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This study was designed to investigate the prognostic value of the number and sites of extracranial metastasis (ECM) in NSCLC patients with BM. NSCLC patients with BM from the Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2015 were enrolled in analysis. Patients from 2010 to 2013 were included in the training set and those from 2014 to 2015 in the validation set. ECM sites among different subtypes of NSCLC were compared by Chi‐square tests. Kaplan–Meier methods and Cox regression models were performed to analyze survival data. Competing‐risks analysis was used to predict cumulative incidence rates for CSS and non‐CSS cause. We included 5974 patients in the training cohort and 3561 patients in the validation cohort. Most (nearly 80%) NSCLC patients with BM showed 0–1 involved extracranial organ, with the most and least common ECM organ being bone and distant lymph nodes (DLNs) among all subtypes of NSCLC, respectively. The number of involved extracranial organs was an independent prognostic factor for patients with BM from NSCLC (p, Prognostic value of extracranial organ involvement the Surveillance, Epidemiology and End Results (SEER) database Tailored treatments would be reasonable for BM patients from NSCLC with different metastasis patterns.

Extracting roads from aerial images is a challenging task in the field of remote sensing. Most approaches formulate road extraction as a segmentation problem and use thinning and edge detection to obtain road centerlines and edge lines, which could produce spurs around the extracted centerlines/edge lines. In this study, a novel regression-based method is proposed to extract road centerlines and edge lines directly from aerial images. The method consists of three major steps. First, an end-to-end regression network based on CNN is trained to predict confidence maps for road centerlines and estimate road width. Then, after the CNN predicts the confidence map, non-maximum suppression and road tracking are applied to extract accurate road centerlines and construct road topology. Meanwhile, Road edge lines are generated based on the road width estimated by the CNN. Finally, in order to improve the connectivity of extracted road network, tensor voting is applied to detect road intersections and the detected intersections are used as guidance for the overcome of discontinuities. The experiments conducted on the SpaceNet and DeepGlobe datasets show that our approach achieves better performance than other methods.

The urachal carcinoma (UrC) was a rare type of malignant tumors. It accounted for 0.5% ∼ 2.0% of all bladder cancers and an estimated 0.01% of all adult cancers. We herein presented one case of a young 35-year-old male, complaining of intermittent hematuria and subabdominal pain. Abdominal computed topographic scan revealed a significant soft tissue mass with 4.7 cm longer axis localized on the anterior bladder wall, invading the anterior abdominal wall. A laparoscopic partial cystectomy was performed with resection of the entire mass up to the umbilical area with pelvic lymph node dissection. The postoperative pathology revealed urachal mucinous adenocarcinoma with stage IIIc in Sheldon system. Six cycles of adjuvant chemotherapy with FOLFIRINOX and radiotherapy of which the target volume including tumor bed and regional lymph drainage were conducted, the patient achieved progression free survival of 21 months after surgery with failure of extensive implantation metastases in abdominal and pelvic cavity. Subsequent hyperthermic intraperitoneal chemotherapy and systemic therapy including targeted therapy and immune-checkpoint inhibitor therapy were scheduled for subsequent therapy. Those metastases were probably due to the implantation of cancer cells during surgery and our treatments including adjuvant chemo-radiotherapy could stand a chance to achieve improvement of local control and increase of progression free survival. The aim of the present case report was to help understand the presentation and management of this tumor and reflect the necessity of adjuvant chemo-radiotherapy for the treatment of advanced patient of UrC.

Competing to set industry standards is a strategic option to a variety of industries. This paper aims to investigate the role of standard drafting in the evolution of enterprises’ competitiveness in multiplex networks of standards. Specifically, network-based measurements are deliberately designed to evaluate the enterprises participation, contribution, and collaboration in drafting standards. By demonstrating the development of the standard system in China’s communication industry, the effectiveness of our measurement system is verified. Accompanied by empirical observation, the data analysis shows that the relevant governmental agencies dominate the whole standard system; basic-technology providers acquire greater competitiveness through participating in the standards drafting than the other kinds of enterprises. Finally, the corresponding managerial suggestions are offered.

BackgroundElderliness is known risk factor for severe progression of COVID-19 due to compromised immunity, however aberrant hyperactive immune response including autoimmunity might be responsible for younger patients.Methods162 patients tested with autoimmunological detections were enrolled, and study of “Severe” cases and “Non-severe” controls was retrospectively analyzed. ResultsMultivariable analysis involving antinuclear autoimmunity manifests correlation of disease severity with middle age and attenuates the risk of age older than 65. Middle age (45≤age≤65) and female turn out to be the risk factors after hierarchical cluster analysis, before which however sex was not correlated. We find antinuclear autoimmunity to be strongly correlated with severity for the middle-aged (OR= 21.000, 95% CI 4.893- 90.126, p< 0.001) and female (OR= 16.044, 95% CI 4.717- 54.568, p< 0.001), especially for the middle-aged female (Pearson R= 0.770, p< 0.001). Incidence of symptoms fever and chest distress, and complication myocardial injury are statistically more frequent in patients with positive antinuclear antibody, compared with those negative. Severe patients with positive antinuclear antibody possess significantly shorter onset of symptoms to severity time (p= 0.021), indicating quicker progression, and interestingly, present more incidence (21%) of post-remission aggravation, compared with those negative (6%). ConclusionsThe presence of antinuclear autoimmunity potentially makes COVID-19 prone to severe progression, especially for the middle-aged and female, probably even quicker.

The demand for timely information about earth’s surface such as land cover and land use (LC/LU), is consistently increasing. Machine learning method shows its advantage on collecting such information from remotely sensed images while requiring sufficient training sample. For satellite remote sensing image, however, sample datasets covering large scope are still limited. Most existing sample datasets for satellite remote sensing image built based on a few frames of image located on a local area. For large scope (national level) view, choosing a sufficient unbiased sampling method is crucial for constructing balanced training sample dataset. Dependable spatial sample locations considering spatial heterogeneity of land cover are needed for choosing sample images. This paper introduces an ongoing work on establishing a national scope sample dataset for high spatial-resolution satellite remote sensing image processing. Sample sites been chosen sufficiently using spatial sampling method, and divided sample patches been grouped using clustering method for further uses. The neural network model for road detection trained our dataset subset shows an increased performance on both completeness and accuracy, comparing to two widely used public dataset.

Exploring the characteristics of safety risks is crucial for deeply understanding and promoting traffic construction safety. Bridge and tunnel construction engineering is of high risk, which has been studied separately, while mega traffic engineering projects often combine them, leading to increased complexity. In this study, a research framework is proposed to explore the risk characteristics of bridge-tunnel hybrid construction engineering, which can be applied in other types of hybrid constructions. The real data with respect to 67 typical bridge and 64 tunnel accidents was collected from the database of a large traffic construction enterprise in China. 146 risk factors and 326 trigger relations are extracted to establish bridge and tunnel construction risk subnetworks. Moreover, a whole risk network is established by combing the two subnetworks together,. With the network scale, diameter, and other metrics, the properties of the risk networks are revealed. The critical risk factors in the construction of bridges and tunnels are identified. The results show that most of the accidents are attributed to management and worker factors, while purely environmental factors do not significantly contribute to the occurrence of the accidents. The results provide some prevention and post-remedy safety suggestions for the management of bridge and tunnel construction.

