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Ou Yang,1 Yuhuan Teng,1 Ruoxi Zhang,2 Jie Qu1 1Department of Cadre Ward, The First Hospital of Jilin University, Changchun, Jilin, 130021, People’s Republic of China; 2Department of Cardiology, Harbin Yinghua Hospital, Harbin, Heilongjiang, 150199, People’s Republic of ChinaCorrespondence: Jie Qu; Ruoxi Zhang, Email qj610714@jlu.edu.cn; ruoxizhang8@qq.comIntroduction: Polymer-free sirolimus-eluting stent (PF-SES) possess multiple properties improving targeted drug elution and in-stent reendothelialization without the presence of polymers. The long-term clinical performance comparison between PF-SES and the latest generation polymer-coated sirolimus-eluting stents (SES), particularly regarding intravascular imaging assessment and in the type 2 diabetes mellitus (DM) population, remains unexplored.Methods: We conducted a retrospective study involving 2646 diabetes patients meeting coronary artery disease (CAD) criteria underwent coronary stents in the real-world. All patients were divided into the PF-SES group and the SES group. Optical coherence tomography (OCT) was used to evaluate the imaging characteristics of in-stent reendothelialization. Patient information between the two groups was systematically compared in hospital and at 5-year follow-up.Results: In terms of basic characteristics, the proportion of current smoker and stable angina patients in the PF-SES group was significantly higher than that in the SES group. The PF-SES group exhibited significantly higher rate of left anterior descending (LAD) lesion and more stents per patients compared to the SES group. The value of minimum lumen area (MLA), neointimal area (NA) and neointimal thickness (NT) were higher in the PF-SES group. Additionally, the occurrence rates of heterogeneous, lipid layer, intimal tears, thrombi, and micro-vessels were notably lower in the PF-SES group compared to the SES group. A higher all-cause mortality was observed in the SES cohort.Discussion: PF-SES could effectively improve in-stent reendothelialization in patients with type 2 DM, with positive effects on survival rate and may, therefore, be considered as an alternative treatment option for improving clinical long-term outcomes.Keywords: Polymer-free, polymer-coated, Nano Plus stent, drug-eluting stents, type 2 diabetes mellitus, optical coherence tomography

Jinhong Zuo,* Xiayang Zeng,* Hongyi Ma, Peng Chen, Xinlei Cai, Zhenyu Fan, Jianpeng Qu Massage Department, Zhejiang Hospital, Hangzhou City, People’s Republic of China*These authors contributed equally to this work and co-first authorsCorrespondence: Jianpeng Qu, Massage Department, Zhejiang Hospital, No. 12 Lingyin Road, Xihu District, Hangzhou City, 310000, People’s Republic of China, Email qjp0007@126.comBackground: Neck-type cervical spondylopathy (NTCS), a common degenerative disorder affecting the spine, poses challenges for patients and society. Research has demonstrated the effectiveness of traditional tuina techniques in treating NTCS, although some limitations still exist. Our study aimed to evaluate the effectiveness of combining regular massage techniques with three methods of neck movement (TCM) therapy for managing NTCS, utilizing musculoskeletal ultrasound measurements.Patients and Methods: In this study, 70 eligible patients with non-traumatic cervical spondylosis will be randomly assigned in a 1:1 ratio to either the experimental group, which will receive Tuina combined with a three-method neck movement treatment, or the control group, which will receive standard Tui Na manipulation. All participants will receive treatment for four weeks. Assessments will be conducted using musculoskeletal ultrasound, the McGill Pain Scale, and the Neck Disability Index (NDI) at three-time points: before treatment, at the end of treatment, and after 12 and 16 weeks of treatment.Conclusion: This paper investigates the utility of musculoskeletal ultrasound as a tool for evaluating the therapeutic efficacy of an integrated Traditional Chinese Medicine (TCM) strategy in alleviating pain and enhancing functional outcomes for patients with NTCS. The objective is to present a clinically viable and long-term treatment option.Trial Registration: Chinese Clinical Trial Registry, ChiCTR2300072648. Registered on June 20, 2023.Keywords: neck-type cervical spondylopathy, randomized controlled trial, therapeutic neck movement techniques, musculoskeletal ultrasonography

Spin–orbit coupling forms the physical basis for quantum materials with non-trivial topology and potential spintronics applications. The Rashba interaction is a textbook model of spin–orbit interactions, with charge carriers undergoing linear, isotropic spin-splitting in momentum space. Recently, non-centrosymmetric semiconductors in the family BiTeX (X = Cl, Br, I) have been identified as exemplary Rashba materials due to the strong splitting of their bulk bands, yet a detailed investigation of their spin textures, and their relationships to local crystal symmetry, is currently lacking. We perform high-efficiency spin-resolved photoemission spectroscopy to directly image the spin texture of surface states of BiTeCl, and we find dramatic deviations from idealized behavior, including a reversal of the spin-polarization near the Fermi level. We show that this behavior can be described by higher-order contributions to the canonical Rashba model with the surface states localized to individual trilayers of the crystal. Due to the prominence of these effects near the Fermi level, they should have a strong impact on the spin-dependent transport of carriers.

