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Jingxia Mao,1,2,&ast; Guibo Yang,1,3,&ast; Qin Su,1,4,&ast; Zhonghong Zeng,1 Jueying Lin,2 Lin Kong,3 Lidun Zhang,4 Lidan Liu,1 Yihua Yang,1 Hongbo Wu1 1Guangxi Reproductive Medical Center, The First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China; 2Department of Obstetrics, The Fifth Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China; 3Department of Obstetrics, The Maternity and Child Health Care of Guangxi Zhuang Autonomous Region, Nanning, People’s Republic of China; 4Department of Obstetrics, The First People’s Hospital of Yulin, Yulin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongbo Wu; Yihua Yang, Guangxi Reproductive Medical Center, The First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China, Email 19587200@qq.com; workyyh@163.comObjective: To assess the safety and efficiency of in vitro fertilization/ intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET) on maternal and neonatal perinatal outcomes in women (≥ 40y) with singleton pregnancies.Methods: This multi-center retrospective cohort study, carried out from January 2018 to June 2023, enrolled 1762 women (≥ 40y) with singleton pregnancies of at least 28 weeks. Participants were divided into two groups: the IVF/ICSI-ET group (204 cases) and the spontaneous conception (SC) group (1558 cases). After 1:2 propensity score matching (PSM), the two groups were compared for maternal and neonatal outcomes. The SC group (1558 cases) was further divided by age into the < 43 years group (1195 cases) and the ≥ 43 years group (363 cases) for subgroup analysis.Results: Adverse maternal and neonatal outcomes were comparable between the IVF/ICSI-ET group and the SC group, with a higher cesarean section rate (78% vs 67.5%, P =0.013), an increased maternal ICU admissions rate (5.5% vs 1.3%, P =0.008), and a lower birth defects rate (1.1% vs 4.6%, P =0.037) in the IVF/ICSI-ET group. Subgroup analysis showed that women aged ≥ 43 years had higher incidences of gestational diabetes, gestational hypertension, cesarean section, and neonatal asphyxia compared to women aged < 43 years.Conclusion: This study indicated IVF/ICSI-ET is relatively safe for women ≥ 40 years with singleton pregnancies. However, advanced maternal age deteriorated maternal and neonatal outcomes, and IVF/ICSI-ET further heightened the risk of cesarean section and maternal ICU admissions. Therefore, enhanced care and vigilance are crucial for women over 40 undergoing IVF/ICSI-ET.Keywords: in-vitro fertilization, intracytoplasmic sperm injection, advanced maternal age, maternal outcomes, neonatal outcomes

Ye Yang,1,&ast; Lin Wang,1,&ast; Zhiyang Zeng,2 Chunmeng He,1 Yanqiu Wang,1 Ying Huang1 1Department of Gastroenterology, Children’s Hospital of Fudan University/National Children’s Medical Center, Shanghai, 201102, People’s Republic of China; 2Department of Central Laboratory, Fengxian Central Hospital Affiliated to Southern Medical University, Shanghai, 201499, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ying Huang, Department of Gastroenterology, Children’s Hospital of Fudan University/National Children’s Medical Center, No. 399 Wanyuan Road, Minhang District, Shanghai, 201102, People’s Republic of China, Tel +86-21-64931727, Email yhuang815@163.comPurpose: Spleen tyrosine kinase (Syk) is a widely-expressed cytoplasmic non-receptor tyrosine kinase involved in regulating various signaling pathways and plays an important role in chronic inflammation and autoimmune diseases. Gain-of-function SYK variants have been implicated in pediatric inflammatory bowel diseases. This study aimed to investigate the effects of gain-of-function SYK variants on the susceptibility to experimental colitis and macrophage function.Methods: Colitis was induced using dextran sodium sulfate and dinitrobenzene sulfonic acid in mice harboring a gain-of-function variant in SYK (SykS544Y). Intestinal inflammation was assessed via disease activity index, histological analysis, and Western blotting. The frequencies of macrophages, phagocytosis, and reactive oxygen species (ROS) production in bone marrow-derived macrophages (BMDM) were measured via flow cytometry. Chemokines and BMDM chemotaxis were analyzed using real-time quantitative reverse transcription polymerase chain reaction and Transwell assays. The expression of nucleotide-binding domain leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome-related proteins were detected using immunohistochemistry, enzyme-linked immunoassay and Western blotting.Results: SykS544Y mice exhibited increased susceptibility to experimental colitis, and macrophage infiltration in colon tissues significantly increased. We observed increased expression of macrophage chemokines in colon tissues and enhanced chemotaxis in SykS544Y BMDM. Additionally, we detected increased levels of fluorescent microspheres and 2.7-dichloride-hydro fluorescein diacetate-labeled ROS in SykS544Y BMDM. Moreover, enhanced levels of NLRP3 inflammasome-related proteins were observed in the colon tissues and BMDM from SykS544Y mice.Conclusion: Gain-of-function variant in SYK may contribute to the pathogenesis of pediatric inflammatory bowel diseases by promoting macrophage migration, phagocytosis, ROS production and activation of NLRP3 inflammasomes.Keywords: inflammatory bowel disease, SYK, gain-of-function variant, macrophage

Weiyong Xu,1,2 Zhenchang Wang,3 Huaqing Yao,1,2 Zifeng Zeng,1,2 Xinping Lan1,2 1Center for Cardiovascular Diseases, Meizhou People’s Hospital, Meizhou, People’s Republic of China; 2Guangdong Provincial Engineering and Technology Research Center for Molecular Diagnostics of Cardiovascular Diseases, Meizhou People’s Hospital, Meizhou, People’s Republic of China; 3Department of Emergency Medicine, Meizhou People’s Hospital, Meizhou, People’s Republic of ChinaCorrespondence: Xinping Lan, Center for Cardiovascular Diseases, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of China, Email lan-xinping@163.comObjective: To investigate the distribution of arteriosclerotic vessels of arteriosclerosis, differential serum lipid profiles, and differences in the proportion of dyslipidaemia between patients with single-site arteriosclerosis and multi-site arteriosclerosis (significant hardening of ≥ 2 arteries).Methods: The data of 6581 single-site arteriosclerosis patients and 5940 multi-site arteriosclerosis patients were extracted from the hospital medical record system. Serum total cholesterol (TC), triglycerides (TGs), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein (Apo) A1, ApoB concentrations and C-reactive protein (CRP) between patients with single-site arteriosclerosis and multi-site arteriosclerosis were collected and analyzed.Results: The most diseased arteries were coronary arteries (n=7099, 33.7%), limb arteries (n=6546, 31.1%), and carotid arteries (n=5279, 25.1%). TC, LDL-C, TC/HDL-C, and LDL-C/HDL-C levels were higher and CRP level was lower in multi-site arteriosclerosis patients than those in single-site arteriosclerosis patients. The TC, LDL-C levels in non-elderly (< 65 years old) female patients were higher and TG/HDL-C, TC/HDL-C, LDL-C/HDL-C levels were lower than those in non-elderly male patients, while the TG, TC, LDL-C, and TG/HDL-C levels in elderly (≥ 65 years old) female patients were higher and LDL-C/HDL-C level was lower than those in elderly male patients. The proportion of dyslipidemia in descending order was as follows: low HDL-C (31.9%), elevated TG (16.9%), elevated TC (9.0%), and elevated LDL-C (4.2%). The levels of TC, LDL-C, TC/HDL-C, and LDL-C/HDL-C in patients with peripheral arteriosclerosis were higher than those in patients with cardio-cerebrovascular arteriosclerosis.Conclusion: There were differences in serum lipid levels in patients with arteriosclerosis with different age, gender and distribution of arteriosclerotic vessels.Keywords: arteriosclerosis, arteriosclerotic vessels, dyslipidemia, serum lipid, CRP

Xue Yang,1,&ast; Man Wu,2,&ast; Tangzhiming Li,3,&ast; Jie Yu,4 Tian Fu,5 Guoping Li,6 Huanwen Xiong,7 Gang Liao,8 Sensen Zhang,9 Shaofeng Li,10 Zhonghua Zeng,11 Chun Chen,12 Benhui Liang,13,14 Zhiguo Zhou,15 Ming Lu16 1Shenzhen Institute of Respiratory Diseases, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, Guangdong, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Shanghai Public Health Clinical Center Affiliated to Fudan University, Shanghai, People’s Republic of China; 3Department of Cardiology, Shenzhen Cardiovascular Minimally Invasive Medical Engineering Technology Research and Development Center, Shenzhen People’s Hospital (The Second Clinical Medical College, The First Affiliated Hospital, Southern University of Science and Technology, Jinan University), Shenzhen, Guangdong, People’s Republic of China; 4Department of Respiratory and Critical Care Medicine, Jiangxi Provincial People’s Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, Jiangxi, People’s Republic of China; 5Department of Respiratory and Critical Care Medicine, Jining No 1. People’s Hospital, Jining, Shandong, People’s Republic of China; 6Department of Respiratory and Critical Care Medicine, Tongde Hospital of Zhejiang Hangzhou, Zhejiang, People’s Republic of China; 7Department of Respiratory and Critical Care Medicine, Gaoxin Branch of The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 8Department of Respiratory and Critical Care Medicine, Shenzhen Hospital of Integrated Traditional Chinese and Western Medicine, Shenzhen, Guangdong, People’s Republic of China; 9Department of Respiratory Medicine, The Third Central Hospital of Tianjin, Tianjin, People’s Republic of China; 10Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of Jiangxi University of Chinese Medicine, Nanchang, Jiangxi, People’s Republic of China; 11Department of Respiratory and Critical Care Medicine, The First People’s Hospital of Fuzhou, Jiangxi, People’s Republic of China; 12Cancer Center, Department of Pulmonary and Critical Care Medicine, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, People’s Republic of China; 13Department of Cardiology, Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 14Department of Structural Heart Disease, National Center for Cardiovascular Disease, China & State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, National Health Commission Key Laboratory of Cardiovascular Regeneration Medicine, National Clinical Research Center for Cardiovascular Diseases, Beijing, People’s Republic of China; 15Department of Pulmonary and Critical Care Medicine, The Affiliated Changsha Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, People’s Republic of China; 16Department of Pulmonary and Critical Care Medicine, the First Affiliated Hospital of Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhiguo Zhou, Department of Pulmonary and Critical Care Medicine, The Affiliated Changsha Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, People’s Republic of China, Email zhouzhiguo1217@163.com Ming Lu, Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, People’s Republic of China, Email 602032934@qq.comIntroduction: C. psittaci pneumonia has atypical clinical manifestations and is often ignored by clinicians. This study analyzed the clinical characteristics, explored the risk factors for composite outcome and established a prediction model for early prediction of composite outcome among C. psittaci pneumonia patients.Methods: A multicenter, retrospective, observational cohort study was conducted in ten Chinese tertiary hospitals. Patients diagnosed with C. psittaci pneumonia were included, and their clinical data were collected and analyzed. The composite outcome of C. psittaci pneumonia included death during hospitalization, ICU admission, and mechanical ventilation. Univariate and multivariable logistic regression analyses were conducted to determine the significant variables. A ten-fold cross-validation was performed to internally validate the model. The model performance was evaluated using various methods, including receiver operating characteristics (ROC), C-index, sensitivity, specificity, positive/negative predictive value (PPV/NPV), decision curve analysis (DCA), and clinical impact curve analysis (CICA).Results: In total, 83 patients comprised training cohorts and 36 patients comprised validation cohorts. CURB-65 was used to establish predictive Model 1. Multivariate logistic regression analysis identified three independent prognostic factors, including serum albumin, CURB-65, and white blood cells. These factors were employed to construct model 2. Model 2 had acceptable discrimination (AUC of 0.898 and 0.825 for the training and validation sets, respectively) and robust internal validity. The specificity, sensitivity, NPV, and PPV for predicting composite outcome in the nomogram model were 91.7%, 84.5%, 50.0%, and 98.4% in the training sets, and 100.0%, 64.7%, 14.2%, and 100.0% in the validation sets. DCA and CICA showed that the nomogram model was clinically practical.Conclusion: This study constructs a refined nomogram model for predicting the composite outcome in C. psittaci pneumonia patients. This nomogram model enables early and accurate C. psittaci pneumonia patients’ evaluation, which may improve clinical outcomes.Keywords: Chlamydia psittaci pneumonia, nomogram, prediction model, composite outcome

Wenguang Deng, Zhiming Zeng, Qingyan Liu, Jingjing Deng, Liyu Wang, Hui Li, Yuenong Zhang The Anesthesiology Surgery Center of The Third Affiliated Hospital of Sun Yat-sen University-Yuedong Hospital, Guangdong, People’s Republic of ChinaCorrespondence: Yuenong Zhang, Email 36856665@qq.com

Xiaojuan Ji,1,&ast; Wenjie Zhu,1,&ast; Hongfei Lu,2 Zhiwei Wu,1 Huaqing Chen,1 Chunli Lin,1 Zhaolin Zeng,1 Cong You,1 Longnian Li1 1Department of Dermatology, First Affiliated Hospital of Gannan Medical University, Joint Organization of Jiangxi Clinical Medicine Research Center for Dermatology, Ganzhou, People’s Republic of China; 2Clinical Laboratory, First Affiliated Hospital of Gannan Medical University, Ganzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Cong You; Longnian Li, Department of Dermatology, First Affiliated Hospital of Gannan Medical University, Ganzhou, People’s Republic of China, Email youcong1987@tmu.edu.cn; li_longnian@foxmail.comObjective: To analyze the antibiotic resistance profile, virulence genes, and molecular typing of Staphylococcus aureus (S. aureus) strains isolated in skin and soft tissue infections at the First Affiliated Hospital, Gannan Medical University, to better understand the molecular epidemiological characteristics of S. aureus.Methods: In 2023, 65 S. aureus strains were isolated from patients with skin and soft tissue infections. Strain identification and susceptibility tests were performed using VITEK 2 and gram-positive bacteria identification cards. DNA was extracted using a DNA extraction kit, and all genes were amplified using polymerase chain reaction. Multilocus sequence typing (MLST) was used for molecular typing.Results: In this study, of the 65 S. aureus strains were tested for their susceptibility to 16 antibiotics, the highest resistance rate to penicillin G was 95.4%. None of the staphylococcal isolates showed resistance to ceftaroline, daptomycin, linezolid, tigecycline, teicoplanin, or vancomycin. fnbA was the most prevalent virulence gene (100%) in S. aureus strains isolated in skin and soft tissue infections, followed by arcA (98.5%). Statistical analyses showed that the resistance rates of methicillin-resistant S. aureus isolates to various antibiotics were significantly higher than those of methicillin-susceptible S. aureus isolates. Fifty sequence types (STs), including 44 new ones, were identified by MLST.Conclusion: In this study, the high resistance rate to penicillin G and the high carrying rate of virulence gene fnbA and arcA of S.aureus were determine, and 44 new STs were identified, which may be associated with the geographical location of southern Jiangxi and local trends in antibiotic use. The study of the clonal lineage and evolutionary relationships of S. aureus in these regions may help in understanding the molecular epidemiology and provide the experimental basis for pathogenic bacteria prevention and treatment.Keywords: Staphylococcus aureus, skin and soft tissue infections, antibiotic resistance, multilocus sequence typing, virulence gene

