Xijia Sun, The Department of Anesthesiology, The First Affiliated Hospital of China Medical University, Shenyang, People’s Republic of China, Tel +86 15840015620, Email xijia0822@163.comBackground: Patients undergoing video-assisted thoracoscopic surgery (VATS) frequently suffered postoperative acute and chronic pains. In recent years, intrathoracic intercostal nerve block (INB) is regularly used thanks to its safety and accuracy, especially under the circumstance of lacking ultrasound or in face of the contraindications of the thoracic paravertebral block (TPVB). However, clinical evidence of comparing TPVB and INB for pain management after VATS has been limited and the observation of the chronic pain has been less than clear.Methods: A total of 180 patients undergoing VATS were randomly divided into three groups: A single multi-point paravertebral nerve block (Group P), intrathoracic intercostal nerve block (Group I), and general anesthesia without any regional block (Group C). Postoperative acute pain was scored at rest and coughing by the Visual Analog Scale (VAS) for recording 24h, 48h and 72h after VATS. All patients were interviewed 1, 3 and 6 months after the surgery to investigate both the incidence and intensity of chronic pains.Results: There were significantly less incidence and intensity of acute pain in Group P and Group I, compared to those in Group C. The patients in Group I showed the least incidence and intensity of chronic pain after 3 months compared with those in Group P and Group C. There are 89 of 98 patients suffering pains after 1 month, which grew into chronic pains after 3 months and 78 of them still suffered chronic pains even after 6 months.Conclusion: The intrathoracic INB offers excellent relief from acute and chronic pains, which does as effectively as TPVB. Besides, one-month postoperative pain could increase the risk of a chronic one.Keywords: video-assisted thoracoscopic surgery, acute pain, chronic pain, intrathoracic intercostal nerve block, paravertebral nerve block

Luo Jindan,&ast; Wang Xiao,&ast; Xie Liping Department of Urology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xie Liping, Department of Urology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China, Email xielp@zju.edu.cnAbstract: Use of α-androgenic receptor blockers remains a mainstay therapeutic approach for the treatment of urological diseases. Silodosin is recommended over other α-blockers for the treatment of lower urinary tract symptoms (LUTS) and benign prostate hyperplasia (BPH), due to its high α1A uroselectivity. Current research data suggest that silodosin is efficacious in the management of various urological diseases. Thus, we herein review the current evidence of silodosin related to its efficacy and tolerability and appraise the available literature that might ultimately aid in management of various urological conditions at routine clinical practice. Literature reveals that silodosin is beneficial in improving nocturia events related to LUTS/BPH. Silodosin exerts effect on relaxing muscles involved in detrusor obstruction, therefore prolonging the need for patients undergoing invasive surgery. Silodosin treatment, either as a monotherapy or combination, significantly improves International Prostate Symptom Score (IPSS) including both storage and voiding symptoms in patients with BPH/LUTS. Patients on other treatment therapies such as phosphodiesterase 5 inhibitors or other α-blockers are well managed with this drug. Steadily, silodosin has proved beneficial in the treatment of other urological disorders such as chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), overactive bladder/acute urinary retention (AUR), premature ejaculation (PE), and prostate cancer post brachytherapy-induced progression. In patients with distal ureteral stones, silodosin treatment is beneficial in decreasing stone expulsion time without affecting stone expulsion rate or analgesic need. Moreover, there were significant improvements in intravaginal ejaculation latency time, quality of life scores, and decrease in PE profile among patients with PE. Silodosin has also demonstrated promising results in increasing the likelihood of successful trial without catheter in patients with AUR and those taking antihypertensive drugs. Reports from Phase II studies have shown promising role of silodosin in the treatment of CP/CPPS as well as facilitating ureteral stone passage. From the robust data in this review, further silodosin treatment strategies in the management of different urological conditions need to be focused on.Keywords: efficacy, benign prostate hyperplasia, ureteral calculi, prostatitis, silodosin, urological

Increasingly, donors that subsidize socially-desirable products in the developing world are shifting from distributing through non-commercial to commercial channels, ceding control of the product price to for-profit intermediaries. This study advises a donor as to how the donor’s loss of price control and the level of consumer awareness—defined as the fraction of the consumer population that is informed of the product’s benefits—influence the donor’s optimal subsidy and utility: First, in shifting to the commercial channel, the donor should increase (decrease) the subsidy when consumer awareness is low (high). Second, with the commercial channel, the donor should be prepared to increase the subsidy as awareness increases, which is contrary to her actions with a non-commercial channel. Third, contrary to the lesson obtained with non-commercial distribution, with commercial distribution the donor can be hurt by increased awareness. This occurs when awareness is moderate. The implication is that a donor that operates in such a setting should be wary in encouraging entities (e.g., governments, non-governmental organizations) to institute campaigns that increase the awareness of the product’s benefits. The intermediary’s decision of whether to target either only informed consumers or the broad market drives our results.