Hui Pei,1 Jie Qu,1 Jianming Chen,1 Guangju Zhao,1 ZhongQiu Lu1,2 1Emergency Department, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China; 2Wenzhou Key Laboratory of Emergency and Disaster Medicine, Wenzhou, People’s Republic of ChinaCorrespondence: ZhongQiu Lu, Email lzq_640815@163.comPurpose: Sepsis-induced cardiomyopathy (SICM) is a prevalent cardiac dysfunction caused by sepsis. Mitochondrial dysfunction is a crucial pathogenic factor associated with adverse cardiovascular adverse events; however, research on SICM remains insufficient.Methods: To investigate the factors contributing to the pathological progression of SICM, we performed a comprehensive analysis of transcriptomic data from the GEO database using bioinformatics and machine learning techniques. CRISPR-Cas9 S100A9 knockout mice and primary cardiomyocytes were exposed to lipopolysaccharide to simulate SICM. Transcriptome analysis and mass spectrometry of primary cardiomyocytes were used to determine the potential pathogenic mechanisms of S100A9. The mitochondrial ultrastructure and mitochondrial membrane potential (MMP) were detected using transmission electron microscopy and flow cytometry, respectively. Pink1/Parkin and Drp1 proteins were detected using Western blotting to evaluate mitochondrial autophagy and division. The mtDNA and mRNA levels of mitochondrial transcription factors and synthases were evaluated using real-time polymerase chain reaction.Results: Bioinformatics analysis identified 12 common differentially expressed genes, including SERPINA3N, LCN2, MS4A6D, LRG1, OSMR, SOCS3, FCGR2b, S100A9, S100A8, CASP4, ABCA8A, and NFKBIZ. Significant S100A9 upregulation was closely associated with myocardial injury exacerbation and cardiac function deterioration. GSEA revealed that myocardial contractile function, oxidative stress, and mitochondrial function were significantly affected by S100A9. Knocking out S100A9 alleviates the inflammatory response and mitochondrial dysfunction. The interaction of S100A9 with ATP5 enhanced mitochondrial division and autophagy, inhibited MMP and ATP synthesis, and induced oxidative stress, which are related to the Nlrp3-Nfkb-Caspase1 and Drp1-Pink1-Parkin signaling pathways. The expression of mitochondrial transcription factors (TFAM and TFBM) and ATP synthetases (ATP6 and ATP8, as well as COX1, COX2, and COX3) was further suppressed by S100A9 in SICM. Targeted S100A9 inhibition by paquinimod partially reversed myocardial mitochondrial dysfunction and oxidative stress.Conclusion: The interaction of S100A9 with ATP5 exacerbates myocardial damage in sepsis by inducing mitochondrial dysfunction and oxidative stress. Keywords: S100A9, SICM, bioinformatics analysis, mitochondrial dysfunction, ATP5

Jinhong Zuo, Xiayang Zeng, Hongyi Ma, Peng Chen, Xinlei Cai, Zhenyu Fan, Jianpeng Qu Massage Department, Zhejiang Hospital, Hangzhou City, People’s Republic of ChinaCorrespondence: Jianpeng Qu, Massage Department, Zhejiang Hospital, No. 12 Lingyin Road, Xihu District, Hangzhou City, 310000, People’s Republic of China, Email qjp0007@126.com

