Search

Chen Wang, Jinping Yuan, Huiwen Yu, Jiaying Lin, Bingxue Bai Department of Dermatology, The Second Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of ChinaCorrespondence: Bingxue Bai, Department of Dermatology, The Second Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China, Email baibingxue@hrbmu.edu.cnBackground: Psoriasis and vitiligo are two common autoimmune skin diseases with increased risk of comorbidities, but the common molecular mechanism about the occurrence of these two diseases is still unknown.Objective: This study aimed to identify the combined genetic profiles and evaluate the potential mechanism underlying the occurrence of this complication.Methods: The Gene Expression Omnibus (GEO) database was used to obtain the gene expression profiles of psoriasis (GSE30999) and vitiligo (GSE75819), and common differentially expressed genes (DEGs) were identified using GEO2R. DEGs were analyzed using functional enrichment analysis, protein-protein interaction (PPI) network and module construction, hub gene identification, and co-expression analysis. And hub genes were identified using Cytoscape software, and the gene expression of hub genes were validated in psoriasis (GSE13355) and vitiligo (GSE65127) datasets and immunohistochemistry at the clinical sample.Results: A total of 164 common DEGs with the same trend (137 upregulated and 27 downregulated) were selected for subsequent analysis. Functional analysis emphasized the important roles of the cell cycle and mitotic cell division, cytoskeletal reorganization, and chromatin remodeling in the complications of these two diseases. Fourteen important hub genes were identified, including BUB1, CEP55, CDK1, TOP2A, CENPF, PBK, MELK, CCNB2, MAD2L1, NUSAP1, TTK, NEK2, CDKN3, and PTTG1. Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) may be an important immune checkpoint in the pathogenesis of the comorbidities.Conclusion: Our study identified hub genes and potential mechanisms underlying psoriasis and vitiligo complications. And we proposed a new spatio-temporal theory and the probable immune checkpoint for the pathogenesis of the comorbidity which may provide new ideas for the further research.Keywords: psoriasis, vitiligo, comorbidity, differentially expressed genes, bioinformatics, mitotic cell division, cell cycle, cytoskeleton, immune checkpoint

Yingrui Ma,1,* Bufan Bai,1,* Deng Liu,1 Rong Shi,2 Qianmei Zhou1,3 1Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Department of Intensive Care Medicine, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 3Shanghai Institute of Stem Cell Research and Clinical Translation, Dongfang Hospital Affiliated to Shanghai Tongji University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Rong Shi, Department of Intensive Care Medicine, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine Shanghai, Shanghai, People’s Republic of China, Email doctorshi@126.com Qianmei Zhou, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China, Email tazhou@163.comBackground: Shenqi Fuzheng Injection (SQFZ) is a traditional Chinese medicine injection consists of extracts of Codonopsis pilosula and Astragalus mongholicus. Combining SQFZ with conventional chemotherapy may improve the therapeutic efficacy and reduce side-effects of chemotherapy. However, the mechanisms of SQFZ reducing cisplatin-induced kidney injury are still unclear.Methods: The main compounds of SQFZ were identified via UPLC-Q-TOF-MS technique. Using multiple databases to predict potential targets for SQFZ. We established a breast cancer model by injecting 4T1 cells into mice. Tumor growth and body weight were observed. Serum blood urea nitrogen (BUN), creatinine (CRE), and glutathione (GSH) levels were measured. The extent of their kidney injury was measured by hematoxylin-eosin staining (HE). Cell apoptosis was identified using Hoechst33258 staining, flow cytometry and TUNEL. We evaluated H2AX and stimulator of interferon genes (STING) expression by immunohistochemistry (IHC), and assessed apoptosis-associated proteins by Western blotting analysis. We also evaluated mitochondrial function. The secretion of the inflammatory cytokines in serum was observed using ELISA assay. The effect of the STING pathway in HK-2 renal tubular epithelial cells exposed to cisplatin alone or combined with SQFZ.Results: The potential targets of SQFZ on kidney injury mainly related to inflammatory responses, oxidation and antioxidant, apoptosis as well as IFN signaling pathway. Cisplatin significantly reduced animal weight, while there were no changes in the combination SQFZ and cisplatin. SQFZ counteracted cisplatin-induced BUN and CRE elevation. SQFZ ameliorated the oxidative stress induced by cisplatin. It diminished cisplatin-induced apoptosis and mitochondrial DNA damage and reversed cisplatin-induced cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)/STING signaling pathway activation. It also improved the mitochondrial dysfunction induced by cisplatin.Conclusions: The results of the present study suggested that SQFZ effectively reduced cisplatin-induced kidney injury by inhibiting cGAS/STING signaling pathway.Keywords: Shenqi Fuzheng Injection, cisplatin, kidney injury, mitochondrial, cGAS/STING, breast cancer, network pharmacology