Shuangjin Liu, Zihao Zeng, Qi Qi, Qin Yang, Yiqiu Hu School of Educational Science, Hunan Normal University, Changsha, 410006, People’s Republic of ChinaCorrespondence: Yiqiu Hu, School of Educational Science, Hunan Normal University, Changsha, 410006, People’s Republic of China, Email fortune2000947@163.comBackground: Based on the gene-environment interaction paradigm, this study explored the effect of peer relationships on adolescent loneliness and the role of psychological resilience and the oxytocin receptor gene (OXTR).Methods: A survey was conducted in a sample of 619 adolescents, and their oral cells were collected for DNA extraction and genotyping.Results: The results showed that (1) both peer relationships and psychological resilience significantly affected adolescent loneliness; (2) psychological resilience partially mediated the relationship between peer relationships and loneliness in adolescents; (3) OXTR gene rs53576 polymorphism moderated both the first and second half of the indirect pathway of the mediation model. Specifically, carriers of the rs53576 polymorphism A/A genotype showed a significantly enhanced effect of peer relationships on adolescent psychological resilience, while carriers of the rs53576 polymorphism G/G genotype showed a significantly enhanced effect of psychological resilience on adolescent loneliness.Conclusion: These findings helped elucidate the developmental mechanisms of adolescent loneliness in terms of peer relationships, psychological resilience, and OXTR gene polymorphisms.Plain Language Summary: A moderated mediation effects analysis was conducted to investigate the effect of peer relationships on adolescent loneliness and the role of psychological resilience and the oxytocin receptor gene (OXTR). The results revealed psychological resilience partially mediated the relationship between peer relationships and loneliness in adolescents; OXTR gene rs53576 polymorphism moderated both the first and second half of the indirect pathway of the mediation model. These findings helped elucidate the developmental mechanisms of adolescent loneliness in terms of peer relationships, psychological resilience, and OXTR gene polymorphisms.Keywords: peer relationship, adolescents, loneliness, psychological resilience, OXTR gene

Zhangrui Zeng,1,&ast; Yueshuai Wei,1,&ast; Caihong Ye,1 Yuan Jiang,1 Chunlin Feng,1 Tongtong Guo,1 Min Song,1 Yinhuan Ding,1 Ping Zhan,2 Jinbo Liu1 1Department of Laboratory Medicine, The Affiliated Hospital of Southwest Medical University, Sichuan Province Engineering Technology Research Center of Molecular Diagnosis of Clinical Diseases, Molecular Diagnosis of Clinical Diseases Key Laboratory of Luzhou, Luzhou, People’s Republic of China; 2Department of Gynaecology, The Affiliated Hospital of Southwest Medical University, Luzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jinbo Liu, Department of Laboratory Medicine, The Affiliated Hospital of Southwest Medical University, Sichuan Province Engineering Technology Research Center of Molecular Diagnosis of Clinical Diseases, Molecular Diagnosis of Clinical Diseases Key Laboratory of Luzhou, Luzhou, People’s Republic of China, Te/Fax +86 0830 3165730, Email liujb7203@swmu.edu.cnPurpose: The isolation rate of carbapenem-resistant Enterobacter cloacae complex (CREC) is continuously increasing. The aims of this study were to investigate the molecular characteristics and risk factors associated with CREC infections.Methods: Bacterial species were identified using the matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) (Bruker Daltonik GmbH, Bremen, Germany), and the hsp60 gene was utilized for further typing. Antimicrobial susceptibilities were assessed through the MicroScan WalkAway 96 Plus system (Siemens, Germany) and the microbroth dilution method. Antimicrobial resistance genes were screened through polymerase chain reaction (PCR), while the homologous relationship was assessed using multilocus sequence typing (MLST). Conjugation experiments were performed to verify whether the plasmid could be transferred. Additionally, logistic regression model was employed to analyze risk factors for CREC infections.Results: 32 strains of CREC bacteria were isolated during the study, yet only 20 were retained for preservation. While the isolates demonstrated resistance to the majority of antibiotics, they exhibited high sensitivity to polymyxin B and tigecycline. All isolates carried the blaNDM resistance gene, including 13 blaNDM-1 isolates and 7 blaNDM-5 isolates. MLST homology analysis revealed the presence of seven known ST types and one new ST type. Conjugation experiments confirmed that 13 isolates were capable of transferring the blaNDM resistance gene to Escherichia coli strain EC600. Single-factor analysis identified multiple primary risk factors for CREC infection, but multivariate analysis did not reveal independent risk factors.Conclusion: This study investigates the molecular characteristics and risk factors associated with CREC infections. The detection rate of CREC strains in our hospital is continuously rising and homology analysis suggested that strains might spread in our hospital, emphasizing the importance of implementing effective preventive measures to control the horizontal transmission of plasmid-mediated antimicrobial resistance genes.Keywords: carbapenem-resistant, Enterobacter cloacae complex, antimicrobial resistance, molecular characteristics, risk factors

Tao Jiang,1,2 Weijian Chen,3 Chao Lu,1,2 Jiyong Yang,3 Ziquan Zeng,1,2 Wenqiang Li,4 Hongsheng Liu,5 Nana Huang,5 Yuhui Chen,6 Wengang Liu1,2 1Department of Orthopedics, Guangdong Provincial Second Hospital of Traditional Chinese Medicine, Guangzhou, 510095, People’s Republic of China; 2Department of Orthopedics, Guangdong Provincial Engineering Technology Research Institute of Traditional Chinese Medicine, Guangzhou, 510095, People’s Republic of China; 3The Fifth Clinical School of Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510095, People’s Republic of China; 4Engineering Technology Research Center for Sports Assistive Devices of Guangdong, School of Sport and Health, Guangzhou Sport University, Guangzhou, 510500, People’s Republic of China; 5Guangdong Huayan Biomedical Science and Technology Center, Guangzhou, 511441, People’s Republic of China; 6Department of Traumatic Surgery, Center for Orthopaedic Surgery, Third Affiliated Hospital of Southern Medical University, Guangzhou, 510630, People’s Republic of ChinaCorrespondence: Wengang Liu, Department of Orthopedics, Guangdong Provincial Second Hospital of Traditional Chinese Medicine, Hengfu Road 60, Yuexiu District, Guangzhou, Guangdong, People’s Republic of China, Email liuwengang74@163.com Yuhui Chen, Department of Traumatic Surgery, Center for Orthopaedic Surgery, Third Affiliated Hospital of Southern Medical University, Guangzhou, 510630, People’s Republic of China, Email ah1990726@163.comBackground: Skin wounds are a prevalent issue that can have severe health consequences if not treated correctly. Nanozymes offer a promising therapeutic approach for the treatment of skin wounds, owing to their advantages in regulating redox homeostasis to reduce oxidative damage and kill bacteria. These properties make them an effective treatment option for skin wounds. However, most of current nanozymes lack the capability to simultaneously address inflammation, oxidative stress, and bacterial infection during the wound healing process. There is still great potential for nanozymes to increase their therapeutic functional diversity and efficacy.Methods: Herein, copper-doped hollow mesopores cerium oxide (Cu-HMCe) nanozymes with multifunctional of antioxidant, antimicrobial and pro-vascularity is successfully prepared. Cu-HMCe can be efficiently prepared through a simple and rapid solution method and displays sound physiological stability. The biocompatibility, pro-angiogenic, antimicrobial, and antioxidant properties of Cu-HMCe were assessed. Moreover, a full-thickness skin defect infection model was utilized to investigate the wound healing capacity, as well as anti-inflammatory and pro-angiogenic properties of nanozymes in vivo.Results: Both in vitro and in vivo experiments have substantiated Cu-HMCe’s remarkable biocompatibility. Moreover, Cu-HMCe possesses potent antioxidant enzyme-like catalytic activity, effectively clearing DPPH radicals (with a scavenging rate of 80%), hydroxyl radicals, and reactive oxygen species. Additionally, Cu-HMCe exhibits excellent antimicrobial and pro-angiogenic properties, with over 70% inhibition of both E. coli and S. aureus. These properties collectively promote wound healing, and the wound treated with Cu-HMCe achieved a closure rate of over 90% on the 14th day.Conclusion: The results indicate that multifunctional Cu-HMCe with antioxidant, antimicrobial, and pro-angiogenic properties was successfully prepared and exhibited remarkable efficacy in promoting wound healing. This nanozymes providing a promising strategy for skin repair.Keywords: Cu-HMCe nanozyme, antioxidation, antibacterial, vascularization, wound healing

Zixue Zeng,1,&ast; Binh Duong Giap,2,&ast; Ethan Kahana,3 Jefferson Lustre,4 Ossama Mahmoud,5 Shahzad I Mian,2 Bradford Tannen,2 Nambi Nallasamy2,6 1School of Public Health, University of Michigan, Ann Arbor, MI, USA; 2Kellogg Eye Center, Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI, USA; 3Department of Computer Science, University of Michigan, Ann Arbor, MI, USA; 4School of Medicine, University of Michigan, Ann Arbor, MI, USA; 5School of Medicine, Wayne State University, Detroit, MI, USA; 6Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA&ast;These authors contributed equally to this workCorrespondence: Nambi Nallasamy, Kellogg Eye Center, University of Michigan, 1000 Wall Street, Ann Arbor, MI, 48105, USA, Tel +1 (734) 763-5506, Fax +1 (734) 936-2340, Email nnallasa@med.umich.eduBackground: The capsulorhexis is one of the most important and challenging maneuvers in cataract surgery. Automated analysis of the anterior capsulotomy could aid surgical training through the provision of objective feedback and guidance to trainees.Purpose: To develop and evaluate a deep learning-based system for the automated identification and semantic segmentation of the anterior capsulotomy in cataract surgery video.Methods: In this study, we established a BigCat-Capsulotomy dataset comprising 1556 video frames extracted from 190 recorded cataract surgery videos for developing and validating the capsulotomy recognition system. The proposed system involves three primary stages: video preprocessing, capsulotomy video frame classification, and capsulotomy segmentation. To thoroughly evaluate its efficacy, we examined the performance of a total of eight deep learning-based classification models and eleven segmentation models, assessing both accuracy and time consumption. Furthermore, we delved into the factors influencing system performance by deploying it across various surgical phases.Results: The ResNet-152 model employed in the classification step of the proposed capsulotomy recognition system attained strong performance with an overall Dice coefficient of 92.21%. Similarly, the UNet model with the DenseNet-169 backbone emerged as the most effective segmentation model among those investigated, achieving an overall Dice coefficient of 92.12%. Moreover, the time consumption of the system was low at 103.37 milliseconds per frame, facilitating its application in real-time scenarios. Phase-wise analysis indicated that the Phacoemulsification phase (nuclear disassembly) was the most challenging to segment (Dice coefficient of 86.02%).Conclusion: The experimental results showed that the proposed system is highly effective in intraoperative capsulotomy recognition during cataract surgery and demonstrates both high accuracy and real-time capabilities. This system holds significant potential for applications in surgical performance analysis, education, and intraoperative guidance systems.Keywords: cataract surgery, capsulotomy, deep learning, image segmentation, image classification

Jin Tu,1– 3,&ast; Feng Jiang,4,&ast; Jieni Fang,2 Luhua Xu,2 Zhicong Zeng,2 Xuanyue Zhang,1 Li Ba,1 Hanjiao Liu,1,3 Fengxia Lin2 1Department of Nursing, Seventh Clinical Medical College, Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, 518100, People’s Republic of China; 2Department of Cardiovascular, Shenzhen Bao’an Traditional Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, 518100, People’s Republic of China; 3Department of Nursing, Shenzhen Hospital of Integrated Traditional Chinese and Western Medicine, Shenzhen, Guangdong, 518100, People’s Republic of China; 4School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 102488, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fengxia Lin, Department of Cardiovascular, Shenzhen Bao’an Traditional Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, 518100, People’s Republic of China, Email szlinfx@163.com Hanjiao Liu, Shenzhen Hospital of Integrated Traditional Chinese and Western Medicine, Shenzhen, Guangdong, 518100, People’s Republic of China, Email liuhanjiao000@163.comBackground: Dendrobium, with profound botanical importance, reveals a rich composition of bioactive compounds, including polysaccharides, flavonoids, alkaloids, and diverse amino acids, holding promise for skin regeneration. However, the precise mechanism remains elusive. Seeking a potent natural remedy for wound healing, exocyst vesicles were successfully isolated from Dendrobium.Aims of the Study: This investigation aimed to employ bioinformatics and in vivo experiments to elucidate target genes of Dendrobium-derived nanovesicles in skin wound healing, focusing on immune infiltration and senescence characteristics.Materials and Methods: C57 mice experienced facilitated wound healing through Dendrobium-derived nanovesicles (DDNVs). Bioinformatics analysis and GEO database mining identified crucial genes by intersecting immune-related, senescence-related, and PANoptosis-associated genes. The identified genes underwent in vivo validation.Results: DDNVs remarkably accelerated skin wound healing in C57 mice. Bioinformatics analysis revealed abnormal expression patterns of immune-related, senescence-related, and pan-apoptosis-related genes, highlighting an overexpressed IL-1β and downregulated IL-18 in the model group, Exploration of signaling pathways included IL-17, NF-kappa B, NOD-like receptor, and Toll-like receptor pathways. In vivo experiments confirmed DDNVs’ efficacy in suppressing IL-1β expression, enhancing wound healing.Conclusion: Plant-derived nanovesicles (PDNV) emerged as a natural, reliable, and productive approach to wound healing. DDNVs uptake by mouse skin tissues, labeled with a fluorescent dye, led to enhanced wound healing in C57 mice. Notably, IL-1β overexpression in immune cells and genes played a key role. DDNVs intervention effectively suppressed IL-1β expression, accelerating skin wound tissue repair.Keywords: plant-derived nanovesicles, Dendrobium, immune infiltration factors, cellular aging, skin injury recovery

Guangxin Zhou,1,2 Wei Zhao,2 Yi Zhang,2 Wenli Zhou,2 Haizhou Yan,2 Yongli Wei,1 Yuming Tang,1 Zijing Zeng,2 Hanrong Cheng1 1Department of Sleep Medicine, Institute of Respiratory Diseases, Shenzhen People’s Hospital, The Second Clinical Medical College of Jinan University, The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, Guangdong, People’s Republic of China; 2OPPO Health, Guangdong OPPO Mobile Telecommunications Co. Ltd., Shenzhen, Guangdong, People’s Republic of ChinaCorrespondence: Hanrong Cheng, Department of Sleep Medicine, Shenzhen People’s Hospital, The Second Clinical Medical College of Jinan University, The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, Guangdong, People’s Republic of China, Email cheng.hanrong@szhospital.comObjective: To evaluate the clinical performance of the OPPO Watch (OW) Sleep Analyzer (OWSA) on OSA screening with polysomnography reference.Methods: We recruited 350 participants using OWSA and PSG simultaneously in a sleep laboratory. The respiratory event index (REI) derived from OWSA and the apnea-hypopnea index (AHI) provided by PSG were compared. SHapley Additive exPlanation (SHAP) values were calculated to explain the model of OWSA.Results: The OWSA-REI (26.5± 18.5 events/h) correlated well with PSG-AHI (33.2± 25.7 events/h; r = 0.91, p < 0.001), with an intraclass correlation coefficient (ICC) of 0.83. Using a threshold of AHI ≥ 15 events/h, the sensitivity, specificity, accuracy, and area under the curve (AUC) were 86.1%, 86.7%, 86.3%, and 0.94, respectively. Bland-Altman analysis showed that OWSA-REI and PSG-AHI were in good agreement (Mean Difference: − 6.7, 95% CI:16.0 to − 29.3 events/h). In addition, the effectiveness of the models in OWSA were also explained by visualizing SHAP values.Conclusion: The OWSA demonstrated a reasonable performance for OSA screening in the clinical setting. In light of this, it is possible for smartwatches to become a complementary tool to PSG, which is particularly useful for larger-scale preliminary screenings.Plain Language Summary: OPPO Watch Sleep Analyzer (OWSA), an emerging sleep-tracking method based on a wearable device, uses a machine learning model to analyze physiological signals including snoring recordings, and other basic anthropometric information to estimate REI. The study evaluated the OSA screening performance of OWSA with PSG-AHI and interpreted the results of the pre-trained machine learning model.OWSA demonstrated consistent clinical diagnostic performance for OSA. The interpretive machine learning models used in OWSA highlighted the impact of multi-modal data on estimation results. Therefore, these types of models are likely to be more widely accepted and promoted in clinical practice.Keywords: obstructive sleep apnea, photoplethysmography, polysomnography, smartwatch

