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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.

The efficient capture and high-activity release of circulating tumor cells (CTCs) remain a challenge for the microfluidic chip. We have fabricated a dual-mode gelatin-polydimethylsiloxane (PDMS) microfluidic chip with a sawtooth columnar microstructure of channels that can capture the efficiency of this substrate up to 95%. Increasing the gelatin temperature to physiologic temperature (37 °C) with a baking table facilitates the overall release of CTCs. With melting of the gelatin substrate, the cells will enter into the PDMS corresponding channel; however, the released cells will be wrapped by a layer of gelatin, which may affect further proliferation of the cells. Another way to release CTCs is to use a matrix metalloproteinase-9 (MMP-9) enzyme to dissolve the gelatin and release the tumor cells with high cellular viability. This dual-mode microfluidic chip has been applied successfully to capturing and releasing CTCs, thus serving as a powerful clinical tool that facilitates the subsequent bioanalysis of CTCs for clinical and biological research.

This paper is devoted to discern long time dynamics through the stochastic low concentration trimolecular oscillatory chemical system with jumps. By Lyapunov technique, this system is proved to have a unique global positive solution, and the asymptotic stability in mean square of such model is further established. Moreover, the existence of random attractor and Lyapunov exponents are obtained for the stochastic homeomorphism flow generated by the corresponding global positive solution. And some numerical simulations are given to illustrate the presented results.

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...

In this paper, we provide several characterizations on weak recurrence of translation operators on weighted Lebesgue spaces and on continuous function spaces. It is shown that the translation operator admits a nonzero nonwandering point if and only if it has a nonzero recurrent point, if and only if it is hypercyclic; that the translation operator admits a nonzero almost periodic point if and only if it is Devaney chaotic. Moreover, every hypercyclic translation operator has infinite topological entropy, but the converse is not true. Finally, we remark that there exists a linear operator which has the specification property on the whole space.

Radioresistance is one of the primary causes responsible for therapeutic failure and recurrence of cancer. It is well documented that reactive oxygen species (ROS) contribute to the initiation and development of gastric cancer (GC), and the levels of ROS are significantly increased in patients with GC accompanied with abnormal expressions of multiple inflammatory factors. It is also well documented that ROS can activate cancer cells and inflammatory cells, stimulating the release of a variety of inflammatory cytokines, which subsequently mediates the tumor microenvironment (TME) and promotes cancer stem cell (CSC) maintenance as well as renewal and epithelial-mesenchymal transition (EMT), ultimately resulting in radioresistance and recurrence of GC.

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.

Current organoid models are limited by the incapability of rapidly fabricating organoids that can mimic the immune microenvironment for a short term. Here, an acoustic droplet-based platform is presented to facilitate the rapid formation of tumor organoids, which retains the original tumor immune microenvironment and establishes a personalized bladder cancer tumor immunotherapy model. In combination with a hydrophobic substrate, the acoustic droplet printer can yield a large number of homogeneous and highly viable bladder tumor organoids in vitro within a week. The generated organoids consist of all components of bladder tumor, including diverse immune elements and tumor cells. By coculturing tumor organoids with autologous immune cells for 2 days, tumor reactive T cells are induced in vitro. Furthermore, it is also demonstrated that these tumor-reactive T cells can also enhance the killing efficiency of matched organoids. Because of the easy operation, repeatability, and stability, the proposed acoustic droplet platform will provide a reliable approach for personalized tumor immunotherapy.

// 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.

Time series data analysis, such as temporal pattern recognition and trend forecasting, plays an increasingly significant part in temporal data statistics and analytics. Yet challenges still exist in the efficiency of pattern extracting and trend prediction for large multivariate time series. The paper proposes a multi-stage clustering approach towards multivariate time series by using dynamic sliding time windows. The segmented multivariate time series are clustered separately in each time window to product first-stage clustering centres, and which are used to generate second-stage clustering results involving all time windows. The method can simplify large scale multivariate time series mining problems through multi-stage clustering on multiple sliding time windows thus achieve improved efficiency. Based on the clustering outcomes, a correlation rules mining method is given to discover frequent patterns in the time series and generate self-correlation rules. Then, the paper presents a probabilist...

