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Qingpeng Xie,1,2,* Jiawen Gu,1,2,* Yujia Sun,3 Jinjia Hong,1,2 Jia Wang,1,2 Na Li,1,2 Yuan Zhang,1,2 Meixian Liu,1,2 Xiaoxuan Zhang,1,2 Xiangyu Zhao,1,2 Xiaohang Chen,1,2 Xing Wang1,2 1Shanxi Medical University School and Hospital of Stomatology, Taiyuan, 030001, People’s Republic of China; 2Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Taiyuan, 030001, People’s Republic of China; 3Nursing College of Shanxi Medical University, Taiyuan, 030001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaohang Chen; Xing Wang, Shanxi Medical University School and Hospital of Stomatology, Taiyuan, 030001, People’s Republic of China, Tel +8618834896163 ; +8613934224604, Email kqyx__cxh@163.com; wangxing@sxmu.edu.cnPurpose: Periodontitis is a chronic inflammatory oral disease that causes defects in periodontal tissue. Conventional therapies are limited, and often lead to high recurrence rates. The emerging concept of medicinal food homology has shed light on the potential of ginger as a therapeutic adjuvant for periodontitis, given its antioxidant and anti-inflammatory properties. However, fresh ginger exhibits poor stability and bioavailability. Ginger exosome-like nanoparticles (GELNs), a derivative of ginger, have not been reported to exert therapeutic effects in periodontitis. This study aimed to explore the therapeutic effects of GELNs on tissue damage caused by periodontitis and their underlying mechanisms of action.Methods: The GELNs composition was analyzed using a widely targeted metabolome. Stability was assessed using nanoparticle tracking analysis (NTA) and zeta potential measurements, flavor was evaluated using an electronic nose, and membrane penetration was studied using confocal microscopy. A periodontitis model was established in SD rats, periodontal clinical indicators were monitored, and histological changes were assessed using H&E and TRAP staining. Co-culture experiments investigate the antioxidant and reparative abilities of GELNs on periodontal ligament fibroblasts (PDLFs) in inflammatory environment. NF-κB protein expression was examined by immunofluorescence and immunohistochemistry.Results: The findings revealed that GELNs demonstrated good stability in different environments and mitigated the pungent taste of the raw ginger. In vivo experiments showed that GELNs improved periodontal clinical parameters and pathology compared with ginger juice. In vitro data suggested that GELNs enhanced the proliferation and migration of PDLFs while reducing the reactive oxygen species (ROS) levels by inhibiting the NF-κB signaling pathway in an inflammatory setting.Conclusion: This study is the first to demonstrate that GELNs have a potential therapeutic effect on periodontitis. GELNs can alleviate oxidative stress (OS) and inflammatory reactions by inhibiting the NF-κB signaling pathway. These findings provide a promising method for the treatment of periodontitis by regulating an unbalanced OS state. Keywords: ginger exosome-like nanoparticles, periodontitis, tissue repair, oxidative stress, periodontal ligament fibroblasts

Qian Xie, Jiarou Chen, Hongyan Yang, Jianlong Liang, Rong Ma, Jialiang Guo, Xuxin Zeng School of Medicine, Foshan University, Foshan, 528000, People’s Republic of ChinaCorrespondence: Rong Ma; Xuxin Zeng, School of Medicine, Foshan University, Foshan, 528000, People’s Republic of China, Email 648510213@qq.com; adhesion2002@163.comAbstract: Herbal pairs are unique combinations of two relatively fixed herbs that are used in clinical practice. This is the most fundamental and straightforward form of multiple herbal treatment that aims to attain specific efficacy through unique methods. Coptidis Rhizoma (“Huanglian” in Chinese) and Magnoliae Officinalis Cortex (“Houpo” in Chinese) which are commonly used in combination and could also be used as important components of other prescriptions to treat damp-heat dysentery, splenic and stomach disorders, and qi stagnation in clinical practice. However, there is currently no summary on the compatibility of Huanglian and Houpo about traditional use, phytochemistry, and pharmacological activity. It was found the combination or separate extraction of the two drugs may affect the main active components, and new components may be produced after the combined extraction. At the same time, Huanglian and Houpo herb pair exhibited antiviral, anti-inflammatory, antibacterial and other pharmacological effects. At present, research mainly focuses on the indicator components of Huanglian and Houpo, such as berberine, magnolol, and magnolol. The models used for pharmacological validation are limited, mainly including ulcerative colitis, pneumonia, bacterial infections, etc. In order to verify the pharmacological activity of the combination of Huanglian and Houpo, it is necessary to try more in vitro and in vivo models. It’s still need to study the compatibility mechanism of the Huanglian and Houpo drug pair, including but not limited to the interactions between different components and the impact of compatibility on efficacy, bioequivalence studies, and the impact of different dosage forms on pharmacokinetics in the future. It’s believed that the systematic review provided comprehensive information for the study of Huanglian-Houpo drug pair, which will help highlight the importance of the Huanglian-Houpo herb pair and provide some clues for future research on this herb pair.Keywords: Coptidis Rhizoma, Magnoliae Officinalis Cortex, drug pair, chemical constituents, pharmacological effects

Taoying Lu,1– 3 Mingyue Fan,1 Jianxiong Cai,4 Aolin Liu,1 Qianwen Xie,2,3 Xiaowen Zhou,1 Bei Chang,1 Lingjia Yin,2,3,5 Guli Jiang,6 Bin Sun,7 Wenyi Tang,7 Darong Wu4 1The Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 2Outcome Assessment Research Team in Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 3Outcome Assessment Research Team in Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, People’s Republic of China; 4State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 5Department of Global Public Health, Karolinska Institutet, Stockholm, Sweden; 6Department of Scientific Research, Guangzhou Cadre Health Management Center, Guangzhou, People’s Republic of China; 7Department of Traditional Chinese Medicine, Guangzhou Cadre Health Management Center, Guangzhou, People’s Republic of ChinaCorrespondence: Darong Wu, State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, 111 Dade Road, Guangzhou, 510120, People’s Republic of China, Tel +86 13808869436, Email darongwu@gzucm.edu.cnBackground: Dampness syndrome is a basic syndrome of many major and chronic diseases. Early screening and identification of dampness syndrome are important. The Dampness Syndrome Scale of Chinese Medicine (DSSCM) was developed to measure the occurrence and severity of dampness syndrome. The measurement characteristics of the DSSCM should be further validated. The objective of this study is to evaluate the reliability and validity of the DSSCM based on a cross-sectional survey.Methods: The development of DSSCM was based on the traditional Chinese medicine (TCM) theory, expert consensus and clinical investigations. Participants were recruited from Guangdong Provincial Hospital of Chinese Medicine and Guangzhou Cadre Health Management Center in Guangdong Province, China. All participants completed the baseline questionnaire and DSSCM. The reliability of the DSSCM was evaluated by internal consistency reliability and test–retest reliability. The factor structure was tested with confirmatory factor analysis (CFA), while discriminant validity was evaluated by calculating the difference between the total score of the DSSCM and its four dimensions for participants with or without dampness syndrome. We used a clinician’s diagnosis of dampness syndrome as a criterion to evaluate the criterion validity. Multivariate regression analysis was used to analyze the associations among gender, age, height, and weight and dampness syndrome.Results: A total of 880 participants were enrolled for psychometric validation and 869 participants were included in the final analyses after exclusion. The mean age of the participants was 42.62± 12.86 years. The Cronbach’s alpha coefficients for the four dimensions of the DSSCM were 0.809, 0.891, 0.816 and 0.780. The ICCs for the four dimensions of the DSSCM were 0.806, 0.674, 0.780 and 0.760. For validity, the results showed that the DSSCM had good content validity, discriminant validity and criterion validity. For the CFA, the root mean square error of approximation (RMSEA) was 0.091; the standardized root mean square residual (SRMR) was 0.074; the comparative fit index (CFI) was 0.766; and the Tucker–Lewis index (TLI) was 0.745. Weight was found to be associated with the total scores of the DSSCM and its three dimensions.Conclusion: The DSSCM has good reliability and validity to support its use as a tool for assessing the severity of dampness syndrome. This study provides empirical evidence for future updates to the DSSCM.Keywords: dampness syndrome, dampness syndrome scale of Chinese medicine, reliability, validity

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

Shi-Yuan Fan,1,&ast; Zi-Chi Zhao,1,&ast; Xing-Lv Liu,1 Ying-Gang Peng,1 Hui-Min Zhu,1 Shi-Fan Yan,2 Yan-Juan Liu,2 Qin Xie,2 Yu Jiang,2 Sai-Zhen Zeng1 1The First Affiliated Hospital of Hunan Normal University (Hunan Provincial People’s Hospital), Changsha, Hunan, 410005, People’s Republic of China; 2Department of Emergency, Institute of Emergency Medicine, Hunan Provincial People’s Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, Hunan, 410005, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Sai-Zhen Zeng, The First Affiliated Hospital of Hunan Normal University (Hunan Provincial People’s Hospital), 61 Jie-Fang West Road, Fu-Rong District, Changsha, Hunan, 410005, People’s Republic of China, Email 55445321@qq.com Yu Jiang, Department of Emergency, Institute of Emergency Medicine, Hunan Provincial People’s Hospital (The First Affiliated Hospital of Hunan Normal University), 61 Jie-Fang West Road, Fu-Rong District, Changsha, 410005, People’s Republic of China, Email jiangyu@hunnu.edu.cnBackground: Globally, the subsequent complications that accompany sepsis result in remarkable morbidity and mortality rates. The lung is among the vulnerable organs that incur the sepsis-linked inflammatory storm and frequently culminates into ARDS/ALI. The metformin-prescribed anti-diabetic drug has been revealed with anti-inflammatory effects in sepsis, but the underlying mechanisms remain unclear. This study aimed to ascertain metformin’s effects and functions in a young mouse model of sepsis-induced ALI.Methods: Mice were randomly divided into 4 groups: sham, sham+ Met, CLP, and CLP+ Met. CLP was established as the sepsis-induced ALI model accompanied by intraperitoneal metformin treatment. At day 7, the survival state of mice was noted, including survival rate, weight, and M-CASS. Lung histological pathology and injury scores were determined by hematoxylin–eosin staining. The pulmonary coefficient was used to evaluate pulmonary edema. Furthermore, IL-1β, CCL3, CXCL11, S100A8, S100A9 and NLRP3 expression in tissues collected from lungs were determined by qPCR, IL-1β, IL-18, TNF-α by ELISA, caspase-1, ASC, NLRP3, P65, p-P65, GSDMD-F, GSDMD-N, IL-1β and S100A8/A9 by Western blot.Results: The data affirmed that metformin enhanced the survival rate, lessened lung tissue injury, and diminished the expression of inflammatory factors in young mice with sepsis induced by CLP. In contrast to sham mice, the CLP mice were affirmed to manifest ALI-linked pathologies following CLP-induced sepsis. The expressions of pro-inflammatory factors, for instance, IL-1β, IL-18, TNF-α, CXCL11, S100A8, and S100A9 are markedly enhanced by CLP, while metformin abolished this adverse effect. Western blot analyses indicated that metformin inhibited the sepsis-induced activation of GSDMD and the upregulation of S100A8/A9, NLRP3, and ASC.Conclusion: Metformin could improve the survival rate, lessen lung tissue injury, and minimize the expression of inflammatory factors in young mice with sepsis induced by CLP. Metformin reduced sepsis-induced ALI via inhibiting the NF-κB signaling pathway and inhibiting pyroptosis by the S100A8/A9-NLRP3-IL-1β pathway.Keywords: sepsis, pediatric, inflammation, pyroptosis, ALI

