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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

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

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

Huijun Qiu,1,* Rui Zheng,1,* Xinyue Wang,1,* Zhuanggui Chen,2,3 Peiying Feng,2,4 Xuekun Huang,1,2 Yuqi Zhou,2,5 Jin Tao,2,6 Min Dai,2,7 Lianxiong Yuan,8 Xiangdong Wang,9 Luo Zhang,9 Qintai Yang1,2 1Department of Otolaryngology-Head and Neck Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, People’s Republic of China; 2Department of Allergy, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, People’s Republic of China; 3Department of Pediatrics, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, People’s Republic of China; 4Department of Dermatology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, People’s Republic of China; 5Department of Pulmonary and Critical Care Medicine, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, People’s Republic of China; 6Department of Gastroenterol, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, People’s Republic of China; 7Department of Traditional Chinese Medicine, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, People’s Republic of China; 8Department of Science and Research, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, People’s Republic of China; 9Department of Otorhinolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qintai YangDepartment 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 ChinaTel +86-20-85252252Fax +86-20-85253336Email yangqint@mail.sysu.edu.cnLuo ZhangDepartment of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, No. 16 Hougou Hutong, Chongnei Street, Donghuamen Street, Dongcheng District, Beijing, 100730, People’s Republic of ChinaTel +86-10-65141136Fax +86-10-85115988Email dr.luozhang@139.comBackground: To explore the epidemiological characteristics of allergic rhinitis (AR) and allergic conjunctivitis (AC) based on the Internet big data.Methods: The Baidu index (BDI) of keywords “allergic rhinitis” and “allergic conjunctivitis” in Mandarin, the daily pollen concentration (PC) released by the Beijing Meteorological Bureau and the volumes of outpatient visits (OV) of the Beijing Tongren Hospital (Beijing) and the Third Affiliated Hospital of Sun Yat-sen University (Guangzhou) from 2017 to 2020 were obtained. The temporal and spatial changes of AR and AC were discussed. The correlations between BDI and PC/OV were analyzed by Spearman correlation analysis.Results: The trends of BDI of “AR”/“AC” in Beijing showed obvious seasonal variations, but not in Guangzhou. The BDI of “AR” and “AC” was consistent with the OV in both cities (r1AR-BJ=0.580, P< 0.001; r1AR-GZ=0.360, P=0.031; r1AC-BJ=0.885, P< 0.001; r1AC-GZ=0.694, P< 0.001). The BDI of “AR” and “AC” was highly consistent with the change of the PC in Beijing (r AR-Pollen=0.826, P< 0.001; r AC-Pollen=0.564, P< 0.001). The OV of AR in Beijing and Guangzhou decreased significantly in the first half of 2020, but there was no significant change in AC. In the first half of 2020, the OV of AC in Beijing was significantly higher than that of AR, while that of AC in Guangzhou was slightly higher than that of AR.Conclusion: The BDI could reflect the real-world situation to some extent and has the potential to predict the epidemiological characteristics of AR and AC. The BDI and OV of AR decreased significantly, but those of AC were still at a high level, during the COVID-19 pandemic, in the environment where most people in Beijing and Guangzhou wore masks without eye protection.Keywords: allergic rhinitis, allergic conjunctivitis, Internet, Baidu, big data, COVID-19

Yi Kuang,1,2 Ming-Xing Xu,1,3 Shu-Wen Yang,1,2 Yang Ding,1,2 Rui Zheng,1,2 John Taplin,4 Shu Li1,5 1CAS Key Laboratory of Behavioural Science, Institute of Psychology, Chinese Academy of Sciences, Beijing, 100101, People’s Republic of China; 2Department of Psychology, University of Chinese Academy of Sciences, Beijing, 100049, People’s Republic of China; 3School of Transportation, Fujian University of Technology, Fuzhou, 350118, People’s Republic of China; 4School of Psychology, University of Adelaide, Adelaide, SA, 5005, Australia; 5Department of Psychology and Behavioral Sciences, Zhejiang University, Hangzhou, 310058, People’s Republic of ChinaCorrespondence: Shu LiCAS Key Laboratory of Behavioral Science, Institute of Psychology, Chinese Academy of Sciences, Beijing, 100101, People’s Republic of ChinaTel +86-10-64841536Fax +86-10-64841536Email lishu@psych.ac.cnIntroduction: The COVID-19 pandemic has received broad public attention and has been subject to social media discussion since the beginning of 2020. Previous research has demonstrated that framing could influence perception and behaviors of audience members in the mass media. The question addressed in this paper concerns which information frame is best for reporting negative news (eg, deaths) and positive news (eg, recoveries or cures) related to the outbreak of COVID-19.Methods: During the Spring Festival holidays of 2020 in China, we investigated a sample of 8170 participants’ risk perceptions and emotional responses to the pandemic, and their willingness to forward updates when the information is presented in different frames by using a 2 (domain: living [good news] vs dying [bad news]) × 2 (count: absolute vs relative) × 2 (population base: excluding population base vs including population base) × 2 (content: text-only vs text-plus-graphic) mixed factorial design, with the first factor being a within-subjects factor and the last three being between-subjects factors.Results: Results indicated that (1) participants were more willing to forward good news (eg, cures) than bad news (eg, deaths); (2) when reporting bad news, the inclusion of the “population base” was effective in minimizing negative emotions; (3) when reporting good news, excluding the “population base” was more effective than including it in order to maximize positive emotions; (4) a text-plus-graphic frame worked better than a text-only frame in lowering the level of risk perception and negative emotions.Discussion: This study is relevant to how individuals and organizations communicate information about this viral pandemic and the probable impact of this news on the general public.Keywords: COVID-19, information frame, perception, emotion