Fengyao Liu,1,2,* Haochen Wang,2,3,* Bingqing Bai,2,4 Han Yin,5 Yuting Liu,2 Yu Wang,2 Quanjun Liu,2 Shuxia Wang,6 Huan Ma,3 Qingshan Geng1,2,5 1School of Medicine, South China University of Technology, Guangzhou, People’s Republic of China; 2Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, People’s Republic of China; 3Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, People’s Republic of China; 4School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou, People’s Republic of China; 5Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, the First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, People’s Republic of China; 6Department of Nuclear Medicine, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Huan Ma, Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, No. 106 Zhongshan Er Road, Guangzhou, People’s Republic of China, Fax +8620-83827812, Email mahuandoctor@163.com Qingshan Geng, Department of Cardiology, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, the First Affiliated Hospital, Southern University of Science and Technology), 1080 Cuizhu Road, Luohu District, Shenzhen, Guangdong, Fax +0755-25533018, Email gengqsh@163.netPurpose: Mental stress induced myocardial ischemia (MSIMI) is regarded as the primary cause of the angina with no obstructive coronary artery disease (ANOCA). Obstructive sleep apnea (OSA) is autonomously linked to obstructive coronary heart disease, hypertension, and sudden cardiac death. Similar to the impact of psychological stress on the cardiovascular system, individuals with OSA experience periodic nocturnal hypoxia, resulting in the activation of systemic inflammation, oxidative stress, endothelial dysfunction, and sympathetic hyperactivity. The contribution of OSA to MSIMI in ANOCA patients is unclear. To explore the prevalence of OSA in ANOCA patients and the correlation between OSA and MSIMI, a prospective cohort of female ANOCA patients was recruited.Patients and Methods: We recruited female patients aged 18 to 75 years old with ANOCA and evaluated MSIMI using positron emission tomography-computed tomography. Subsequently, Level III portable monitors was performed to compare the relationship between OSA and MSIMI.Results: There is higher REI (7.8 vs 2.6, P=0.019), ODI (4.7 vs 9.2, P=0.028) and percentage of OSA (67.74% vs 33.33%, P=0.004) in MSIMI patients. The patients diagnosed with OSA demonstrated higher myocardial perfusion imaging scores (SSS: 1.5 vs 3, P = 0.005, SDS: 1 vs 3, P = 0.007). Adjusted covariates, the risk of developing MSIMI remained 3.6 times higher in OSA patients (β=1.226, OR = 3.408 (1.200– 9.681), P = 0.021).Conclusion: Patients with MSIMI exhibit a greater prevalence of OSA. Furthermore, the myocardial blood flow perfusion in patients with OSA is reduced during mental stress.Keywords: obstructive sleep apnea, mental stress induced myocardial ischemia, angina with no obstructive coronary artery disease, myocardial perfusion imaging