ObjectiveTo investigate the impact of the human papillomavirus (HPV) status on head and neck squamous cell carcinoma (HNSCC) arising from different anatomic subsites.MethodsHNSCC patients with known HPV status from the Surveillance, Epidemiology, and End Results (SEER) database between 2010–2015 were included in our analysis. Patients were classified into three categories of HNSCC according to Site recode ICD-O-3/WHO 2008 and Primary Site-labeled, namely, oropharynx, hypopharynx, and nasopharynx. Logistic regression model was conducted to evaluate the relationship between patient characteristics and HPV status. Kaplan-Meier methods and COX regression analysis were used to analyze survival data.ResultsA total of 9,943 HNSCC patients with known HPV status from the SEER database were enrolled, with 6,829 (68.7%) HPV-positive patients. HPV-positive and HPV-negative HNSCC were distinct and had different clinical and socioeconomic features (all P < 0.001). Primary sites, socioeconomical factors (age, sex, marital status, and race), and pathological features (TNM stage and grade) were closely related with HPV status (all P < 0.001). HPV-positive status was a favorable prognostic marker in HNSCC patients with cancers of the oropharynx and hypopharynx (all P < 0.001), but was not in nasopharyngeal carcinoma patients (P = 0.843). A total of 8,933 oropharyngeal carcinoma (OPC) and 558 hypopharyngeal carcinoma (HPC) patients were divided into the training and validation cohorts with a ratio of 1:1. Significant prognostic factors of the OS yielded by multivariate COX analysis in the training cohort were integrated to construct nomograms for OPC and HPC patients. The prognostic models showed a good discrimination with a C-index of 0.79 ± 0.007 and 0.73 ± 0.023 in OPC and HPC, respectively. Favorable calibration was reflected by the calibration curves. Additionally, corresponding risk classification systems for OPC and HPC patients based on the nomograms were built and could perfectly classify patients into low-risk, intermediated-risk, high-risk groups. OS in the three risk groups was accurately differentiated and showed a good discrimination.ConclusionHPV positivity was associated with an improved survival in HNSCC patients with cancers of the oropharynx and hypopharynx. Nomograms and corresponding risk classification systems were constructed to assist clinicians in evaluating the survival of OPC and HPC patients.

Background Severe cases of coronavirus disease 2019 (COVID-19) among pediatric patients are more common in children less than 1 year of age. Our aim is to address the underlying role of immunity and inflammation conditions among different age groups of pediatric patients. Methods We recruited pediatric patients confirmed of moderate COVID-19 symptoms, admitted to Wuhan Children's Hospital from January 28th to April 1st in 2020. Patients were divided into four age groups (≤ 1, 1–6, 7–10, and 11–15 years). Demographic information, clinical characteristics, laboratory results of lymphocyte subsets test, immune and inflammation related markers were all evaluated. Results Analysis included 217/241 (90.0%) of patients with moderate clinical stage disease. Average recovery time of children more than 6 years old was significantly shorter than of children younger than 6 years (P = 0.001). Reduced neutrophils and increased lymphocytes were significantly most observed among patients under 1 year old (P n = 12, 30.0%, P n = 13, 32.5%, P P P P P P = 0.007), interleukin (IL)-10 (P = 0.011), IL-6 (P = 0.008), lactate dehydrogenase (P P = 0.007). Conclusion The higher rate of severe cases and long course of COVID-19 among children under 1 year old may be due to the lower production of antibodies and serum complements of in this age group.

The COVID-19 outbreak caused by SARS-CoV-2 challenges the medical system by interfering with routine therapies for many patients with chronic diseases. In patients with cancer receiving immune checkpoint inhibitors (ICIs), difficulties also arise from the incomplete understanding of the intricate interplay between their routine treatment and pathogenesis of the novel virus. By referring to previous ICI-based investigations, we speculate that ICIs themselves are not linked to high-infection risks of respiratory diseases or inflammation-related adverse effects in patients with cancer. Moreover, ICI treatment may even enhance coronavirus clearance in some patients with malignant tumor by boosting antiviral T-cell responsiveness. However, the ‘explosive’ inflammation during COVID-19 in some ICI-treated patients with cancer was illustrated as exuberant immunopathological damage or even death. In case of the COVID-19 immunopathogenesis fueled by ICIs, we propose a regular monitor of pathogenic T-cell subsets and their exhaustion marker expression (eg, Th17 and interleukin (IL)-6-producing Th1 subsets with surface programmed death 1 expression) to guide the usage of ICI. Here we aimed to address these considerations, based on available literature and experience from our practice, that may assist with the decision-making of ICI administration during the pandemic.

Background: Asymptomatic carriers were positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) without developing symptoms, which might be a potential source of infection outbreak. Here, we aim to clarify the epidemiologic and influencing factors of asymptomatic carriers in the general population. Methods: In our hospital, all hospital staff have received throat swab RT-PCR test, plasma COVID-19 IgM/IgG antibodies test and chest CT examination. We analyzed the correlation between infection rates and gender, age, job position, work place and COVID-19 knowledge training of the staff. After that, all asymptomatic staff were re-examined weekly for 3 weeks. Findings: A total of 3764 hospital staff were included in this single-center cross-sectional study. Among them, 126 hospital staff had abnormal findings, and the proportion of asymptomatic infection accounted for 0.76% (28/3674). There were 26 staff with IgM+, 73 with IgG+, and 40 with ground glass shadow of chest CT. Of all staff with abnormal findings, the older they are, the more likely they are to be the staff with abnormal results, regardless of their gender. Of 3674 hospital staff, the positive rate of labor staff is obviously higher than that of health care workers (HCWs) and administrative staff (P0.05). The positive rate of HCWs who participated in the COVID-19 knowledge training was lower than those did not participate in early training (P 0.05). During 3 weeks follow-up, all asymptomatic patients did not present the development of clinical symptoms or radiographic abnormalities after active intervention in isolation point. Interpretation: To ensure the safety of resumption of work, institutions should conduct COVID-19 prevention training for staff and screening for asymptomatic patients, and take quarantine measures as soon as possible in areas with high density of population. Funding: The Key Project for Anti-2019 novel Coronavirus Pneumonia from the Ministry of Science and Technology, China; Wuhan Emergency Technology Project of COVID-19 epidemic, China.

Abnormal coagulation parameters and potential benefits of anticoagulant therapy in general population with novel coronavirus pneumonia (COVID-19) have been reported. However, limited data are available on cancer patients. Coagulation indexes and inflammation parameters in 57 cancer patients with SARS-CoV-2 infection with different severity were retrospectively analyzed. We found that D-dimer levels were increased in 33 patients (57.9%, median: 790 ng/mL). Compared with ordinary type patients, severe and critical ill patients had decreased MPV values (P = 0.006), prolonged PT (median: 13.3 vs. 11.5 vs. 11.4 s, P < 0.001), significant higher D-dimer levels (median: 2,400 vs. 940 vs. 280 ng/mL, P < 0.001), higher PCT levels (median: 0.17 vs. 0.055 vs. 0.045 ng/mL, P = 0.002), higher IL-6 (median: 20.6 vs. 2.3 vs. 3.0 pg/mL, P = 0.040), and decreased PaO2 (median: 68 vs. 84 vs. 96 mm Hg, P < 0.001). Importantly, three patients, one severe and two critical ill type, with increased D-dimer survived after anticoagulant therapy with continuous heparin infusion. Increased D-dimer levels positively correlated with increased PCT levels (r = 0.456, P = 0.002) and IL-6 levels (r = 0.501, P = 0.045). A negative correlation between D-dimer levels and PaO2 levels (r = −0.654, P = 0.021) were also existed. Cancer patients with COVID-19 showed prominent hypercoagulability associated with severe inflammation, anticoagulation therapy might be useful to improve the prognosis and should be immediately used after the onset of hypercoagulability.

MicroRNAs (miRNAs) can participate in many behaviors of various tumors. Prior studies have reported that miR-15b-5p in different tumors can either promote or inhibit tumor progression. In breast cancer, the role of miR-15b-5p is unclear. The main objective of this paper is to explore miR-15b-5p effects and their mechanisms in breast cancer using both in vitro and in vivo experiments. This study showed that miR-15b-5p expression was upregulated in breast cancer compared with normal breast tissue and was positively correlated with poor overall survival in patients. Knockdown of miR-15b-5p in MCF-7 and MD-MBA-231 breast cancer cells restrained cell growth and invasiveness and induced apoptosis, whereas overexpression of miR-15b-5p achieved the opposite effects. We next revealed a negative correlation between miR-15b-5p and heparanase-2 (HPSE2) expression in breast cancer. Knockdown of miR-15b-5p significantly increased HPSE2 expression at both mRNA and protein levels in breast cancer cells in vitro. The underlying mechanisms of miR-15-5p in breast cancer were investigated using luciferase activity reporter assay and rescue experiments. In addition, miR-15b-5p knockdown significantly inhibited tumor growth in a xenograft model in mice. In summary, we showed that miR-15b-5p promotes breast cancer cell proliferation, migration, and invasion by directly targeting HPSE2. Accordingly, miR-15b-5p may serve both as a tool for prognosis and as a target for therapy of breast cancer patients.