Qian Xie,1,&ast; Chang Liu,1,&ast; Fen Liu,2 Xuehe Zhang,1 Zhiyang Zhang,1 Xin An,1 Yining Yang,3– 6 Xiaomei Li1 1Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, People’s Republic of China; 2State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Clinical Medical Research Institute, the First Affiliated Hospital of Xinjiang Medical University, Urumqi, People’s Republic of China; 3Department of Cardiology, People’s Hospital of Xinjiang Uyghur Autonomous Region, Urumqi, People’s Republic of China; 4Xinjiang Key Laboratory of Cardiovascular Homeostasis and Regeneration Research, Urumqi, People’s Republic of China; 5State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Xinjiang Medical University, Urumqi, People’s Republic of China; 6Key Laboratory of Cardiovascular Disease Research, First Affiliated Hospital of Xinjiang Medical University, Urumqi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yining Yang, Department of Cardiology, People’s Hospital of Xinjiang Uygur Autonomous Region, 91 Tianchi Road, Urumqi, 830054, People’s Republic of China, Tel +86-991-4361690, Email yangyn5126@163.com Xiaomei Li, Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, 137 Liyushan South Road, Urumqi, 830054, People’s Republic of China, Tel +86-991-4362611, Email lixm505@163.comPurpose: Metabolic Syndrome (MS) greatly increases the risk of heart disease and Heart Failure(HF). Insulin Resistance (IR) is considered to be the key to the pathophysiology of MS. The purpose of this study was to evaluate the predictive effect of different alternative indicators of IR on adverse cardiovascular events in patients with MS complicated with HF.Methods: Patients with HF who were diagnosed with MS in the heart center of the first affiliated Hospital of Xinjiang Medical University were selected continuously. The baseline data of the patients in the group were compared. The diagnostic value of alternative indexes of IR was evaluated by the working characteristic curve of subjects. The relationship between different alternative indicators of IR and survival rate was evaluated by survival curve. COX regression was used to analyze the effects of different alternative indicators of IR on the risk of end-point events.Results: The levels of TyG, TyG-BMI, TyG-WC, TG/HDL-C and METS-IR were significantly increased in patients with Major Adverse Cardiovascular Events (MACEs). Among the five alternative indexes of IR, METS-IR had the highest AUC (0.691, 95% CI:0.657– 0.752, P < 0.001) in predicting MACEs. No matter which alternative index of IR was used, the survival rate of MACEs in High group was significantly decreased. TyG, TyG-BMI, TyG-WC, TG/HDL-C and METS-IR can independently predict the occurrence of MACEs events, even if some confounding factors are adjusted.Conclusion: Our study shows that alternative indicators of IR, especially METS-IR, are independently associated with adverse cardiovascular events in patients with MS and HF.Keywords: insulin resistance indexes, metabolic syndrome, heart failure, predictive

Tao Sun,1,2 Shilin Xiao,1 Miaomiao Wang,1 Qian Xie,1 Liang Zhang,1 Mingfu Gong,1 Dong Zhang,1 Chunyu Zhou1 1Department of Radiology, Xinqiao Hospital, Army Medical University, Chongqing, People’s Republic of China; 2Faculty of Materials Science and Chemistry, China University of Geosciences, Wuhan, People’s Republic of ChinaCorrespondence: Dong Zhang; Chunyu Zhou, Department of Radiology, Xinqiao Hospital, Army Medical University, No. 183, Xinqiao Street, Shapingba District, Chongqing, People’s Republic of China, Tel +86 23 68763842, Email hszhangd@tmmu.edu.cn; zhouchy@tmmu.edu.cnAbstract: Acute liver injury (AIL), a fatal clinical disease featured with a swift deterioration of hepatocyte functions in the short term, has emerged as a serious public health issues that warrants attention. However, the effectiveness of existing small molecular antioxidants and anti-inflammatory medications in alleviating AIL remains uncertain. The unique inherent structural characteristics of liver confer it a natural propensity for nanoparticle capture, which present an opportunity to exploit in the formulation of nanoscale therapeutic agents, enabling their selective accumulation in the liver and thereby facilitating targeted therapeutic interventions. Significantly increased reactive oxygen species (ROS) accumulation and inflammation response have been evidenced to play crucial roles in occurrence and development of AIL. Nanozymes with ROS-scavenging capacities have demonstrated considerable promise in ROS elimination and inflammation regulation, thereby offering an appealing therapeutic instrument for the management of acute liver injury. In this review, the mechanisms of different type of ALI were summarized. In addition, we provide a comprehensive summary and review of the available ROS-scavenging nanozymes, including transition metal-based nanozymes, noble metal nanozymes, carbon-based nanozymes, and some other nanozymes. Furthermore, the challenges still need to be solved in the field of ROS-scavenging nanozymes for ALI alleviation are also discussed.Keywords: acute liver injury, nanozyme, ROS-scavenging, antioxidant, anti-inflammation

Xuehe Zhang,1,&ast; Jixin Zhang,1,&ast; Fen Liu,2 Wenling Li,1 Tong Zhang,1 Binbin Fang,2 Zhiyang Zhang,1 Qian Xie,1 Yining Yang,3 Xiaomei Li1 1Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, People’s Republic of China; 2State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Clinical Medical Research Institute, the First Affiliated Hospital of Xinjiang Medical University, Urumqi, People’s Republic of China; 3Department of Cardiology, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yining Yang, Department of Cardiology, People’s Hospital of Xinjiang Uygur Autonomous Region, 91 Tianchi Road, Urumqi, 830054, People’s Republic of China, Tel +86-991-4361690, Email yangyn5126@163.com Xiaomei Li, Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, 137 Liyushan South Road, Urumqi, 830054, People’s Republic of China, Tel +86-991-4362611, Email lixm505@163.comPurpose: There is a lack of research on nutritional status and poor prognosis in patients with metabolic syndrome and heart failure. This study evaluated the relationship between nutritional status as defined by the PNI and adverse outcomes in patients with metabolic syndrome and heart failure.Methods: A total of 1048 heart failure patients with metabolic syndrome admitted to the Heart Center of the First Affiliated Hospital of Xinjiang Medical University from January 2015 to December 2019 were consecutively. PNI was used to assess their nutritional status.Results: A total of 51.0% of the patients were in the nonmalnutrition group (PNI≥ 45), 27.9% were in the mild malnutrition group (40≤PNI< 45), and 21.1% of patients were in the malnutrition group (PNI< 40). At 36 months of follow-up, after adjusting for other confounding factors, malnutrition (PNI< 40) was independently associated with all-cause death (HR: 1.787, 95% CI: 1.451– 2.201, P< 0.001) and cardiovascular death (HR: 1.837, 95% CI: 1.467– 2.301, P< 0.001). PNI showed additional prognostic predictive value when included in the established risk factor model, both for all-cause death (AUC: 0.620, 95% CI: 0.579– 0.661, P< 0.001) and cardiovascular death (AUC: 0.596, 95% CI: 0.555– 0.636, P< 0.001).Conclusion: In patients with metabolic syndrome and heart failure, malnutrition assessed by PNI is an independent predictor for all-cause death and cardiovascular death, and PNI is negatively correlated with the occurrence of adverse outcomes.Keywords: prognostic nutritional index, metabolic syndrome, heart failure, malnutrition, prognosis

Li Zhou,1 Lai Wei,1 Yalin Chu,1 Qinhong Xie2 1Department of Health Management, School of Management, Zunyi Medical University, Zunyi, People’s Republic of China; 2Center for Mental Health Research, School of Management, Zunyi Medical University, Zunyi, People’s Republic of ChinaCorrespondence: Qinhong Xie, Center for Mental Health Research, School of Management, Zunyi Medical University, Zunyi, People’s Republic of China, Email xqinhongzmc@163.comObjective: The current study aimed to explore comprehensively college graduates’ negative life experiences, coping strategies, and enlightenment in a qualitative way.Methods: This was a qualitative study. Purposeful sampling was used to select 31 college graduates majoring in various subjects from a Chinese University. The one-on-one semi-structured interviews were conducted online through Tencent QQ/WeChat and were recorded and transcribed verbatim. A phenomenological approach was used to guide this research in the data collection and analysis. Thematic analysis was used to identify themes across interviews around their negative life experiences, coping strategies, and enlightenment.Results: College graduates’ negative life experiences were mainly focused on three aspects: negative work experience (eg, lack of adaptation, busy schedule, low salary), negative personal life experience (eg, multiple pressure, psychological problems, the hardship of life), and negative social life experience (eg, the incomprehension of those around you, complex interpersonal relationship, social complexity). The coping strategies they used can be classified into two categories: emotion-focused strategies (eg, accepting reality, self-persuasion, keeping a positive attitude), and problem-focused strategies (eg, goal-setting, asking for help to solve the problem, persistence). As for life enlightenment, six themes emerged: accept life, strive to life, love life, cherish life, recognize life, and learn to live.Conclusion: College graduates’ negative experiences came from multiple levels, and they use multiple coping strategies to deal with the challenges. Our results provide important guidance for researchers and policymakers to design effective and targeted intervention programs to improve college graduates’ coping abilities in response to negative life experiences and help them better transition from school to work. Specifically, future research and intervention to promote college graduates’ mental health should target various social-ecological levels, focus on promoting coping from an ecological perspective, as well as facilitate post-traumatic growth to help them grow from negative life experiences and cope positively.Keywords: college graduates, negative life experiences, coping, enlightenment, qualitative research, COVID-19 pandemic

Zike Sheng,1 Junjie Li,2 Chihua Chen,3 Jing Xie,4 Yumin Xu,5 Huijuan Zhou,1 Qing Xie1 1Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Pulmonary and Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 3Department of Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 4Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 5Department of Infection Control/Department of Nursing, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of ChinaCorrespondence: Huijuan Zhou, Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Building 36, 197 Ruijin Er Road, Shanghai, 200025, People’s Republic of China, Tel +86-21-64370045-680419, Fax +86-21-64454930, Email hjzhou419@163.comIntroduction: Human melioidosis is an emerging infectious disease in tropical areas of China, and chronic melioidosis can be a rare cause of fever of unknown origin (FUO). Timely diagnosis may improve the prognosis of melioidosis.Case Presentation: We report a case of melioidosis with splenic abscesses caused by Burkholderia pseudomallei in a 57-year-old man, who presented with FUO. Positron emission tomography/computed tomography (PET/CT) revealed multiple hypermetabolic lesions in the spleen. The spleen biopsy was conducted and metagenomics next-generation sequencing (mNGS) of the spleen specimen identified the presence of B. pseudomallei, confirming the diagnosis of melioidosis. Antimicrobial treatment was initiated with intravenous meropenem, followed by oral faropenem. During the follow-up, the patient was in good condition except having a low-grade fever occasionally. A splenectomy was performed, and subsequent culture and mNGS of the spleen pus were both positive for B. pseudomallei. Histopathological characteristics of chronic splenic melioidosis were noted.Conclusion: Melioidosis is a serious endemic disease, and it is critical to raise awareness about this disease.Keywords: melioidosis, Burkholderia pseudomallei, metagenomics next-generation sequencing, splenectomy