Shan Chen,1 Houming Liu,1 Tianpin Li,1 Wenjie Lai,1 Lei Liu,1 Youchun Xu,2 Jiuxin Qu1 1Department of Clinical Laboratory, Shenzhen Third People’s Hospital, National Clinical Research Center for Infectious Diseases, The Second Affiliated Hospital of Southern University of Science and Technology, Shenzhen, Guangdong Province, 518112, People’s Republic of China; 2Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing, 100084, People’s Republic of ChinaCorrespondence: Jiuxin Qu, Department of Clinical Laboratory, Shenzhen Third People’s Hospital, National Clinical Research Center for Infectious Diseases, The Second Affiliated Hospital of Southern University of Science and Technology, Shenzhen, People’s Republic of China, Email Qujiuxin@163.com Youchun Xu, Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing, People’s Republic of China, Email CYX040198@163.comBackground: The currently used conventional susceptibility testing for drug-resistant Mycobacterium tuberculosis (M.TB) is limited due to being time-consuming and having low efficiency. Herein, we propose the use of a microfluidic-based method to rapidly detect drug-resistant gene mutations using Kompetitive Allele-Specific PCR (KASP).Methods: A total of 300 clinical samples were collected, and DNA extraction was performed using the “isoChip®” Mycobacterium detection kit. Phenotypic susceptibility testing and Sanger sequencing were performed to sequence the PCR products. Allele-specific primers targeting 37 gene mutation sites were designed, and a microfluidic chip (KASP) was constructed using 112 reaction chambers to simultaneously detect multiple mutations. Chip validation was performed using clinical samples.Results: Phenotypic susceptibility of clinical isolates revealed 38 rifampicin (RIF)-resistant, 64 isoniazid (INH)-resistant, 48 streptomycin (SM)-resistant and 23 ethambutol (EMB)-resistant strains, as well as 33 multi-drug-resistant TB (MDR-TB) strains and 20 strains fully resistant to all four drugs. Optimization of the chip-based detection system for drug resistance detection showed satisfactory specificity and maximum fluorescence at a DNA concentration of 1× 101 copies/μL. Further analysis revealed that 76.32% of the RIF-resistant strains harbored rpoB gene mutations (sensitivity, 76.32%; specificity 100%), 60.93% of the INH-resistant strains had katG gene mutations (sensitivity, 60.93%; specificity, 100%), 66.66% of the SM-resistant strains carried drug resistance gene mutations (sensitivity, 66.66%; specificity, 99.2%), and 69.56% of the EMB-resistant strains had embB gene mutations (sensitivity, 69.56%; specificity, 100%). Further, the overall agreement between the microfluidic chip and Sanger sequencing was satisfactory, with a turnaround time of the microfluidic chip was approximately 2 hours, much shorter than the conventional DST method.Conclusion: The proposed microfluidic-based KASP assay provides a cost-effective and convenient method for detecting mutations associated with drug resistance in M. tuberculosis. It represents a promising alternative to the traditional DST method, with satisfactory sensitivity and specificity and a much shorter turnaround time.Graphical Abstract: Keywords: Mycobacterium tuberculosis, multidrug-resistance, drug resistance, resistance-conferring gene mutations, polymerase chain reaction, microfluidic analytical techniques, Sanger sequencing

Chao Tang,1,2,* Xiaoqing Deng,1,* Jingru Qu,1 Yahui Miao,1 Lei Tian,1 Man Zhang,1 Xiaoyu Li,1 Bei Sun,1 Liming Chen1 1NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, 300134, People’s Republic of China; 2The Affiliated Huzhou Hospital, Zhejiang University School of Medicine (Huzhou Central Hospital), Huzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Liming Chen; Bei Sun, No. 6 North Huanrui Road, Beichen District, Tianjin, People’s Republic of China, Email xfx22081@vip.163.com; sun_peipei220@hotmail.comBackground: Diabetic kidney disease (DKD) is a major diabetic microvascular complication. Fatty acid-induced lipotoxicity and apoptosis were associated with the exacerbation of DKD. However, the association of lipotoxicity with renal tubular apoptosis and the effects of fenofibrate on DKD are not fully understood.Methods: Eight-week-old db/db mice were given fenofibrate or saline by gavage for 8 weeks. Human kidney proximal tubular epithelial (HK2) cells stimulated with palmitic acid (PA) and high glucose (HG) were used as a model of lipid metabolism disorders. Apoptosis was assessed with or without fenofibrate. The AMP-activated protein kinase (AMPK) activator 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) and AMPK inhibitor Compound C were used to determine the involvement of AMPK and Medium-chain acyl-CoA dehydrogenase (MCAD) in the regulation of lipid accumulation by fenofibrate. MCAD silencing was achieved by small interfering RNA (siRNA) transfection.Results: Fenofibrate reduced triglyceride (TG) content and lipid accumulation in DKD. Importantly, renal function and tubular cell apoptosis were significantly improved by fenofibrate. Fenofibrate reduced apoptosis, accompanied by increased activation of the AMPK/FOXA2/MCAD pathway. MCAD silencing resulted in apoptosis and lipid accumulation despite fenofibrate treatment.Conclusion: Fenofibrate improves lipid accumulation and apoptosis through the AMPK/FOXA2/MCAD pathway. MCAD may be a potential therapeutic target of DKD, and the use of fenofibrate as a treatment for DKD warrants further study.Keywords: fenofibrate, diabetic kidney disease, renal tubular cell, apoptosis, lipid accumulation, MCAD