Background: The outbreak of a new coronavirus (2019-nCoV) induced pneumonia (NCP) in the central city of Wuhan in China poses a threat to the public health Thi

Background: Coronavirus disease 2019 (COVID-19) has been widely spread and caused tens of thousands of deaths, mainly in patients with severe COVID-19. Methods: Patients with COVID-19 were retrospectively analyzed. Clinical characteristics were compared, and LASSO regression as well as multivariate analysis were used to screen variables and establish prediction model. Findings: A total of 2529 patients with COVID-19 was retrospectively analyzed, and 452 eligible severe COVID-19 were used for finally analysis. In training cohort, the median age was 66·0 years while it was 73·0 years in non-survivors. Patients aged 60-75 years accounted for the largest proportion of infected populations and mortality toll. Anti-SARS-CoV-2 antibodies were monitored up to 54 days, and IgG levels reached the highest during 20-30 days. About 60.2% of severe patients had complications. Acute myocardial injury was the earliest injured organ, whereas the time from acute kidney injury to death was the shortest. Age, diabetes, coronary heart disease (CHD), percentage of lymphocytes (LYM%), procalcitonin (PCT), serum urea, C reactive protein and D-dimer (DD), were identified associated with mortality by LASSO binary logistic regression. Then multivariate analysis was performed to conclude that old age, CHD, LYM%, PCT and DD remained independent risk factors for mortality. Based on the above variables, a scoring system of COVID-19 (CSS) was established and divided into low-risk and high-risk groups. This model displayed good discrimination (AUC=0·919) and calibration (P =0·264). The complications in low-risk and high-risk groups were significantly different. We also found that the use of corticosteroids in low-risk groups increased hospital stays by 4·5 days (P =0·036) and durations of disease by 7·5 days (P =0 · 012) compared with no corticosteroids. Interpretation: Old age, CHD, LYM%, PCT and DD were independently related to mortality. CSS was useful for predicting in-hospital mortality and complications, and it could help clinicians to identify high-risk patients with poor prognosis. Funding Statement: This work was supported by the Key Project for Anti-2019 novel Coronavirus Pneumonia from the Ministry of Science and Technology, China (grant number 2020YFC0845500). Declaration of Interests: All authors declare no competing interests. Ethics Approval Statement: This study was conducted according to the principles of Helsinki and approved by the Ethics Committee of Zhongnan Hospital of Wuhan University (No.2020063).

Background: Asymptomatic carriers were positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) without developing symptoms, which might be a

China, who owns the largest automobile consuming market, is becoming the largest automobile manufacturing country. However, a gap still lies between China and other traditional automobile manufacturing countries in terms of design capability and production efficiency. Standardization can effectively promote technological innovation and industrial upgradation, which enhances the overall performance of the automobile industry. This paper aims at identifying the structural problem in the automobile standard citation network in China, since the citation relationship reflects the transmission and development of knowledge or technologies. To this end, a dynamic standard citation network model is developed for ease of extraction of standard data at any time points. A set of complex network metrics at both node and network level are chosen with rational explanations in the context of automobile industry. With the data collected from publicized Web sites, the topological evolution of this network is analyzed as well. We significantly show that the standard citation networks at different time periods are generally loosely connected and contain too many isolated nodes. Meanwhile, the critical nodes in the standard citation network also change dynamically. We suggest that these isolated standards should be integrated into the citation network through revision activities.

This paper focuses on multiple-block warehouses with ultra-narrow aisles and access restriction. These new features observed from one of the largest online retailers in China allow order pickers en...

Background/Aims: MicroRNAs (miRNAs) regulate the expressions of cancer-related genes, and are involved in the development and progression of various human cancers. Here, we performed further analyses to determine whether let-7d is functionally linked to Jab1 in breast cancer. Methods: In situ hybridization and immunohistochemical analyses were used to determine the level of let-7d and Jab1 in breast cancer clinical specimens and its correlation with clinicopathological data. Let-7d overexpressing breast cancer cell lines combined with mouse models bearing cell-derived xenografts were used to assess the functional role of let-7d both in vitro and in vivo. Results: In this study, we found that let-7d was downregulated in breast cancer tissues, coupled with the elevations of Jab1 protein expressions, compared with paired adjacent noncancerous breast tissues. Let-7d overexpression significantly suppressed the proliferation and invasion in MCF-7 and MDA-MB-231 cells. Dual luciferase reporter assay indicated that Jab1 was the direct target of let-7d. Stepwise studies from in vitro and in vivo experiments indicated that let-7d overexpression inhibited cell growth and decreased Jab1 expressions in breast cancer cells and nude mice tumor tissues. Statistical analyses demonstrated that breast cancer patients with low levels of let-7d or high levels of Jab1 had a significant correlation with worse prognosis. Conclusion: These findings provide novel insights into molecular mechanism of let-7d and Jab1 in tumor development and progression of breast cancer, and thus let-7d/Jab1 are novel potential therapeutic targets for breast cancer patients.

Background: Multiple myeloma is a hematological malignant disease in which clonal plasma cells proliferate abnormally. NIR-II fluorophores have great application prospects for cancer treatment. Methods: Multiple detection techniques were used to evaluate effect and mechanisms of the novel small-molecule NIR-II fluorophores probe on multiple myeloma cells in vitro experiment. In vivo MM.1S Luc+ B-NSG mouse model was built to assess the role of probe in multiple myeloma treatment. Results: The novel small-molecule NIR-II fluorophores probe shown high affinity with multiple myeloma cells and specific myeloma imaging in vivo. More importantly, the probe could effectively induce tumor death with 808 nm laser irradiation in a dose-dependent manner. Further, Confocal found that the probe was mainly distributed in mitochondria and significantly reduced the mitochondrial membrane potential with laser irradiation. Moreover, Reactive Oxygen Species (ROS) level was notably increased and the up-regulation expression of cleaved poly ADP-ribose polymerase (PARP) was detected after treated with the probe and laser irradiation. Consistent with the previous results, the disease was alleviated obviously in probe laser-treated group. Conclusions: Our work confirm for the first time that the specific imaging and remarkable photodynamic therapy (PDT) effect of a novel NIR-II fluorophores probe to multiple myeloma. It provides the foundation for application of NIR-II fluorophores from solid tumor to non-solid tumor. Disclosures No relevant conflicts of interest to declare.

