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Li F, Wang F, Zhu C, Wei Q, Zhang T, Zhou YL. Int J Nanomedicine. 2018;13:2295–2307. The Editor and Publisher of International Journal of Nanomedicine wish to retract the published article. Concerns were raised regarding the integrity of the data and an investigation found overlap in images from Figure 4. Specifically, The image used in Figure 4D, 48 hours, Scramble has regions of overlap with Figure 4D, 48 hours, miR-221 inhibitor. The authors responded to our queries and provided data associated with the reported study. However, despite the authors’ assistance, a satisfactory explanation for how the images came to be duplicated could not be provided, and the validity of the published work could not be verified. The decision was made to retract the article and the authors were notified of this. We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.

Can Zhu,1 Yuning Liu,2 Haiying Wu1 1Department of Obstetrics and Gynecology, Henan Provincial People’s Hospital, Zhengzhou City, Henan Province, 450003, People’s Republic of China; 2Department of Neonatal Intensive Care Unit, Henan Provincial People’s Hospital, Zhengzhou City, Henan Province, 450003, People’s Republic of ChinaCorrespondence: Haiying WuDepartment of Obstetrics and Gynecology, Henan Provincial People’s Hospital, No. 7 Weiwu Road, Jinshui District, Zhengzhou City, Henan Province, 450003, People’s Republic of ChinaEmail haiyingwuhenan@163.comBackground: CircRNA actin-related protein 2 homolog (circACTR2) has been reported to participate in high glucose-induced disorders, while its role in gestational diabetes mellitus (GDM) is unknown. This study analyzed the expression pattern of circACTR2 in GDM and evaluated its predictive value for GDM and its adverse events.Methods: C\ircACTR2 expression in plasma of 200 pregnant females with a gestational age of about 1 month was analyzed once per month using RT-qPCR. The development of GDM was monitored until delivery. Adverse events, including premature delivery, miscarriage, intrauterine distress, intrauterine death, fetal malformation, intrauterine infection, hypertension, and macrosomia, were recorded.Results: During the follow-up, a total of 70 patients were diagnosed with GDM. The 70 GDM patients showed significantly higher plasma circACTR2 levels compared to the remaining 130 pregnant females. With the median plasma circACTR2 level in the first month as the cutoff value, the 200 patients were divided into the high and low circACTR2 level groups, and their GDM-free curves were plotted and compared. Patients in high circACTR2 level group showed a higher incidence of GDM. Moreover, among the 70 patients diagnosed with GDM, high circACTR2 levels were also closely correlated with higher rates of premature delivery, miscarriage, intrauterine death, fetal malformation, intrauterine infection, and hypertension, but not with macrosomia and intrauterine distress.Conclusion: CircACTR2 is overexpressed in GDM. The increased plasma circACTR2 levels in pregnant women predict GDM, and higher plasma circACTR2 levels in GDM patients predict multiple adverse events.Keywords: gestational diabetes mellitus, circACTR2, adverse events

Heming Lu,1,* Yuying Wu,2,* Xu Liu,1 Huixian Huang,1 Hailan Jiang,1 Chaohua Zhu,1 Yuping Man,3 Pei Liu,4 Xianglong Li,1 Zhaohong Chen,1 Xianfeng Long,1 Qiang Pang,1 Shan Deng,1 Junzhao Gu1 1Department of Radiation Oncology, People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530021, People’s Republic of China; 2Department of Gynecology, People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530021, People’s Republic of China; 3Department of Radiology, People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530021, People’s Republic of China; 4Department of Oncology, Youjiang Medical University for Nationalities, Baise, 533000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Heming LuDepartment of Radiation Oncology, People’s Hospital of Guangxi Zhuang Autonomous Region, No. 6 Taoyuan Road, Nanning, 530021, People’s Republic of ChinaTel +86-771-218-6806Email luhming3632@163.comPurpose: To evaluate the role of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in predicting early treatment response.Materials and Methods: Patients with locally advanced cervical cancer (LACC) treated with concurrent chemoradiotherapy (CCRT) were enrolled. Pelvic DCE-MRI scans were performed before RT (pre-RT), in the middle of RT (mid-RT), and at the end of RT (post-RT), separately. Parameters (ie, Ktrans, Kep, and Ve) were measured. Pre-, mid-, and post-RT Ktrans were denoted as Ktrans-preTx, Ktrans-midTx, and Ktrans-postTx, respectively. And the same denoting rule also went for Kep and Ve. Difference for the same parameter such as Ktrans measured between two consecutive time points was calculated as second Ktrans value minus first Ktrans value. The differences in Ktrans between pre-RT and post-RT, between pre-RT and mid-RT, and between mid-RT and post-RT were denoted as ΔKtrans-post-preTx, ΔKtrans-mid-preTx, and ΔKtrans-post-midTx, respectively, and the same denoting rule was also applied to Kep and Ve.Results: A total of 57 patients were enrolled. After the treatment, 31 patients had complete response (CR group). The remaining 26 patients had partial response (NCR group). Significant differences were found in Ktrans-postTx, Kep-postTx, Ve-midTx, ΔKtrans-post-preTx, ΔKtrans-post-midTx, ΔKep-post-preTx, ΔKep-mid-preTx and ΔKep-post-midTx between the two groups. Receiver operating characteristic (ROC) analysis for their performances in predicting treatment response showed an area under curve (AUC) of 0.656– 0.849, sensitivity of 61.3– 93.5%, specificity of 46.1– 73.1%, and maximal Youden Index of 36.5– 66.6. Among those parameters, Kep-postTx was the best, and its AUC, sensitivity, specificity, maximal Youden Index, and cutoff value were 0.849, 87.1%, 73.1%, 60.2, and 0.341, respectively. These combined parameters showed an AUC of 0.952, with sensitivity of 87.1%, specificity of 96.1%, and maximal Youden Index of 83.2.Conclusion: DCE-MRI parameters can predict early treatment outcome. Among those parameters, Kep-postTx is the best predictor. The combination of multi-parameters can increase the predictive potency.Keywords: cervical cancer, locally advanced disease, dynamic contrast-enhanced magnetic resonance imaging, concurrent chemoradiotherapy, prognosis prediction

Yue Qiu,1,&ast; Daojiong Lin,2,&ast; Yi Xu,3,&ast; Yibing Cheng,4 Fang Wang,5 Qingxiong Zhu,6 Chunhui Zhu,6 Chaomin Wan,7 Yu Zhu,7 Jianning Tong,8 Rui Li,8 Qionghua Zhou,2 Minxia Chen,3 Qingwen Shan,9 Zhiqiang Zhuo,10 Caihong Wang,10 Shiyong Zhao,11 Wen Song,11 Mei Zeng1 1Department of Infectious Diseases, Children’s Hospital of Fudan University, ShangHai, People’s Republic of China; 2Department of Infectious Diseases, Hainan Women and Children’s Medical Center, Haikou, People’s Republic of China; 3Department of Infections Disease, Guangzhou Women and Children’s Medical Center, Guangzhou, People’s Republic of China; 4Department of Emergency, Children’s Hospital Affiliated to Zhengzhou University (Henan Children’s Hospital), Zhengzhou, People’s Republic of China; 5Department of Infections Disease, Children’s Hospital Affiliated to Zhengzhou University (Henan Children’s Hospital), Zhengzhou, People’s Republic of China; 6Department of Infection Diseases, Children’s hospital of Jiangxi Province, Nanchang, People’s Republic of China; 7Department of Pediatrics, West China Second Hospital, Sichuan University, Chengdu, People’s Republic of China; 8Department of Pediatric, Gastroenterology and Infectious Diseases, Qingdao Women and Children’s Hospital, Qingdao, People’s Republic of China; 9Department of Pediatrics, The First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China; 10Department of Infectious Diseases, Xiamen Children’s Hospital, Xiamen, People’s Republic of China; 11Department of Infectious Diseases, Hangzhou Children’s Hospital, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mei ZengDepartment of Infectious Diseases, Children’s Hospital of Fudan University, 399 Wanyuan Road, Shanghai, 201102, People’s Republic of ChinaTel +86-21-64931132Email zengmeigao@aliyun.comObjective: To assess clinical characteristics, outcomes and antimicrobial resistance of invasive Klebsiella pneumoniae (KP) infections in Chinese pediatric patients in hospital and community settings.Methods: This retrospective study was conducted in the nine tertiary hospitals during 2016– 2018. The 324 pediatric inpatients who had KP isolated from blood and cerebrospinal fluid and had complete medical records reviewed were included. We analyzed the risk factors, outcomes and antimicrobial resistance pattern of KP-infected patients based on comparison between healthcare-associated KP infections (HAI) and community-acquired infections.Results: Of the 324 enrolled patients, 275 (84.9%) were clinically defined as HAI, including 175 (63.6%) neonates and 100 (36.4%) aged > 28 days. The overall prevalence of CRKP was 38.2% (43.4% in HAI verse 8.7% in CAI, P < 0.05). Prematurity (odds ratio (OR): 37.07, 95% CI: 8.29– 165.84), hematologic malignancies (OR: 15.52, 95% CI: 1.89– 127.14) and invasive mechanical ventilation (OR: 13.09, 95% CI: 1.66– 103.56) were independent risk factors for HAI. Patients from rural area (OR: 1.94, 95% CI: 1.12– 3.35), invasive mechanical ventilation (OR: 2.33, 95% CI: 1.25– 4.33), antibiotic therapy prior to admission (OR: 2.33, 95% CI: 1.25– 4.33) and prior hospital stay in the past 30 days (OR: 3.46, 95% CI: 1.87– 6.41) were associated with healthcare-associated CRKP infections. Organ dysfunction was independently correlated with poor outcomes (OR: 2.92, 95% CI: 1.23– 6.95).Conclusion: Pediatric invasive KP infections and high prevalence of CRKP infections largely occurred in healthcare settings in China. The adequate and intensified infection control measures should be focused on high-risk hematologic patients, neonatal patients and intubated patients.Keywords: Klebsiella pneumoniae, healthcare-associated infections, children

Xiao-Ming Zhang,1 Xinjuan Wu,1 Yunfen Ma,1 Chen Zhu,1 Jing Cao,1 Ge Liu,1 Fang-Fang Li,1 Andy SK Cheng2 1Department of Nursing, Chinese Academy of Medical Sciences - Peking Union Medical College, Peking Union Medical College Hospital (Dongdan Campus), Beijing, 100730, People’s Republic of China; 2Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, Hong Kong, People’s Republic of ChinaCorrespondence: Xinjuan Wu Tel/Fax +86 10 69156114Email wuxinjuan@sina.comBackground: Immobile patients often suffer from malnutrition and low calf circumference (CC), a potential surrogate marker of low muscle mass, which has been widely explored as a link with mortality among patients with inconsistent results. In addition, studies comparing CC, BMI, and albumin to predict mortality among immobile patients are limited. The aim of our study was to compare the performance of these three parameters for predicting mortality among immobile patients.Methods: This is a secondary analysis of our previous study consisting of immobile patients, age> 18 years. Data were collected between November 2015 and March 2016 by trained nurses through a case report form (CRF) that included clinical data and sociodemographic variables. In addition, anthropometric parameters, including body weight, height and calf circumference, were also measured. The outcome of our study was mortality with follow-up length being 90 days. Multivariate linear and logistic regression analysis were adopted to identify the association between CC and mortality, and a receiver operating characteristic curve analysis was also used to compare the performance of CC, BMI, and albumin.Results: Of the 387 patients who were included (51.42% male), with an average age of 61.22 (SD=15.18), the prevalence of mortality was 5.43%. The results showed that, after full adjustment, calf circumference was a protective factor for reducing the risk of mortality (OR=0.79; 95%CI:0.65– 0.96). Meanwhile, immobile patients with low calf circumference had an increased risk of mortality, compared to those whose condition was normal (OR=4.24; 95%CI:1.07– 16.74). Receiver operating characteristic curve analysis showed that CC combined with albumin (AUC=0.812; 95% CI=0.733– 0.890) had the highest AUC value compared to calf circumference (AUC=0.759; 95%CI:0.662– 0.856), BMI (AUC=0.653; 95%CI:0.538– 0.767) and albumin (AUC=0.735; 95% CI:0.638– 0.832), respectively, in predicting mortality in immobile patients.Conclusion: The relationship between calf circumference and mortality was significantly negative and low calf circumference was associated with a high risk of 90-day mortality, compared to those with normal calf circumference. The combined calf circumference with albumin had good discrimination in predicting mortality among immobile patients. Therefore, it can routinely be used in a clinical setting by medical staff to predict mortality in immobile patients, as it is easy to obtain.Keywords: calf circumference, immobile patients, albumin, mortality