Sheng Ye,1 Huichun Xiao,1 Jian Chen,1 Di Zhang,1 Li Qi,1 Ting Peng,2 Yanyang Gao,2 Qianbing Zhang,3 Jinqing Qu,2 Lei Wang,4 Ruiyuan Liu1 1Guangdong Provincial Key Laboratory of Medical Image Processing, School of Biomedical Engineering, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China; 2School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou, Guangdong, People’s Republic of China; 3Cancer Research Institute, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China; 4College of Materials and Chemical Engineering, Key Laboratory of Inorganic Nonmetallic Crystalline and Energy Conversion Materials, China Three Gorges University, Yichang, People’s Republic of ChinaCorrespondence: Jinqing Qu; Ruiyuan Liu, Email cejqqu@scut.edu.cn; ruiyliu@smu.edu.cnIntroduction: The high concentration of glutathione (GSH) and hydrogen peroxide (H2O2) levels within the tumor microenvironment (TME) are the major obstacle to induce the unsatisfactory anticancer treatment efficiency. The synergistic cancer therapy strategies of the combination the GSH depletion enhanced chemodynamic therapy (CDT) with photothermal therapy (PTT) have been proved to be the promising method to significantly improve the therapeutic efficacy.Methods: The copperphosphotungstate was incorporated into polyanilines to design copperphosphotungstate doped polyaniline nanorods (CuPW@PANI Nanorods) via chemical oxidant polymerization of aniline. The low long-term toxicity and biocompatibility were evaluated. Both in vitro and in vivo experiments were carried out to confirm the GSH depletion enhanced CDT/NIR-II PTT synergistic therapy.Results: CuPW@PANI Nanorods feature biosafety and biocompatibility, strong NIR-II absorbance, and high photothermal-conversion efficiency (45.14%) in NIR-II bio-window, making them highly applicable for photoacoustic imaging and NIR-II PTT. Moreover, CuPW@PANI Nanorods could consume endogenous GSH to disrupt redox homeostasis and perform a Fenton-like reaction with H2O2 to produce cytotoxic •OH for the enhanced CDT. Furthermore, NIR-II photothermal-induced local hyperthermia accelerates •OH generation to enhance CDT, which realizes high therapeutic efficacy in vivo.Conclusion: This study provides a proof of concept of GSH-depletion augmented chemodynamic/NIR-II photothermal therapy.Keywords: copperphosphotungstate, NIR-II absorption nanorods, NIR-II photothermal therapy, GSH depletion, chemodynamic therapy, synergistic therapy

Yiting Chen,1,&ast; Anda Zhao,2,&ast; Jiajun Lyu,3 Yabin Hu,4 Yong Yin,4 Jiajie Qu,5 Shilu Tong,1,4,6,7 Shenghui Li1,8 1School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 3Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China; 4Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 5Childcare Department, Shanghai Municipal Education Commission, Shanghai, People’s Republic of China; 6School of Public Health, Institute of Environment and Population Health, Anhui Medical University, Hefei, People’s Republic of China; 7School of Public Health and Social Work, Queensland University of Technology, Brisbane, Australia; 8MOE-Shanghai Key Laboratory of Children’s Environmental Health, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shenghui Li, School of Public Health, Shanghai Jiao Tong University, 227 South Chongqing Road, Huangpu District, Shanghai, 200025, People’s Republic of China, Tel +86-21-63846590, Email lsh9907@163.com; submission9907@163.com Shilu Tong, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, 1678 Dongfang Road, Pudong New Area, Shanghai, 200127, People’s Republic of China, Tel +86-21-38625635, Email tongshilu@scmc.com.cnPurpose: To examine whether parasomnia symptoms are associated with increased odds of childhood asthma and wheeze, and the role of preterm birth.Patients and Methods: The Shanghai Children’s Allergy Study was cross-sectionally conducted in 31 kindergartens and 17 primary schools in Shanghai, China. After excluding the missing data of gestational week and child’s age, this study included a total of 16,487 individuals with a mean age of 7.74 years and 52.4% of males. The association between parasomnia symptoms and wheeze/asthma was assessed by univariate and multivariate analyses. The interaction effects of parasomnias and preterm birth were primarily evaluated by P for multiplicative interaction, and the relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP), and synergy index (SI) were also measured.Results: Parasomnias, especially rapid eye movement (REM) parasomnia symptoms, were associated with an increased risk of childhood wheeze/asthma, and the interaction between parasomnia and preterm birth exhibited an excess risk of current wheeze (RERI, 1.43; 95% CI, 0.41– 2.45) and ever asthma (RERI, 0.75; 95% CI, 0.01– 1.50). In the stratification analyses, the combination of parasomnia symptoms and preterm birth had higher odds of wheeze/asthma. And the odds of current wheeze (OR, 4.55; 95% CI, 1.69– 12.25; p=0.003) and ever asthma (OR, 6.17; 95% CI, 2.36– 16.11; p< 0.001) were much higher in cumulative parasomnia symptoms plus very preterm birth. And sensitive analyses were further conducted in populations without sleep disordered breathing (SDB), and an allergen test subgroup, yielding similar results.Conclusion: Parasomnia symptoms are associated with increased odds of childhood wheeze/asthma, and the odds were even higher in premature population. The findings suggest that parasomnia symptoms, as a developmental sleep disorder, are supposed to be closely watched among children who have asthma or are at risk for asthma, and that preterm children deserve more attention.Keywords: sleep, sleep disorders, premature, respiratory allergies

