Search

Juncai Lv,1,* Weiwei Yan,1,* Ran Zhang,1 Xi Chen,1,2 Ziyuan Ren,1,2 Dawei Chen,1 Jinming Yu1 1Department of Radiation Oncology and Shandong Provincial Key Laboratory of Precision Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, People’s Republic of China; 2Cheeloo College of Medicine, Shandong University Cancer Center, Jinan, Shandong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jinming Yu; Dawei Chen, Department of Radiation Oncology and Shandong Provincial Key Laboratory of Precision Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, People’s Republic of China, Tel +86-531-8798-4777, Fax +86-531-8798-4079, Email sdyujinming@163.com; dave0505@yeah.netPurpose: There exists a dearth of research concerning non-small cell lung cancer (NSCLC) patients experiencing overall progressive disease concomitant with shrinking lesions after immunotherapy. This is a special type of mixed response. We aim to evaluate the clinical characteristics and treatment options of these patients during immunotherapy.Patients and Methods: We categorized patients into two groups: Progressive Disease with Mixed Responses (PDMR) (n = 31) and Progressive Disease with None Mixed Responses (PDNMR) (n = 144), depending on whether at least one target lesion had shrunk by ≥ 30% at the point of overall progression. Computed tomography scans and magnetic resonance imaging were utilized to evaluate the clinicopathological significance of these patients, and a multivariate analysis was conducted to scrutinize the clinical characteristics and prognosis-influencing factors in these patients.Results: Patients in the PDMR group had worse staging and a greater proportion of previous radiotherapy. The median overall survival (mOS 22 vs 36.4 months; P = 0.019) and median progression-free survival (mPFS 5.83 vs 9.03 months; P = 0.031) of the PDMR group were shorter than PDNMR group. Longer subsequent OS with continued immunotherapy after PDMR compared with patients who do not continue with immunization after PDMR (mOS 23.9 vs 6.5 months; P = 0.024).Conclusion: PDMR was primarily observed in stage IV patients and previously irradiated patients. OS and PFS were inferior in patients with PDMR compared to patients with PDNMR. The continuation of immunotherapy in PDMR patients could extend their survival.Keywords: non-small cell lung cancer, immunotherapy, mixed response, progression

Kaiyue Zhang, Chunnan Li, Peitong Wu, Xiaochen Gao, Xueqin Feng, Jiaming Shen, Nanxi Zhang, Xuesheng Hu, Shuo Wang, Hui Zhang, Jingwei Lv, Jiaming Sun Jilin Ginseng Academy, Changchun University of Chinese Medicine, Changchun, Jilin, People’s Republic of ChinaCorrespondence: Jiaming Sun; Jingwei Lv, Changchun University of Chinese Medicine, No. 1035, Boshuo Road, Nanguan District, Changchun, 130117, People’s Republic of China, Tel +0431-86763809, Fax + 8676 3968, Email Sun_jiaming2000@163.com; jingwei-lv@hotmail.comPurpose: Zhixiao Tang (ZXT), a traditional Chinese compound prescription, has been used clinically to treat pneumonia in China. However, the underlying mechanism of ZXT treatment in pneumonia is still unclear. The present study aimed to reveal the potential mechanism of ZXT in pneumonia using a strategy combining metabolomics and network pharmacology.Methods: Initially, the chemical compositions were identified by UPLC-QE-Orbitrap-MS, while the prediction of potential signal pathways was performed through network pharmacology. To assess the anti-inflammatory properties of ZXT in the context of pneumonia, models of 16HBE cells induced by LPS and zebrafish induced by CuSO4 were established to measure levels of inflammatory markers and apoptosis. Subsequently, the differential changes of endogenous metabolites in cells caused by ZXT were examined using metabolomics technology, and the molecular docking analysis of key targets was carried out using Autodock Vina software. Ultimately, the validation of the primary pathways and targets was conducted through quantitative RT-PCR and Western blot techniques.Results: A total of 75 compounds were identified through UPLC-QE-Orbitrap-MS analyses. Network pharmacological analysis shows that it plays an anti-inflammatory role in C-type lectin receptor signaling pathway. After ZXT intervention, the inflammatory factors and apoptosis in cells were significantly reduced. Metabonomics analysis showed that 18 metabolites changed significantly. Four key genes were identified, which exhibited partial compatibility with the findings of network pharmacology. Molecular docking analysis confirmed the substantial affinity of the primary targets for ZXT. Furthermore, ZXT exerted a suppressive effect on neutrophil migration, down-regulated the expression of pro-inflammatory cytokine genes, and inhibited the up-regulation of the Dectin-1/SYK/NF-κB signaling pathway. In vivo cell experiments also yielded consistent experimental outcomes.Conclusion: This study enhances comprehension of the pharmacological mechanism underlying ZXT’s efficacy in pneumonia treatment, thereby establishing a scholarly basis for future research and clinical utilization of ZXT in pneumonia management. Keywords: Zhixiao Tang, pneumonia, network pharmacology, integrated metabolomics, 16HBE, Zebrafish

Yunhan Zhang,1,&ast; Yuyun Chen,2,&ast; Jilin Lv,1 Xiao Xiang,1 Peiyao Wang,1 Wei Feng,1 Zhenhua Guo1 1Department of Neonatal Surgery, Children’s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development, Chongqing Key Laboratory of Structural Birth Defect and Reconstruction, Chongqing, People’s Republic of China; 2Fujian Children’s Hospital, Fujian Branch of Shanghai Children’s Medical Center, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, People’s Republic of China&ast;These authors have contributed equally to this workCorrespondence: Zhenhua Guo, Department of neonatal surgery, Children’s Hospital of Chongqing Medical University, 20 Jinyu Road, Yubei District, Chongqing, 400025, People’s Republic of China, Tel +86-23-68370286, Email zhguo@cqmu.edu.cnBackground: This study aims to investigate the potential significance of mean platelet volume (MPV) and platelet distribution width (PDW) in predicting surgical neonatal necrotizing enterocolitis (NEC) and establish the correlation between MPV/PDW levels and the severity/prognosis of NEC.Methods: A retrospective study was conducted on a cohort of 372 patients diagnosed with NEC. The patients were categorized into two groups based on whether they underwent surgical therapy. Univariate /multivariate analysis were employed to compare the MPV and PDW between the two groups. Moreover, patients in surgical group were categorized into multiple subgroups based on intraoperative findings and postoperative prognosis, and the levels of MPV and PDW were compared among these subgroups.Results: Of the 372 patients, the operative group exhibited significantly higher levels of MPV and PDW than the nonoperative group (P < 0.05). Logistic regression analysis revealed that MPV (OR = 4.895, P < 0.001) and PDW (OR = 1.476, P < 0.001) independently associated with surgical NEC. The analysis of the receiver operating characteristic (ROC) curve revealed that the area under the curve (AUC) was 0.706 for MPV alone, with a cut-off value of 11.8 fL. Similarly, the AUC was 0.728 for PDW alone, with a cut-off value of 16%. However, when MPV and PDW were combined, the AUC increased to 0.906 for predicting surgical NEC. In accordance with the intraoperative findings, the levels of MPV and PDW were found to be higher in the large area necrosis group than in the partial or mild necrosis group (P < 0.01). Furthermore, the MPV and PDW values in the death group were significantly greater than those in the survival group (P =0.040, P =0.008).Conclusion: MPV and PDW may serve as potentially valuable indicators for determining the need for surgical intervention and predicting the prognosis of patients with NEC.Keywords: mean platelet volume, platelet distribution width, necrotizing enterocolitis, neonatal

Yumei Wu,1– 3,&ast; Chunhua Zeng,1– 3,&ast; Jiajia Lv,1– 3 Hongyu Li,1– 3 Jie Gao,1– 3 Zhidong Liu,4 Zeli Yuan1– 3 1Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, 563000, People’s Republic of China; 2Key Laboratory of Biocatalysis & Chiral Drug Synthesis of Guizhou Province, School of Pharmacy, Zunyi Medical University, Zunyi, 563000, People’s Republic of China; 3Guizhou International Scientific and Technological Cooperation Base for Medical Photo-Theranostics Technology and Innovative Drug Development, Zunyi Medical University, Zunyi, 563000, People’s Republic of China; 4Engineering Research Center of Modern Chinese Medicine Discovery and Preparation Technique, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhidong Liu, Tianjin University of Traditional Chinese Medicine, No. 10 Poyanghu Road, Tianjin, Jinghai District, 301617, People’s Republic of China, Email lonerliuzd@163.com Zeli Yuan, Zunyi Medical University, Zunyi, 563000, People’s Republic of China, Email zlyuan@zmu.edu.cnBackground: Combination therapy offers superior therapeutic results compared to monotherapy. However, the outcomes of combination therapy often fall short of expectations, mainly because of increased toxicity from drug interactions and challenges in achieving the desired spatial and temporal distribution of drug delivery. Optimizing synergistic drug combination ratios to ensure uniform targeting and distribution across space and time, particularly in vivo, is a significant challenge. In this study, cRGD-coated liposomes encapsulating optimized synergistic cepharanthine (CEP; a chemotherapy drug) and IR783 (a phototherapy agent) were developed for combined chemotherapy and photothermal therapy in vitro and in vivo.Methods: An MTT assay was used to evaluate the combination index of CEP and IR783 in five cell lines. The cRGD-encapsulated liposomes were prepared via thin-film hydration, and unencapsulated liposomes served as controls for the loading of CEP and IR783. Fluorescence and photothermal imaging were used to assess the efficacy of CEP and IR783 encapsulated in liposomes at an optimal synergistic ratio, both in vitro and in vivo.Results: The combination indices of CEP and IR783 were determined in five cell lines. As a proof-of-concept, the optimal synergistic ratio (1:2) of CEP to IR783 in 4T1 cells was evaluated in vitro and in vivo. The average diameter of the liposomes was approximately 100 nm. The liposomes effectively retained the encapsulated CEP and IR783 in vitro at the optimal synergistic molar ratio for over 7 d. In vivo fluorescence imaging revealed that the fluorescence signal from cRGD-CEP-IR783-Lip was detectable at the tumor site at 4 h post-injection and peaked at 8 h. In vivo photothermal imaging of tumor-bearing mice indicated an increase in tumor temperature by 32°C within 200 s. Concurrently, cRGD-CEP-IR783-Lip demonstrated a significant therapeutic effect and robust biosafety in the in vivo antitumor experiments.Conclusion: The combination indices of CEP and IR783 were successfully determined in vitro in five cell lines. The cRGD-coated liposomes encapsulated CEP and IR783 at an optimal synergistic ratio, exhibiting enhanced antitumor effects and targeting upon application in vitro and in vivo. This study presents a novel concept and establishes a research framework for synergistic chemotherapy and phototherapy treatment. Keywords: drug delivery, liposomes, synergistic effects, phototherapy

Xiaoqian Shang,1,&ast; Naifeisha Maimaiti,1,&ast; Jiahui Fan,1 Liang Wang,2 Yuanyuan Wang,3 Hu Sun,3 Jie Lv,1 Xiufeng Zhang,4 Jing Wang,4 Xiumin Ma1 1State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Clinical Laboratory Center, Tumor Hospital Affiliated to Xinjiang Medical University, Urumqi, Xinjiang, 830011, People’s Republic of China; 2The Fifth Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, 830011, People’s Republic of China; 3First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, 830011, People’s Republic of China; 4Department of Respiratory Medicine, Second Affiliated Hospital of Hainan Medical University, Haikou, Hainan, 570100, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiumin Ma, State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Clinical Laboratory Center, Tumor Hospital Affiliated to Xinjiang Medical University, Urumqi, Xinjiang, 830011, People’s Republic of China, Email maxiumin1210@sohu.com Jing Wang, Department of Respiratory Medicine, Second Affiliated Hospital of Hainan Medical University, Haikou, Hainan, 570100, People’s Republic of China, Email tlfwj@163.comBackground: Macrophage play a significant work in the development of tuberculosis. This study aims to investigate the relationship between TREM2 and macrophage polarization, as well as the related cytokines.Methods: This study involved 43 pulmonary tuberculosis patients and 37 healthy controls. Enzyme-linked immunosorbent assay (ELISA) was used to detect the expression levels of M1/M2 macrophage-related cytokines IL-10 and IL-12 in the peripheral blood of pulmonary tuberculosis patients. The relative mRNA expression levels of TREM2, IL-10 and IL-12 were detected using quantitative real-time PCR (qRT-PCR). Additionally, Spearman rank correlation analysis was used to preliminarily assess the correlation between TREM2 and M1 / M2 macrophages. Hematoxylin-eosin (HE) staining was performed to observe the pathological manifestations of pulmonary tuberculosis lesions. Immunohistochemical (IHC) staining was used to observe the localization of the macrophage-specific molecule CD68, the M1 specific molecule iNOS, the M2 specific molecule CD163, and TREM2.Results: The lesions of pulmonary tuberculosis patients showed Langhans multinucleated macrophages and tuberculous granulomas. The ELISA results indicated that the expression levels of IL-10 and IL-12 were significantly increased in peripheral blood of pulmonary tuberculosis patients. Additionally, the relative mRNA expression levels of TREM2, IL-10 and IL-12 were also significantly higher in the pulmonary tuberculosis group. Furthermore, a positive correlation was observed between TREM2 and IL-10, which are secreted by M2 macrophages. IHC revealed significant positivity of TREM2 and macrophage-related markers in tuberculous granuloma. Specifically, TREM2 and M2 macrophage marker CD163 were significantly expressed in the cytoplasm and membrane of Langhans multinucleated macrophages.Conclusion: The role of macrophage polarization in pulmonary tuberculosis is significant, and further investigation is needed to understand relationship between TREM2 and M2 macrophages.Keywords: tuberculosis, TREM2, macrophage