Qian Xie,1,* Shi Gao,1,* Rui Tian,2 Guohao Wang,3,4 Zainen Qin,5 Minglong Chen,1 Wenhui Zhang,1 Qiang Wen,1 Qingjie Ma,1 Lei Zhu1 1Department of Nuclear Medicine, China-Japan Union Hospital of Jilin University, NHC Key Laboratory of Radiobiology, School of Public Health of Jilin University, Changchun, 130033, People’s Republic of China; 2Department of Ophthalmology Second Hospital, Jilin University, Changchun, 130033, People’s Republic of China; 3Cancer Centre, Faculty of Health Sciences, University of Macau, Macau, SAR, 999078, People’s Republic of China; 4Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Macau, SAR, 999078, People’s Republic of China; 5Department of Oral Radiology, Guangxi Medical University College of Stomatology, Nanning, 530021, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qingjie Ma; Lei Zhu, Email maqj@jlu.edu.cn; zeh.ray8@gmail.comIntroduction: Combination therapy is a promising approach to promote the efficacy and reduce the systemic toxicity of cancer therapy. Herein, we examined the potency of a combined chemo-phototherapy approach by constructing a hyaluronidase- and reactive oxygen species-responsive hyaluronic acid nanoparticle carrying a chemotherapy drug and a photosensitizer in a tumor-bearing mouse model. We hypothesized that following decomposition, the drugs inside the nanocomplex will be released in the tumors to provide effective tumor treatment. We aimed to design a smart drug delivery system that can improve traditional chemotherapy drug delivery and enhance the therapeutic efficacy in combination with photodynamic therapy.Methods: Hydrophilic hyaluronic acid (HA) was covalently modified with a hydrophobic 5β-cholanic acid (CA) via an ROS-cleavable thioketal (tk) linker for a targeted co-deliver of 10-Hydroxy camptothecin (HCPT) and Chlorin e6 (Ce6) into tumors to improve the efficiency of combined chemo-photodynamic therapy.Results: The obtained HA-tk-CA nanoparticle carrying HCPT and Ce6, named HTCC, accumulated in the tumor through the enhanced permeable response (EPR) effect and HA-mediated CD44 targeting after intravenous administration. Upon laser irradiation and hyaluronidase degradation, HTCC was disrupted to release HCPT and Ce6 into the tumors. Compared to the monotherapy approach, HTCC demonstrated enhanced tumor growth inhibition and minimized systemic toxicity in a tumor-bearing mouse model.Conclusion: Our results suggested that controlled dual-drug release not only improved tumor drug delivery efficacy, but also reduced systemic side effects. In addition to HCPT and Ce6 delivery, the HA-tk-CA nanocomplex can be used to deliver other drugs in synergistic cancer therapy. Since most current combined therapy uses free drugs with distinct spatiotemporal distributions, the simultaneous co-delivery of dual drugs with a remote on-demand drug delivery nanosystem provides an alternative strategy for drug delivery design.Keywords: chemotherapy, photodynamic therapy, hyaluronic acid, responsive nanoparticle, drug delivery

Qiaoyi Xie,1 Xiaote Zhang,2 Wei Cui,1 Yajiao Pang1 1Department of Pediatrics, The Affiliated People’s Hospital of Ningbo University, Ningbo, People’s Republic of China; 2Department of Otolaryngology Head and Neck Surgery, Ningbo Yinzhou No.2 Hospital, Ningbo, People’s Republic of ChinaCorrespondence: Qiaoyi Xie, Department of Pediatrics, The Affiliated People’s Hospital of Ningbo University, No. 251, Baizhang East Road, Ningbo, 315040, People’s Republic of China, Tel + 86 0574-87016888, Email qiaoyi_xie@126.comObjective: The individualized prediction of treatment regimens of macrolide-unresponsive Mycoplasma pneumoniae pneumonia (MUMPP) is scarce. The aim of this study was, therefore, to evaluate the relevant data of patients and construct a nomogram for identifying refractory Mycoplasma pneumoniae pneumonia (RMPP) among children continued to be treated with macrolide after the confirmation of MUMPP, providing a reference for the choice of treatment regimen.Methods: We performed a retrospective study involving 162 children who continued to be treated with macrolide (azithromycin) after the confirmation of MUMPP without antibiotic changes between January 2020 and January 2022. We collected data on clinical feature, hospitalization period, treatments, laboratory data, extrapulmonary symptoms, parapneumonic effusion, and connections with other respiratory pathogens. In addition, the independent risk factors for RMPP were determined through univariate and multivariate analyses, and then a nomogram was constructed and validated.Results: In this study, the multivariate logistic regression analysis showed that age, leukocyte count, neutrophil proportion, serum procalcitonin, and lactate dehydrogenase were independent risk factors for RMPP. Using the five independent associated factors, the nomogram for identification of RMPP was constructed. Moreover, the area under the ROC curve (AUC) was 0.925 (95% CI: 0.882– 0.968) for the nomogram showing excellent discrimination. The calibration curve, close to the 45-degree line, exhibited good calibration of nomogram.Conclusion: We constructed and validated a visual and user-friendly nomogram for individualized prediction of RMPP risk in children who continued to be treated with macrolide after the confirmation of MUMPP based on five variables. According to the nomogram model, continuation of macrolide should be considered rather than second-line antibiotics including tetracyclines (doxycycline or minocycline) and fluoroquinolones for MUMPP children with low predictive values.Keywords: nomogram, refractory, Mycoplasma pneumoniae, pneumonia, children

Jianbing Wu,1,&ast; Jie Zhang,1,&ast; Qiangli Xie,2 Xiaohuan He,3 Zhangchao Guo,1 Bo Zheng,4 Sisong Wang,5 Qiumei Yang,6 Chunfu Du1 1Department of Neurosurgery, Ya’an People’s Hospital, Ya’an, 625000, People’s Republic of China; 2Department of Cardiovascular Medicine, Chengdu Qingbaijiang District People’s Hospital, Chengdu, 610300, People’s Republic of China; 3Department of the Fifth Dispatched Outpatient, The General Hospital of Western Theater Command, Chengdu, 610083, People’s Republic of China; 4Department of Neurology, Ya’an People’s Hospital, Ya’an, 625000, People’s Republic of China; 5Department of Neurosurgery, the Chengdu 363 Affiliated Hospital of Southwest Medical University, Chengdu, 610041, People’s Republic of China; 6Department of Geriatrics, Luzhou People’s Hospital, Luzhou, 646000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chunfu Du, Department of Neurosurgery, Ya’an People’s Hospital, 358 Chenghou Road, Ya’an, Sichuan, 625000, People’s Republic of China, Tel +86-835-2862065, Email 1012036559@qq.comPurpose: Neuroinflammation is considered a critical pathological process in various central nervous system (CNS) diseases and is closely related to neuronal death and dysfunction. Bergaptol is a natural 5-hydroxyfurocoumarin found in lemon, bergamot and other plants. Some studies have confirmed its anti-cancer, anti-inflammatory and anti-atherogenic functions, indicating that it may have significant medicinal value. In this study, we investigated the potential effect of Bergaptol in vitro and in vivo neuroinflammatory models.Methods: Mice were injected with LPS (40 μg/kg) into the hippocampal CA1 region and then injected intraperitoneally with Bergaptol (10, 20 and 40 mg/kg) once a day for two weeks. In addition, to verify the effect of Bergaptol on BV2 cells, Bergaptol with different concentrations (5, 10 and 20 μg/mL) was firstly incubated for 1 hour, then LPS with a concentration of 1 μg/mL was added and incubated for 23 hours.Results: Bergaptol treatment significantly improved the cognitive impairment induced by LPS. In addition, Bergaptol significantly inhibited the reduction of dendritic spines and the mRNA level of inflammatory factors (TNF-α, IL-6 and IL-1β) in hippocampal induced by LPS. In vitro, Bergaptol inhibited the production of TNF-α, IL-6 and IL-1β from LPS-treated BV-2 cells. In addition, Bergaptol treatment significantly reduced the phosphorylation levels of JAK2, STAT3 and p65 in LPS-stimulated BV-2 cells.Conclusion: In conclusion, our results suggest that Bergaptol alleviates LPS-induced neuroinflammation, neurological damage and cognitive impairment by regulating the JAK2/STAT3/P65 pathway, suggesting that Bergaptol is a promising neuroprotective agent.Keywords: Bergaptol, neuroinflammation, LPS, JAK2/STAT3/p65

Zike Sheng,1,&ast; Junjie Li,2,&ast; Tingting Chen,3 Yan Zhu,4 Xueping Yu,5 Xiuhua He,5 Yijuan Zheng,5 Cuiping Ma,6 Minghui Zheng,5 Peiyun Wang,1 Ziqiang Li,1 Yumin Xu,7 Qing Xie,1 Zhijun Su,5 Sumei Chen5 1Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 3Department of Pharmacy, The First Hospital of Quanzhou Affiliated to Fujian Medical University, Quanzhou, People’s Republic of China; 4Clinical Laboratory, The First Hospital of Quanzhou Affiliated to Fujian Medical University, Quanzhou, People’s Republic of China; 5Department of Infectious Diseases, The First Hospital of Quanzhou Affiliated to Fujian Medical University, Quanzhou, People’s Republic of China; 6Department of Infection Control, The First Hospital of Quanzhou Affiliated to Fujian Medical University, Quanzhou, People’s Republic of China; 7Department of Infection Control, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhijun Su; Sumei Chen, Department of Infectious Diseases, The First Hospital of Quanzhou Affiliated to Fujian Medical University, Licheng District, Quanzhou, People’s Republic of China, Tel +86-595-22277011 ; +86-595-22277173, Fax +86-595-222781, Email su2366@sina.com; chensm561119190@sina.comPurpose: Hypervirulent Klebsiella pneumoniae (hvKP) is emerging globally and can cause various infections. This study aimed to investigate the clinical and microbiological characteristics of bloodstream infection (BSI) caused by hvKP.Patients and Methods: The clinical data of hospitalized patients with K. pneumoniae BSI were retrospectively analyzed. The K. pneumoniae strains were collected and re-identified, and antimicrobial susceptibility testing was performed using the broth microdilution method. Capsular serotypes and virulence genes were detected using polymerase chain reaction, and hvKP was defined as aerobactin positive. Molecular typing was done by multilocus sequence typing. The hvKP and classic K. pneumoniae (cKP) subgroups were compared.Results: Of the 66 nonrepetitive BSI K. pneumoniae strains included, 29 (43.9%) were hvKP. In these BSI hvKP strains, salmochelin and yersiniabactin accounted for 86.2% and 72.4%, respectively. The prevalence of rmpA, iroBCD cluster, ybtS, clbA, and allS was 89.7%, 86.2%, 72.4%, 51.7%, and 41.4%, respectively, which were all significantly different between the hvKP and cKP subgroups. Serotypes K1 and K2 were strongly associated with hypervirulence (P < 0.05). Nineteen sequence types were scattered in the 29 hvKP strains, and the most common was ST23 (24.1%). None of the hvKP strains were carbapenem resistant. Compared with cKP, hvKP was more capable of developing a liver abscess. However, the 30-day mortality rate was lower (13.8% vs 21.6%) in the hvKP subgroup than in the cKP subgroup.Conclusion: This study demonstrated a high proportion of hvKP in BSI K. pneumoniae, most of which were RmpA and siderophore producing, and of multiclonal origin.Keywords: capsular serotypes, hypervirulence, infection, mortality, sequence type

Suipeng Chen,1,&ast; Mengjiao Kuang,1,&ast; Ying Qu,1,2 Shirui Huang,1 Binbin Gong,1 Suzhen Lin,1 Huiyan Wang,1 Guiye Wang,1 Hongqun Tao,1 Jian Yu,1 Zuqin Yang,3 Minghua Jiang,1 Qipeng Xie1 1Department of Laboratory Medicine, The Second Affiliated Hospital & Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325035, People’s Republic of China; 2Department of Clinical Laboratory, Wenzhou People’s Hospital, The Third Affiliated Hospital of Shanghai University, The Third Clinical Institute Affiliated to Wenzhou Medical University, Wenzhou, Zhejiang, 325035, People’s Republic of China; 3Newborn Department of Pediatrics, The Second Affiliated Hospital & Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325035, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qipeng Xie, Department of Laboratory Medicine, The Second Affiliated Hospital & Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325035, People’s Republic of China, Tel +86 15157787159, Email pandon2002@163.comObjective: Sepsis remains a major cause of neonatal death. To better characterize the inflammatory response during neonatal sepsis, we compared the differences in serum cytokines and chemokines between full-term neonates with sepsis and without infection.Methods: We enrolled 40 full-term neonates with sepsis and 26 full-term neonates without infection as controls between October 2016 and June 2018. Forty cytokines /chemokines in serum were analyzed using the Luminex Bead Immunoassay System.Results: Our results showed that serum IL-6, IL-8, TNF-α, IL-1β, MIF, CXCL13, CXCL1, CXCL2, CXCL5, CXCL6, CXCL16, CCL27, CCL2, CCL8, CCL3, CCL20, CCL23, and CX3CL1 levels were significantly increased in neonates with sepsis compared to those in the control group (all p< 0.05). The levels of serum CCL20, and IL-17 were higher in late-onset sepsis (LOS) than those in early-onset sepsis (EOS) (all p< 0.05). Conversely, serum CXCL16 was lower in LOS than that in EOS (p< 0.05).Conclusion: Our findings revealed that excessive pro-inflammatory cytokines might be involved in neonatal sepsis. In addition, chemokines significantly increased the recruitment of immune cells after infection to participate in the anti-infection defense of neonates, but this could lead to damage.Keywords: neonatal sepsis, cytokines, chemokines