Jun Hou,1,&ast; Dezhi Zheng,2,&ast; Xudong Wen,3,&ast; Wenjing Xiao,4 Fei Han,5 Hongmei Lang,6 Shiqiang Xiong,1 Wei Jiang,5 Yonghe Hu,4 Mengshan He,7 Pan Long4,5 1Department of Cardiology, Chengdu Third People’s Hospital/Affiliated Hospital of Southwest Jiaotong University, Chengdu, People’s Republic of China; 2Department of Cardiovascular Surgery, the 960th Hospital of the PLA Joint Logistic Support Force, Jinan, People’s Republic of China; 3Department of Gastroenterology and Hepatology, Chengdu First People’s Hospital, Chengdu, People’s Republic of China; 4School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu, People’s Republic of China; 5Department of Ophthalmology, the General Hospital of Western Theater Command, Chengdu, People’s Republic of China; 6The Center of Obesity and Metabolic Diseases, Department of General Surgery, Chengdu Third People’s Hospital & the Affiliated Hospital of Southwest Jiaotong University, Chengdu, People’s Republic of China; 7Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi’an, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Pan Long, Department of Ophthalmology, the General Hospital of Western Theater Command, Rongdu Avenue #270, Chengdu, People’s Republic of China, Tel +86-181-9125-6132, Email longpan1005@qq.com Yonghe Hu, School of Materials Science and Engineering, Southwest Jiaotong University, No. 111, North First Section of the Second Ring Road, Chengdu, People’s Republic of China, Tel +86-138-8059-6789, Email huyonghe789@sina.comPurpose: High-altitude environment mainly with hypobaric hypoxia could induce pathological alterations in ocular tissue. Previous studies have mostly focused on sporadic case reports and simulated high-altitude hypoxia experiments. This aim of this study was to explore the proteomic and morphological changes of ocular tissue in mice at real altitude environment.Methods: In this study, mice were flown from Chengdu (elevation: 500 m) to Lhasa (elevation: 3600 m). After exposure for 1day, 3, 6, 10, 20, 30, and 40days, the mice were euthanatized to obtain blood and ocular tissue. Serological tests, ocular pathological examinations, integral ocular proteomics analysis, and Western blot were conducted.Results: We focused on acute phase (1– 3 days) and chronic phase (> 30 days) during high-altitude acclimatization. Serum interleukin-1 was increased at 3 days, while superoxide dismutase, interleukin-6, and tumor necrosis factor-α showed no statistical changes. H&E staining demonstrated that the cornea was edematous at 3 days and exhibited slower proliferation at 30 days. The choroid showed a consistently significant thickening, while there existed no noticeable changes in retinal thickness. Overall, 4073 proteins were identified, among which 71 and 119 proteins were detected to have significant difference at 3 days and 40 days when compared with the control group. Functional enrichment analysis found the differentiated proteins at 3 days exposure functionally related with response to radiation, dephosphorylation, negative regulation of cell adhesion, and erythrocyte homeostasis. Moreover, the differential profiles of the proteins at 40 days exposure exhibited changes of regulation of complement activation, regulation of protein activation cascade, regulation of humoral immune response, second-messenger-mediated signaling, regulation of leukocyte activation, and cellular iron homeostasis. Interestingly, we found the ocular proteins with lactylation modification were increased along high-altitude adaptation.Conclusion: This is the first work reporting the ocular proteomic and morphological changes at real high-altitude environment. We expect it would deep the understanding of ocular response during altitude acclimatization.Keywords: altitude response, ocular proteomics analysis, cornea edema, choroid thickening, post-translational modification