Wei He,&ast; Quan Zhou,&ast; Jiaheng Lv,&ast; Yujie Shen, Hao Liu, Huilin Yang, Peng Yang, Tao Liu Department of Orthopaedics, The First Affiliated Hospital of Soochow University, Suzhou, 215006, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Peng Yang; Tao Liu, Department of Orthopaedics, The First Affiliated Hospital of Soochow University, No. 899 Pinhai Road, Suzhou, Jiangsu, 215006, People’s Republic of China, Tel +86-512-67781420, Fax +86-512-67781165, Email ypspine@163.com; liutao821108@163.comBackground: Few studies have focused on percutaneous kyphoplasty (PKP) in the treatment of thoracic osteoporotic vertebral compression fractures (OVCFs) with intervertebral cleft (IVC). Hence, the objective of this retrospective study was to compare the clinical and radiographic outcomes of PKP in elderly patients with thoracic OVCFs, with or without IVC.Methods: A total of 106 patients were enrolled in this study and divided into two groups: the IVC group and the NIVC group (without IVC). Radiographic measures included anterior vertebral height (AVH), thoracic kyphosis (TK), lumbar lordosis (LL), pelvic incidence (PI), pelvic tilt (PT), and sacral slope (SS). Clinical function measures included Oswestry disability index (ODI) and visual analog scale (VAS) scores.Results: There were no significant differences in the preoperative basic data between the groups classified as IVC and NIVC. However, both groups showed significant improvements in AVH and TK throughout the follow-up periods compared to the preoperative measurements (P< 0.05). The recovery of AVH in the IVC group was found to be inferior to that in the NIVC group at 3 years after operation (P< 0.05). There were no significant differences in LL, PI, PT and SS in both groups compared with the preoperative results and no statistically significant differences between the two groups at the same follow-up time (P> 0.05). The VAS and ODI scores during all follow-up periods were significantly lower than those before operation (P< 0.05). At 3 years after operation, the VAS and ODI scores of the IVC group were higher than those of the NIVC group (P< 0.05).Conclusion: PKP is an adoptable measure to treat thoracic OVCFs with or without IVC. Our study revealed that the NIVC group was superior to the IVC group in terms of improved vertebral height and pain recovery at long-term follow-up (3 years).Keywords: percutaneous kyphoplasty, thoracic, osteoporotic vertebral compression fracture, intervertebral cleft, sagittal balance

Cong Xia,1 Ting Wei,2,3 Qi Tang,2,3 Hongying Zheng,2,3 Mei Sun,2,3 Gang Chen,2,3 Jun Lv2,3 1School of Health Management Anhui Medical University, Hefei, People’s Republic of China; 2School of Public Health, Fudan University, Shanghai, People’s Republic of China; 3China Research Center on Disability, Fudan University, Shanghai, People’s Republic of ChinaCorrespondence: Gang Chen; Jun Lv, School of Public Health, Fudan University, 130 Dong’an Road, Xuhui District, Shanghai, 200032, People’s Republic of China, Tel +86-13661432703 ; +86-13671684324, Email gchen@shmu.edu.cn; lujun@shmu.edu.cnPurpose: To investigate the family support, anxiety, depression, health-related quality of life (HRQoL), and their associations among parents and grandparents of children with disabilities.Methods: This is a cross-sectional study and a total of 327 family caregivers were included. Chi-square test, Mann–Whitney U-test, and two independent t-test were used to identify the intergenerational differences in sociodemographic characteristics, received family support, anxiety, depression, and HRQoL. Eight generalized linear models were developed to examine the associations in both generations.Results: Parents and grandparents were most in need of rehabilitation and financial support, but both populations received the least amount of financial support. 33.6% and 36.1% of family caregivers had the risk of anxiety and depression and found no significant intergenerational differences. As for HRQoL, intergenerational differences were found in the physical component score, but not found in the mental component score. Among parents, childcare support of respite care and household tasks assistance was negatively associated with their depression (p< 0.05), professional support of appropriate surgery for children (p< 0.05) and psychological support from professional psychologists (p< 0.01) were negatively associated with their anxiety and depression, psychological support from relatives and friends was negatively associated with their depression (p< 0.05) whereas was positively associated with their mental HRQoL (p< 0.01). As for grandparents, financial support for daily living expenses was negatively associated with depression (p< 0.05), and psychological support from families was negatively associated with depression (p< 0.05) whereas was positively associated with mental HRQoL (p< 0.05). However, no relationship was found between family support and anxiety among grandparents. Notably, no association was found between family support and physical HRQoL among both populations.Conclusion: Both parents and grandparents had high risks of anxiety, depression and low levels of mental HRQoL. To efficiently improve psychological health, care providers and policymakers may consider intergenerational differences and provide targeted family support.Keywords: mental health, health-related quality of life, family support, children with disabilities, intergenerational differences

Kang Li,1,2,&ast; Xianhai Zeng,1,2,&ast; Peng Liu,1,2 Xiaoxia Zeng,2 Jie Lv,3 Shuqi Qiu,1,2 Peng Zhang1,2 1Department of Graduate and Scientific Research, Zunyi Medical University Zhuhai Campus, Zhuhai, Guangdong, People’s Republic of China; 2Department of Otorhinolaryngology, Longgang Otorhinolaryngology Hospital & Shenzhen Key Laboratory of Otorhinolaryngology, Shenzhen Institute of Otorhinolaryngology, Shenzhen, Guangdong, People’s Republic of China; 3School of Computer Science and Engineering, Yulin Normal University, Yulin, Guangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shuqi Qiu; Peng Zhang, Longgang Otorhinolaryngology Hospital & Shenzhen Key Laboratory of Otorhinolaryngology, Shenzhen Institute of Otorhinolaryngology, No. 3004 Longgang Avenue, Shenzhen, Guangdong, People’s Republic of China, Tel +86-755-28989999, Fax +86-755-28980505, Email qiuqi6685@163.com; zhangpeng2600@163.comAbstract: Head and neck squamous cell carcinoma (HNSCC), which originates in the head or neck tissues, is characterized by high rates of recurrence and metastasis. Inflammation is important in HNSCC prognosis. Inflammatory cells and their secreted factors contribute to the various stages of HNSCC development through multiple mechanisms. In this review, the mechanisms through which inflammatory factors, signaling pathways, and cells contribute to the initiation and progression of HNSCC have been discussed in detail. Furthermore, the diagnostic and therapeutic potential of targeting inflammation in HNSCC has been discussed to gain new insights into improving patient prognosis.Keywords: inflammation, head and neck squamous cell carcinoma, HNSCC, mediators, progression, therapy

Bili Liu, Dan Ge, Yue Shan, Yanping Li, Juan Lv, Shuzhi Gan Department of Ultrasound, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, 310007, People’s Republic of ChinaCorrespondence: Bili Liu, Department of Ultrasound, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, No. 453 Stadium Road, Xihu District, Hangzhou, Zhejiang Province, 310007, People’s Republic of China, Tel +86-057185827841, Email lbili_bl1@163.comObjective: Based on the analysis of the images of acromial slide, we explored the application of percutaneous ultrasound-guided subacromial bursography (PUSB) on rotator cuff tear (RCT) in diagnosing elderly patients with shoulder pain.Methods: Eighty-five patients who were clinically diagnosed with RCT and underwent PUSB examination in the department of ultrasound in our hospital were enrolled as the subjects. Independent samples t-test was used to analyze the general characteristics. Based on the gold standard of shoulder arthroscopy, the diagnostic efficacy of ultrasound, magnetic resonance imaging (MRI), and PUSB was evaluated. The sensitivity, specificity, positive and negative predictive values, and accuracy were calculated as well. The consistency of these techniques with shoulder arthroscopy in diagnosing the RCT stage was additionally compared using Kappa test.Results: In patients with large full-thickness RCT, the 100% detection rate was achieved by the techniques of ultrasound, MRI, and PUSB. For patients with small full-thickness RCT, the detection rate of PUSB (100%) was evidently higher than those of ultrasound and MRI. Similar results were shown in the detection rates of patients with bursal-side partial-thickness RCT (90.5%) and articular-side partial-thickness RCT (86.9%). More importantly, the sensitivity, specificity, and accuracy of PUSB in patients with both full-thickness RCT and partial-thickness RCT were significantly better than those of ultrasound and MRI.Conclusion: PUSB has a better efficacy in the detection of RCT than ultrasound and MRI, showing its feasibility as an important imaging method to evaluate the degree of RCT.Keywords: rotator cuff tear, percutaneous ultrasound-guided subacromial bursography, shoulder pain, acromial slide cystography, diagnosis

Jingyu Lv,1,&ast; Qing Qiu,2,&ast; Baojuan Ye,1,&ast; Qiang Yang1 1Center of Mental Health Education and Research, School of Psychology, School of Education, Jiangxi Normal University, Nanchang, People’s Republic of China; 2School of Intercultural Studies, Post-Doctoral Research Station of Psychology, Jiangxi Normal University, Nanchang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qing Qiu, Jiangxi Normal University, 99 Ziyang Avenue, Nanchang, 330022, People’s Republic of China, Tel +86-185-79113027, Email qiuqing26@qq.comPurpose: The COVID-19 pandemic had triggered a serious crisis that had brought stress and challenges to primary school principals, as well as having a dramatic impact on their mental health. This study explored the relationship between cognitive fusion and depression among primary school principals during COVID-19, as well as the mediating role of psychological vulnerability and the moderation role of self-esteem in this process.Patients and Methods: Cognitive Fusion Questionnaire (CFQ), Center for Epidemiological Studies Depression Scale (CES-D), psychological vulnerability scale, and self-esteem scale were used to measure 279 rural primary school principals. The data were analyzed by adopting Pearson’s correlations and moderated mediation analysis.Results: The results revealed that: (1) There were significant relationships among cognitive fusion, depression, psychological vulnerability and self-esteem. (2) The results showed that psychological vulnerability mediated the link between cognitive fusion and depression. (3) Self-esteem moderated the associations between cognitive fusion and depression, and also moderated the associations between cognitive fusion and psychological vulnerability. The relationship between cognitive fusion and depression was weaker for primary school principals with high levels of self-esteem. In contrast, the relationship between cognitive fusion and psychological vulnerability was stronger for primary school principals with low levels of self-esteem.Conclusion: Psychological vulnerability played a mediating role in the relationship between cognitive fusion and depression. Moreover, self-esteem moderated the effect of cognitive fusion on depression, and also the effect of cognitive fusion on psychological vulnerability.Keywords: COVID-19 pandemic, cognitive fusion, psychological vulnerability, depression, self-esteem, primary school principals

Zhang W, Yang X, Lv J, An S. Clin Cosmet Investig Dermatol. 2022;15:97–105. We, the Editors and Publisher of Clinical, Cosmetic and Investigational Dermatology, have retracted the following article. Following publication of the article, concerns were raised about the duplication of images from Figure 4 with images from other unrelated articles. Specifically, Images for Figure 4A and 4B have been duplicated with images in Figure 4A from Xu L, Ni N, Gao H, Hu P. MicroRNA‑1301‑3p promotes the progression of non‑small cell lung cancer by targeting Thy‑1 and predicts poor prognosis of patients. Oncology Letters. 2021;21:327. https://doi.org/10.3892/ol.2021.12589; Figure 4A from Dong A, Zhang J, Sun W, Hua H, Sun Y. Upregulation of miR-421 predicts poor prognosis and promotes proliferation, migration, and invasion of papillary thyroid cancer cells. Journal of the Chinese Medical Association. 2020;83(11):991–996. https://doi.org/10.1097/JCMA.0000000000000426; and Figure 4a from Long K, Zeng Q, Dong W. The clinical significance of microRNA-409 in pancreatic carcinoma and associated tumor cellular functions. Bioengineered. 2021;12(1):4633–4642. https://doi.org/10.1080/21655979.2021.1956404. The authors did not respond to our queries and were unable to provide an explanation for the duplicated images or provide data for the study. As verifying the validity of published work is core to the integrity of the scholarly record, we are therefore retracting the article and the authors were notified of this. We have been informed in our decision-making by our editorial policies and COPE guidelines. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as ‘Retracted’.