Abstract For the global telecom operators, mobile data services have gradually taken the part of traditional voice services to become the main revenue growth point. However, during the upgrading period of new generation networks (such as 5G), new mobile data services are still at the stage of exploration; the network capabilities and the application scenarios are unmatured. In this phase, it is incomplete and misleading to simply measure the performance of new services from one dimension, such as data traffic or revenue, and the measurement should be dynamically changed according to the development of the new services. Therefore, telecom operators want to improve the existing performance measurement from the aspect of integrity and dynamics. In this paper, we propose mobile-data-service development index (MDDI) and build a quantitative model to dynamic measure the overall performance of mobile data services. To approach a fuller understanding, we creatively bring investment indicators and networks reliability indicators into performance indicators system and discuss the relationships among subindices and the selection of outcome criteria in MDDI. In the part of empirical research, we use the model to analyze the dynamic characteristics of a new mobile data service in China and summarize the development strategies of every stage. The findings can also give guidelines for new services of 5G and other new generation networks in the future.

Yaping Han,1,2 Lei Huang,1,2 Chengcheng Liu,1,2 Xu Huang,3 Ruiying Zheng,1,2 Yanfei Lu,1,2 Wenying Xia,1,2 Fang Ni,1,2 Yaning Mei,1,2 Genyan Liu1,2 1Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu Province, People’s Republic of China; 2National Key Clinical Department of Laboratory Medicine, Jiangsu Province Hospital, Nanjing Medical University, Nanjing, 210029, Jiangsu Province, People’s Republic of China; 3Department of Laboratory Medicine, Children’s Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu Province, People’s Republic of ChinaCorrespondence: Genyan LiuDepartment of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu Province, People’s Republic of ChinaTel +86 25-6830-3453Fax +86 25- 8372-4440Email liugenyan@njmu.edu.cnObjective: Nosocomial infection caused by carbapenem-resistant Klebsiella pneumoniae (CRKP) is a great threat to severely ill patients. Here we report an outbreak of K. pneumoniae ST15 isolates co-producing KPC-2, CTX-M-15, and SHV-28 in the cardiac surgery intensive care unit (CSICU) of a tertiary hospital.Materials and Methods: From November 2019 to August 2020, all non-duplicated CRKP isolates were collected from the CSICU. The VITEK-2 compact system was used for bacterial identification and antimicrobial susceptibility testing. Clinical data were retrieved from electronic case records. All strains were also subjected to antibiotic resistance genes detection. Clonal relationships were analyzed by multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE).Results: A total of 28 non-duplicated CRKP isolates were collected, including 23 strains belonging to ST15 and 5 strains belonging to ST11. All ST15 isolates were susceptible to amikacin, tigecycline, polymyxin B and ceftazidime/avibactam, but resistant to carbapenems, cephalosporins, quinolones, tobramycin and gentamicin. The detection of resistant determinants showed that 21 strains of ST15 CRKP co-harboured blaKPC-2, blaCTX-M-15, blaSHV-28, blaTEM-1, blaOXA-1 and aac(6ʹ)-Ib-cr. All the 28 CRKP isolates were classified into five PFGE patterns (A, B, C, D and E), of which type A and B belonged to ST15 and type C, D and E belonged to ST11. PFGE type A was the predominant clonotype of this nosocomial infection and belonged to ST15.Conclusion: K. pneumoniae ST15 co-producing KPC-2, CTX-M-15, SHV-28, TEM-1, OXA-1 and aac(6ʹ)-Ib-cr is the predominant clone spread in the CSICU. Surveillance and comprehensive infection control measures should be strengthened in clinical practice.Keywords: Klebsiella pneumoniae ST15, carbapenem-resistant, KPC-2, multidrug resistance, resistance gene

