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Purpose The purpose of this paper is to study the influence of different rolling deformation parameters on the morphology, microstructure and mechanical properties of Inconel 718 superalloy in hybrid plasma arc and micro-rolling (HPAMR) additive manufacturing. Design/methodology/approach In this paper, different deformation strains are designed, which are as-deposited, 15% and 30%. Two straight walls are fabricated by HPAMR for each kind of deformation. One wall underwent post-deposition heat treatment, and the other wall is treated without heat treatment. These samples are further investigated to evaluate the effects of deformation on the morphology, microstructure and mechanical properties. Findings As compared to as-deposited samples, the morphology can be significantly improved, the generation of defects and microporosity inside the alloy can be suppressed, and finer equiaxed crystals can be obtained with deformation of 30%. With heat treatment and 30% deformation, the Laves phase at the grain boundary is completely disappearing, more γ” and γ' strengthening phase is precipitated in the crystal and the size of the strengthening phase is smaller. Mechanical properties have been significantly improved. Practical implications HPAMR technology is used to successfully manufacture Inconel 718 superalloy aero-engine casing. Originality/value Compared with plasma arc additive manufacturing, HPAMR technology adds a rolling process, which can effectively improve the morphology of walls, refine internal grains, eliminate defects and microporosity, increase precipitation of strengthening phase and improve mechanical properties. It provides an optional manufacturing method for the integrated manufacturing of Inconel 718 parts.

Gemcitabine (GEM) resistance is a major challenge for chemotherapy of pancreatic cancer. Previous studies have reported on the role of long noncoding RNA (lncRNA) in tumorigenesis of pancreatic cancer, however, the involvement of lncRNA in the development of GEM resistance of pancreatic cancer remains unclear. In the present study, we demonstrated that the antisense RNA1 of HIF1α (HIF1A-AS1) was significantly elevated in the GEM-resistant pancreatic cancer cells. Gain- and lost-of-function experiments validated that HIF1A-AS1 promoted GEM resistance of pancreatic cancer cells both in vitro and vivo. We further revealed that HIF1A-AS1 upregulated HIF1α expression and thus promoted glycolysis to enhance GEM resistance of pancreatic cancer cells. Mechanistically, HIF1A-AS1 facilitated the interaction between serine/threonine kinase AKT and Y-box–binding protein 1 (YB1), which promoted phosphorylation of YB1 (pYB1). Meanwhile, HIF1A-AS1 recruited pYB1 to HIF1α mRNA that consequently promoted translation of HIF1α. Furthermore, HIF1α promoted HIF1A-AS1 transcription by directly binding to the HIF1α response element in the promoter area of HIF1A-AS1 to form a positive feedback. Consistently, both HIF1A-AS1 and HIF1α were upregulated in pancreatic cancer tissues and associated with poor overall survival. Together, our results underline a reciprocal loop of HIF1A-AS1 and HIF1α that contributes to GEM resistance of pancreatic cancer and indicate that HIF1A-AS1 might serve as a novel therapeutic target for GEM resistance of pancreatic cancer.Significance:These findings show that a reciprocal feedback of HIF1A-AS1 and HIF1α promotes gemcitabine resistance of pancreatic cancer, which provides an applicable therapeutic target.

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Titanium alloys have many advanced applications where they are subject to fatigue. Here, we compare the fatigue crack growth resistance and microstructures of TC4-DT alloys fabricated by wire-arc additive manufacturing (WAAM; sample S1) and in-situ rolled WAAM (sample S2) followed by quasi-β heat treatment. Sample S2 had superior fatigue crack growth resistance, which is mainly attributed to its finer defects and finer α phase. The critical size of the defects related to fatigue performance was calculated. The majority of defects in sample S2 were smaller than the critical size, while several coarse defects (∼1.91 mm) were observed in sample S1. Multiple secondary cracks could be detected near the fracture surface in sample S2, leading to long and tortuous fatigue crack propagation paths. Therefore, in-situ rolling can improve the fatigue properties of titanium alloys fabricated by additive manufacturing.

It has been reported that clustered miRNAs can be transcribed coordinately and exhibit similar functions by regulating the same targets. miR-1/133a and miR-206/133b are well-characterized miRNA clusters. However, the effect of these clusters on EGFR-TKI resistance is not clear. In this study, we demonstrated that lentivirus-mediated HGF overexpression was able to induce gefitinib resistance in non-small cell lung cancers with EGFR sensitive mutations. miR-1/133a and miR-206/133b clusters could overcome HGF induced gefitinib resistance. Furthermore, the clusters were more effective than individual miRNA. Transcriptome RNA sequencing and bioinformatics analysis revealed that multiple pathways, including ���EGFR tyrosine kinase inhibitor resistance��� pathway, were involved in anti-resistance mechanisms of miR-1/133a and miR-206/133b clusters. Western blotting results confirmed the inhibitory effect of miRNA clusters on MET expression and downstream pathway activation. In conclusion, miR-1/133a and miR-206/133b clusters are able to exhibit the synergetic effect on overcoming HGF-induced gefitinib resistance in NSCLC and the mechanisms are through targeting multiple genes related to gefitinib resistance.