In an online order picking system, customer orders arrive in real time and the picking information is updated dynamically. One challenging problem is how to process customer orders in a timely manner. In this paper, a nonparametric heuristic method, Green Area, is presented to address the real-time online order batching problems. By nonparametric, we mean that our method is independent of the parameters of a warehouse layout and the characteristics of customer orders; these parameters facilitates the implementation in real life. The advantages of this method are verified under different scenarios by simulations. Specifically, the influences of the arrival rate, the number of order pickers and the number of orders in the order service time are discussed. The results demonstrate that the Green Area method leads to shorter order service times than traditional methods for optimal batch sizes. Finally, we demonstrate that the Green Area method can be applied to online order picking systems with variable arrival rates.

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.

Acute myeloid leukemia (AML) is a common type of hematological malignancy that can progress rapidly. AML has a poor prognosis and a high incidence of relapse due to therapeutic resistance. Azelaic acid (AZA), a small molecular compound is known to exhibit antitumor effect on various tumor cells. This study aimed to evaluate the antiproliferative and immunoregulatory effects of AZA against AMLviathe activation of the notch signaling pathway. We found that AZA can inhibit the proliferation of AML cells. In addition, laser confocal microscopy showed AZA-treated AML cells began to swelling and undergo cytoplasmic vacuolization. Importantly, AZA promoted the proliferation of NK and T cells and increased the secretion of TNF-αand IFN-γ. AZA also increased the expression levels of CD107a and TRAIL in NK cells, and CD25 and CD69 in T cells to influence their activation and cytotoxic ability. AZA-treated NK cells can kill AML cells more efficiently at the single-cell level as observed under the microfluidic chips. Further mechanistic analysis using protein mass spectrometry analysis and Notch signaling reporter assay demonstrated that Notch1and Notch2 were up-regulated and the Notch signaling pathway was activated. Moreover, combining AZA with the Notch inhibitor, RO4929097, decreased the expression of Notch1and Notch2, and downstream HES1 and HEY1, which rendered AML cells insensitive to AZA-induced apoptosis and alleviated AZA-mediated cytotoxicity in AML. In vivo, AZA relieved the leukemic spleen infiltration and extended the survival. The percentage of CD3-CD56+NK cells and CD4+CD8+T cells as well as the secretion of cytotoxic cytokines was increased after the treatment of AZA. The overall findings reveal that AZA is a potential Notch agonist against AML in activating the Notch signaling pathway.

Base editors (BEs) are widely used in precise gene editing due to their simplicity and versatility. However, their efficiencies are hindered by various obstacles. Considering the chromatin microenvironment as a possible obstacle, here, we demonstrate a further development of the proxy-clustered regularly interspaced short palindromic repeats strategy, termed Proxy-BE, to increase gene editing efficiency. Specifically, a nuclease-dead Cas9 (dCas9) was bound to the sequence about 20-30 base pair away from the target site, potentially improving access to the DNA and, thus, providing a better editing microenvironment for base editors. Our findings confirm that nuclease-dead Streptococcus pyogenes Cas9 can assist the base editors SaKKH-BE3 and dCpf1-BE to double their canonical base editing efficiency. This work provides a new approach to enhance base editing, extending its scope for biological research and gene therapy.

Radiotherapy is used to treat gastric cancer (GC); however, radioresistance challenges the clinical outcomes of GC, and the mechanisms of radioresistance in GC remain poorly understood. Here, we report that the TGF-β receptor inhibitor, LY2109761 (LY), is a potential radiosensitizer both in vitro and in vivo. As per the Cancer Genome Atlas database, TGF-β overexpression is significantly related to poor overall survival in GC patients. We demonstrated that the TGF-β/SMAD4 signaling pathway was activated in both radioresistant GC cells and radioresistant GC patients. As a TGF-β receptor inhibitor, LY can enhance the activities of irradiation by inhibiting cell proliferation, decreasing clonogenicity and increasing apoptosis. Moreover, LY attenuated the radiation-induced migration and invasion, epithelial-mesenchymal transition (EMT), inflammatory factor activation, immunosuppression, and cancer stem cell characteristics of GC cells, thus leading to radiosensitization of the GC cells. We confirmed that LY reduced tumor growth, inhibited TGF-β/SMAD4 pathway activation and reversed irradiation-induced EMT in a tumor xenograft model. Our findings indicate that the novel TGF-β receptor inhibitor, LY, increases GC radiosensitivity by directly regulating the TGF-β/SMAD4 signaling pathway. These findings provide new insight for radiotherapy in GC patients.