Yicheng Wen,1,&ast; Xiaofang Xie,1,&ast; Ping Xu,2,&ast; Chengcheng Yang,1 Zhichen Zhu,1 Jie Zhu,1 Jingnan Lv,1 Haifang Zhang,1 Liang Chen,3,4 Hong Du1 1Department of Clinical Laboratory, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, People’s Republic of China; 2Department of Clinical Laboratory, The Fifth People’s Hospital of Suzhou, Suzhou, Jiangsu, People’s Republic of China; 3Hackensack Meridian Health Center for Discovery and Innovation, Nutley, NJ, USA; 4Department of Medical Sciences, Hackensack Meridian School of Medicine, Nutley, NJ, USA&ast;These authors contributed equally to this workCorrespondence: Hong Du, Department of Clinical Laboratory, The Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Suzhou, Jiangsu, People’s Republic of China, Email hong_du@126.comBackground: Shewanella genus, as an important carrier of resistance genes, has the potential to transmit resistance to many antimicrobials in many circumstances, especially in aquatic environment. The aim of the study was to describe the risk of Shewanella xiamenensis in hospital environment through analysis of genomic comparison and resistance status.Methods: Seven S. xiamenensis strains were isolated from hospital wastewater. PCR and Sanger sequencing were carried out for detection of common carbapenemase genes. Antimicrobial susceptibility testing was performed to determine the antimicrobial profile. Whole genome sequencing was applied, and sequences were further used for genomic analysis.Results: Seven Shewanella xiamenensis were all positive for blaNDM and blaOXA-48. Antimicrobial susceptibility testing showed all Shewanella xiamenensis were resistant to cefotaxime, ceftazidime, imipenem, meropenem, gentamycin and trimethoprim-sulfamethoxazole. Whole genome sequencing and phylogenetic analysis demonstrated the diversity of Shewanella xiamenensis despite isolating from one wastewater pool.Conclusion: To the best of our knowledge, this is the first report of detection of three types blaOXA-48-like genes in one hospital in China. And we have detected multi-drug resistant S. xiamenensis from hospital wastewater. This emphasizes that the presence of naturally existing carbapenemases in the environment may be significantly overlooked and that the blaOXA-48-like genes in China may originate through the horizontal gene transfer from S. xiamenensis to Enterobacterales rather than import from other countries.Keywords: OXA-48, NDM, Shewanella xiamenensis, hospital wastewater, reservoir, horizontal transmission, surveillance, New Delhi metallo-β-Lactamase

Jinchang Lv, Biao Hou, Jiangang Song, Yunhua Xu, Songlin Xie Department of Hand and Foot Microsurgery, The affiliated Nanhua Hospital of University of South China, Hengyang, People’s Republic of ChinaCorrespondence: Songlin Xie, Department of Hand and Foot Microsurgery, The affiliated Nanhua Hospital of the University of South China, Hengyang, People’s Republic of China, Tel +86 13975404959, Email xiesonglin0929@163.comAbstract: Ferroptosis is an iron-dependent mode of cell death. It can occur through two major pathways, exogenous (or transporter-dependent) and endogenous (or enzyme-regulated) pathways are activated by biological or chemical inducers, and glutathione peroxidase activity is inhibited, which causes intracellular iron accumulation and lipid Peroxidation. Ferroptosis is closely related to the pathological process of many diseases. How to intervene in the occurrence and development of related diseases by regulating ferroptosis has become a hot research topic. At present, studies have shown that ferroptosis is found in common diseases such as tumors, inflammatory diseases, bacterial infections, pulmonary fibrosis, hepatitis, inflammatory bowel disease, neurodegenerative diseases, kidney injury, ischemia-reperfusion injury and skeletal muscle injury. This article reviews the characteristics and mechanism of ferroptosis, and summarizes how ferroptosis participates in the pathophysiological process in various systemic diseases of the body, which may provide new references for the treatment of clinical diseases in the future.Keywords: ferroptosis, mechanisms of ferroptosis, iron metabolism, cell death, systemic diseases

Xiaohong Sun, Jie Lv, Zhenghuan Wu, Jun Shi, Hongwei Huang Department of Neurology, People’s Hospital of Liyang, Changzhou, Jiangsu, 213300, People’s Republic of ChinaCorrespondence: Hongwei Huang, Department of Neurology, People’s Hospital of Liyang, No. 70 West Jianshe Road, Changzhou, 213300, Jiangsu Province, People’s Republic of China, Tel/Fax +86 051968091818, Email hhw2hjyyq@vip.163.comBackground and Aim: Serum uric acid to serum creatinine ratio (SUA/SCr) is associated with metabolic and cardiovascular diseases. We aimed to investigate the association between SUA/SCr and stroke recurrence among young adults with ischemic stroke.Methods: A total of 428 young patients with ischemic stroke were included in the present study. SUA/SCr was calculated from the concentration of serum uric acid and creatine (uric acid/creatine). Cox proportional regression models were performed to evaluate the association between SUA/SCr and stroke recurrence. Kaplan–Meier curves were used to compare recurrence rates in different quantiles of SUA/SCr.Results: During a median follow-up of 3.14 years, 51 (10.7%) patients had stroke recurrence. Multivariable analyses indicated that SUA/SCr was associated with stroke recurrence after being adjusted for potential confounders (quantile four versus quantile one: hazard ratio: 3.420; 95% confidence interval: 1.426– 8.200; P = 0.006). Kaplan–Meier curves revealed that patients with a high concentration of SUA/SCr had an increased stroke recurrence risk. The time-dependent receiver operating characteristic curve showed that the area under the curve for SUA/SCr was above 0.7 during follow-up. Restricted cubic spline presented an increasing trend for the link between SUA/SCr and stroke recurrence among young adults.Conclusion: SUA/SCr was positively associated with the risk of stroke recurrence among young adults with ischemic stroke. Further prospective studies are warranted to assess the causality between SUA/SCr and the development of stroke recurrence among young adults.Keywords: ischemic stroke, recurrence, young adults, uric acid

Zeyu Wang,1,&ast; Yonghe Zhou,2,3,&ast; Pengzhi Yu,2,3 Yonggang Liu,3,4 Mei Mei,5 Zhuo Bian,2 Wei Shao,2 Jinxia Lv,2 Xin Li,2 Wei Lu,1,3,6 Liang Xu3,6 1Department of Hepatobiliary Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin’s Clinical Research Center for Cancer, Tianjin, 300060, People’s Republic of China; 2Ultrasound department, Tianjin Second People’s Hospital, Tianjin, 300192, People’s Republic of China; 3Tianjin Research Institute of Liver Diseases, Tianjin, 300192, People’s Republic of China; 4Pathology Department, Tianjin Second People’s Hospital, Tianjin, 300192, People’s Republic of China; 5Department of Gastroenterology, Tianjin Haihe Hospital, Tianjin, 300350, People’s Republic of China; 6Department of Hepatology, Tianjin Second People’s Hospital, Tianjin, 300192, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Lu; Liang Xu, Email luwei1966@126.com; xuyangliang2004@sina.comBackground: At present, there is a lack of cheap, effective and convenient detection methods for hepatitis B-related liver fibrosis, especially in the developing area.Aim: To evaluate the non-invasive methods for the significant and advanced fibrosis stage in chronic hepatitis B virus (HBV) patients in basic hospitals and to assess their diagnostic utility.Methods: The study included 436 consecutive naive HBV individuals who had their livers biopsied. They were examined in one week using aspartate aminotransferase-to-aspartate aminotransferase ratio (AAR), age-platelet index (API), aspartate aminotransferase-to-platelet ratio index (APRI), fibrosis-4 (FIB-4), Forns, gamma-glutamyl transpeptidase-to-platelet ratio (GPR), S-index and transient elastography (TE). Scheuer scoring system was used to determine the histologic fibrosis grades (S0–S4). The diagnostic effectiveness was assessed using AUROCs and the DeLong test, both of which were based on statistical comparisons.Results: For both substantial (≧S2) and advanced (≧S3) fibrosis phases, TE had good diagnostic performance in determining the hepatic fibrosis. Similar diagnostic performance was shown with Forns and S-index when it came to detecting fibrosis stages lower than S3. One model’s diagnostic value was not significantly improved by combining serum models. Correlation coefficients between clinical features and fibrosis phases were greatest for Forns (r = 0.397), S-index (r = 0.382) and TE (r = 0.535) when compared to other variables.Conclusion: This investigation showed that Forns and S-index may be helpful strategies for detecting advanced fibrosis in HBV patients admitted to community hospitals.Keywords: hepatitis B virus, non-invasive, basic hospital, transient elastography, Forns, S-index

Qiyun Jiang,1,2 Dan Gong,1,2 Huiqi Li,3 Donglan Zhang,4 Suzhen Hu,5 Qinghua Xia,6 Hong Yuan,7 Peng Zhou,6 Yiying Zhang,7 Xing Liu,8 Mei Sun,1,2 Jun Lv,1,2 Chengyue Li1,2 1Department of Health Policy and Management, School of Public Health, Fudan University, Shanghai, People’s Republic of China; 2Research Institute of Health Development Strategies, Fudan University, Shanghai, People’s Republic of China; 3School of Public Health and Community Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden; 4Department of Health Policy and Management, College of Public Health, University of Georgia, Athens, GA, USA; 5Department of Medical Affairs, Liaocheng People’s Hospital, Liaocheng, People’s Republic of China; 6Department of Chronic Disease Prevention and Control, Changning District Center for Disease Control and Prevention, Shanghai, People’s Republic of China; 7Department of Chronic Disease Prevention and Control, Jiading District Center for Disease Control and Prevention, Shanghai, People’s Republic of China; 8Department of Epidemiology, School of Public Health, Fudan University, Shanghai, People’s Republic of ChinaCorrespondence: Chengyue Li; Jun Lv, Department of Health Policy and Management, School of Public Health, Fudan University, P.O. Box 177, 130 Dong’an Road, Shanghai, 200032, People’s Republic of China, Tel +86-21-33561022 ; +86-21-33563953, Fax +86-21-33563380, Email lichengyue@fudan.edu.cn; lujun@shmu.edu.cnPurpose: This study aimed to develop a screening tool based on a risk scoring approach that could identify individuals at high risk for hypertension in Shanghai, China.Methods: A total of 3147 respondents from the 2013 Shanghai Chronic Disease and Risk Factor Surveillance were randomly divided into the derivation group and validation group. The coefficients obtained from multivariable logistic regression were used to assign a score to each variable category. The receiver operating characteristic (ROC) curve was used to find the optimal cut-off point and to evaluate the screening performance.Results: Age, family history of hypertension, having diabetes, having dyslipidemia, body mass index, and having abdominal obesity contributed to the risk score. The area under the ROC curve was 0.817 (95% CI: 0.797– 0.836). The optimal cut-off value of 20 had a sensitivity of 83.4%, and a specificity of 64.3%, demonstrating good performance.Conclusion: We developed a simple and valid screening tool to identify individuals at risk for hypertension. Early detection could be beneficial for high-risk groups to better manage their conditions and delay the progression of hypertension and related complications.Keywords: Eastern China, high-risk population, hypertension, risk scoring method, screening tool