Aineng Peng,1 Jianbo Chai,2 Haiyuan Wu,1 Bing Bai,3 Huihui Yang,1 Weizhi He,1 Yonghou Zhao2 1Heilongjiang University of Chinese Medicine, Harbin, 150040, People’s Republic of China; 2Heilongjiang Mental Hospital, Harbin, 150036, People’s Republic of China; 3Tongde Hospital of Zhejiang Province, Hangzhou, 311100, People’s Republic of ChinaCorrespondence: Yonghou Zhao, Heilongjiang Mental Hospital, 153 Hengdao Street, Harbin, Heilongjiang, 150036, People’s Republic of China, Tel +86 13904638645, Email zyszbx2020@126.comAbstract: Schizophrenia is a disease with a complex pathological mechanism that is influenced by multiple genes. The study of its pathogenesis is dominated by the dopamine hypothesis, as well as other hypotheses such as the 5-hydroxytryptamine hypothesis, glutamate hypothesis, immune-inflammatory hypothesis, gene expression abnormality hypothesis, and neurodevelopmental abnormality hypothesis. The first generation of antipsychotics was developed based on dopaminergic receptor antagonism, which blocks dopamine D2 receptors in the brain to exert antipsychotic effects. The second generation of antipsychotics acts by dual blockade of 5-hydroxytryptamine and dopamine receptors. From the third generation of antipsychotics onwards, the therapeutic targets for antipsychotic schizophrenia expanded beyond D2 receptor blockade to explore D2 receptor partial agonism and the antipsychotic effects of new targets such as D3, 5-HT1A, 5-HT7, and mGlu2/3 receptors. The main advantages of the second and third generation antipsychotics over first-generation antipsychotics are the reduction of side effects and the improvement of negative symptoms, and even though third-generation antipsychotics do not directly block D2 receptors, the modulation of the dopamine transmitter system is still an important part of their antipsychotic process. According to recent research, several receptors, including 5-hydroxytryptamine, glutamate, γ-aminobutyric acid, acetylcholine receptors and norepinephrine, play a role in the development of schizophrenia. Therefore, the focus of developing new antipsychotic drugs has shifted towards agonism or inhibition of these receptors. Specifically, the development of NMDARs stimulants, GABA receptor agonists, mGlu receptor modulators, cholinergic receptor modulators, 5-HT2C receptor agonists and alpha-2 receptor modulators has become the main direction. Animal experiments have confirmed the antipsychotic effects of these drugs, but their pharmacokinetics and clinical applicability still require further exploration. Research on alternative targets for antipsychotic drugs, beyond the dopamine D2 receptor, has expanded the potential treatment options for schizophrenia and gives an important way to address the challenge of refractory schizophrenia. This article aims to provide a comprehensive overview of the research on therapeutic targets and medications for schizophrenia, offering valuable insights for both treatment and further research in this field.Keywords: schizophrenia, target, neurotransmitter, antipsychotic drugs

Abstract:

Yu Ni,1,* Yuqin Chen,2,* Xuheng Jiang,3 Tao Pu,1 Ling Zhang,4 Shaobin Li,2 Linhong Hu,1 Bing Bai,1 Tingting Hu,1 Limei Yu,2 Yibin Yang1,2 1Department of Nephrology, Affiliated Hospital of Zunyi Medical University, Zunyi, 563003, People’s Republic of China; 2Key Laboratory of Cell Engineering of Guizhou Province, Zunyi City, Affiliated Hospital of Zunyi Medical University, Zunyi, 563003, People’s Republic of China; 3Department of Emergency, Affiliated Hospital of Zunyi Medical University, Zunyi, 563003, People’s Republic of China; 4Zhuhai Campus of Zunyi Medical University, Zhuhai, 519041, People’s Republic of China*These authors contributed equally to this workCorrespondence: Limei Yu, Department of Nephrology, Affiliated Hospital of Zunyi Medical University, Zunyi, 563003, People’s Republic of China, Email ylm720@sina.com Yibin Yang, Key Laboratory of Cell Engineering of Guizhou Province, Zunyi City, Affiliated Hospital of Zunyi Medical University, Zunyi, 563003, People’s Republic of China, Email yyb1011@sina.comBackground and Aims: Diabetic kidney disease (DKD) is a prevalent and intractable microvascular complication of diabetes mellitus (DM), the process of which is closely related to abnormal expression of angiogenesis-regulating factors (ARFs). Stem cell transplantation might be a novel strategy for treating DKD. This study aims to explore the effect of transplantation of human amniotic mesenchymal stem cells (hAMSCs) on renal microangiopathy in a type 1 DKD rat model (T1DRM).Methods: Seventy-two rats were randomly divided into three groups, including normal control group, DKD group, and hAMSCs transplantation group. T1DRM was established using a rat tail vein injection of streptozotocin (STZ) (55 mg/kg). hAMSCs were obtained from placental amniotic membranes during cesarean delivery and transplanted at 3 and 4 weeks through penile veins. At 6, 8, and 12 weeks following transplantation, blood glucose levels, renal function, pathological kidney alterations, and the expressions of ARFs’ mRNA and protein were analyzed.Results: In T1DRM, transplanted hAMSCs that were homed at the injured site of kidneys increased ARFs’ expression and decreased blood glucose levels. Compared to the DKD group, the levels of 24-h urinary protein, serum creatinine, urea, and kidney injury molecule-1 (KIM-1) were reduced in hAMSCs transplantation group. In terms of renal pathology such as the degree of basement membrane thickening, hAMSCs transplantation was also less severe than the DKD group, thereby alleviating kidney injury.Conclusion: hAMSCs transplantation might ameliorate STZ-induced chronic kidney injury through increasing ARFs’ expression in kidneys and lowering blood glucose levels.Keywords: DKD, hAMSCs, renal microangiopathy, angiogenesis-regulating factors