// Lingling Chen 1,2,* , Chunyan Liu 1,* , Jianfeng Gao 1 , Zhiwen Xie 3 , Lawrence W.C. Chan 4 , Damien J. Keating 5 , Yibin Yang 6 , Jiazhong Sun 7 , Fuling Zhou 8 , Yongchang Wei 9 , Xiuli Men 10 and Sijun Yang 1 1 ABSL-3 Laboratory at the Center for Animal Experiment and Institute of Animal Model for Human Disease, Wuhan University School of Medicine, Wuhan, P. R. China 2 Department of Cell Biology, College of Life Science, Nanjing Normal University, Nanjing, Jiangsu, P.R. China 3 School of Bioscience and Technology , Weifang Medical University, Weifang Shandong, P.R. China 4 Department of Health Technology and Informatics, Hong Kong Polytechnic University, Hong Kong, Hong Kong 5 Department of Human Physiology and Centre for Neuroscience, Flinders University, Adelaide, South Australia, Australia 6 Department of Endocrinology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, P.R. China 7 Department of Respiratory, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, P.R. China 8 Department of Hematology and Radiation, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, P.R. China 9 Department of Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, P.R. China 10 School of Basic Medical Sciences, North China University of Science and Technology, Tangshan, P.R. China * These authors have contributed equally to this work Correspondence to: Sijun Yang, email: // Keywords : Miro1, mitophagy, insulin resistance, HFD, diabetes, Pathology Section Received : June 26, 2017 Accepted : August 29, 2017 Published : September 16, 2017 Abstract Mitochondrial function is essential to meet metabolic demand of pancreatic beta cells respond to high nutrient stress. Mitophagy is an essential component to normal pancreatic β-cell function and has been associated with β-cell failure in Type 2 diabetes (T2D). Our previous studies have indicated that mitochondrial Rho (Miro) GTPase-mediated mitochondrial dysfunction under high nutrient stress leads to NOD-like receptor 3 (NLRP3)-dependent proinflammatory responses and subsequent insulin resistance. However, the in vivo mechanism by which Miro1 underlies mitophagy has not been identified. Here we show firstly that the expression of Miro is reduced in human T2D and mouse db/db islets and in INS-1 cell line exposed to high glucose and palmitate. β-cell specific ablation of Miro1 (Miro1f/f: Rip-cre mice, or (IKO) under high nutrient stress promotes the development of hyperglycemia. β-cells from IKO mice display an inhibition of mitophagy under oxidative stress and induces mitochondrial dysfunction. Dysfunctional mitophagy in IKO mice is represented by damaged islet beta cell mitochondrial and secretory capacity, unbalanced downstream MKK-JNK signalling without affecting the levels of MEK, ERK or p38 activation and subsequently, impaired insulin secretion signaling via inhibition IRS-AKT-Foxo1 pathway, leading to worsening glucose tolerance in these mice. Thus, these data suggest that Miro1 may be responsible for mitophagy deficiency and β-cell dysfunction in T2D and that strategies target Miro1 in vivo may provide a therapeutic target to enhance β-cell mitochondrial quality and insulin secretion to ameliorate complications associated with T2D.

// Weijie Ma 1, * , Xi Chen 1, * , Lu Ding 2, * , Jianhong Ma 3, * , Wei Jing 4 , Tian Lan 1 , Haseeb Sattar 5 , Yongchang Wei 6 , Fuling Zhou 3 and Yufeng Yuan 1 1 Department of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China 2 Department of Clinical Hematology, Zhongnan Hospital of Wuhan University, Wuhan, China 3 Department of Gynaecology and Obstetrics, Zhongnan Hospital of Wuhan University, Wuhan, China 4 Department of Clinical Laboratory Medicine and Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University, Wuhan, China 5 Department of Clinical Pharmacy, Wuhan Union Hospital, Affiliated Hospital, Tongji Medical College, Huazhong University of Science And Technology, Wuhan, China 6 Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China * These authors have contributed equally to this work Correspondence to: Yufeng Yuan, email: yuanyf1971@whu.edu.cn Keywords: long non-coding RNA, prognosis, survival, clinicopathology, prostate cancer Received: March 06, 2017 Accepted: April 25, 2017 Published: May 07, 2017 ABSTRACT The abnormally expressed LncRNAs played irreplaceable roles in the prognosis of prostate cancer (PCa). Therefore, we conducted this systematic review and meta-analysis to summarize the association between the expression of LncRNAs, prognosis and clinicopathology of PCa. 18 eligible studies were recruited into our analysis, including 18 on prognosis and 9 on clinicopathological features. Results indicated that aberrant expression of LncRNAs was significantly associated with biochemical recurrence-free survival (BCR-FS) (HR = 1.55, 95%CI: 1.01–2.37, P < 0.05), recurrence free survival (RSF) (HR = 3.07, 95%CI: 1.07–8.86, P < 0.05) and progression free survival (PFS) (HR = 2.34, 95%CI: 1.94–2.83, P < 0.001) in PCa patients. LncRNAs expression level was correlated with several vital clinical features, like tumor size (HR = 0.52, 95%CI: 0.28–0.95, P = 0.03), distance metastasis (HR = 4.55, 95%CI: 2.26–9.15, P < 0.0001) and histological grade (HR = 6.23, 95% CI: 3.29–11.82, P < 0.00001). Besides, down-regulation of PCAT14 was associated with the prognosis of PCa [over survival (HR = 0.77, 95%CI: 0.63–0.95, P = 0.01), BCR-FS (HR = 0.61, 95%CI: 0.48–0.79, P = 0.0001), prostate cancer-specific survival (HR = 0.64, 95%CI: 0.48–0.85, P = 0.002) and metastasis-free survival (HR = 0.61, 95%CI: 0.50-0.74, P < 0.00001)]. And, the increased SChLAP1 expression could imply the worse BCR-FS (HR = 2.54, 95%CI: 1.82-3.56, P < 0.00001) and correlate with Gleason score (< 7 vs ≥ 7) (OR = 4.11, 95% CI: 1.94-8.70, P = 0.0002). Conclusively, our present work demonstrated that LncRNAs transcription level might be potential prognostic markers in PCa.

Background: Multiple myeloma (MM) is a hematology malignant disease originated from B-cell line and still incurable. Compound Kushen Injection (CKI) as a Traditional Chinese Medicines are promising agents in our previous research for treating cancer. The effect of CKI on multiple myeloma was still unknown. Methods: In vitro experiment, flow cytometry was used to evaluate effect of CKI on multiple myeloma cells. Optofluidic chip was applied to detect effect at single-cell level. And in vivo RPMI-8226 GFP+ B-NSG mouse model was built to assess the role of CKI in multiple myeloma treatment. Results: CKI inhibited MM cells proliferation of and increased its apoptosis rate. And the cell cycle of MM cells was also arrested by CKI treatment. In contrast, CKI has few toxic effects on mesenchymal stem cells (MSCs) and MC3T3 cells. At the single-cell level, MM cells was died in time and dose dependent manner. Transcriptome find that the expression of MYC and TERT in CKI-treated RPMI-8226 cells was significantly down-regulated and confirmed by qRT-PCR and Western blot. Overexpression of TERT can partly reverse the inhibition effect of CKI on RPMI-8226 cells. B-NSG mouse was injected with GFP+ RPMI-8226 cells through caudal vein, and the disease was partially alleviated by decreased tumor burden in the CKI-treated group. Furthermore, it is surprising that in animal models with myeloma bone disease, the bone mass was higher in CKI treatment group than control. Conclusions: CKI inhibits MM cells through the MYC/TERT signaling pathway and improve the quality of life of MM mouse. Our findings provide preclinical evidence to show that CKI could be a promising candidate in human MM therapy. Disclosures No relevant conflicts of interest to declare.

Longnoncoding RNAs (lncRNAs) are significantly correlated with cancer pathogenesis, development, and metastasis. Microarray analysis showed that lncRNA MRPS30-DT is overexpressed in breast carcinoma; however, the function of MRPS30-DT in breast cancer tumorigenesis remains unclear. In situ hybridization and immunohistochemical analysis were used to evaluate the expression levels of MRPS30-DT and Jab1 in clinical samples of breast carcinoma and their relation to survival outcome. qRT-PCR was used to measure MRPS30-DT and Jab1 mRNA expressions. Protein levels were detected using Western blot. Cell proliferation and invasion ability were evaluated via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), colony formation, and transwell assays. MRPS30-DT was knocked down in breast cancer cells to investigate its potential functional roles in cell growth and metastasis in vitro and in vivo. We found that MRPS30-DT was upregulated in breast cancer specimens and was accompanied by high Jab1 expression compared with that of paired para-carcinoma tissues. Knocking down MRPS30-DT significantly inhibited cancer cell proliferation and invasion and induced apoptosis in breast cancer cells. Similarly, knocking down MRPS30-DT in MDA-MB-231 cells significantly suppressed tumor growth. Furthermore, knocking down MRPS30-DT markedly reduced Jab1 expression in breast cancer cells and murine carcinoma. Statistical analyses suggested that high MRPS30-DT or Jab1 levels in breast cancer patients were positively correlated with poor prognoses. These data indicate the possible mechanisms of MRPS30-DT and Jab1 in breast cancer; thus, MRPS30-DT and Jab1 may be novel prognostic biomarkers and potential therapeutic targets for breast cancer treatment.