Jie Jiang,1,2,* Bo She,3,4,* Rui Zheng1,2 1Department of Clinical Laboratory, The First People’s Hospital of Yunnan Province, Kunming, Yunnan, People’s Republic of China; 2Department of Clinical Laboratory, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, People’s Republic of China; 3PET/CT Center, The First People’s Hospital of Yunnan Province, Kunming, Yunnan, People’s Republic of China; 4PET/CT Center, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Rui Zheng Tel +86-0871-63638430Email ynkmzheng@gmail.comAbstract: Eggerthella lenta is part of the normal bacterial flora of the intestinal tract, but may cause life-threatening infections. E. lenta has been isolated from blood, abscesses, wounds, skin ulcers, and intra-abdominal infections. However, due to historical difficulties with laboratory identification by conventional biochemical methods, some cases of E. lenta infection have previously gone undiagnosed, especially in China where E. lenta infections are very rare. Recently, matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), a new type of technology, has made it possible to identify E. lenta. We report a case of postoperative infection caused by E. lenta which was treated successfully using meropenem.Keywords: Eggerthella lenta, MALDI-TOF, intra-abdominal abscess, bloodstream infection, anaerobic bacteria

Long Hu,1 Wei Lin,2 Tiancheng Xu,1 Dongjie Liang,1 Guangze Xiang,1 Rujie Zheng,1 Changzuan Zhou,1 Qinxue Dai,3 Danyun Jia3 1Department of Cardiovascular Medicine, The Heart Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang, People’s Republic of China; 2Department of Pediatric Intensive Care Unit, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325027, Zhejiang, People’s Republic of China; 3Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang, People’s Republic of ChinaCorrespondence: Danyun Jia; Qinxue DaiDepartment of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical University, Nanbaixiang, Ouhai District, Wenzhou City 325000, Zhejiang Province, People’s Republic of ChinaTel/Fax +86-577-88581162Email 529365150@qq.com; 653091408@qq.comBackground: Admission lactate level has been reported as a useful marker of mortality. In this study, we compared the relative value of different lactate indices to predict survival in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI).Methods: This was a retrospective observational study including consecutive patients with STEMI undergoing primary PCI who admitted to the Coronary Care Unit of the First Affiliated Hospital of Wenzhou Medical University between 2014 and 2017. The predictive value of lactate indices for mortality was compared using receiver operator characteristic (ROC) analysis, and DeLong’s test was used to compare the AUC. We compared the AUC between GRACE score and GRACE score + lactate index.Results: A total of 1080 patients were included. Fifty-nine died in 30 days and 68 died in 180 days. Most lactate indices (Lacadm, Lac24max, Lac24min and Lac24tw) were significantly lower in survivors (all P< 0.001). In Cox proportional hazards model, each lactate index showed as an independent factor of 30-day and 180-day mortality except LacΔ. Kaplan–Meier curves demonstrated that the patients of higher lactate indices group had higher rates of mortality (all P< 0.0001, except LacΔ P=0.0485). In receiver operator characteristic analysis, Lac24max was significantly larger than Lacadm(P< 0.001) while the AUC value for Lacadm was similar to Lac24min and Lac24tw. Lac24tw improved the predictive probability of 30-day mortality (P=0.0415). Lac24max improved the predictive probability of GRACE score for both 30-day and 180-day mortality (P< 0.05).Conclusion: In patients with STEMI undergoing primary PCI, most lactate indices are all associated with 30-day and 180-day mortality except LacΔ. In prediction of both 30-day and 180-day mortality, Lac24max is superior to Lacadm and significantly enhances the ability of risk stratification and prognostic evaluation when adding Lac24max to the GRACE score.Keywords: STEMI, lactate indices, hyperlactatemia, mortality