Bing Bai, Zhiqiong Guo Business School, Jiangsu Normal University, Xuzhou, 221116, People’s Republic of ChinaCorrespondence: Zhiqiong Guo, Email joan_monday@163.comBackground: Improving the health status of users through the use of digital health information systems has drawn the attention of practitioners and academics under the tide of the digital revolution, specifically in the time of global pandemic of COVID-19, and as a result, online medical consultation has developed rapidly.Purpose: Empirical studies, however, are lacking in terms of gaining insight into use digital health information system driven by the digital revolution under COVID-19 and identifying the factors for retaining users and encouraging their continuing use. To solve this problem, this study seeks to explore the factors that influence users’ intention to use digital health information system.Methods: This study extended the Unified Theory of Acceptance and Use of Technology (UTAUT) model by introducing components of perceived risks into the model. Structural equation modeling was adopted to evaluate the research model based on an empirical survey of 241 users in China.Results: As indicated by the results, users’ continuance usage behavior to digital health information system is shaped by intention to use and facilitating conditions, with effort expectancy, social influence, perceived ease of use and perceived enjoyment exerting indirect positive effects on continuance usage behavior via intention to use. In contrast, perceived risk and perceived cost have indirect negative impact on continuance usage behavior.Conclusion: The findings of this study can not only help the practitioners better understand the users’ continuance usage behavior towards digital health information system driven by digital revolution in the time of COVID-19 pandemic and further tap into the potential market but also make up the short of traditional technology acceptance model explanatory by the extended UTAUT model.Keywords: digital health information system, online medical, continuance usage behavior, UTAUT model

In this project, the creation and application of computer-based fault detection methods for transmission lines with multiple terminals are discussed.These methods are part of a fault-finding system that precisely locates the fault site by using voltage and current signal measurements from smart electronic devices installed on transmission-line terminals. The transformer loading, connection type, and electrical characteristics are all data that the algorithms have access to. The power system components used by the fault-location techniques are likewise presented in this project’s phase component models.

The COVID-19 pandemic has formed significant disruptions in the education system, prompting profound changes in students' psychosocial well-being and adjustment to face-to-face classes. This study aimed to assess the psychosocial well-being and adjustment levels of secondary school students transitioning to in-person classes and to design a school-based mental health program. This present study employed a quantitative, descriptive research design using the Pagsusuri sa Sikososyal para sa Balik Eskwela (PSBE), an adopted questionnaire from the Department of Education's Psychosocial Activity Pack, to gather data from 375 secondary school students, 212 were junior high school students, and 163 were senior high school students. Further, 197 were females, and 178 were males. Notable findings indicated that students generally exhibited strong psychosocial well-being skills upon returning to face-toface classes, with an overall rating of 3.75. In contrast, their psychosocial adjustment to the return of in-person classes was rated at 3.96, denoting high interest. However, learners expressed concerns regarding their ability to articulate thoughts and feelings and demonstrate strengths and abilities in school activities. These results carry implications for guidance and counseling services, implementing a mental health awareness program, integrating the Psychosocial Support Activity Pack in the Homeroom Guidance, and future research in this field. [ABSTRACT FROM AUTHOR]

