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Rong Huang,1,&ast; Rui Zheng,2,&ast; Shui Fu,1 Zuo Jie Li3 1Clinical Laboratory Department, First People’s Hospital of Linping District, Hangzhou, Zhejiang Province, People’s Republic of China; 2Department of Central Laboratory, Taizhou Hospital of Zhejiang Province, Taizhou, People’s Republic of China; 3Clinical Laboratory Department, The People’s Hospital of Cangnan Zhejiang, Wenzhou, Zhejiang Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zuo Jie Li, Clinical Laboratory Department, The People’s Hospital of Cangnan Zhejiang, No. 2288 Yucang Road, Cangnan County, Wenzhou, Zhejiang Province, 325800, People’s Republic of China, Tel +86 577-64810162, Email 15088908102@163.comObjective: Pertussis is a highly contagious respiratory disease, and early diagnosis and timely treatment are crucial for reducing complications and transmission. In this study, we analyzed the prevalence of pertussis and assessed the value of the WBC and lymphocyte percentage in its screening.Methods: A retrospective analysis was conducted on global pertussis data from the past decade. Patients who recently underwent pertussis nucleic acid detection and complete blood count (CBC) in our hospital were selected. Based on the results, 538 patients were classified into the pertussis group, and 595 into the control group. White blood count (WBC) and lymphocyte percentages were compared, diagnostic efficacy was calculated, and evaluate their application value in the diagnosis of pertussis.Results: In the past decade, the global incidence of pertussis first decreased, then increased. In China and Zhejiang province, it fluctuated but showed an upward trend recently. In Zhejiang Province, pertussis was more prevalent in summer and winter and rose last year. Between 2018 and 2020, most pertussis cases in China were infants under 1 year old. Last year, only 1.12% of patients in our hospital were infants, with more patients over 5 years old. WBC, lymphocyte percentage, and platelet count (PLT) was higher in the pertussis group (P < 0.05). Logistic regression showed that WBC, lymphocyte percentage, and PLT were correlated with pertussis infection. Sequential analysis showed that the WBC, lymphocyte percentage, and Youden’s index for both combined were 0.124, 0.082, and 0.044, respectively.Conclusion: The global incidence of pertussis is rising, with significant increases among adolescents and adults. Improved prevention and control strategies are needed. WBC and lymphocyte percentage serve as auxiliary diagnostic indicators, but their efficacy is limited.Keywords: pertussis, epidemiology, WBC, lymphocyte percentage, diagnostic competence

Xiaoxi Fan,1,2,&ast; Wenli Zhang,2,3,&ast; Ruihan Zheng,1 Yucong Zhang,1 Xianhui Lai,4 Jibo Han,5 Zimin Fang,1 Bingjiang Han,5 Weijian Huang,1 Bozhi Ye,1,2 Shanshan Dai1,6 1The Key Laboratory of Cardiovascular Disease of Wenzhou, Department of Cardiology, the First Affiliated Hospital of Wenzhou Medical University, Zhejiang, People’s Republic of China; 2The Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China; 3Department of Cardiovascular Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 4Department of Cardiology, Yuhuan County People’s Hospital of Zhejiang Province, Taizhou, People’s Republic of China; 5Department of Cardiology, the Second Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, People’s Republic of China; 6The Key Laboratory of Emergency and Disaster Medicine of Wenzhou, Department of Emergency, the First Affiliated Hospital of Wenzhou Medical University, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shanshan Dai; Bozhi Ye, Email shanshandai137@163.com; fredye2012@163.comAim: Hypertensive nephropathy is a common complication of hypertension. However, no effective measures are currently available to prevent the progression of renal insufficiency. Gasdermin D (GSDMD) is a crucial mediator of pyroptosis that induces an excessive inflammatory response. In the present study, we aimed to determine the effect of GSDMD on the pathogenesis of hypertensive nephropathy, which may provide new insights into the treatment of hypertensive nephropathy.Methods: C57BL/6 (wild-type, WT) and Gsdmd knockout (Gsdmd−/−) mice were subcutaneously infused with angiotensin II (Ang II) via osmotic mini-pumps to establish a hypertensive renal injury model. Recombinant adeno-associated virus serotype 9 (AAV9) carrying GSDMD cDNA was used to overexpress GSDMD. Renal function biomarkers, histopathological changes, and inflammation and fibrosis indices were assessed. Transcriptome sequencing (RNA-seq) and cleavage under targets and mentation (CUT & Tag) experiments were performed to identify the downstream pathogenic mechanisms of GSDMD in hypertensive nephropathy.Results: GSDMD was activated in the kidneys of mice induced by Ang II (P < 0.001). This activation was primarily observed in the renal tubular epithelial cells (P < 0.0001). GSDMD deficiency attenuated renal injury and fibrosis induced by Ang II (P < 0.0001), whereas Gsdmd overexpression promoted renal injury and fibrosis (P < 0.01). Mechanistically, GSDMD increased Ang II–induced GATA binding protein 2 (GATA2) transcription factor expression (P < 0.01). GATA2 also bound to the aquaporin 4 (Aqp4) promoter sequence and facilitated Aqp4 transcription (P < 0.001), leading to renal injury and fibrosis. Moreover, treatment with GI-Y1, an inhibitor of GSDMD, alleviated Ang II–induced renal injury and fibrosis (P < 0.01).Conclusion: GSDMD plays an important role in the development of hypertensive nephropathy. Targeting GSDMD may be a therapeutic strategy for the treatment of hypertensive nephropathy. Keywords: gasdermin D, hypertensive nephropathy, pyroptosis, angiotensin II, aquaporin 4, GATA binding protein 2