Gastric cancer (GC) is one of the most common cancers, with a high incidence of cancer death. Despite various therapeutic approaches, the cures and prognosis of advanced GC remain poor. Natural killer (NK) cells, which are known as important lymphocytes in innate immunity, play vital roles in suppressing GC initiation, progression, and metastases. A wide range of clinical settings shows that increasing the number of NK cells or improving NK cell antitumor activity is promising in GC patients. NK cell adoptive therapy (especially expanded NK cells) is a safe and well-tolerated method, which can enhance NK cell cytotoxicity against GC. Meanwhile, cytokines, immunomodulatory drugs, immune checkpoint blockades, antibodies, vaccines, and gene therapy have been found to directly or indirectly activate NK cells to improve their killing activity toward GC. In this review, we summarize recent advancements in the relationship between NK cells and GC and point out all the innovative strategies that can enhance NK cells' function to inhibit the growth of GC.

Shengxuening (SXN) tablet is extracted from the excrement of the silkworm and has effects on hematopoiesis. The main components of SXN are chlorophyll derivatives and sodium iron chlorophyllin (SIC). The present study aims to investigate the efficiency and safety of SXN on iron deficiency anemia. This phase IV, multicenter, open-label, randomized clinical trial was conducted in 31 hospitals in China from June 2001 to April 2002. Adults and children were randomly divided into low-dose (L-SXN), medium-dose (M-SXN), and high-dose (H-SXN) groups, respectively. The course of treatment was 1 month. Peripheral hemogram levels and iron status were examined before and after treatment. Adults in all three dose groups demonstrated a significant increase in hemoglobin (HGB) concentration. Children who received SXN treatment in medium and high doses also demonstrated increased HGB concentration. Reticulocyte counts increased at the end of treatment in the M-SXN and H-SXN adult groups and in the M-SXN child group. For both children and adults, SXN in the three dose groups was found to significantly elevate red blood cell level, mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration. The total effective rate in the SXN-treated group reached 84.8%. The incidence of adverse events was 4.07%. The most common side effects were nausea (2.83%), diarrhea (0.74%), and rash (0.25%). SXN was proved to be efficient and safe for adults and children with iron deficiency anemia.

Background. The mechanisms of crosstalk between depression and gastric cancer (GC) remain ill defined. Given that reactive oxygen species (ROS) is involved in the pathophysiology of both GC and depression, we try to explore the activities of ROS in the development of GC and GC-related depression. Methods. 110 patients with newly diagnosed GC were recruited in our study. The clinical characteristics of these patients were recorded. Inflammation and oxidative stress markers were detected by ELISA. The depression status of patients with GC was assessed during follow-up. The association between ROS, ABL1, and inflammation factors was evaluated in H2O2-treated GC cell lines and The Cancer Genome Atlas (TCGA) database. The effect of ABL1 on inflammation was detected with Imatinib/Nilotinib-treated GC cell lines. A chronic mild stress- (CMS-) induced patient-derived xenograft (PDX) mice model was established to assess the crosstalk between depression and GC. Results. Depression was correlated with poor prognosis of patients with GC. GC patients with depression were under a high level of oxidative status as well as dysregulated inflammation. In the CMS-induced GC PDX mice model, CMS could facilitate the development of GC. Additionally, tumor bearing could induce depressive-like behaviors of mice. With the treatment of ROS, the activities of ABL1 and inflammatory signaling were enhanced both in vitro and in vivo, and blocking the activities of ABL1 inhibited inflammatory signaling. Conclusions. ROS-activated ABL1 mediates inflammation through regulating NF-κB1 and STAT3, which subsequently leads to the development of GC and GC-related depression.

In facing the challenge of PM2.5 pollution across China, an overall macro-evaluation of the spatiotemporal pollution distribution and health risk of PM2.5-bound heavy metals at a national level is urgently needed. This study involved a bibliometric analysis of 8 PM2.5-bound heavy metals (Cd, Cr, Hg, As, Pb, Cu, Zn, Ni) in the 27 major cities across China from 2013 to 2019 that was combined with valid data from the published scientific literature. Based on time weight vector, the spatiotemporal metal distributions and their integrated enrichment factors were analyzed, and then a fuzzy health risk assessment model was established to synthetically screen regional priority control regions/pollutants, and explore the pollution trend. The integrated concentrations of As (19.44 ng/m3) and Cd (4.12 ng/m3) in most cities exceeded the limits of the Chinese Ambient Air Quality Standards, while Hg (0.81 ng/m3) and Pb (137.10 ng/m3) did not. Spatially, PM2.5-bound heavy metal pollution generally increased from southern to northern China, with North and Northwest of China being relatively hot regions. For integrated health risks, children (3.31) faced higher non-carcinogenic risks than adults (1.69), with As, Cd, and Cr as the main contributors. The total carcinogenic risk varied from 4.86 × 10−6 to 1.3 × 10−3. The total carcinogenic risk of 77.78% of major cities has reached Grade V (moderate-high risk) or above, and the risk contributions of Cr and As accounted for the largest proportion. The temporal variations showed that the pollution had a recent declining trend in most cities. Finally, 10 major cities and their corresponding metals were determined as the priority control cities/metals. The targeted risk management policies were developed for the identified hierarchical hot cities and their priority pollutants to control were based on the regional pollution trend and source characteristics.

Cancer stem cell theory indicates cancer stem cells are the key to promote tumor invasion and metastasis. Studies showed that BMI-1 could promote self-renew, differentiation and tumor formation of CSCs and invasion/metastasis of human cancer. However, whether BMI-1 could regulate invasion and metastasis ability of CSCs is still unclear. In our study, we found that up-regulated expression of BMI-1 was associated with tumor invasion, metastasis and poor survival of pancreatic cancer patients. CD133+ cells were obtained by using magnetic cell sorting and identified of CSCs properties such as self-renew, multi-differentiation and tumor formation ability. Then, we found that BMI-1 expression was up-regulated in pancreatic cancer stem cells. Knockdown of BMI-1 expression attenuated invasion ability of pancreatic cancer stem cells in Transwell system and liver metastasis capacity in nude mice which were injected CSCs through the caudal vein. We are the first to reveal that BMI-1 could promote invasion and metastasis ability of pancreatic cancer stem cells. Finally, we identified that BMI-1 expression activating PI3K/AKT singing pathway by negative regulating PTEN was the main mechanism of promoting invasion and metastasis ability of pancreatic CSCs. In summary, our findings indicate that BMI-1 could be used as the therapeutic target to inhibiting CSCs-mediated pancreatic cancer metastasis.

As an emerging service-oriented manufacturing paradigm, Cloud Manufacturing (CMfg) is expected to provide smart networked platforms that enable efficient global collaborations among cloud service providers in a product lifecycle. The service provider cooperative relationship (SPCR) plays a crucial part in cloud service scheduling and thus potentially influences the operational performance of a CMfg platform. The guaranteed SPCR could ensure service quality and reduce the interaction costs among service providers in the process of collaborative manufacturing tasks, thereby having a positive impact on the operational efficiency of a CMfg platform. The cost reduction and quality assurance, however, usually make the cost-effective services more attractive for an increasing number of manufacturing tasks and lead to load imbalance in a CMfg platform, thus having a negative impact on the operational efficiency. The impact mechanism of SPCR on a CMfg platform is still unclear from an evolutionary perspective. In this paper, we propose a CMfg platform evolution model (CPEM) to investigate the impacts of SPCR on the operational performance of a CMfg platform. Three quantitative metrics, from the perspective of cloud consumer, cloud operator, and cloud service provider, respectively, are established to support the performance evaluation. The results of contrast experiments reveal the impacts of SPCR on a CMfg platform.

Risk management is crucial and indispensable to the success of projects, while identifying critical risks is the fundamental step in devising the corresponding safety measures. To fully exploit the value of richly accumulated accidental cases, this paper presents a data-driven research framework for proposing effective safety enhancing strategies based on risk networks in construction engineering, spanning the whole process from extracting accident chains from accidents to construct a risk network to devising safety measures. Aiming at the weighted heterogeneity of the risk network, both the performance metrics at network level and critical-risk identification metrics at node level are deliberately designed. These metrics then enable the proposing of a series of safety-enhancing strategies. In the case study, based on the accident-related data in China’s bridge-and-tunnel hybrid projects, different safety-enhancing strategies are compared through simulation experiments and analyzed to verify their effectiveness on optimizing costs and improving safety. Finally, based on results from simulations, relevant managerial suggestions are proposed.