We present a broadband spectral analysis of the soft-intermediate and soft states using Insight-HXMT observations of the black hole binary MAXI J1348–630 during its outburst in 2019. We employ a combination of reflection and continuum fitting methods to measure the spin of the black hole and determine a spin of a = 0.79 ± 0.13, which is consistent with most of the previous results. Additionally, we investigate some sources of systematic uncertainty that could bias the measurement. The valid spectral hardening factor can partially account for the spin evolution observed during the outburst. Other potential factors, such as assumptions about the corona's structure and their interaction with reflected photons, can also affect the accuracy of spin measurements. Furthermore, our analysis reveals that MAXI J1348–630 exhibits a significantly high disk density (∼1022 cm−3), with a moderate iron abundance of approximately 2.5 times solar. [ABSTRACT FROM AUTHOR]

GRS 1716–249 is a stellar-mass black hole in a low-mass X-ray binary that underwent a giant outburst in 2016–17. In this paper, we use simultaneous observations from the Hard X-ray Modulation Telescope (Insight-HXMT) and the Nuclear Spectroscopic Telescope Array (NuSTAR) to determine its basic parameters. The observations were performed during the softest part of the outburst and the spectra show clear thermal disk emission and reflection features. We fit the X-ray energy spectra using the joint fitting method of the continuum and reflection components with the kerrbb2 + relxill model. Since there is a possibility that the distance to this source was previously underestimated, we used the latest distance parameter of 6.9 kpc in our study, in contrast to previous works, where the distance was set at 2.4 kpc. Through a spectral fitting of the black hole mass at 6.4 M⊙, we observe a strong dependence of the derived spin on the distance: a* = 0.972−0.005+0.004 at an assumed distance of 2.4 kpc and a∗ = 0.464−0.007+0.016 at an assumed distance of 6.9 kpc, at a confidence level of 90%. When considering the uncertainties in the distance and black hole mass, there will be a wider range of spin with a*< 0.78. The fitting results with the new distance indicate that GRS 1716–249 harbors a moderate spin black hole with an inclined (i ∼ 40 − 50°) accretion disk around it. Additionally, we have also found that solely using the method of reflection component fitting, while ignoring the constraints on the spin from the accretion disk component will result in an extremely high spin. [ABSTRACT FROM AUTHOR]

Qingen Da,1,2,&ast; Mingming Ren,2,&ast; Lei Huang,2 Jianhua Qu,1 Qiuhua Yang,3 Jiean Xu,4 Qian Ma,4 Xiaoxiao Mao,4 Yongfeng Cai,4 Dingwei Zhao,4 Junhua Luo,5 Zilong Yan,1 Lu Sun,2 Kunfu Ouyang,2 Xiaowei Zhang,6 Zhen Han,2 Jikui Liu,1 Tao Wang2 1Department of Hepatobiliary Surgery, Peking University Shenzhen Hospital, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, People’s Republic of China; 2Department of Cardiovascular Surgery, Peking University Shenzhen Hospital, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, People’s Republic of China; 3Vascular Biology Center, Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, GA, USA; 4Shenzhen Graduate School, Peking University, Shenzhen, People’s Republic of China; 5Department of Urological Surgery, Peking University Shenzhen Hospital, Shenzhen, People’s Republic of China; 6School of Basic Medical Sciences, Peking University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jikui Liu, Department of Hepatobiliary Surgery, Peking University Shenzhen Hospital, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, People’s Republic of China, Email liu8929@126.com Tao Wang, Department of Cardiovascular Surgery, Peking University Shenzhen Hospital, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, People’s Republic of China, Email szwangtao@126.comObjective: We aimed to explore the prognostic patterns of ferroptosis-related genes in papillary renal cell carcinoma (PRCC) and investigate the relationship between ferroptosis-related genes and PRCC tumor immune microenvironment.Methods: We obtained the mRNA expression and corresponding clinical data of PRCC from the public tumor cancer genome atlas database (TCGA). The PRCC patients were randomly divided into two cohort, training cohort and verification cohort, respectively. Univariate Cox regression, LASSO Cox regression, multivariate Cox regression analysis were utilized to construct ferroptosis signature for PRCC patients. And then, risk prognostic model was established and verified. The correlation of ferroptosis-related signature with survival and immune microenvironment was systematically analyzed.Results: A 4-genes ferroptosis signature (CDKN1A, MIOX, PSAT1, and RRM2) was constructed. Multivariate Cox regression assay indicates that the risk score of ferroptosis signature was an independent prognostic indicator (HR=1.391, p< 0.001). The survival curve shows that the high-risk group has a poorer prognosis than the low-risk group (p< 0.001). The risk prognostic model was established based on prognostic factors of clinical-stage, hemoglobin, and risk score. The time-dependent receiver operating characteristic curve (ROC) analysis proves the predictive capacity of the ferroptosis signature, the 3 years area under the curve (AUC) is 0.890, and the 5 years AUC is 0.733. Further analysis suggested that cell cycle, pentose phosphate pathway, P53 signaling pathway were significantly enriched in the high-risk group. The significantly different fractions of dendritic cells resting, macrophage cells, and T cells follicular helper were observed in risk groups.Conclusion: This study implicates a ferroptosis signature which has a good predict capacity of the prognosis in PRCC patients. Ferroptosis-related genes may have a key role in the process of anti-tumor and serve as therapeutic targets for PRCC.Keywords: papillary renal cell carcinoma, ferroptosis, gene signature, prognosis model, tumor immune microenvironment