Xiaoyi Li,1,&ast; Zhen Zeng,2,&ast; Xingying Fan,1,3 Wenju Wang,4 Xiaobo Luo,4 Junli Yang,1 Yue Chang1,3,&ast; 1School of Medicine and Health Management, Guizhou Medical University, Guiyang, Guizhou Province, People’s Republic of China; 2Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou Province, People’s Republic of China; 3Center of Medicine Economics and Management Research, Guizhou Medical University, Guiyang, Guizhou Province, People’s Republic of China; 4School of Public Health, Guizhou Medical University, Guiyang, Guizhou Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yue Chang; Xingying Fan, School of Medicine and Health Management, Guizhou Medical University, Gui’an New District, Guiyang, Guizhou Province, People’s Republic of China, Email 4567401@qq.com; 741284752@qq.comPurpose: The purpose of this study was to investigate the prescribing patterns and usage trends of systemic glucocorticoids in primary care institutions located in Southwest China from 2018 to 2021.Materials and Methods: A retrospective cross-sectional analysis of systemic glucocorticoids prescriptions was conducted in 32 primary care institutions located in Southwest China between 2018 and 2021. Prescriptions of systemic glucocorticoids were classified as appropriate or inappropriate use. Inappropriate use was further classified into (1) inappropriate indications and (2) inappropriate selection of glucocorticoids. Generalized estimation equations were employed to investigate the factors associated with inappropriate utilization of systemic glucocorticoids. The seasonal autoregressive integrated moving average (SARIMA) model was employed to predict the rate of inappropriate glucocorticoids prescriptions.Results: A total of 203,846 (92.89%) prescriptions were included, both the number of systemic glucocorticoids prescriptions and inappropriate prescriptions increased in winter. Diseases of the respiratory system (68.90%) were the most frequent targets of systemic glucocorticoids use. Of all prescriptions, 73.18% exhibited inappropriate indications, while 0.05% demonstrated inappropriate selection. The utilization of systemic glucocorticoids was deemed inappropriate for diseases of the respiratory system (94.19%), followed by diseases of the digestive system (87.75%). Physicians, who were female or younger than 33 years old, possess lower levels of education and professional titles and exhibit a higher likelihood of inappropriately prescribing systemic glucocorticoids. The phenomenon of inappropriate glucocorticoids use was commoner among male patients aged 65 years and older. After conducting model verification, it was determined that the SARIMA model could be used to predict the monthly rate of inappropriate systemic glucocorticoids prescriptions in primary care institutions in southwest China.Conclusion: The inappropriate use of systemic glucocorticoids remains a significant concern in primary care institutions. In this regard, continuing education and professional knowledge training of physicians should be strengthened in the future.Keywords: systemic glucocorticoids, primary care institutions, prescription patterns, inappropriate use, usage trends

Zhaoyinqian Li,1– 3,&ast; Tingting Li,1– 4,&ast; Jingyang Tang,1– 3 Li Huang,1– 3 Yinhuan Ding,1– 3 Zhangrui Zeng,1– 3 Jinbo Liu1– 3 1Department of Laboratory Medicine, the Affiliated Hospital of Southwest Medical University, Luzhou, People’s Republic of China; 2Sichuan Province Engineering Technology Research Center of Molecular Diagnosis of Clinical Diseases, Luzhou, People’s Republic of China; 3Molecular Diagnosis of Clinical Diseases Key Laboratory of Luzhou, Luzhou, People’s Republic of China; 4Department of Laboratory Medicine, West China Fourth Hospital, Sichuan University, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jinbo Liu, Department of Laboratory Medicine, the Affiliated Hospital of Southwest Medical University, No. 25, Taiping Street, Jiangyang District, Luzhou, Sichuan, 646000, People’s Republic of China, Tel/Fax +86 08303165730, Email liujb7203@swmu.edu.cnIntroduction: The prevalence of diabetic foot ulcers (DFUs) is increasing, leading to a huge financial burden and human suffering. Furthermore, antibiotic resistance is an urgent problem in the realm of clinical practice. Antimicrobial peptides are an effective and feasible strategy for combating infections caused by drug-resistant bacteria. Therefore, we investigated the in vitro antimicrobial ability of the lipopeptide surfactin, either alone or in combination with conventional antibiotics, against the standard and clinical strains of Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA), isolated from patients with DFUs.Methods: The minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) of surfactin on the selected strains were evaluated by a microbroth dilution technique. The growth curves of the selected strains with and without surfactin were measured, and transmission electron microscopy was used to observe the structure of surfactin-treated bacterial cells. The biofilm inhibitory abilities of surfactin were assessed by crystal violet staining. The antimicrobial interactions between surfactin and conventional antibiotics were established using a checkerboard assay, as well as determining the mutant prevention concentration. The inhibitory effect of surfactin on penicillinase was tested by iodometry.Results: The MIC and MBC values of surfactin ranged from 512 to 1024 μg/mL and 1024 to 2048 μg/mL, respectively. Moreover, surfactin significantly prevented the S. aureus biofilm formation and displayed limited toxicity on human red blood cells. The synergies between surfactin and ampicillin, oxacillin, and tetracycline against S. aureus were revealed. In vitro resistance was not readily produced by surfactin. The action of surfactin may be by disrupting bacterial cell membranes and inhibiting penicillinase.Conclusion: Surfactin appears to be a potential option for the treatment of DFUs infected with MRSA, as it is capable of improving antimicrobial activities and can be used alone or in combination with conventional antibiotics to prevent or postpone the emergence of resistance.Keywords: surfactin, antimicrobial peptides, diabetic foot ulcers, methicillin-resistant Staphylococcus aureus, synergistic effect

Zhaomin Zeng,1,2 Hua Liao,1,2 Fan Hu,2,3 Fumin Zhao,2,4 Hongyan Liu,1,2 Qing Hu,1,2 Haiyan Yu1,2 1Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, People’s Republic of China; 2Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, People’s Republic of China; 3Department of Paediatric Cardiology, West China Second University Hospital, Sichuan University, Chengdu, People’s Republic of China; 4Department of Radiology, West China Second University Hospital, Sichuan University, Chengdu, People’s Republic of ChinaCorrespondence: Haiyan Yu, Department of Obstetrics and Gynecology, West China Second University Hospital, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, No. 20, 3rd Section, South Renmin Road, Chengdu, Sichuan, 610041, People’s Republic of China, Email fanjy422@163.comIntroduction: Lymphatic malformation (LM), most commonly present in the neck area, is benign vascular malformations of the lymphatic system. In an infant, however, LM poses a high risk of adverse outcomes.Case Presentation: We present a case with a giant fetal LM. Through ultrasonography, at 23+ weeks of gestation, a septate cystic mass 7.2× 6.5× 6.3 cm in size was found on the right side of the fetus’s neck. After extensive counseling by the multidisciplinary team, the parents chose to continue the pregnancy. Severe fetal tracheal compression was observed at 29 weeks by magnetic resonance imaging (MRI). At 31 weeks and 5 days, owing to suspected fetal distress, an emergency cesarean section was performed and a male baby weighing 1720 g was delivered. The mass was 10× 16× 8 cm in size and ex utero intrapartum treatment (EXIT) was implemented. Due to progressive growth of the mass secondary to intralesional bleeding, an intralesional injection of bleomycin was administered three days later. This injection was repeated at the age of 1 month and 8 days. The baby was followed up and, by a year after his birth, LM had disappeared. The baby has since been in good health.Conclusion: Accurate prenatal diagnosis and regular monitoring of a fetus with LM may improve prognosis. It is essential to have a trained multidisciplinary team to evaluate the condition of the fetus and the neonate and to provide treatment based on the evaluation. Our experience with intralesional bleomycin injection for the treatment of a giant fetal neck LM in a preterm infant had a favorable outcome. Long-term follow-up by a multidisciplinary team is needed in such cases.Keywords: fetal lymphatic malformation, sclerotherapy, tracheal compression

Hongyan Liu,1,2 Zhaomin Zeng,1,2 Hua Liao,1,2 Qing Hu,1,2 Haiyan Yu1,2 1Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, People’s Republic of China; 2Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, People’s Republic of ChinaCorrespondence: Haiyan Yu, Department of Obstetrics and Gynecology, West China Second University Hospital, No. 20, 3rd Section, South Renmin Road, Chengdu, Sichuan, 610041, People’s Republic of China, Email fanjy422@163.comIntroduction: Umbilical artery thrombosis is a rare complication associated with poor perinatal outcomes. The incidence of umbilical artery thrombosis in pregnancy is estimated from 0.0025% to 0.045%. Prenatal screening and diagnosis of umbilical artery thrombosis is usually performed by ultrasonography. Up to now, no treatment consensus has been achieved.Case Presentation: We present a case of dichorionic diamniotic twin pregnancy complicated with selective termination of one twin with lymphoid cystic tumor at 14 weeks and 2 days of gestation and the alive twin occurred single umbilical artery thrombosis at 35 weeks and 6 days of gestation. The emergency cesarean section was performed after emergency admission. A healthy male baby was delivered weighing 2690g with Apgar scores of 10 and 10 at 1 and 5 minutes, respectively, whereas the dead fetus weighed 10 g. Thrombosis was observed throughout one of the umbilical artery of the alive fetus. The woman and the infant are followed up closely and both in good condition.Conclusion: The number and morphology of umbilical arteries should be carefully observed during pregnancy. Individualized management of umbilical artery thrombosis should be based on clinical conditions. Timely termination of pregnancy if necessary could be suitable to improve adverse pregnancy outcomes.Keywords: umbilical artery thrombosis, adverse pregnancy outcome, twin pregnancy

Zheng Zeng,1,&ast; Yuanyuan Lu,2,&ast; Fuquan Zhang,3 Jie Zhang,1 Wenjun Zhang,1 Chunli Luo,1 Yuping Guo,4 Junfang Yan,1 Lang Yu1 1Department of Radiation Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 2Department of Radiation Oncology, Yijishan Hospital, The First Affiliated Hospital of Wannan Medical College, Wuhu, Anhui, People’s Republic of China; 3Department of Radiation Oncology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, People’s Republic of China; 4Gynecological Radiotherapy Ward, The Third Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Junfang Yan; Lang Yu, Department of Radiation Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, No.1 Shuaifuyuan Wangfujing, Dongcheng District, Beijing, 100730, People’s Republic of China, Tel +86-10-6915-5485, Fax +86-10-6512-4875, Email yanjunfang@pumch.cn; Lay227215@163.comPurpose: Endometrial carcinoma (EC) is a common gynecological malignancy. Vaginal cuff brachytherapy (VBT) is an adjuvant treatment for EC. Since a single-channel cylinder sometimes delivers inadequate dose coverage to the vaginal apex, three-dimensional (3D) printing technology can be used to achieve satisfactory dose distribution. Here, we report the first case of an EC patient with Herlyn-Werner-Wunderlich syndrome (HWWS) treated with VBT using 3D-printed applicators.Case Presentation: Here, we present a case study of an endometrial cancer patient with HWWS who underwent surgery. During adjuvant radiotherapy, 3D-printed applicators were used in VBT. To accomplish the reconstruction of the source pathways on magnetic resonance imaging, catheters with copper sulfate were placed in two 3D-printed applicators. The early tolerance of this treatment was positive. During the 6-month follow-up, locoregional recurrence was not detected.Conclusion: Our findings strongly indicate that VBT with 3D-printed applicators may be a reasonable treatment option for EC with HWWS.Keywords: personalized brachytherapy, Herlyn-Werner-Wunderlich syndrome, endometrial cancer, 3D-printed applicator

Xiujuan Chang,1,&ast; Shumin Yu,2,&ast; Jianzhi Pang,1 Wei Zhang,1 Huifang Kong,1 Jiagan Huang,1 Guojie Zhang,1 Huixin Zhang,1 Yueyue Gu,1,3 Yan Chen,1 Bin Yang,1 Jingping Liu,4 Zhen Zeng1– 3 1Department of Liver Disease Medicine, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100039, People’s Republic of China; 2 302 Clinical Medical School Peking University, Beijing, 100039, People’s Republic of China; 3The Fifth School of Clinical Medicine, Anhui Medical University, Hefei, Anhui Province, 230032, People’s Republic of China; 4Oncology Department, Electric Power Hospital of Beijing, Beijing, 100073, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhen Zeng, Department of Liver Disease Medicine, The Fifth Medical Center of Chinese PLA General Hospital, No. 100 West 4th Ring Middle Road, Beijing, 100039, People’s Republic of China, Tel +86 15010540233, Email zengzhen1970@sina.comBackground: We explore the dose–efficacy relationship of lenvatinib plus anti-PD-1 in patients with unresectable hepatocellular carcinoma (u-HCC) infected with hepatitis B virus (HBV) in real-world practice. Furthermore, we identify the population sensitive to lenvatinib plus anti-PD-1 treatments.Methods: This retrospective study included 70 patients treated with lenvatinib plus at least 3 cycles of anti-PD-1 and 140 with lenvatinib alone. Stabilized inverse probability of treatment weighting (SIPTW) was used to balance clinical features between the two groups. The overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs) were analyzed. Subpopulation treatment effect pattern plot (STEPP) estimated treatment-effect differences between the two groups.Results: The median age was 54 years, and 189 (90%) cases were male. A total of 180 (85%) patients were infected with HBV. A slowly increasing 12-month survival rate was with the cycles of anti-PD-1, and 5 cycles and more of anti-PD-1 appeared the most beneficial and stable survival rate. The lenvatinib plus at least 3 cycles anti-PD-1 group had better OS (21.4 vs 14 months, p = 0.041), PFS (8.0 vs 6.3 months, p = 0.015) than the lenvatinib alone group in unadjusted cohorts, and the SIPTW adjusted cohorts had confirmed it. For patients with portal vein trunk invasion (PVTI) or extrahepatic spread (EHS) combined with Child-Pugh class B (CPB), lenvatinib plus anti-PD-1 made the 12-month survival rate increase by 38%, while, in the other population, it did only 18%. The two groups had similar AEs (p ≥ 0.05).Conclusion: The lenvatinib combined with at least 3 cycles of anti-PD-1 was efficacy and safe for u-HCC patients infected with HBV. Especially, patients with PVTI or EHS combined with CPB may benefit most from the combination therapy.Graphical Abstract: Keywords: hepatocellular carcinoma, real-world study, anti-PD-1, lenvatinib