Xiaoxiao Qu,1,&ast; Shishi Wang,1,&ast; Ying Qu,2 Huiyan Wang,1 Xuanmei Ye,1 Luming Tang,3 Qipeng Xie1 1Department of Clinical Laboratory, The Second Affiliated Hospital & Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, People’s Republic of China; 2Department of Clinical Laboratory, Wenzhou People’s Hospital, The Third Affiliated Hospital of Shanghai University, The Third Clinical Institute Affiliated to Wenzhou Medical University, Wenzhou, Zhejiang, 325035, People’s Republic of China; 3Emergency Department, The Second Affiliated Hospital & Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qipeng Xie, Department of Clinical Laboratory, The Second Affiliated Hospital & Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325035, People’s Republic of China, Tel +86 151 577 87159, Email pandon2002@163.comPurpose: To clarify the distribution of pathogenic bacteria by analyzing the bacterial susceptibility characteristics and risk factors for adult sepsis in The Wenzhou city, Zhejiang province, China, and to aid early diagnosis, monitoring, and prognosis prediction in cases of bacterial sepsis.Patients and Methods: We retrospectively analyzed 329 patients with sepsis admitted to the Second Affiliated Hospital of Wenzhou Medical University between January 2018 and March 2021. Laboratory data were collected before and after treatment; moreover, the bacterial susceptibility characteristics and risk factors for sepsis were comprehensively analyzed using the Sequential Organ Failure Assessment (SOFA) score.Results: The SOFA score was negatively correlated with the prognosis (P < 0.05). We isolated 47 pathogenic strains from blood culture samples, including 29 gram-positive strains, 18 gram-negative strains. The most common gram-negative pathogens in blood cultures are Klebsiella pneumoniae and Escherichia coli, while the most common gram-positive pathogens are Staphylococcus aureus and Staphylococcus hominis. Gram-negative pathogens had resistance rates of 77% and 62.5% to ciprofloxacin and ceftriaxone, respectively. Gram-positive bacteria had a high resistance to penicillin at 100%. Prognostic factors for sepsis included patients’ consciousness, SOFA score, prothrombin time, international normalized ratio, fibrinogen, D-dimer, and aspartate aminotransferase (P < 0.05). Of these, the D-dimer level could predict the outcome of patients with sepsis (AUC = 0.661, P < 0.05).Conclusion: The pathogens detected in adult sepsis in Wenzhou are mainly Klebsiella pneumoniae, Escherichia coli, Staphylococcus aureus, and Staphylococcus hominis. The pathogens exhibited differences in drug susceptibility. The optimal antibiotics should be chosen based on the principles of rational use and drug susceptibility. Combined with D-dimer levels, these parameters can be used to determine the optimal strategy for preventing and treating pathogenic bacteria.Keywords: adult sepsis, drug susceptibility characteristics, risk factors, D-dimer

Qingqing Xie,1 Caixia Sun,2 Zhenghua Fei,1 Xujing Yang1 1Department of Radiation and Medical Oncology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, People’s Republic of China; 2Department of Nursing, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, People’s Republic of ChinaCorrespondence: Xujing YangDepartment of Radiation and Medical Oncology, The First Affiliated Hospital of Wenzhou Medical University, No. 2 Fuxue Lane, Wenzhou, 325000, People’s Republic of ChinaEmail wzyyysj7979@126.comBackground: Tumor immunotherapy is a promising therapeutic strategy for patients with advanced cancers, and some tumors have profound and durable tumor regression. However, immunotherapy is still in the clinical trial stage with elusive long-term effects and complications as a new strategy. It is unclear whether patients possess an accurate understanding of the clinical benefits associated with these agents.Objective: To investigate the anxiety and depression of patients with advanced cancer who received immunotherapy using programmed death-1 or programmed death-ligand 1 after multiline treatment failure, explore the influencing factors, and provide a reference for clinical medical staff and psychological support for patients.Methods: The Hospital Anxiety and Depression Scale was used to calculate the anxiety and depression scores before and after 1, 2, and 3 courses of treatment, respectively. The patients with anxiety and depression were counted. Purposive sampling was used to conduct face-to-face semi-structured interviews with 21 patients to find out the reasons. The obtained data were analyzed and collated using Colaizzi’s phenomenological method.Results: One hundred and twenty-six patients with advanced cancers were included in the study. Before and after 1, 2 and 3 courses of treatment, 18.26%, 23.0%, 50% and 54% of patients suffered from anxiety and depression, respectively. The proportion of patients with anxiety and depression during immunotherapy kept increasing, mainly due to therapeutic efficacy below expectation, lack of timely information after treatment, lack of awareness of treatment and drugs, and lack of family and social support.Conclusion: Patients with advanced tumors after multiline treatment failure are susceptible to anxiety and depression during immunotherapy. It is necessary to test the emotional state of patients in time and carry out early intervention. Nursing staffs and medical staffs should adopt personalized measures to meet the psychological needs of patients.Keywords: anxiety, depression, cancer, immunotherapy, quality of life

Lei Xia,1 Wei Liang,2 Dan Que,2 Qichao Xie2 1Cancer Center, The Second Affiliated Hospital of Chongqing Medical University, Chongqing City, 400000, People’s Republic of China; 2Department of Oncology, The Third Affiliated Hospital of Chongqing Medical University, Chongqing City, 400000, People’s Republic of ChinaCorrespondence: Qichao Xie Tel +86 23-60353465Email qichaoxieyubei@163.comBackground: The role of circRNA circ_0071662 has been studied in bladder cancer. The present study aimed to analyze its involvement in esophageal squamous cell carcinoma (ESCC).Methods: Patients with ESCC (n = 66), esophageal ulcer (EU, n = 66), or gastroesophageal reflux disease (GERD, n = 66) and healthy controls (n = 66) were enrolled in this study. Plasma samples were collected from all patients and controls. ESCC and paired non-tumor tissue samples were collected from ESCC patients. Circ_0071662 levels in these samples were determined by RT-qPCRs. Diagnostic and prognostic values of circ_0071662 for ESCC were analyzed with ROC curve and survival curve analyses.Results: Circ_0071662 level was decreased in ESCC, but not in GERN and EU compared to the controls and in ESCC tissues compared to the non-tumor tissues. Plasma circ_0071662 was closely correlated with patients’ tumor size but not with other clinical features. Decreased plasma circ_0071662 levels separated ESCC patients from GERN patients, EU patients, and healthy controls. Low plasma circ_0071662 levels were closely correlated with worse survival outcomes of ESCC patients.Conclusion: Circ_0071662 is lowly expressed in ESCC and may serve as a potential diagnostic and prognostic biomarker for ESCC.Keywords: esophageal squamous cell carcinoma, circ_0071662, diagnosis, prognosis

Taiyong Bi,1 Qinhong Xie,1,2 Jianhui Gao,1 Tao Zhang,1 Hui Kou1 1Center for Mental Health Research in School of Management, Zunyi Medical University, Zunyi, People’s Republic of China; 2School of Criminal Justice, China University of Political Science and Law, Beijing, People’s Republic of ChinaCorrespondence: Taiyong Bi; Hui Kou Email bitaiyong@126.com; kouhuizmu@163.comBackground: Empathy is shown to affect the attentional processing of painful stimuli and emotional stimuli. However, whether the attentional effects on emotional stimuli depend on emotional valence and the nature of the relationship between the attentional effects on different stimuli are still unknown.Methods: In the present study, 25 high-empathy (HE) participants and 25 low-empathy (LE) participants were recruited to perform dot-probe tasks on painful stimuli and emotional stimuli.Results: The results showed that HE individuals had weak attentional disengagement to painful pictures. More importantly, regarding emotional pictures, HE individuals showed attentional avoidance to negative emotion pictures, while LE individuals showed attentional bias to positive emotion pictures. Correlation analysis showed that the attentional bias score and attentional disengagement score were only associated with each other within the same category of stimuli (painful, positive or negative stimuli).Conclusion: These results revealed that HE individuals mainly showed attentional avoidance to negative stimuli, while LE individuals mainly showed attentional bias to positive stimuli.Keywords: empathy, attentional bias, attentional disengagement, painful stimuli, emotional stimuli

Teng Zhou,1,2,* Mengjiao Kuang,1,* Shirui Huang,1 Jizhen Li,1 Qipeng Xie1 1Department of Laboratory Medicine, The Second Affiliated Hospital & Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, People’s Republic of China; 2The Second Clinical Medical College, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qipeng XieDepartment of Laboratory Medicine, The Second Affiliated Hospital & Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, People’s Republic of ChinaTel +86 15157787159Email pandon2002@163.comObjective: Central nervous system infections (CNSI) are serious diseases that endanger human health. Identifying pathogens and their susceptibility to antibiotics, and promptly using antibiotics under this guidance is essential for treatment. The purpose of this study is to investigate the pathogen characteristics of CNSI patients, which can help clinicians choose appropriate empiric antibiotic .Methods: We retrospectively collected data on CNSI patients with cerebrospinal fluid (CSF) culture positive from 2012 to 2020, including demographic characteristics, laboratory data, pathogenic bacteria, and antimicrobial susceptibility test results.Results: A total of 166 patients with 168 isolates out of 8188 patients were available for data analysis. Among the isolates, Gram-positive bacteria, Gram-negative bacteria and fungi accounted for 59.5%, 36.3%, and 4.2%, respectively. Among newborns, children under 12, and patients over 12, the most isolated strains were Streptococcus agalactiae (24/46, 52.2%), Streptococcus pneumoniae (21/68, 30.9%) and Staphylococcus epidermidis (10/54, 18.5%), respectively. Streptococcus agalactiae is more sensitive to linezolid and vancomycin. Streptococcus pneumoniae is more sensitive to vancomycin. Staphylococcus epidermidis is more sensitive to clindamycin and rifampicin. The sugar content in the CSF of Gram-negative bacteria of children ≤ 12 years old was significantly lower than that of Gram-positive bacteria (P< 0.05).Conclusion: We comprehensively studied the etiological characteristics and antimicrobial resistance patterns of positive cerebrospinal fluid cultures in Wenzhou City, Zhejiang Province from 2012 to 2020, which can provide valuable strategies for preventing pathogens and improving evidence-based treatment.Keywords: cerebrospinal fluid, bacterial culture, drug resistance, epidemiological characteristics