Tingting Yang,1,* Dandan Li,1– 3,* Yifan Zhang,1 Long Zhang,2,3 Hong Li,4 Gong-Jun Ji,1– 3 Zhenhai Yang,5 Lei Zhang,1,3 Chunyan Zhu,1,3,* Kai Wang1– 3,6 1School of Mental Health and Psychological Sciences, Anhui Medical University, Hefei, 230022, People’s Republic of China; 2Department of Neurology, the First Affiliated Hospital of Anhui Medical University, Hefei, 230022, People’s Republic of China; 3Anhui Province Key Laboratory of Cognition and Neuropsychiatric Disorders, Hefei, 230022, People’s Republic of China; 4Department of Neurological Rehabilitation of Children, Anhui Provincial Children’s Hospital, Hefei, 230022, People’s Republic of China; 5Department of Rehabilitation therapy, The First Clinical Medical College of Anhui Medical University, Hefei, 230022, People’s Republic of China; 6Institute of Artificial Intelligence, Hefei Comprehensive National Science Center, Hefei, 230022, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lei Zhang; Chunyan ZhuSchool of Mental Health and Psychological Sciences, Anhui Medical University, Hefei, People’s Republic of ChinaEmail zhanglei17236@aliyun.com; ayswallow@126.comObjective: Previous research found that autism spectrum disorder (ASD) was characterized by eye avoidance of threatening facial expressions. However, it still remains unclear as to whether these abnormalities are present in parents of children with ASD. Our study aimed to investigate the gaze patterns of parents of children with ASD in the threatening facial expressions.Methods: Thirty-four parents of children with ASD and 35 parents of typically developing (TD) children participated in our study. We investigated the total fixation time of participants when they viewed different facial expression (eg, happy, fearful, angry, sad) videos and examined changes in the fixation duration over time.Results: We observed the following: a) the total fixation time of the parents of children with ASD on the eyes of fearful faces was significantly shorter than that of the normal group, and the difference lasted for five seconds (four to six seconds, eight to nine seconds) throughout the process; and b) The parents of children with ASD avoided the eyes of angry expression faces at around five seconds after the stimulus onset.Conclusion: We concluded that parents of children with ASD tended to avoid the eyes of threatening expression faces while viewing the dynamic emotions video.Keywords: parents of children with ASD, total fixation time, threatening facial expressions

Hong Li, Kehong Bi, Saran Feng, Yan Wang, Chuansheng Zhu Department of Hematology, Shandong Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250014, ChinaCorrespondence: Kehong BiDepartment of Hematology, Shandong Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, No. 16766 Jingshi Road, Jinan City, Shandong Province, 250014, ChinaEmail KehongBiRoad@163.comPurpose: CircRNA circ_POLA2 has been reported as an oncogene in lung cancer, while its role in other malignancies is unknown. This study aimed to explore the role of circ_POLA2 in acute myeloid leukemia (AML).Methods: The expression levels of circ_POLA2, mature miR-34a and miR-34a precursor in bone marrow mononuclear cells (BMMNCs) from AML patients (n = 50) and healthy controls (n = 50) were determined by RT-qPCR. Correlations among them were analyzed by Pearson’s correlation coefficient. Overexpression of circ_POLA2 was achieved in AML cell lines, followed by the measurement of the expression levels of mature miR-34a and miR-34a precursor. The role of circ_POLA2 and miR-34a in regulating AML cell proliferation was assessed by CCK-8 assay.Results: Circ_POLA2 was upregulated in AML and inversely correlated with mature miR-34a, but not miR-34a precursor. In AML cells, overexpression of circ_POLA2 decreased the expression levels of mature miR-34a, but not miR-34a precursor. Cell proliferation analysis showed that the overexpression of miR-34a attenuated the effects of overexpression of circ_POLA2 on cell proliferation.Conclusion: Circ_POLA2 is upregulated in AML and promotes cell proliferation by suppressing the production of mature miR-34a.Keywords: circ_POLA2, acute myeloid leukemia, miR-34a, maturation

Chao Zhu,1– 5 Shuang Wen,6 Junyong Li,1– 3,5 Hongyu Meng,1– 3,5 Junzhe Zhang,1– 3,5 Kuo Zhao,1– 3,5 Ling Wang,1– 3,5 Yingze Zhang1– 3,5,7 1Department of Orthopaedic Surgery, Third Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China; 2Key Laboratory of Biomechanics of Hebei Province, Shijiazhuang, People’s Republic of China; 3NHC Key Laboratory of Intelligent Orthopaedic Equipment, Third Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China; 4Department of Orthopedics, The Affiliated Jiangning Hospital with Nanjing Medical University, Nanjing, People’s Republic of China; 5Orthopaedic Research Institution of Hebei Province, Shijiazhuang, People’s Republic of China; 6Department of Immunology, Nanjing Medical University, Nanjing, People’s Republic of China; 7Chinese Academy of Engineering, Beijing, People’s Republic of ChinaCorrespondence: Yingze Zhang Email suryzz@163.comBackground: Fingolimod (FTY720), a novel immunomodulator, was found to suppress the severity of collagen-induced arthritis (CIA) in mice. However, the potential molecular mechanisms are still unknown, and the effect of FTY720 on the recruitment of immune cells in the affected joints in the CIA model is not clear.Materials and Methods: Following the oral administration of FTY720 (2 mg/kg) was treated into CIA mice per day for 35 days, intravital microscopy and immunofluorescence assays were performed to examine immune cell recruitment in the affected joints. Human MH7A synoviocytes were stimulated with tumour necrosis factor (TNF)-α and incubated with FTY720. Interleukin-1β (IL-1β), interleukin-6 (IL-6), and interleukin-8 (IL-8) mRNA and protein expression were evaluated using RT-PCR and enzyme-linked immunosorbent assay, respectively. Signal transduction pathway protein expression was measured by Western blotting. Nuclear translocation of nuclear factor (NF)-κB was also analyzed by fluorescence microscopy.Results: In vivo experiments showed that FTY720 inhibited the recruitment of CD4+ lymphocytes in the affected joints of CIA mice. FTY720 reduced the secretion of IL-1β, IL-6, and IL-8 from TNF-α-stimulated MH7A cells in a dose-dependent manner. FTY720 also inhibited TNF-α-induced phosphorylation of NF-κBp65 and IκBα, as well as NF-κBp65 nuclear translocation, in a dose- and time-dependent manner. Interestingly, FTY720 blocked PI3K/Akt, the upstream targets of the NF-κB pathway.Conclusion: Our findings demonstrated that oral administration of FTY720 exerted beneficial effects in CIA mice by inhibiting CD4+ T lymphocyte recruitment to the affected joints. Our data also indicated that FTY720 inhibited TNF-α-induced inflammation by suppressing the AKT/PI3K/NF-κB pathway in MH7A cells.Keywords: FTY720, rheumatoid arthritis, NF-κB, MH7A, CD4+ T lymphocytes

Xiao-Ming Zhang,1,* Jing Jiao,1,* Jing Cao,1 Na Guo,1 Chen Zhu,1 Zhen Li,1 Xinjuan Wu,1 Tao Xu2 1Department of Nursing, Chinese Academy of Medical Sciences - Peking Union Medical College, Peking Union Medical College Hospital (Dongdan Campus), Beijing, 100730, People’s Republic of China; 2Department of Epidemiology and Statistics, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & School of Basic Medicine, Peking Union Medical College, Beijing, 100005, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xinjuan Wu; Tao Xu Tel +86 18612671300, Fax +86 1069156114Email wuxinjuan@sina.com; xutaosd@126.comObjective: There have been studies exploring the association between handgrip and depression among community-dwelling adults; however, evidence for this association among hospitalized older adults is scarce. We aimed to use a larger-scale population from multiple centers to explore the association between low handgrip strength and depression.Methods: This was a cross-sectional study that included hospitalized patients aged 65 years or older from different hospitals in China. Depression was assessed by a short-form Chinese Geriatric Depression Scale (GDS-15) with a cutoff value of 5 points or more. Dominant hand handgrip strength was assessed by a dynamometer. A generalized additive model and multivariable regression analysis were conducted.Results: There were 9,368 participants, with an average age of 72.4 (SD=5.7) in the final analysis. The prevalence of low handgrip strength and depressive symptoms among older Chinese hospitalized patients was 50.3% and 16.3%, respectively. There seemed to be a nonlinear relationship between handgrip strength and depression, and curve fitting and threshold analyses indicated that when handgrip strength was less than 35.6 kg, the depression risk decreased significantly with increasing handgrip strength. However, this association between handgrip strength and depression was not significant when the handgrip strength was greater than 35.6 kg. In addition, after adjusting for potential confounders, older patients with low handgrip strength had an increased risk of depression compared to those with normal handgrip strength (OR=1.46; 95% CI=1.27– 1.68). The subgroup analysis found the results were unchanged.Conclusion: Our study indicates that low handgrip strength was associated with a higher risk of depression among older Chinese hospitalized patients, implying that early patient screening for handgrip strength and initiating effective intervention programs, such as resistance training and nutritional supplements, could be helpful for older patients.Keywords: handgrip strength, depression, hospitalized, older adults

Shengwei Wang,1 Hao Cui,2 Keshan Ji,3 Changsheng Zhu,4 Xiaohong Huang,3 Yongqiang Lai,1 Shuiyun Wang4 1Cardiovascular Surgery Center, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vascular Diseases, Beijing, People’s Republic of China; 2Department of Cardiovascular Surgery, Mayo Clinic, Rochester, MN, USA; 3Special Medical Treatment Center, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 4Department of Cardiovascular Surgery, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of ChinaCorrespondence: Yongqiang LaiCardiovascular Surgery Center, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vascular Diseases, No. 2, Anzhen Road, Chaoyang District, Beijing, 100029, People’s Republic of ChinaEmail yongqianglai@yahoo.comShuiyun WangDepartment of Cardiovascular Surgery, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 167, Beilishi Road, Xicheng District, Beijing, 100037, People’s Republic of ChinaEmail wsymd@sina.comPurpose: Obstructive sleep apnea (OSA) and myocardial fibrosis are associated with cardiac arrhythmia. The purpose of this study was to explore the relationship between OSA and myocardial fibrosis, as well as their impact on cardiac arrhythmia in hypertrophic obstructive cardiomyopathy (HOCM) patients.Methods: We prospectively studied 151 consecutive patients with a confirmed diagnosis of HOCM at the Fuwai Hospital between September 2017 and 2018. Polysomnography, Holter electrocardiography, and cardiac magnetic resonance imaging were performed on all patients. Myocardial fibrosis was reflected by late gadolinium enhancement (LGE), detected using cardiac magnetic resonance imaging.Results: Myocardial fibrosis, measured using LGE%, was found to increase with increasing OSA severity [6.8% (3.6– 12.9%), 6.1% (3.4– 10.0%), 9.6% (5.5– 14.5%), and 15.5% (9.3– 20.0%) for no-OSA, mild OSA, moderate OSA, and severe OSA, respectively; p=0.003]. LGE% correlated with the New York Heart Association functional classifications (p=0.018), septal thickness (p=0.026), and apnea-hypopnea index (AHI) (p< 0.001). The prevalence of isolated premature ventricular contraction (PVC) (p=0.028), paired PVC (p=0.036), ventricular bigeminy (p=0.005)/trigeminy (p< 0.001), non-sustained ventricular tachycardia (NSVT) (p=0.001), isolated premature atrial contraction (PAC) (p=0.032), and supraventricular tachycardia (p=0.029) was significantly higher in patients with OSA. Additionally, LGE% and AHI were independent risk factors for isolated PVC (OR: 1.04, p=0.001 and OR: 1.07, p=0.039, respectively), ventricular bigeminy (OR: 1.04, p=0.003 and OR: 1.26, p=0.002, respectively)/trigeminy (OR: 1.07, p=0.040 and OR: 1.06, p=0.001, respectively), and NSVT (OR: 1.17, p< 0.001 and OR: 1.08, p< 0.001, respectively) after adjustment for age, sex, and other parameters.Conclusion: Both OSA and LGE% were associated with a greater likelihood and increased frequency of ventricular arrhythmias (including NSVT) in patients with HOCM. Thus, the severity of OSA was independently associated with more severe myocardial fibrosis in patients with HOCM.Keywords: hypertrophic obstructive cardiomyopathy, obstructive sleep apnea, cardiac arrhythmia

Xiao-Ming Zhang,1,* Jing Jiao,1,* Chen Zhu,1 Na Guo,1 Ying Liu,1 Dongmei Lv,2 Hui Wang,3 Jingfen Jin,4 Xianxiu Wen,5 Shengxiu Zhao,6 Xin-Juan Wu,1 Tao Xu7 1Department of Nursing, Chinese Academy of Medical Sciences - Peking Union Medical College, Peking Union Medical College Hospital (Dongdan Campus), Beijing, 100730, People’s Republic of China; 2Department of Nursing, The Second Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China; 3Department of Nursing, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 4Department of Nursing, The Second Affiliated Hospital Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 5Department of Nursing, Sichuan Provincial People’s Hospital, Chengdu, People’s Republic of China; 6Department of Nursing, Qinghai Provincial People’s Hospital, Xining, People’s Republic of China; 7Department of Epidemiology and Statistics, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & School of Basic Medicine, Peking Union Medical College, Beijing, 100005, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xin-Juan Wu; Tao Xu Tel/Fax +010 86 6915 6114Email wuxinjuan@sina.com; xutaosd@126.comPurpose: Studies exploring the association of cognitive frailty and mortality have been mainly based on community settings or nursing home settings. The aim of our study was to explore the association between cognitive frailty and 30-day mortality among older Chinese inpatients.Patients and Methods: A national cohort study was performed in different hospitals in China. A baseline survey was conducted from October 2018 and February 2019. Trained investigators collected the 30-day mortality. Cognitive impairment and frailty were defined by the Mini-Cog and FRAIL scale, respectively. Multivariate regression was used to explore the association between cognitive impairment and frailty status with 30-day mortality.Results: Of these participants, there were 3891 (41.91%) women and 5392 (58.09%) men, with an average age of 72.41 (SD=5.72). The prevalence of cognitive frailty was 5.44%. After adjusting for age, gender, education, depression and activities of daily living (ADL), the odds ratios (ORs) for 30-day mortality among inpatients were 3.43 (95% CI: 1.80– 6.55) for cognitive frailty, 1.85 (95% CI: 1.01– 3.41) for frailty only, and 1.43 (95% CI: 0.77– 2.65) for cognitive impairment only compared to the reference group (neither frailty nor cognitive impairment). In addition, the discrimination of 30-day mortality was higher among patients with cognitive frailty (area under the curve =0.676 [95% CI: 0.621– 0.731]) than either frailty (area under the curve =0.644 [95% CI: 0.594– 0.694]) or cognitive impairment (area under the curve = 0.606 [95% CI: 0.556– 0.655]) separately. Stratified analysis showed that these associations still existed when grouped by gender.Conclusion: Our study found that Chinese inpatients with cognitive frailty had a higher risk of 30-day mortality than those without frailty and cognitive impairment, suggesting that clinicians should be encouraged to perform early screening of patients with frailty and cognitive impairment and carry out effective interventions to reverse cognitive frailty syndrome.Keywords: frailty, cognitive impairment, mortality, older adults, Chinese; inpatients