Bo Zhao, Xiaoxu Yu, Rui Chen, Rui Zheng Department of Pulmonary and Critical Care Medicine, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, People’s Republic of ChinaCorrespondence: Rui ZhengDepartment of Pulmonary and Critical Care Medicine, Shengjing Hospital of China Medical University, No. 36 Sanhao Street, Heping District, Shenyang 110004, Liaoning Province, People’s Republic of ChinaTel +86 24-9661521211Email zhengr@sj-hospital.orgPurpose: To evaluate the efficacy and safety of 500 mg of nemonoxacin administered orally once daily to outpatients with community-acquired pneumonia (CAP).Patients and Methods: Patients with CAP who received nemonoxacin monotherapy were selected from outpatients who visited the Department of Pulmonary and Critical Care Medicine of Shengjing Hospital of China Medical University between July and December 2018. Their characteristics, pneumonia-related symptoms, treatment effects, and adverse reactions were recorded.Results: In total, 337 patients with CAP were administered 500 mg of nemonoxacin orally once daily for 8.24 ± 3.73 days. Fourteen patients were lost during the follow-up period. At the end of the follow-up period, information on 323 patients (132 males and 191 females) with a median age of 52 (P25, P75: 34, 61) years was collected. On the basis of CRB-65 scores, 273 and 50 cases were classified to have low and intermediate risks, respectively. After 3 days of treatment, the symptom improvement rate was 61.3% (198 patients). Improved symptoms or cures were evident in 98.14% (317 patients) of the patients after treatment was completed. Five (1.55%) patients were hospitalized for poor treatment efficacy, and one (0.31%) patient was diagnosed with lung cancer despite improved symptoms. During oral therapy, there were three cases of skin and three cases of gastrointestinal adverse events, an incidence of 1.86%. Based on subsequent re-examinations and telephonic follow-ups, 93.50% (302 cases) of patients were satisfied with treatment effects.Conclusion: In treating outpatients with mild-to-moderate CAP, nemonoxacin can effectively control symptoms, reducing medical costs and saving patient time. Importantly, this is a safe and effective therapeutic approach as it is well tolerated with few side effects.Keywords: monotherapy, tolerability, CRB-65 score, symptom improvement

Haiyan Qin,1,* Yidan Guo,2,* Yikun Li,3,4 Rui Zheng3,4 1Department of Infection Prevention and Control, The First People’s Hospital of Kunming City, Kunming, Yunnan, People’s Republic of China; 2Yunnan Provincial Center of Disease Control and Prevention, Kunming, Yunnan, People’s Republic of China; 3Department of Clinical Laboratory, The First People’s Hospital of Yunnan Province, Kunming, Yunnan, People’s Republic of China; 4Department of Clinical Laboratory, the First People’s Hospital of Yunnan Province, Kunming, Yunnan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Rui Zheng Tel +86 871-63638430Email ynkmzheng@gmail.comPurpose: Salmonella enterica serovar Typhimurium infection is common in foodborne diseases, but its isolation from surgical incisions is rare. Our aim in this study was to trace the transmission source of a surgical incision infected with S. Typhimurium in a Yunnan Province hospital patient and elucidate the underlying molecular mechanisms of antibiotic resistance.Methods: Primers were designed to amplify the drug-resistance genes using polymerase chain reaction (PCR). Susceptibility to antibiotics was determined using Etest strips. Macrorestriction profiles were analyzed using pulsed-field gel electrophoresis (PFGE) and XbaI. The two isolates were characterized using agglutination tests and multilocus sequence typing (MLST).Results: MLST analysis revealed that S. Typhimurium isolates SM043 and SM080 belonged to the same genotype, ST34, and PFGE revealed that SM043 and SM080 had high similarity. The isolates were both resistant to third-generation cephalosporins. SM043 harbored the antibiotic resistance genes blaCTX-M-15, blaTEM-1, qnrS-1, qnrB, and acc-3, whereas blaCTX-M-15, blaTEM-1, blaCMY-2, qnrS-1, and acc-3 were detected in SM080.Conclusion: The surgical incision infection by S. Typhimurium may have been hospital-acquired. Thus, it is critical to strengthen hospital sanitation by addressing hand hygiene and sterilization of the operational environment to avoid outbreaks of nosocomial Salmonella infections.Keywords: Salmonella, healthcare-associated infection, cephalosporins, antibiotic resistance, nosocomial infection