Conventional ultrasound technology based on spot scanning or phased array encounters significant challenge in real-time imaging with a single detector. In this paper, we present a Hadamard acoustic correlated imaging based on photoacoustic modulation with one transducer. The process of accurately generating the Hadamard acoustic field is to apply the carbon-nanotubes–polydimethylsiloxane composite to absorb the optimized Hadamard basis pattern. Taking advantage of correlated imaging, our system without scanning can reduce imaging artifacts and its resolution could be about four times higher than that of traditional ultrasound imaging. The use of a single transducer rather than an array of transducers can reduce the cost of the imaging system. Therefore, the proposed scheme can find applications in biomedical imaging and nondestructive evaluation. [ABSTRACT FROM AUTHOR]

Zhongxiang Xiao,1,2 Fengli Xu,3 Xiaona Zhu,1 Bin Bai,1 Lu Guo,4 Guang Liang,1 Xiaoou Shan,3 Yali Zhang,2 Yunjie Zhao,2 Bing Zhang1,2 1Affiliated Yueqing Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325600, People’s Republic of China; 2Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China; 3Department of Pediatrics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, People’s Republic of China; 4Department of Pharmacy, The First People’s Hospital of Huzhou, Huzhou, Zhejiang 313000, People’s Republic of ChinaCorrespondence: Bing ZhangAffiliated Yueqing Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325600, People’s Republic of ChinaTel +86-577-61575506Email zhangbing197102@163.com Yunjie ZhaoChemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, People’s Republic of ChinaTel +86-577-86699892Email aabye1100@aliyun.comBackground: Acute lung injury (ALI) is characterized by high prevalence and high mortality. Thus far, no effective pharmacological treatment has been made for ALI in clinics. Inflammation is critical to the development of ALI. Curcumin analog C66, having reported as an inhibitor of c-Jun N-terminal kinase (JNK), exhibits anti-inflammatory property both in vitro and in vivo. However, whether C66 is capable of reducing lipopolysaccharide (LPS)-induced ALI through the inhibition of inflammation by targeting JNK remains unknown.Methods: Intratracheal injection of LPS was employed to build a mouse ALI model. H&E staining, wet/dry ratio, immunofluorescence staining, inflammatory cell detection, and inflammatory gene expression were used to evaluate lung injury and lung inflammation. In vitro, LPS was used to induce the expression of inflammatory cytokines both in protein and gene levels.Results: The results of our studies showed that the pretreatment with C66 and JNK inhibitor SP600125 was capable of attenuating the LPS-induced ALI by detecting pulmonary edema, pathological changes, total protein concentration, and inflammatory cell number in bronchoalveolar lavage fluid (BALF). Besides, C66 and SP600125 also suppressed LPS-induced inflammatory cytokine expression in BALF, serum, and lung tissue. In vitro, LPS-induced production of TNF-α and IL-6 and gene expression of TNF-α, IL-6, IL-1β, and COX-2 could be inhibited by the pretreatment with C66 and SP600125. It was found that C66 and SP600125 could inhibit LPS-induced phosphorylation of JNK both in vitro and in vivo.Conclusion: In brief, our results suggested that C66 protects LPS-induced ALI through the inhibition of inflammation by targeting the JNK pathway. These findings further confirmed the pivotal role of JNK in ALI and implied that C66 is likely to serve as a potential therapeutic agent for ALI.Keywords: acute lung injury, lipopolysaccharide, JNK, C66, inflammation

Xiao Z, Xu F, Zhu X, et al. Drug Des Devel Ther. 2019;1:4161–4171. The authors have advised Funding section on page 4170 should be: Funding This study was supported by the Natural Science Funding of China (21572166 to Y.Z., and 81770850 to X.S.), Zhejiang Provincial Natural Science Funding (LY19H310001 to B.Z., and LY17H050007 to X.S.), and Project for Science and Technology of Huzhou (2015GY08 to L.G.). Read the original article