Shuang Cao,1,2,* Xin Gao,1,* Guangjian Bai,1,* Baoquan Xin,1,* Tao Wang,1 Jiashi Cao,1 Kai Lv,1 Chengzhang Zhu,1 Xiangzhi Ni,1 Weiwei Zou,3 Yejin Zhou,2 Jianru Xiao,1 Tielong Liu1 1Orthopedic Oncology Center, Department of Orthopedics, Changzheng Hospital, Second Military Medical University, Shanghai, People’s Republic of China; 2Department of Orthopedics, Third Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, People’s Republic of China; 3Department of Radiology, Changzheng Hospital, Second Military Medical University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Tielong Liu; Jianru XiaoOrthopedic Oncology Center, Department of Orthopaedics, Changzheng Hospital, No. 415 Fengyang Road, Huangpu District, Shanghai, People’s Republic of ChinaTel +86-21-81886843Fax +86-21-63520020Email liutielongvip@163.com; xiaojianruvvip@163.comPurpose: Spinal tuberculosis (TB) and metastatic tumor (MT) are common diseases with similar manifestations. Although pathological evaluation is the gold standard to confirm diagnosis, performing biopsies in all patients is not feasible. This study is aimed to create a scoring system to facilitate the differential diagnosis of spinal TB and MT before invasive procedures.Methods: Altogether, 447 patients with spinal TB (n=198) and MT (n=249) were retrospectively analyzed. Patients were randomly assigned at 2:1 ratio to a training cohort and a validation cohort. Clinical, laboratory, and radiological diagnostic factors were identified by χ2 and multiple logistic regression analyses. The scoring system was then established based on the identified independent diagnostic factors scored by regression coefficient β value, with the cut-off value being determined by ROC curve. The sensitivity and specificity of the system was calculated by comparing the predicted diagnosis with their actual pathological diagnosis.Results: This scoring system was composed of 5 items: pain worsens at night (0 or 2 points), CRP value (0 or 3 points), tumor marker values (0 or 2 points), skip lesions (0 or 3 points), and intervertebral space destruction (0 or 3 points). Patients scoring higher than 7.5 could be diagnosed as spinal TB, otherwise, MT. According to the internal validation, the sensitivity and specificity of the system were 87.9% and 91.6%, respectively.Conclusion: This study established and validated a scoring system which could be used to differentiate spinal TB from MT, thus helping clinicians in quick and accurate differential diagnosis.Keywords: scoring system, differential diagnosis, spine, tuberculosis, metastatic tumor

Liping Zou, Guiping Cheng, Chengcheng Xu, Heyu Liu, Yingying Wang, Nianyu Li, Xiaorong Fan, Changhong Zhu, Wei Xia Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of ChinaCorrespondence: Wei XiaInstitute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, People’s Republic of ChinaTel/Fax +86 27 8369 2651Email tjxiawei@hust.edu.cnPurpose: The toxicity of copper nanoparticle (CuNP) exposure in the ovaries has attracted attention recently, but the precise molecular mechanism involved requires further investigation. We investigated the cytotoxicity of CuNPs in ovarian granulosa cells and the protective effect of heme oxygenase 1 (HO-1) against CuNP-induced damage.Methods: Human ovarian granulosa cells (COV434) were treated with CuNPs, and cytotoxicity was evaluated using Cell Counting Kit-8 and flow cytometry assays. Oxidative stress was identified using biochemical markers of oxidation and anti-oxidation. The protein levels of mitogen-activated protein kinase 14 (MAPK14), phospho-MAPK14, nuclear factor erythroid 2-related factor 2 (Nrf2), and HO-1 were measured by immunoblotting. Subsequently, for oxidative stress parameter detection, the cells were pre-treated with hemin to induce HO-1 expression prior to CuNP treatment.Results: Exposure to CuNPs decreased cell viability and the mitochondrial membrane potential, increased the apoptosis rate, and induced oxidative stress. Furthermore, hemin pretreatment induced HO-1 expression in cells, which partially reduced the accumulation of reactive oxygen species induced by CuNPs and increased the levels of antioxidant enzymes.Conclusion: CuNPs exert cytotoxic effects on human ovarian granulosa cells by inducing oxidative stress, and may induce HO-1 expression via the MAPK14-Nrf2 signaling pathway. Moreover, HO-1 protects against oxidative stress induced by CuNPs.Keywords: copper nanoparticles, cytotoxicity, oxidative stress, heme oxygenase 1

Hanfang Jiang,1 Qing Meng,2 Xiaorong Liu,2 Hongyu Chen,2 Chunqing Zhu,2 Yunsheng Chen2 1Clinical Laboratory, Institute of Pediatrics, Shenzhen Children’s Hospital, Shenzhen, Guangdong, People’s Republic of China; 2Clinical Laboratory, Shenzhen Children’s Hospital, Shenzhen, Guangdong, People’s Republic of ChinaCorrespondence: Yunsheng ChenClinical Laboratory, Shenzhen Children’s Hospital, Shenzhen, Guangdong, People’s Republic of ChinaEmail chenyunshenglw@163.comIntroduction: To determine the phenotypes and genotypes of invasive Streptococcus pneumoniae (S. pneumoniae), 108 strains were isolated from paediatric patients with invasive pneumococcal diseases (IPDs) in Shenzhen from 2014 to 2018.Methods: Serotype profiles were defined by multiplex PCR of the capsule gene. Pneumococcal surface protein A (PspA) classification was performed through pspA gene sequencing. Antimicrobial resistance was examined by broth microdilution. Multilocus sequence typing (MLST) was determined based on next-generation sequencing data.Results: Eighty-one S. pneumoniae of 17 serotypes were finally collected. The coverage of the 13-conjugated polysaccharide vaccine (PCV13) was 88.9%. After the introduction of PCV13, the nonvaccine serotypes were added by serotypes 15b, 16F and 20. Vaccine serotype 3 increased by four serious cases. The pspA family 1 and pspA family 2 are predominant. The multiple drug resistance rate is 91.3%. None of the nonmeningitis isolates were resistant to penicillin, while 98.8% of all the isolates were resistant to erythromycin.Discussion: This work characterizes the molecular epidemiology of invasive S. pneumoniae in Shenzhen. Continued surveillance of serotype distribution and antimicrobial susceptibility is necessary to alert antibiotic-resistant nonvaccine serotypes and highly virulent serotypes.Keywords: Streptococcus pneumoniae, invasive pneumococcal disease, PspA family, serotype, antimicrobial resistance

Defeng Qing,1,* Yuying Wu,2,* Xu Liu,1,* Hailan Jiang,1,* Chaohua Zhu,1,* Pei Liu,3 Junming Dang,4 Xianglong Li,1 Zhaohong Chen,1 Xianfeng Long,1 Qiang Pang,1 Luxing Peng,1 Shan Deng,1 Junzhao Gu,1 Renfeng Zhao,2 Changyi Chen,2 Heming Lu1 1Department of Radiation Oncology, People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning 530021, People’s Republic of China; 2Department of Gynecology, People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning 530021, People’s Republic of China; 3Department of Radiation Oncology, Youjiang Medical University for Nationalities, Baise 533000, People’s Republic of China; 4Department of Oncology, Guangxi University of Chinese Medicine, Nanning 530001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Heming LuDepartment of Radiation Oncology, People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning City 530021, People’s Republic of ChinaTel +86-771-218-6504Email luhming3632@163.comPurpose: We aimed to evaluate the long-term survival outcomes of concurrent chemoradiotherapy (CCRT) combined with nimotuzumab followed by surgery in patients with locally advanced cervical cancer (LACC).Patients and Methods: Patients received whole pelvic intensity-modulated radiation therapy (IMRT) and concomitantly with weekly cisplatin (40 mg/m2) or nedaplatin (30 mg/m2) and weekly nimotuzumab (200 mg). After assessment of the treatment response, patients then underwent radical surgery.Results: Between June 2013 and July 2016, 33 patients with FIGO IB2–IIIB cervical cancer were recruited. Clinical complete response and partial response were observed in 8 (24.3%) and 23 patients (69.7%), respectively. Twenty-seven patients (81.8%) were successfully treated with radical hysterectomy and pelvic lymphadenectomy: 9 (33.3%) showed pathological complete response; 10 (37.1%) showed partial response and 8 (29.6%) presented with persistent macroscopic/microscopic residual carcinoma. For the intention-to-treat population, the median follow-up time was 53.7 months. Locoregional recurrence and distant metastases were observed in three and seven patients, respectively. The 5-year overall survival, progression-free survival, locoregional recurrence-free survival, and distant metastasis-free survival were 81.5%, 72.7%, 90.9%, and 78.3%, respectively. Both acute and late toxicities were manageable and mainly limited to grade 1 or 2.Conclusion: Concurrent chemoradiotherapy combined with nimotuzumab followed by surgery for patients with LACC is safe and results in excellent long-term treatment outcomes. Further randomized controlled studies are warranted to confirm the findings.Keywords: locally advanced cervical cancer, neoadjuvant chemotherapy, intensity-modulated radiotherapy, anti-EGFR monoclonal antibody, radical surgery

Ce Zhu,* Xiang Wang,* Xinxin Yang,* Jing Sun, Bujian Pan, Weiteng Zhang, Xiaodong Chen, Xian Shen Department of Gastrointestinal Surgery, The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xian ShenDepartment of Gastrointestinal Surgery, The Second Affiliated Hospital of Wenzhou Medical University, No. 109 West College Road, Wenzhou, Zhejiang Province, People’s Republic of ChinaTel +86 577 8800 2709Email shenxian5166@gmail.comPurpose: The relationship between liver function and colorectal cancer without liver metastases has not been explored. Therefore, we investigated whether the preoperative albumin-bilirubin grade could predict the prognosis of patients with colorectal cancer (CRC) undergoing radical resection, and we designed a quantifiable predictive model.Patients and Methods: We retrospectively analyzed data from 284 patients with CRC who underwent radical resection in the Second Affiliated Hospital of the Wenzhou Medical University between January 2011 and January 2016. Patients were divided in two groups according to the calculated cut-off: the high albumin-bilirubin (>-2.48) grade and low albumin-bilirubin (≤-2.48) grade group. Kaplan–Meier curves were constructed to compare the overall survival (OS) between the two groups. Univariate and multivariate analyses were performed to identify the independent risk factors for postoperative complications and OS.Results: Patients with a high albumin-bilirubin grade (n = 165, 58.1%) had a higher rate of postoperative complications (38.2% versus 17.6%, P < 0.001), especially medical (19.4% versus 6.7%, P = 0.002) and severe complications (1.7% versus 7.3%, P = 0.032). They also had a shorter OS (mean survival time, 47.6 versus 54.3 months, P = 0.005), especially patients with tumor-node-metastasis stage III (42.7 months versus 51.6 months, P = 0.036). Age ≥ 70 years (odds ratio [OR] = 2.22, P = 0.003) and high albumin-bilirubin grade (OR = 2.71, P = 0.001) were independent risk factors for postoperative complications, while age ≥ 70 years (hazard ratio [HR] = 2.65, P < 0.001), high albumin-bilirubin grade (HR = 1.81, P = 0.033), tumor-node-metastasis stage II (HR = 13.83, P = 0.010) and III (HR = 23.66, P = 0.002) were independent risk factors of OS.Conclusion: Preoperative albumin-bilirubin grade could predict postoperative complications (especially medical and severe complications) and OS in patients with CRC, especially in those with tumor-node-metastasis stage III.Keywords: colorectal cancer, albumin-bilirubin, liver function, prognosis, postoperative complications