Jiawei Shen,1,&ast; Yan Hu,2,&ast; Jie Lv,1 Huiying Zhao,1 Bin Wang,1 Shuguang Yang,1 Anqi Du,1 Shuang Liu,2 Youzhong An1 1Department of Critical Care Medicine, Peking University People’s Hospital, Beijing, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Peking University International Hospital, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Youzhong An, Department of Critical Care Medicine, Peking University People’s Hospital, Beijing, People’s Republic of China, Email bjicu_bmc@163.comObjective: In this study, we aim to classify hematological patients with the pneumonia-associated acute respiratory syndrome (ARDS) into different groups that were characterized by distinct early responsiveness to corticosteroids, describe the microbiota signatures of the non-responders and responders, and compare the prognosis of the two groups.Methods: Hematological patients with ARDS were included and treated with mechanical ventilation and corticosteroid. According to the early improvement to the corticosteroid therapy, patients were classified as non-responders and responders. The lung microbiota signatures and the outcomes of the non-responders and responders were compared.Results: Fifty patients were included in this study. Twenty-eight patients were classed as non-responders and 22 as responders. Compared to the non-responders, responders had higher serum levels of IL-6, IL-8, TNF-α and CRP, their lung microbiota was with lower alpha diversity and enriched with virus species. The responders had an overall higher ventilator free days than the non-responders [4 (0– 6) vs 6 (0– 10), p=0.034], for survivors the difference was more significant [5 (3– 6) vs 8 (3– 10), p=0.012]. Survival analysis showed that there was no difference in survival rate between the two groups over time (Log-rank p=0.073). When non-responders were stratified into subgroups of patients with infection or co-infection, those non-responders with co-infection had significantly lower survival rate than other patients (Log-rank p= 0.028).Conclusion: For hematological patients with pneumonia-associated ARDS, the responders of corticosteroids had higher ventilator free days at day 28 than the non-responders. The microbiota signatures were distinct in the two groups. The non-responders with coinfections had the lowest survival rate when compared to the non-responders with no coinfections and the responders.Keywords: microbiota, acute respiratory distress syndrome, corticosteroid, hematologic neoplasms

Jing Lv,1 Zhifei Zhang,2 Zhigang Gao3 1Shandong University of Finance and Economics, Jinan, 250014, People’s Republic of China; 2Tongji University, Shanghai, 201804, People’s Republic of China; 3Shanghai University of Political Science and Law, Shanghai, 201804, People’s Republic of ChinaCorrespondence: Zhigang GaoShanghai University of Political Science and Law, No. 7989, Wai Qingsong Highway, Qingpu District, Shanghai, 201701, People’s Republic of ChinaTel +86 21-39225126Email gaozhigang@shupl.edu.cnPurpose: Employee voice has been considered as an important means to understand the cutting-edge information, gain social status and performance advantage for leaders, employees and the organization, respectively. However, our knowledge about how and when employees’ emotions influence voice remains limited.Design/Methodology/Approach: In order to better illustrate the role of emotion on voice, based on emotion as social information theory and similarity attraction theory, we proposed a research model through which emotion recognition ability affects voice via perceived ambidextrous leadership. A sample of 182 comprised of full-time employees and their 43 immediate supervisors was collected through questionnaires in China, and analyzed via hierarchical regression method.Findings: We found that subordinate’s emotional recognition ability has a significant positive effect on promotive and prohibitive voice, and that perceived ambidextrous leadership plays a significant mediating role between subordinate’s emotional recognition ability and promotive voice, while no mediating role is found between subordinate’s emotional recognition ability and prohibitive voice. In addition, in contrast to leader-subordinate gender dissimilarity, leader-subordinate gender similarity is more effective in strengthening the impact of emotion recognition ability on perceived ambidextrous leadership, and thus promotes employee voice.Originality/Value: This research not only advances our understanding of employee voice, but also provides specific reference for management practices from the perspective of gender.Keywords: emotion recognition ability, perceived ambidextrous leadership, leader-subordinate gender similarity, promotive voice, prohibitive voice

Wei Zhang,1 Xiaowen Yang,2 Jianping Lv,1 Shichang An3 1Department of Cosmetic Plastic Surgery, Weifang People’s Hospital, Weifang, Shandong, 261000, People’s Republic of China; 2Department of Stomatology, The People’s Hospital of Zhaoyuan City, Yantai, Shandong, 265400, People’s Republic of China; 3Department of Oral and Maxillofacial Surgery, Weifang People’s Hospital, Weifang, Shandong, 261000, People’s Republic of ChinaCorrespondence: Shichang AnDepartment of Oral and Maxillofacial Surgery, Weifang People’s Hospital, 151 Guangwen Street, Weifang, Shandong, 261000, People’s Republic of China, Tel +86-0536-8192557, Email anshichang2021@163.comPurpose: This study aimed to investigate the correlation between miR-196a expression and the progression and prognosis of cutaneous squamous cell carcinoma (CSCC).Patients and Methods: Tissue samples and corresponding paracancerous tissue samples from 117 patients with CSCC were collected. The qRT-PCR analysis was used to detect the expression levels of miR-196a. Kaplan–Meier curve and Cox regression analyses were used to analyze the relationship between miR-196a expression and patients’ prognosis. The CCK-8 and transwell assays were used to explore the effects of miR-196a on the abilities of cell proliferation, migration, or invasion.Results: miR-196a expression was significantly up-regulated in CSCC tissues or cell lines, compared with adjacent normal tissues or cell lines, respectively. High expression of miR-196a was associated with positive lymph node metastasis, high TNM stages, and a lower five-year survival rate. The expression level of miR-196a was up-regulated and the proliferation, migration or invasion ability of cells were significantly increased accordingly.Conclusion: miR-196a is highly expressed in CSCC, thus affecting the occurrence and development of CSCC. More importantly, miR-196a was shown to have potential as a prognostic marker for CSCC.Keywords: miR-196a, progression, prognosis, cutaneous squamous cell carcinoma

Jiamo Li,1 Jianing Jiang,1,2 Jinyan Lv,1 Ru Zhang,1 Wenting Chen,1,2 Shiyi Li,1 Qianchen Jin,1 Gang Wang1,2 1Department of Medical Oncology, The Affiliated Zhongshan Hospital of Dalian University, Dalian, Liaoning Province, People’s Republic of China; 2The Key Laboratory of Biomarker, High-Throughput Screening and Target Translation of Breast and Gastrointestinal Cancer, Dalian, Liaoning Province, People’s Republic of ChinaCorrespondence: Gang WangDepartment of Medical Oncology, The Affiliated Zhongshan Hospital of Dalian University, Dalian, Liaoning Province, 116001, People’s Republic of ChinaTel/Fax +86-411-6289737Email 1136566004@qq.comAbstract: Anti-γ-aminobutyric acid type β receptor (anti-GABABR) antibody-associated encephalitis is a type of autoimmune encephalitis. According to current literature, its pathogenesis is reported to be closely related to tumor factors. However, diagnosis can be difficult because of the rarity of cases, limited clinical understanding, and a lack of specificity in clinical manifestation and imaging presentation. Clinical trials have demonstrated that immunotherapy can prolong the survival of patients with small cell lung cancer; however, in some cases, immunotherapy may induce anti-GABABR antibody-associated encephalitis. Patients who develop this encephalitis during immunotherapy often delay treatment because the cause is not clearly identified. In this study, we report a case of a 61-year-old man with a confirmed diagnosis of small cell lung cancer who had acute onset of cognitive impairment and seizures after two cycles of durvalumab (AstraZeneca UK Limited) combination chemotherapy. This reaction was initially considered as an immune-related adverse event (irAE) caused by durvalumab treatment, and the patient was eventually considered to have a paraneoplastic neurological disorder caused by the primary tumor. This report raises awareness of the symptoms of cognitive impairment and seizures in patients with small cell lung cancer, and the possible adverse events associated with immunotherapy. This case also highlights the importance of detecting anti-GABABR antibodies in patients with small cell lung cancer.Keywords: anti-GABABR antibody, autoimmune encephalitis, immunotherapies, small cell lung cancer, durvalumab

Junxing Lv,1 Qinghao Zhao,1 Jingang Yang,1 Xiaojin Gao,1 Xuan Zhang,1 Yunqing Ye,1 Qiuting Dong,1 Rui Fu,1 Hui Sun,1 Xinxin Yan,1 Wei Li,2 Yuejin Yang,1 Haiyan Xu1 On behalf of the China Acute Myocardial Infarction Registry Study Group1Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, People’s Republic of China; 2Medical Research & Biometrics Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, People’s Republic of ChinaCorrespondence: Haiyan Xu; Yuejin YangDepartment of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, People’s Republic of ChinaTel +8610-88396082Email xuhaiyan@fuwaihospital.org; yangyjfw@126.comBackground: Length of stay (LOS) in patients with ST-segment elevation myocardial infarction (STEMI) is directly associated with financial pressure and medical efficiency. This study aimed to determine impact of LOS on short-term outcomes and associated factors of LOS in patients with ST-segment elevation myocardial infarction (STEMI) after primary percutaneous coronary intervention (PPCI).Methods: A total of 3615 patients with STEMI after PPCI in the China Acute Myocardial Infarction registry were included in the analysis. Predictors of prolonged LOS were analyzed by multivariate logistic regression model with generalized estimating equation. The impact of LOS on 30-day clinical outcomes was assessed.Results: The median LOS was 9 (7, 12) days. Patients with a longer LOS (> 7 days) were older, more often in lower-level hospitals, had more periprocedural complications and hospitalization expense. Fourteen variables, such as weekend admission and lower-level hospitals, were identified as independent associated factors of prolonged LOS. There were no significant difference in 30-day major adverse cardiac and cerebrovascular events (MACCE), readmission, and functional status between patients with LOS≤ 7d and LOS> 7d after multivariate adjustment and propensity score matching. However, patients who discharged over one week had better medication adherence (adjusted odds ratio: 0.817, 95% confidence interval: 0.687– 0.971, P=0.022). Significant interaction was observed in medication use between gender and LOS (Pinteraction=0.038).Conclusion: Patients with STEMI undergoing PPCI experienced a relatively long LOS in China, which resulted in more medical expenses but no improvement on 30-day MACCE, readmission, and functional recovery. Poor 30-day medication adherence with short LOS reflects unsatisfying transition of management from hospital to community. More efforts are needed to reduce LOS safely and improve the efficiency of medical care.Keywords: length of stay, ST-segment elevation myocardial infarction, primary percutaneous coronary intervention, prognosis

Chunxiao Liao,1 Wenjing Gao,1 Weihua Cao,1 Jun Lv,1 Canqing Yu,1 Shengfeng Wang,1 Zengchang Pang,2 Liming Cong,3 Hua Wang,4 Xianping Wu,5 Liming Li1 1Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, 100191, People’s Republic of China; 2Qingdao Center for Diseases Control and Prevention, Qingdao, 266033, People’s Republic of China; 3Zhejiang Center for Disease Control and Prevention, Hangzhou, 310051, People’s Republic of China; 4Jiangsu Center for Disease Control and Prevention, Nanjing, 210009, People’s Republic of China; 5Sichuan Center for Disease Control and Prevention, Chengdu, 610041, People’s Republic of ChinaCorrespondence: Liming Li; Wenjing GaoDepartment of Epidemiology and Biostatistics, School of Public Health, Peking University, 38 XueYuan Road, HaiDian District, Beijing, 100191, People’s Republic of ChinaTel +86 10 82801528Fax +86 10 82801528 Ext. 322Email lmlee@vip.163.com; wenjinggao@bjmu.edu.cnBackground: Obesity is a heterogeneous condition in terms of metabolic status. Different obesity phenotypes have various health risks. The aim of this work was to define different subtypes of obesity and investigate their relationship with inflammatory-cardiometabolic abnormalities among Chinese adult twins.Methods: The analyses used data from 1113 adult twins in 4 provinces (Shandong, Zhejiang, Jiangsu and Sichuan) from Chinese National Twin Registry (CNTR) which collected detailed information. We defined those with 0 or 1 metabolic syndrome (MetS) components excluding waist circumference as metabolically healthy, and those with waist circumference ≥ 90 cm (for men) and ≥ 85 cm (for women) as obese. The two-category obesity status and metabolic states are combined to generate four metabolic/obesity phenotypes. High sensitivity C reactive protein (hsCRP) was measured to assess underlying inflammation and homeostasis model assessment of insulin resistance (HOMA-IR) was calculated as surrogate measure of insulin resistance. Mixed-effect linear regression models and fixed-effect linear regression models were used to analyse the correlation between HOMA-IR, hsCRP and different metabolic/obesity phenotypes.Results: In cross-sectional analyses of 1113 individuals (mean [SD] age, 46.6 [12.9] years; 463 obese [41.6%]), 20.3% obese twins were metabolic healthy and 64.2% non-obese twins were metabolic unhealthy. Serum HOMA-IR level was higher in metabolically unhealthy non-obesity (MUNO) (β=0.42, 95% CI: 0.21– 0.64), metabolically healthy obesity (MHO) (β=0.68, 95% CI: 0.36– 1.00) and metabolically unhealthy obesity (MUO) (β=0.69, 95% CI: 0.46– 0.91) twins, compared with their metabolically healthy non-obesity (MHNO) counterparts. HsCRP was similar between MHO and MUO, which differed significantly to metabolic healthy non-obesity (MHNO).Conclusion: MHO and MUNO phenotypes were common in Chinese twin population. Both phenotypes were associated with elevated IR and hsCRP which may not be benign and need to be concerned.Keywords: metabolic status, insulin resistance, chronic inflammation, twin study