Yongsheng Zhao,1,* Renyan Zheng,2,* Dong Ning,1 Fei Xie1 1Department of Thoracic Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, Sichuan; 2Department of Integrated Western and Chinese Colorectal and Anal Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, Sichuan*These authors contributed equally to this workCorrespondence: Yongsheng Zhao Tel +86 13551910279Email zhaoyongss321@163.comPurpose: To investigate the role of miR-625 on the invasion, migration, and epithelial–mesenchymal transition (EMT) of non-small cell lung carcinoma (NSCLC) cells, and the related mechanisms.Materials and Methods: The expression levels of miR-625 and Resistin mRNA in 80 pairs of NSCLC and para-cancerous lung tissues were analyzed by RT-PCR. The relationship between miR-625 and Resistin was predicted by bioinformatics and verified by a dual-luciferase gene reporter assay. NSCLC cells were transfected with Resistin plasmids, si-Resistin plasmids, miR-625 mimics, or miR-625 inhibitors, and proliferation, invasion, and migration were determined by CCK-8, Transwell, and wound scratch assays, respectively. EMT-related proteins were determined by Western blot assay. A xenograft model of NSCLC was established in nude mice to validate the in vitro findings.Results: MiR-625 was significantly downregulated in NSCLC tissue compared to paired para-cancerous lung tissues, while Resistin was markedly increased in tumor tissue. The expression levels of miR-625 and Resistin were negatively correlated in NSCLC tissues, and high levels of Resistin correlated with greater tumor differentiation, more advanced clinical staging, and lymph node metastasis. Furthermore, Resistin was a target gene of miR-625, and the latter downregulated Resistin to inhibit the EMT, proliferation, invasion, and migration of NSCLC cells in vitro, likely via the PI3K/AKT/Snail signaling pathway. Finally, miR-625 also inhibited the tumorigenic effect of NSCLC cells in vivo by downregulating Resistin.Conclusion: MiR-625 acts as a tumor suppressor in NSCLC and inhibits tumor cell invasion and metastasis by blocking the Resistin/PI3K/AKT/Snail pathway and by decreasing EMT.Keywords: miR-625, resistin, EMT, invasion, migration, PI3K/AKT/snail

Gangling Tong,1,* Shuluan Li,2,* Lin Lin,3,* Lirui He,1 Li Wang,1 Guoqing Lv,1 Ruinian Zheng,4 Shubin Wang1 1Department of Oncology, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, People’s Republic of China; 2National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, Guangdong 518116, People’s Republic of China; 3Department of Oncology, Shenzhen Second People’s Hospital, Shenzhen, Guangdong 518036, People’s Republic of China; 4Department of Oncology, Affiliated Dongguan People’s Hospital, Southern Medical University, Dongguan, Guangdong 523000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ruinian ZhengDepartment of Oncology, Affiliated Dongguan People’s Hospital, Southern Medical University, Wandao Road (South), Xinguyong Village, Wanjiang District, Dongguan, Guangdong 523000, People’s Republic of ChinaTel +86-769-28637071Email 13450023449@163.comShubin WangDepartment of Oncology, Peking University Shenzhen Hospital, Lianhua Road (North), Futian District, Shenzhen, Guangdong 518036, People’s Republic of ChinaTel/Fax +86-755-83923333 Email wangshubin2013@163.comBackground: The aim of this study was to evaluate the efficacy and safety of trastuzumab, combined with the FLOT regimen, in the perioperative treatment of resectable HER-2-positive advanced gastric cancer.Methods: Overall, 45 patients were divided into two groups; 29 patients in the experimental group were treated with trastuzumab combined with FLOT and 16 patients in the control group were treated with FLOT alone. The primary endpoint was objective response rate (ORR), and the secondary endpoints were disease control rate (DCR), tumor regression grade (TRG), surgical margin, side effects, and overall survival.Results: In the experimental and control groups, ORR was 72.4% and 43.8% (p=0.226), DCR was 89.7% and 87.5%, R0 resection rate was 96.5% and 93.7%, total/subtotal tumor regression grade was 17.2% and 6.3%, partial tumor regression grade was 27.6% and 18.7% (p=0.468), and 2-year survival rate was 78.1% and 73.9% (p=0.932), respectively. The common side effects were agranulocytosis and vomiting. There was no significant difference between the two groups.Conclusion: Trastuzumab combined with FLOT has a good curative effect and safety profile in the perioperative treatment of patients with resectable HER-2-positive advanced gastric cancer. In addition, trastuzumab + FLOT had the same result as FLOT alone, as there was no significant benefit with the addition of T in the group studied.Keywords: gastric cancer, HER2, perioperative chemotherapy, trastuzumab