Yandi Tan,1,* Shiqi Yang,1,* Yao Ma,2 Jinlin Li,1 Qian Xie,1 Chaoqi Liu,1 Yun Zhao1 1Medical College of China Three Gorges University, Yichang, Hubei, People’s Republic of China; 2Department of Ultrasonography, Yichang Central People’s Hospital, Yichang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yun Zhao; Chaoqi LiuMedical College of China Three Gorges University, Yichang, Hubei, 443000, People’s Republic of ChinaEmail zhaoyun@ctgu.edu.cn; ctgulcq@163.comPurpose: Immune checkpoint inhibitors (ICIs) and sonodynamic therapy (SDT) are types of immunotherapy. In order to combine soluble programmed cell death protein 1 (sPD-1)-mediated immune checkpoint therapy and chlorin e6 (Ce6)-assisted SDT, nanobubbles (NBs) were generated to simultaneously load sPD-1 and Ce6.Materials and Methods: The sPD-1/Ce6-NBs, which were prepared by thin-film hydration and mechanical oscillation, had a stable physical condition, and delivered sPD-1 and Ce6 in a targeted manner. NBs could strengthen tumor suppression by increasing tumor-targeting accumulation of Ce6 and sPD-1, and by inducing ultrasound-targeted NB destruction. A mouse H22 cell hepatoma xenograft model was used to evaluate the synergetic immunotherapeutic effect and mechanism of sPD-1/Ce6-NBs.Results: By observing the tumor inhibition rate, tissue and cell apoptosis, apoptosis-related genes and protein expression, the best immunotherapeutic effect was exhibited by the sPD-1/Ce6-NBs group. The immunotherapeutic mechanism initially demonstrated that when tumor cells were transfected by sPD-1 delivered by NBs, which downregulated the expression of programmed death-ligand 1 (PD-L1) in tumor cells, and blocked the PD-1/PD-L1 signaling pathway, which improved T-cell-mediated tumor inhibition. Furthermore, ICIs combined with SDT induced immunogenic cell death by translocating calreticulin to the cell surface and then synergistically enhancing antitumor immune responses.Conclusion: In conclusion, sPD-1/Ce6-NBs were successfully designed. Ultrasound-mediated sPD-1/Ce6-NBs are potentially effective delivery systems for combination immunotherapy of hepatocellular carcinoma.Keywords: immune checkpoint inhibitors, ultrasonics, drug delivery, tumor therapy, nanomaterials

Xianyun Xu,1,* Qiongjun Xie,2,* Mingfeng Xie,3 Yong Zeng,3 Qian Liu1 1Key Laboratory of Prevention and treatment of cardiovascular and cerebrovascular diseases of Ministry of Education, Jiangxi Provincial Clinical Research Center for Vascular Anomalies, Basic Medical School, Gannan Medical University, Ganzhou, Jiangxi, 341000, People’s Republic of China; 2Basic Medical School, Gannan Medical University, Ganzhou, Jiangxi, 341000, People’s Republic of China; 3Department of Pediatric Surgery, Jiangxi Provincial Clinical Research Center for Vascular Anomalies, Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases of Ministry of Education, The First Affiliate Hospital of Gannan Medical University, Ganzhou, Jiangxi, 341000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qian LiuKey Laboratory of Prevention and treatment of cardiovascular and cerebrovascular diseases of Ministry of Education, Jiangxi Provincial Clinical Research Center for Vascular Anomalies, Basic Medical School, Gannan Medical University, Ganzhou, Jiangxi, 341000, People’s Republic of ChinaEmail liuqiangmu2017@126.comBackground: Small nucleolus RNA Host Gene 8 (SNHG8) belongs to a subgroup with long non-coding RNAs. LncRNA SNHG8 presents up-regulated in miscellaneous cancers, like gastric cancer, liver cancer, and esophageal squamous cell cancer. Nevertheless, the expression pattern and the pathological function of lncRNA SNHG8 in breast cancer remain obscure.Methods: We examined the expression levels of lncRNA SNHG8 in the tissue samples and cell lines from breast cancer via RT-qPCR in the present study. The functions of lncRNA SNHG8 on the progression of breast cancer cell were examined by CCK-8, EdU, Transwell chamber assays, and flow cytometry analyses. The expression of proteins was assessed using Western blot assay.Results: We found that proliferation, migration, and invasion of breast cancer cells were significantly inhibited due to knockdown of lncRNA SNHG8, while inducing apoptosis of these cells. Mechanistically, SNHG8 functioned as an inhibitor of miR-634 in tumor tissues.Conclusion: LncRNA SNHG8 sponged the miR-634 to increase the expression level of ZBTB20, thus further aggravating the malignancy of breast cancer. Hence, the lncRNA SNHG8-miR-634-ZBTB20 axis may be a promising therapeutic target to treat breast cancers.Keywords: small nucleolus RNA host gene 8, microRNA-634, breast cancer, ZBTB20

Wei Fu, Shanshan Xu, Xiang Dong, Qing Xie, Yadong Gao Department of Allergology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, People’s Republic of ChinaCorrespondence: Yadong Gao; Wei FuDepartment of Allergology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, 430071, People’s Republic of ChinaTel +86 15071384536Email gaoyadong@whu.edu.cn; fuwei0511@163.comAbstract: Aspirin is clinically widely used to inhibit platelet aggregation after coronary intervention. Herein we describe a case of aspirin-induced thrombocytopenia that may be related to allergy to aspirin. A 47‐year‐old man developed a delayed hypersensitivity reaction to aspirin, with pruritus, purpura and thrombocytopenia, increased peripheral blood eosinophils and enlarged inguinal lymph node. All the symptoms disappeared in 2 years after stopping aspirin. Aspirin-induced thrombocytopenia related to allergy is rarely reported. Aspirin hypersensitivity should be taken into consideration in case of unexplained thrombocytopenia in patients taking aspirin. Aspirin “allergy”-induced thrombocytopenia may involve both aspirin related IgG and IgE antibodies.Keywords: aspirin, allergy, thrombocytopenia, platelets

Qian Xie,1,* Tao Wen,2,* Aiyun Yang,2 Xue Zhang,2 Bo Chen,3 Jie Meng,2 Jian Liu,2 Ning Gu,4 Haiyan Xu2 1Division of Nephrology, Peking University Third Hospital, Beijing, 100191, People’s Republic of China; 2Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, 100005, People’s Republic of China; 3Materials Science and Devices Institute, Suzhou University of Science and Technology, Suzhou, 215009, People’s Republic of China; 4State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210096, People’s Republic of China*These authors contributed equally to this workCorrespondence: Haiyan XuInstitute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, 100005, People’s Republic of ChinaEmail xuhy@pumc.edu.cnNing GuState Key Laboratory of Bioelectronics, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210096, People’s Republic of ChinaEmail guning@seu.edu.cnBackground: Contrast-enhanced magnetic resonance imaging (MRI) is a powerful diagnostic tool for many diseases. In many situations, the contrasts are repeatedly administrated in order to monitor and assess the disease progression.Objective: To investigate and compare the biological effects of γ-Fe2O3 nanoparticle (NP) and gadolinium dimeglumine (Gd-DTPA) with high and multiple doses on the kidney of healthy mice.Methods: Polydextrose sorbitol carboxymethyl ether coated γ-Fe2O3 NP with hydrodynamic size of 68.2 nm and clinically applied Gd-DTPA were employed on healthy mice with the repeatedly intravenous administration of high doses. The cell viability of human umbilical vein endothelial cells (HUVEC) in high doses of these two contrast agents were measured using the xCELLigence Real-Time Cell Analysis (RTCA) S16 Instrument. The biological effects of γ-Fe2O3 NP and Gd-DTPA on the kidney were obtained using a biochemical automatic analyzer and multiple proinflammatory factor kit on the serum. Histopathological and immunohistochemistry analysis were taken on kidney tissues.Results: It showed that the proinflammatory responses elicited by the γ-Fe2O3 NPs were weaker than that by Gd-DTPA, evidenced by the relatively much lower level of IL-1β, IL-6, IL-18, TNF-α, C-reactive protein (CRP) and Ferritin. At the same time, the γ-Fe2O3 NPs did not have the biochemical index elevated, while the Gd-DTPA did.Conclusion: The γ-Fe2O3 NPs induced weaker proinflammatory effects in reference to the Gd-DTPA, indicating better renal safety. Therefore, it is suggested that γ-Fe2O3 NPs should be safer and optional choice when repeated contrast-enhanced MRI is necessary.Keywords: iron oxide nanoparticles, proinflammatory, cytokines, renal function

Tao Li,1,2 Xin Li,1 Hui Chen,3 Kai-Zhao Huang,1 Qi Xie,1,2 Han-Yu Ge,1 Shen-Meng Gao,4 Jian-Hua Feng,4 Jun-Jun Yang,1 Zhan-Guo Chen,1 Xiao-Qun Zheng1,2 1Department of Laboratory Medicine, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China; 2School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, The Key Laboratory of Laboratory Medicine, Ministry of Education of China, Wenzhou, Zhejiang, People’s Republic of China; 3Department of Emergency, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China; 4Department of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Zhan-Guo Chen; Xiao-Qun ZhengDepartment of Laboratory Medicine, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of ChinaTel +86-13968806755; +86-13906653839Email steve0577@126.com; jszhengxq@163.comPurpose: Red blood cell distribution width (RDW) has been considered as a potential indicator of the effects of treatment or as a prognostic indicator for various malignancies. Most chronic myeloid leukemia (CML) patients are in the chronic phase, but some have transformed to accelerated phase or blast phase (blast crisis). However, the clinical significance of RDW in CML remains limited.Patients and Methods: In the present study, detailed clinical information and the RDW of 168 healthy people and 153 CML patients (106 patients for the training cohort and 47 patients for the validation cohort) were retrospectively assessed.Results: Multivariate analysis demonstrated that patient age (OR, 1.081; 95CI% 1.039∼ 1.125; p < 0.001), platelet counts (OR, 0.997; 95CI% 0.994∼ 0.999; p = 0.001) and RDW at admission (OR,1.469; 95CI% 1.121∼ 1.925; p = 0.005) were significantly associated with the patients with advanced phase. Among CML patients in the chronic phase, higher RDW was significantly associated with overall survival (OS; p = 0.0008) and the event-free survival (EFS; p = 0.0221) among CML patients with chronic phase, but not with Transformation-free survival (TFS; p = 0.0821). Furthermore, higher RDW was associated with higher mortality compared to patients with low RDW (CML-associated deaths; p < 0.0001). In addition, a decline in RDW is associated with the treatment of CML patients with tyrosine kinase inhibitors, especially at 6 and 12 months after the start of treatment.Conclusion: Higher RDW is a potential prognostic biomarker for chronic CML patients.Keywords: red blood cell distribution width, chronic myeloid leukemia, chronic phase, adverse prognosis

Yu Liu,1 Shirui Huang,2 Mengjiao Kuang,2 Huiyan Wang,2 Qipeng Xie2 1Department of Cardiothoracic Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325035, People’s Republic of China; 2Department of Laboratory Medicine, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, People’s Republic of ChinaCorrespondence: Qipeng XieDepartment of Laboratory Medicine, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, People’s Republic of ChinaTel +86-15157787159Email pandon2002@163.comBackground: LARGE1 plays a pivotal role in glycosylation of alpha-Dystroglycan (α-DG) and is aberrantly downregulated in cell lines originating from epithelium-derived cancers including lung cancer. However, the expression of LARGE1 and its clinical significance in NSCLC are not clear.Materials and Methods: The data were collected from the TCGA database to investigate LARGE1 expression in stage I–III NSCLC and explore its associations with clinicopathological parameters and overall survival of patients. The prognostic role of LARGE1 was examined in subgroups according to clinical features and treatments. The results were validated in external cohorts from the NCBI GEO database. Gene Set Enrichment Analysis (GSEA) was performed to investigate the potential molecular mechanisms during LARGE1 alteration in NSCLC.Results: LARGE1 was aberrantly downregulated in NSCLC compared with adjacent tissues and normal lung tissues and in tumors with advanced stage compared with early stage. There was only a trend of association between high LARGE1 with OS in multivariate analysis. Surprisingly, high LARGE1 was significantly associated with improved OS in a subgroup of the patients with adjuvant chemotherapy (ACT) and a significant interaction between LARGE1 expression and ACT was found. Improved OS after ACT was also found in patients with high LARGE1 compared to those with low LARGE1. When combining LARGE1 expression and ACT, compared with patients with non-ACT, HR of low LARGE1/ACT was 0.592 (95% CI=0.432– 0.813, P=0.0012), and HR of high LARGE1/ACT was 0.124 (95% CI=0.031– 0.505, P=0.0036). The results were verified in two external cohorts from the GEO database. GSEA indicated that LARGE1 might downregulate cell cycle pathway to improve ACT sensitivity and subsequently the prognosis in NSCLC.Conclusion: High LARGE1 can be used to identify the patients with resected stage I–III NSCLC most likely to benefit from adjuvant chemotherapy.Keywords: NSCLC, LARGE1, mRNA, overall survival, adjuvant chemotherapy, benefit