Xin Zhao,1,2,&ast; Yue Ge,1,3,&ast; Yuan Zhang,1 WenJie Zhang,1 HongBin Hu,1 LuLan Li,1 Tong Sha,1 ZhenHua Zeng,1 Feng Wu,1 ZhongQing Chen1 1Department of Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 2The First Clinical Medical School, Southern Medical University, Guangzhou, People’s Republic of China; 3Department of School of Nursing, Southern Medical University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: ZhongQing Chen; Feng Wu, Department of Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China, Tel +86 13503049103 ; +86 15915751705, Email zhongqingchen2008@163.com; wishuhappy@126.comBackground: Next-generation sequencing of the metagenome (mNGS) is increasingly used in pathogen diagnosis for infectious diseases due to its short detection time. The time for Oxford Nanopore Technologies (ONT) sequencing-based etiology detection is further shortened compared with that of mNGS, but only a few studies have verified the time advantage and accuracy of ONT sequencing for etiology diagnosis. In 2022, a study confirmed that there was no significant difference in sensitivity and specificity between ONT and mNGS in suspected community-acquired pneumonia patients, which there was no clinical study verified in patients with SHAP.Methods: From October 24 to November 20, 2022, 10 patients with severe hospital-acquired pneumonia (SHAP) in the Nanfang Hospital intensive care unit (ICU) were prospectively enrolled. Bronchoalveolar lavage fluid (BALF) was collected for ONT sequencing, mNGS, and traditional culture. The differences in pathogen detection time and diagnostic agreement among ONT sequencing, mNGS, traditional culture method, and clinical composite diagnosis were compared.Results: Compared with mNGS and the traditional culture method, ONT sequencing had a significant advantage in pathogen detection time (9.6± 0.7 h versus 24.7± 2.7 h versus 132± 58 h, P < 0.05). The agreement rate between ONT sequencing and the clinical composite diagnosis was 73.3% (kappa value=0.737, P < 0.05).Conclusion: ONT sequencing has a potential advantage for rapidly identifying pathogens.Keywords: Oxford Nanopore Technologies, Nanopore sequencing, metagenomic next-generation sequencing, severe hospital-acquired pneumonia, pathogen

Xiaolong Zhang,1,&ast; Zhiyin Lei,2,&ast; Ying Wu,3 Yuanyuan Song,4 Xiaoling Wu,3,5 Bo Yang,2 Jianmei Fan,2 Shixu Feng,2 Liping Wu,2 Lingyan Li,2 Qin Dai,2 Zhen Zeng,2 Mei Feng,3 Tingting Zhang3 1Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Jiajia Central Health Center of Chengdu Eastern New Area, Chengdu Eastern New Area, Sichuan Province, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University/West China School of Nursing, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China; 4Department of Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China; 5Department of Nursing, Sanya People’s Hospital/West China (Sanya) Hospital, Sichuan University, Sanya, Hainan Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ying Wu, Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University/West China School of Nursing, Sichuan University, No. 37 Guoxue Alley, Chengdu, Sichuan Province, 610041, People’s Republic of China, Tel +86-18980606932, Email 358383278@qq.comPurpose: To investigate the prevalence and risk factors for chronic obstructive pulmonary disease (COPD) in a rural area in western China with severe air pollution.Patients and Methods: 10% of local residents aged 40 years and above were included using a convenience sampling method. This was a cross-sectional study. A self-designed questionnaire was used to collect participants’ demographic data. The screening program was comprised of two steps: First, a portable electronic spirometer was used for COPD screening. Those participants with FEV1/FVC ratio < 0.7 were then referred to a confirmatory pulmonary function (PF) test. COPD was confirmed according to the 2020 Global Initiative for Chronic Obstructive Lung Disease criteria.Results: A total of 4577 participants aged 40 years old or above were included in the final analysis. Examination with a mobile spirometer identified 1159 individuals for confirmatory testing; after that, of the 1159 individuals, 889 were diagnosed with COPD by the confirmatory PF test. The prevalence of COPD among the target group was 19.4%. Older age, male sex (odds ratio [OR] = 1.537, 95% confidence interval [CI] 1.246– 1.894), smoking history (OR = 1.338, 95% CI 1.069– 1.675), family history of respiratory disease (OR = 1.625, 95% CI 1.350– 1.957), education level (OR = 0.735, 95% CI 0.617– 0.876), overweight (OR = 0.614, 95% CI 0.517– 0.730) and obesity (OR = 0.572, 95% CI 0.449– 0.721) were identified as independent factors associated with COPD. The screening program helped earlier detection of COPD in 719 participants.Conclusion: COPD was highly prevalent in the rural area studied. Rural residents who were older, current or ever-smokers, male and those who had a lower education level were more vulnerable to developing COPD. The COPD screening program may be helpful for earlier disease detection in rural health-care settings.Keywords: chronic obstructive pulmonary disease, prevalence, primary care, pulmonary function test, risk factors

Xinping Lan,1– 3 Zhenchang Wang,3,4 Zifeng Zeng,1– 3 Huaqing Yao,1– 3 Weiyong Xu,1– 3 Yuxian Zhang1– 3 1Center for Cardiovascular Diseases, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of China; 2Guangdong Provincial Engineering and Technology Research Center for Molecular Diagnostics of Cardiovascular Diseases, Meizhou, People’s Republic of China; 3Guangdong Provincial Key Laboratory of Precision Medicine and Clinical Translational Research of Hakka Population, Meizhou, People’s Republic of China; 4Department of Emergency Medicine, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of ChinaCorrespondence: Xinping Lan, Center for Cardiovascular Diseases, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, No. 63 Huangtang Road, Meijiang District, Meizhou, People’s Republic of China, Tel +753-2131-057, Email lan-xinping@163.comBackground: Hypertensive patients have a younger trend, and studies on the role of genetic factors in hypertension susceptibility have been inconsistent. Aldehyde dehydrogenases 2 (ALDH2) and apolipoprotein E (APOE) are involved in the pathophysiological processes of hypertension. To investigate the relationship of ALDH2 and APOE polymorphisms with hypertension in middle-aged (30– 59 years old) and elderly (≥ 60 years old) persons.Methods: Two thousand six hundred and ten hypertensive patients and 1921 controls were included (between 30 and 100 years old). The genotypes of common polymorphisms in APOE and ALDH2 genes (APOE rs429358, rs7412, and ALDH2 rs671) of the subjects were analyzed by polymerase-chain reaction (PCR)-microarray. Statistical analyses (Student’s t-test, Mann–Whitney U-test, χ2 test, and logistic regression analysis) were performed with SPSS v21.0.Results: There were 4531 participants (66.60 ± 12.10 years old) in this study, including 3057 (67.5%) males and 1474 (32.5%) females. There were no significant differences in distributions of ALDH 2 rs671, APOE rs429358/rs7412 genotypes and alleles between hypertensive patients and controls. Persons with ALDH2 rs671 G/A or A/A genotype were less likely to have hypertension (G/A+A/A vs G/G: gender-, age-, smoking-, and drinking-adjusted OR 0.885, 95% CI 0.785– 0.997, P=0.045), while ALDH2 rs671 A/A+APOE rs429358 or rs7412 wild-type genotype may decrease the risk of hypertension. In middle-aged group, ALDH2 rs671 G/A+APOE rs429358 T/C carriers (adjusted OR 0.547, 95% CI 0.350– 0.856, P=0.008), and ALDH2 rs671 A/A+APOE rs7412 C/C genotypes (adjusted OR 0.567, 95% CI 0.361– 0.891, P=0.014) were less likely to have hypertension. In elderly group, APOE rs7412 T/T carriers were more likely to have hypertension (rs671 T/T vs C/C: adjusted OR 4.755, 95% CI 1.075– 21.027, P=0.040; rs671 T/T vs C/C or C/T: adjusted OR 4.734, 95% CI 1.071– 20.928, P=0.040).Conclusion: Polymorphism–polymorphism interactions of ALDH2 rs671 and APOE rs429358/rs7412 may effect on hypertension susceptibility. Different genotypes comparison shows different roles in middle-aged and elderly people, respectively.Keywords: apolipoprotein E, aldehyde dehydrogenases, polymorphism, hypertension

Bowen Chen1,2 &ast;, Jin Lei1,3 &ast;, Haitao Zhao,4 Jinghui Dong,5 Zhen Zeng,1 Yinyin Li,1 Lingxiang Yu,1 Lin Zhou,6 Aiying Jia,5 Yinying Lu,1– 3 Jiamin Cheng1 1Senior Department of Hepatology, The Fifth Medical Center of PLA General Hospital, Beijing, People’s Republic of China; 2Peking University 302 Clinical Medical School, Beijing, People’s Republic of China; 3Guizhou Medical University Clinical Medical School, Guiyang, People’s Republic of China; 4Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 5Radiology Department, The Fifth Medical Center of PLA General Hospital, Beijing, People’s Republic of China; 6Department of Oncology, The Fifth Medical Center of PLA General Hospital, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiamin Cheng; Yinying Lu, Senior Department of Hepatology, The Fifth Medical Center of PLA General Hospital, No. 100, Middle Road of the West 4th Ring, Beijing, 100039, People’s Republic of China, Tel +86-10-66933294 ; +86-10-66933380, Email chengjiamin300@163.com; luyinying1973@163.comPurpose: To explore the efficacy and safety of sorafenib- or lenvatinib-based combination therapy with PD-1 inhibitors in elderly patients aged ≥ 75 years with unresectable hepatocellular carcinoma (uHCC).Patients and Methods: Systemic therapy-naïve uHCC patients who received first-line sorafenib- or lenvatinib-based combination therapy with PD-1 inhibitors were continually reviewed. The primary endpoint was overall survival (OS), and the secondary endpoints were progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR) in accordance with the Response Evaluation Criteria in Solid Tumors version 1.1. Adverse events (AEs) and immune-related AEs (irAEs) were also evaluated. Groups and subgroups were separated at the ages of 65 and 75 years and compared with 1:1 matching.Results: Total 169 eligible patients were enrolled, including 24 aged ≥ 75 years. Median progression-free survival (PFS) and overall survival (OS) in these 24 elderly patients were 4.6 (95% CI: 2.6– 6.6) months, and 17.0 (95% CI: 11.2– 22.8) months, with 3-, 6-, 12-month OS rate at 82.90%, 73.70%, and 57.50%. Age ≥ 75 years was confirmed to be a risk factor influencing PFS among patients aged ≥ 65 years. Adverse events (AEs) were recorded in all these 24 elderly patients, with seven patients experiencing immune-mediated AEs (irAEs). Nearly 30% of elderly patients stopped treatment due to AEs (16% of these due to irAEs). No statistical differences were found in all efficacy endpoints at the cutoff age of 65 years.Conclusion: For patients aged ≥ 75 years, application of PD-1 inhibitors in combination with sorafenib or lenvatinib is promising, but this has to be done with caution and needs to be confirmed by future prospective studies.Keywords: hepatocellular carcinoma, elderly, PD-1 inhibitors, efficacy, safety

Tingting Li,&ast; Zhaoyinqian Li,&ast; Li Huang, Jingyang Tang, Zixuan Ding, Zhangrui Zeng, Yao Liu, Jinbo Liu Department of Laboratory Medicine, the Affiliated Hospital of Southwest Medical University, Lu Zhou, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jinbo Liu, Department of Laboratory Medicine, the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of China, Tel +86 08303165730, Email liujb7203@swmu.edu.cnObjective: Diabetic foot ulcers (DFUs) and ESKAPE pathogens have attracted attention globally, but the role of ESKAPE pathogens in diabetic foot infection is not well described. The purpose of this study was to evaluate the clinical features, antimicrobial resistance, and risk factors for ESKAPE infection in patients with DFUs.Methods: A retrospective study was conducted on 180 patients with diabetic foot infection admitted to The Affiliated Hospital of Southwest Medical University (Luzhou, China), from January 2017 to April 2021. Antimicrobial susceptibilities of all isolates were determined. Multivariate logistic regression analysis was performed to analyze the independent risk factors for ESKAPE infection, multidrug-resistant (MDR)-ESKAPE infection, MDR-pathogen infection, and severe group in patients with DFUs.Results: A total of 206 isolates were collected, of which 42.2% were ESKAPE pathogens. The independent risk factors for ESKAPE infection were cigarette smoking (OR = 1.958; 95% CI, 1.015– 3.777) and peripheral vascular disease (OR = 2.096; 95% CI, 1.100– 3.992), while alcohol consumption (OR = 2.172; 95% CI, 1.104– 4.272) was the independent risk factor for MDR-pathogen infection. Additionally, the independent risk factors for severe DFU group were invasive treatment (OR = 326.642; 95% CI, 76.644– 1392.08), the duration of systemic antibiotic treatment (OR = 0.918; 95% CI, 0.849– 0.992), and length of hospital stay (OR = 1.145; 95% CI, 1.043– 1.256). No independent risk factors for MDR-ESKAPE infection were found.Conclusion: Our data established the microbiological features of ESKAPE pathogens and clinical manifestations of diabetic foot infection, and provide support for monitoring and management of ESKAPE infection in patients with DFUs in southwest China.Keywords: diabetic foot ulcers, ESKAPE pathogens, infection, antimicrobial resistance, risk factors

Herui Li,&ast; Yiming Ma,&ast; Zihang Zeng, Lijuan Luo, Tiao Li, Huihui Zeng, Yan Chen Department of Respiratory and Critical Care Medicine, the Second Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yan Chen; Huihui Zeng, Department of Respiratory and Critical Care Medicine, the Second Xiangya Hospital, Central South University, 139 Renmin Road, Changsha, 410011, Hunan, People’s Republic of China, Email chenyan99727@csu.edu.cn; bonemarrow@csu.edu.cnBackground: Surgical and medical treatments are applied to pulmonary cryptococcosis (PC) in the real world, while the prognosis of different therapies is uncertain. This study investigated diagnosis, real-world therapy, follow-up outcomes, and prognosis factors, aiming to deepen our understanding of PC.Methods: Patients pathologically diagnosed with PC were retrospectively reviewed and followed up. Further comparisons and subgroup analyses were conducted in surgical and nonsurgical treatment individuals. Univariable and multivariable logistic regression methods were used to explore the risk factors associated with treatment failure.Results: One hundred and sixty-three patients were included in this study, of whom 92 underwent surgical removal of VATS or open lung surgery (68 of them received postoperative antifungal treatment) and 71 got antifungal drugs only. Compared with nonsurgical patients, surgical patients were more immunocompetent (73 [79.3%] cases vs 33 [46.5%]), showed milder symptoms and more limited pulmonary lesions. Although they had instant treatment response owing to lesions resection, there is no significant advantage in the rate of treatment failure. Multivariable regression showed independent predictive factors associated with treatment failure were polymorphonuclear (PMN)> 6.30&ast;109/L, albumin (Alb) < 40g/L and antifungal dosage < 400mg/d. Further analysis among patients with different immune statuses or symptoms demonstrated that sufficient antifungal dosage could reduce the rate of treatment failure.Conclusion: PC showed variable and nonspecific clinical features. PC patients with limited nodules/masses and mild symptoms often led to misdiagnosis and unnecessary lung resections. The potential risk factors including higher PMN and hypoalbuminemia could help clinicians to identify PC patients with poor treatment efficiency at an early stage. To note, sufficient antifungal dosage may improve the treatment outcomes.Keywords: pulmonary cryptococcosis, diagnosis, antifungal treatment, clinical features, surgery