Over recent years, online purchase platforms of fruits are increasingly emerged to advance the e-commerce development and improve quality of human life. Unfortunately, we empirically observed that a lot of enterprises selling fruits online have suffered from bankruptcy due to a lot of complicated factors, such as inefficient logistics, low acceptance of online platforms, and financial risks. One of the root causes responsible for such an unanticipated phenomenon is related to the purchase intention, which motivates us to investigate what are the dominant factors affecting the online purchase intention of fruits. The results can be of great significance to the development of fruit e-commerce enterprises in online marketing. Based on the technology acceptance model (TAM) and perceived risk theory (PRT), this research developed an integrated theoretical model to explore the influential factors underlying consumers' intention to purchase fruits online. A web-based survey of 344 consumers with ages below 30 was used to test the hypotheses in our theoretical model. Through sample collection with questionnaires, a structural equation model is developed to compute the coupling relationship between influential factors and purchase intention. The results reveal that fruit quality and price are dominantly affecting the willingness of consumers to purchase fruit. Surprisingly, we found that e-commerce platforms, information quality, and perceived risk are less significant. Finally, some specific suggestions are recommended for fruit e-commerce enterprises in devising effective marketing strategies.

To overcome the deficiency of ultrasonic sensor and camera, this paper proposed a method of autonomous parking based on the self-driving car, using HDL-32E LiDAR. First the 3-D point cloud data was preprocessed. Then we calculated the minimum size of parking space according to the dynamic theories of vehicle. Second the rapidly-exploring random tree algorithm (RRT) algorithm was improved in two aspects based on the moving characteristic of autonomous car. And we calculated the parking path on the basis of the vehicle’s dynamics and collision constraints. Besides, we used the fuzzy logic controller to control the brake and accelerator in order to realize the stably of speed. At last the experiments were conducted in an autonomous car, and the results show that the proposed automatic parking system is feasible and effective.

Therapeutic leukapheresis is a rapid and effective method to reduce early mortality of patients with hyperleukocytic leukaemia (HLL). However, few studies on factors influencing the efficiency have been reported. In this study, 67 cases who underwent leukapheresis were retrospectively analysed and factors related to the collection efficiency of leukapheresis (CEWBC) were also evaluated. Paired t test showed that there was a significant decrease in statistics of white blood cell (WBC) counts after apheresis. The results of two independent samples nonparametric test suggested that WBC counts, platelet (PLT) counts, haematocrit (HCT), hemoglobin (HGB), serum chlorine (Cl) and globulin (GLB) before leukapheresis correlated with the CEWBC. Multiple linear regression analysis with background stepwise variable selection indicated that only WBC and HCT before leukapheresis had an influence on CEWBC significantly. Kaplan-Meier analysis and Cox regression model indicated that lymphocyte (LY) and mean corpuscular hemoglobin (MCH) pre-apheresis as independent factors significantly affected the prognostic survival of patients with HLL. Moreover, platelets and red blood cell were contaminated in the product of leukapheresis. It is an urgent problem to be solved in order to realise higher efficacy and higher purity of WBC collection to improve the survival of patients with HLL through optimising instruments.

Prefabricated construction has become increasingly popular over the recent years, given its benefits including higher construction speed, lower cost, and improved quality. To facilitate the operations of prefabricated construction, various technologies have in parallel been introduced. However, due to its project-based feature and the involvement of numerous Small and Medium Enterprises (SMEs), the adoption of information technologies is insufficient and varies between SMEs, thereby hindering the improvement of the efficiency of prefabricated construction. Considering these issues and aiming at realizing lean prefabricated construction, this paper proposes an integrated cloud-based Internet of Things (IoT) platform through exploiting the concept of cloud asset. Its operation model has also been worked out to enable SMEs to adopt IoT technologies economically and flexibly. Besides, to make the platform compatible and scalable on managing diverse physical assets in different companies and scenarios, a unified cloud asset data model is proposed. Furthermore, an IoT service-sharing module is developed to support different levels of service-sharing on the platform. Finally, a real-life prefabricated construction project in Hong Kong and several lab-based LEGO construction models are adopted to verify the feasibility and effectiveness of the proposed platform.

Multiple myeloma-associated antigen-1 (MMSA-1) is a novel multiple myeloma (MM)-associated antigen which has been recently identified. Herein, we have tried to examine its clinical significance by studying the relationship between its expression and selected clinicopathological features. We extracted mononuclear cells from the bone marrow of MM patients and healthy donors and compared the MMSA-1 expression by RT-PCR and Western blot analysis. In addition, we also analyzed MMSA-1 expression in patients that were grouped based on selected clinical parameters. Moreover, the impact of MMSA-1 on patients' survival was also explored. MMSA-1 mRNA and protein were significantly upregulated in MM patients in comparison with healthy donors. Moreover, among the newly diagnosed and relapsed/refractory patients, the MMSA-1 expression was higher in relapsed/refractory patients. In addition, MMSA-1 mRNA expression not only showed significantly higher correlation with clinical parameters such as age, Durie and Salmon stage, bone lesion condition, albumin, creatinine and lactate dehydrogenase but also has a close relationship with myeloma bone disease-related cytokines, genetic abnormalities and treatment response. Multivariate COX analysis predicted MMSA-1 and LDH levels to be independently associated with a poor progression-free survival and overall survival in myeloma patients. Our findings provide initial proof of concept that MMSA-1 is a potent gene that is specifically expressed in MM patients and could be a feasible biomarker and independent prognostic factor.

Aim: To identify independent factors predicting overall survival (OS) of breast cancer (BC) patients. Patients & methods: Two hundred and eighty one women with BC were recruited and clinical characteristics including lymphovascular invasion, clinical stage of Tumor Node Metastasis and positive axillary lymph nodes were documented; immunohistochemistry/fluorescence in situ hybridization was used to examine the expression of estrogen receptor, progesterone receptor, HER2 and Ki-67; major depressive disorder was assessed with Diagnostic and Statistical Manual of Mental Disorders V. Results: Multivariable analyses indicated that in BC patients, lymphovascular invasion, Tumor Node Metastasis, pN, Ki-67 and major depressive disorder were significantly negatively correlated with OS; estrogen receptor was significantly positively associated with OS. Conclusion: Early diagnostic approaches and effective psychologic intervention are indispensable for BC patients.

This paper focuses on the discrete-time automatic pipeline, inventory and order-based production control system (APIOBPCS), a well-established production and inventory control model. The feedback mechanism within the replenishment rule enables the model to mitigate the bullwhip effect, but introduces a stability problem. In this research, a comprehensive stability analysis is conducted for arbitrary lead times using difference equation theory. On the basis of stability, a state space approach is advocated to analyse the impact of replenishment parameters, demand processes, and lead times on the robustness of the bullwhip effect. The stability results demonstrate that the production control system can easily be destabilised without incorporating the work-in-progress (WIP) feedback loop. Furthermore, it reveals that the stability problem for long lead times can be simplified with the stability condition independent of the lead time. The results obtained in this study provide useful guidelines for the select...

Depression is the most common psychiatric disorder among cancer patients. Studies have not only highlighted that leptin and its receptor (LepRb) are independent poor prognostic factors in gastric cancer (GC) patients but also shown that the leptin-LepRb is necessary for antidepressant-like behaviors. In this study, we examined the serum and tissue leptin-LepRb expression in GC patients. Enzyme-linked immunosorbent assay showed that depressive GC patients had significantly higher serum leptin-LepRb than healthy donors. Leptin-LepRb levels in GC tissues were also significantly higher than in matched paracarcinoma tissues using real-time RT-PCR. Moreover, we observed that both serum and tissue leptin-LepRb were significantly higher in depressive GC patients than those in nondepressive GC patients. Further, the patients with high tumor stage tend to have higher leptin-LepRb mRNA levels than that with low tumor stage. Together, our findings suggest that leptin-LepRb plays an important role in the pathogenesis and depression in GC. Leptin-LepRb therefore could be a potential diagnostic marker and therapeutic target in GC patients with depression.