Yi Yang,1 Wei Xiao,2 Xingtai Liu,1 Yan Zhang,1 Xin Jin,1 Xiao Li1 1Department of Clinical Laboratory, The Third Clinical Medical College of the Three Gorges University, Gezhouba Central Hospital of Sinopharm, Yichang, People’s Republic of China; 2Department of Gastroenterology, Xianning central Hospital, The First Affiliated Hospital of Hubby University of Science and Technology, Xianning, People’s Republic of ChinaCorrespondence: Xiao Li, Department of Clinical Laboratory, The Third Clinical Medical College of the Three Gorges University, Gezhouba Central Hospital of Sinopharm, Yichang, 443002, People’s Republic of China, Tel +86 717-672020, Email yi8847307962629@126.comPurpose: Acute kidney injury (AKI) is a frequent complication of severe acute pancreatitis (AP) and carries a very poor prognosis. The present study aimed to construct a model capable of accurately identifying those patients at high risk of harboring occult acute kidney injury (AKI) characteristics.Patients and Methods: We retrospectively recruited a total of 424 consecutive patients at the Gezhouba central hospital of Sinopharm and Xianning central hospital between January 1, 2016, and October 30, 2021. ML-assisted models were developed from candidate clinical features using two-step estimation methods. The receiver operating characteristic curve (ROC), decision curve analysis (DCA), and clinical impact curve (CIC) were performed to evaluate the robustness and clinical practicability of each model.Results: Finally, a total of 30 candidate variables were included, and the AKI prediction model was established by an ML-based algorithm. The areas under the ROC curve (AUCs) of the random forest classifier (RFC) model, support vector machine (SVM), eXtreme gradient boosting (XGBoost), artificial neural network (ANN), and decision tree (DT) ranged from 0.725 (95% CI 0.223– 1.227) to 0.902 (95% CI 0.400– 1.403). Among them, RFC obtained the optimal prediction efficiency via adding inflammatory factors, which are serum creatinine (Scr), C-reactive protein (CRP), platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), neutrophil-to-albumin ratio (NAR), and CysC, respectively.Conclusion: We successfully developed ML-based prediction models for AKI, particularly the RFC, which can improve the prediction of AKI in patients with AP. The practicality of prediction and early detection may be greatly beneficial to risk stratification and management decisions.Keywords: acute pancreatitis, acute kidney injury, serum cytokines, cystatin-C, machine learning algorithms, prediction

Simin Wu,1 Weihua Hu,1 Wei Xiao,1 Yongxia Li,2 Yan Huang,1 Xu Zhang1 1Department of Respiratory Medicine, The First Affiliated Hospital of Yangtze University, Jingzhou, 434000, Hubei, People’s Republic of China; 2Department of Respiratory Medicine, The Second Affiliated Hospital of Kunming Medical University, Kunming, 650000, Yunnan, People’s Republic of ChinaCorrespondence: Weihua Hu; Wei Xiao Tel +86-18163137571; +86-18972161798Email huweihua@yangtzeu.edu.cn; 99xw@sina.comAbstract: Gardnerella vaginalis is a pathogen responsible for bacterial vaginosis, which is commonly found in female vaginas and rarely causes infections outside the female genitalia. Here, we report the use of metagenomic next-generation sequencing (mNGS) to detect and confirm pulmonary infection and pleural effusion caused by G. vaginalis in a 47-year-old man. The patient’s symptoms and imaging improved after 2 weeks of oral ornidazole, and he was cured after 3 months. Overall, the findings of this case demonstrate that mNGS is a useful tool for diagnosis of unexplained lung infections and pleural effusions. Its effectiveness in rapid and accurate etiological diagnosis and monitoring of diseases can allow detection of the etiology of difficult cases that return negative results after traditional cultures.Keywords: Gardnerella vaginalis, lung infection, metagenomic next-generation sequencing