Jianpin Ye,1,&ast; Zhiwei Zeng,2,&ast; Yuxian Chen,3 Zhenkun Wu,3 Qingwei Yang,4 Tao Sun2 1Outpatient Department Laboratory, Xiamen Aviation, Xiamen, Fujian, People’s Republic of China; 2Center for Precision Medicine, School of Medicine and School of Biomedical Sciences, Huaqiao University, Xiamen, Fujian, People’s Republic of China; 3Taokang Institute of Neuro Medicine, Xiamen, Fujian, People’s Republic of China; 4Department of Neurology, Zhongshan Hospital, School of Medicine, Xiamen University, Xiamen, Fujian, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tao Sun, Center for Precision Medicine, School of Medicine and School of Biomedical Sciences, Huaqiao University, Xiamen, Fujian, People’s Republic of China, Email taosun@hqu.edu.cnBackground: Both genetic and environmental factors strongly affect serum uric acid (SUA) concentrations. The incidence of hyperuricemia tends to be younger in the Chinese population. In particular, we have found a high prevalence of hyperuricemia among Chinese flight attendants, aged from 20 to 40, in our survey. This study aims to evaluate whether there is an association between gene polymorphisms and hyperuricemia among Chinese flight attendants.Methods: A total of 532 flight attendants with high and normal serum uric acid levels were recruited. Allele-specific polymerase chain reaction (AS-PCR) was performed using blood samples of enrolled subjects.Results: Previous studies have reported single nucleotide polymorphisms (SNPs) that are tightly associated with uric acid levels. Among them, six SNPs that are strongly associated with SUA or gout in Asians, for instance ABCG2 (rs2231142, rs72552713 and rs2231137), GCKR (rs780094), SLC2A9 (rs1014290) and SLC17A1 (rs1183201), were selected for AS-PCR analyses. We found that SNPs such as ABCG2 rs2231142, GCKR rs780094 and SLC2A9 rs1014290 are strongly associated with hyperuricemia in male flight attendants, and SLC2A9 rs1014290 among female flight attendants.Conclusion: Our study provides evidences of an association between SNPs and hyperuricemia in the Chinese flight attendants, and highlights the significance of improving diagnostics and prevention of disease development in uric acid metabolism disorders and gout using these SNPs.Keywords: serum uric acid, hyperuricemia, single nucleotide polymorphisms, flight attendants

Xin Meng,1 Ziling Zeng,2 Yunda Wang,3 Shuai Guo,1 Chunjuan Wang,2 Baojie Wang,1 Shougang Guo1,2 1Department of Neurology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People’s Republic of China; 2Department of Neurology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, People’s Republic of China; 3Department of Neurosurgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, People’s Republic of ChinaCorrespondence: Shougang Guo, Department of Neurology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jing Wu Road, Huaiyin District, Jinan, Shandong, 250021, People’s Republic of China, Tel +86-13220585081, Fax +86-531-87937741, Email guoshougang1124@163.comPurpose: To evaluate the efficacy and safety of low dosages of rituximab (RTX) in the treatment of MuSK-antibody-positive MG patients.Patients and Methods: We retrospectively analyzed the data of MuSK-antibody-positive MG patients who were treated with low dosages of RTX from January 2018 to October 2021. The long-term treatment response to RTX was assessed by Myasthenia Gravis Foundation of America (MGFA) post-interventional status (PIS), Myasthenia Gravis Status and Treatment Intensity (MGSTI), dosage of steroid, MG-related activities of daily living (MG-ADL) and myasthenic muscle score (MMS) at the end of follow-up.Results: Clinical improvement was observed in all eight patients with follow-up for 8 to 29 months after treatment. At the last visit, complete stable remission had been achieved in one patient, pharmacologic remission in three patients, minimal manifestations status in three patients and improved in one patient based on the MGFA-PIS criteria. MGSTI level 2 or better had been reached in six (75%) patients at the last visit. The steroid dosage decreased from 60 mg at baseline to 15 mg at the last follow-up (p = 0.011). The average MG-ADL score decreased from 11 (range 7 to 15) to 0 (range 0 to 3; p = 0.011), and the MMS improved from 38.5 (range 24 to 60) to 100 (range 90 to 100; p = 0.012). These differences were all statistically significant. During RTX treatment and subsequent follow-up, 1 patient reported minor post-infusion malaise.Conclusion: Low-dose RTX is effective and safe for treating anti-MuSK antibody positive MG patients. A long-term response is observed after treatment. Larger prospective studies are required to provide further evidence.Keywords: myasthenia gravis, rituximab, low-dose, muscle-specific kinase

Han Cen,1– 3 Qin-Wen Wen,4 Han-Qing Zhang,4 Hang Yu,4 Zhen Zeng,2 Ting Jin,2 Ting-Hui Wang,4 Wen Qin,4 Hua Huang,4 Xiu-Di Wu4 1Institute of Geriatrics, The Affiliated Hospital of Medical School, Ningbo University, Ningbo, Zhejiang, People’s Republic of China; 2Department of Preventive Medicine, Medical School of Ningbo University, Ningbo, Zhejiang, People’s Republic of China; 3Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, Zhejiang, People’s Republic of China; 4Department of Rheumatology, Ningbo First Hospital, Ningbo Hospital of Zhejiang University, Ningbo, Zhejiang, People’s Republic of ChinaCorrespondence: Xiu-Di Wu, Department of Rheumatology, Ningbo First Hospital, Ningbo Hospital of Zhejiang University, 59 Liuting Road, Ningbo, Zhejiang, 315010, People’s Republic of China, Tel +86 574 87085588, Fax +86 574 87291583, Email awu1100@aliyun.comPurpose: To investigate the associations between genetic polymorphisms within transporter genes and clinical response to methotrexate (MTX) in Chinese rheumatoid arthritis (RA) patients.Patients and Methods: A total of 100 RA patients receiving MTX were prospectively followed up for approximately 3 months to determine the clinical response based on several criteria, including European League Against Rheumatism (EULAR) good and moderate response, disease activity score in 28 joint counts – erythrocyte sedimentation rate (DAS28-ESR) low disease activity (LDA), change in DAS28-ESR (ΔDAS28-ESR) and ΔDAS28-ESR > 0.6. Fifty-four single nucleotide polymorphisms (SNPs) within seven transporter genes, including SLC19A1, ABCB1, ABCC1∼ 4 and ABCG2, were genotyped.Results: Multivariable analysis revealed that SLC19A1 rs12659 and rs3788200, ABCC2 rs3740066, rs4148396 and rs717620 were significantly associated with EULAR good and moderate response, and ABCC2 rs3740066 and rs717620 were significantly associated with DAS28-ESR LDA, and ABCB1 rs1128503, rs4148737 and ABCC3 rs2277624, rs4148416 were significantly associated with ΔDAS28-ESR. Moreover, 12 genetic polymorphisms were found to be significantly associated with ΔDAS28-ESR > 0.6. With adjustment for corresponding confounders, SLC19A1 TGAA haplotype consisting of rs1051266, rs1131596, rs12659 and rs3788200 was significantly associated with EULAR good and moderate response and ΔDAS28-ESR > 0.6 compared with the most common haplotype CAGG. The ABCC2 haplotype TTT composed of rs717620, rs4148396 and rs3740066 was significantly associated with EULAR good and moderate response and ΔDAS28-ESR > 0.6 compared with the most common haplotype CCC.Conclusion: Our results highlight the potential of genetic polymorphisms within transporter genes, particularly SLC19A1 and ABCC2, as predictors of clinical response to MTX in Chinese RA patients.Keywords: rheumatoid arthritis, methotrexate, transporter, single-nucleotide polymorphism, clinical response

Jin Chen,1,&ast; Min Gong,1,&ast; Zhuo Huang,1 Fang Wang,2 Yajing Wang,3 Zuquan Hu,1 Zhu Zeng,1 Yun Wang2 1Key Laboratory of Biology and Medical Engineering/Immune Cells and Antibody Engineering Research Center of Guizhou Province, School of Biology and Engineering, Guizhou Medical University, Guiyang, 550025, People’s Republic of China; 2Key Laboratory of Infectious Immune and Antibody Engineering of Guizhou Province, School of Basic Medical Sciences, Guizhou Medical University, Guiyang, 550025, People’s Republic of China; 3The Affiliated Stomatological Hospital of Guizhou Medical University, Guizhou Medical University, Guiyang, 550025, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhu Zeng, Key Laboratory of Biology and Medical Engineering/Immune Cells and Antibody Engineering Research Center of Guizhou Province, School of Biology and Engineering, Guizhou Medical University, Guiyang, 550025, People’s Republic of China, Email zengzhu@gmc.edu.cn Yun Wang, Key Laboratory of Infectious Immune and Antibody Engineering of Guizhou Province, School of Basic Medical Sciences, Guizhou Medical University, Guiyang, 550025, People’s Republic of China, Tel/Fax +86851-88174044, Email wangyun@gmc.edu.cnPurpose: Gastric injury is a major issue for long-term administration of aspirin. In this work, we tried to explore the possibility of using BLG to alleviate aspirin-induced gastric injury, because of excellent abilities of BLG in loading drug molecules.Methods: Various spectroscopic techniques and molecular docking methods were applied to investigate the interaction mechanism between BLG and aspirin. Animal experiments were performed to figure out the effects of taking aspirin-BLG on the stomach.Results: Our results demonstrate that aspirin could bind with BLG to form stable aspirin-BLG complex (the binding constant Kb= 2.051 × 103 M− 1). The formation process is endothermic (∆H> 0) and the main acting force is hydrophobic force. Our data also show that the aspirin-BLG complex is formed with a higher affinity in simulated gastric fluid and could remain stable for several hours, which might arise from its special binding mode under acidic condition and the resistance of BLG to gastric digestion. Furthermore, animal models (rats with aspirin-induced gastric damage) were built. The results of animal experiments reveal that the oral administration of aspirin-BLG could cause less damage to gastric tissue, and it also hardly triggers obvious inflammatory responses.Conclusion: This study would contribute to an in-depth understanding of the interaction mechanism between BLG and aspirin. It is reasonable to believe that using BLG to bind with aspirin would be a potential way to alleviate the aspirin-induced gastric injury.Graphical Abstract: Keywords: beta-lactoglobulin, aspirin, gastric injury, static quenching, molecular docking

Jingchen Hao,1,&ast; Zhangrui Zeng,1,&ast; Xue Xiao,2 Yinhuan Ding,1 Jiamin Deng,3 Yueshuai Wei,1 Jinbo Liu1 1Department of Laboratory Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, People’s Republic of China; 2Department of Laboratory Medicine, Southwest Medical University, Luzhou, 646000, Sichuan, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jinbo Liu, Department of Laboratory Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of China, Tel/Fax +86 830 3165730, Email liulab2019@163.comBackground: Colistin is one of the few options for treating carbapenem-resistant Enterobacterales (CREs). There is little available information about the epidemic status of colistin-resistant CREs in Southern Sichuan, China. This study mainly investigated the genomic and phenotypic characteristics of an extensively drug resistant E. coli LZ00114 isolated from Luzhou, China.Materials and Methods: In 2020, LZ00114 was isolated from the urine of a patient with hydronephrosis and urinary tract infection in Luzhou, China. We assessed the resistance profile of LZ00114 in the presence and absence of the protonophore carbonyl cyano-m-chlorophenylhydrazine (CCCP) and 1-(1-naphthylmethyl)-piperazine (NMP) by antimicrobial susceptibility testing. The growth kinetics, motility, and pathogenicity of LZ00114 were determined to evaluate its microbial characteristics. In combination with whole genome sequencing (WGS) and real-time reverse transcription PCR (RT-PCR), we comprehensively analyzed the resistance mechanisms of LZ00114.Results: LZ00114 was resistant to various antimicrobial agents, including meropenem, tetracycline, ciprofloxacin, gentamicin, fosfomycin, and polymyxin B. Notably, CCCP reversed the resistance of LZ00114 to polymyxin B. LZ00114 displayed high pathogenicity in the infection model (P< 0.01) compared with the Lab-WT strain, and its growth rate and motility were not significantly different from the Lab-WT strain. WGS and conjugation revealed that LZ00114 belonged to ST410 and carried a blaNDM-5-harboring self-transmissible IncX3 plasmid and a multi-replicon IncFII/FIA/FIB plasmid carrying blaOXA-1-blaCTX-M-55-tet(B)-aac(6’)-Ib-cr-dfrA17-sul1-fosA3. Comparative genomics revealed genetic relatedness between LZ00114 and strains isolated from other regions. Furthermore, there were point mutations in pmrA (S29G, G144S), pmrB (D283G, Y358N), marR (G103S, Y137H), emrA (I219V), and emrD (G323D) of LZ00114. RT-PCR confirmed the overexpression of efflux pumps and PmrABC in LZ00114.Conclusion: This study provides valuable information for the surveillance of antimicrobial resistance and a theoretical basis for the prevention and control of colistin-resistant E. coli. There is still a need to be vigilant about the clone spread of the high-risk clone group E. coli ST410.Keywords: E. coli, antimicrobial resistance, whole genome sequencing, colistin, carbonyl cyanide m-chlorophenylhydrazine, CCCP, ST410

Feng-jia Chen,1,2,&ast; Li-juan Du,1,2,&ast; Zhimin Zeng,1,2,&ast; Xin-yan Huang,1,2 Chang-yi Xu,1,2 Wei-ping Tan,1,2 Can-mao Xie,1,2 Yu-xia Liang,1,2 Yu-biao Guo1,2 1Division of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China; 2Institute of Pulmonary Diseases, Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yu-biao Guo; Yu-xia Liang, Tel +86 20 8775 5766, Email guoyb@mail.sysu.edu.cn; liangyx69@mail.sysu.edu.cnPurpose: PTPRH inhibits EGFR activity directly in cancer patients and activated EGFR induces goblet cell hyperplasia and mucus hypersecretion in asthma. However, the function of PTPRH in asthma remains unknown. The purpose of this study was to access the association of PTPRH with asthma and its underlying mechanism.Patients and Methods: We examined the PTPRH level in asthma patients (n = 108) and healthy controls (n = 35), and analyzed the correlations between PTPRH and asthma-related indicators. Human bronchial epithelial cell (HBECs) transfected with PTPRH and asthma mouse model were set up to investigate the function of PTPRH.Results: The expression of PTPRH was significantly increased and correlated with pulmonary function parameters, including airway obstruction, and T-helper2 (Th2) associated markers in asthma patients. PTPRH increased in the house dust mite (HDM)-induced asthmatic mice, while Th2 airway inflammation and Muc5ac suppressed when treated with PTPRH. Accordingly, PTPRH expression was markedly increased in IL-13-stimulated HBECs but PTPRH over-expression suppressed MUC5AC. Moreover, HBECs transfected with over-expressed PTPRH inhibited the phosphorylation of EGFR, ERK1/2 and AKT, while induced against PTPRH in HBECs dephosphorylated of EGFR, ERK1/2 and AKT.Conclusion: PTPRH reduces MUC5AC secretion to alleviate airway obstruction in asthma via potential phosphorylating of EGFR/ERK1/2/AKT signaling pathway, which may provide possible therapeutic implications for asthma.Keywords: asthma, PTPRH, human bronchial epithelial cells, EGFR/ERK1/2/AKT, MUC5AC