Background: Small Cell Lung Cancer (SCLC) represents the most aggressive pulmonary neoplasm and is often diagnosed at late stage with limited survival, despite combined chemotherapies. The purpose of this study was to investigate the effect of anlotinib on SCLC and the potential molecular mechanisms. Methods: Cell viability was assessed by CCK-8 assay to determine the adequate concentration of anlotinib. Then, effects of anlotinib on cell apoptosis, cell cycle distribution, migration and invasion were analyzed by flow cytometry, PI staining, wound healing assay and transwell assay, respectively. The protein expression of c-met and ERK1/2 pathways in H446 cells were assessed by western blot analysis. Result: In this study, we found that anlotinib significantly reduced the cell viability of H446 cells, induced G2/M cell cycle arrest and decreased invasion and migration of H446 cells. Futhermore, we also found that anlotinib could suppress c-met signal transduction and activate the ERK1/2 pathway in H446 cells. More importantly, c-met was involved in the effects of anlotinib on migration and invasion in H446 cells. Conclusion: Taken together, our results demonstrated that anlotinib was a potential anticancer agent that inhibited cell proliferation, migration and invasion via suppression of the c-met pathway and activation of the ERK1/2 pathway in H446 cells.

Benefiting from the large-scale commercial use of 5G, smart campuses have attracted increasing research attention in recent years and are expected to revolutionize traditional campus activities. However, there are some obstacles that hinder the practical deployment of MEC (multi-access edge computing). First, traditional information infrastructures on campus cannot support latency-sensitive and computing-intensive smart applications, such as AR/VR, live interactive lectures and digital twin experiments. In addition, the mixture of old and new applications, isolated data islands and heterogeneous equipment management introduce more challenges. Moreover, the existing MEC framework proposed by ETSI and 3GPP cannot meet the specific deployment requirements of smart campuses, e.g., educational data security, real-time interactive applications, heterogeneous connections, and others. In this paper, we propose a 5G-based architecture for smart education information infrastructure; a new dedicated cloud architecture eMEC (educational multi-access edge computing) is defined. It consists of a UGW (universal access gateway) and an eMEP (educational multi-access edge computing platform), making it possible to satisfy education-specific requirements and long-term evolution. Furthermore, we implement the framework and conduct real-world field tests for eMEC in a university campus. Based on the framework and practical field tests, we also conduct a measurement study to unveil the spatial-temporal characteristics of mobile users in the smart campus and discuss exploiting them for better network performance. The experimental results show that the system achieves satisfactory performance in terms of both throughput and latency.

Tachyarrhythmia originating from around the coronary artery remains a great clinical challenge for electrophysiologists. This study explored the feasibility of using phosphorus-32 (P-32) as a new energy source to treat tachyarrhythmia around the coronary artery. Four points of the left ventricle of seven Bama mini-pigs and femoral artery of pig4-7 were selectively radiated in protocol by a self-designed radiation catheter. The voltage mapping showed a significantly lower voltage at the irradiated sites 30 days after the procedure compared with that before the irradiation for pigs2-7（1.77 vs 4.39，p＜0.001）. No obvious stenosis was observed in the coronary artery and femoral artery at the irradiation site. P-32 internal radiotherapy can change the electrical properties of cardiomyocytes, but it has few effects on the coronary and femoral artery. P-32 could be a complementary or alternative treatment for tachyarrhythmia originating from around the coronary artery.

Madecassic acid (MA), a triterpene compound isolated from Centella Asiatica herbs, has previously been shown to attenuate colitis induced by DSS in mice. In the present study, we address whether and how MA ameliorates colitis-associated colorectal cancer (CAC), which accounts for a considerable proportion of colorectal cancer.CAC was induced by AOM/DSS in mice, and MA was administered orally once a day. To identify the source cells of IL-17 and the target cells for MA reducing the expression of IL-17 in the colons of CAC mice, single-cell suspensions were prepared from the colons of CAC mice and analyzed by flow cytometry. An adoptive transfer experiment was performed to verify the importance of the decreasing γδT17 cell population in the anti-CAC effect of MA.Oral administration of MA reduced the burden and incidence of tumors in the CAC mice. MA decreased the number of MDSCs in the colon tissues of CAC mice and ameliorated anti-tumor immune responses. MA could prevent the migration of MDSCs by inhibiting the activation of γδT17 cells and the expression of chemokines. The population of activated-γδT17 cells in the tumor microenvironment of CAC mice positively correlated with the number of MDSCs and tumors as well as tumor load. Moreover, the anti-CAC effect of MA was significantly counteracted by the adoptive transfer of γδT17 cells.MA alleviates CAC by blocking the recruitment of MDSCs to increase the population of anti-tumor immune cells in tumor microenvironment via inhibition of the activation of γδT17 cells.