Weilong Xiao1,2 &ast;, Binghai Sun1 &ast;, Hui Zhou,3 Liting Fan,1,2 Changkang Sun,1 Yanhong Shao4 1College of Teacher Education, Zhejiang Normal University, Jinhua, Zhejiang, People’s Republic of China; 2Key Laboratory of Intelligent Education Technology and Application of Zhejiang Province, Zhejiang Normal University, Jinhua, Zhejiang, People’s Republic of China; 3Jinhua Advanced Research Institute, Jinhua, Zhejiang, People’s Republic of China; 4Zhejiang International Studies University, Hangzhou, Zhejiang, People’s Republic of China&ast; These authors contributed equally to this workCorrespondence: Changkang SunCollege of Teacher Education, Zhejiang Normal University, 688 Yingbin Road, Jinhua, 321004, Zhejiang, People’s Republic of ChinaEmail 1158067980@qq.comYanhong ShaoZhejiang International Studies University, 299 Liuhe Road, Xihu District, Hangzhou, 310013, Zhejiang Province, People’s Republic of ChinaEmail yhshao2003@126.comPurpose: People choose actions that maintain their moral self-regard. This paper explains how one’s moral actions influence moral self-regard. The moral threshold model (MTM) has been proposed by scholars and tested using a limited sample. However, whether the MTM is universally applicable among people is still unknown.Participants and Methods: Our sample comprised 1761 individuals living in China, a collectivist culture, who were recruited to test the two main hypotheses of the MTM. Participants engaged in a hypothetical investment task.Results: 1) When the beneficiary was a prosocial cause, participants showed stronger preferences for smaller guaranteed positive payouts over larger uncertain ones; 2) as compared to making decisions for charities, when a participant made decisions exclusively for themselves, the maximum potential benefit was more likely to influence participant behavior.Conclusion: The current study provides initial evidence for the validity of using the worst outcome avoidance (WOA) hypothesis of MTM among members of China’s collectivist culture, indicating that the WOA hypothesis of MTM may have universal application.Keywords: collectivist culture, morality, moral self-regard, prosocial behavior, egoistic behavior

Weilong Xiao,1,2,&ast; Hui Zhou,3,&ast; Xinwei Li,1 Xue Lin4 1School of Teacher Education, Zhejiang Normal University, Jinhua, People’s Republic of China; 2School of Education, Fujian Polytechnic Normal University, Fuzhou, People’s Republic of China; 3Jinhua Advanced Research Institute, Jinhua, People’s Republic of China; 4Psychological Counseling Center of Student Affairs Office, Zhangzhou City College, Zhangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xinwei Li; Xue Lin Email Lixinwei0417@126.com; 564056074@qq.comPurpose: Previous studies have investigated the relationship between alexithymia and problematic mobile phone use (PMPU). However, yet gaps in identifying the internal mechanisms of this relationship remain. Hence, based on the Interaction of Person–Affect–Cognition–Execution model, the current research examined the mediating roles of college students’ social interaction anxiousness (SIA) and boredom proneness (BPS) in the relationship between alexithymia and PMPU.Methods: A total of 1300 college students (Mage = 20.36 years, SD = 0.97) were recruited from two universities in the southeast of China to complete a series of questionnaires, including the Toronto alexithymia scale, SIA scale, BPS scale, and mobile phone addiction index questionnaire. In order to conduct conservative predictions, the demographic variables (ie, gender) were controlled as covariates.Results: The results of multiple mediation analysis showed that (1) alexithymia was positively linked with PMPU; (2) both SIA and BPS mediated the link between alexithymia and PMPU; and (3) a serial indirect pathway emerged (ie, alexithymia → SIA → BPS → PMPU).Conclusion: These findings indicated that alexithymia could influence PMPU in a simple indirect way (parallel mediation) and in a complex indirect way (serial mediation). Besides, these findings provide some insights into the prevention and intervention of PMPU.Keywords: alexithymia, social interaction anxiousness, boredom proneness, problematic mobile phone use, college students