Wenyu Zhang,1,&ast; Linquan Li,1,&ast; Yaguang Wu,1 Chengzhilin Li,1 Zi’ang Xu,1 Nianlei Zhang,1 Xinyu Wang,1 Yingchun Zhao,1 Tingjian Zu,1 Qingbin He,1 Jianwei Jiao,2 Runxiao Zheng1 1School of Clinical and Basic Medical Sciences, Medical Science and Technology Innovation Center, Shandong Provincial Hospital, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, 250000, People’s Republic of China; 2State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Runxiao Zheng, Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, 250000, People’s Republic of China, Email zhengrunxiao@sdfmu.edu.cn Jianwei Jiao, State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, People’s Republic of China, Email jwjiao@ioz.ac.cnIntroduction: Immunotherapy has led to a paradigm shift in reinvigorating treatment of cancer. Nevertheless, tumor associated macrophages (TAMs) experience functional polarization on account of the generation of suppressive metabolites, contributing to impaired antitumor immune responses.Methods: Hence, metabolic reprogramming of tumor microenvironment (TME) can synergistically improve the efficacy of anti-tumor immunotherapy. Herein, we engineered an iron-based nanoplatform termed ERFe3O4 NPs. This platform features hollow Fe3O4 nanoparticles loaded with the natural product emodin, the outer layer is coated with red blood cell membrane (mRBCs) inserted with DSPE-PEG2000-galactose. This effectively modulates lactate production, thereby reversing the tumor immune suppressive microenvironment (TIME).Results: The ERFe3O4 NPs actively targeted TAMs on account of their ability to bind to M2-like TAMs with high expression of galectin (Mgl). ERFe3O4 NPs achieved efficient ability to reverse TIME via the production of reducing lactate and prompting enrichment iron of high concentrations. Furthermore, ERFe3O4 NPs resulted in heightened expression of CD16/32 and enhanced TNF-α release, indicating promotion of M1 TAMs polarization. In vitro and in vivo experiments revealed that ERFe3O4 NPs induced significant apoptosis of tumor cells and antitumor immune response.Discussion: This study combines Traditional Chinese Medicine (TCM) with nanomaterials to synergistically reprogram TAMs and reverse TIME, opening up new ideas for improving anti-tumor immunotherapy. Keywords: metabolic immunotherapy, nanoparticles, reprograming, iron oxide, macrophages

Jun Yan,1 Rongrong Zheng,1 Zhongdong Zhang,1 Jinchuan Shi,1 Tingbo Yan,2 Hong Liu,3 Feng Li1 1The Second Infectious Disease Department, Xixi Hospital of Hangzhou, Hangzhou, 310023, People’s Republic of China; 2Radiology Department, Xixi Hospital of Hangzhou, Hangzhou, 310023, People’s Republic of China; 3Pathology Department, Xixi Hospital of Hangzhou, Hangzhou, 310023, People’s Republic of ChinaCorrespondence: Feng Li, The Second Infectious Disease Department, Xixi Hospital of Hangzhou, No. 2 Hengbu Street, Liuxia Town, Xihu District, Hangzhou, 310023, People’s Republic of China, Email lfnice@foxmail.comBackground: Non-tuberculous mycobacteria (NTM) are a group of mycobacteria that are commonly found in the environment and can cause disease in humans. The symptoms of NTM infection can be similar to those of tuberculosis, making diagnosis challenging. The morbidity associated with NTM is increasing, and clinical management can be challenging.Case Description: This report details the case of a 32-year-old male who was found to have multiple enlarged and partially necrotic lymph nodes in the neck, axilla, mediastinum, and retroperitoneum. The causative agent was rapidly identified as Mycobacterium paracondontium through pathogen-targeted sequencing (tNGS). After two weeks of treatment with azithromycin, moxifloxacin, rifabutin, and amikacin, the patient’s uncomfortable symptoms had resolved, and he is currently undergoing further review.Conclusion: It is imperative that clinicians remain vigilant for the presence of NTM, particularly those that are rare, given their pervasiveness in the environment. Prompt diagnosis is of paramount importance, and molecular identification techniques represent a crucial tool in this regard. In vitro drug sensitivity testing should be conducted whenever feasible to guarantee the administration of an efficacious treatment regimen.Keywords: non-tuberculous mycobacteria, Mycobacterium paracondontium, lymph nodes, case report