Yang Dong,* Dongfei Wang,* Jialan Lv, Zhicheng Pan, Rui Xu, Jie Ding, Xiao Cui, Xudong Xie, Xiaogang Guo Department of Cardiology, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaogang GuoDepartment of Cardiology, The First Affiliated Hospital of Zhejiang University School of Medicine, No. 79 Qing Chun Road, Hangzhou 310006, People’s Republic of ChinaTel + 86-13867441856Email gxg22222@zju.edu.cnPurpose: We aimed to study the Meta-analysis Global Group in Chronic Heart Failure (MAGGIC) risk model’s prognostic value and relationship with left ventricular remodeling in dilated cardiomyopathy.Patients and Methods: Dilated cardiomyopathy patients were prospectively recruited and underwent clinical assessments. MAGGIC risk score was calculated. Patients were followed up for adverse events and echocardiography. Primary endpoints were all-cause mortality and first rehospitalization due to heart failure. Secondary endpoint was left ventricular remodeling defined as a decline in left ventricular ejection fraction > 10% or an increase in left ventricular end-diastolic diameter > 10%. Survival status was examined using Cox regression analysis. The model’s ability to discriminate adverse events and left ventricular remodeling was calculated using a receiver operating characteristics curve.Results: In total, 114 patients were included (median follow-up time = 31 months). The risk score was independently related to adverse events (2-year all-cause mortality: hazard ratio [HR] = 1.122; 95% confidence interval [CI], 1.043– 1.208; 1-year first rehospitalization due to heart failure: HR = 1.094; 95% CI, 1.032– 1.158; 2-year first rehospitalization due to heart failure: HR = 1.088; 95% CI, 1.033– 1.147, all P < 0.05). One-year change in left ventricular end-diastolic diameter was correlated with the risk score (r = 0.305, P = 0.002). The model demonstrated modest ability in discriminating adverse events and left ventricular remodeling (all areas under the curve were 0.6– 0.7).Conclusion: The MAGGIC risk score was related to adverse events and left ventricular remodeling in dilated cardiomyopathy.Keywords: dilated cardiomyopathy, left ventricular remodeling, prognosis, risk model

Lili Zou,1,* Mingliang Ning,2,* Wenjuan Wang,1 Yuemei Zheng,1 Liping Ma,1 Jing Lv3 1Department of Anesthesiology, General Hospital of NingXia Medical University, Yinchuan, NingXia 750000, People’s Republic of China; 2Department of Oncological Surgery, General Hospital of NingXia Medical University, Yinchuan, NingXia 750000, People’s Republic of China; 3Department of Anesthesiology, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jing LvDepartment of Anesthesiology, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430000, People’s Republic of ChinaTel/Fax +86-27-85351618Email EmiliaAndrewsvpq@yahoo.comBackground: Natural products have shown neuroprotective effects in neurodegenerative conditions. Naringenin is a natural flavonoid with various pharmacological activities especially antioxidant, anti-inflammatory and neuroprotective properties. We investigated the effects of naringenin on anesthetic propofol-induced impacts on neonatal mouse brain development and consequent long-term neurocognitive impacts during adulthood.Materials and Methods: Female C57Bl/6 and male CD-1 mice and postnatal day 7 (P7) pups were exposed to propofol (2.5 mg/kg) and propofol with naringenin (50 mg/kg). Mice pups were allowed to grow until week 10 (adulthood), and memory and learning were assessed.Results: Propofol caused neurodegeneration by inducing apoptosis in the neonatal mouse brains while naringenin administration prevented neuronal cell loss by preventing neuronal apoptosis in neonatal mouse brains. Propofol caused degenerative alterations in metabolic factors pH, PO2, glucose and lactate, which were subsequently restored by naringenin treatment. Propofol-exposed mice, when developed into adults, showed long-term neuronal deficits, impaired neurocognitive functions, and memory and learning restrictions.Conclusion: Administration of naringenin to propofol-exposed mice resulted in significant neuroprotective effects by restoring long-term neurocognitive functions. The molecular mechanism behind the effects of naringenin was mediated by suppressing apoptosis and preventing cellular inflammation. These findings suggest that propofol administration requires careful consideration and that naringenin may prevent neurodegeneration and neurocognitive functions.Keywords: naringenin, propofol, neonatal, neurodegeneration, apoptosis, cognitive functions

Jiawei Lv,1 Kai Zhuang,1 Xiyu Jiang,1 Heqing Huang,1,2 Shijian Quan1 1Department of Pharmacology, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, People’s Republic of China; 2Laboratory of Pharmacology & Toxicology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, People’s Republic of ChinaCorrespondence: Heqing Huang; Shijian QuanDepartment of Pharmacology, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, No. 232 East Wai Huan Road, Guangzhou 510006, People’s Republic of ChinaTel +86 1 392 211 9719Email huangheq@mail.sysu.edu.cn; quansj@gzucm.edu.cnPurpose: Glomerular sclerosis and renal interstitial fibrosis are the most important pathologies in the development of kidney damage under diabetic conditions. Smad3 plays antagonistic roles in high glucose-induced renal tubular fibrosis, which is an important treatment target for diabetic nephropathy (DN). Formononetin (FMN) has multiple effects on diabetic vascular complications including DN. However, whether it plays an anti-fibrosis role by regulating smad3 is unclear. The purpose of this study was to evaluate the renoprotective effect of FMN by suppressing smad3 expression in db/db mice.Methods: FMN was orally administered to db/db mice with a dose of 25 or 50 mg/kg/day for 8 weeks. At the end of the study, serum, urine, and kidney samples were collected for biochemical and pathological examinations. The expressions of proteins and mRNA associated with renal fibrosis were determined by biochemical, histological, immunofluorescence, and real-time PCR analysis.Results: The results showed that FMN substantially improved the glucolipid metabolism, reduced the oxidative stress, and protected renal function in db/db mice. Meanwhile, protein and mRNA expression of smad3 and related regulatory factor of extracellular matrix deposition were significantly suppressed.Conclusion: The present study suggested that FMN has a good renoprotective effect in DN, which plays an anti-fibrosis role in db/db mice by suppressing the expression of smad3.Keywords: formononetin, diabetic nephropathy, db/db mice, renal fibrosis, expression of smad3, antioxidants

Pengfei Zhu,1 Han Liang,2 Xiangbo Huang,1 Qinglei Zeng,2 Yanmin Liu,2 Jun Lv,2 Liang Ming1 1Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China; 2Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of ChinaCorrespondence: Jun LvDepartment of Infectious Diseases, the First Affiliated Hospital of Zhengzhou University, 1 # Jianshe East Road, Zhengzhou, Henan 450052, People’s Republic of ChinaEmail lvjun558@126.comLiang MingDepartment of Clinical Laboratory, the First Affiliated Hospital of Zhengzhou University, 1 # Jianshe East Road, Zhengzhou, Henan 450052, People’s Republic of ChinaEmail bright3072@126.comBackground and Aim: Dysexpression of circular RNAs has been identified in multiple types of cancer. Hsa_circ_0004018 was reported to be significantly downregulated in hepatocellular carcinoma (HCC) and to display HCC-stage-specific expression features. However, the role of hsa_circ_0004018 in HCC progression remains unclear.Methods: The expression of hsa_circ_0004018 or microRNA-626 (miR-626) was detected in tumor tissues and paired non-tumor tissues from HCC patients, as well as in one normal human liver cell line and 5 HCC cell lines by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay, dye exclusion assay, clonogenic assay, scratch migration assay and transwell assay were used to measure cell proliferation and migration capacity, respectively. Luciferase report assay and RNA pull down assay were performed to explore the regulatory effect of certain molecules on the expression of target genes.Results: We found that the expression of hsa_circ_0004018 was lower in tumor tissues than in their paired non-tumor tissues from 28 out of 41 HCC patients. The difference in the expression between tumor tissues and non-tumor tissues was statistically significant (p< 0.001). Further analysis revealed that such lower expression in tumor tissues was much more common in bigger tumor size group (≥ 5cm) compared with the smaller tumor size group (< 5cm) (85% vs 42%, p=0.0007). Similarly, hsa_circ_0004018 was downregulated in HCC cell lines. Additionally, a negative correlation between hsa_circ_0004018 and miR-626 expression was noticed in HCC tissues. Moreover, we observed that hsa_circ_0004018 interacted with miR-626/DKK3 and contributed to HCC cell proliferation and migration through inhibiting Wnt/β-catenin signaling pathway in vitro. Furthermore, hsa_circ_0004018 blocked xenograft tumor growth in vivo through inhibiting Wnt/β-catenin signaling pathway by targeting miR-626/DKK3.Conclusion: We revealed that hsa_circ_0004018/miR-626/DKK3 regulatory axis may be a possible novel therapeutic target for HCC.Keywords: circular RNA, competing endogenous RNA, Wnt/β-catenin signaling pathway, hepatocellular carcinoma

Yihan Sun,1 Guofeng Li,1 Qi Zhou,1 Danyue Shao,2 Jingwei Lv,3 Jianhua Zhou1 1School of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun 130117, People’s Republic of China; 2Second School of Clinical Medicine, Beijing University of Chinese Medicine, Beijing 100029, People’s Republic of China; 3Jilin Ginseng Academy, Changchun University of Chinese Medicine, Changchun 130117, People’s Republic of ChinaCorrespondence: Jianhua ZhouSchool of Traditional Chinese Medicine, Changchun University of Chinese Medicine, 1035 Boshuo Road, Jingyue National High-Tech Industrial Development Zone, Changchun 130117, People’s Republic of ChinaTel +86-15948000805Email jianhuazhou1334@sohu.comObjective: To investigate the effect of erianin on tumor growth and immune response in human colorectal cancer cells (CRC).Methods: The effect of erianin on tumor growth was determined by CCK8 and colony formation assay. Western blotting was used to evaluate the expression levels of relevant proteins and qRT-PCR was used to evaluate the mRNA level of the relevant gene. The transcriptional activity of β-catenin was determined by dual-luciferase reporter assay. Cellular thermal shift assay was used to quantify drug–target interactions. The cell surface CD47 was assessed by flow cytometry. The enrichment of H3K27 acetyl marks on CD47 promoter was evaluated by chromatin immunoprecipitation assay. Phagocytosis assay was used to determine the phagocytic activity of macrophage. In vivo role of erianin was studied on xenograft models.Results: We found that erianin significantly decreased cell survival, colony formation, induced cell cycle arrest, and led to cell apoptosis in SW480 and HCT116 cells. Mechanism analysis demonstrated that erianin inhibited the nuclear translocation and transcriptional activity of β-catenin, which might result from erianin-β-catenin interaction. In addition, the downstream gene expressions, such as c-Myc and cyclin D1, was decreased. More interestingly, erianin decreased the expression of CD47 by regulating H3K27 acetyl marks enrichment on CD47 promoter. Consequently, macrophage-mediated phagocytosis was increased. Our in vivo experiments further confirmed the inhibitory effect of erianin on tumor growth.Conclusion: In summary, erianin could inhibit CRC cells growth and promoted phagocytosis, which suggested erianin as a potential therapeutic strategy for CRC patients.Keywords: erianin, colorectal cancer, β-catenin, CD47, macrophage

Ainian Chen,1 Lingling Zhong,1 Keju Ju,1 Ting Lu,1 Jia Lv,2 Hua Cao1 1Department of Neurology, The Affiliated Huai’an No.1 People’s Hospital of Nanjing Medical University, Huai’an, Jiangsu 223300, People’s Republic of China; 2Department of Neurosurgery, The Affiliated Huai’an No.1 People’s Hospital of Nanjing Medical University, Huai’an, Jiangsu 223300, People’s Republic of ChinaCorrespondence: Hua CaoDepartment of Neurology, The Affiliated Huai’an No. 1 People’s Hospital of Nanjing Medical University, 01 Huanghe Road West, Huai’an 223300, Jiangsu, People’s Republic of ChinaTel/Fax +86 13861565810Email hacan979@yeah.netBackground: Glioblastoma (GBM) is the most common primary malignant tumor in adult central nervous system and results in disappointing survival outcomes. Although the diagnosis and therapy approach have been developed recently, the prognosis of GBM remains poor. A novel, minimally invasive biomarker for GBM is necessary for early diagnosis or prognosis prediction.Methods: All circRNAs were detected by qRT-PCR in GBM samples including training and validation sets. We used the risk score analysis to assume the diagnosis ability for GBM. The receiver operating characteristic curve was also employed.Results: Among the 14 candidates, circRNA, circNT5E, circFOXO3, circ_0001946, circ_0029426, circ-SHPRH, and circMMP9 were detected with increased levels in the training set. Further investigation in the validation set indicated that circFOXO3, circ_0029426, and circ-SHPRH might be the fingerprints for GBM compared with controls. The risk score analysis revealed that the combination of three circRNAs could distinguish the GBM from healthy control with the area under curve value of 0.980 and 0.906, respectively.Conclusion: The three circRNAs might be novel fingerprints for predicting the occurrence of GBM.Keywords: glioma, circRNA, plasma, biomarker, serum