BackgroundHepatic Stellate Cell (HSC) represents a key factor in liver fibrosis. Early-stage liver fibrosis is still reversible and is intimately associated with the state of HSC. KLF4 has been shown to play a pivotal role in a wide array of physiological and pathological processes. MethodsIn this study, we examined the effect of Kruppel-like factor 4 (KLF4) on the proliferation, apoptosis and phenotype of HSC in resting state in human HSC LX-2 cells, and the role KLF4 plays in the maintenance of the resting state of HSC, with an attempt to provide an experimental basis for the diagnosis, treatment and prognosis evaluation of liver fibrosis. We designed a KLF4 lentiviral vector and a KLF4 shRNA lentiviral vector, to up-regulate and silence KLF4 expression in LX-2 cells by transfection. We examined LX-2 cell proliferation by plate cloning and CCK8 assay, flow cytometrically detected cell cycle distribution and cellular apoptosis rate and determined some quiescence and activation markers of HSC by Western blotting. ResultsOur result showed that E-cadherin and ZO-1, dubbed quiescent HSC markers, were significantly increased. N-cadherin while a-AMA, known as activated HSC marker, was significantly decreased. In contrast, cell proliferation and apoptosis rate were elevated in LX-2 cells whose KLF4 expression had been silenced. Conclusions Our results indicated that KLF4 inhibited the proliferation and activation of human HSC LX-2 and might be a key regulatory protein in the maintenance of quiescence of HSC and might serve as a target for the inhibition of hepatic fibrosis.

The exocyst, an evolutionarily conserved octomeric protein complex, has been demonstrated as an essential component for vesicle tethering during cell exocytosis, and participates in various physiological processes in the cell. Although subunits of the exocyst complex have been reported to be involved in the regulation of TGF-β induced cancer cell migration and epithelial-mesenchymal transition (EMT), the potential function of Sec3 in these regulated processes remains unclear. Here, we show that Sec3 knockdown abolishes TGF-β stimulated A549 lung cancer cell migration in vitro and causes defects in the regulated EMT process. In addition, we find that depletion of Sec3 significantly inhibits TGF-β stimulated Akt phosphorylation in A549 cells, whereas the increase of Smad2 phosphorylation is unaffected. Furthermore, replenishment of an RNAi-resistant form of Sec3 is shown to restore the defects of TGF-β induced cell migration, EMT and Akt signaling activation. In summary, our study provides evidence that Sec3 is involved in TGF-β induced cell migration and EMT processes, presumably through the regulation of PI3K/Akt signaling activation in A549 cancer cells.

Background COPD is characterized by progressive development of airflow limitation. Small airway functional and structural disease is considered pivotal in the pathology of early COPD. We used pulmonary function (PFT) and digital lung three-dimensional (3D) imaging technology to detect small airway functional and structural disease that applied for screening early COPD. Methods 136 patients underwent PFT and CT at the 903th Hospital of People Liberation Army from January 2018 to January 2019, including 90 in the observation group and 46 in the control group. We tested the associations between digital lung 3D imaging technology parameters and PFT. Then, we detected small airway functional and structural disease by comparing digital lung 3D imaging technology parameters and PFT between the observation and control groups. Results There were correlations between digital lung 3D imaging technology parameters and PFT. Furthermore, compared with generation 5 bronchus, there were significant correlations between FEV1/FVC with generation 7 WT (r = -0.592; p p p p p P

In this paper, a high-frequency frequency scanning antenna based on metasurface is designed. The antenna proposed here consists of three parts: an 1 × 16 unequal divider, 16 BJ900 waveguides and 160 metasurface. The proposed antenna is fed by a standard waveguide BJ900 with periodic metasurface covered on it. The working band is 76–81 GHz. To realize two-dimension beam scanning, an unequal divider is designed. After the final optimization, we can get from the simulation results that the working angle is 30° in both two dimension and the radiation efficiency can reach -0.1 dB. The total realized gain of the antenna can reach 20 dB.