Chaoping Yang,1,&ast; Jing Xie,2,&ast; Qianjun Chen,2 Qiongyin Yuan,3 Jianping Shang,4 Haibo Wu,5 Youhua Yang,6 Mingfang Wang,7 Xiaolan Shu,8 Jing Yue,9 Danna Tu,10 Ying Lin,1,&ast; Ronghao Zheng,4,&ast; Xiaolin Wu4 1Nursing Department, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2Department of Pediatric Nephrology, Rheumatology, and Immunology, Maternal and Child Health Hospital of Hubei Province, Hubei University of Medicine, Shiyan, Hubei, People’s Republic of China; 3Obstetrical department, Huanggang Maternal and Child Health Hospital, Hubei, People’s Republic of China; 4Department of Pediatric Nephrology, Rheumatology, and Immunology, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 5School of Health and Nursing, Wuchang University of Technology, Wuhan, People’s Republic of China; 6Department of Basic Medical Sciences, School of Medicine, Jianghan University, Wuhan, People’s Republic of China; 7Department of Pediatric Gastroenterology, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 8Department of Pediatric Intensive Care Unit (PICU), Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 9Emergency Department, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, People’s Republic of China; 10Department of Pediatric Cardiology, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ronghao Zheng, Department of Pediatric Nephrology, Rheumatology, and Immunology, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, 745 Wu Luo Road, Hongshan District, Wuhan, Hubei Province, 430070, People’s Republic of China, Email hytwo2001@126.com Ying Lin, Nursing department, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China, Email 523933025@qq.comPurpose: The knowledge, attitude, and practices (KAP) concerning antibiotics by healthcare students have the potential impact on controlling antibiotic abuse and antimicrobial resistance (AMR) growth. This study aims to evaluate the levels and explore the associated factors with KAP on antibiotic use and AMR in Chinese nursing students.Methods: A cross-sectional survey using a self-administered questionnaire consisting of demographics and selected features and KAP on antibiotic use and AMR was conducted to measure KAP levels among nursing students at various universities in Hubei Province, China. The logistic regression analyses were performed to analyze the potential factors associated with the KAP.Results: The survey eventually included a total of 1959 nursing students. The mean scores for KAP were 57.89 ± 26.32, 55.00 ± 12.50, and 71.88 ± 15.63, respectively. Regarding knowledge, 54.3% of participants were unaware that antibiotic was ineffective against viral infections. Regarding attitude, 36% of participants agreed that current antibiotic abuse existed; 96.2% of participants thought it necessary to set up a special course on antibiotics. Regarding practice, only 48.4% of participants usually purchased antibiotics with a prescription. Multivariable analyses indicated that lack of discussion on AMR in school courses was an independent risk factor against KAP, respectively. The main knowledge sources of antibiotic being outside the classroom was an independent risk factor related to knowledge and practice. The average score > 80 points was an independent protective factor related to knowledge and practice.Conclusion: The KAP level on antibiotic use and AMR among Hubei nursing students was general and required further strengthening. Nursing students with risk factors should be prioritized in educational interventions. The findings of our study pointed out some directions for tailored interventions to improve the training on antibiotics.Keywords: antibiotic use, antimicrobial resistance, knowledge, attitude, practice, nursing students

Quinoidal-aromatic conjugated polymers hold great application potential in organic field-effect transistors (OFETs). However, the development of high mobility quinoidal-aromatic conjugated polymers still lags behind the more popular donor-acceptor (D-A) conjugated polymers, mainly owing to the lack of a rational design strategy and efficient building block. Herein, a novel quinoid-donor-acceptor (Q-D-A) strategy is demonstrated to modulate the energy-level and boost the charge carrier transport mobility of conjugated polymers as opposed to the D-A system. On the basis of this strategy, a quinoidal-aromatic conjugated polymer, namely PAQM-BT, is designed and synthesized. With the combined use of quinoid, donor and acceptor units in the backbone, the resulting Q-D-A polymer PAQM-BT displays the narrowest bandgap with the deepest-lying lowest unoccupied molecular orbital (LUMO) energy level, highest backbone coplanarity, enhanced thin-film crystallinity and smallest effective hole mass in comparison with the corresponding D-A polymer PT3B1 and quinoid-donor (Q-D) polymer PAQM-3T. Benefitting from the more effective intra- and inter-chain charge transport, as corroborated by experiment and theoretical calculations, OFET devices based on PAQM-BT exhibit a highly boosted hole mobility of up to 5.10 cm2 V-1 s-1, which is one and four orders of magnitude higher than that of PAQM-3T and PT3B1, respectively, and is among the highest for quinoidal-aromatic conjugated polymers. The potent Q-D-A strategy not only allows the energy level to be modulated but also leads to effective charge carrier transport, opening up possibilities to the development of high mobility quinoidal-aromatic conjugated polymers based on a variety of quinoids, donors, and acceptors. This journal is

Jingjing Song,&ast; Yuyan Gao,&ast; Yufei Wang, Huan Dai, Xiaoxiao Jia, Qiangwei Xiang, Hui Zhang, Rongying Zheng, Weixi Zhang Department of Pediatric Allergy and Immunology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, 325027, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Weixi Zhang, Email zhangweixi112@163.comPurpose: To compare the anxiety, depression and sleep quality of mothers of healthy control children and mothers of children with atopic dermatitis (AD) of varying severity, both before and after treatment.Methods: A total of 120 parent–child dyads participated in the study. These dyads were divided into four subgroups of 30 patients each: mild AD, moderate AD, severe AD, and control groups. The children’s symptoms, their mothers’ psychological status, and their mothers’ sleep quality were evaluated using the Scoring of Atopic Dermatitis (SCORAD), the Hospital Anxiety and Depression Scale (HADS), and the Pittsburgh Sleep Quality Index (PSQI), respectively, before and after a one-month comprehensive treatment.Results: SCORAD, representing differences in severity of children’s AD, decreased significantly after one month’s treatment (p < 0.001). Anxiety in mothers significantly decreased in all AD severity groups after treatment (p < 0.05). However, for depression, only the mothers in the mild and moderate AD groups showed a decrease after treatment (p < 0.05). The PSQI total score also decreased in the mild AD group after treatment (p < 0.05).Conclusion: The most severe effect was seen in the psychology and sleep quality of mothers of children with severe AD. After one month of treatment, the psychological health and sleep quality of the mothers in the mild AD group significantly improved, while those of mothers in the moderate and severe AD groups showed partial improvement.Keywords: atopic dermatitis, mothers, sleep quality, psychological health, questionnaire