Wei Zhang,1,* Yiwu Zhou,1,* Bin Bai,1 Shikai Yu,1 Jing Xiong,1 Chen Chi,1 Jiadela Teliewubai,1 Jue Li,2 Jacques Blacher,3 Yi Zhang,1 Yawei Xu1 1Department of Cardiology, Shanghai Tenth People’s Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China; 2Department of Prevention, School of Medicine, Tongji University, Shanghai, People’s Republic of China; 3Diagnosis and Therapeutic Center, Hôtel-Dieu, Paris Descartes University, AP-HP, Paris, France *These authors contributed equally to this work Background: Left ventricular hypertrophy (LVH) is one of the preclinical manifestations of hypertensive target organ damage (TOD). However, it remains unclear which electrocardiographic criterion perform better in diagnosing LVH. Purpose: To investigate the consistency of LVH diagnosed by electrocardiography (ECG) and echocardiography (ECHO). Taking LVH by ECHO as reference, to compare three different ECG criteria (Sokolow-Lyon, Cornell and Cornell Product criteria) and find the best ECG indicator for identifying LVH in community-based elderly Chinese. Patients and methods: Echocardiography and electrocardiography were applied to define LVH in 1789 elderly Chinese aged >65 years old in communities located at the northern Shanghai. Echocardiographic LVH (ECHO-LVH) was defined by left ventricular mass indexed for Body Surface Area (LVM/BSA) or for height2.7 (LVM/height2.7). Electrocardiographic LVH (ECG-LVH) was defined by Sokolow-Lyon (SL), Cornell and Cornell Product (CP) criteria. ECHO-LVH was defined by LVM/BSA≥125 g/m2 in male or ≥110 g/m2 in female (LVH1); LVM/BSA≥115 g/m2 in male, or ≥95 g/m2 in female (LVH2) and LVM/height2.7 ≥51 g/m2.7 in male or ≥47 g/m2.7 in female (LVH3). Results: As compared with SL and Cornell criteria, CP had the greatest correlation coefficient in the association with echocardiography-defined LVH, except for LVM/BSA in men. Of note, CP criterion had the greatest area under curve of ROC than Cornell criterion and the SL index, not only in total population but also in subgroups classified by blood pressure. Conclusion: In ECG-LVH criteria, CP criterion complies better than SL index and Cornell criterion in assessing cardiac hypertrophy. Keywords: left ventricular hypertrophy, electrocardiography, echocardiography, population study, accuracy

Lina Tang,1,* Yijie Chen,1,* Zhongshi Du,1 Zhaoming Zhong,1 Qin Chen,2 Lichun Yang,3 Ruoxia Shen,3 Yan Cheng,4 Zizhen Zhang,4 Ehui Han,5 Zhihong Lv,5 Lijun Yuan,6 Yong Yang,6 Yinrong Cheng,7 Lei Yang,7 Shengli Wang,8 Baoyan Bai,8 Jun Luo2 1Department of Ultrasound, Fujian Cancer Hospital and Fujian Medical University Cancer Hospital, Fuzhou 350014, Fujian Province, China; 2Department of Ultrasound, Sichuan Provincial People’s Hospital, Chengdu 610072, Sichuan Province, China; 3Department of Ultrasound, The Third Affiliated Hospital of Kunming Medical University and Yunnan Cancer Hospital, Kunming 650118, Yunnan Province, China; 4Department of Ultrasound, Qujing City First People’s Hospital, Qujing 655000, Yunnan Province, China; 5Department of Ultrasound, Huangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic University, Edong Healthcare Group, Huangshi 435000, Hubei Province, China; 6Department of Ultrasound, Tangdu Hospital, Fourth Military Medical University, Xi’an 710032, Shanxi Province, China; 7Department of Ultrasound, Chengdu First People’s Hospital, Chengdu 610000, Sichuan Province, China; 8Department of Ultrasound, Yanan University Affiliated Hospital, Yan’an 716000, Shanxi Province, China *These authors contributed equally to this work Purpose: To evaluate a classification model of contrast-enhanced ultrasound (CEUS) and examine the characteristics of patients with false-negative diagnosis. Patients and methods: A retrospective secondary analysis of a multicenter trial of CEUS for breast cancer diagnosis (from August 2015 to April 2017) was undertaken. Patients (n=1,023) with Breast Imaging Reporting and Data System 4–5 lesions on B-mode ultrasound underwent CEUS. Pathological diagnoses were available from surgical or biopsy specimens for correlation. Lesion maximum diameter (LMD), distance to the papilla (DtP), distance from the superficial edge of the lesion to the skin (DtS), distance from the deep edge of the lesion to the pectoralis muscle (DtPM), and body mass index (BMI) were evaluated. Results: Median age and BMI were 48.0 and 41.2 years and 23.2 and 22.4 kg/m2 for patients with malignant and benign lesions, respectively. Overall sensitivity, specificity, and accuracy of CEUS for malignancy were 89.4%, 65.3%, and 75.8%, respectively. The patients with true-positive and false-negative diagnosis (ie, with malignant lesion) were older than those with false-positive and true-negative diagnosis (ie, with benign lesion). Patients with true-positive and false-positive diagnoses had higher BMI than patients with true-negative and false-negative diagnoses (P=0.004). Patients with true-positive and false-negative diagnoses had larger LMD and DtP, as well as smaller DtS and DtPM. Conclusion: Older age, higher BMI, larger LMD and DtP, and smaller DtS and DtPM were associated with malignant lesions on CEUS. Patients with these characteristics should undergo further imaging. Keywords: breast cancer, ultrasound, contrast-enhanced ultrasound