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.

A problem-specific routing algorithm integrating ant colony optimization (ACO) and integer-coded genetic algorithm (GA) is developed to address the newly observed limitations imposed by ultranarrow aisles and access restriction, which exist in the largest e-commerce enterprise with self-run logistics in China. Those limitations prohibit pickers from walking through the whole aisle, and the access restriction even allows them to access the pick aisles only from specific entrances. The ant colony optimization is mainly responsible for generating the initial chromosomes for the genetic algorithm, which then searches the near-optimal solutions of picker-routing with our novel chromosome design by recording the detailed information of access modes and subaisles. To demonstrate the merits of the proposed algorithm, a comprehensive simulation for comparison is conducted with 12 warehouse layouts with real order information. The simulation results show that the proposed hybrid algorithm is superior to dedicated heuristics in terms of solution quality. The impacts of the parameters with respect to warehouse layout on the picking efficiency are analyzed as well. Setting more connect aisles and cross aisles is suggested to effectively optimize the picking-service efficiency in the presence of access limitations.

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.

Curcumin shows growth-inhibition against tumor cells through multi-target mechanisms. Nevertheless, the poor stability and pharmacokinetics considerably limit its clinical functions. Increased effort has been put into the chemical alteration of curcumin to find potential analogues with improved bioavailability and antitumor activities. In this study, the antitumor activity of a novel curcuminoid (B63) in nasopharyngeal carcinoma (NPC) was examined. The MTT and colony formation assays were used to detect NPC cell viability and proliferation. Flow cytometry was used to detect cell cycle distribution. The Annexin V/PI staining assay and cleavage PARP and cleavage caspase-3 expression were used to examine apoptosis. Western blotting was used to examine the protein expression of endoplasmic reticulum (ER) stress pathway markers, XBP-1, ATF-4 and CHOP. The suppressive effect of B63 on tumor growth was examined in vivo by subcutaneously inoculated NPC in a tumor model using nude mice. Treatment with B63 potentially caused growth inhibition and apoptosis in NPC cells in a dose- and time-responsive manner. Its antitumor effect was associated with the ER stress activation. Nevertheless, the same dose of curcumin did not activate ER stress. In addition, knockdown of Chop attenuated B63-induced cell viability inhibition, suggesting that the apoptotic pathway is ER stress-dependent. The tumor volume and weight were significantly reduced by pretreating the NPC cells with B63 before implantation in the in vivo mouse model. B63 exhibited a more potent antitumor action than curcumin in NPC. These observations on the novel compound B63 indicate a novel candidate for NPC therapy.

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.

The setting of air quality standards is highly significant in controlling widespread pollutants and mitigating environmental risks. The selection of influential drafting units is a major step for the improvement of the systematicness, harmony, and compatibility of standard systems, which further leads to high air quality. To this end, this paper presents a novel social network-based methodology to assess the influence of drafting units based on a dynamic two-layer standard network model with the publicized data of the national air quality standards of China. Firstly, network theory metrics are aggregated with the Technique for Order of Preference by Similarity to Ideal Solution (TOPSIS) to evaluate their importance dynamically; Secondly, three measurements of participation degree, cooperation degree, and contribution degree are deliberately designed to assess the influence of drafting units. The results show that most of the key standards vary over time driven by policy reform, while the volatility of critical drafting units is relatively stable. It is also interesting to find that most of the influential drafting units are research institutes rather than enterprises. In view of the results, we assert that government agencies should strategically support influential drafting units and encourage them to make great efforts in drafting important standards.