Yuzhen Yin,1 Hui Yang,2 Zhuo Liu,3 Jie Tan,2 Chunrong Zhu,4 Minbin Chen,5 Rengui Zhou,6 Lei Wang,7 Jun Qian2,8 1Department of Tumor Center, The Affiliated Jiangsu Shengze Hospital of Nanjing Medical University, Suzhou, Jiangsu, People’s Republic of China; 2Department of Oncology, Suzhou Municipal Hospital, Suzhou, Jiangsu, People’s Republic of China; 3Department of Oncology, Zhangjiagang First People’s Hospital, Zhangjiagang, Jiangsu, People’s Republic of China; 4Department of Oncology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, People’s Republic of China; 5Department of Oncology, The First People’s Hospital of Kunshan, Kunshan, Jiangsu, People’s Republic of China; 6Department of Oncology, The 904th Hospital of the Joint Logistics Support Force of the Chinese People’s Liberation Army, Wuxi, Jiangsu, People’s Republic of China; 7Department of Breast Surgery, The First People’s Hospital of Changzhou, Changzhou, Jiangsu, People’s Republic of China; 8Department of Oncology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of ChinaCorrespondence: Jun QianDepartment of Oncology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, 155 Hanzhong Road, Qinhuai District, Nanjing, Jiangsu, People’s Republic of ChinaEmail junqian0415@126.comLei WangDepartment of Breast Surgery, The First People’s Hospital of Changzhou, No. 185, Juqian Street, Changzhou, Jiangsu, People’s Republic of ChinaEmail 592722409@qq.comBackground: Human epidermal growth factor receptor 2 (HER2) is a member of the ErbB family and is a key proto-oncogene in solid tumors. This pilot study investigated the safety and efficacy of pyrotinib in HER2-positive non-breast advanced solid tumors.Patients and Methods: Twenty-five patients with HER2-positive advanced solid tumors excluding breast cancer were enrolled to receive pyrotinib-based therapy. The primary end point was progression-free survival (PFS).Results: The median PFS and overall survival (OS) were 3.5 months (95% CI: 2.2– 5.0 months) and 9.6 months (95% CI: 4.4– 9.9 months), respectively. Ten patients with lung cancer and 9 patients with gastric cancer had a median PFS of 2.5 months (95% CI: 0.97– 6.53 months) and 2.9 months (95% CI: 1.50– 7.17 months), respectively. The median OS was 9.9 months (95% CI: 4.4– 9.9 months) in patients with lung cancer and 5.9 months (95% CI: 4.0– 9.6 months) in patients with gastric cancer. No statistical significance of a median OS was observed, nonetheless, patients receiving > 3 lines had a numerically lower median OS than those receiving ≤ 3 lines of treatment (9.9 vs 5.1 months, P = 0.706). All 23 patients were available for efficacy evaluation. The objective response rate (ORR) was 52.17% and disease control rate (DCR) was 91.3%. The ORR for lung cancer was 44.4% and for gastric cancer was 50%. In addition, the DCR for lung cancer was 77.8% and for stomach cancer was 100%. Moreover, patients receiving ≤ 3 lines of treatment had a numerically higher DCR than those receiving > 3 lines of treatment (94.1% vs 83.3%, P = 0.462). The most common treatment-related adverse events (TRAEs) were diarrhea (92%), but only 5 (20%) patients reported grade 3 diarrhea which could be well controlled.Conclusion: Pyrotinib-based therapy demonstrates promising efficacy for HER2-positive advanced solid tumors excluding breast cancer and toxicities could be well controlled. The study is a pilot study motivating larger studies to elucidate the safety and efficacy of pyrotinib in non-breast solid tumors.Keywords: pyrotinib, HER2-positive, solid tumor

Zongguang Tai,1,2,* Jinyuan Ma,1,* Jianing Ding,1,* Huijun Pan,1 Rongrong Chai,1 Congcong Zhu,1 Zhen Cui,1 Zhongjian Chen,1 Quangang Zhu1 1Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai 200443, People’s Republic of China; 2Department of Pharmacy, Changhai Hospital, Second Military Medical University, Shanghai 200433, People’s Republic of China*These authors contributed equally to this workCorrespondence: Quangang Zhu; Zhongjian ChenShanghai Skin Disease Hospital, Tongji University School of Medicine, Baode Road 1278, Shanghai 200443, People’s Republic of ChinaTel +86 21 61833155; +86 21 61833007Fax +86 21 61833021Email qgzhu@126.com; aajian818@163.comPurpose: The clinical management of patients with castration-resistant prostate cancer (CRPC) is difficult. However, novel treatment methods are gradually being introduced. Considering the adverse effects of traditional treatments, recent studies have investigated gene therapy as a method to combat CRPC; but, the application of long non-coding (lnc) RNA in gene therapy remains scarce, despite their promise. Therefore, it is imperative to develop a system that can efficiently deliver lncRNA for the treatment of CRPC. Here, we investigated the efficacy of a delivery system by introducing the plasmid-encoding tumor suppressor lncRNA MEG3 (pMEG3) in CRPC cells.Materials and Methods: An EpDT3 aptamer-linked poly(amidoamine) (PAMAM) dendrimer targeting EpCAM was used to deliver pMEG3 in CRPC cells. The PAMAM-PEG-EpDT3/pMEG3 nanoparticles (NPs) were tested using in vitro cellular assays including cellular uptake, entry, and CCK-8 measurement, and tumor growth inhibition, histological assessment, and safety evaluations in in vivo animal models.Results: The EpDT3 aptamer promoted endocytosis of PAMAM and PAMAM-PEG-EpDT3/pMEG3 NPs in CRPC cells. PAMAM-PEG-EpDT3/pMEG3 NPs exhibited a significant anti-CRPC effect, both in vivo and in vitro, when compared to that of unfunctionalized PAMAM-PEG/pMEG3 NPs.Conclusion: PAMAM-PEG-EpDT3/pMEG3 NPs can potentially improve gene therapy in CRPC cells.Keywords: long non-coding RNA MEG3, castration-resistant prostate cancer, gene therapy, dendrimer

Ting Chen,1 Li Yao,1 Chunyan Zhu2 1Department of Critical Care Medicine, The Second People’s Hospital of Hefei, Hefei, Anhui 230009, People’s Republic of China; 2Department of Critical Care Medicine, The First Affiliated Hospital of USTC, Division of Life Science and Medicine, University of Science and Technology of China, Hefei, Anhui 230032, People’s Republic of ChinaCorrespondence: Chunyan ZhuDepartment of Critical Care Medicine, The First Affiliated Hospital of USTC, Division of Life Science and Medicine, University of Science and Technology of China, Hefei, Anhui 230032, People’s Republic of ChinaTel +86-551-62282731Fax +86-551-62283409Email chunyanzhu0509@126.comBackground: Massive hemoptysis in pregnancy is very rare but can be life-threatening for both the pregnant woman and fetus. Extracorporeal membrane oxygenation (ECMO) is extremely rare in the treatment of severe hemoptysis in pregnancy. Here we describe the case of massive hemoptysis in the second trimester of pregnancy successfully treated with a combination of venovenous (VV)-ECMO, and bronchial artery embolization combined with fiberoptic bronchoscopy–assisted CO2 cryotherapy.Case Presentation: A 34-year-old patient at 28 2/7 weeks gestation with a history of hemoptysis for 3 days was transferred to our care. Massive hemoptysis completely blocked the trachea and main bronchus, and a ventilator could not carry out ventilation. ECMO was performed immediately when oxygenation was not maintained. A right lower bronchial artery hemorrhage was found by bronchial arteriography under ECMO, and embolization with microcoils and gelatin sponge particles was then performed. An emergency bedside carbon dioxide cryo-thrombectomy was performed under fiberoptic bronchoscopy because of obstruction of the trachea and main bronchus. Endotracheal cryotherapy was repeated (for a total three times) until bronchoscopic evaluation confirmed no obstruction of the trachea and no active bleeding in the airway. On day 7, ECMO was successfully evacuated. On day 15, the patient was extubated. On day 17, the tracheotomy was closed and replaced by nasal oxygen inhalation. On day 20, the patient was discharged from hospital. The patient has had no recurrence of hemoptysis in 3-month follow-up.Conclusion: VV-ECMO combined with carbon dioxide cryotherapy in the treatment of pregnancy complicated with massive hemoptysis is an effective treatment, when massive hemoptysis completely blocked the trachea.Keywords: VV-ECMO, bronchial artery embolization, carbon dioxide freezing, pregnancy, massive hemoptysis

Wei Su,1 Cuiling Zhu,1 Xin Zhang,1 Jun Xie,2 Qingxian Gong2 1School of Management Science and Engineering, Shandong University of Finance and Economics, Jinan, Shandong, People’s Republic of China; 2Shunneng Network Technology Limited Company, Jinan, Shandong, People’s Republic of ChinaCorrespondence: Wei Su; Xin Zhang Email suwei@sdufe.edu.cn; zhangxin@sdufe.edu.cnPurpose: Missed appointments in outpatient registration pose challenges for hospital administrators, especially in the context of China’s shortage of medical resources. Previous studies have identified factors that affect healthcare access via traditional appointment systems. Few studies, however, have specifically investigated Internet appointment systems. Therefore, this study explored the key factors related to missed appointments made on the Internet appointment system of a general hospital in Jinan, Shandong Province.Methods: Online appointment data were collected from the outpatient department of a general hospital in Jinan from September 2017 to February 2018. Logistic regression was used to analyze the relative importance of eight variables: gender, age, interval between scheduling and appointment, day of the week, physician’s academic rank, appointment fee, previous missed appointments, and clinical department.Results: A total of 48,777 online appointment records were collected, which included a 15% no-show rate. The key factors associated with no-shows included age, interval between scheduling and appointment, previous missed appointments, and clinical department. No significant relationships were found between no-shows and gender, day of the week, and appointment fee.Conclusion: No-show rates were influenced by many factors. Based on this study’s findings, targeted measures can be taken to decrease no-show frequency and improve medical efficiency.Keywords: online appointments, no-show appointments, influential factors, logistic regression

Shuihong Li,1,* Xiaodan Wei,2,* Sisi Li,1 Cuiming Zhu,1 Chunhui Wu2 1Institution of Pathogenic Biology, Hengyang Medical College, University of South China, Hengyang 421001, Hunan, People’s Republic of China; 2School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu 610054, Sichuan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shuihong LiInstitution of Pathogenic Biology, Hengyang Medical College, University of South China, Hengyang 421001, Hunan, People’s Republic of ChinaTel/Fax +86 734 8282907Email zhoubaoxi520@163.comChunhui WuSchool of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu 610054, Sichuan, People’s Republic of ChinaTel/Fax +86 28 83203353Email wuchunhui@uestc.edu.cnAbstract: In the past few years, we have witnessed great development and application potential of various up-conversion luminescent nanoparticles (UCNPs) in the nanomedicine field. Based on the unique luminescent mechanism of UCNPs and the distinguishable features of cancer biomarkers and the microenvironment, an increasing number of smart UCNPs nanoprobes have been designed and widely applied to molecular imaging, cancer diagnosis, and treatment. Considerable technological success has been achieved, but the main obstacles to oncology nanomedicine is becoming an incomplete understanding of nano–bio interactions, the challenges regarding chemistry manufacturing and controls required for clinical translation and so on. This review highlights the progress of the design principles, synthesis and surface functionalization preparation, underlying applications and challenges of UCNPs-based probes for cancer bioimaging, diagnosis and treatment that capitalize on our growing understanding of tumor biology and smart nano-devices for accelerating the commercialization of UCNPs.Keywords: multimodal imaging, cancer biomarkers, tumor microenvironment

Ce Zhu,* Xiang Wang,* Sian Chen,* Xinxin Yang, Jing Sun, Bujian Pan, Weiteng Zhang, Xiaodong Chen, Yingpeng Huang Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yingpeng Huang Department of Gastrointestinal SurgeryThe Second Affiliated Hospital of Wenzhou Medical University, No. 109 West College Road, Wenzhou, Zhejiang Province People’s Republic of ChinaTel +86 13587616686Email 171121477@qq.comPurpose: The liver function index can predict the prognosis of hepatocellular carcinoma and many other non-neoplastic diseases. We aimed to determine whether the preoperative albumin–bilirubin (ALBI) grade could predict the prognosis of patients with gastric cancer (GC).Patients and Methods: Data of 243 patients with GC who underwent radical resection were collected retrospectively. Patients were divided into the high ALBI (>− 2.34) and low ALBI (≤− 2.34) grade groups. Overall survival was analyzed between the two groups using the Kaplan–Meier curves. Univariate and multivariate analyses identified the independent factors associated with postoperative complications and overall survival.Results: The postoperative complication rates were higher in the high ALBI grade group than in the low ALBI grade group (P=0.005). The high ALBI grade group also had worse overall survival (P< 0.001), especially TNM stage II–III patients (stage II, P=0.043; stage III, P< 0.001). In the high ALBI grade group, patients with TNM stage III not undergoing chemotherapy had significantly worse survival times (P=0.001). High ALBI grade (P=0.032), Charlson score of 1– 2 (P=0.007), and laparotomy surgery (P=0.045) were independent risk factors for postoperative complications. High ALBI grade (P=0.005), age ≥ 70 years (P=0.002), nutritional risk screening score 2002 score of 5– 6 (P=0.019), tumor located in the cardia (P=0.020), diffuse tumor (P< 0.001), and TNM stage III (P< 0.001) were independent risk factors for overall survival.Conclusion: Preoperative ALBI grade could predict postoperative complications and overall survival of patients with GC, especially those with TNM stages II–III. This grading method has the advantages of preoperative availability, simplicity, and objectivity and aids in improving preoperative prognosis prediction and in achieving better outcomes of postoperative chemotherapy.Keywords: gastric cancer, albumin–bilirubin, liver function, prognosis, postoperative complications