Jian Qu,1,2 Ting-Ting Qi,1,2 Qiang Qu,3,4 Wen-Ming Long,5 Ying Chen,6 Yue Luo,7 Ying Wang1,2 1Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, 410011, People’s Republic of China; 2Institute of Clinical Pharmacy, Central South University, Changsha, 410011, People’s Republic of China; 3Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, 410078, People’s Republic of China; 4National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410078, People’s Republic of China; 5Department of Pharmacy, Jingzhou District, Second People’s Hospital of Huaihua City, Huaihua, 418400, People’s Republic of China; 6Department of Pharmacy, Wuhan University, Renmin Hospital, Wuhan, 430060, People’s Republic of China; 7Department of Pharmacy, The People’s Hospital of Liuyang, Liuyang, 410300, People’s Republic of ChinaCorrespondence: Ying Wang, Department of Pharmacy, The Second Xiangya Hospital, Central South University, Institute of Clinical Pharmacy, Central South University, No. 139 Middle Renmin Road, Changsha, 410011, People’s Republic of China, Tel +86-15173198700, Fax +86-731-85292072, Email wangying5211@csu.edu.cnBackground: The increasing prevalence of carbapenem-resistant Gram-negative bacteria (CR-GNB) represents a global healthcare crisis. This study explored the efficacy and safety of Polymyxin B (PMB)-based regimens and factors influencing their effectiveness.Methods: Patients with CR-GNB infections treated with PMB for more than three days were enrolled in this retrospective study from 1st June 2018 to 30th April 2020. Data were collected on patient characteristics, bacterial culture, and drug-sensitivity test results; anti-infection treatment regimens, particularly details of PMB use; and adverse drug reactions. Clinical and microbiological efficacy, mortality, and safety of PMB-based regimens in CR-GNB infected patients were evaluated. Univariate analysis and multivariate logistic regression analyses were used to assess factors influencing efficacy and mortality.Results: A total of 373 CR-GNB strains were cultured from 268 patients. About 41.04% of patients used PMB loading dose of 1.01 (0.84– 1.69) mg/kg. Maintenance dose was 0.85 (0.82– 1.00) mg/kg q12h. The clinical efficacy rate was 36.57% (98/268), the total bacterial clearance rate of PMB was 39.42%, and the all-cause mortality rate was 33.96%. The adverse drug reaction rate was 19.58%, among which the incidence of renal toxicity was highest (8.21%). Multivariate logistic regression analysis showed that clinical efficacy, bacterial clearance rate, and all-cause mortality were associated with patient-related facts, including mechanical ventilation use, underlying diseases (such as respiratory disease), the type and site of CR-GNB infection, and PMB administration timing and loading dose.Conclusion: PMB is a relatively safe and effective antibiotic drug for treatment of critically ill patients with CR-GNB infection; however, PMB use should be subject to guidelines recommendations for early administration, loading administration, and adequate administration, which could help to improve the clinical efficacy, microbiological efficacy, and mortality.Keywords: polymyxin B, carbapenem-resistant Gram-negative bacteria, clinical efficacy, bacterial elimination, mortality, adverse effect