Yiqun Huang, Yong Zou, Luhui Lin, Xudong Ma, Ruiji Zheng Department of Hematology, Zhangzhou Affiliated Hospital of Fujian Medical University, 363000 Zhangzhou, People’s Republic of China Background: miR-101 is reported to be associated with cell proliferation and apoptosis. However, it is unknown whether miR-101 expression affects cell proliferation and apoptosis in diffuse large B cell lymphoma (DLBCL). The aim of the present study was to investigate the expression of miR-101 and its effect on cell proliferation and apoptosis in DLBCL. Methods: miR-101 expression was detected in 30 cases of patients with DLBCL and normal lymph node by qRT-PCR. Then, miR-101 expression was up-regulated and down-regulated in Originated Cell Line-Large Lymphoma 8 (OCL-LY8) cell line, respectively. MTT and flow cytometry assay were used to evaluate the effect of miR-101 on cell proliferation and apoptosis, respectively. As KDM1A was confirmed to be as a specific target of miR-101 by TargetScanHuman, the relationship between MiR-101 and KDM1A was further investigated. Results: miR-101 expression in patients with DLBCL was significantly reduced compared those in normal lymph node (P

The viable but non culturable (VBNC) state is a condition in which bacterial cells are viable and metabolically active, but resistant to cultivation using a routine growth medium. We investigated the ability of V. parahaemolyticus to form VBNC cells, and to subsequently become resuscitated. The ability to control VBNC cell formation in the laboratory allowed us to selectively isolate VBNC cells using fluorescence activated cell sorting, and to differentiate subpopulations based on their metabolic activity, cell shape and the ability to cause disease in Galleria mellonella. Our results showed that two subpopulations (P1 and P2) of V. parahaemolyticus VBNC cells exist and can remain dormant in the VBNC state for long periods. VBNC subpopulation P2, had a better fitness for survival under stressful conditions and showed 100% revival under favourable conditions. Proteomic analysis of these subpopulations (at two different time points: 12 days (T12) and 50 days (T50) post VBNC) revealed that the proteome of P2 was more similar to that of the starting microcosm culture (T0) than the proteome of P1. Proteins that were significantly up or down-regulated between the different VBNC populations were identified and differentially regulated proteins were assigned into 23 functional groups, the majority being assigned to metabolism functional categories. A lactate dehydrogenase (lldD) protein, responsible for converting lactate to pyruvate, was significantly upregulated in all subpopulations of VBNC cells. Deletion of the lactate dehydrogenase (RIMD2210633:ΔlldD) gene caused cells to enter the VBNC state significantly more quickly compared to the wild-type, and adding lactate to VBNC cells aided their resuscitation and extended the resuscitation window. Addition of pyruvate to the RIMD2210633:ΔlldD strain restored the wild-type VBNC formation profile. This study suggests that lactate dehydrogenase may play a role in regulating the VBNC state.

The formation of persister cells is one mechanism by which bacteria can survive exposure to environmental stresses. We show that Campylobacter jejuni 11168H forms persister cells at a frequency of 10−3 after exposure to 100 × MIC of penicillin G for 24 h. Staining the cell population with a redox sensitive fluorescent dye revealed that penicillin G treatment resulted in the appearance of a population of cells with increased fluorescence. We present evidence, to show this could be a consequence of increased redox protein activity in, or associated with, the electron transport chain. These data suggest that a population of penicillin G treated C. jejuni cells could undergo a remodeling of the electron transport chain in order to moderate membrane hyperpolarization and intracellular alkalization; thus reducing the antibiotic efficacy and potentially assisting in persister cell formation.

Rui Zheng,1 Quanbo Liu,1 Tianxu Wang,1 Lili Wang,1 Yong Zhang2 1Department of Respiratory Medicine, Shengjing Hospital of China Medical University, Shenyang, China; 2Department of Pathology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang, China Background: FAM98A, a novel protein, is expressed in ovarian and colorectal cancer tissues. However, the association between FAM98A expression and the clinicopathological characteristics of non-small cell lung cancer (NSCLC) remains undetermined. Materials and methods: The FAM98A expression pattern was determined in NSCLC samples and corresponding adjacent normal lung tissues using immunohistochemical staining and Western blotting. The association of FAM98A expression with clinicopathological characteristics was measured in 131 NSCLC samples. Finally, the overexpression and inhibition of FAM98A was performed in the A549 and SPC-A1 cell lines to explore its role in the development of lung cancer. Results: Western blot analysis of 20 paired NSCLC samples showed that expression of FAM98A was higher in lung cancer tissues than in the corresponding adjacent normal lung tissues (p