Gang Wang, 1, 2,* Jinqi Gao, 3,* Jinyan Lv, 1 Xi Chen, 1 Jinyu Wu, 1 Ruoyu Wang, 1, 2 Jianing Jiang 1, 2 1Department of Medical Oncology, The Affiliated Zhongshan Hospital of Dalian University, Dalian, Liaoning Province, People’s Republic of China; 2The Key Laboratory of Biomarker, High-Throughput Screening and Target Translation of Breast and Gastrointestinal Cancer, Dalian, Liaoning Province, People’s Republic of China; 3Department of Intervention, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ruoyu Wang; Jianing JiangDepartment of Medical Oncology, The Affiliated Zhongshan Hospital of Dalian University, Dalian, Liaoning Province 116001, People’s Republic of ChinaTel/Fax +86-411-62897370; +86-411-62897233Email wangruoyu1963@163.com; jing_jianing@126.comAbstract: Cabozantinib has been shown to have potent anti-ROS1 activity in many solid malignancies, particularly against those with solvent-front resistance mutations following crizotinib therapy. With regard to the most common CD74-ROS1 fusion, the efficacy of cabozantinib has only been demonstrated in vitro. Therefore, we evaluate the efficacy of cabozantinib in a patient with advanced non-small-cell lung cancer (NSCLC) harboring a CD74-ROS1 fusion in the present study. A 40-year-old female patient presented with 1-month history of cough, white sputum and chest pain. Chest CT scan revealed a consolidation in the middle lobe of the right lung together with multiple cavity lesions spreading in both lungs. Histopathological analysis of biopsy samples from the lesion in the middle lobe of the right lung suggested lung adenocarcinoma. After two lines of chemotherapy and EGFR-TKI therapy, a CD74-ROS1 rearrangement was detected and the patient was administered with cabozantinib for 1.5 years. Since cabozantinib resistance developed, crizotinib therapy was applied and demonstrated clinical effectiveness until now. Together, we report the first case of cabozantinib effectiveness in treating a CD74-ROS1-positive advanced NSCLC patient. Crizotinib remained as an effective therapeutic option following the acquisition of cabozantinib resistance.Keywords: cabozantinib, CD74-ROS1 fusion, NSCLC, crizotinib

Liangliang Huang,1,* Yuhuai Cai,1,* Yi Luo,1 Daigang Xiong,1 Zeyu Hou,1 Junyuan Lv,1 Feng Zeng,1 Yan Yang,2,3 Xiaoming Cheng1 1Medical Center of Breast and Thyroid Disease, Affiliated Hospital of ZunYi Medical University, ZunYi, Guizhou 563003, People’s Republic of China; 2Department of Clinical Laboratory, Affiliated Hospital of ZunYi Medical University, ZunYi, Guizhou 563003, People’s Republic of China; 3College of Laboratory Medicine, Zunyi Medical University, Zunyi, Guizhou 563003, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaoming ChengMedical Center of Breast and Thyroid Disease, Affiliated Hospital of ZunYi Medical University, 149 Dalian Road, ZunYi, Guizhou 563003, People’s Republic of ChinaTel +8613985248883Email cxm1688@sina.comYan YangDepartment of Clinical Laboratory, Affiliated Hospital of ZunYi Medical University, 149 Dalian Road, ZunYi, Guizhou 563003, People’s Republic of ChinaTel +8618183468796Fax +86851-28608316Email yy623yy@163.comPurpose: Juxtaposed with another zinc finger gene 1 (JAZF1) is involved in gluconeogenesis, insulin sensitivity, cell differentiation, lipid metabolism and inflammation, but its role in carcinoma remains inexplicit.Patients and methods: We explored the JAZF1 expression in human papillary thyroid cancer (PTC) tissues, adjacent normal thyroid tissues and nodular goitre tissues, as well as Ki67 expression in PTC tissues, using immunohistochemistry staining. Western blotting and RT-qPCR were performed to explore the JAZF1 expression levels in Nthy-ori 3–1, BCPAP and TPC-1 cells. BCPAP cells overexpressing JAZF1 were constructed using an Adv-JAZF1-GFP recombinant adenovirus vector. Next, the cell proliferation assay, colony formation assay, cell cycle analysis, apoptosis and immunofluorescence were performed. The mRNA expression level of nuclear factor-κB p65 (NF-κB p65) was examined using RT-qPCR. The expression of Bcl-2, Bax, transforming growth factor beta-activated kinase 1 (TAK1), NF-κB p65 and NF-κB p-p65 were examined using Western blotting.Results: The expression of JAZF1 in human PTC tissues was downregulated compared with adjacent thyroid tissues or nodular goitre. Additionally, JAZF1 expression was associated with the location and lymph node metastasis of PTC. The expression level of JAZF1 had a negative correlation with Ki67 labelling index (LI). Compared to Nthy-ori 3–1 cells and TPC-1 cells, BCPAP cells expressed the lowest JAZF1. JAZF1 overexpressed significantly inhibited proliferation, caused G0/G1 cell cycle arrest and promoted apoptosis in BCPAP cells. Furthermore, JAZF1 overexpressed in BCPAP cells clearly upregulated the expression level of Bax protein, whereas decreased the expression of Bcl-2, TAK1, NF-κB but did not affect the mRNA or protein expression level of NF-κB p65.Conclusion: JAZF1 inhibits proliferation and induces apoptosis in BCPAP cells by suppressing the activation of TAK1/NF-κB signalling pathways, suggesting that JAZF1 may serve as a reliable molecular marker in PTC.Keywords: Juxtaposed with another zinc finger gene 1, papillary thyroid cancer, TAK1, NF-κB

You-ting Lin,1 Xue Yang,2 Jing-wei Lv,2 Xue-wu Liu,2,* Sheng-jun Wang2,* 1Department of Neurology, Shandong Provincial Hospital, Shandong University, Ji’nan, People’s Republic of China; 2Department of Neurology, Qilu Hospital, Shandong University, Ji’nan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Sheng-jun Wang;Xue-wu LiuDepartment of Neurology, Qilu Hospital, Shandong University, 107# Wen Hua Xi Road, Ji’nan 250012, Peoples Republic of ChinaEmail junwang9999@sina.com; qiluliuym66@163.comBackground: Although antibody-mediated immune responses are considered pathogenic and responsible for neural injury in anti-leucine-rich glioma-inactivated protein 1 (anti-LGI1) encephalitis, previous studies have indicated that cytokines and chemokines might play roles in the pathogenic process by serving as B cell enhancers. In this study, we detected the profiles of cytokines and chemokines in the cerebral fluid (CSF) and serum of patients with anti-LGI1 encephalitis to identify potential biomarkers.Methods: Sixteen patients diagnosed with anti-LGI1 encephalitis and nine patients diagnosed with noninflammatory neurologic disorders were included in the study. Cytokines and chemokines including IL-6, IL-10, IL-17, CXCL12, CXCL13, BAFF and HMGB1 in serum and CSF were measured.Results: The serum and CSF levels of CXCL13 were significantly higher in patients with anti-LGI1 encephalitis (36.32±34.71 pg/mL and 2.23±2.41 pg/mL, respectively) than in controls (10.84±5.02 pg/mL and 0.34±0.21 pg/mL, respectively). There was no significant difference in serum or CSF levels of IL-6, IL-10, IL-17, CXCL12, BAFF and HMGB1 between the two groups.Conclusion: CXCL13 is a potential biomarker of active inflammation in anti-LGI1 encephalitis. The distinctive response of cytokines and chemokines might be closely linked to the mechanisms underlying this condition.Keywords: leucine-rich glioma-inactivated protein 1, CXCL13, cytokine, encephalitis, biomarker

Jiling Lv,1,2 Fang Zhang,3 Congying Zhai,2 Gejin Wang,4 Yan Qu1 1Department of Intensive Care Unit, Affiliated Qingdao Municipal Hospital of Qingdao University, Qingdao 266071, Shandong, People’s Republic of China; 2Department of Respiratory Medicine, The First Hospital of Zibo, Zibo 255200, Shandong, People’s Republic of China; 3Department of Radiotherapy, Yantai Affiliated Hospital of Binzhou Medical University, Yantai 26400, Shandong, People’s Republic of China; 4Department of Nursing, Zibo Vocational Institute, Zibo 255314, Shandong, People’s Republic of ChinaCorrespondence: Yan QuThe Intensive Care Unit, Qingdao Municipal Hospital Affiliated to Qingdao University, 1 Jiaozhou Road, Qingdao 266071, Shandong, People’s Republic of ChinaTel +8613668892506Email qdquyan@aliyun.comPurpose: B-cell lymphoma-2 (Bcl-2) associated athanogene 1 (Bag-1) is a multifunctional protein, and Bag -1 overexpression is associated with progression, metastasis, and drug resistance in lung cancer. This study assessed the effects of Bag-1 siRNA on sensitization of cisplatin on non-small cell lung cancer (NSCLC) cells.Material and methods: NSCLC A549 cell line was transfected with Bag-1 or negative control siRNA and then treated with cisplatin for cell viability, CCK-8, LDH, and flow cytometry assays. The Ca2+ levels were analyzed using Fluo-3/AM fluorescence staining, and the protein levels were assessed using Western blot analysis.Results: Bag-1 siRNA significantly knocked down Bag-1 expression and inhibited cell invasion versus the negative control siRNA, while Bag-1 silence sensitized cisplatin to induce A549 cells to apoptosis by induction of cell cycle G1 arrest. At protein level, Bag-1 silence reduced the expression ratio of Bcl-2 to Bcl-2 associated X protein (Bax), downregulated activity of the PI3K/AKT and mitogen-activated protein kinase (MAPK) pathways, and potently upregulated the calcium signaling-mediated pathway.Conclusion: This study demonstrated that Bag-1 silencing sensitized A549 to cisplatin to enhance A549 cell apoptosis by modified multiple gene pathways. Further study will evaluate the usefulness of Bag-1 siRNA as a potential targeting therapy for NSCLC.Keywords: bag-1, apoptosis, non-small cell lung cancer, chemotherapy

Jia Mi,1,* Wenda He,1,* Jiawei Lv,1 Kai Zhuang,1 Heqing Huang,1,2 Shijian Quan1 1School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 2Laboratory of Pharmacology & Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Heqing Huang; Shijian QuanDepartment of School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, No. 232 East Wai Huan Road, Guangzhou 510006, People’s Republic of ChinaTel +86 1 392 211 9719Email Huangheq@mail.sysu.edu.cn quansj@gzucm.edu.cnPurpose: Activation of the hypothalamus-pituitary-adrenal (HPA) axis pathway is closely related to insulin resistance (IR), glucose, and lipid metabolism disorders in type 2 diabetes mellitus (T2DM). Berberine (BBR) has effect on regulating disorder of glucose and lipid metabolism in T2DM. In fact, activation of the HPA axis pathway is closely related to IR, glucose, and lipid metabolism disorders in T2DM. Here, we investigated whether the therapeutic effect of BBR on T2DM rats is acted through the HPA axis pathway. Methods: In this research, we investigated the effects of BBR on the HPA-axis pathway-related indicators and expression of skeletal muscle glucose transporter 4 (GLUT4) in the high-fat diet and streptozotocin-induced T2DM rats, and identify its possible mechanism of improving IR in T2DM.Results: BBR significantly reduced fasting blood glucose, total cholesterol, and low-density lipoprotein cholesterol in model rats. It also improved the abnormalities of the high-density lipoprotein cholesterol, the insulin resistance index, the insulin sensitivity index, glucagon, and insulin levels. BBR decreased levels of hypothalamic Orexin-A, the OX2R receptor, the corticotropin-releasing hormone, the pituitary and the plasma adrenocorticotropic hormone, as well as serum and urine corticosterone. At the same time, BBR increased mRNA and protein expressions of GLUT4 in skeletal muscles of model rats as well.Conclusion: Those results suggested that BBR can exert inhibition on the HPA-axis and increased skeletal muscle expression of GLUT4 proteins, which may be one of the important mechanisms in BBR to improve IR and regulating glucose and lipid metabolism in T2DM rats.Keywords: berberine, type 2 diabetes mellitus, insulin resistance, the HPA-axis, GLUT4