Guolan Wu,1– 3 Huili Zhou,1,2 Duo Lv,1,2 Ruling Zheng,4 Lihua Wu,1 Songxia Yu,1,2 Jiejing Kai,1,2 Nana Xu,1,2 Lie Gu,5 Nanfang Hong,5 Jianzhong Shentu1,2 1Department of Clinical Pharmacy, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 2Zhejiang Provincial Key Laboratory for Drug Evaluation and Clinical Research, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 3Polytechnic Institute, Zhejiang University, Hangzhou, People’s Republic of China; 4The Fifth Affiliated Hospital, College of Medicine, Guangzhou Medical University, Guangzhou, People’s Republic of China; 5Hainan Honz Pharmaceutical Co. Ltd, Haikou, Hainan, People’s Republic of ChinaCorrespondence: Jianzhong Shentu, Email stjz@zju.edu.cnPurpose: Suramin is a multifunctional molecule with a wide range of potential applications, including parasitic and viral diseases, as well as cancer.Methods: A double-blinded, randomized, placebo-controlled single ascending dose study was conducted to investigate the safety, tolerability, and pharmacokinetics of suramin in healthy Chinese volunteers. A total of 36 healthy subjects were enrolled. All doses of suramin sodium and placebo were administered as a 30-minute infusion. Blood and urine samples were collected at the designated time points for pharmacokinetic analysis. Safety was assessed by clinical examinations and adverse events.Results: After a single dose, suramin maximum plasma concentration (Cmax) and area under the plasma concentration–time curve from time zero to the time of the last measurable concentration (AUClast) increased in a dose-proportional manner. The plasma half-life (t1/2) was dose-independent, average 48 days (range 28– 105 days). The cumulative percentages of the dose excreted in urine over 7 days were less than 4%. Suramin can be detected in urine samples for longer periods (more than 140 days following infusion). Suramin was generally well tolerated. Treatment-emergent adverse events (TEAEs) were generally mild in severity.Conclusion: The PK and safety profiles of suramin in Chinese subjects indicated that 10 mg/kg or 15 mg/kg could be an appropriate dose in a future multiple-dose study.Keywords: suramin, clinical pharmacokinetics, antiviral, safety, drug repurposing

Lei Huang,1,2 Chengcheng Liu,1,2 Zhanjie Li,3 Xu Huang,1,4 Ruiying Zheng,1,2 Zhixin Shi,1,2 Xin Hong,1,2 Yufeng Qin,5 Genyan Liu1,2 1Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 2Branch of National Clinical Research Center for Laboratory Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 3Department of Infection Control, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 4Department of Laboratory Medicine, the Children’s Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 5School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of ChinaCorrespondence: Genyan Liu, Department of Laboratory Medicine, The First Affiliated Hospital with Nanjing Medical University, Nanjing, 210029, People’s Republic of China, Tel +86 25 68308025, Fax +86 25 83724440, Email liugenyan@njmu.edu.cnObjective: To investigate the transmission pathway of a MRSA prevalence in a pancreatic surgery ward in a Chinese teaching hospital.Methods: Molecular epidemiology investigations were carried out combined PFGE, MLST, SCCmec typing and whole-genome sequencing for 20 successive MRSA isolates (2 isolates from the ward environment). Resistance and virulence genes were detected using specific PCR. Bacterial identification and AST were performed using the Vitek 2 Compact System. Clinical data of enrolled cases were retrieved from electronic case records.Results: From January 2020 to May 2020, successive isolated 20 MRSA strains were clarified to 2 PFGE patterns (A = 19, B = 1) in the ward. Both isolates from environment and patients belonged to sequence type ST5-SCCmec II-spa type t311. MRSA-related resistance genes mecA, blaZ, ermA, ant(4’)-Ia and norA were found in each clone. All 20 isolates carried tst, hlg, hla, eta, eap, fnbA and seo virulence genes, other virulence genes such as sea, sec, seb, seg, sei, sem, sen, ebpS and fnbB were also found in partial stains. All patients had fever symptom, 27.8% were accompanied by diarrhea, 88.9% had undergone surgery or invasive procedures within 30 days. Finally, 94.4% of these patients recovered.Conclusion: This study confirmed a prevalence of ST5-MRSA-II-t311 clone in a surgery ward, indicated MRSA is a risk factor for post-surgery nosocomial infection and hand hygiene and environmental surveillance should not be ignored.Keywords: methicillin-resistantStaphylococcus aureus, ST5, SCCmec II, spa type t311, diarrhea, virulence genes

We investigate localized in-plane strains on the microscale, induced by arrays of biased surface electrodes patterned on piezoelectrics. Particular focus is given to the influence that adjacent electrode pairs have on one another to study the impact of densely packed electrode arrays. We present a series of X-ray microdiffraction studies to reveal the spatially resolved micrometer-scale strain distribution. The strain maps with micrometer-scale resolution highlight how the local strain profile in square regions up to 250 x 250 lm2 in size is affected by the surface electrodes that are patterned on ferroelectric single-crystal [Pb(Mg1/3Nb2/3)O3]x-[PbTiO3]1−x. The experimental measurements and simulation results show the influence of electrode pair distance, positioning of the electrode pair, including the angle of placement, and neighboring electrode pair arrangements on the strength and direction of the regional strain. Our findings are relevant to the development of microarchitected strain-mediated multiferroic devices. The electrode arrays could provide array-addressable localized strain control for applications including straintronic memory, probabilistic computing platforms, microwave devices, and magnetic-activated cell sorting platforms.