Wentao Deng,1,* Juhui Qiu,1,* Shaoting Wang,1 Zhi Yuan,1 Yuefeng Jia,2 Hailin Tan,2 Jiru Lu,1 Ruqiang Zheng1 1Department of Urinary Surgery, Dongying People’s Hospital, Dongying, 2Department of Urinary Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China *These authors contributed equally to this work Abstract: In this study, we performed the characterization and synthesis of biocompatible and targeted albumin and graphene oxide (GO) dual-carrier paclitaxel (PTX) nanoparticles for photothermal-triggered tumor therapy. PTX absorbed on GO nanosheets as cores were coated with human serum albumin (HSA), following surface conjugation with monoclonal antibodies (mAb) against vascular endothelial growth factor (VEGF; denoted as mAbVEGF) via polyethylene glycol linker to form targeted nanoparticles (PTX-GHP-VEGF). The spherical nanoparticles were 191±5 nm in size with good stability and biocompatibility. GO functioned as the first carrier and a near infrared absorber that can generate photothermal effects under 5-minute 808-nm laser irradiation to thermal trigger the release of PTX from the second carrier HSA nanoparticles. The mechanism of thermal-triggered drug release was also investigated preliminarily, in which the heat generated by GO induced swelling of PTX-GHP-VEGF nanoparticles which released the drugs. In vitro studies found that PTX-GHP-VEGF can efficiently target human SW-13 adrenocortical carcinoma cells as evaluated by confocal fluorescence microscopy as well as transmission electron microscopy, and showed an obvious thermal-triggered antitumor effect, mediated by apoptosis. Moreover, PTX-GHP-VEGF combined with near infrared irradiation showed specific tumor suppression effects with high survival rate after 100 days of treatment. PTX-GHP-VEGF also demonstrated high biosafety with no adverse effects on normal tissues and organs. These results highlight the remarkable potential of PTX-GHP-VEGF in photothermal controllable tumor treatment. Keywords: paclitaxel, graphene oxide, human serum albumin, tumor targeting, photothermal-triggered tumor therapy

Seyin Zou,1,3,† Nuo Cao,1,† Du Cheng,2 Rongqin Zheng,4 Jin Wang,4 Kangshun Zhu,4 Xintao Shuai1,2 1Center of Biomedical Engineering, Zhongshan School of Medicine, 2PCFM Lab of Ministry of Education, School of Chemistry and Chemical Engineering, 3Department of Laboratory Medicine,The Third Affiliated Hospital, Guangzhou Medical University, 4The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China †These authors contributed equally to this workAbstract: A folate conjugated ternary copolymer, FA–PEG–PEI–PCL, of poly(ethylene glycol) (PEG), poly(ethylene imine) (PEI), and poly(ε-caprolactone) (PCL) was synthesized. The copolymer self-assembled into cationic micelles capable of co-delivering siRNA and the anticancer drug doxorubicin (DOX). This dual functional nanocarrier demonstrated low cytotoxicity and high performance in drug/siRNA delivery. Upon the codelivery of siRNA, targeting the Bcl-2 gene, and DOX, using the folate-targeted nanocarrier, DOX-induced apoptosis in the skov-3 cells overexpressing folate receptor was significantly enhanced through a mechanism of downregulating the antiapoptotic protein Bcl-2, while simultaneously upregulating the proapoptotic protein Bax. This work suggested that the combination of Bcl-2 siRNA and DOX therapies is feasible, based on our dual functional nanocarrier, which set up a good basis for a future in vivo test.Keywords: codelivery, gene silencing, chemotherapy, apoptosis, tumor targeting