Linggang Zhu,1,2 Chu Zhu,1 Xuanxuan Wang,1 Hai Liu,1 Yanhong Zhu,1 Xiaonan Sun1 1Department of Radiation Oncology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of China; 2Department of Radiation Oncology, Taizhou Cancer Hospital, Taizhou, Zhejiang Province, People’s Republic of ChinaCorrespondence: Xiaonan SunDepartment of Radiation Oncology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, 3 Qingchun East Road, Hangzhou Zhejiang Province 310000, People’s Republic of ChinaTel +86 571 8609 6916Fax +86 571 8604 4817Email sunxiaonan@zju.edu.cnBackground: Radiotherapy and chemotherapy are the main clinical treatments for biliary tract cancers (BTCs). Patients with advanced disease have a very poor prognosis, yet no molecular targets have been proven effective for the adjuvant therapy of BTCs. In this study, we aimed to explore the effect of combination treatment with icotinib hydrochloride (IH) and fluzoparib (FZ) on radiosensitivity and clarify its underlying mechanism in the HCCC-9810 and GBC-SD human BTC cell lines.Methods: Cell proliferation was measured by Cell Counting Kit-8 (CCK-8) assay. The cell cycle distribution and apoptosis were analyzed by flow cytometry. The phosphorylation of EGFR and its downstream signaling molecules and the expression of RAD51 were measured by Western blot analysis. γ-H2AX foci in the cellular nuclei were visualized using immunofluorescence staining. A colony formation assay was performed to demonstrate cell radiosensitivity with IH and FZ combination treatment.Results: In the HCCC-9810 and GBC-SD human BTC cell lines, combined treatment with IH and FZ with synergetic radiation significantly inhibited cell proliferation, redistributed the cell cycle, enhanced apoptosis and delayed DNA damage repair by suppressing activation of the EGFR signaling pathway and attenuating expression of the homologous recombination (HR) protein RAD51.Conclusion: This study demonstrates that combined treatment with IH and FZ may be an applicable therapy to enhance the radiosensitivity of BTCs and that RAD51 may serve as a biomarker for this combination treatment.Keywords: icotinib hydrochloride, fluzoparib, biliary tract cancer, EGFR, PARP, radiotherapy

Chenyu Yang,1,2,* Yixiu Wang,3 Weijie Xue,4 Yuwei Xie,3 Qian Dong,1,2,* Chengzhan Zhu2,3,* 1Department of Pediatric Surgery, The Affiliated Hospital of Qingdao University, Qingdao 266003, People’s Republic of China; 2Shandong Provincial Key Laboratory of Digital Medicine and Computer-Assisted Surgery, Qingdao 266003, People’s Republic of China; 3Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Qingdao University, Qingdao 266003, People’s Republic of China; 4Department of Gastrointestinal Surgery, The Affiliated Hospital of Qingdao University, Qingdao 266003, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qian DongDepartment of Pediatric Surgery, The Affiliated Hospital of Qingdao University, Qingdao 266003, People’s Republic of ChinaEmail dong_qdu1963@163.comChengzhan ZhuDepartment of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Qingdao University, Qingdao 266003, People’s Republic of ChinaEmail zhu_405@163.comPurpose: Autophagy plays an important role in the occurrence and development of hepatocellular carcinoma (HCC). We aimed to develop an autophagy-related genes signature predicting the prognosis of HCC and to depict a competing endogenous RNA (ceRNA) network.Methods: Differentially expressed autophagy-related genes (DE-ATGs), miRNAs and lncRNAs and clinical data of HCC patients were extracted from TCGA. The GO and KEGG analysis were performed to investigate the gene function. Univariate and multivariate Cox regression analysis were used to identify a prognostic signature with the DE-ATGs. And a nomogram, adapted to the clinical characteristics, was established. Then, we established a ceRNA network related to autophagy genes.Results: We screened out 27 differentially expressed genes which were enriched in GO and KEGG pathways related to autophagy and cancers. In univariate and multivariate Cox regression analysis, BIRC5, HSPB8, and SQSTM1 were screened out to establish a prognostic risk score model (AUC=0.749, p< 0.01). Kaplan–Meier survival analysis showed that the overall survival of high-risk patients was significantly worse. Furthermore, the signature was validated in the other two independent databases. The nomogram, including the autophagy-related risk signature, gender, stage and TNM, was constructed and validated (C-index=0.736). Finally, the ceRNA network was established based on DE-ATGs, differentially expressed miRNAs and lncRNAs.Conclusion: We constructed a reliable prognostic model of HCC with autophagy-related genes and depicted a ceRNA network of DE-ATGs in HCC which provides a basis for the study of post-transcriptional modification and regulation of autophagy-related genes in HCC.Keywords: competing endogenous RNA, ceRNA, autophagy-related genes, hepatocellular carcinoma, HCC, TCGA

Hengrui Liang,1,* Caichen Li,1,* Yi Zhao,1,* Shen Zhao,2,* Jun Huang,1 Xiuyu Cai,2,3 Bo Cheng,1 Shan Xiong,1 Jianfu Li,1 Wei Wang,1 Changbin Zhu,4 Weiwei Li,5 Jianxing He,1 Wenhua Liang1 1Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou, People’s Republic of China; 2Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China; 3Department of General Internal Medicine, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China; 4BGI Genomics, BGI-Shenzhen, Shenzhen 518083, People’s Republic of China; 5BGI-Guangzhou Medical Laboratory, BGI-Shenzhen, Guangzhou 510006, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jianxing He; Wenhua LiangDepartment of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou 510120, People’s Republic of ChinaTel +86-20-83337792Fax +86-20-83350363Email liangwh1987@163.comObjective: Differences in efficacy of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) have been observed between non-small cell lung cancer (NSCLC) patients with 19 exon deletion (19Del) and L858R mutation. We explored whether the total number or pattern of concomitant mutations of 19Del and L858R may explain their different sensitivities.Patients and Methods: This study contained the mutational profiles of EGFR-mutated NSCLC patients from two cohorts: Guangzhou (G1) and database (G2). Concomitant mutation status and EGFR-TKI response information were retrieved.Results: A total of 403 patients covered 283 genes in the G1 and 803 patients with a different gene set in the G2 were included. Similar prevalence of total concomitant mutation number was observed in both G1 ( 19Del 32.48% vs L858R 30.45%; P=0.68) and G2 ( 19Del 74.9% vs L858R 73.2%; P=0.65) cohorts. Only HGF/c-Met pathway same more related to L858R mutation. EGFR-TKI response information was recorded for 134 patients in the G2 cohort. 19Del showed a higher objective response (OR) rate compared with L858R, regardless of concomitant mutations. Compared to patients with OR, non-OR patients had more concomitant mutations, both in 19Del (53.8% vs 83.3%; P=0.021) and L858R (51.4% vs 77.8%; P=0.029). In particular, total concomitant mutations (OR=0.27; P=0.03), sensitive EGFR mutations (OR=2.21; P=0.04), and T790M (OR=0.244; P=0.02) significantly affected the TKI response.Conclusion: Concomitant mutations were widespread in 19Del and L858R and were associated with poorer OR to EGFR-TKIs. However, 19Del and L858R had similar numbers and patterns of concomitant mutations, which might not explain the different sensitivity to EGFR-TKI.Keywords: epidermal growth factor receptor mutation, 19Del, L858R, non-small cell lung cancer, concomitant mutation

Shuang Xu,1 Dan Xu,1 Liang Wen,2 Chen Zhu,3 Ying Yang,1 Shuang Han,1 Peng Guan4 1School of Library and Medical Informatics, China Medical University, Shenyang, Liaoning, People’s Republic of China; 2Department of Neurosurgery, The General Hospital of Shenyang Military Command, Shenyang, Liaoning, People’s Republic of China; 3Department of Neurosurgery, The First Hospital of China Medical University, Shenyang, Liaoning, People’s Republic of China; 4Department of Epidemiology, School of Public Health, China Medical University, Shenyang, Liaoning, People’s Republic of ChinaCorrespondence: Peng GuanDepartment of Epidemiology, School of Public Health, China Medical University, Shenyang 110122, Liaoning, People’s Republic of ChinaEmail pguan@cmu.edu.cnBackground: The treatment of post-traumatic stress disorder (PTSD) has long been a challenge because the symptoms of PTSD are multifaceted. PTSD is primarily treated with psychotherapy and medication, or a combination of psychotherapy and medication. The present study was designed to analyze the literature on medications for PTSD and explore high-frequency common drugs and low-frequency burst drugs by burst detection algorithm combined with Unified Medical Language System (UMLS) and provide references for developing new drugs for PTSD.Methods: Publications related to medications for PTSD from 2010 to 2019 were identified through PubMed, Web of Science Core Collection, and BIOSIS Previews. SemRep and SemRep semantic result processing system were performed to extract the set of drug concepts with therapeutic relationship according to the semantic relationship of UMLS. Kleinberg’s burst detection algorithm was applied to calculate the burst weight index of drug concepts by a Java-based program. These concepts were sorted according to the frequency and the burst weight index.Results: Four hundred and fifty-nine treatment-related drug concepts were extracted. The drug with the highest burst weight index was “Psilocybine”, a hallucinogen, which was more likely to be a hotspot for the pharmacotherapy of PTSD. The highest frequency concept was “prazosin”, which was more likely to be the focus of research in the medications for PTSD.Conclusion: The present study assessed the medication-related literature on PTSD treatment, providing a framework of burst words detection-based method, a baseline of information for future research and the new attempt for the discovery of textual knowledge. The bibliometric analysis based on the burst detection algorithm combined with UMLS has shown certain feasibility in amplifying the microscopic changes of a specific research direction in a field, it can also be used in other aspects of disease and to explore the trends of various disciplines.Keywords: post-traumatic stress disorder, burst detection, Kleinberg’s algorithm, burst word, Unified Medical Language System, SemRep

Lan Cui,1,* Wentao Liu,1,* Hao Liu,1 Qian Qin,1,2 Shuangxia Wu,1 Suqin He,1,3 Zhenya Zhang,4 Xinchang Pang,1 Chengshen Zhu1 1School of Materials Science and Engineering, Zhengzhou University, Zhengzhou 450001, People’s Republic of China; 2Bio & Soft Matter, Institute of Condensed Matter and Nanosciences, Universite Catholique de Louvain, Louvain-la-Neuve B-1348, Belgium; 3Henan Key Laboratory of Advanced Nylon Materials and Application, Zhengzhou University, Zhengzhou 450001, People’s Republic of China; 4Department of Chemistry, Changwon National University of Korea, Changwon-city, Gyeongnam-do 51140, Republic of Korea*These authors contributed equally to this workCorrespondence: Wentao Liu; Hao LiuSchool of Materials Science and Engineering, Zhengzhou University, Zhengzhou 450001, Henan Province, People’s Republic of ChinaEmail wtliu@zzu.edu.cn; hliu@zzu.edu.cnBackground: Although pH and redox sensitiveness have been extensively investigated to improve therapeutic efficiency, the effect of disulfide bonds location and pH-triggered charge-reversal on cascade-targeting still need to be further evaluated in cancer treatment with multi-responsive nanoparticles.Purpose: The aim of this study was to design multi-responsive DOX@MSNs-COS-NN-CMC, DOX@MSNs-COS-SS-CMC and DOX@MSNs-COS-CMC-SS and systematically investigate the effects of disulfide bonds location and charge-reversal on the cancer cell specificity, endocytosis mechanisms and antitumor efficiency.Results: In vitro drug release rate of DOX@MSNs-COS-SS-CMC in tumor environments was 7-fold higher than that under normal physiological conditions after 200 h. Furthermore, the fluorescence intensity of DOX@MSNs-COS-SS-CMC and DOX@MSNs-COS-CMC-SS was 1.9-fold and 1.3-fold higher than free DOX at pH 6.5 and 10 mM GSH. In addition, vesicular transport might be a factor that affects the uptake efficiency of DOX@MSNs-COS-SS-CMC and DOX@MSNs-COS-CMC-SS. The clathrin-mediated endocytosis and endosomal escape of DOX@MSNs-COS-SS-CMC enhanced cellular internalization and preserved highly controllable drug release into the perinuclear of HeLa cells. DOX@MSNs-COS-SS-CMC exhibited a synergistic chemotherapy in preeminent tumor inhibition and less side effects of cardiotoxicity.Conclusion: The cascade-targeting of charge-reversal and disulfide bonds shielding would be a highly personalized strategy for cervical cancer treatment.Keywords: disulfide bonds, pH-triggered charge-reversal, redox sensitive, chitosan oligosaccharide, human cervical carcinoma therapy