Hanrui Zheng,1,* Qian Xie,2,* Mei Zhan,1 Chaohui Jin,1 Qiu Li3,4 1Department of Pharmacy, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 2International Medical Center/Ward of General Practice, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 3Department of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 4West China Biomedical Big Data Center, Sichuan University, Chengdu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chaohui JinDepartment of Pharmacy, West China Hospital, Sichuan University, Chengdu, People’s Republic of ChinaTel +86-28-85421763Email 695025422@qq.comQiu LiDepartment of Medical Oncology, Cancer Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, People’s Republic of ChinaTel +86-28-85423262Email fbqiu9@163.comBackground: Helicobacter pylori (H. pylori) eradication therapy has been shown to reduce the risk of gastric cancer in patients who have a family history of gastric cancer in first-degree relatives. The aim of this study was to assess the cost-effectiveness of H. pylori eradication therapy in a select population in the People’s Republic of China.Methods: A Markov model was applied to evaluate the cost-effectiveness of H. pylori eradication therapy. The long-term costs of H. pylori eradication therapy were calculated from the Chinese perspective. Health outcomes were measured by quality-adjusted life years (QALYs). Epidemiological information and health utilities used in the model were collected from published literatures or statistical bureaus. A sensitivity analysis was conducted to explore the influence of parameters on the uncertainty of the model.Results: Compared with the no eradication therapy group, H. pylori eradication therapy prolonged an average of 4.52 QALYs (32.64 QALYs vs 28.12 QALYs) and saved $3227.07 ($2472.83 vs $5699.90). The cost-effectiveness analysis demonstrated that no H. pylori eradication therapy cost more and produced less QALYs. It was dominated by H. pylori eradication therapy. The one-way sensitive analyses proved that the results were robust to the fluctuations of the input parameters.Conclusion: H. pylori eradication therapy not only reduced the risk of gastric cancer in first-degree relatives of patients with gastric cancer but also was an economical strategy with lower costs and greater efficacy.Keywords: Helicobacter pylori, eradication therapy, gastric cancer, cost-effectiveness analysis

Junjie Li,1,* Qingqing Xu,2,3,* Sean Ogurek,4 Ziqiang Li,5 Peiyun Wang,5 Qing Xie,5 Zike Sheng,5 Minggui Wang2,3 1Department of Respiratory and Critical Care Medicine, Shanghai Institute of Respiratory Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China; 2Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, People’s Republic of China; 3Key Laboratory of Clinical Pharmacology of Antibiotics, Ministry of Health, Shanghai, People’s Republic of China; 4Brain Tumor Center, Division of Experimental Hematology and Cancer Biology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA; 5Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qing Xie; Zike ShengDepartment of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Building 36, 197 Ruijin Er Road, Shanghai 200025, People’s Republic of ChinaTel +86-21-64370045 ext 680419; Tel +86-21-64370045 ext 680403Fax +86-21-64454930Email xieqingrjh@163.com; shengz12@fudan.edu.cnIntroduction: Drug efflux pumps are critical for resistance in Gram-negative organisms, but there are limited data on the role they play in decreased susceptibility to β-lactam/β-lactamase inhibitor combinations. In this study, we aimed to investigate the impact of efflux pump AcrAB on piperacillin–tazobactam (TZP) and ceftolozane–tazobactam (C/T) susceptibility in tigecycline-non-susceptible Klebsiella pneumoniae (TNSKP) strains.Methods: A tigecycline gradient was used to obtain various TNSKP strains, and in conjunction with the gradient derived strains, a TNSKP clinical strain (TNSKP24) was also included. Minimum inhibitory concentrations (MICs) of antibiotics were determined by the broth microdilution method, and whole-genome sequencing (WGS) was carried out to analyze genomic changes. PCR and sequencing were performed to confirm mutations in ramR, acrR, and the intergenic region of ramR-romA, and qRT-PCR was applied to evaluate levels of gene expression. In-frame acrB knockout and complementation were performed in 3 TNSKP strains.Results: Two derivatives of K. pneumoniae K2606 (K2606-4 and K2606-16) and TNSKP24 overexpressed efflux pump AcrAB were obtained for further study. The MICs of TZP and C/T exhibited a 4- to 8-fold increase in K2606-4 and K2606-16, respectively, when compared with K2606 (TZP, 2/4 μg/mL; C/T, 0.25/4 μg/mL). Deletion of acrB decreased the MICs of TZP and C/T by 4- to 16-fold in TNSKP24, K2606-4, and K2606-16, respectively, and complementation of acrB increased the MICs of these agents. MICs of clavulanate, sulbactam, and avibactam in the presence of β-lactam compounds did not change after acrB deletion and subsequent introduction of complementation mutants.Conclusion: This study highlights that decreased susceptibility to TZP and C/T could be caused by the multidrug efflux pump AcrAB in TNSKP strains.Keywords: drug efflux pump, Enterobacteriaceae, multidrug resistance, β-lactam/β-lactamase inhibitor combinations

Jialyu Huang,* Qin Xie,* Jiaying Lin, Xuefeng Lu, Jing Zhu, Hongyuan Gao, Renfei Cai, Yanping Kuang Department of Assisted Reproduction, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, People’s Republic of China*These authors contributed equally to this workCorrespondence: Renfei Cai; Yanping KuangDepartment of Assisted Reproduction, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai 200011, People’s Republic of ChinaTel +86-21-2327 1699 Ext 5539Fax +86-21-6313 6856Email cairenfei070@sina.com; kuangyp9hospital@126.comPurpose: Dydrogesterone (DYG) is an alternative progestin in progestin-primed ovarian stimulation (PPOS) protocol with weaker pituitary suppression than medroxyprogesterone acetate (MPA) in normal ovulatory women. However, the endocrinological characteristics, oocyte retrieval and pregnancy outcomes of DYG application in polycystic ovarian syndrome (PCOS) patients undergoing in vitro fertilization (IVF) remain unclear.Patients and methods: This retrospective cohort study included 420 PCOS patients who underwent controlled ovarian stimulation with human menopausal gonadotropin (hMG) and DYG (n=105) or MPA (n=315) from January 2014 to December 2017. Baseline characteristics of the two groups were balanced with propensity score matching using the nearest-neighbor random matching algorithm in a ratio of 1:3. The primary outcome measure was the number of oocytes retrieved. Other main outcome measures included the number of viable embryos, incidence of premature luteinizing hormone (LH) surge and live birth rate per frozen-thawed embryo transfer (FET) cycle.Results: A similar number of oocytes was retrieved in the two protocols (16.1±6.5 vs 15.1±10.0, P=0.342). Patients in both groups achieved consistent LH suppression with no premature LH surge detected. In the DYG + hMG group, the mean LH levels were significantly higher than the MPA + hMG group on cycle day 9–11 and trigger day (all P

Lingyang Hua,1 Fengchun Hua,2 Hongda Zhu,1 Jiaojiao Deng,1 Daijun Wang,1 Shihai Luan,1 Hailiang Tang,1 Yihui Guan,2 Qing Xie,1 Ye Gong1,3 1Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, People’s Republic of China; 2Department of Nuclear Medicine and PET Center, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, People’s Republic of China; 3Department of Critical Medicine, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, People’s Republic of ChinaCorrespondence: Ye GongDepartment of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, No. 12 Middle Wulumuqi Road, Jingan District, Shanghai 200040, People’s Republic of ChinaTel +86 138 1793 9896Email drgongye@163.com Qing XieDepartment of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, No. 12 Middle Wulumuqi Road, Jingan District, Shanghai 200040, People’s Republic of ChinaTel +86 21 5288 7030Fax +86 21 5288 7218Email neurosurgeon.qing@gmail.comObjective: This study aims to evaluate the potential role of 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) in detecting high-grade meningiomas and predicting the prognosis of patients after meningioma surgery.Patients and methods: A total of 124 patients met the final inclusion criterion. Tumor to gray ratio (TGR) was compared with Ki-67 labeling index, and its correlations with pre-operative neurological function and treatment status were also evaluated. Receiver-operating characteristic (ROC) curve was drawn to determine a cut-off value which could discriminate meningioma of different grades. Prognostic factors including TGR were analyzed using Kaplan-Meier survival curve and cox proportional model.Results: The TGR of higher World Health Organization (WHO) grade meningioma was significantly higher than that in lower grade (p < 0.001), and it was correlated with the Ki-67 labeling index (p < 0.001, r = 0.1545). The TGR of 1.30 was the best cutoff value for the detection of high grade (WHO grade II&III) meningioma from low grade (WHO grade I) according to ROC analysis, with a sensitivity of 61.5%, the specificity of 86.7%, and accuracy of 81.5%. The TGR (p < 0.001), treatment status (p = 0.035), tumor grade (p < 0.001) and Ki-67 labeling index (p < 0.001) were significantly associated with progression-free survival (PFS). Cox proportional hazards model demonstrated that TGR (p = 0.013) was an independent prognostic factor for PFS.Conclusion: A high uptake of FDG was correlated with a more proliferative biological behavior and is a risk factor for tumor recurrence.Keywords: meningioma, 18F-FDG PET, molecular imaging, clinical characteristic, prognosis

Jialyu Huang,* Qin Xie,* Jiaying Lin, Xuefeng Lu, Ningling Wang, Hongyuan Gao, Renfei Cai, Yanping KuangDepartment of Assisted Reproduction, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, People’s Republic of China*These authors contributed equally to this workPurpose: Dydrogesterone (DYG) has been demonstrated to be an alternative progestin in the progestin-primed ovarian stimulation (PPOS) protocol with comparable oocyte retrieval and pregnancy outcomes. However, its safety regarding neonatal outcomes and congenital malformations is still unclear.Patients and methods: This retrospective cohort study included 3556 live-born infants after in vitro fertilization and vitrified embryo transfer cycles using the DYG + human menopausal gonadotropin (hMG) protocol (n=1429) or gonadotropin-releasing hormone (GnRH)-agonist short protocol (n=2127) from January 2014 to December 2017. Newborn information was gathered from standardized follow-up questionnaires and/or access to medical records within 7 days after birth. Associations between ovarian stimulation protocols and outcome measures were analyzed by binary logistic regression after adjusting for confounding factors.Results: In both singletons and twins, birth characteristics regarding mode of delivery, newborn gender, gestational age, birthweight, length at birth and Z-scores were comparable between the two protocols. For adverse neonatal outcomes, the two protocols showed no significant differences on the rates of low birthweight, very low birthweight, preterm birth, very preterm birth, small-for-gestational age, large-for-gestational age and early neonatal death after adjustment. Furthermore, the incidence of major congenital malformations in the DYG + hMG protocol (1.12%) was similar to that in the GnRH-agonist short protocol (1.08%), with the adjusted odds ratio of 0.98 (95% confidence interval [CI]: 0.40–2.39) and 0.90 (95% CI: 0.33–2.41) in singletons and twins, respectively.Conclusion: Our data suggested that compared with the conventional GnRH-agonist short protocol, application of DYG in the PPOS protocol was a safe option for the newborn population without compromising neonatal outcomes or increasing congenital malformation risks.Keywords: neonatal outcomes, congenital malformations, dydrogesterone, progestin-primed ovarian stimulation, in vitro fertilization