Triple-negative breast cancer (TNBC) is an aggressive subgroup of breast cancer lack of effective target therapy. This study was to investigate the prognostic role of p53 and Ki-67 in 156 cases of TNBC patients. Logistic regression analysis was used to examine the association between clinical parameters and recurrence. Univariate and multivariate analyses were used to examine the association between clinical characteristics and disease-free survival (DFS) or overall survival (OS). Survival analyses using the Kaplan-Meier method were performed to examine the association between p53/Ki-67 and DFS and OS. Our data showed that p53 was positive in 71.3% and the Ki-67 high index was in 82.8% of TNBC. Elevated p53 and Ki-67 were associated with histological grade. The tumor size, lymph node involvement, and p53 expression are associated with risk of recurrence. Tumor size, lymph node involvement, family history, Ki-67 and p53 are independent variables associated with either DFS or OS. TNBC patients with positive p53 or Ki-67 high index or family history of cancer have a significant association with worse prognosis. This study suggests that p53, Ki-67 and family history are useful prognostic markers in TNBC.

We assessed the clinical effectiveness and safety of CKI (compound Kushen injection) plus standard induction chemotherapy for treating adult acute leukemia (AL). We randomly assigned 332 patients with newly diagnosed AL to control (n= 165, receiving DA (daunorubicin and cytarabine) or hyper-CVAD (fractionated cyclophosphamide, doxorubicin, vincristine, and dexamethasone)) or treatment (n= 167, receiving CKI and DA or hyper-CVAD) groups. Posttreatment, treatment group CD3+, CD4+, CD4+/CD8+, natural killer (NK) cell, and immunoglobulin (IgG, IgA, and IgM) levels were significantly higher than those of the control group (p< 0.05), and CD8+ levels were lower in the treatment group than in the control group (p< 0.05). Treatment group interleukin- (IL-) 4 and IL-10 levels were significantly higher compared to the control posttreatment (bothp< 0.05) as were complete remission, overall response, and quality of life (QoL) improvement rates (p< 0.05). The control group had more incidences of grade 3/4 hematologic and nonhematologic toxicity (p< 0.05). Responses to induction chemotherapy, QoL improvement, and adverse events incidence between control group patients with acute myeloid leukemia and acute lymphocytic leukemia were not significantly different. CKI plus standard induction chemotherapy is effective and safe for treating AL, possibly by increasing immunologic function.

Depression is a common symptom among gastric cancer (GC) patients and serves as a potential indication of poor prognosis and advanced cancer clinical stage. However, the molecular mechanism of depression‑associated poor prognoses of GC patients remains unclear. Recent studies have revealed that GC patients with depression are under high levels of oxidative stress (OS) status that is accompanied by the dysfunction of numerous proto‑oncogenes, including the ABL proto‑oncogene 1 (ABL1), which is a non‑receptor tyrosine kinase. Recent evidence indicates that ABL1 was dysregulated in both major depressive disorder (MDD) and cancer patients with depression, and high levels of reactive oxygen species (ROS) can lead to the activation of ABL1 in response to OS and that activated ABL1 subsequently contributes to development of GC via interactions with the downstream targets and corresponding signaling pathways. In this review, we examine the evidence to illuminate the molecular mechanism of ABL1 in the progression of GC patients with depression and identify out new and effective methods for the initial and long‑term treatment of GC.

// Fuling Zhou 1, 2, * , Ming Li 1, * , Yongchang Wei 1, 3, * , Kevin Lin 4 , Yue Lu 4 , Jianjun Shen 4 , Gary L. Johanning 1 , Feng Wang-Johanning 1 1 Viral Oncology Program, Center for Cancer and Metabolism, SRI International, Menlo Park, California, USA 2 Department of Clinical Hematology, Zhongnan Hospital, Wuhan University, Wuhan, Hubei, China 3 Department of Radiation and Medical Oncology, Zhongnan Hospital, Wuhan University, Wuhan, Hubei, China 4 Department of Epigenetics and Molecular Carcinogenesis, Science Park, The University of Texas MD Anderson Cancer Center, Smithville, Texas, USA * Co-first authors Correspondence to: Feng Wang-Johanning, email: feng.wang-johanning@SRI.com Keywords: HERV-K, breast cancer, shRNA, Ras signaling, tumorigenesis and metastasis Received: April 22, 2016 Accepted: August 11, 2016 Published: August 20, 2016 ABSTRACT Human endogenous retrovirus type K (HERV-K) Env protein was previously demonstrated to be overexpressed in human breast cancer (BC) cells and tissues. However, the molecular pathways driving the specific alterations are unknown. We now show that knockdown of its expression with an shRNA (shRNAenv) blocked BC cell proliferation, migration, and invasion. shRNAenv transduction also attenuated the ability of BC cells to form tumors, and notably prevented metastasis. Mechanistically, downregulation of HERV-K blocked expression of tumor-associated genes that included Ras, p-RSK, and p-ERK. The major upstream regulators influenced by HERV-K knockdown were p53, TGF- β1, and MYC. Of interest, when the HERV-K env gene was overexpressed in shRNAenv-transduced BC cells using an HERV-K env expression vector, Ras/Raf/MEK/ERK pathway signaling was restored. CDK5, which alters p53 phosphorylation in some cancers, was upregulated and p53 was downregulated when HERV-K was overexpressed. CDK5 is also a mediator of TGF-β1-induced epithelial-mesenchymal transition and migration in cancer cells, and is involved in tumor formation. Importantly, reductions in migration, invasion, and transformation of BC cells stably transduced with shRNAenv was reversed after adding back a vector with a synonymous mutation of HERV-K env . Taken together, these results indicate that HERV-K Env protein plays an important role in tumorigenesis and metastasis of BC.

This study investigated the connection among the oxidative stress, depression and expression of specific genes involved in DNA-damage signaling pathways in patients with colorectal carcinoma (CRC).A unique Dukes'C subset of patients with newly diagnosed colorectal adenocarcinoma were assessed using the Hamilton Depression Rating Scale (HAMD), Zung Self-rating Depression Scale (SDS), Zung Self-rating Anxiety Scale (SAS), Symptom Checklist 90 (SCL-90) and other multiple-item questionnaires. Oxidative-stress-related parameters in sera and the expression of genes were monitored during a pretreatment period.Eighty-two eligibility cases were divided into 2 groups based on an HAMD score cutoff of 20: the mean score was 28.29 in Group A (depression, n=52) and 16.50 in Group B (nondepression, n=30). The serum total antioxidant capacity, catalase, and superoxide dismutase concentrations were lower in Group A, whereas those of nitric oxide and malondialdehyde were higher in Group A. Importantly, the 8-hydroxy-deoxyguanosine level was higher in Group A than in Group B (P.05). Microarray analysis revealed that the expressions of p34, PA26, and ABL were higher in Group A, whereas those of HRAD51, CR6, and XRCC3 were higher in Group B.Oxidative stress is capable of causing neuronal toxicity via lipid peroxidation, DNA damage, and abnormalities of gene expression, and therefore is a possible pathogenic mechanism underlying depression in patients with CRC.