Hongping Sun,1,&ast; Hong Su,1,&ast; Rendong Zheng,1 Chao Liu,1 Yu Wang,2 Changqian Fang2 1Endocrine and Diabetes Center, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, 210028, People’s Republic of China; 2Department of Endocrinology, Nanjing Lishui District Hospital of Traditional Chinese Medicine, Nanjing, 211200, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Rendong Zheng; Chao Liu, Endocrine and Diabetes Center, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, No. 100, Shizi Street, Hongshan Road, Nanjing, 210028, People’s Republic of China, Tel +86 159 9623 8035 ; +86 133 3780 6688, Fax +86-025-85608778, Email zhrd2000@sina.com; liuchao@nfmcn.comObjective: To determine whether the uric acid/high‑density lipoprotein cholesterol ratio (UHR) is associated with visceral fat area (VFA) in patients with type 2 diabetes mellitus (T2DM).Methods: Participants aged 18– 70 years with a diagnosis of T2DM were recruited from the National Metabolic Management Center from January 2020 to July 2022. Medical data collected for all participants included medical history, general measures, carotid intima-media thickness, abdominal VFA, and subcutaneous fat area (SFA). The participants were divided into groups according to VFA ≥ 100 cm2 (n=109) and VFA < 100 cm2 (n=100).Results: Compared with the VFA < 100 cm2 group, the VFA ≥ 100 cm2 group had higher height, weight, body mass index (BMI), waist circumference (WC), hip circumference (HC), SFA, fasting plasma glucose, fasting insulin, C peptide, homeostatic model assessment of insulin resistance (HOMA-IR), alanine transaminase (ALT), aspartate transaminase, γ-glutamine acyltransferase (γ-GGT), uric acid (UA), triglyceride (TG), and UHR measurements and lower high-density lipoprotein cholesterol (HDL-C) (P< 0.05). No significant difference was observed between the groups for age, duration of T2DM, diastolic blood pressure, systolic blood pressure, IMT, glycosylated hemoglobin, total cholesterol, and low-density lipoprotein cholesterol. Positive correlations were found between the UHR and height, weight, BMI, WC, HC, C peptide, ALT, γ-GGT, TG, and UA, as well as between VFA and these variables (P< 0.05). Both the UHR and VFA were negatively correlated with HDL-C (P< 0.05). Positive correlations were observed between VFA and the UHR as well as UA (P< 0.05), and a negative correlation was found between VFA and HDL-C (P< 0.05). Multivariate linear stepwise regression identified BMI, WC, UHR, SFA, and HC as influencing factors for VFA (P< 0.05).Conclusion: UHR was positively associated with VFA in T2DM patients and may be a useful and convenient additional tool for metabolic risks in these patients.Keywords: hyperglycemia, dyslipidemia, insulin resistance, visceral adiposity

Rui Zheng,1,&ast; Yaxian Jiang,1,&ast; Cheng Yan,2,&ast; Yikun Li,1 Xiaozhou Song,3 Pengcheng Zheng4 1Department of Clinical Laboratory, The First People’s Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, People’s Republic of China; 2Medical School, Kunming University of Science and Technology, The First People’s Hospital of Yunnan, Kunming, People’s Republic of China; 3Department of Infection Control, The First People’s Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, People’s Republic of China; 4Department of Pharmacy, The First People’s Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Pengcheng Zheng, Department of Pharmacy, The First People’s Hospital of Yunnan Province, No. 157 of Jingbi Road, Kunming, People’s Republic of China, Tel +86 013888116045, Email zpc1997@163.com Xiaozhou Song, Department of Infection Control, The First People’s Hospital of Yunnan Province, No. 157 of Jingbi Road, Kunming, People’s Republic of China, Tel +86 013888144965, Email 13888144965@163.comIntroduction: Ventilator-associated pneumonia (VAP) is an ICU (intensive care unit)-acquired pulmonary parenchymal infection that is complicated by mechanical ventilation and is associated with high morbidity and mortality. Klebsiella pneumoniae (KPN) is known to asymptomatically colonize the gastrointestinal tract and may increase the incidence of corresponding VAP. Our study aims were to investigate the exact origin of the carbapenem-resistant Klebsiella pneumoniae (CRKP) causing VAP in our patient.Methods: Various environmental samples, including the patient’s anal swab, were collected in order to find the source of the bacteria. Minimum inhibitory concentrations (MICs) for antimicrobial agents were determined according to the guidelines of the Clinical and Laboratory Standards Institute (CLSI); resistant genes were detected by using PCR and sequencing; clone relationships were analyzed by using multilocus-sequence typing (MLST) and pulsed field gel electrophoresis (PFGE). The IAP values were obtained via urinary catheter.Results: One CRKP strain was detected in the patient’s anal swab; this strain was confirmed with the same gene type as the strain isolated from the sputum. We found that the patient’s intra-abdominal pressure (IAP) was 29.41, 27.06, 24.12, and 22.66 mmHg; the IAP was either equal to or above 12 mmHg, on the operation day and the following three days. Intra-abdominal hypertension (IAH) occurred during the patient’s hospitalization and was considered to be caused by the surgical procedure. Meanwhile, we found that there was a correlation between IAH and the detection of CRKP in the sputum. The findings suggested that his VAP was caused by intestinal colonial KPN, and not from the environment.Discussion: Our research illustrated that the ST11 KPC-2-producing strain colonized the intestinal tract and caused the development of VAP when the IAP was elevated. Routine screening for the intestinal carriage of CRKP, among patients in ICUs, can limit and prevent current and future outbreaks.Keywords: ventilator-associated pneumonia, intra-abdominal pressure, intra-abdominal hypertension, Klebsiella pneumoniae, healthcare-associated infection