Yun Xie,1 Qin Li,2 Zhanwei Gao,3 Jiaming Sun,4 Dong Li,5 Candice Harvey,6 Jiazhi Qu,7 Sean Snow,8 Qingfeng Li1 1Plastic Surgery Department of Shanghai 9th People’s Hospital, Shanghai, People’s Republic of China; 2Plastic Surgery Department of General Hospital of Guangzhou Military Command of PLA, Guangzhou, Guangdong, People’s Republic of China; 3Plastic Surgery Department of Japan Friendship Hospital, Chaoyang, Beijing, People’s Republic of China; 4Plastic Surgery Department of Union Hospital Tongji Medical College Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China; 5Plastic Surgery Department of Peking University Third Hospital, Haidian, Beijing, People’s Republic of China; 6Allergan Aesthetics, an AbbVie Company, Marlow, UK; 7Allergan Aesthetics, an AbbVie Company, Beijing, People’s Republic of China; 8Allergan Aesthetics, an AbbVie Company, Irvine, CA, USACorrespondence: Qingfeng Li, Shanghai 9th People’s Hospital, No. 639, Zizaoju Road, Shanghai, 200011, People’s Republic of China, Tel + 86-21-53315615, Fax + 86-21-63089567, Email dr.liqingfeng@yahoo.comPurpose: Hyaluronic acid injectable gels are commonly used to treat nasolabial folds (NLFs). We evaluated the safety and effectiveness of VYC-17.5L for correcting NLFs in Chinese subjects.Patients and Methods: This prospective, multicenter, double-blind, within-subject‒controlled study randomized adults with moderate-to-severe NLFs to VYC-17.5L treatment (initial and touch-up) in 1 NLF and control (without lidocaine) in the contralateral NLF. Effectiveness endpoints at 6 months included noninferiority of VYC-17.5L to control in NLF Severity Scale response rate (primary endpoint), subject-reported procedural pain (11-point scale), and investigator and subject assessments using the Global Aesthetic Improvement Scale (GAIS).Results: A total of 175 subjects were included. The primary endpoint was met, with response rates of 84.2% for VYC-17.5L and 82.5% for control. Mean pain scores after initial and touch-up treatments were 2.4 for VYC-17.5L versus 5.2 for control (P < 0.001) and 2.0 versus 3.3 (P < 0.001), respectively. Investigator-rated GAIS scores were 86.5% for VYC-17.5L versus 86.0% for control. There were no between-group differences in subject-rated GAIS scores. Safety profiles were comparable for VYC-17.5L and control.Conclusion: VYC-17.5L was noninferior to control without lidocaine for correcting moderate-to-severe NLFs in Chinese subjects and was superior to control in reducing procedural pain.Keywords: hyaluronic acid, dermal fillers, lidocaine

A novel technology for extracting vanadium from molten converter vanadium slag was studied at the laboratory scale by oxidation and calcification. The effect of the cooling method, CaO addition, and reaction time on the phases of calcified vanadium slag was studied. Under the action of oxygen and CaO, the molten vanadium slag underwent calcification reaction to form acid-soluble calcium vanadate phase and the feasibility of its main chemical reaction was calculated by Factsage8.1. The calcified vanadium slag was leached by H2SO4 solution and characterized by the XRF, XRD, SEM, and EDS techniques. Compared with the traditional process, the new process saved much energy, and it was faster and more efficient. The XRD results showed that CaV2O5, Ca7V4O17, and Ca3V2O8 were gradually formed in the molten vanadium slag with increasing CaO addition. However, when too much CaO was added, Ca2SiO4 and CaTiO3 were also formed. These phases wrapped part of the vanadium and reduced the leaching rate of vanadium. When the mass ratio of Ca to V was 0.75, under the optimal acid leaching conditions (particle size of calcified vanadium slag less than 0.075 mm, leaching temperature 90 ℃, H2SO4 concentration 200 g.L-1, liquid-to-solid ratio 6:1 ml.g-1, leaching time 60 min, and stirring speed 300r.min-1), the leaching rate of vanadium from calcified vanadium slag could exceed 90%. The new process not only saved energy and reduced emissions, but also reached the average level of the existing vanadium extraction process.