Background The increase in the levels of reactive oxygen species (ROS) in acute myeloid leukemia (AML) patients has been previously described; thus, it is important to regulate ROS levels in AML. Methods Flow cytometry were used to assess the in vitro effect of compound kushen injection (CKI). Quantitative proteomics were used to analyse the mechanism. The AML patient-derived xenograft (PDX) model were used to evaluate the in vivo effect of CKI. Results We found that intracellular ROS levels in AML cells were decreased, the antioxidant capacity were increased when treated with CKI. CKI inhibited the proliferation of AML cells and enhanced the cytotoxicity of AML cells, which has few toxic effects on haematopoietic stem cells (HSCs) and T cells. At the single-cell level, individual AML cells died gradually by CKI treatment on optofluidic chips. CKI promoted apoptosis and arrested cell cycle at G1/G0 phase in U937 cells. Furthermore, higher peroxiredoxin-3 (Prdx3) expression levels were identified in CKI-treated U937 cells through quantitative proteomics detection. Mechanically, the expression of Prdx3 and peroxiredoxin-2 (Prdx2) was up-regulated in CKI-treated AML cells, while thioredoxin 1 (Trx1) was reduced. Laser confocal microscopy showed that the proteins Prdx2 could be Interacted with Trx1 by CKI treatment. In vivo, the survival was longer and the disease was partially alleviated by decreased CD45+ immunophenotyping in peripheral blood in the CKI-treated group in the AML PDX model. Conclusions Antioxidant CKI possess better clinical application against AML through the Prdxs/ROS/Trx1 signalling pathway. Electronic supplementary material The online version of this article (10.1186/s13046-018-0948-3) contains supplementary material, which is available to authorized users.

This paper studies one type of delayed memristor-based fractional-order neural networks (MFNNs) on the finite-time stability problem. By using the method of iteration, contracting mapping principle, the theory of differential inclusion, and set-valued mapping, a new criterion for the existence and uniqueness of the equilibrium point which is stable in finite time of considered MFNNs is established when the order $ \alpha $ satisfies $ {0 . Then, when ${1 , on the basis of generalized Gronwall inequality and Laplace transform, a sufficient condition ensuring the considered MFNNs stable in finite time is given. Ultimately, simulation examples are proposed to demonstrate the validity of the results.

In current study, we have found that several magnetic nanoparticles (MNPs) are able to absorb DNA molecules, and surface engineering would be beneficial to tune such interaction. We then have focused on the assembly of polyethylenimine (PEI) coated MNPs (PEI-MNPs) with ssDNA (single-stranded DNA) and found this assembly is mediated by two forces, namely the electrostatic interactions of surface charges of MNPs and the phosphate backbones of DNA; as well as the coordination of exterior iron ions (especially Fe3+) of MNPs and DNA phosphate backbones. The fluorescence of dye-labeled DNA is significantly quenched when being complexed with PEI-MNPs, which is proved to be caused by static quenching. This PEI-MNPs interact with DNA, which could be harnessed for devising a novel type of aptasensor. This has been examplified by the selective and sensitive detection of lipopolysaccharide (LPS). The LOD (limit of detection) is ∼35 ng/mL and the linear range from 50 ng/mL to 10 μg/mL. Compared with widely used graphene oxide (GO)‒ssDNA aptamer sensors, we also have demonstrated that the PEI-MNPs based sensor is able to better avoid non-specific DNA displacement by interfering proteins, generating more satisfactory signal-to-background ratio. Our proposed sensor could be a supplement to classic GO‒DNA sensors. In summary, our work provides fundamental understanding of MNPs‒DNA interactions and also paves the way for developing novel MNPs based sensing approaches, which would contribute to nano‒bio interface and DNA-assisted bio-analysis, DNA-coordinated nano-materials and DNA-directed assembly.

In this work, we developed a feasible way to package bulk acoustic waves chip with sandwich structure by inserting a polydimethylsiloxane (PDMS) layer as the adhesive between cover glass and silicon substrate. After spin-coating and curing process, a PDMS layer was formed on one side of the cover glass and then bonded to the silicon substrate with microchannels by oxygen plasma treating. Both simulation and experiment showed that the chip was not leaking and the acoustic waves produced by the piezoelectric transducer could be propagated through the PDMS layer. Finally, a standing wave field was formed in the microchannels. Compared with traditional chip bonded by anodic bonding, simulation results showed that this packaging method did decrease the acoustic pressure in the channel, but the reduction was acceptable. After optimizing the experimental parameters, we successfully aggregated 15-μm silica spheres under a very low input power (21 dBm) at a flow velocity of 1 ml/h, and the enrichment efficiency of silica spheres was greater than 97%.