Currently there are no targeted therapeutic strategies for estrogen receptor (ER)-negative breast cancer (ENBC), which constitutes 30-40% of breast cancer cases and is prone to metastasize and recur. Distant metastasis accounts for 90% of cancer-associated deaths. The majority of deaths from breast cancer are caused by distant metastasis developed in lung, liver, bone, or brain. However, to date it remains a challenge and unmet need to treat existing metastasis and block new metastasis in cancer patients. Dysregulated glucose and energy metabolism is critically involved in the development and progression of various cancers via promoting aberrant cell growth, malignant transformation and metastasis, but the potential role of glucose/energy metabolism in ENBC progression and metastasis has scarcely been explored heretofore, thus representing a key knowledge gap and a potential avenue for anticancer targeting. A number of anticancer metabolic and biogenetic therapies have been developed, yet none of them has progressed to clinical use, due to their limited potency, specificity or drug properties such as toxicity and poor bioavailability. We recently identified a novel small molecule HJC0152 that significantly suppresses ENBC xenograft tumor growth and blocks ER-negative mammary tumor development in mouse models. HJC0152 treatment for 24-72 hours differentially modulates protein expression of HK1, PFK-L, PFKFB2, ENO2, PDH, PDK1, PGAM1 and ALDOA in a time-dependent manner. HJC0152 also regulates the transcription of genes involved in glucose and mitochondrial energy metabolism, including the subunits of mitochondrial respiratory chain complexes. Functional assessments of mitochondrial complexes demonstrate that HJC0152 significantly inhibits Complexes IV but increases Complex V (ATP synthase) function, while Complexes I and II function is minimally affected. Migration and invasion of MDA-MB-231 cells are significantly inhibited by HJC0152 treatment. In vivo, HJC0152 administrated either before, concurrent with or after tail vein injection of MDA-MB-231 cells dramatically blocks the development of lung macro- and micro-metastasis in all groups. These results suggest that HJC0152 can specifically reprogram/restore the dysregulated glucose metabolism by inducing specific glycolytic enzyme expression and mitochondrial respiratory chain function, likely via targeting one or more upstream signal molecule(s) that regulates glucose and energy metabolism, thereby suppressing breast cancer progression to metastasis. This work was supported by Grants P50 CA097007, P30DA028821, and R21MH093844 (J.Z.) from the NIH, CPRIT (J.Z.), John Sealy Memorial Endowment Fund (J.Z.), DFI Seed Grants from MD Anderson Cancer Center (Q.S.), and Holden Family Research Grant in Breast Cancer Prevention from the Prevent Cancer Foundation (Q.S). Citation Format: Hao Zou, Na Ye, Hui Pang, Dan Zhang, Ruping Yan, Haijun Chen, Guoshuai Cai, Lili Wang, Zhengduo Yang, Haiying Chen, Grace Xu, Yingchao Zhang, Ritu Arora, Ming Tan, Yongchang Wei, Jia Zhou, Qiang Shen. Reprogramming glucose metabolism and energy production with a small molecule HJC0152 suppresses breast cancer development and progression to metastasis. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 329.

Tao Wu,1 Min Jiao,1 Li Jing,1 Min-Cong Wang,1 Hai-Feng Sun,2 Qing Li,1 Yi-Yang Bai,1 Yong-Chang Wei,1 Ke-Jun Nan,1 Hui Guo1 1Department of Medical Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, 2Department of Oncology, Shaanxi Cancer Hospital, Xi’an, People’s Republic of China Abstract: Association of Notch-1 expression with prognosis of patients with hepatocellular carcinoma (HCC) remains controversial. We conducted a meta-analysis to reevaluate the association of Notch-1 expression with clinicopathological characteristics and prognosis of HCC. PubMed, Embase, Web of Science, and China National Knowledge Infrastructure were searched to look for relevant studies. The association between Notch-1 expression and clinicopathological parameters and overall survival (OS) was then reassessed using the meta-analysis for odds ratio (OR) or hazard ratio (HR) and 95% confidence interval (CI). A total of seven studies, including 810 HCC patients, were eligible for the meta-analysis. Our data showed that high Notch-1 expression was able to predict poor OS (HR 1.50, 95% CI 1.17–1.83, P=0.0001). The pooled OR showed that high Notch-1 expression was significantly associated with tumor metastasis (OR 0.37, 95% CI 0.16–0.86, P=0.02) and tumor size >5cm (OR 0.48, 95% CI 0.26–0.88, P=0.02). In contrast, there was no association between high Notch-1 expression and tumor differentiation, late TNM stage, tumor number, and portal vein invasion of HCC. In conclusion, Notch-1 overexpression might predict poorer survival and more aggressive behavior in patients with HCC. Keywords: hepatocellular carcinoma, Notch-1, prognosis, clinicopathological features, meta-analysis

The results of several recent studies indicated that free radicals are involved in the biochemical mechanisms that underlie neuropsychiatric disorders. In the present study, we evaluated changes in oxidative stress and human 8-hydroxyguanine glycosylase1 gene (hOGG1) expression in depressive patients with acute leukemia. Ninety two cases were assessed using the Zung self-rating depression scale (SDS) and multiple-item questionnaires. We measured total antioxidant capacity (T-AOC) and the concentrations of reactive oxygen species (ROS), superoxide dismutase (SOD), malondialdehyde (MDA) and nitric oxide (NO) during a pre-treatment period. The steady-state expression of hOGG1 mRNA transcripts was monitored. The incidence of depression was 47.83%. There was a significant decrease in serum T-AOC and SOD concentrations in depressive patients compared to the control subjects, whereas the opposite was the case for serum concentrations of ROS, NO and MDA. Real-time polymerase chain reaction (PCR) revealed that hOGG1 mRNA expression was greater in depressive patients than in the controls. Person correlation analysis revealed that depression was correlated positively with sex, the course of the disease and hOGG1 mRNA expression; depression was correlated negatively with T-AOC. Based on these results, we conclude that the antioxidant system is impaired in leukemic patients with affective disorders. Therefore, oxidative stress may play an important role in the pathophysiology of depression.

AIM: A study was performed to investigate the impact of comorbid anxiety and depression (CAD) on quality of life (QOL) and cellular immunity changes in patients with digestive tract cancers. METHODS: One hundred and fifty-six cases of both sexes with cancers of the digestive tract admitted between March 2001 and February 2004 in the Department of Medical Oncology, First Affiliated Hospital of Xi’an Jiaotong University were randomly enrolled in the study. Depressive and anxiety disorder diagnoses were assessed by using the Structured Clinical Interview for DSM-IV. All adult patients were evaluated with the Hamilton depressive scale (HAMD, the 24-item version), the Hamilton anxiety scale (HAMA, a modified 14-item version), quality of life questionnaire-core 30 (QLQ-C30), social support rating scale (SSRS), simple coping style questionnaire (SCSQ), and other questionnaires, respectively. In terms of HAMD ≥ 20 and HAMA ≥ 14, the patients were categorized, including CAD (n = 31) in group A, anxiety disorder (n = 23) in group B, depressive disorder (n = 37) in group C, and non-disorder (n = 65) in group D. Immunological parameters such as T-lymphocyte subsets and natural killer (NK) cell activities in peripheral blood were determined and compared among the four groups. RESULTS: The incidence of CAD was 21.15% in patients with digestive tract cancers. The average scores of social support was 43.67±7.05 for 156 cases, active coping 20.34±7.33, and passive coping 9.55±5.51. Compared with group D, subjective support was enhanced slightly in group A, but social support, objective support, and utilization of support reduced, especially utilization of support with significance (6.16 vs 7.80, P

Recent data from several studies suggest that oxidative stress is involved in the biochemical mechanisms that underlie neuropsychiatric disorders. The present study was designed to investigate oxidative stress status in depressive patients with gastric adenocarcinoma (GA) at TNM stage III. Oxidative stress, depression and expression of specific genes were monitored during a pretreatment period. Serum total antioxidant capacity, catalase, superoxide dismutase concentrations, and antisuperoxide anion capacity (A-ASC) were significantly decreased in depressive patients compared to control subjects, whereas serum malondialdehyde (MDA) levels were significantly increased. Importantly, the formation of 8-hydroxy-deoxyguanosine (8-OHdG) accumulated. Furthermore, SYBR Green real-time PCR revealed that the expression levels of human oxoguanine glycosylase 1 and APEX nuclease 1 (APEX1) were increased in depressive patients. Pearson correlation analysis revealed that depression was positively correlated with SAS, SCL-90, MDA, 8-OHdG and APEX1, but negatively correlated with A-ASC. Thus, this study confirms oxidative imbalance in depressive patients with GA, and oxidative stress may play a role in the onset and exacerbation of depression.