Zhaofu Zeng, Yan Song, Xin He, Haizhen Yang, Fang Yue, Mengqing Xiong, Ke Hu Department of Respiratory and Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of ChinaCorrespondence: Ke HuDepartment of Respiratory and Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan, 430060, People’s Republic of ChinaTel +86 1897 103 5988Email huke-rmhospital@163.comPurpose: Chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) are associated with polycythemia. However, there still remain unanswered questions about the relationship between overlap syndrome (OVS), where OSA and COPD coexist, and polycythemia. Here, we aimed to establish the prevalence of polycythemia in OVS patients and to explore the impact of OSA on polycythemia.Patients and Methods: Patients with COPD underwent overnight polysomnography (PSG), pulmonary function tests, echocardiography, and complete blood counts. All patients were ethnic Han Chinese and free of prolonged oral corticosteroid use, hematological system disease, severe systemic disease, and other sleep-disordered breathing. OVS was defined as COPD patients with an apnea–hypopnea index ≥ 15 events/h, and polycythemia was defined as an Hb > 165 g/L in men and > 160 g/L in women.Results: Eight-hundred and eighty-six patients with COPD were included in the analysis. The prevalence of polycythemia was significantly higher in OVS patients than COPD-alone patients (6.4% vs 2.9%, p < 0.05). The prevalence of polycythemia increased with OSA severity (χ2 = 7.885, p = 0.007), but not in GOLD grade 3– 4 COPD patients (χ2 = 0.190, p = 0.663). After adjusting for confounders, percentage of total sleep time with SaO2 < 90% (TS90) remained independently associated with an increased odds of polycythemia (OR 1.030, 95% CI 1.015– 1.046) and, with an increase in TS90, the hemoglobin increased, especially in GOLD grade 1– 2 patients (p < 0.05).Conclusion: Patients with OVS have a higher prevalence of polycythemia than those with COPD alone, and TS90 is an independent factor for polycythemia, especially in GOLD1-2 COPD patients.Keywords: chronic obstructive pulmonary disease, obstructive sleep apnea, overlap syndrome, polycythemia

Rirong Chen,1,&ast; Li Li,1,&ast; Chao Li,2 Yuhan Su,2 Yingfan Zhang,1 Xiaobai Pang,2 Jieqi Zheng,2 Zhirong Zeng,1 Min-Hu Chen,1 Shenghong Zhang1 1Division of Gastroenterology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of China; 2Department of Clinical Medicine, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shenghong ZhangDivision of Gastroenterology, The First Affiliated Hospital, Sun Yat-Sen University, No. 58 Zhongshan Road 2, Guangzhou, 510080, People’s Republic of ChinaTel +86 20-87755766Fax +86 20-87332916Email shenghongzhang@163.comObjective: Endoscopic remission is the primary therapeutic target and associated with clinical outcome in Crohn’s disease (CD). Non-invasive and accurate biomarkers are important in monitoring endoscopic remission frequently. Our study aimed at investigating the predictive capacity of prealbumin and retinol-binding protein 4 (RBP4) for identifying endoscopic remission.Methods: From June 2018 to December 2020, 515 endoscopy procedures (332 in the training cohort and 183 in the validation cohort) were enrolled in this multicentre retrospective cohort study. Blood samples were collected for prealbumin or RBP4 testing with 7 days before the endoscopy. A simple Endoscopic Score for CD (SES-CD) was performed to evaluate endoscopic activity and defined endoscopic remission. The area under receiver operating characteristic curve (AUROC), sensitivity, specificity, positive predictive value and negative predictive value were performed to assess the predictive capacity of the biomarkers.Results: Serum concentration of prealbumin and RBP4 was demonstrated to be higher in patients with endoscopic remission and significantly negatively correlated with SES-CD in the training cohort. The AUROC of prealbumin and specificity of prealbumin and RBP4 were larger than that of C-reactive protein in the training cohort and the validation cohort. The model combining prealbumin and faecal calprotectin had the largest AUROC (0.842 [95% CI: 0.775– 0.908]). Furthermore, in both cohorts, prealbumin had a larger AUROC than C-reactive protein for identifying endoscopic remission in patients with anti-tumour necrosis factor therapy.Conclusion: Prealbumin and RBP4 were promising biomarkers for identifying endoscopic remission, especially in patients with anti-tumour necrosis factor therapy.Keywords: Crohn’s disease, endoscopic remission, prealbumin, retinol-binding protein 4

Zhaoyinqian Li,&ast; Jingling Xie,&ast; Jiaxin Yang, Siyi Liu, Zixuan Ding, Jingchen Hao, Yinhuan Ding, Zhangrui Zeng, Jinbo Liu Department of Laboratory Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jinbo LiuDepartment of Laboratory Medicine, The Affiliated Hospital of Southwest Medical University, Taiping Street, Luzhou, 646000, Sichuan, People’s Republic of ChinaTel +86 0830 3165730Email Liulab2019@163.comObjective: This study aimed to determine the clinical manifestations, antimicrobial resistance, molecular characteristics, and risk factors for ESKAPE pathogens infection in burn patients.Methods: A retrospective study of 187 burn patients infected with ESKAPE pathogens was conducted at the Department of Plastic and Burn Surgery of the Affiliated Hospital of Southwest Medical University (Luzhou, China) from October 2018 to June 2021. All strains were identified using a MicroScan WalkAway 96 Plus System, and antimicrobial susceptibilities were determined using the VITEK system or the disk diffusion method. The antimicrobial resistance genes of multi-drug resistant ESKAPE (MDR-ESKAPE) were detected by polymerase chain reaction (PCR). The multivariable logistic regression analysis was used to estimate the risk factors for ESKAPE infection and MDR-ESKAPE infection.Results: A total of 255 strains were isolated in various types of clinical specimens from 187 burn patients, of which 47.5% were ESKAPE pathogens (121/255). Among these, MDR-ESKAPE pathogens accounted for 55% (67/121). Additionally, aph3ʹIII, mecA, blaSHV, blaTEM, blaPDC, and blaSHV were the most prevalent genes detected in Enterococcus faecalis, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp., respectively. The independent risk factors for ESKAPE infection were total body surface area (TBSA) > 30– 50% (odds ratio [OR] = 10.428; 95% confidence interval [CI], 2.047 to 53.108), TBSA > 50% (OR = 15.534; 95% CI, 1.489 to 162.021), and parenteral nutrition (OR = 3.597; 95% CI, 1.098 to 11.787). No independent risk factors were found for MDR-ESKAPE infection.Conclusion: Clinical staff should be alert to the risk of nosocomial infection with ESKAPE pathogens in burn patients receiving parenteral nutrition and under TBSA > 30%. Full attention should also be paid to the ESKAPE resistance, strict adherence to infection control protocols for the rational use of antimicrobial agents, and enhanced clinical standardization of antimicrobial agents management.Keywords: burn, ESKAPE pathogens infection, antimicrobial resistance, risk factors

Mengxiong Li,1,&ast; Zhi Zeng,2,&ast; Aiqing Zhang,3 Qingjian Ye,4 Shujun Su,4 Tingting Xia5 1Department of Obstetrics and Gynecology, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong, 518107, People’s Republic of China; 2The Department of Reproductive Medicine Center, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, 510000, People’s Republic of China; 3Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, 510630, People’s Republic of China; 4Department of Gynecology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, 510630, People’s Republic of China; 5Center for Reproductive Medicine, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, 510630, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tingting Xia Tel +86-020-85256032Email xiatting@mail.sysu.edu.cnObjective: Dysfunction of cumulus granulosa cells has been suggested as a contributor to abnormal folliculogenesis and the development of polycystic ovary syndrome (PCOS), but the underlying molecular mechanisms remain unclear. Recent studies indicate that circular RNAs (circRNAs) exert important roles for diseases. We aimed to screen crucial circRNAs of PCOS patients and predict their functions.Methods: The high-throughput datasets of circRNAs (GSE145296), microRNAs (miRNAs; GSE72274) and messenger RNAs (mRNAs; GSE155489) in cumulus cells of PCOS patients and controls were collected from the Gene Expression Omnibus database. Differentially expressed circRNAs (DECs), miRNAs (DEMs) and protein-coding genes (DEGs) were identified by the limma method. The weighted correlation network analysis (WGCNA) was conducted using the DECs to mine PCOS-associated modules. Hub DECs in modules were defined as both of |gene significance| and |module membership| > 0.8. The downstream effectors of hub DECs were predicted by constructing DEC-DEM-DEG ceRNA and DEC-RNA binding protein (RBP) networks. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed to explore the functions of circRNAs.Results: A total of 3614 DECs, 3544 DEGs and 1469 DEMs were identified between PCOS and controls. WGCNA analysis yielded five PCOS-related modules, of which 190 DECs were hub circRNAs. Seventeen hub DECs, nine DEMs, and 315 DEGs were identified to construct the ceRNA network, while 56 hub DECs and two DEGs (MBNL2, RBPMS) constituted the circRNA-RBP network. Five hub DECs (hsa_circ_0063309, hsa_circ_0054275, hsa_circ_0056196, hsa_circ_0018108 and hsa_circ_0070987) were overlapped between ceRNA and DEC-MBNL2 regulatory networks and thus they may be pivotal for PCOS. Furthermore, hsa_circ_0099109 could interact with the RBP gene RBPMS. Function analyses showed these circRNAs were inflammation-, apoptosis- or steroidogenesis-related.Conclusion: Aberrant expression of six circRNAs that function as RBP regulators or miRNA sponges may be possible mechanisms underlying the pathogenesis of PCOS by affecting apoptosis and steroidogenesis in cumulus cells.Keywords: circular RNAs, competitive endogenous RNAs, polycystic ovary syndrome, RNA-binding proteins, weighted gene co-expression network analysis

Jiamin Cheng,1,&ast; Yinyin Li,1,&ast; Xiaohui Wang,2,&ast; Zheng Dong,1 Yan Chen,1 Rui Zhang,1 Jiagan Huang,1 Xueyuan Jin,1 Jianfei Yao,2 Aifang Ge,2 Lele Song,2,3,&ast; Yinying Lu,1 Zhen Zeng1 1Comprehensive Liver Cancer Department, The Fifth Medical Center of the Chinese PLA General Hospital, Beijing, 100039, People’s Republic of China; 2HaploX Biotechnology, Shenzhen, Guangdong Province, People’s Republic of China; 3Department of Radiotherapy, The Eighth Medical Center of the Chinese PLA General Hospital, Beijing, 100091, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yinying Lu; Zhen ZengComprehensive Liver Cancer Department, The Fifth Medical Center of the Chinese PLA General Hospital, Beijing, 100039, People’s Republic of ChinaEmail luyinying1973@163.com; zengzhen1970@sina.comBackground: Immunotherapy combined with VEGF inhibitor has become the new first-line therapy for advanced or metastatic hepatocellular carcinoma (HCC). However, the biomarkers for response and prognosis stratification of HCC first-line combined immunotherapy have not been clarified.Methods: Here, we obtained the genomic alteration data from pre-therapeutic samples of 103 HCC patients using a 605-gene NGS test, and obtained the transcriptional and T cell receptor (TCR) diversity data from 18 patients who underwent the first-line combined immunotherapy using RNAseq and TCR sequencing, respectively. Patients received sorafenib/sintilimab or lenvatinib/sintilimab combined first-line therapy and the response was assessed at 3– 6 cycles of therapy.Results: No stratification of response was found in high-frequency key driver gene mutations, including TP53 and TERT. However, significantly higher ratio of progression (PD) was found in patients carrying MDM4 amplification. Similarly, FGF/3/4/19 amplifications could also result in high ratio of PD. The mRNA and lncRNA levels of eight genes related to hepatic metabolism and immune microenvironment exhibited significant differences between PR/SD and PD group, including DGKI, TNFSF14, CHST4, ACTIN1, PFKP, SLC51B, LCK and ERN1, suggesting stratification of response. Furthermore, moderate correlation was identified between the stratification genes (CHST4, SLC51B and ERN1) and immune factors (TIGIT, CD34, ICAM1, CCL5, CXCL9 and CXCL10), suggesting potential roles of these factors in immunoregulation. Strong linear correlation was found between any two of the three indexes for TCR CDR3 diversity, including Shannon–Wiener Index, Simpson index and evenness. However, no significant difference was found in the three indexes between the PR/SD and PD group, suggesting no stratification of response by these indexes.Conclusion: We identified several potential biomarkers for response stratification in the first-line combined immunotherapy. MDM4 was capable of predicting disease progression, and a panel mRNA and lncRNA of eight genes may also predict the response. Further validation is needed to verify these biomarkers.Keywords: hepatocellular carcinoma, HCC, immunotherapy, mRNA, lncRNA, TCR, sintilimab, sorafenib, lenvatinib

Zhaoyinqian Li,&ast; Zixuan Ding,&ast; Jia Yang,&ast; Yao Liu, Xinrui Jin, Jingling Xie, Tingting Li, Yinhuan Ding, Zhangrui Zeng, Jinbo Liu Department of Laboratory Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jinbo LiuDepartment of Laboratory Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, People’s Republic of ChinaTel/Fax +86 830 3165730Email Liulab2019@163.comBackground: Carbapenem-resistant Klebsiella pneumoniae (CRKP) infection has attracted worldwide concern and became a serious challenge for clinical treatment. The aims of this study were to evaluate the molecular characteristics and risk factors for CRKP infection.Methods: All the CRKP strains were screened for antimicrobial resistance genes, virulence genes, and integron by polymerase chain reaction (PCR). Plasmid typing was performed by plasmid conjugation assay and PCR-based replicon typing (PBRT). The genetic environments of blaKPC-2 and blaNDM-1 were analyzed by using overlapping PCR and molecular typing was performed by multi-locus sequence typing (MLST). Risk factors for CRKP infection were analyzed by logistic regression model.Results: All the 66 CRKP isolates were multidrug-resistant, but all of them were susceptible to tigecycline and polymyxin B. Among the CRKP isolates, 42 blaKPC-2-positive strains were identified carrying IncFII plasmids. Meanwhile, 24 blaNDM-positive strains were found on lncX3 plasmids, including 20 blaNDM-1 isolates and 4 blaNDM-5 isolates. Most of CRKP isolates contained several virulence genes and the class I integron (intl1). The genetic environments of blaKPC-2 and blaNDM-1 revealed that the conserved regions (tnpA-tnpR-ISkpn8-blaKPC-2) and (blaNDM-1-bleMBL-trpF-tat) were associated with the dissemination of KPC-2 and NDM-1. ST11 was the most common type in this work. Hematological disease, tracheal cannula, and use of β-lactams and β-lactamase inhibitor combination were identified as independent risk factors for CRKP infection.Conclusion: This study established the resistance pattern, molecular characteristics, clonal relatedness, and risk factors of CRKP infection. The findings of the novel strain that co-harboring blaNDM-5 and blaIMP-4, and the novel ST4495 indicated that the brand-new types have spread in Southwest China, emphasizing the prevent and control the further dissemination of CRKP isolates are highly needed.Keywords: carbapenem-resistant Klebsiella pneumoniae, molecular characteristics, genetic environments, plasmid, risk factors