Yaqian Zhou,1,* Xingyu Zhu,2,* Shangyang Lin,1 Chenqi Zhu,1 Li Wu,1 Rui Chen,1 Zhipeng Chen,1 Weidong Li1,3 1College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, People’s Republic of China; 2Department of Pharmacy and Traditional Chinese Medicine, Jiangsu College of Nursing, Huaian 223001, People’s Republic of China; 3Engineering Center of State Ministry of Education for Standardization of Chinese Medicine Processing, Nanjing University of Chinese Medicine, Nanjing 210023, People’s Republic of China*These authors contributed equally to this workCorrespondence: Weidong LiEngineering Center of State Ministry of Education for Standardization of Chinese Medicine Processing, Nanjing University of Chinese Medicine, Nanjing 210023, People’s Republic of ChinaEmail liweidong0801@163.comObjective: To prepare xanthatin (XA)-loaded polydopamine (PDA) nanoparticles (PDA-XA-NPs) and to investigate their adhesion and bioavailability.Materials and methods: PDA-XA-NPs were synthesized and characterized using transmission electron microscopy, zeta potential analysis and encapsulation efficiency analysis. Their in vitro release kinetics and inhibitory effects on gastric cancer were studied. The adhesion of PDA-XA-NPs was evaluated by in vivo imaging atlas. The pharmacokinetics of PDA-XA-NPs and XA was compared.Results: PDA-XA-NPs had a spherical shape, a particle size of about 380 nm, an encapsulation efficiency of (82.1 ± 0.02) % and a drug loading capacity of (5.5 ± 0.1)%. The release of PDA-XA-NPs in PBS was stable and slow, without being affected by pH. The adhesion capacity of PDA-XA-NPs for mucin was significantly higher than that of bulk drug. The gastric mucosal retention of PDA-XA-NPs reached 89.1% which significantly exceeded that of XA. In vivo imaging showed that PDA-XA-NPs targeting the stomach were retained for a period of time. The pharmacokinetics study showed that PDA-XA-NPs had a longer retention time and a slower drug release than those of XA. In vitro experiments confirmed that PDA-XA-NPs exerted similar inhibitory effects on gastric cancer to those of XA, which lasted for a period of time.Conclusion: High-adhesion NPs were constructed. Gastric cancer was targeted by orally administered PDA-XA-NPs, as a potentially feasible therapy. Eventually, the bioavailability of XA was increased.Keywords: xanthatin, polydopamine, nanoparticles, gastric cancer, target, pharmacokinetics

Tianping Luo,1 Yuan Gao,1 Guangyan Zhangyuan,2 Xiaoliang Xu,3 Cailin Xue,1 Lei Jin,1 Wenjie Zhang,3 Chunfu Zhu,1 Beicheng Sun,3 Xihu Qin1 1Department of Hepatobiliary Surgery, The Affiliated Changzhou NO. 2 People’s Hospital of Nanjing Medical University, Changzhou, Jiangsu Province 213164, People’s Republic of China; 2Liver Transplantation Center of the First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu Province 210029, People’s Republic of China; 3Department of Hepatobiliary Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu Province 210008, People’s Republic of ChinaCorrespondence: Xihu QinDepartment of Hepatobiliary Surgery, The Affiliated Changzhou NO. 2 People’s Hospital of Nanjing Medical University, Changzhou, Jiangsu Province 213164, People’s Republic of ChinaEmail qinxihu@126.comBackground: Hepatocellular carcinoma (HCC) is a very belligerent primary liver tumor with high metastatic potential. Aberrant expression of lncRNAs drives tumorous invasion and metastasis. Whether lncRNAs engage mechanisms of liver cancer metastasis remains largely unexplored.Patients and Methods: We collected HCC tissues from the tumors and their adjacent normal samples in the Chinese population and analyzed the levels of lncRNAs by microarray analysis. The gain- and loss-of-function analysis demonstrated that PCBP1-AS1 accelerated tumorous growth and metastasis in vivo and in vitro. Moreover, we used RNA-pulldown assay to show that PCBP1-AS1 physically interacted with polyC-RNA-binding protein 1 (PCBP1); meanwhile, PCBP1-AS1 was indeed detected in RIP with the PCBP1 antibody. Mechanistically, we first explored the relationship between PCBP1‐AS1 and PCBP1 in HCC cell lines.Results: Here we show that PCBP1-AS1, identified by microarray analysis on pre- and post-operative HCC plasma specimens, was highly expressed in human HCC, clinically verified as a prometastatic factor and markedly associated with poor prognosis in patients with hepatocellular carcinoma. PCBP1‐AS1 was negatively related with PCBP1 at the messenger RNA and protein expression levels. PCBP1-AS1 triggered PRL-3 and AKT in HCC tumor cells. Additionally, the double knockout of PCBP1 and PCBP1-AS1 abolished the PCBP1-AS1-induced PRL-3-AKT signalling pathway activation.Conclusion: The upregulation of PCBP1-AS1 enhances proliferation and metastasis in HCC, thus regulating the PCBP1-PRL-3-AKT signalling pathway.Keywords: hepatocellular carcinoma, long non-coding RNA, PCBP1-AS1, poly(C)-binding protein 1, AKT, hepatocarcinogenesis, metastasis

He Huang,1,* Xinxin Yang,2,* Jing Sun,2,* Ce Zhu,2 Xiang Wang,2 Yunpeng Zeng,2 Jingxuan Xu,2 Chenchen Mao,2 Xian Shen2,3 1Department of General Surgery, The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China; 2Department of Gastrointestinal Surgery, The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China; 3Department of Gastrointestinal Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chenchen Mao; Xian ShenDepartment of Gastrointestinal Surgery, The Second Affiliated Hospital, Wenzhou Medical University, No. 109 West College Road, Wenzhou, Zhejiang Province, People’s Republic of ChinaTel +86 577 8800 2709Email 578117567@qq.com; shenxian5166@gmain.comPurpose: Although peritoneal metastasis (PM) is associated with poor prognosis in gastric cancer (GC) patients, it is difficult to discriminate preoperatively. Our previous study has demonstrated visceral fat area (VFA) is a better obesity index than body mass index (BMI) in predicting abdominal metastasis. This study aimed to further explore the relationship between obesity and PM.Patients and Methods: VFA was retrieved for 859 consecutive patients undergoing radical gastrectomy between January 1, 2009, and December 31, 2013. A receiver operating characteristic curve analysis was used to determine the BMI-specific cutoff values for VFA. Univariate and multivariate analyses evaluating the risk factors for PM at different BMI levels were performed.Results: The optimal cutoff values for VFA were 67.28, 88.03, and 175.32 cm2 for low, normal, and high BMI patients, respectively, and 18 (15.52%), 220 (40.15%), and 61 (31.28%) patients were classified as having high VFA in each group. Univariate logistic regression revealed that the association between high VFA and PM was not dependent on BMI (odds ratio [OR]=9.048, P=0.007 for low BMI, OR=3.827, P< 0.001 for normal BMI, and OR=2.460, P=0.049 for high BMI). In multivariate logistic regression analysis, high VFA (OR=3.816, P< 0.001) and vascular invasion (OR=1.951, P=0.039) were independent risk factors for PM only in the normal BMI group.Conclusion: VFA only effectively predicted PM for GC patients with normal BMI, rather than those with low and high BMI. More attentions should be paid to those GC patients with high VFA and normal BMI.Keywords: gastric cancer, peritoneal metastasis, obesity, visceral fat area, body mass index

Shuhan Liu,1 Jing Yang,2 Xudong Peng,3 Jingjing Li,4 Cunjing Zhu2 1Department of Reproductive Medicine, Jining First People’s Hospital, Jining 272000, People’s Republic of China; 2Department of Gynecology, Jining First People’s Hospital, Jining 272000, People’s Republic of China; 3Department of Ophthalmology, The Affiliated Hospital of Qingdao University, Qingdao 266000, People’s Republic of China; 4Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao 266000, People’s Republic of ChinaCorrespondence: Cunjing Zhu Tel +86-0537-60566666Email zhucunjing@126.comObjective: Ovarian cancer (OC) is the leading cause of death among gynecological tumors; however, no effective treatment is currently available. Fucoidan, which is extracted from marine algae, has significant anti-cancer effects. The aim of this study was to determine the effects of fucoidan on the proliferation and apoptosis of OC cells through inhibition of the PI3K/Akt signaling pathway.Methods: Human ovarian normal epithelial cells (IOSE80) and human OC cells (SKOV-3, A2780, OVCAR-3, TOV-112D, and Caov-3) were selected to verify the safety of fucoidan at various doses in SKOV-3 and Caov-3 cells as well as a xenograft mouse model using various molecular biology techniques.Results: Fucoidan had no significant effect on normal ovarian epithelial cells, but had significantly inhibited the proliferation of OC cells, induced cell cycle arrest at the G0/G1 phase, increased the proportion of apoptotic cells and expression of pro-apoptotic proteins, and inhibited the expression of PI3K and phosphorylation of Akt, which could be partly rescued by IGF-1.Conclusion: Fucoidan had anti-tumor effects both in vivo and in vitro via a mechanism that is related to the inhibition of the PI3K/Akt signaling pathway.Keywords: ovarian cancer, fucoidan, cell cycle, apoptosis, PI3K/Akt

Yangyang Wang,1,2,* Shuchang Wang,1,* Chunchao Zhu,1 Hui Cao,1 Zizhen Zhang,1 Enhao Zhao1 1Department of Gastrointestinal Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, People’s Republic of China; 2State Key Laboratory for Oncogenes and Related Genes, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200240, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zizhen Zhang; Enhao ZhaoDepartment of Gastrointestinal Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai 200127, People’s Republic of ChinaTel +8618800299532Fax +86-21-58394262Email zzzhang16@hotmail.com; microzhaoenhao@163.comPurpose: Adenocarcinoma of the esophagogastric junction (AEG) patient immune characteristics were analyzed in this study, and these features were compared with patient clinical pathology and prognosis.Patients and Methods: The clinicopathological data and prognostic information of 96 AEG patients who were admitted to Ren Ji Hospital between December 2008 and December 2015 were collected. PD-1/PD-L1, Tim-3/Gal-9, and CD3/CD8/Foxp3 expression in these patients, as well as the correlation of the expression of these molecules with clinicopathological data and survival time, were analyzed. Comparisons of count data were performed using the chi-square test or Fisher’s exact test. The survival rate and survival curves were calculated and drawn, respectively, with the Kaplan–Meier method, and the Log rank test was used for survival analysis.Results: The positive rate for PD-L1 and Gal-9 in these AEG patients was 30.21% and 31.25%, respectively. Tim-3 positivity had a close relationship with patient Siewert type. CD8+ T cell infiltration and patient TNM stage, as well as CD3+CD8+ T cell infiltration and patient Lauren type, had a close relationship based on analysis of the correlation between immune factor expression and clinicopathological data. The group with high CD8+ T cell infiltration had an improved survival rate, while the combined analysis of Tim-3 and Gal-9 expression showed that the double-positive group had a significantly poorer prognosis than groups with other Tim-3 and Gal-9 expression patterns. The PD-L1 expression level had a close relationship with T cell infiltration in AEG patients, especially CD3+ and CD8+ T cell infiltration.Conclusion: Tim-3 expression was higher in patients with Siewert type I tumors than in patients with tumors of other Siewert types. Patients with high CD8+ T cell infiltration had a better prognosis than patients with low CD8+ T cell infiltration, and CD8+ T cell infiltration was closely related to AEG patient TNM stage. The Tim-3 and Gal-9 double-positive group showed poor prognosis, and immune therapy could be recommended for these AEG patients.Keywords: AEG, adenocarcinoma of the esophagogastric junction, Siewert type, immune characteristic, survival prognosis

Jie Chen,1 Jingwen Luo,2 Xia He,3 Chenjing Zhu3 1Department of Oncology, Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of China; 2Department of Oncology, West China School of Medicine, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 3Department of Radiation Oncology, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of ChinaCorrespondence: Xia He; Chenjing ZhuDepartment of Radiation Oncology, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, Jiangsu Tel/Fax +86-28-85475576Email hexiabm@163.com; drchenjingzhu@gmail.comIntroduction: We performed this study to explore the diagnostic accuracies and cutoff values of contrast-enhanced computed tomography (CT) and magnetic resonance imaging (MRI) for the detection and diagnosis of metastatic retropharyngeal lymph nodes (RLNs) in patients with nasopharyngeal carcinoma (NPC).Methods: One hundred and twenty-eight patients with a total of 159 RLNs were included in the study. The sizes of maximal and minimal axial diameters of each node on both contrast-enhanced CT and MRI images were measured. The characteristics of the RLNs (malignant or benign), as well as the survival of patients, were classified based on the results of follow-up MRI.Results: RLN size cutoffs of 4– 11 mm for minimal axial diameter were used. We found that MRI showed higher sensitivity while CT demonstrated higher specificity. The reasonable criterion for the diagnosis of metastatic RLNs in MRI was a minimal axial diameter of ≥ 6 mm, which yielded a sensitivity, specificity and diagnostic odds ratio (DOR) of 0.71, 0.82 and 10.88.Conclusion: The radiologic criteria that should be used for the assessment of RLN metastases in NPC patients are nodes with a minimal axial diameter of ≥ 6 mm on MR images.Keywords: retropharyngeal lymph node, metastasis, nasopharyngeal carcinoma, cutoff, MRI