Nai-Li Wei,1,2,* Zi-Fang Quan,3,4,* Tong Zhao,1,* Xu-Dong Yu,4 Qiang Xie,1 Jun Zeng,1 Fu-Kai Ma,1 Fan Wang,1 Qi-Sheng Tang,1 Heng Wu,3 Jian-Hong Zhu11Fudan University Huashan Hospital, Department of Neurosurgery, State Key Laboratory for Medical neurobiology, Institutes of Brain Science, Shanghai Medical College-Fudan University, Shanghai, 20040, People’s Republic of China; 2Department of Neurosurgery, The Second Hospital of Lanzhou University, Lanzhou Gansu China, 730030, People’s Republic of China; 3Department of Neurology, The First Affiliated Hospital, University of South China, Hengyang, Hunan, 421001, People’s Republic of China; 4Institute of Neuroscience, Medical College, University of South China, Hengyang, Hunan, 421001, People’s Republic of China *These authors contributed equally to this workBackground: Stress-related obesity might be related to the suppression of the hypothalamic-pituitary- adrenocortical axis and dysregulation of the metabolic system. Chronic stress also induces the dysregulation of the reward system and increases the risk of food addiction, according to recent clinical findings. However, few studies have tested the effect of chronic stress on food addiction in animal models.Purpose: The objective of this study was to identify whether chronic stress promotes food addiction or not and explore the possible mechanisms.Method: We applied adaily 2 hrsflashing LED irradiation stress to mice fed chow or palatable food to mimic the effect of chronic stress on feeding. After 1 month of chronic stress exposure, we tested their binge eating behaviors, cravings for palatable food, responses for palatable food, and compulsive eating behaviors to evaluate the effect of chronic stress on food addiction-like behaviors. We detected changes in the levels of various genes and proteins in the nucleus accumbens (NAc), ventral tegmental area (VTA) and lateral hypothalamus using qPCR and immunofluorescence staining, respectively.Results: Behaviors results indicated chronic stress obviously increased food addiction score (FAS) in the palatable food feeding mice. Moreover, the FAS had astrong relationship with the extent of the increase in body weight. Chronic stress increased the expression of corticotropin-releasing factor receptor 1(CRFR1) was increased in the NAc shell and core but decreased in the VTA of the mice fed with palatable food. Chronic stress also increased expression of both dopamine receptor 2 (DR2) and mu-opioid receptor (MOR) in the NAc.Conclusion: Chronic stress aggravates the FAS and contributed to the development of stress-related obesity. Chronic stress drives the dysregulation of the CRF signaling pathway in the reward system and increases the expression of DR2 and MOR in the nucleus accumbens.Keywords: chronic stress, obesity, food addiction, dopamine receptor 2, mu-opioid receptor, nucleus accumbens

Caijun Dai,1,* Huihua Qiu,2,* Qiqi Huang,2,* Pinglang Hu,2 Xianchai Hong,2 Junwei Tu,1 Qiangli Xie,2 Haiyan Li,2 Wenwei Ren,2 Shuhong Ni,1 Fujian Chen3 1Jinhua Municipal Central Hospital, Jinhua 321000, China; 2The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China; 3Anji County People’s Hospital, Huzhou 313300, China *These authors contributed equally to this work Purpose: Night shift is associated with adverse physical and psychological health outcomes such as poor sleep quality and depressive symptoms. We aimed to compare sleep quality as well as depressive symptoms in nurses working night shifts to those working day shifts only and explore the association between sleep quality and depressive symptoms among nurses. Patients and methods: Eight hundred sixty-five nurses were enrolled in the current study. Sleep quality and depressive symptoms among nurses were evaluated by the Pittsburgh Sleep Quality Index (PSQI) and Hospital Anxiety and Depressive Disorders Rating Scale (HADS), respectively. Results: PSQI and HADS scores were both significantly higher in the nurses working night shifts (P

Shankun Zhao,1,* Qiang Xie,2,* Redian Yang,1,* Jiamin Wang,1 Chaofeng Zhang,1 Lianmin Luo,1 Zhiguo Zhu,1 Yangzhou Liu,1 Ermao Li,1 Zhigang Zhao1 1Department of Urology and Andrology, Minimally Invasive Surgery Center, Guangdong Provincial Key Laboratory of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China; 2Department of Reproduction, Southern Medical University Affiliate Dongguan People’s Hospital, Dongguan, China *These authors contributed equally to this work Objective: To assess whether radiotherapy (RT) for prostate cancer (PCa) was a risk factor for secondary bladder cancer (BLCa) through a meta-analysis.Materials and methods: The MEDLINE, Embase, and the Cochrane Library were systematically searched for all studies investigating the risk of BLCa in patients with RT. The association between RT and risk of BLCa was summarized using hazard ratio with a 95%CI. The protocol for this meta-analysis is available from PROSPERO (CRD42018090075).Results: Overall, 619,479 participants (age: 57–79 years) were included from 15 studies, 206,852 of whom were patients who received RT. Synthesis of results indicated that RT was significantly associated with an increased risk of BLCa compared with the risk in those who received radical prostatectomy or non-RT (overall HR=1.6, 95%CI: 1.33–1.92, P

Lin Yang,1–3 Wenzhuo He,1–3 Qiankun Xie,1–3 Shousheng Liu,1–3 Pengfei Kong,1–3 Chang Jiang,1–3 Bei Zhang,1–3 Liangping Xia1–3 1Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China; 2State Key Laboratory of Oncology in Southern China, Guangzhou, China; 3Collaborative Innovation Center for Cancer Medicine, Guangzhou, China Background: Population-based incidence evaluations and prognosis assessments of brain metastasis (BM) at diagnosis of colorectal cancer (CRC) are lacking. Our study sought to determine the incidence of BM in CRC patients, median survival of patients with BM, and the risk factors of BM in CRC.Patients and methods: Patients diagnosed with CRC were identified using the Surveillance, Epidemiology, and End Results database. Multivariable logistic and Cox regression analyses were performed to identify predictors of the presence of BM at CRC diagnosis and the factors associated with poor survival. Kaplan–Meier analysis was used to estimate the survival difference between subgroups.Results: We identified 170,793 adult patients diagnosed with CRC between 2010 and 2013. From these patients, we identified 401 patients with BM at the time of CRC diagnosis, which represents 0.23% of the entire patient CRC cohort and 1.3% of the patients with metastatic disease to any site. Median survival of patients with BM was 7.0 months, and the survival could increase to 15.59 months if there was no metastasis to other organs. We found that extracranial metastases number, tumor site, and pathology type were associated with BM at CRC diagnosis.Conclusion: The findings of this study indicate the incidence and prognosis for patients with BM at the time of CRC diagnosis. Our findings lend support for positive treatment for BM without metastasis to other organs. Keywords: colorectal cancer, brain metastasis, tumor site, prognosis

Lei Yan,1,* Chuanwu Zhu,2,* Jing Li,3,* Liwen Chen,1 Yezhou Ding,1 Zhujun Cao,1 Kehui Liu,1,4 Lanyi Lin,1 Weiliang Tang,1 Qing Xie,1 Yumin Xu,1 Shisan Bao,5 Hui Wang1 1Department of Infectious Diseases, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; 2Department of Infectious Diseases, The Fifth People’s Hospital of Suzhou, Jiangsu 215007, China; 3Department of Infectious Diseases, Huai-An Fourth People’s Hospital, Jiangsu 223002, China; 4Department of Infectious Diseases, Rui Jin Hospital North, Shanghai Jiao Tong University School of Medicine, Shanghai 201801, China; 5Discipline of Pathology, School of Medical Sciences and Bosch Institute, Charles Perkin Centre, University of Sydney, Sydney, NSW, Australia *These authors contributed equally to this work Background and aims: Chronic hepatitis B (CHB) patients rarely achieve hepatitis B surface antigen (HBsAg) loss with nucleoside/nucleotide analog therapy. Methods: In this retrospective study, it was evaluated that the rate of HBsAg loss in the HBe antigen negative (HBeAg−) patients (n=101) treated with entecavir (ETV) for ≥24 weeks followed by switching to (n=22) or adding on (n=26) pegylated interferon (PEG-IFN), and continuing ETV (n=53). Results: HBsAg clearance rate at week 48 was 9% (2/22), 15% (4/26), and 0% (0/53) (P1 log IU/mL at week 48) in the switch-to, add-on, and ETV monotherapy CHB patients was 60%, 40%, and 2%, respectively (P0.2 log IU/mL. Keywords: chronic hepatitis B, HBsAg, PEG-IFN, entecavir, switch-to, add-on

Jian Gong,1 Huiyan Wang,1 Wenwen Lou,1 Guiye Wang,1 Hongqun Tao,1 Huaikai Wen,1 Yu Liu,2 Qipeng Xie1 1Department of Laboratory Medicine, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, People’s Republic of China; 2Department of Cardiothoracic Surgery, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325035, People’s Republic of China Background: Lung cancer is the leading cause of cancer-related death worldwide and it is critical to discover specific biomarkers to provide better individualized treatment and subsequently better prognosis. The sirtuins (SIRT1–7) have been reported to be involved in cancers including non-small cell lung cancer (NCSLC), however, the results are not consistent and not all the seven sirtuins are explored and compared. Methods: TCGA data was downloaded and used to investigate and compare the associations of sirtuins mRNA levels with clinicopathological parameters and prognosis in NSCLC. Results: Our results suggested SIRT1, SIRT3, SIRT4, and SIRT7 were highly expressed in adenocarcinoma (ADC) patients and female patients while SIRT5 were highly expressed in squamous cell carcinoma (SCC) patients and male patients. Associations of high SIRT7 with younger onset age, high SIRT1 with distant metastasis and low T stage, and high SIRT4 with high T stage and TNM stage were also found. Kaplan-Meier plot curves and univariate Cox proportional regression analyses indicated that high SIRT2, SIRT4, and SIRT6 expressions were associated with longer overall survival (OS) time. Multivariate analyses indicated that SIRT2 and SIRT6 were still associated with OS. For recurrence-free survival (RFS), high SIRT1 expression was significantly associated with shorter RFS time while high SIRT2-3 and SIRT5-7 expressions were associated with longer RFS time in univariate analyses. After adjusting the confounding factors, significant associations were still found in SIRT1-2 and SIRT5-7 but not in SIRT3. We also stratified the patients by combining SIRT1 and SIRT2 and revealed that the combination of SIRT1 and SIRT2 was a better prediction model for RFS in NSCLC. To preliminarily understand the potential mechanisms of sirtuins in NSCLC carcinogenesis, the genes co-expressed with sirtuins were analyzed and annotated. Conclusion: sirtuins might be the potential therapy targets and prognostic biomarkers in NSCLC. Keywords: sirtuins, NSCLC, clinical features, overall survival, recurrence-free survival

Xue Yuan,1,2 Qian Xie,1 Keyu Su,1 Zhijie Li,3 Dong Dong,3 Baojian Wu1,2 1Research Center for Biopharmaceutics and Pharmacokinetics, College of Pharmacy, 2Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, 3International Ocular Surface Research Centre and Institute of Ophthalmology, School of Medicine, Jinan University, Guangzhou, China Abstract: Arenobufagin (ABG) is a major active component of toad venom, a traditional Chinese medicine used for cancer therapy. However, poor aqueous solubility limits its pharmacological studies in vivo due to administration difficulties. In this study, we aimed to develop a polymeric nanomicelle (PN) system to enhance the solubility of ABG for effective intravenous delivery. ABG-loaded PNs (ABG-PNs) were prepared with methoxy poly (ethylene glycol)-block-poly (D,L-lactic-co-glycolic acid) (mPEG-PLGA) using the solvent-diffusion technique. The obtained ABG-PNs were 105 nm in size with a small polydispersity index of 0.08. The entrapment efficiency and drug loading were 71.9% and 4.58%, respectively. Cellular uptake of ABG-PNs was controlled by specific clathrin-mediated endocytosis. In addition, ABG-PNs showed improved drug pharmacokinetics with an increased area under the curve value (a 1.73-fold increase) and a decreased elimination clearance (37.8% decrease). The nanomicelles showed increased drug concentrations in the liver and lung. In contrast, drug concentrations in both heart and brain were decreased. Moreover, the nanomicelles enhanced the anticancer effect of the pure drug probably via increased cellular uptake of drug molecules. In conclusion, the mPEG-PLGA-based nanomicelle system is a satisfactory carrier for the systemic delivery of ABG. Keywords: bufanolide steroid, arenobufagin, nanomicelles, mPEG-PLGA