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.

This paper presents some analytical results on production and order dynamics in the context of a discrete-time VMI supply chain system composed of one retailer and one manufacturer. We firstly derive the lower bound and upper bound on the range of inventory fluctuations for the retailer under unknown demand. We prove that the production fluctuations can be interestingly smoothed and stabilized independent of the delivery frequency of the manufacturer used to satisfy the retailer’s demand, even if the retailer subsystem is unstable. The sufficient and necessary stability condition for the whole supply chain system is obtained. To further explore the production fluctuation problem, the bullwhip effect under unknown demand is explored based on a transfer function model with the purpose of disclosing the influences of parameters on production fluctuations. Finally, simulation experiments are used to validate the theoretical results with respect to inventory and production fluctuations.

The horizontal interaction between retailers, coupled with replenishment rules and time delays, makes the dynamics in supply chain systems highly complicated. This paper aims to explore the impacts of lateral transshipments on the stability, bullwhip effect, and other performance measurements in the context of a two-tiered supply chain system composed of one supplier and two retailers. In particular, we developed a unified discrete-time state space model to address two different scenarios of placing orders. Analytical stability results are derived, through which we found that inappropriate lateral transshipment policies readily destabilize the supply chain system. Moreover, the lead time of lateral transshipments further complicates the stability problem. Theoretical results are validated through simulation experiments and the influences of system parameters on performance measures are investigated numerically. Numerical simulations show that lateral transshipments help improve the customer service level for both retailers. It is also interesting to observe that the demand of the two retailers can be satisfied even if only one retailer places orders from the upstream supplier.

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.

A supply chain network might exhibit complex dynamics in the face of increasingly volatile and uncertain environment. The impact of network structure and collaboration on the dynamics and robustness of supply chain network, however, remains to be explored. In this paper, a unified state space model for a two-layer supply chain network composed of multiple distributors and multiple retailers is developed. A robust control algorithm is advocated to reduce both order and demand fluctuations for unknown demand. Numerical simulations demonstrate that the robust control approach has the advantage to reduce both inventory and order fluctuations. In the simulation experiment, it is interesting to notice that complex network structure and collaborations might contribute to the reduction of inventory and order oscillations. This paper yields new insights into the overestimated bullwhip effect problem and helps us understand the complexities of supply chain networks.

Human epididymis protein 4 (HE4) is a recognized biomarker in ovarian and endometrial cancer and over-expressed in pancreatic adenocarcinoma. The diagnostic value of HE4 in pancreatic adenocarcinoma remains unknown. Here we elucidate mRNA, protein and serum level of HE4 in pancreatic adenocarcinoma. HE4 mRNA level in tumor adjacent tissues and pancreatic adenocarcinoma tissues were tested by real time-PCR. Tissue microarray containing normal, adenocarcinoma, and adjacent pancreatic tissue was tested by immunohistochemistry (IHC). Serum level of HE4, carbohydrate antigen 19-9 (CA19-9), carbohydrate antigen 15-3 (CA15-3) and carbohydrate antigen 125 (CA125) were detected by ELISA assay in control and tumor patients. Further we compared the sensitivity and specificity of determining HE4, CA19-9, CA15-3, and CA125 for diagnosis of pancreatic adenocarcinoma and assessed the complementary diagnostic value of HE4, CA19-9, CA15-3 and CA125. Real time PCR showed significantly increased HE4 mRNA level in pancreatic adenocarcinoma compared with control. Result of IHC showed that HE4 significantly higher expressed in the human pancreatic carcinoma tissues than in both normal and adjacent non-tumorous pancreatic tissues, and the staining intensity is inversely correlated with the clinical stage. HE4 was highly expressed in early stage of pancreatic adenocarcinoma. Serum HE4 level is higher in cases with pancreatic adenocarcinoma than in the controls. Serum HE4 levels could research to a sensitivity of 45.83% and specificity of 93.75% when the Cutoff was set at 4.59 ng/mL. The Combined HE4 and CA19-9 increased the sensitivity to 83.33%, and interestingly, the combination of HE4 with CA15-3 led to the most powerful sensitivity of 87.5%. Combined with CA19-9 and CA15-3, HE4 could be a potential biomarker to improve the diagnostic power for pancreatic adenocarcinoma.