Junwei Tong,1– 3,&ast; Xiangui Meng,1– 3,&ast; Qingyang Lv,1– 3,&ast; Hongwei Yuan,1– 3 Weiquan Li,1– 3 Wen Xiao,1– 3 Xiaoping Zhang1– 3 1Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 2Shenzhen Huazhong University of Science and Technology Research Institute, Shenzhen, 518000, People’s Republic of China; 3Institute of Urology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoping Zhang; Wen XiaoDepartment of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, Hubei Province, 430022, People’s Republic of ChinaFax +86 85776343Email xzhang@hust.edu.cn; xiaowenx11@163.comBackground: Increasing evidence indicated that the aberrant expression of the cytoplasmic FMR1-interacting protein (CYFIP) family might possess critical role and potential functions in cancer. But the role of CYFIP2 in clear cell renal cell carcinoma (ccRCC) is still uncharacteristic.Methods: We investigated the Cancer Genome Atlas Kidney Clear Cell Carcinoma (TCGA-KIRC) database for the expression profile, clinicopathological variables, clinical prognosis information, and promoter methylation levels of CYFIPs in ccRCC. The aberrant CYFIP2 protein expression was validated by the Human Protein Atlas (HPA) and Clinical Proteomic Tumor Analysis Consortium (CPTAC). Quantitative real-time polymerase chain reaction (qRT-PCR) was used to uncover CYFIP2 mRNA levels in 28 pairs of ccRCC cancer tissues. Kaplan–Meier analysis, univariate and multivariate Cox proportional hazard regression were performed to assess CYFIPs’ prognosis value. Gene set enrichment analysis (GSEA) was used to determined hallmark functions, gene ontology of CYFIP2. TIMER database was utilized to assess the correlation with immune infiltration in ccRCC.Results: Results showed CYFIP2 was downregulated in ccRCC, relative to paired normal tissues in TCGA-KIRC database and 28 pairs of clinical samples (P < 0.0001). Similarly, a decreased CYFIP2 protein expression was confirmed by ccRCC tissues. The results showed CYFIP2 was negatively regulated by promoter DNA methylation. Survival analysis results showed CYFIP2 could be an independent biomarker for ccRCC and its reduction predicted a poor overall survival (OS) and disease-free survival (DFS). GSEA showed CYFIP2 was involved in metabolic pathways and epithelial–mesenchymal transition (EMT). Immune infiltration analysis revealed that a list of immune markers was significantly correlated with CYFIP2 expression especially with CD4+ cells and CD8+ cells in ccRCC.Conclusion: These results show that CYFIP2 was downregulated in ccRCC patients and predicted an unfavorable prognosis. CYFIP2 might be a potential novel prognostic molecule, and related to immune infiltration, the metabolism, as well as EMT process in ccRCC. CYFIP2 could act as tumor suppressor gene in ccRCC and positive modulation of CYFIP2 might lead to development of a novel strategy for ccRCC treatment.Keywords: CYFIP2, ccRCC, methylation, prognosis, immune infiltration

Wei-xiong Xiao,&ast; Yu-ting Zhu,&ast; Zhi-chao Zhang, Min Luo, Ming-ping Ma Department of Radiology, Fujian Provincial Hospital, Provincial Clinical College of Fujian Medical University, Fuzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Min Luo; Ming-ping MaDepartment of Radiology, Fujian Provincial Hospital, Provincial Clinical College of Fujian Medical University, No. 134 East Street, Gulou District, Fuzhou, 350001, People’s Republic of ChinaTel +86 59187557768Email radiodrluo@163.comObjective: To investigate the value of dual energy CT enterography (DECTE) in evaluating the activity of Crohn’s disease (CD).Methods: The endoscopy and imaging data of 29 patients with CD confirmed by clinic and pathology were analyzed retrospectively. The clinical CD activity index (CDAI) was used as the disease activity grouping standard, 29 patients with CD were grouped into activity groups, 18 patients in the active group (CDAI ≥ 150) with 36 intestinal segments, and 11 patients in the remission group (CDAI < 150) with 20 intestinal segments.The virtual single energy CT value, slope of energy spectrum curve and iodine content were analyzed to evaluate the evaluation of intestinal CD activity by DECTE.Results: There were statistically significant differences in virtual single energy CT value (except 90 keV and 100 keV virtual single energy CT value), curve slope and iodine content between remission group and active group (P < 0.05), and has more diagnostic value for active phase (AUC > 0.5). ① Virtual single energy CT value: the AUC of 60 keV in arterial phase was the highest (0.924). The specificity of diagnosing CD in active stage was high (95%). ② Curve slope: the AUC of portal vein phase was the largest (0.731). The specificity of diagnosing CD in active stage was higher (85%). ③ Iodine content: the AUC of arterial phase was the highest (0.885). The specificity of diagnosing CD lesions in the active stage was 100%.Conclusion: The virtual single energy CT value, energy spectrum curve slope and iodine content can provide reference for clinical accurate diagnosis of CD activity.Keywords: Crohn’s disease, computed tomography, dual energy CT, virtual single

Abstract Alpha(α)Klotho, a soluble transmembrane protein, facilitates calcium-phosphorus homeostasis through feedback between bone and kidney and is a potential systemic biomarker for bone-kidney health during spaceflight. We determined if: (1) plasma αKlotho was reduced after both spaceflight aboard the ISS and hindlimb unloading (HU); and (2) deficiency could be reversed with exercise. Both spaceflight and HU lowered circulating plasma αKlotho: plasma αKlotho recovered with exercise after HU.