Wenting Gong,1,&ast; Wen Tang,2,&ast; Lan Luo,3 Furong Zhang,1 Chenyang Cai,1 Jiangyan Zhang,1 Xiaolin Wu,4 Jianping Shang,4 Xiaolan Shu,2 Ting Wang,5 Danna Tu,6 Zhengjiang Jin,7,&ast; Ronghao Zheng4,&ast; 1Department of pharmacy, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2Department of Pediatric Intensive Care Unit, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 3Department of Child Health, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 4Department of Pediatric Nephrology, Rheumatology, and Immunology, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 5Department of Pediatric Neurology, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 6Department of Pediatric Cardiology, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 7Department of Clinical Laboratory, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ronghao Zheng, Department of Pediatric Nephrology, Rheumatology, and Immunology, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, 745 Wu luo Road, Hongshan District, Wuhan, 430070, Hubei Province, People’s Republic of China, Tel +86 02787169267, Email hytwo2001@126.com Zhengjiang Jin, Department of Clinical Laboratory, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, 745 Wu luo Road, Hongshan District, Wuhan, 430070, Hubei Province, People’s Republic of China, Email king199735@126.comPurpose: To explore the trends and correlation between antibiotics consumption and antimicrobial resistance in children in a specialist hospital from 2016– 2021 in China.Patients and Methods: This retrospective study investigated data on the consumption of antibiotics and antimicrobial resistance in children. Antibiotics consumption was expressed as defined daily doses (DDDs)/1000 patient-days based on the Guidelines for Anatomical Therapeutic Chemical. The trends in antibiotics consumption and antimicrobial resistance rates were analyzed by linear regression, while Spearman correlation analysis was employed to evaluate their correlations.Results: An increasing trend in the annual consumption of carbapenems and monobactams was detected (all P< 0.05). A significant upward trend was detected in the annual resistance rates of Enterococcus faecium to ciprofloxacin, Streptococcus pneumonia to ceftriaxone, Acinetobacter baumannii to carbapenems, Enterobacter cloacae to carbapenems, Pseudomonas aeruginosa to ceftazidime, and Escherichia coli to cefepime, while the annual resistance rates of Escherichia coli to carbapenems had a significant downward trend (all P< 0.05). The consumption of cephalosporin/β-lactamase inhibitor (C/BLI) combinations and carbapenems had significant positive correlations with the resistance rates of Acinetobacter baumannii to carbapenems (r=0.763, P< 0.001; r=0.806, P< 0.001), Enterobacter cloacae to carbapenems (r=0.675, P< 0.001; r=0.417, P=0.043), and Pseudomonas aeruginosa to ceftazidime (r=0.625, P=0.001; r=0.753, P< 0.001), respectively. Also, increasing consumption of monobactams was related to the upward resistance rates of Acinetobacter baumannii to carbapenems (r=0.557, P=0.005) and Enterobacter cloacae to carbapenems (r=0.507, P= 0.011).Conclusion: This study demonstrated significant positive associations between antibiotics consumption and specific antimicrobial resistance rates. The current findings pointed out some directions to pursue in controlling the prevalence of certain resistant bacterial strains in children.Keywords: antibiotic consumption, antimicrobial resistance, correlation, children

Zhao Y, Zheng R, Ning D, Xie F. Cancer Manag Res. 2020;12:4171–4180. We, the Editors and Publisher of Cancer Management and Research, have retracted the following article. Following publication of the article, concerns were raised about the duplication of images from Figures 1 and 3 with images from other unrelated articles. Specifically, The images for Figure 1F have been duplicated with images for Figure 1C and 1D from Fang C, Jiang B, Shi X, Fan C. Hes3 Enhances the Malignant Phenotype of Lung Cancer through Upregulating Cyclin D1, Cyclin D3 and MMP7 Expression. International Journal of Medical Sciences. 2019;16(3):470-476. https://doi.org/10.7150/ijms.28139. Images for Figure 3C, A459 and 3G, H226 have been duplicated with images for Figures 2h and 2i, and 5a and 5b from Zhang X, Liu L, Deng X, et al. MicroRNA 483-3p targets Pard3 to potentiate TGF-β1-induced cell migration, invasion, and epithelial–mesenchymal transition in anaplastic thyroid cancer cells. Oncogene. 2019;38:699–715. https://doi.org/10.1038/s41388-018-0447-1. Images for Figure 3D, A549 and 3H, H226 have been duplicated with images for Figure 9A, CNE2 and 9B, 5-8F from Liang TS, Zheng YJ, Wang J, et al. RETRACTED ARTICLE: MicroRNA-506 inhibits tumor growth and metastasis in nasopharyngeal carcinoma through the inactivation of the Wnt/β-catenin signaling pathway by down-regulating LHX2. J Exp Clin Cancer Res. 2019;38:97. https://doi.org/10.1186/s13046-019-1023-4. When approached for an explanation, the authors were cooperative but were unable to provide a sufficient explanation for the image duplication or provide original data for their study. As verifying the validity of published work is core to the integrity of the scholarly record, we are therefore retracting the article and the authors have agreed with this decision. We have been informed in our decision-making by our editorial policies and COPE guidelines. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as ‘Retracted’.