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.

Reactive oxygen species (ROS) plays a key role in carcinogenesis by aberrantly inducing signaling networks that initiatiate tumorigenesis and stimulate tumor progression. MicroRNAs (miRNAs) comprise a novel class of endogenous, small, noncoding RNAs that negatively regulate approximately 30% of the genes in a cell via degradation or translational inhibition of their target mRNAs. However, the effects of ROS on miRNAs expression and the role of miRNAs in ROS-mediated injury on carcinogenesis are uncertain. Using UV spectrophotometry and enzyme-linked immunosorbent assay (ELISA), we examined tissues from human gastric cancers and tissues adjascent to gastric cancer and normal gastric tissues and found that total anti-oxidation competence (T-AOC), superoxide dismutase (SOD) and catalase (CAT) concentrations were lower in gastric cancer patients compared to the control subjects, while the concentrations of DNA oxidative damage product 8-oxo-deoxyguanosine (8-OHdG) was higher. To determine the potential role of miRNA in gastric carcinogenesis, real-time quantitative polymerase chain reaction (QPCR) analysis was performed. We found that human 8-oxoguanine DNA N-glycosylase 1 (hOGG1) mRNA and miR-21 expression were significantly upregulated in gastric cancer tissues than in the adjacent normal gastric tissues. Furthermore, the expression of programmed cell death 4 protein (PDCD4) in gastric cancer tissues was significantly lower than in adjacent normal gastric tissues. The expression of miR-21 and PDCD4 was highly correlated with the degree of differentiation, tumor staging, local lymphatic node metastasis and remote metastasis. Expression of miR-21 was negatively correlated with T-AOC, SOD and CAT, but positively correlated with 8-OHdG and hOGG1mRNA. In addition, the relative expression of PDCD4 was negatively correlated with miR-21. These results suggest that the defensive balance of oxidation and antioxidant system in patients with GC was impaired, resulting in enhanced oxidative tissue injury, which may directly contribute to gastric carcinogenesis. Thus we conclude that ROS promotes gastric carcinogenesis via upregulating miR-21 expression which in turn down-regulates the expression of PDCD4 in gastric cancer cells.

In recent years, poor air quality has brought serious threats to public health and sustainable development. The air quality standard is an effective prerequisite to ensure the quality of the air. The citation relationships between air quality standards at a certain time point, which reflect technological development and knowledge transition, form a complex network. In this study, an integrated multi-criteria decision making method is proposed to measure the criticality of standards based on a dynamic citation network model. In particular, the Entropy Weight (EW) method is used to set the weights of each node measurement to avoid subjectiveness, while the TOPSIS method is employed to measure the criticality for each air quality standard. A case study based on the data of 444 of China’s national air quality standards reveals that the complex network method facilitates the identification of critical standards effectively. In addition, we found that there exist some structural problems in China’s air quality standard system: the connectivity between standards is insufficient; critical standards are lacking; and the critical standards change over time following the issue of national policies. Finally, policy suggestions are recommended on strengthening inter-standard citation, attaching importance to the revision of critical standards, and the dynamics of critical standards.

This paper is devoted to discern long time dynamics through the stochastically perturbed Heroin epidemic model under non-degenerate noises (SPHE). The SPHE is proved to have a unique global positive solution, and the unique stationary measure of this system under the non-degenerate case is further established as R 0 > 1 . Moreover, the extinction of the SPHE is obtained as R 0 1 .

This paper presents an investigation on the dynamics of a supply chain system under stock-dependent demand. Considering the feature of piecewise linearity, a switched linear model composed of three subsystems is developed. Based on the switched model, some analytical stability results are derived. Simulation experiments are designed to verify the stability results and observe nonlinear dynamics. We show that stock-dependent demand not only leads to different stability results but also makes nonlinear dynamics more complicated. We also reveal that the nonlinear dynamics of the switched model, such as chaotic and periodic fluctuations of inventory and order, are essentially caused by switching frequently among subsystems due to uncertainties of inventory status. The results obtained in this paper help us understand the dynamic complexities of supply chain system and provide guidelines for selecting decision parameters to improve overall performance.