Yulong Lin, Yalin Wang, Jie Lv, Nannan Wang, Jing Wang, Meng LiCollege of Pharmaceutical Sciences, Hebei Medical University, Shijiazhuang 050017, People’s Republic of ChinaPurpose: Acetylcholinesterase (AChE) plays a critical role in the transmission of nerve impulse at the cholinergic synapses. Design and synthesis of AChE inhibitors that increase the cholinergic transmission by blocking the degradation of acetylcholine can serve as a strategy for the treatment of AChE-associated disease. Herein, an operational targeted drug delivery platform based on AChE-responsive system has been presented by combining the unique properties of enzyme-controlled mesoporous silica nanoparticles (MSN) with clinical-used AChE inhibitor.Methods: Functionalized MSNs were synthesized by liquid phase method and characterized by using different analytical methods. The biocompatibility and cytotoxicity of MSNs were determined by hemolysis experiment and MTT assay, respectively. Comparison of AChE activity between drug-loading system and inhibitor was developed with kits and by ELISA method. The efficacy of drug-loaded nanocarriers was investigated in a mouse model.Results: Compared with AChE inhibitor itself, the inhibition efficiency of this drug delivery system was strongly dependent on the concentration of AChE. Only AChE with high concentration could cause the opening of pores in the MSN, leading to the controlled release of AChE inhibitor in disease condition. Critically, the drug delivery system can not only exhibit long duration of drug action on AChE inhibition but also reduce the hepatotoxicity in vivo.Conclusion: In summary, AChE-responsive drug release systems have been far less explored. Our results would shed lights on the design of enzyme controlled-release multifunctional system for enzyme-associated disease treatment.Keywords: acetylcholinesterase inhibitor, controlled drug release, mesoporous silica nanoparticles, drug action, hepatotoxicity

Jincai Lv,* Bailong Liu,* Xiaoyue Quan, Cheng Li, Lihua Dong, Min LiuDepartment of Radiation Oncology, The First Hospital, Jilin University, Changchun 130021, People’s Republic of China*These authors contributed equally to this work Background: Intramedullary spinal cord metastases (ISCM) in malignancies is a devastating issue with limited research. This study aims to identify the clinical features, management, prognostic factors, and outcomes of this special entity.Methods: A retrospective review of 61 patients of ISCM diagnosed and treated in our institute from June 2010 to March 2018 was conducted (lost to follow-up: 3). Data were retrieved according to the items including age, gender, primary tumor, interval to the ISCM occurrence, ISCM segments, and other synchronous metastases. The interventions, response, prognostic factors, and outcomes of ISCM were systematically analyzed.Results: Lung cancer (67.21%) was the commonest ISCM source, followed by breast cancer (14.75%). In total, 9.84% of patients presented with ISCM initially. The mean span from the primaries to ISCM was 18.77 months (range=0–10 years). The thoracic segment was most commonly involved (77.05%), followed by cervical (39.34%), lumbar level (34.43%), and conus medullaris (6.56%). The management of ISCM was challenging, since 55.74% of individuals had a poor physical condition (PS=3–4) and 72.41% had widespread dissemination synchronously (≥2 organs). Radiotherapy (RT) attained an objective response rate (ORR) of 61.90% or 62.50% and a local control rate (LCR) of 90.48% or 87.50% for symptoms used alone or with other strategies, respectively. ISCM bears a dismal prognosis, with a median overall survival (OS) of 4 months. Patients with only one segment involved had an apparently better prognosis than those with 2–4 involved segments (median OS=7.0 vs 3.0 months) (P

Sen Zheng,1,* Huita Wu,2,* Fei Wang,1,* Jie Lv,1 Jing Lu,1 Qinliang Fang,1 Fuqiang Wang,1 Yuyan Lu,1 Sheng Zhang,1 Yaping Xu,3 Qing Bao,1 Chengrong Xie,1 Zhenyu Yin11Department of Hepatobiliary Surgery, Zhongshan Hospital, Xiamen University, Fujian Provincial Key Laboratory of Chronic Liver Disease and Hepatocellular Carcinoma, Xiamen 361004, Fujian, People’s Republic of China; 2Department of Oncology, Zhongshan Hospital, Xiamen University, Xiamen 361004, Fujian, People’s Republic of China; 3Key laboratory of functional and clinical translational medicine, Xiamen Medical College, Xiamen 361004, Fujian, People’s Republic of China*These authors contributed equally to this workBackground: Due to the high recurrence and metastasis rate, the clinical outcomes of patients with hepatocellular carcinoma (HCC) are still unsatisfactory. Hepatitis B virus X-interacting protein (HBXIP) has been reported to play crucial roles in carcinogenesis.Purpose: We aimed to reveal the functional significance and underlying mechanism of HBXIP in HCC metastasis.Methods: Cell transwell assay, in vivo metastasis model, real-time PCR, western blot analysis, luciferase reporter and chromatin immunoprecipitation assays were applied.Results: Here, we detected the HBXIP expression level and determined its clinical significance in HCC. We found that HBXIP was significantly upregulated in HCC tissues, and correlated with vascular invasion, tumor metastasis and worse prognosis of HCC patients. HBXIP enhanced cell migration and invasion in vitro, and promoted the metastasis of HCC in vivo. Furthermore, we confirmed that HBXIP increased MMP15 expression through association with proto-oncogene c-myc. Depletion of c-myc abolished HBXIP-mediated MMP-15 upregulation. We also observed a positive correlation between HBXIP and MMP15 expression in HCC tissues.Conclusion: Our results establish a novel function for HBXIP-MMP15 regulation in HCC metastasis and suggest its candidacy as a new prognostic biomarker and therapeutic target for HCC metastasis.Keywords: c-myc, MMP15, HBXIP, metastasis

Youbing Tu,1 Yubing Liang,2 Yong Xiao,1 Jing Lv,1 Ruicong Guan,1 Fei Xiao,1 Yubo Xie,1,* Qiang Xiao3,* 1Department of Anesthesiology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China; 2Department of Anesthesiology, The Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, China; 3Department of Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China *These authors contributed equally to this work Background: Propofol is a commonly used general anesthetic for the induction and maintenance of anesthesia and critical care sedation in children, which may add risk to poor neurodevelopmental outcome. We aimed to evaluate the effect of propofol toward primary hippocampal neurons in vitro and the possibly neuroprotective effect of dexmedetomidine pretreatment, as well as the underlying mechanism.Materials and procedures: Primary hippocampal neurons were cultured for 8 days in vitro and pretreated with or without dexmedetomidine or phosphorylation inhibitors prior to propofol exposure. Cell viability was measured using cell counting kit-8 assays. Cell apoptosis was evaluated using a transmission electron microscope and flow cytometry analyses. Levels of mRNAs encoding signaling pathway intermediates were assessed using qRT-PCR. The expression of signaling pathway intermediates and apoptosis-related proteins was determined by Western blotting.Results: Propofol significantly reduced cell viability, induced neuronal apoptosis, and downregulated the expression of the BDNF mRNA and the levels of the phospho-Erk1/2 (p-Erk1/2), phospho-CREB (p-CREB), and BDNF proteins. The dexmedetomidine pretreatment increased neuronal viability and alleviated propofol-induced neuronal apoptosis and rescued the propofol-induced downregulation of both the BDNF mRNA and the levels of the p-Erk1/2, p-CREB, and BDNF proteins. However, this neuroprotective effect was abolished by PD98059, H89, and KG501, further preventing the dexmedetomidine pretreatment from rescuing the propofol-induced downregulation of the BDNF mRNA and p-Erk1/2, p-CREB, and BDNF proteins.Conclusion: Dexmedetomidine alleviates propofol-induced cytotoxicity toward primary hippocampal neurons in vitro, which correlated with the activation of Erk1/2/CREB/BDNF signaling pathways. Keywords: hippocampus, propofol, dexmedetomidine, extracellular signal-regulated MAP kinases, cyclic AMP response element-binding protein, brain-derived neurotrophic factor

Min Liu,1 Lei Zhang,2 Liang Guo,3 Jincai Lv,1 Weiyan Shi,1 Bailong Liu1 1Department of Radiation Oncology, The First Hospital, Jilin University, Changchun 130021, China; 2Department of Radiology, The First Hospital, Jilin University, Changchun 130021, China; 3Department of Pathology, The First Hospital, Jilin University, Changchun 130021, China Abstract: Intestinal metastasis from breast cancer (BC) is rarely encountered in clinical practice. Nonspecific symptoms and long latency result in misdiagnosis as a primary intestinal tumor. Therefore, increased awareness of bowel metastasis secondary to BC and a thorough understanding of the clinical and molecular features, and intervention of bowel metastasis are fundamental to avoid the delay of correct diagnosis and management. Herein, we documented a BC patient who experienced progressive bellyache and vomiting 16 years after simplified radical mastectomy. Abdominal CT scan revealed localized thickening of the small intestine wall and lumen narrowing, initially diagnosed as a primary intestinal tumor. The subsequent operation resolved the intestinal obstruction and confirmed the diagnosis of intestinal involvement of BC. Radical local treatment followed by systemic intervention contributed to a better outcome. Our case indicates that intestinal metastasis should be included in the diagnostic checklist in patients presented with any intestinal symptom even with a remote history of BC. Our case is of great value in its rarity and calls for the awareness of clinicians for this special entity to guarantee the accurate and prompt diagnosis and treatment, and optimize the patient’s prognosis. Keywords: intestinal metastasis, breast cancer, surgery, combined treatment

Xiaopeng Zhu,1,* Min Liu,1,* Jincai Lv,1 Liang Guo,2 Cheng Li,1 Lihua Dong,1 Bailong Liu1 1Department of Radiation Oncology, The First Hospital, Jilin University, Changchun 130021, China; 2Department of Pathology, The First Hospital, Jilin University, Changchun 130021, China *These authors contributed equally to this work Abstract: The treatment of repeatedly recurrent carcinoma of the floor of the mouth (FOM) is challenging. There is no standard strategy for such patients with poor physical condition after multiple lines of treatment. Angiogenesis is a key in tumor initiation, growth, and dissemination. Apatinib, a potent tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor 2 (VEGFR2), has been approved for the treatment of late-stage gastric or gastroesophageal junction adenocarcinoma that is resistant to at least two lines of chemotherapy. Its application in intractable FOM squamous carcinoma has never been described before. Herein, we present the case of a heavily treated patient with FOM squamous carcinoma undergoing a third local relapse in the right region of the neck and anterior cervical region. Oral apatinib was administered daily at a dose of 250 mg. There was clear and rapid efficacy that led to complete remission. However, giant, deep ulcers formed due to tumor necrosis. The patient eventually died of massive bleeding resulting from the major cervical vascular rupture caused by tumor necrosis and erosion. This case is novel and instructional, highlighting that apatinib might be effective, with manageable toxicity, for certain patients with refractory head and neck squamous cell carcinoma (HNSCC). The advantages and disadvantages of apatinib should be carefully evaluated, and close surveillance and quick intervention as required are critical to reduce fatal cancer-associated complications. The role of apatinib in recurrent or metastatic HNSCC needs to be clarified by multicenter trials in the near future. Keywords: apatinib, head and neck squamous cell carcinoma, recurrent, lethal bleeding, VEGFR2, TKI

Jing Zhao,1 Ming Zou,1 Jinyan Lv,2 Yingmin Han,1 Guangzhi Wang,3 Gang Wang2 1Department of Pharmacy, Affiliated Zhongshan Hospital of Dalian University, Dalian, People’s Republic of China; 2Department of Oncology, Affiliated Zhongshan Hospital of Dalian University, Dalian, People’s Republic of China; 3Department of General Surgery, The Second Hospital of Dalian Medical University, Dalian, People’s Republic of China Abstract: Osimertinib is commonly used in pulmonary adenocarcinoma patients who are resistant to first-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors and carry the T790M mutation. However, the use of osimertinib may result in the development of further resistance, most commonly via the cis-C797S mutation. Herein, we report a case of a lung cancer patient harboring triple EGFR mutations of L858R, T790M, and cis-C797S who was treated with a combination of osimertinib, bevacizumab, and brigatinib. The above 3 mutations were detected by circulating tumor DNA analysis after osimertinib treatment. Subsequently, the patient received combination therapy of osimertinib and bevacizumab; the partial relief obtained was negated by later disease progression. The regimen was then changed to osimertinib, bevacizumab, and brigatinib combination therapy. Partial remission was observed, and a significant reduction in EGFR mutations was detected. This case represents the first evidence that 1) bevacizumab combined with osimertinib can significantly relieve tumor growth and respiratory symptoms in non-small-cell lung cancer patients with osimertinib resistance and 2) the clinical use of osimertinib, bevacizumab, and brigatinib is effective as combination therapy for pulmonary adenocarcinoma in the presence of triple EGFR mutations of L858R, T790M, and cis-C797S. These combination therapies may provide potential novel treatment options for pulmonary adenocarcinoma patients. Keywords: pulmonary adenocarcinoma, EGFR-T790M, EGFR cis-C797S, drug resistance mechanisms