Xiaonan Zhang,1,&ast; Huimin Fang,1,&ast; Zhigang Zeng,1 Kaijun Zhang,1 Zhanyi Lin,1,2 Gang Deng,1 Weiping Deng,1 Lichang Guan,1 Xuebiao Wei,1 Xinyi Li,2 Lei Jiang,1– 3 Lishu Xu1– 3 1Guangdong Provincial Geriatrics Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, People’s Republic of China; 2School of Medicine, South China University of Technology, Guangzhou, 510641, People’s Republic of China; 3The Second School of Clinical Medicine, Southern Medical University, Guangzhou, 510515, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lei Jiang; Lishu Xu Tel +86-20-83827812; +86-20-13660032429Email jianglei@smu.edu.cn; xulishu70@163.comPurpose: Gastric cancer is a common tumor type associated with nutritional and immune status. The aim of the current study was to investigate the prognostic value of a preoperative prognostic nutritional index (PNI), composed of nutritional factors and immune factors in elderly patients undergoing gastric cancer surgery.Patients and Methods: A total of 454 patients undergoing gastric cancer surgery were divided into two groups based on preoperative PNI scores: ≤ 45.1 (n = 307) and > 45.1 (n = 147). Survival analysis was performed using the Kaplan–Meier method and Log rank tests. Univariate and multivariate analyses were conducted to identify independent prognostic factors using a Cox proportional hazards model.Results: According to the X-tile program, the optimal cutoff value for predicting overall survival (OS) with the PNI was 45.1. The receiver operating characteristic analysis revealed that PNI exhibited 70.6% sensitivity and 56.5% speci&filig;city for predicting death during long-term follow-up. The cumulative incidence of postoperative 4-year mortality indicated that the risk of death increased significantly for PNI ≤ 45.1. In multivariate analysis, preoperative PNI was a significant independent predictor of mortality. In the age-stratified subgroup analysis, preoperative PNI was more sensitive for the old elderly subgroup than for the young elderly subgroup.Conclusion: Preoperative PNI is a sensitive and specific prognostic predictor among elderly patients undergoing gastric cancer surgery.Keywords: elderly patients, gastric cancer, prognostic nutritional index, radical gastrectomy

Rui Chen,1 Xi Wang,2,3 Shixian Zhou,2,4 Zongyue Zeng2 1Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 2Department of Laboratory Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 3Key Laboratory of Diagnostic Medicine Designated by the Ministry of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 4Department of Pathology, Central Hospital of Jiangjin District, Chongqing, 402260, People’s Republic of ChinaCorrespondence: Zongyue ZengDepartment of Laboratory Medicine, The First Affiliated Hospital of Chongqing Medical University, No.1 Youyi Road, Yuzhong District, Chongqing, 400016, People’s Republic of ChinaTel +86 23-8895-5532Email zengzongyue@126.comIntroduction: Growing evidence suggests that long non-coding RNAs (lncRNAs), such as lncRNA HOXA-AS2, are critical regulators involved in human cancer. However, the biological functions and detailed mechanisms underlying how lncRNA HOXA-AS2 affects oral squamous cell carcinoma (OSCC) remain unexplored.Methods: The expression of lncRNA HOXA-AS2 and miR-567 was determined in OSCC cell lines and clinical tissues by quantitative real-time PCR (qRT-PCR). Target site prediction and luciferase report assays were used to explore their potential interaction and binding sites between lncRNA HOXA-AS2 and miR-567. Overexpression or silencing expression of lncRNA HOXA-AS2 was performed to confirm that miR-567 was suppressed by lncRNA HOXA-AS2. WST-1 assay, crystal staining assay, and cell cycle analysis were used to assess the cell viability and proliferation ability. The target gene of miR-567 was predicted by Targetscan and validated by luciferase report assay as well as qRT-PCR and Western Blot. Xenograft nude mice model was done to demonstrate that lncRNA HOXA-AS2 promoted cell proliferation via targeting miR-567/CDK8 in vivo.Results: LncRNA HOXA-AS2 was up-regulated in OSCC cells and tissues with the expression of miR-567 decreased. The tissue lncRNA HOXA-AS2 expression was found to positively correlate with the TNM stage and lymph node metastasis of OSCC patients. In terms of the mechanism, we found that lncRNA HOXA-AS2 negatively regulates miR-567 expression via a direct interaction. Functionally, overexpression of lncRNA HOXA-AS2 significantly promoted OSCC cell proliferation, while knockdown of lncRNA HOXA-AS2 significantly inhibited it. We also observed that miR-567 directly targets the 3ʹ UTR of CDK8. Moreover, silencing lncRNA HOXA-AS2 inhibited tumor growth with the expression of miR-567 increased and CDK8 decreased in vivo.Conclusion: LncRNA HOXA-AS2 was up-regulated in OSCC, and its up-regulation correlated with poor clinical outcomes. The lncRNA also promoted OSCC cell proliferation by directly binding to miR-567, leading to an increase in CDK8 expression. The potential prognostic value of lncRNA HOXA-AS2 should be explored in future studies.Keywords: LncRNA HOXA-AS2, MiR-567, CDK8, Oral squamous cell carcinoma, Tumor progression

Zhaoyinqian Li,&ast; Zixuan Ding,&ast; Yao Liu, Xinrui Jin, Jingling Xie, Tingting Li, Zhangrui Zeng, Zhibin Wang, Jinbo Liu Department of Laboratory Medicine, the Affiliated Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jinbo LiuDepartment of Laboratory Medical, Affiliated Hospital of Southwest Medical University, 25 Taiping Street, Luzhou, 646000, Sichuan, People’s Republic of ChinaTel/Fax +86 0830 3165730Email Liulab2019@163.comBackground: Acinetobacter baumannii is an important pathogen in clinical infections, and biofilm formation is an effective way for A. baumannii to survive under external pressures. In this study, the aims were to examine the antimicrobial resistance, biofilm formation, and biofilm-specific resistance in clinical isolates of A. baumannii.Materials and Methods: A total of 104 clinical A. baumannii isolates were collected from a large teaching hospital in Southwest China. The antibiotics susceptibilities were tested, and biofilm-forming ability was evaluated by crystal violet staining by confocal laser scanning microscopy (CLSM). Minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), minimum biofilm inhibitory concentration (MBIC), and minimum biofilm eradication concentration (MBEC) of ciprofloxacin, meropenem, and ceftazidime were tested on selected strains by broth microdilution method. Biofilm-associated genes were detected by polymerase chain reaction (PCR), and expression of genes at planktonic stage and biofilm stage were analyzed by real-time reverse transcription PCR (RT-PCR).Results: Multidrug-resistant (MDR) isolates accounted for 65.4%, but no strain was resistant to tigecycline and polymyxin B. Moreover, non-MDR strains tended to form stronger biofilms than MDR strains, and a negative correlation between biofilm-forming ability and resistance profiles to each of tested antimicrobials were observed. The MBECs and MBICs of ciprofloxacin, ceftazidime, and meropenem were evidently increased compared with MICs and MBCs among all tested strains. Additionally, the biofilm formation ability of the csuD-positive strains was stronger than that of the csuD-negative strains. The strains in MDR group had higher carrying rate of csuA and csuD genes than non-MDR group, while non-MDR strains possessed more ompA gene than MDR group. Finally, abaI gene was significantly up-regulated after biofilm formation.Conclusion: These results revealed valuable data for the negative correlation between antimicrobial resistance and biofilm formation, as well as phenotypic and genotypic characteristics of biofilm formation in A. baumannii.Keywords: Acinetobacter baumannii, biofilm formation, antimicrobial resistance, gene expression

Ting Jiang,1,* Shuang Liu,1,* Xiaojun Wu,2,* Xiaoqing Liu,3 Weizhan Li,4 Shanfei Yang,1 Peiqiang Cai,5 Shaoyan Xi,6 Zhifan Zeng,1 Yuanhong Gao,1 Gong Chen,2 Weiwei Xiao1 1Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China; 2Department of Colorectal Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China; 3Department of Radiation Oncology, Guangzhou Concord Cancer Center, Guangzhou, People’s Republic of China; 4Department of Radiation Oncology, Panyu Center Hospital, Guangzhou, People’s Republic of China; 5Department of Radiology, Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China; 6Department of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Gong Chen; Weiwei Xiao Email chengong@sysucc.org.cn; xiaoww@sysucc.org.cnPurpose: This study aimed to predict the risks of distant metastasis (DM) of locally advanced rectal cancer (LARC) patients with pathological complete response (pCR) after neoadjuvant chemoradiotherapy (NACRT) and total mesorectal excision (TME), and to find the association between adjuvant chemotherapy (ACT) and their survival outcomes.Methods and Materials: A total of 242 patients with LARC achieving pCR after NACRT were enrolled in this retrospective study. We developed a nomogram model using logistic regression analyses for predicting risk of DM. The model performance was evaluated by the concordance index and calibration curve. Survival was determined using Kaplan–Meier survival curve.Results: Age, pre-operative CEA, pre-treatment CEA and distance of tumor to anal verge were identified as significantly associated variables that could be enrolled in the model to predict the risk of DM for pCR patients. The nomogram we created had a bootstrapped-concordance index of 0.731 (95% CI = 0.627 to 0.834) and was well calibrated. The high risk group was more likely to develop DM than low risk group (total score) (95% CI = 1.439 to 6.493, P = 0.0036). The 1-year, 3-year, and 5-year distant metastasis-free survival (DMFS) for the low and high risk groups (total score ≤ 90 vs > 90) was 97.8%, 94.2%, 94.2% and 91.3%, 83.4%, 81.8%, respectively (P = 0.0036). DM occurred within 1 and 2 years after TME surgery was 33.3% and 55.6% for the low risk group, and 47.3% and 84.2% for the high risk group. The value of ACT was assessed among the whole cohort, patients with cT3-4, with cN+ or with either DM risk group, but no significant difference was observed concerning DMFS whether ACT was given or not (all P > 0.05). Active treatment after DM was more beneficial than palliative treatment (P < 0.001).Conclusion: The nomogram model, including age, pre-operative CEA, pre-treatment CEA and distance to anal verge, predicted the probability of DM among LARC patients achieving pCR after NACRT. The effects of ACT were not seen in different subgroups, while closer clinical follow-up may have greater contribution to pCR patients in the first 2 years, especially for patients with relatively higher risk to develop DM. It is suggested that timely active treatment can bring survival benefit for pCR patients developing DM after NACRT.Keywords: locally advanced rectal cancer; LARC, pathological complete response; pCR, adjuvant chemotherapy; ACT, distant metastasis; DM

Ning Zhang,1 Changqing Zhang,2 Zhihong Zeng,1 Jiyong Zhang,1 Shengnan Du,1 Chunde Bao,3 Zhe Wang1 1Longwood Biopharmaceuticals, Shanghai, People’s Republic of China; 2Department of Orthopaedics, Shanghai Sixth People’s Hospital, Shanghai, People’s Republic of China; 3Department of Rheumatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of ChinaCorrespondence: Zhe Wang Email zhe.wang@lwbiopharma.comBackground: Research on JAK family members as therapeutic targets for autoimmune diseases has brought tofacitinib and baricitinib into clinical for the treatment of rheumatoid arthritis and other autoimmune diseases. Despite the potent efficacy of these first-generation JAK inhibitors, their broad-spectrum JAK inhibition and adverse events warrant development of a JAK1-specific inhibitor to improve their safety profile.Methods: In this study, we characterized a JAK1-specific inhibitor, LW402, on biochemical and human whole-blood assays. We further evaluated the therapeutic efficacy of LW402 in a rat adjuvant-induced arthritis (rAIA) model and a mouse collagen-induced arthritis (mCIA) model. The safety of LW402 was evaluated in both SpragueDawley rats and cynomolgus monkeys.Results: LW402 exhibited potent nanomolar activity against JAK1 and showed a 45-fold selectivity for inhibition of JAK1- over JAK2-dependent signaling induced by either IL6 or GM-CSF in human whole-blood assays. In the rAIA model, oral dosing of LW402 resulted in a dose-dependent improvement in disease symptoms, including reduction in paw swelling, marked reduction in the inflammatory-cell infiltration to synovial tissue, and protection of articular cartilage and bone from damage. The therapeutic efficacy of LW402 correlated well with the plasma exposure of LW402 and the extent of pSTAT3 inhibition in white blood cells. LW402 also effectively eased disease symptoms in the mCIA model. Toxicity studies in the Sprague Dawley rats and cynomolgus monkeys established a ≥ 5x therapeutic window for LW402 as drug exposures of toxicity study NOAEL dose and pharmacology study ED50 dose were compared.Conclusion: We developed a novel JAK1-specific inhibitor LW402 with potent efficacy in rAIA and mCIA models. We established a good safety profile for LW402 in toxicity studies, and the overall superiority of LW402 should translated well to the clinical setting for the treatment of RA and other autoimmune diseases.Keywords: rheumatoid arthritis, JAK1 inhibitor, rat-AIA model, mouse CIA

Ran Zhao,1,* Chao Wang,1,* Chao Sun,1 Kun Jiang,1 Shengnan Wu,2 Fen Pan,2 Zeyu Zeng,1 Yijing Hu,1 Xiaoyan Dong1 1Department of Respiratory, Shanghai Children’s Hospital, Shanghai Jiaotong University, Shanghai, 200062, People’s Republic of China; 2Clinical Laboratory of Shanghai Children’s Hospital, Shanghai Jiaotong University, Shanghai, 200062, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaoyan DongDepartment of Respiratory, Shanghai Children’s Hospital, Shanghai Jiaotong University, No. 355 Luding Road, Shanghai, 200062, People’s Republic of ChinaEmail dongxy@shchildren.com.cnPurpose: Autosomal dominant hyper-IgE syndrome (HIES) is a rare primary immune deficiency syndrome caused mainly by mutations in the signal transducer and activator of transcription 3 (STAT3) gene. More information on STAT3 mutations is still needed, and further investigation is warranted. A girl with HIES carrying a novel STAT3 mutation who had no obvious apparent symptoms but presented with a severe necrotizing pulmonary infection is described here. We analysed dynamic changes in blood cells and a series of inflammatory factors in the bronchoalveolar lavage fluid (BALF) before and after each bronchoscopic lavage to relieve her severe pulmonary abscess.Patients and Methods: Whole-exome sequencing and Sanger sequencing were used to identify novel STAT3 mutations. Flow cytometry was used for immune analysis of Th17 cells and inflammatory cytokines.Results: A novel de novo mutation in STAT3 (c.1552C>T, p.Arg518*) was identified in this patient. The number of eosinophils decreased after each bronchoscopy procedure. Elevated interleukin (IL)-8 and IL-1β levels were detected in her right lung BALF in the acute phase, but they were reduced after four bronchoscopic lavage procedures and the administration of antimicrobial medicine.Conclusion: More information on STAT3 mutations is needed to investigate the relationship between the genotype and HIES phenotype. Bronchoscopic lavages are recommended instead of surgery to relieve acute severe pulmonary abscesses and necrotizing pulmonary infections in paediatric patients with HIES.Keywords: hyper-IgE syndrome, infection, lung alveolar lavage fluid, pulmonary infection