Zi Wang,1,* Ming Lin,1,* Qing Xie,1 Hao Sun,1 Yazhuo Huang,1 DanDan Zhang,1 Zhang Yu,1 Xiaoping Bi,1 Junzhao Chen,1 Jing Wang,2 Wodong Shi,1 Ping Gu,1 Xianqun Fan1 1Department of Ophthalmology, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, 2Biomaterials and Tissue Engineering Laboratory, College of Chemistry & Chemical Engineering and Biotechnology, Donghua University, Shanghai, People’s Republic of China *These authors contributed equally to this work Background: Tissue engineering has become a promising therapeutic approach for bone regeneration. Nanofibrous scaffolds have attracted great interest mainly due to their structural similarity to natural extracellular matrix (ECM). Poly(lactide-co-ε-caprolactone) (PLCL) has been successfully used in bone regeneration, but PLCL polymers are inert and lack natural cell recognition sites, and the surface of PLCL scaffold is hydrophobic. Silk fibroin (SF) is a kind of natural polymer with inherent bioactivity, and supports mesenchymal stem cell attachment, osteogenesis, and ECM deposition. Therefore, we fabricated hybrid nanofibrous scaffolds by adding different weight ratios of SF to PLCL in order to find a scaffold with improved properties for bone regeneration.Methods: Hybrid nanofibrous scaffolds were fabricated by blending different weight ratios of SF with PLCL. Human adipose-derived stem cells (hADSCs) were seeded on SF/PLCL nanofibrous scaffolds of various ratios for a systematic evaluation of cell adhesion, proliferation, cytotoxicity, and osteogenic differentiation; the efficacy of the composite of hADSCs and scaffolds in repairing critical-sized calvarial defects in rats was investigated.Results: The SF/PLCL (50/50) scaffold exhibited favorable tensile strength, surface roughness, and hydrophilicity, which facilitated cell adhesion and proliferation. Moreover, the SF/PLCL (50/50) scaffold promoted the osteogenic differentiation of hADSCs by elevating the expression levels of osteogenic marker genes such as BSP, Ocn, Col1A1, and OPN and enhanced ECM mineralization. In vivo assays showed that SF/PLCL (50/50) scaffold improved the repair of the critical-sized calvarial defect in rats, resulting in increased bone volume, higher trabecular number, enhanced bone mineral density, and increased new bone areas, compared with the pure PLCL scaffold.Conclusion: The SF/PLCL (50/50) nanofibrous scaffold facilitated hADSC proliferation and osteogenic differentiation in vitro and further promoted new bone formation in vivo, suggesting that the SF/PLCL (50/50) nanofibrous scaffold holds great potential in bone tissue regeneration. Keywords: human adipose-derived mesenchymal stem cells, silk fibrin, poly(lactide-co-ε-caprolactone), proliferation, osteogenesis

Qingwen Xie,1 Tian Zhou,2 Lawrence Yen,2 Mina Shariff,3 Tuong Nguyen,3 Kenneth Kami,3 Pingping Gu,3 Liang Liang,2 Jianyu Rao,2 Rong Shi1 1Department of Preventive Medicine, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China; 2Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California at Los Angeles, 3Department of Research, DRM Resources, Costa Mesa, CA, USA Background: Osteoarthritis is a common chronic disease affecting aged populations. Conventional therapies tend to result in side effects when used long-term. Arthro-7® (Robinson Pharma, Orange County, CA, USA) has been used by osteoarthritis patients for more than 10 years in the USA and has showed promising effects at relieving osteoarthritis-related symptoms. A previous small, double-blind study has shown some positive effects of Arthro-7 in relieving symptoms of osteoarthritis. The current study was performed specifically in osteoarthritis patients with mild to moderate arthralgia. Methods: A total of 100 subjects over the age of 50 years old who were diagnosed with osteoarthritis and had at least one of the related symptoms were recruited to the study. After primary evaluation, 64 eligible males and females with mild or moderate degrees of arthralgia were randomly assigned 12-week treatment with either Arthro-7 or placebo. The primary outcome measurement was changes in the scores of the related symptoms before and after treatment, using the modified Western Ontario and McMaster Universities Arthritis Index (WOMAC) 3.1 questionnaire. Prior to and at the end of the study, evaluations of symptom scores were recorded. Additionally, self-reported overall changes were recorded at the end of 2, 4, and 8 weeks of treatment and at the end of the study (12 weeks). Results: Arthro-7 improved most symptoms significantly compared with placebo, as indicated by significant reductions in symptom scores. In the Arthro-7 group, 74.5% of the participants reported symptom improvement over the study period versus only 16.3% in the placebo group. Conclusion: In this study, Arthro-7 has shown potent effects in improving and relieving osteoarthritis-related symptoms, particularly joint pain, anchylosis, and difficulty going down stairs. Keywords: joint pain, anchylosis, arthroncus, WOMAC 3.1

Shanyuan Zheng,1,2 Xiaoling Li,1 Yibo Zhang,1 Qiang Xie,3 Yum-Shing Wong,2 Wenjie Zheng,1 Tianfeng Chen,1,3,41Department of Chemistry, Jinan University, Guangzhou, China; 2School of Life Sciences, The Chinese University of Hong Kong, Hong Kong, China; 3Wu Jing Zong Dui Hospital of Guangdong Province, Guangzhou, China; 4State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou, ChinaAbstract: Gray selenium (Se) is one of the most widely used Se sources with very limited biocompatibility and bioactivity. In the present study, a simple method for the preparation of ultrasmall selenium nanoparticles (SeNPs) through direct nanolization of gray selenium by polyethylene glycol (PEG) was demonstrated. Monodisperse and homogeneous PEG-SeNPs with ultrasmall diameters were successfully prepared under optimized conditions. The products were characterized using various microscopic and spectroscopic methods, and the results suggest that the amphoteric properties of PEG and the coordination between oxygen and selenium atoms contributed to the formation of ultrasmall nanoparticles. PEG-SeNPs exhibited stronger growth inhibition on drug-resistant hepatocellular carcinoma (R-HepG2) cells than on normal HepG2 cells. Dose-dependent apoptosis was induced by PEG-SeNPs in R-HepG2 cells, as evidenced by an increase in the sub-G1 cell population. Further investigation on the underlying molecular mechanisms revealed that depletion of mitochondrial membrane potential and generation of superoxide anions contributed to PEG-SeNPs-induced apoptotic cell death in R-HepG2 cells. Our results suggest that PEG-SeNPs may be a candidate for further evaluation as a chemotherapeutic agent for drug-resistant liver cancer, and the strategy to use PEG200 as a surface decorator could be a highly efficient way to enhance the anticancer efficacy of nanomaterials.Keywords: selenium, PEG, nanolization, drug resistance, apoptosis

Wenrui Wang,1,* Rongrong Zhu,1,* Qian Xie,1 Ang Li,1 Yu Xiao,1 Kun Li,1 Hui Liu,2 Daxiang Cui,3 Yihan Chen,1 Shilong Wang11East Hospital, School of Life Science and Technology, Tongji University, Shanghai, People’s Republic of China; 2Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, People’s Republic of China; 3National Key Laboratory of Nano/Micro Fabrication Technology, Shanghai Jiao Tong University, Shanghai, People’s Republic of China*These authors contributed equally to this studyAbstract: Curcumin has shown considerable pharmacological activity, including anti-inflammatory, but its poor bioavailability and rapid metabolization have limited its application. The purpose of the present study was to formulate curcumin-solid lipid nanoparticles (curcumin-SLNs) to improve its therapeutic efficacy in an ovalbumin (OVA)-induced allergic rat model of asthma. A solvent injection method was used to prepare the curcumin-SLNs. Physiochemical properties of curcumin-SLNs were characterized, and release experiments were performed in vitro. The pharmacokinetics in tissue distribution was studied in mice, and the therapeutic effect of the formulation was evaluated in the model. The prepared formulation showed an average size of 190 nm with a zeta potential value of -20.7 mV and 75% drug entrapment efficiency. X-ray diffraction analysis revealed the amorphous nature of the encapsulated curcumin. The release profile of curcumin-SLNs was an initial burst followed by sustained release. The curcumin concentrations in plasma suspension were significantly higher than those obtained with curcumin alone. Following administration of the curcumin-SLNs, all the tissue concentrations of curcumin increased, especially in lung and liver. In the animal model of asthma, curcumin-SLNs effectively suppressed airway hyperresponsiveness and inflammatory cell infiltration and also significantly inhibited the expression of T-helper-2-type cytokines, such as interleukin-4 and interleukin-13, in bronchoalveolar lavage fluid compared to the asthma group and curcumin-treated group. These observations implied that curcumin-SLNs could be a promising candidate for asthma therapy.Keywords: airway hyperresponsiveness, pharmacokinetics, curcumin, solid lipid nanoparticles

Abstract Background The completion of the sequencing of human, mouse and rat genomes and knowledge of cross-species gene homologies enables studies of differential gene expression in animal models. These types of studies have the potential to greatly enhance our understanding of diseases such as liver cancer in humans. Genes co-expressed across multiple species are most likely to have conserved functions. We have used various bioinformatics approaches to examine microarray expression profiles from liver neoplasms that arise in albumin-SV40 transgenic rats to elucidate genes, chromosome aberrations and pathways that might be associated with human liver cancer. Results In this study, we first identified 2223 differentially expressed genes by comparing gene expression profiles for two control, two adenoma and two carcinoma samples using an F-test. These genes were subsequently mapped to the rat chromosomes using a novel visualization tool, the Chromosome Plot. Using the same plot, we further mapped the significant genes to orthologous chromosomal locations in human and mouse. Many genes expressed in rat 1q that are amplified in rat liver cancer map to the human chromosomes 10, 11 and 19 and to the mouse chromosomes 7, 17 and 19, which have been implicated in studies of human and mouse liver cancer. Using Comparative Genomics Microarray Analysis (CGMA), we identified regions of potential aberrations in human. Lastly, a pathway analysis was conducted to predict altered human pathways based on statistical analysis and extrapolation from the rat data. All of the identified pathways have been known to be important in the etiology of human liver cancer, including cell cycle control, cell growth and differentiation, apoptosis, transcriptional regulation, and protein metabolism. Conclusion The study demonstrates that the hepatic gene expression profiles from the albumin-SV40 transgenic rat model revealed genes, pathways and chromosome alterations consistent with experimental and clinical research in human liver cancer. The bioinformatics tools presented in this paper are essential for cross species extrapolation and mapping of microarray data, its analysis and interpretation.

Eu2Ge3Li1.16Mg0.84, orthorhombic, Cmcm (no. 63), a = 4.577(1) Å, b = 19.534(4) Å, c = 7.223(2) Å, V = 645.7 Å3, Z = 4, Rgt(F) = 0.030, wRref(F2) = 0.072, T = 293 K.

Ge2LiYb, orthorhombic, Pnma (no. 62), a = 7.939(2) Å, b = 3.882(1) Å, c = 10.524(3) Å, V = 324.4 Å3, Z = 4, Rgt(F) = 0.030, wRref(F2) = 0.064, T = 293 K.

Eu2Ge3Li, orthorhombic, Pnnm (no. 58), a = 10.968(2) Å, b = 11.687(2) Å, c = 4.5482(7) Å, V = 583.0 Å3, Z = 4, Rgt(F) = 0.023, wRref(F2) = 0.048, T = 293 K.