Weifeng Kong,1 Qingwu Wu,1 Yubin Chen,1 Yong Ren,2 Weihao Wang,1 Rui Zheng,1 Huiyi Deng,1 Tian Yuan,1 Huijun Qiu,1 Xinyue Wang,1 Xin Luo,1 Xuekun Huang,1 Qintai Yang,1 Gehua Zhang,1 Yana Zhang1 1Department of Otolaryngology-Head and Neck Surgery, the Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People’s Republic of China; 2Guangdong Provincial Key Laboratory of Digestive Cancer Research, the Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, People’s Republic of ChinaCorrespondence: Yana Zhang; Gehua Zhang, Department of Otolaryngology-Head and Neck Surgery, the Third Affiliated Hospital of Sun Yat-Sen University, No. 600 Tianhe Road, Guangzhou, 510630, People’s Republic of China, Tel +86-20-85252310, Email zhangyn95@mail.sysu.edu.cn; zhanggeh@mail.sysu.edu.cnPurpose: Histopathologic characterizations of central compartment atopic disease (CCAD) by whole-slide imaging remains lacking. We aim to study clinical presentations and cellular endotyping diagnosis of Chinese CCAD using artificial intelligence (AI).Methods: A total of 72 patients diagnosed with chronic rhinosinusitis with nasal polyps (CRSwNP) were enrolled. CCAD was defined by positive result of serology specific IgE, endoscopic and radiological findings. The aeroallergen sensitization status, endoscopic results, radiological findings, and symptoms were evaluated and compared between patients with CCAD (n=14), eosinophilic CRSwNP (ENP, n=32) and non-eosinophilic CRSwNP (NENP, n=26). The cellular endotypes including eosinophils, neutrophils, lymphocytes, and plasma cells were analyzed by the AI chronic rhinosinusitis evaluation platform 2.0.Results: CCAD was most common in male (71.43%). The positive rate of aeroallergen in patients with CCAD is 100%, which is much higher than those in patients with ENP (40.63%) and NENP (23.08%). Allergic rhinitis incidence was found to be 57.14% in Chinese CCAD subjects, which is obviously higher when compared with those in patients with ENP (21.88%) or NENP (0.00%). The presence of asthma was not significantly different between groups. Chinese CCAD population demonstrated mild symptoms and lower endoscopic and radiological scores than those in patients with ENP and NENP. For cellular endotypes in CCAD subjects, the median of eosinophils, neutrophils, lymphocytes, and plasma cells was 26.55%, 0.49%, 60.85%, and 7.33%, respectively. The proportion of eosinophils in nasal tissue and peripheral blood mononuclear cells from the CCAD group is between the proportions in those patients with ENP and NENP.Conclusion: Chinese CCAD was associated with aeroallergen sensitivity, and displayed an eosinophil-dominant inflammatory pattern. Thus, proper management with allergy control and topical steroids could be recommended for CCAD treatment.Keywords: central compartment atopic disease, deep learning, chronic rhinosinusitis with nasal polyps, eosinophil, aeroallergen

Yue Fang,1,&ast; Zulqarnain Baloch,1,&ast; Wei Zhang,2 Ying Hu,2 Rui Zheng,3 Yuzhu Song,1 Wenlin Tai,2 Xueshan Xia1 1The Affiliated AnNing First Hospital & Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, Yunnan, 650500, People’s Republic of China; 2The 2nd Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, 650101, People’s Republic of China; 3The First Hospital of Yunnan Province & The Affiliated Hospital, Kunming University of Science and Technology, Kunming, Yunnan, 650034, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuzhu Song; Xueshan Xia, Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, Yunnan, 650500, People’s Republic of China, Tel +86-871-65920756, Fax +86-871-65920570, Email syzzam@126.com; oliverxia2000@aliyun.comIntroduction: The prevalence of carbapenem-resistant Pseudomonas aeruginosa is increasing persistently, particularly in burn ward isolates. Here, we investigate the prevalence of carbapenem-resistant Pseudomonas aeruginosa in a burn ward of a provincial-level hospital at Kunming, Yunnan province, China.Methods: A total of 118 P. aeruginosa strains were isolated from 57 hospitalized patients, and their MICs were measured. Carbapenem-resistant isolates were selected for multilocus sequence typing (MLST). Carbapenem-resistance mechanisms were identified by examining carbapenemase genes and OprD protein and Carba-NP testing. Representative isolates were further characterized by de novo sequencing for carbapenemase molecular background.Results: Among 118 P. aeruginosa isolates, 54 (54/118,45.8%) were carbapenem-resistant Pseudomonas aeruginosa, and 3 genotypes were found (ST292, ST244, and ST2446). Non-carbapenemase-producing ST292 was the most prevalent ST, followed by ST2446 and ST244. A novel 13-bp oprD deletion was found in the ST292 clone, which formed the truncated outer membrane protein and may cause carbapenem resistance. ST244 and ST2446 harbored blaIMP-45 and blaIMP-87, respectively. blaIMP-45 is located in a megaplasmid, together with aac(6’)-Ib3, blaOXA-1, catB3, qnrVC6, armA, msr(E), mph(E), aph(3’)-Ia, tetC/tetR, aac(6’)-Ib3, floR, mexC-mexD-oprJ, fosA and lead to extensive drug resistance. ST2446 contains a carbapenem-resistant gene blaIMP-87 on the chromosome and is acquired by a novel gene cassette array (blaIMP-87-ant(2”)-Ia-blaOXA-10-aac(6’)-Ib3) of class 1 integron.Discussion: For the first time, ST244, ST292 and ST2446 are reported emerging in burn patients, with distinctive carbapenem-resistance mechanisms, respectively. The obtained results highlight the need to surveillance carbapenem-resistant isolates in burn patients.Keywords: P. aeruginosa, carbapenem-resistance, oprD, blaIMP