Xinxin Yang1*, Ruiyuan Zheng2*, Yunpeng Cai2, Meiling Liao2, Weien Yuan1,2, Zhenguo Liu11Department of Neurology, Xinhua Hospital (affiliated to Shanghai Jiaotong University School of Medicine), 2School of Pharmacy, Shanghai Jiaotong University, Shanghai, People's Republic of China*Xinxin Yang and Ruiyuan Zheng contributed equally to this workBackground: Levodopa remains the most effective drug in the treatment of Parkinson's disease. However, long-term administration of levodopa induces motor complications, such as levodopa-induced dyskinesia. The mechanisms underlying levodopa-induced dyskinesia are not fully understood.Methods: In this study, we prepared levodopa methyl ester (LDME)/benserazide-loaded nanoparticles, which can release LDME and benserazide in a sustained manner. Dyskinesia was induced in rats by repeated administration of levodopa then treated with LDME plus benserazide or the same dose of LDME/benserazide-loaded nanoparticles. Apomorphine-induced rotations and abnormal involuntary movements (AIMs) were measured on treatment days 1, 5, 10, 15, and 20. In addition, the levels of phosphorylated dopamine- and cyclic adenosine monophosphate-regulated phosphoprotein of 32 kDa, extracellular signal-regulated kinases 1/2, and ΔfosB were determined by Western blot. Tau levels were determined by Western blot and immunohistochemistry. Dynorphin levels in the striatum and cortex of rats were measured using enzyme-linked immunosorbent assay.Results: Over the course of levodopa treatment, the rats developed abnormal AIMs, classified as locomotive, axial, orolingual, and forelimb dyskinesia. The degree of reduction of apomorphine-induced rotations was comparable in dyskinetic rats treated with LDME plus benserazide or LDME/benserazide-loaded nanoparticles. The axial, limb, and orolingual (ALO) AIMs of dyskinetic rats treated with LDME/benserazide-loaded nanoparticles were 14 ± 2.5, 9 ± 2.0, and 10 ± 2.1 on treatment days 10, 15, and 20, respectively, which were significantly reduced compared with dyskinetic rats treated with LDME plus benserazide (25 ± 3.7, 27 ± 3.8, and 25 ± 3.5, respectively). The locomotive AIMs of dyskinetic rats treated with LDME/benserazide-loaded nanoparticles were 2.3 ± 0.42, 1.7 ± 0.35, and 1.6 ± 0.37 on treatment days 10, 15, and 20, respectively, which were also reduced compared with dyskinetic rats treated with LDME plus benserazide (4.4 ± 0.85, 4.7 ± 0.95 and 4.8 ± 0.37, respectively). Western blot showed that the levels of phosphorylated dopamine- and cyclic adenosine monophosphate-regulated phosphoprotein of 32 kDa, extracellular signal-regulated kinases 1/2, tau, and ΔfosB in dyskinetic rats treated with LDME/benserazide-loaded nanoparticles were 134.6 ± 14.1, 174.9 ± 15.1, 134.2 ± 19.3, and 320.5 ± 32.8, respectively, which were significantly reduced compared with those of dyskinetic rats treated with LDME plus benserazide (210.3 ± 19.7, 320.8 ± 21.9, 340.4 ± 27.1, and 620.7 ± 48.3, respectively). Immunohistochemistry indicated that the level of phosphorylated tau was (7.2 ± 1.1) × 104 in dyskinetic rats treated with LDME/benserazide-loaded nanoparticles. However, the tau level was only (14.6 ± 2.3) × 104 in LDME plus benserazide-treated dyskinetic rats. There was a significant difference between the two groups. Enzyme-linked immunosorbent assay showed that dynorphin levels in the striatum and cortex of dyskinetic rats treated with LDME/benserazide-loaded nanoparticles were 5.7 ± 1.2 and 4.8 ± 0.87, respectively, which were significantly reduced compared with LDME plus benserazide-treated dyskinetic rats (13.3 ± 2.1 and 8.1 ± 1.1 for the striatum and cortex, respectively).Conclusion: Results suggest that LDME/benserazide-loaded nanoparticles can be used to reduce the expression of dyskinesia in dyskinetic rats.Keywords: Parkinson’s disease, levodopa-induced dyskinesia, ∆fosB, dopamine, cAMP-regulated phosphoprotein of 32 kDa, extracellular signal-regulated kinases 1/2, tau

Tinghui Yin1*, Ping Wang1*, Rongqin Zheng1, Bowen Zheng1, Du Cheng2, Xinling Zhang1, Xintao Shuai21Department of Medical Ultrasonic, Third Affiliated Hospital, 2PCFM Laboratory of the Ministry of Education, School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou, People's Republic of China*These authors contributed equally to this workAbstract: The fabrication and initial applications of nanobubbles (NBs) have shown promising results in recent years. A small particle size is a basic requirement for ultrasound contrast-enhanced agents that penetrate tumor blood vessel pores to allow for targeted imaging and therapy. However, the nanoscale size of the particles used has the disadvantage of weakening the imaging ability of clinical diagnostic ultrasound. In this work, we fabricated a lipid NBs contrast-enhanced ultrasound agent and evaluated its passive targeting ability in vivo. The results showed that the NBs were small (436.8 ± 5.7 nm), and in vitro ultrasound imaging suggested that the ultrasonic imaging ability is comparable to that of microbubbles (MBs). In vivo experiments confirmed the ability of NBs to passively target tumor tissues. The NBs remained in the tumor area for a longer period because they exhibited enhanced permeability and retention. Direct evidence was obtained by direct observation of red fluorescence-dyed NBs in tumor tissue using confocal laser scanning microscopy. We have demonstrated the ability to fabricate NBs that can be used for the in vivo contrast-enhanced imaging of tumor tissue and that have potential for drug/gene delivery.Keywords: phospholipids, ultrasound, contrast agent, tumor-targeted

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