Zhibing Tang,1,2,* Lin Zhao,1,3,* Zaixing Yang,3 Zhaohui Liu,4 Jia Gu,3 Bing Bai,3 Jinlian Liu,2 Jiaying Xu,3 Huilin Yang1 1Department of Orthopedics, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou, China; 2Department of Orthopaedic Surgery, Suzhou Kowloon Hospital, Shanghai Jiaotong University School of Medicine, Suzhou, China; 3Institute of Quantitative Biology and Medicine, SRMP and RAD-X, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou, China; 4Department of Anatomy and Histology and Embryology, Basic Medical and Biological Sciences, School of Medicine, Soochow University, Suzhou, China *These authors contributed equally to this work Background: Graphene and its derivative graphene oxide (GO) have been implicated in a wide range of anticancer effects. Purpose: The objective of this study was to systematically evaluate the toxicity and underlying mechanisms of GO on two osteosarcoma (OSA) cancer cell lines, MG-63 and K7M2 cells. Methods: MG-63 and K7M2 cells were treated by GO (0-50 µg/mL) for various time periods. Cell viability was tested by MTT and Live/Dead assays. A ROS Detection Kit based on DHE oxidative reaction was used for ROS detection. An Annexin V-FITC Apoptosis Kit was used for apoptosis detection. Dansylcadaverine (MDC) dyeing was applied for seeking unspecific autophagosomes. Western blot and Immunofluorescence analysis were used for related protein expression and location.Results: K7M2 cells were more sensitive to GO compared with MG-63 cells. The mechanism was attributed to the different extent of the generation of reactive oxygen species (ROS). In K7M2 cells, ROS was easily stimulated and the apoptosis pathway was subsequently activated, accompanied by elevated expression of proapoptosis proteins (such as caspase-3) and decreased expression levels of antiapoptosis proteins (such as Bcl-2). A ROS inhibitor (N-acetylcysteine) could alleviate the cytotoxic effects of GO in K7M2 cells. However, the production of ROS in MG-63 cells was probably inhibited by the activation of an antioxidative factor, nuclear factor-E2-related factor-2, which translocated from the cytoplasm to the nucleus after GO treatment, while a nuclear factor-E2-related factor-2 inhibitor (ML385) significantly increased ROS production in MG-63 cells when combined with GO treatment. In addition, autophagy was simultaneously stimulated by characteristic autophagosome formation, autophagy flux, and increased the expression level of autophagy-related proteins (such as LC3I to LC3II conversion, ATG5, and ATG7). Conclusion: This paper proposes various underlying mechanisms of the anticancer effect of GO. The novel synthetic use of GO with an oxidizing agent is the key step for further potential applications in clinical OSA cancer therapy. Keywords: graphene oxide, osteosarcoma cancer, ROS, apoptosis, autophagy