Huiyi Deng,1,&ast; Meijiao Li,2,&ast; Rui Zheng,1,&ast; Huijun Qiu,1 Tian Yuan,1 Weihao Wang,1 Qintai Yang,1 Zijie Long,3 Xuekun Huang1 1Department of Otorhinolaryngology-Head and Neck Surgery, Department of Allergy, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 2Department of Otorhinolaryngology-Head and Neck Surgery, Tung wah Hospital of Sun Yat-sen University, Dongguan, People’s Republic of China; 3Department of Hematology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xuekun HuangDepartment of Otolaryngology-Head and Neck Surgery, Department of Allergy, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of ChinaTel +86 020-85252239Fax +86 020-85253210Email xuekunhuang@163.comZijie LongDepartment of Hematology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of ChinaTel +86 020-85253601Fax +86 020-85253210Email longzij@mail.sysu.edu.cnBackground: Hippo-Yes-associated protein (YAP) pathway plays an important role in epithelial cell proliferation and inflammation development in chronic rhinosinusitis with nasal polyps (CRSwNP). However, the underlying mechanisms remain unclear.Objective: This study intends to investigate the role of YAP and the nuclear factor kappa-B (NF-κB) pathway in cell proliferation and the expression of epithelium-derived cytokines in nasal polyps (NP).Methods: The expression levels of YAP, TEA domain family member 1 (TEAD1), Ki-67, and NF-κB as well as interleukin (IL-) 33, IL-25 and thymic stromal lymphopoietin (TSLP) in sinonasal mucosa, primary nasal epithelial cells (NPECs), and human nasal epithelial RPMI 2650 cells were detected. NPECs were cultured and treated with verteporfin (VP), YAP shRNA or BAY 11– 7082.Results: The hippo pathway effector YAP, Ki-67, p65 NF-κB, and cyclin D1 were significantly increased in NP compared with control mucosa, which was accompanied by overexpression of IL-33, IL-25, and TSLP. Pharmaceutical inhibition of YAP by VP suppressed cell proliferation of RPMI 2650 cells by blocking cell cycle progression at G0/G1 without inducing obvious cell apoptosis. Furthermore, lentiviral transfection-mediated knockdown of hippo pathway activity reduced the expression of IL-33, IL-25, TSLP as well as p65 NF-κB in RPMI 2650 cells. Downregulation of NF-κB pathway with BAY 11– 7082 in NPECs could decrease the mRNA level of TSLP, IL-33 and IL-25 accordingly.Conclusion: Inhibition of hippo pathway suppressed nasal epithelial cell proliferation and declined the expression of epithelium-derived cytokines via the NF-κB pathway in NPECs.Keywords: NF-κB signalling pathway, yes-associated protein, cell cycle progression, cell proliferation, nasal polyps

Ran Zheng, Yang Ruan, Yiqun Yan, Zhihao Lin, Naijia Xue, Yaping Yan, Jun Tian, Xinzhen Yin, Jiali Pu, Baorong Zhang Department of Neurology, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang, 310009, People’s Republic of ChinaCorrespondence: Baorong Zhang; Jiali PuDepartment of Neurology, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang, People’s Republic of ChinaFax +86-571-87784752Email brzhang@zju.edu.cn; jialipu@zju.edu.cnBackground: Inflammasome-induced neuroinflammation is a key contributor to the pathology of Parkinson’s disease (PD). NLR family pyrin domain-containing 3 (NLRP3) inflammasome activation has been implicated in PD in postmortem human PD brains, indicating it as a potential target for PD treatment. Melatonin, a multitasking molecule, has been found to have anti-inflammatory activities, mediated by silence information regulator 1 (SIRT1). However, whether and how melatonin is involved in inflammasome-induced neuroinflammation in PD pathogenesis remains unclear.Methods: We investigated the potential anti-inflammatory effects of melatonin in vitro and in vivo, using 1-methyl-4-phenylpyridinium (MPP+)-simulated BV2 and primary microglia cell models, and a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced murine PD model, with or without melatonin treatment. Rotarod, grip strength, and open-field tests were performed to measure the effects of melatonin on MPTP-induced motor disorders. Degeneration of dopaminergic neurons was evaluated by immunofluorescence. Changes in microglia were examined by immunofluorescence and Western blotting, and the expression levels of the involved signaling molecules were assessed by Western blotting and enzyme-linked immunosorbent assay (ELISA). Intracellular reactive oxygen species (ROS) was detected using fluorescent probes via flow cytometry.Results: We found that melatonin significantly alleviated motor dysfunction and prevented MPTP-induced neurotoxicity in dopaminergic neurons. Additionally, melatonin reduced MPTP-induced microglial activation and suppressed NLRP3 inflammasome activity, and also inhibited IL-1β secretion. Moreover, in MPP+-primed BV2 cells, melatonin markedly restored the downregulation of SIRT1 and attenuated the activation of the NLRP3 inflammasome. This was reversed by SIRT1 inhibitor treatment.Conclusion: In conclusion, our data demonstrated that melatonin attenuates neuroinflammation by negatively regulating NLRP3 inflammasome activation via a SIRT1-dependent pathway in MPTP-induced PD models. These findings provide novel insights into the mechanism underlying the anti-inflammatory effects of melatonin in PD.Keywords: inflammasomes, melatonin, NLRP3, Parkinson disease, sirtuin 1