Zhenpeng Yang,1,2,&ast; Shuai Lu,1,2,&ast; Yuying Wang,1,2 Huazhen Tang,1,2 Bing Wang,1,2 Xibo Sun,1,3 Jinxiu Qu,1,2 Benqiang Rao1,2 1Department of Gastrointestinal Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Key Laboratory of Cancer FSMP for State Market Regulation, Beijing Shijitan Hospital, Beijing, People’s Republic of China; 3Department of Breast Surgery, The Second Affiliated Hospital of Shandong First Medical University, Taian, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Benqiang Rao Tel +86 13521237767Email raobenqiang@bjsjth.cnObjective: This study aims at exploring the relationship between necroptosis-related miRNAs and colon cancer prognosis.Methods: We downloaded the miRNA sequencing data from the TCGA, and eight differentially expressed necroptosis-related miRNAs were screened. Then, we used Cox regression analysis to establish a prediction model of necroptosis-related miRNA. Finally, the prognosis related miRNAs were used to predict the target genes, and functional analysis was used to explore the potential mechanism of these target genes.Results: The miRNA-seq data of 444 COAD cases were downloaded from TCGA. We identified 8 differentially expressed miRNAs (has-miR-16-5p, has-miR-141-3p, has-miR-148a-3p, has-miR-425-5p, has-miR-7-5p, has-miR-223-3p, has-miR-200a-5p, and has-miR-500a-3p), then Cox analysis was performed for determining eight-miRNA signature prognostic biomarkers with obviously different OS. The area under the curve (AUC) of receiver operating characteristic (ROC) curve for predicting 1-, 3-, and 5-year survival were 0.663, 0.653 and 0.639, respectively. The multivariate analysis also implied that the risk score was an independent prognostic factor considering other confounding factors (HR = 1.847, 95% CI = 1.197– 2.848, P = 0.006). According to the Kaplan–Meier analysis, the expression of hsa-miR-500a-3p (P = 0.003), hsa-miR-16-5p (P = 0.004) and hsa-miR-148a-3p (P = 0.035) significantly affected OS outcomes. We predicted the target genes of these three miRNAs and then screened 10 hub genes (CCND1, SMAD3, SMAD2, CDK1, TGFB2, CDC25A, CHEK1, VEGFA, CCNE1, WEE1). In addition, CHEK1 was associated with the survival prognosis.Conclusion: Our study demonstrated that necroptosis is closely associated with colon cancer, and the model of eight necroptosis-related miRNAs are potentially useful prognostic biomarkers and therapeutic targets for colon cancer.Keywords: necroptosis, colon cancer, prognosis

Yu-Xin Wen,1,2,* Qiang Qu,3,4,* Wen-Ming Long,5 Yue Luo,6 Hai-Hui Zhuang,1 Xin-Qi Teng,1 Jian Qu1 1Department of Pharmacy, The Second Xiangya Hospital, Central South University; Institute of Clinical Pharmacy, Central South University, Changsha, 410011, People’s Republic of China; 2Department of Pharmacy, Lixian People’s Hospital in Hunan, Lixian, 415500, People’s Republic of China; 3Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, 410078, People’s Republic of China; 4National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410078, People’s Republic of China; 5Department of Pharmacy, Jingzhou District, Second People’s Hospital of Huaihua City, Huaihua, 418400, People’s Republic of China; 6Department of Pharmacy, The People’s Hospital of Liuyang, Liuyang, 410300, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jian QuDepartment of Pharmacy, The Second Xiangya Hospital, Central South University; Institute of Clinical Pharmacy, Central South University, No. 139 Middle Renmin Road, Changsha, 410011, People’s Republic of China, Tel +86-15973190614, Fax +86-731-85292072Email qujianstanley@csu.edu.cnPurpose: This study investigates the nephrotoxicity and efficacy assessment of polymyxin B (PMB) use in renal transplant patients.Patients and Methods: This retrospective study included adult (> 18 years of age) renal transplant patients who received PMB intravenous drip for more than 72 hours. Efficacy assessment of PMB included clinical treatment efficacy, microbiological efficacy at the end of PMB treatment, and in-hospital all-cause mortality. Nephrotoxicity of PMB was evaluated for further group comparison.Results: We enrolled 235 renal transplant patients in our study. After PMB treatment, 45 patients occurred PMB-nephrotoxicity, and the nephrotoxicity rate was 19.15%. Among them, 44 patients were RIFLE R stage, and one patient was RIFLE I stage. The dose of PMB used in patients was 40.0 (40.0– 50.0) mg q12h with a loading dose of 41.8± 9.8 mg. Multivariate logistic regression analysis showed that ICU admission, vasoactive agents, aminoglycosides, creatinine clearance rate before PMB use, and mean total hospital stay were independent risk factors of PMB-nephrotoxicity in kidney transplant patients. The clinical effective rate was 97.9%, and the microbiological clean rate was 66.7%.Conclusion: Our study demonstrated that PMB low dose regimens might achieve good efficacy and less nephrotoxicity in renal transplant patients. We should evaluate the severity of the infection and renal function of patients, avoid the combined use of other nephrotoxic drugs, and minimize the course of use to reduce the occurrence of PMB-nephrotoxicity.Keywords: polymyxin B, nephrotoxicity, renal transplant patients, adverse reactions