Yong Xiao,1,* Lifang Zhou,2,* Youbing Tu,1 Yuantao Li,3 Yubing Liang,4 Xu Zhang,1 Jing Lv,1 Yu Zhong,1 Yubo Xie1 1Department of Anesthesiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China; 2Department of Anesthesiology, Institute of Cardiovascular Diseases, The First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China; 3Department of Anesthesiology, Shenzhen Maternity & Child Healthcare Hospital, Southern Medical University, Shenzhen, People’s Republic of China; 4Department of Anesthesiology, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, People’s Republic of China *These authors contributed equally to this work Background: Propofol induces short- and long-term neurotoxicity. Our previous study showed that dexmedetomidine (Dex) can attenuate the propofol-induced acute neurotoxicity in rodents by enhancing the PI3K/Akt signaling. However, whether treatment of young rats with Dex could protect them from long-term neurotoxicity induced by propofol is unclear. Materials and methods: Seven-day-old male Sprague Dawley rats were randomized and injected intraperitoneally with saline (100 µL, NS), propofol (100 mg/kg), Dex (75 µg/kg), propofol (100 mg/kg) plus Dex (25, 50 or 75 µg/kg), 10% dimethyl sulfoxide (DMSO, 100 µL) or TDZD-8 (a GSK3β inhibitor, 1 mg/kg), or intracerebroventricularly with DMSO (5 µL) or LY294002 (a PI3K inhibitor, 25 µg/5 µL DMSO). Other rats in the experimental group were injected with the same doses of propofol, Dex and LY294002 or TDZD-8. All the rats were monitored until they were 9 weeks old. Their spatial learning and memory were tested by Morris water maze. The neuronal apoptosis, expression of PSD95, expression and phosphorylation of Akt and GSK3β and synaptic ultrastructures were determined by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling, immunohistochemistry, Western blot and transmission electron microscopy assays, respectively. Results: Compared with the NS control group, young rats injected with intralipid, Dex, TDZD-8, LY294002 or DMSO alone did not show any significant change as they aged. Propofol significantly increased the escape latency time, hippocampal neuroapoptosis and synaptic ultrastructural changes but decreased the relative levels of PSD95 expression, and Akt and GSK3β phosphorylation in the developing hippocampus of the rats. The neuronal toxic effects of propofol were significantly mitigated by the pretreatment with a higher dose of Dex. The neuroprotective effect of Dex was enhanced by the treatment with TDZD-8, but was completely abrogated by the treatment with LY294002. Conclusion: Our results indicated that the pretreatment of young rats with Dex attenuated the propofol-induced long-term neurotoxicity in their developing hippocampus by enhancing the PI3K/Akt signaling. Keywords: propofol, dexmedetomidine, long-term neurotoxicity, PI3K, hippocampus

Anan Yu,1,* Jieqiong Lv,1,* Fang Yuan,1 Zihua Xia,1 Kaiyan Fan,1 Gang Chen,1,2 Jialin Ren,1 Cuicui Lin,1 Shijie Wei,1,2 Fan Yang1,2 1Department of Pharmaceutics, 2Guangdong Provincial Engineering Center of Topical Precise Drug Delivery System, Guangdong Pharmaceutical University, Guangzhou, Guangdong, China *These authors contributed equally to this work Purpose: This study aimed to develop a novel methoxy poly(ethylene glycol)-poly(lactide) (mPEG-PLA)/D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) mixed micelle drug delivery system to improve lamotrigine (LTG) distribution in the hippocampus.Methods: LTG-loaded mPEG-PLA/TPGS mixed micelles and LTG-loaded mPEG-PLA micelles were formulated, and their characteristics, particle size, surface morphology, and release behavior in vitro were researched. Then, a microdialysis sampling technique coupled with two validated chromatographic systems was developed for the continuous measurement of the protein-unbound form of LTG in the rat plasma and hippocampus after administering two kinds of micelles and LTG solution intranasally. Results: The drug loading and mean size of LTG-loaded micelles and LTG-loaded mixed micelles prepared with optimal formulation were 36.44%±0.14%, 39.28%±0.26%, 122.9, and 183.5 nm, respectively, with a core–shell structure. The cumulative release rate in vivo of LTG-loaded mixed micelles was 84.21% at 24 hours and showed more sustained release while that of LTG-loaded micelles was 80.61% at 6 hours. The Tmax and area under concentration-time curve from zero to time of last quantifiable concentration of LTG solution, LTG-loaded micelles, and LTG-loaded mixed micelles were 55, 35, and 15 minutes and about 5,384, 16,500, and 25,245 (min·µg)/L in the hippocampus, respectively.Conclusion: The results revealed that LTG-loaded mPEG-PLA/TPGS mixed micelles enhanced the absorption of LTG at the nasal cavity and reduced the efflux of LTG in the brain, suggesting that the function of TPGS inhibited P-glycoprotein and LTG-loaded mPEG-PLA/TPGS mixed micelles had the potential to overcome refractory epilepsy. Keywords: epilepsy, intranasal administration, lamotrigine, P-glycoprotein, blood brain barrier, TPGS

Xiaohai Cui,1–3,* Jing Zhang,1,* Jiajun Lv,4 Yan Yan,1 Xu Liu,1 Jizhao Wang,1 Yi Lv,2,3,5 Jia Zhang1 1The Second Department of Thoracic Surgery, 2Institute of Advanced Surgical Technology and Engineering, The First Affiliated Hospital of Xi’an Jiaotong University, 3Shaanxi Provincial Regenerative Medicine and Surgical Engineering Research Center, 4Xi’an Jiaotong University Health Science Center, 5Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China *These authors have contributed equally to this work Background: Forkhead box Q1 (FOXQ1, also known as HFH1), a member of the forkhead transcription factor family, has been demonstrated to be overexpressed in multiple tumors and is thought to be an indicator of poor clinical outcomes. Methods: A meta-analysis using qualified relevant literature was performed to evaluate the prognostic significance of FOXQ1 in various malignant solid tumors. A search of electronic databases was conducted in MEDLINE, Embase, and the Cochrane Library to identify relevant studies published from 1966 to July 30, 2016, and the studies were identified by further evaluation. The pooled hazard ratios (HRs) with 95% confidence intervals (CIs) for analyses were assessed to investigate the association between FOXQ1 expression and overall survival (OS) of patients with malignant solid tumors. Results: A total of 1,520 patients from six studies (seven cohorts) with multiple malignant solid tumors were included. For OS, high FOXQ1 expression could significantly predict worse outcome with the pooled HR of 1.38 (95% CI: 1.17–1.59; P

Junhong Lv,1 Shaohuan Lin,1 Panli Peng,2 Changqing Cai,2 Jianming Deng,1 Mingzhi Wang,1 Xuejun Li,1 Rongsheng Lin,3 Yu Lin,4 Ailing Fang,5 Qiling Li5 1Thoracic Surgeons Department, 2Oncology No 2 Department, Guangdong No 2 Provincial People’s Hospital, Guangzhou, 3Department of Oncology, Shunde Longjiang Hospital, Foshan, 4Department of Gastroenterology, Puning Overseas Chinese Hospital, 5Galactophore Department, Puning Maternity and Child Care Hospital, Puning, People’s Republic of China Abstract: Esophageal squamous cell carcinoma (ESCC) is often diagnosed at late incurable stage and lacks effective treatment strategy. Bufadienolides are cardiotonic steroids isolated from the skin and parotid venom glands of the toad Bufo bufo gargarizans Cantor with novel anticancer activity. However, there is little information about the effects and action mechanisms of bufadienolides on ESCC cells. In this study, the in vitro and in vivo anti-ESCC activities of bufadienolides, including bufalin (Bu) and arenobufagin (ArBu), were examined and the underlying molecular mechanisms were elucidated. The results showed that ArBu exhibited higher anticancer efficacy than Bu against a panel of five ESCC cells, with IC50 values ranging from 0.8 µM to 3.6 µM. However, ArBu showed lower toxicity toward Het-1A human normal esophageal squamous cells, indicating its great selectivity between cancer and normal cells. Moreover, ArBu effectively induced ESCC cell apoptosis mainly by triggering caspase activation through intrinsic and extrinsic pathways. Treatment of ESCC cells also significantly activated p53 signaling by enhancing its phosphorylation. Interestingly, transfection of cells with p53 small interfering RNA significantly inhibited the ArBu-induced p53 phosphorylation and the overall apoptotic cell death. Furthermore, ArBu also demonstrated novel in vivo anticancer efficacy by inhibiting the tumor growth through activation of p53 pathway. Taken together, these results demonstrate the p53-targeting therapeutic potential of bufadienolides against ESCC. Keywords: arenobufagin, apoptosis, esophageal squamous cell carcinoma, p53

Jie Lv, Wei Ou, Xiao-Hua Zou, Yin Yao, Jin-Li Wu Department of Anesthesia, Guizhou Medical University Affiliated Hospital, Guiyang, People’s Republic of China Abstract: The study aimed to explore the effect of dexmedetomidine (DEX) on hippocampal neuron development process and on molecular expression of brain-derived neurotrophic factor (BDNF)-tyrosine receptor kinase B (TrkB) signaling pathway in neonatal rats. The hippocampal neuron cells were isolated from newborn neonatal rats and cultured in vitro. One control group and three treated groups with 1, 10, and 100 µmol/L DEX were used for the study. Cell activity and apoptosis were detected by the MTT and terminal deoxynucleotidyl transferase-mediated biotinylated uridine triphosphate (UTP) nick end labeling assays. The synaptophysin (SYN) and postsynaptic density 95 (PSD95) were detected by quantitative polymerase chain reaction. There was no difference in the viability of neuron cells among the different dose groups of DEX and the control group during days 2-10 (P>0.05). Compared to the control group, there was no significant difference (P>0.05) in the expressions of SYN and PSD95 in the groups treated with 1 and 10 µmol/L DEX, whereas significant difference in the expression was observed in the group treated with 100 µmol/L DEX (P

Ying Qian,1,2 Yanning Liu,3 Qiuyue Yan,1,2 Juan Lv,2 Xiaoyan Ni,2 Yunlu Wu,1,2 Xuejun Dong1,2 1The Key Laboratory of Laboratory Medicine, Ministry of Education of China; School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, Zhejiang, People's Republic of China; 2Shaoxing People's Hospital, Shaoxing Hospital of Zhejiang University, Shaoxing, Zhejiang, People's Republic of China; 3State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, Zhejiang, People's Republic of ChinaPurpose: One of the most challenging aspects of breast carcinoma chemotherapy is the rapid acquirement of drug resistance. Improving the sensitivity to chemotherapeutic drugs is very important for successful treatment. Mus81 plays an important role in maintaining the stability of the genome and DNA repair. However, recent studies suggested that Mus81 expression levels correlate well with resistance to DNA-damaging drugs. The present study aimed to investigate the role of Mus81 on the chemosensitivity of breast carcinoma cells in response to 5-fluorouracil (5-FU), a chemotherapeutic drug that is widely used for treatment of breast malignancies.Methods: The expression of Mus81 in MCF-7 and T47D cells was suppressed by small interfering RNA (siRNA). mRNA and protein levels of Mus81 were analyzed by quantitative real-time polymerase chain reaction and Western blot. Cell viability and colony survival were determined by Cell Counting Kit-8 and plate colony formation assay, respectively. Cell cycle and apoptosis were detected by flow cytometry.Results: 5-FU inhibited the cell viability of MCF-7 and T47D cells in a concentration-dependent manner. We found that the Mus81-silenced MCF-7 and T47D cells exhibited decreased cell viability and clonogenic survival, but increased G2 accumulation, in response to 5-FU. In addition, Mus81 deficiency resulted in increased apoptosis and p53 expression in MCF-7 after 5-FU treatment. However, Mus81 deficiency did not affect the apoptosis of T47D cells with 5-FU.Conclusion: Taken together, our data suggest that Mus81 inhibition significantly increased the chemosensitivity of MCF-7 and T47D cells in response to 5-FU. Thus, Mus81 siRNA is potentially a useful adjuvant strategy for breast cancer chemotherapy.Keywords: Mus81, siRNA, 5-FU, breast carcinoma, hemosensitivity, p53