Shuang-long Li, Yong-liang Zhu, Chun-yang Zhu, Shao-bin Li, Zi-heng Li, Xiang-jun Qiu Medical College of Henan University of Science and Technology, Luoyang 471023, People’s Republic of ChinaCorrespondence: Xiang-jun QiuMedical College of Henan University of Science and Technology 471023, People’s Republic of ChinaTel +86 13698882699 Fax + 86 379-64830346 Email lyxiangjun@126.comAbstract: A method for the simultaneous determination of parecoxib and its metabolite valdecoxib in beagle plasma by UPLC-MS/MS was developed and validated. After the plasma was extracted by acetonitrile precipitation, the analytes were separated on an Acquity UPLC BEH C18 column (2.1 mm × 50 mm, 1.7 μm) using acetonitrile-formic acid as the mobile phase in gradient mode. The analytes were monitored by multiple reaction monitoring (MRM) in electrospray negative ion mode. The mass transfer pairs were m/z 368.97→ 119.01 for parecoxib, m/z 312.89→ 118.02 for valdecoxib, and m/z 379.98→ 316.02 for celecoxib (internal standard, IS). The correlation coefficients of parecoxib and valdecoxib ranged from 5 to 4000 ng/mL were greater than 0.9998. The recovery of parecoxib and valdecoxib was greater than 82.54%. The inter- and intra-day precision RSD values were 1.36∼ 3.65% and 2.28∼ 5.91%, respectively. The accuracy of RE values were − 1.38%∼ 1.96%. Finally, the matrix effect (ME) and stability were also within acceptable criteria. This method had been successfully applied to the pharmacokinetics of parecoxib and valdecoxib in beagle plasma after injection of parecoxib (1.33 mg/kg, intramuscular injection).Keywords: parecoxib, valdecoxib, UPLC-MS/MS, pharmacokinetics

Qingjuan Chen,1,* Chenjing Zhu,2,* Yingying Jin,3 Xiaomin Si,4 Wan Jiao,4 Wenjing He,4 Wei Mao,4 Ming Li,1 Guomin Luo1 1Department of Oncology, Yongchuan Hospital of Chongqing Medical University, Chongqing 40016, People’s Republic of China; 2Department of Radiation Oncology, Jiangsu Cancer Hospital and Jiangsu Institute of Cancer Research and The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, Jiangsu 210009, People’s Republic of China; 3Department of Oncology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi Province 710004, People’s Republic of China; 4Department of Oncology, Xianyang Center Hospital, Xi’an, Shaanxi Province 712000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qingjuan ChenDepartment of Oncology, Yongchuan Hospital of Chongqing Medical University, Chongqing 40016, People’s Republic of ChinaEmail dr.qingjuan.chen@outlook.comBackground: Lung cancer is one of the most common malignancies around the world. The lack of early diagnosis and effective treatment strategies contributes to the poor prognosis of patients with lung cancer. Recent studies have implied the role of long non-coding RNAs (lncRNAs) in oncogenesis. The purpose of our study was to identify specific lncRNAs which were correlated with non-small cell lung cancer (NSCLC) and their potential functions.Materials and Methods: The global plasma lncRNA profiling was performed using LncPathTM Human Cancer Array, and 11 lncRNAs were then selected for quantitative reverse transcription PCR (qRT-PCR) validation in 138 plasma samples from 69 NSCLC patients and 69 healthy controls (HCs). A noteworthy lncRNA, RP11-438N5.3, the function of which was previously unknown, was further explored on the aspect of the correlation of its expression level with clinicopathological factors.Results: The results revealed that plasma level of RP11-438N5.3 was significantly lower in NSCLCs than that in HCs (p < 0.01). Receiver operating characteristic (ROC) analyses showed that the area under the ROC curve (AUC) for plasma RP11-438N5.3 was 0.814 (95% CI, 0.743– 0.885; p< 0.01). High expression of RP11-438N5.3 in plasma correlated with favorable prognosis for NSCLC patients (Hazard ratio = 2.827; 95% CI: 1.036 to 7.718; p = 0.024; Cox regression analysis). Moreover, we found that the plasma level of stromal interaction molecule 1 (STIM1) mRNA was remarkably higher in NSCLC compared with HC (p< 0.01), and the AUC for STIM1 was 0.753 (95% CI, 0.673– 0.833; p< 0.01), RP11-438N5.3 and STIM1 were inversely correlated with each other.Conclusion: Our results indicated that RP11-438N5.3 and STIM1 might provide a new strategy for NSCLC diagnosis. Furthermore, increased circulating RP11-438N5.3 level holds great potential in indicating a beneficial prognosis in NSCLC patients.Keywords: long non-coding RNA, biomarker, non-small cell lung cancer, RP11-438N5.3, stromal interaction molecule 1

Jin Yu, Caifeng Zhu, Jiazhen Yin, Dongrong Yu, Feng Wan, Xuanli Tang, Xue Jiang Department of Nephrology, Guangxing Hospital Affiliated to ZheJiang Chinese Medical University (Key Laboratory of Zhejiang Province, Management of Kidney Disease), Hangzhou 310007, People’s Republic of ChinaCorrespondence: Xue JiangDepartment of Nephrology, Guangxing Hospital Affiliated to ZheJiang Chinese Medical University (Key Laboratory of Zhejiang Province, Management of Kidney Disease), Hangzhou 310007, People’s Republic of ChinaEmail monica_jiang@163.comObjective: Podocyte damage is common in many renal diseases characterized by proteinuria. Transient receptor potential cation channel protein 6 (TRPC6) plays an important role in renal function through its regulation of intracellular Ca2+ influx and RhoA/ROCK pathways. Chinese herb Stephania tetrandra, with the main active component being tetrandrine, has been used for the treatment of various kidney diseases for several years and has shown a positive effect. This study aimed at investigating the effect and mechanism of tetrandrine in podocyte damage induced by high expression of TRPC6.Methods: Immortalized, differentiated murine podocytes, MPC5 were treated with valsartan (0– 800 μM) and tetrandrine (0– 40 μM) for 48 h. The maximum safe concentrations of valsartan and tetrandrine were selected using a cell viability assay. MPC5 podocytes stably expressing TRPC6 were constructed using a lentivirus packaging system, followed by treatment with valsartan, tetrandrine, and Y-27632 for 48 h and U73122 (10 μM) for 10 min. The RhoA/ROCK pathway and podocyte-specific proteins (nephrin and synaptopodin) levels were quantified. Podocyte apoptosis and intracellular Ca2+ concentration were measured.Results: Maximum safe concentrations of 100 μM valsartan and 10 μM tetrandrine showed no observable toxicity in podocytes. MPC5 podocytes stably expressing TRPC6 had higher intracellular Ca2+ influx, apoptotic percentages, and expression of RhoA/ROCK proteins, but lower expression of nephrin and synaptopodin proteins. U73122 treatment for 10 min did not inhibit TRPC6, but suppressed RhoA/ROCK protein. Y-27632 decreased ROCK1 expression, but did not influence the expression of TRPC6 protein. Both 100 μM valsartan and 10 μM tetrandrine for 48 h significantly inhibited intracellular Ca2+ influx, apoptosis, and RhoA/ROCK pathway, and increased nephrin and synaptopodin proteins in podocytes stably expressing TRPC6.Conclusion: Elevated TRPC6 expression can lead to podocyte injury by inducing intracellular Ca2+ influx and apoptosis of podocytes, and this effect may be mediated by activation of the RhoA/ROCK1 pathway. Tetrandrine can alleviate podocyte injury induced by TRPC6 expression through inhibition of the RhoA/ROCK pathway, suggesting a protective role in podocyte damage.Keywords: tetrandrine, transient receptor potential cation channel protein 6, podocyte, RhoA/ROCK pathway

Jiayue Luo, Tianzhu Long, Yuanxuan Cai, Yuan Teng, Zhe Fan, Zhen Liang, Cairong Zhu, Hongmin Ma, Guanhua Li Department of Breast Surgery, Guangzhou Women and Children`s Medical Center, Guangzhou Medical University, Guangzhou, Guangdong 510623, People’s Republic of ChinaCorrespondence: Guanhua Li; Hongmin MaDepartment of Breast Surgery, Guangzhou Women and Children`s Medical Center, Guangzhou Medical University, Guangzhou, Guangdong 510623, People’s Republic of ChinaTel/Fax +86 20 8188 6332Email dr.liguanhua@hotmail.com; dr_mahongmin@sina.com.cnBackground: Lactational breast abscess, a complication from lactational mastitis, is a common cause of breastfeeding discontinuation. No consensus has been reached regarding the necessity of antibiotics in this disease. The purpose of this trial is to determine if surgical drainage is non-inferior to drainage together with a standard course of antibiotics, in the treatment of lactational breast abscess.Methods: Breastfeeding females with breast abscess from 18 to 50 years old are eligible for study inclusion. An expected number of 306 patients will be randomly allocated in parallel to the intervention arm (simple drainage without antibiotics) or the control arm (abscess drainage with standard 5-day-course of antibiotics). The primary outcomes include the time to resolution of breast abscess and disease recurrence rate. Secondary outcomes of interests are 3-day-improvement proportion, rate of continuing breastfeeding, treatment failure rate, procedural-related complications, and length of hospital stay. An expected non-inferiority margin for the difference in the primary outcome of interest is set at 1 day, on the basis of a one-sided 97.5% confidence interval.Discussion: This trial will provide first-hand evidence on whether simple abscess drainage is non-inferior to drainage together with a standard course of antibiotics, in lactational mothers with breast abscess. The indication of antibiotic prophylaxis could be revised if non-inferiority is set up, and guidelines for lactational breast abscess require amendments correspondingly.Trial Registration: This study has been registered in the Chinese Clinical Trial Registry, and the trial registration number is ChiCTR1900024008.Keywords: lactational breast abscess, antibiotics, drainage, randomized controlled trial, study protocol

Chengcheng Zhu,1 Huafeng Ding,1 Junwen Yang,1 Yihui Zhou,1 Yonghong Luo,1 Suhua Shi,1 Ying Zhang,1 Yalan Wei,2 Guantai Ni1 1Departments of Gynecology and Obstetrics, Yi Jishan General Hospital of Wannan Medical College, Wuhu, Anhui, People’s Republic of China; 2Departments of Gynecology and Obstetrics, General Hospital of Wuhu Second People’s Hospital, Wuhu, Anhui, People’s Republic of ChinaCorrespondence: Guantai Ni; Yalan WeiDepartments of Gynecology and Obstetrics, Yi Jishan General Hospital of Wannan Medical College, 2 Zheshan West Road, Wuhu, Anhui 241000, People’s Republic of ChinaTel +86-138 5532 0259Email 12sunhl14@163.com; 603329457@qq.comIntroduction: Proline hydroxylase 2 (PHD2) is involved in tumorigenesis. This study aimed to examine PHD2 and hypoxia-inducible factor 1α (HIF-1α) expression in different endometrial tissues and explore the correlations between PHD2 and HIF-1α expression with clinicopathological characteristics of endometrial cancer.Methods: We collected 50 tissue sections of endometrial adenocarcinoma, 30 of atypical endometrial hyperplasia, and 30 of control normal endometrium. The expression of PHD2 was detected by PCR, Western blot, and immunohistochemical analysis.Results: PHD2 mRNA and protein levels reduced in endometrial cancer tissues compared to normal endometrium (p

Zhaofei Wan,1 Yan Fan,2 Xiaojun Liu,1 Jiahong Xue,1 Zhenhua Han,1 Canzhan Zhu,1 Xinhong Wang1 1Department of Cardiovascular Medicine, Second Affiliated Hospital of Medical College, Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 2Department of Cardiovascular Medicine, Gansu Provincial Hospital, Lanzhou, People’s Republic of ChinaCorrespondence: Xinhong WangDepartment of Cardiovascular Medicine, Second Affiliated Hospital of Medical College, Xi’an Jiaotong University, 157 Xiwu Road, Xi’an, Shaanxi 710004, People’s Republic of ChinaTel +86 298 632 0430Email wangxinhongshx@163.comBackground: NLRP3 inflammasome can be activated by high glucose and links inflammation and metabolic disease. This study aimed to investigate the role of NLRP3 inflammasome in hyperglycemia-induced endothelial inflammation and diabetic atherosclerosis.Methods: NLRP3 levels in peripheral blood mononuclear cell (PBMC) and plasma IL-1β level were measured in diabetes patients. The activation of NLPR3 was detected in diabetic ApoE−/− mice and human umbilical vein endothelial cells (HUVECs).Results: Compared with healthy controls, NLRP3 expression levels in PBMC and plasma IL-1β level were significantly higher in diabetes patients but considerably decreased after lifestyle interventions and medicine. Moreover, carotid atherosclerosis was significantly related to plasma IL-1β level in diabetes patients. In diabetic atherosclerosis mouse model, NLRP3 knockdown suppressed NLRP3 inflammasome activation, inhibited the expression of adhesion molecules ICAM-1 and VCAM-1 in intima, reduced atherosclerosis and stabilized atherosclerotic plaque. In vitro, the expression of NLRP3 inflammasome components and the secretion of IL-1β were augmented by high glucose in HUVECs. Moreover, either high glucose or IL-1β promoted the expression of adhesion molecules, which were suppressed by NLRP3 knockdown or IL-1β receptor antagonist.Conclusion: These findings provide novel insights into pathological mechanisms of diabetic atherosclerosis and have potential therapeutic implications for cardiovascular complications in diabetes.Keywords: NLRP3 inflammasome, diabetes, atherosclerosis, inflammation