Su-ping Guo,1,2,* Chen Chen,1,2,* Zhi-fan Zeng,1,2 Qiao-xuan Wang,1,2 Wu Jiang,2,3 Yuan-hong Gao,1,2 Hui Chang1,2 1Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China; 2State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China; 3Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yuan-hong Gao; Hui ChangDepartment of Radiation Oncology, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, Guangdong, 510060, People’s Republic of ChinaTel +86-13560182168; +86-13480295989Email gaoyh@sysucc.org.cn; changhui@sysucc.org.cnBackground: Serum lipids have been reported as prognosticators for malignancies, including rectal cancer (RC). Yet, their value in predicting the response of RC to neoadjuvant chemoradiotherapy (NACRT) remains unknown. This study aimed to assess the predictive abilities of serum lipids for a bad response, and to build a serum lipid-based prediction model.Methods: In total, 751 patients diagnosed with stage cII–III RC and treated with NACRT plus surgery from January 2007 to August 2018 were retrospectively reviewed and randomly divided into two data sets, in a ratio of 1:1. Receiver operating characteristics (ROC) analysis was conducted in the development set to select possible predictors of bad NACRT response from pathoclinical factors, including serum lipids. Multivariate logistic regression was conducted to further determine independent predictors, which were then used to develop a prediction index (PI). Finally, the PI was verified in the validation set, through ROC analysis and chi-squared test.Results: Five independent predictors were identified: tumor length ≥ 4 cm, cT4 stage, carcinoembryonic antigen ≥ 5.0 ng/mL, irradiation with three-dimensional conformal radiotherapy technique, and apolipoprotein A-I ≤ 1.20 g/L. Each of them was assigned a number of points. In the validation set, the area under the curve of PI appeared as 0.642 (95% confidence interval 0.586– 0.697). The sensitivity, specificity, positive and negative predictive values, and concordance were 72.3%, 52.3%, 63.8%, 61.9%, and 63.0%, respectively.Conclusion: Serum apolipoprotein A-I was found to correlate negatively with the RC response to NACRT. It could serve as a biomarker for guiding individualized treatment and a potential target for improving sensitivity to chemoradiation.Keywords: rectal cancer, radiotherapy, apolipoprotein A-I, tumor response, prediction model

Zhaojun Yu,1– 3 Jianbiao Huang,1– 3 Huanhuan Deng,1,3 Zhihua Zeng,1 Leihong Deng,4 Xiangda Xu,1 Haichao Chao,1 Tao Zeng1 1Department of Urology, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, People’s Republic of China; 2Department of Urology, The People’s Hospital Affiliated to Nanchang University, Nanchang, 330006, People’s Republic of China; 3Medical Department, Nanchang University, Nanchang, 330006, People’s Republic of China; 4Department of Ultrasound, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, People’s Republic of ChinaCorrespondence: Tao ZengDepartment of Urology, The Second Affiliated Hospital of Nanchang University, No. 1 Minde Road, Nanchang, Jiangxi Province, 330006, People’s Republic of ChinaTel +8613607919171Email Taozeng40709@sina.comPurpose: To explore the application of the neobladder-urethral drag-and-bond anastomosis technique in laparoscopic radical cystectomy (LRC) with ileal orthotopic neobladder (IONB) reconstruction.Patients and Methods: This is a retrospective cohort study on a procedure performed by a single surgeon. From January 2014 to December 2018, we identified 43 male bladder cancer patients who received LRC with IONB reconstruction. These patients were divided into two groups, with 22 patients undergoing neobladder-urethral drag-and-bond anastomosis (NUDA) and 21 patients undergoing neobladder-urethral anastomosis under laparoscopy (NUAL). Anastomosis time, catheter removal time, postvoid residual (PVR), maximum urinary flow rate (Q-max), urine leakage and anastomotic stenosis were used to evaluate the simplicity and surgical effect of the two groups.Results: Both groups demonstrated similar tumor characteristics. A significant difference in neobladder-urethral anastomosis time was found between the NUDA group and the NUAL group (14.6 ± 0.4 vs 70 ± 2.5 min, P< 0.0001), and there was no significant difference in other characteristics.Conclusion: The neobladder-urethral drag-and-bond anastomosis technique in LRC and IONB reconstruction, with its shorter learning curve, was easier and more convenient than neobladder-urethral anastomosis under laparoscopy.Keywords: drag-and-bond anastomosis, neobladder-urethral anastomosis, laparoscopic radical cystectomy, ileal orthotopic neobladder, bladder cancer

Qingwen Deng, Junhong Lu, Zhichao Zeng, Yuhang Zheng, Wenbin Liu Department of Health Management, School of Public Health, Fujian Medical University, Fuzhou 350122, People’s Republic of ChinaCorrespondence: Wenbin LiuDepartment of Health Management, School of Public Health, Fujian Medical University, Room 108 in the Building for School of Public Health, No. 1 Xuefubei Road, Minhou District, Fuzhou 350122, People’s Republic of ChinaTel + 86 13799983766Email wenbinliu126@126.comBackground: Limited diffusion of health technology has greatly halted the improvement of resource integration and healthcare outcomes. The importance of understanding the dynamics of health technology diffusion is increasingly highlighted. However, the dynamic mechanism of health technology diffusion in the context of the integrated care system (ICS) remained largely unknown.Purpose: To develop and validate the scale on Dynamics of Health Technology Diffusion in Integrated Care System (DHTDICS) for providing an instrument to investigate the health technology diffusion in the ICS in China, by taking the Des-gamma-Carboxy Prothrombin (DCP) test as an example.Methods: Based on previous classical theories such as the theory of planned behavior (TPB), technology acceptance model (TAM), and technology-organization-environment framework (TOE), the scale with 34 items was initially developed. It was tested in a cross-sectional questionnaire survey including 246 participants from February to August 2019 in China. Cronbach’s alpha, corrected item-total correlation, and factor loadings were used to assess reliability. Exploratory factor analysis and confirmatory factor analysis were applied to evaluate the validity by assessing factor structures and correlations.Results: Reliability analysis revealed excellent internal consistency. Acceptable validity was confirmed through tests of convergent validity and discriminant validity. Regarding the domains that DHTDICS contributes, the results highlighted 4 domains: personal beliefs (including dimensions of attitudes, subjective norms and perceived behavioral control), technical drivers (including dimensions of ease of use and price rationality), organizational readiness (including dimensions of organizational culture, technology absorptive willingness and technology sharing willingness), and external environment (dimension of industry competition pressure).Conclusion: The findings confirmed the reliability and validity of the scale on DHTDICS. The scale will be not only a scientific tool in determining the dynamics of health technology diffusion in the ICS, but also a helpful reference for developing future interventions to promote health technology diffusion.Keywords: health technology diffusion, dynamics, scale development, integrated care system, validity, reliability, China

Shuyi He,1– 3,* Jingyu Li,1– 3,* Mingjian Chen,1– 3 Liehua Deng,4 Yuxin Yang,1– 3 Zhaoyang Zeng,1– 3 Wei Xiong,1– 3 Xu Wu1– 3 1NHC Key Laboratory of Carcinogenesis and Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute and School of Basic Medical Science, Central South University, Changsha, People’s Republic of China; 2Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 3Hunan Key Laboratory of Translational Radiation Oncology, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, People’s Republic of China; 4Department of Critical Care Medicine, Affiliated Hospital of Guangdong Medical University, Zhanjiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xu WuCentral South University, 110 Xiangya Road, Kaifu District, Changsha City, Hunan Province 410078, People’s Republic of ChinaEmail wuxu1028@csu.edu.cnIntroduction: Near-infrared (NIR) hyperthermia agents are promising in cancer photothermal therapy due to their deeper penetration ability and less side effects. Spherical gold nanoshell and graphene-based nanomaterials are two major NIR hyperthermia agents that have been reported for photothermal therapy of cancer. Herein, we constructed a two-dimensional graphene oxide-template gold nanosheet (GO@SiO2@AuNS) hybrid that could destruct cancer cells with efficient photothermal effect.Methods: Graphene oxide was coated with a layer of mesoporous silica, which provided binding sites for gold seeds. Then, seed-growth method was utilized to grow a layer of gold nanosheet to form the GO@SiO2@AuNS hybrid, which possessed great biocompatibility and high photothermal conversion efficiency.Results: With the irradiation of NIR laser (808 nm) with low power density (0.3 W/cm2), GO@SiO2@AuNS hybrid showed a photothermal conversion efficiency of 30%, leading to a temperature increase of 16.4 °C in water. Colorectal cancer cells (KM12C) were killed with the treatment of GO@SiO2@AuNS hybrid under NIR irradiation.Conclusion: The GO@SiO2@AuNS hybrid may expand the library of the 2D nanostructures based on gold for cancer photothermal therapy.Keywords: graphene oxide, gold nanosheets, photothermal therapy, near-infrared

Fanghui Li,1,* Dongze Li,1,* Jing Yu,2 Yu Jia,1 Ying Jiang,1 Tengda Chen,1 Yongli Gao,1 Zhi Wan,1 Yu Cao,1 Zhi Zeng,1 Rui Zeng1,3 1Department of Emergency Medicine and Laboratory of Emergency Medicine, Deep Underground Space Medical Center, West China Hospital, and Disaster Medical Center, Sichuan University, Chengdu, People’s Republic of China; 2West China School of Nursing, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 3Department of Cardiology, West China Hospital, Sichuan University, Chengdu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Rui ZengDepartment of Cardiology, West China Hospital, Sichuan University, 37 Guoxue Road, Chengdu 610041, Sichuan, People’s Republic of ChinaTel +86-28-85423248Fax +86-28-85582944Email zengrui_0524@126.comBackground: The Barthel index (BI) is a widely used assessment tool for evaluating physical performance in activities of daily living (ADL). The association between BI scores and mortality in hospital and during follow-up of acute coronary syndrome (ACS) patients remains unclear. The present study investigated whether the BI score could be used as a predictor for mortality of ACS.Methods: We investigated ACS patients from the multi-center Retrospective Evaluation of Acute Chest Pain (REACP) study. The association between BI scores and all-cause mortality of patients with ACS was analyzed by Cox proportional hazards models. The primary endpoint was all-cause death and the secondary endpoint was cardiac death during follow-up.Results: Among 2908 patients with ACS enrolled, 277 (9.5%) patients died within a median follow-up time of 10.6 months. Patients with lower BI had higher risks of mortality, compared with those with higher BI in ACS patients. Kaplan–Meier analysis revealed that patients with lower BI had worse survival rates than patients with higher BI (P < 0.001). After adjustment for potential influencing factors, multivariate Cox regression analysis showed that the BI was independently associated with all-cause mortality and cardiac mortality, respectively.Conclusion: The BI at admission has the powerful potential to provide useful prognostic information of early risk stratification, and routine recording of the BI at the ED visit may help in decision-making and health care planning for patients with ACS.Keywords: Barthel index, activities of daily living, acute coronary syndrome, prognosis, mortality

Jing Zhu,1,2,* Zhiling Zhao,3,* Bin Wu,4 Zhihong Shi,5 Qingrong Nie,6 Zhen Fu,7 Zhaofu Zeng,1 Weihua Hu,1 Minglin Dong,1 Mengqing Xiong,1 Ke Hu1 1Department of Respiratory and Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan, Hubei, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, The People’s Hospital of China Three Gorges University, Yichang, Hubei, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine, Beijing Chaoyang Hospital, Capital Medical University, Beijing, People’s Republic of China; 4Institute of Respiratory Diseases, Department of Respiratory, The Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, People’s Republic of China; 5Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Xian Jiaotong University, Xian, Shanxi, People’s Republic of China; 6Division of Respiratory Disease, Liangxiang Hospital of Yanjing Medical College, Capital Medical University, Beijing, People’s Republic of China; 7Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ke Hu Email huke-rmhospital@163.comObjective: The aim of this study was to explain “obesity paradox” in chronic obstructive pulmonary disease (COPD) by evaluating the effect of body mass index (BMI) on lung function in Chinese patients with COPD.Methods: A total of 1644 patients diagnosed with COPD were recruited from four Chinese tertiary hospitals and were divided into four groups including underweight, normal weight, overweight and obese according to BMI classification standard. The medical data of these patients were collected and used for the multiple linear regression analyses.Results: After adjustment for age, sex, educational level, economic status, smoking status, alcohol consumption, duration of COPD history, events of acute exacerbation in previous year, hypertension, diabetes mellitus, cardiovascular disease, cerebrovascular disease and osteoporosis, BMI had a curvilinear correlation with the forced expiratory volume in the first second (FEV1) in patients with Global Initiative for Obstructive Lung Disease (GOLD) 1– 2 grade (first-order coefficient β, 0.09; 95% CI, 0.03– 0.16; second-order coefficient β, − 0.002; 95% CI, − 0.003–-0.001; P< 0.01). However, BMI had a positive correlation with FEV1 in patients with GOLD 3– 4 grade (β, 0.01; 95% CI, 0.008– 0.017; P< 0.01) when BMI was used as a quantitative variable. When BMI was used as a qualitative variable, only FEV1 in overweight group with GOLD 1– 2 grade was significantly higher than that of normal weight group (P< 0.01). Interestingly, both overweight and obese groups had higher FEV1 in GOLD 3– 4 grade compared with normal weight group (β, 0.06; 95% CI, 0.02– 0.11; β, 0.11; 95% CI, 0.04– 0.18; P< 0.01). The effect of BMI on predicted percentage of FEV1 (FEV1%) was similar to that of FEV1 in different GOLD grades.Conclusion: Obesity only had a protective effect on lung function in COPD patients with GOLD 3– 4 grade rather than GOLD 1– 2 grade.Trial Registry: ClinicalTrials.gov, No.: NCT 03182309, URL: www.clinicaltrials.gov.Keywords: overweight, obesity

Zeliang Wei,1,2 Haibo Wang,3 Guang Xin,1 Zhi Zeng,1 Shiyi Li,1 Yue Ming,1 Xiaoyu Zhang,1 Zhihua Xing,1 Li Li,2 Youping Li,1 Boli Zhang,1,4 Junhua Zhang,4 Hai Niu,1,5 Wen Huang1 1Laboratory of Ethnopharmacology, West China Medical School, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 2Department of Dermatology, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 3Textile Institute, College of Light Industry, Textile and Food Engineering, Sichuan University, Chengdu, People’s Republic of China; 4Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China; 5College of Mathematics, Sichuan University, Chengdu, Sichuan, People’s Republic of ChinaCorrespondence: Wen Huang; Hai Niu Email huangwen@scu.edu.cn; niuhai@scu.edu.cnBackground: The metastasis, one of the biggest barriers in cancer therapy, is the leading cause of tumor deterioration and recurrence. The anti.-metastasis has been considered as a feasible strategy for clinical cancer management. It is well known that diosgenin could inhibit tumor metastasis and doxorubicin (DOX) could induce tumor apoptosis. However, their efficient delivery remains challenging.Purpose: To address these issues, a novel pH-sensitive polymer-prodrug based on diosgenin nanoparticles (NPs) platform was developed to enhance the efficiency of DOX delivery (DOX/NPs) for synergistic therapy of cutaneous melanoma, the most lethal form of skin cancer with high malignancy, early metastasis and high mortality.Methods and Results: The inhibitory effect of DOX/NPs on tumor proliferation and migration was superior to that of NPs or free DOX. What is more, DOX/NPs could combine mitochondria-associated metastasis and apoptosis with unique internalization pathway of carrier to fight tumors. In addition, biodistribution experiments proved that DOX/NPs could efficiently accumulate in tumor sites through enhancing permeation and retention (EPR) effect compared with free DOX. Importantly, the data from in vivo experiment revealed that DOX/NPs without heart toxicity significantly inhibited tumor metastasis by exerting synergistic therapeutic effect, and reduced tumor volume and weight by inducing apoptosis.Conclusion: The nanocarrier DOX/NPs with satisfying pharmaceutical characteristics based on the establishment of two different functional agents is a promising strategy for synergistically enhancing effects of cancer therapy.Keywords: anti-metastasis, antitumor, self-assembly, codelivery, doxorubicin