Xiaodong Chen,1,* Yunpeng Zeng,1,* Yunshi Huang,2 Jingxuan Xu,1 Weiyang Meng,3 Xiang Wang,1 Ce Zhu,2 Guanbao Zhu,2 Chenchen Mao,1 Xian Shen1,21Department of Gastrointestinal Surgery, The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China; 2Department of Gastrointestinal Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China; 3Department of Emergency Medical, The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Chenchen Mao; Xian ShenDepartment of Gastrointestinal Surgery, The Second Affiliated Hospital of Wenzhou Medical University, No. 109 West College Road, Wenzhou, Zhejiang Province, People’s Republic of ChinaTel +86 05 778 800 2709Email 578117567@qq.com; shenxian5166@gmail.com*These authors contributed equally to this workBackground: Cachexia affects nearly 50–80% of cancer patients, and most studies have only focused on elderly patients. We investigated preoperative cachexia in gastric cancer (GC) patients by age group and comprehensively analyzed the impact of preoperative cachexia on the prognosis of GC patients in all age groups.Methods: In total, 575 patients were prospectively analyzed. The effect of preoperative cachexia on overall survival (OS) in all the patients and in patients with different age groups were investigated using log-rank test and Cox proportional hazards regression, respectively.Results: In total, 35.8% (206 of 575) individuals were diagnosed with cachexia. The median survival of cachexia patients (29.2 months) was shorter than that of non-cachexia patients (35.7 months). Cachexia (HR =1.976, P

Zhidu Song,1 Hailiang Wang,2 Fangwei Zong,1 Chao Zhu,1 Ying Tao3 1Department of Ophthalmology, The Second Hospital of Jilin University, Changchun, Jilin 130022, People’s Republic of China; 2Department of Neurosurgery, The Second Hospital of Jilin University, Changchun, Jilin 130031, People’s Republic of China; 3Department of Anesthesiology, The Third Hospital of Jilin University, Changchun, Jilin 130033, People’s Republic of ChinaCorrespondence: Ying TaoDepartment of Anesthesiology, The Third Hospital of Jilin University, No.2 Xiantai Road, Changchun, Jilin 130033, People’s Republic of ChinaTel +86 1 868 668 6675Fax +86 4 318 539 5237Email taoying.med@yahoo.comBackground: MicroRNAs have been reported to participate in the initiation and progression of retinoblastoma (RB), most common malignancy in children. The refractory mechanisms of chemoresistance and the toxicity of chemotherapies hindered the treatment especially on young children. Novel RB therapies are urgently required. MiR-506 is probed to be associated with the tumorigenesis of various cancers whilst the role of this miR in RB remains unclear.Methods: Here, the impact of miR-506 on RB cell survival in vitro and tumorigenesis in vivo was examined. MiR-506 expression was examined in human RB samples and cell lines as compared with healthy tissues and non-RB cells. EdU staining and colony formation assay were performed to determine the effect of miR-506 on RB cell growth. TdT-mediated dUTP nick end labeling (TUNEL) staining and flow cytometry analysis were applied to detect the apoptotic cell number after miR-506 was downregulated in RB cells. Furthermore, dual-luciferase reporter assay was utilized to confirm the direct interaction between miR-506 and SIRT1 gene.Results: MiR-506 expression was upregulated in 20 human RB samples from patients as well as in human RB cell lines, WERI-Rb1 and Y79, as compared to that in healthy tissues and non-RB cells. In contrast, the expression of sirtuin 1 (SIRT1), known as NAD-dependent deacetylase, was downregulated in RB samples and cell lines. Aberrant reduced miR-506 expression impaired survival and proliferation of WERI-Rb1 and Y79 cells. The depletion of miR-506 expression promoted apoptosis of the two RB cell lines. The results of bioinformatics analysis and dual-luciferase assay exhibited that miR-506 targeted the 3ʹ-untranslated region of SIRT1 on silencing purpose. The SIRT1 silencing lessened the miR-506 inhibition on RB cell proliferation and undermined apoptosis.Conclusion: The results provided an insight into the role of miR-506 during RB development and offered potential pharmaceutical strategy for RB diagnosis.Keywords: retinoblastoma, miR-506, apoptosis, SIRT1

Jingxuan Xu,* Xiaodong Chen,* Xiang Wang, Ce Zhu, Yuanbo Hu, Xinxin Yang, Chongyong Xu, Xian Shen Department of Gastrointestinal Surgery, The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chongyong Xu; Xian ShenDepartment of Gastrointestinal Surgery, The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang Province, People’s Republic of ChinaTel +86 0577 8800 2709Email stony693100@163.com; shenxian5166@gmail.comBackground: Hyponatremia and hypocalcemia are common in patients with cancer, but their prognostic impact in patients who underwent gastric cancer (GC) surgery has not been investigated. Therefore, this study aimed to determine the postoperative prognostic impact of hyponatremia and hypocalcemia in patients undergoing curative gastrectomy by age group.Materials and methods: GC patients preoperatively diagnosed with hyponatremia or hypocalcemia who underwent elective radical gastrectomy were retrospectively evaluated. The patients were divided into the elderly group (≥60 years) and the young group (

Xiuli Zhang,* Zhen Tan,* Ting Kang, Chuanying Zhu, Siyu ChenDepartment of Oncology, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of ChinaCorrespondence: Siyu ChenDepartment of Oncology, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, 1665 Kongjiang Road, Shanghai 200092, People’s Republic of ChinaTel +86 21 2507 7642Email siyu.chen@shsmu.edu.cn*These authors contributed equally to this workPurpose: Gastric carcinogenesis is a multistep process and is the second-highest cause of cancer death worldwide with a high incidence of invasion and metastasis. MicroRNAs (miRNAs) engage in complex interactions with the machinery that controls the transcriptome and concurrently target multiple mRNAs. Recent evidence has shown that miRNAs are involved in the cancer progression, including promoting cell-cycle, conferring resistance to apoptosis, and enhancing invasiveness and metastasis. Here, we aim to elucidate the roles of miRNAs, especially microRNA-4665-3p (miR-4665-3p), in the inhibitory effect of arsenic sulfide in gastric cancer (GC).Methods: The arsenic sulfide-induced miRNA expression alterations in AGS cells was determined by miRNA microarray. RT-PCR was used to further verify the arsenic sulfide-regulated miRNAs in GC tissues. The inhibition of miR-4665-3p on the migration and invasion of GC cells were determined by wound healing assay and transwell assay. Western blot analysis was used to detect the expression of EMT related proteins and the putative target of miR-4665-3p.Results: The miR-4665-3p was up-regulated by arsenic sulfide and showed inhibition upon the migration and invasion of GC cells. MiRBase and Western blotting indicated that miR-4665-3p directly down-regulated the oncoprotein GSE1. Morphological observation also indicated that the up-regulation of miR-4665-3p inhibits the EMT in GC cells.Conclusion: Our data demonstrates that the increased expression of miR-4665-3p induced by arsenic sulfide suppresses the cell invasion, metastasis and EMT of GC cells, and has the potential to be a novel therapeutic target in GC.Keywords: arsenic sulfide, miR-4665-3p, gastric cancer, invasion, migration

Tao Wang,1,* Jie Yu,1,* Min Liu,1,* Yanliang Chen,1 Caiyun Zhu,1 Lin Lu,2 Mingzhu Wang,2 Lingfeng Min,3 Xinxin Liu,4 Xizhi Zhang,1 Johannes A Gubat,5 Yong Chen1 1Department of Medical Oncology, Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu, China; 2Department of Medical Oncology, Dalian Medical University, Dalian, Liaoning, China; 3Department of Respiratory Medicine, Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu, China; 4Department of Gastrointestinal Surgery, Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu, China; 5Division of Oncology and Pathology, Department of Clinical Sciences, Lund University, Lund, Sweden *These authors contributed equally to this work Purpose: Fluoropyrimidine plus platinum (FP) is currently the standard treatment for esophageal cancer (EC). In recent years, taxane-based chemotherapy has also been used and has shown good efficacy in EC. This study aims to investigate the advantages of taxane-based over FP chemotherapy, as well as discuss its drawbacks, in the treatment of EC. Patients and methods: A literature search was done for studies comparing clinical outcomes between taxane-based and FP chemotherapy in EC. Pooled analyses were performed to compare the efficacy and grade 3/4 adverse events in patients who received neoadjuvant chemotherapy (NACT), neoadjuvant chemoradiotherapy (NACRT), or definitive chemoradiotherapy (dCRT). Subgroup analyses were also conducted in esophageal squamous cell carcinoma (ESCC). Results: Thirty-one studies with a total of 3,912 patients were included in the analysis. Better long-term survival was found in patients who received taxane-based NACT (progression-free survival (PFS): pooled HR=0.58, P=0.0008; and overall survival (OS): pooled HR=0.50, P

Ningbo Li,1 Shanna Guo,1 Qingli Wang,2 Guangyou Duan,3 Jiaoli Sun,1 Yi Liu,1 Jin Zhang,1 Cong Wang,1 Changmao Zhu,1 Jingyu Liu,4 Xianwei Zhang1 1Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; 2Department of Anesthesiology, Wuhan General Hospital of Guangzhou Military, Wuhan, China; 3Department of Anesthesiology, Xinqiao Hospital, Third Military Medical University, Chongqing, China; 4Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, China Purpose: Congenital insensitivity to pain with anhidrosis (CIPA) is a rare inherited disorder whose core clinical features consist of no response to noxious stimuli and inability to sweat under any conditions. Our goal was to characterize the details of phenotypic and genotypic features in Chinese CIPA patients.Patients and methods: Personal data and clinical information were investigated by interview and physical examination. DNA was extracted from blood samples of patients and their available familial members and subjected to genetic analysis.Results: A total of 41 Han Chinese CIPA patients from 35 unrelated families were recruited. The distribution of patients was mainly in the central and southern regions of China, with a male to female ratio of 3:1 and a mortality rate of 7.3%. Heterogeneity of clinical features, including pain insensitivity, temperature sensation, and complications, were cataloged. Interestingly, some patients had “visceral pain” sensation, and there was a significant difference in temperature perception and thermal pain between individuals. The incidence of bone and joint fractures was 49%. The characteristics of 19 mutations of NTRK1 in 41 patients, with five novel mutations, were identified. More than 63% of patients had the splice mutation, c.851–33 T>A, which strongly suggests that it may be a common pathogenic site in Han Chinese patients.Conclusion: Current findings expand our knowledge about the spectrum of phenotypic features and the racial characteristics of NTRK1 mutations of CIPA patients in the Han Chinese population. Keywords: congenital insensitivity to pain with anhidrosis, HASN IV, phenotype, NTRK1, mutation, Chinese

Fuyin Yang,1–4 Lan Chen,5 Xinyu Fang,6 Ke Zheng,1 Cheng Zhu,1 Chaoqun Xu,1 Chen Zhang,6 Wei Tang11Wenzhou Kangning Hospital, School of Mental Health, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China; 2Faculty of Arts and Science, New York University Shanghai, Shanghai, China; 3Shanghai Key Laboratory of Brain Functional Genomics (Ministry of Education), School of Psychology and Cognitive Science, East China Normal University, Shanghai 200062, China; 4NYU-ECNU Institute of Brain and Cognitive Science at NYU Shanghai, Shanghai, China; 5School of Mental Health, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China; 6Schizophrenia Program, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200232, ChinaObjectives: It has been well documented that elevation of serum prolactin (PRL) level and weight gain are common in patients receiving treatment with atypical antipsychotics. The existing evidences show that serum PRL is elevated in schizophrenic patients treated with olanzapine. However, little is known about the long-term effects of olanzapine on PRL levels and weight gain in female patients with schizophrenia. Materials and methods: This study addressed this issue by investigating the relationship between serum PRL level and body mass index (BMI). Seventy-nine female patients with first-episode schizophrenia were recruited and received olanzapine monotherapy for 12 weeks. Serum PRL level and BMI were measured at baseline and at 4, 8, 12 weeks. Thirty-five age-matched healthy female individuals were recruited as controls. The severity of psychiatric symptoms was evaluated using the Positive and Negative Syndrome Scale. Results: The olanzapine treatment for 12 weeks significantly increased serum PRL (P

Ying Li, Dandan Yang, Yian Wang, Zhan Li, Chunyan Zhu Drug Delivery Research Center, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100193, People’s Republic of China Background: To establish the combination of doxorubicin (DOX) and silybin (SLB) in oral hepatic-targeting liposomes with the goal of reducing cardiotoxic side effects and improve oral hepatoma treatment. Methods: Distearoylphosphatidylethanolamine–polyethylene glycol–cholic acid-modified liposomes (CA-LP) were used to encapsulate DOX and SLB (CA-LP–DOX/SLB), and the hepatic targeting, efficacy against hepatoma and cardioprotective effects were evaluated by cell toxicity, scratch and apoptosis in vitro studies, and pharmacokinetics and pharmacodynamics in vivo studies. Results: In vitro cell studies showed that CA-LP–DOX/SLB inhibited HepG2 cell proliferation and HCC97H cell migration, and protected H9c2 cells. In vivo pharmacokinetics demonstrated that the CA-LP–DOX/SLB-treated group showed higher liver accumulation and lower heart accumulation of DOX relative to those in the CA-LP–DOX and LP–DOX-treated groups. In vivo pharmacodynamic studies showed that the CA-LP–DOX/SLB-treated group not only efficiently inhibited growth but also induced significantly less tissue damage than that observed in the CA-LP–DOX-treated group. Conclusion: Concurrent administration of DOX and SLB via CA-LP provided a viable strategy to mitigate acute DOX-induced cardiotoxicity. Keywords: doxorubicin, silybin, hepatic targeting via oral administration, cholic acid transporter, anti-hepatoma, biodistribution in vivo