Current in vivo selections for hematopoietic stem cell (HSC)-based gene therapy are drug dependent and not without risk of cytotoxicity or tumorigenesis. We developed a new in vivo selection system with the non-phosphorylatable Bcl2 mutant Bcl2T69A/S70A/S87A (Bcl2AAA), which makes in vivo selection drug independent and without risk of cytotoxicity or tumorigenesis. We demonstrated in HSC-transplanted mice that Bcl2AAA facilitated efficient in vivo selection in the absence of any exogenously applied drugs under both myeloablative and non-myeloablative conditioning. In mice transplanted with retrovirally transduced sca-1-positive bone marrow cells, the marked cell level increased from 26.38% of input transduced cells to 92.61 ± 0.95% of peripheral blood cells for myeloablative transplantation or to 37.82 ± 6.35% for non-myeloablative transplantation 6 months after transplantation. Bcl2AAA did not induce tumorigenesis and does not influence hematopoiesis and the function of the reconstituted blood system. However, the high-level constitutive expression of Bcl2AAA mediated by retroviral vector induced exhaustion of the marked cells after tertiary transplantation. Fortunately, low-level constitutive expression of Bcl2AAA driven by an internal promoter in lentiviral vector could both maintain the marked cell level (24.13 ± 5.27%, 27.17 ± 5.51%, 24.33 ± 5.08%, and 22.07 ± 4.44% for primary, secondary, tertiary, and quaternary recipients) and avoid the exhaustion of the marked cells even in quaternary recipients. Importantly, the low-level constitutive expression of Bcl2AAA did not induce tumorigenesis. Thus, the in vivo selection employing the low-level constitutive expression of Bcl2AAA provides a general platform which is relevant for widespread applications of gene therapy.

Objective To explore the protective function of vitamin D (VD)/vitamin D receptor (VDR) on the development of oral lichen planus (OLP) and elaborate the underling mechanism of it. Methods H&E staining, myeloid Peroxidase (MPO) assays, quantitative PCR (qPCR), western blotting and Elisa were used to test the human biopsies and serum. QPCR, western blotting, Elisa and siRNA transfection were also performed in LPS-induced keratinocytes to observe the functions of vitamin D and VDR. Results The lack of VDR in the diseased biopsies from OLP patients was associated with activated helper T-cell type 1 (Th1)-driven inflammatory response. Importantly, the status of serum 25-hydroxyvitamin D of OLP patients was reduced consistently. In a cultured cell model, 1,25(OH)2D3 could downregulate excessive production of pro-inflammatory factors induced by lipopolysaccharide (LPS) in keratinocyte HaCat cells. Mechanistically, even though LPS-induced cytokines in keratinocytes were inhibited both by nuclear factor-κB (NF-κB) inhibitor and by activator protein 1 (AP-1) inhibitor, VDR-dependent 1,25(OH)2D3 blocked the activation of phosphorylated-NF-κB p65 rather than c-Jun/c-Fos in the presence of LPS stimulation. Conclusion These results suggest that 1,25(OH)2D3 plays an anti-inflammatory role in OLP by mediating NF-κB signaling pathway but not AP-1 signaling pathway with a VDR-dependent manner, predicting vitamin D supplement may be a potential strategy for the OLP management. This article is protected by copyright. All rights reserved.

Background: Diabetes Mellitus (DM) accelerates progress of lung cancer. Hyperglycemia, a critical feature of DM, promotes lung cancer metastasis. Mogroside V is a triterpenoid glycoside from Siraitia grosvenorii. Interestingly, mogroside V not only plays an anti-diabetic role, but also has anti-tumor effects. Objective: In this study, we investigated the metastatic efficiency of mogroside V in lung cancer cells cultured in hyperglycemia. Methods: Two lung cancer cell lines-A549 and H1299 were cultured in normoglycemia (5.5mM glucose) and hyperglycemia (25mM glucose). Cellular proliferation was tested by MTT, invasion was examined by transwell assay, migration was measured by wound healing assay, cytoskeleton was stained by Phalloidin-TRITC and the expressions of EMT markers and Rho-GTPase family protein were detected by western blot. Results: Hyperglycemia promoted the invasion and migration of A549 and H1299 cells compared with normoglycemia. Mogroside V inhibited the hyperglycemia-induced invasion and migration. Hyperglycemia promoted epithelial-mesenchymal transition (EMT), while mogroside V could reverse this process through up-regulating E-Cadherin expression and down-regulating N-Cadherin, Vimentin, Snail expressions. Furthermore, mogroside V fractured microfilaments and reduced Rho A, Rac1, Cdc42 and p-PAK1 expressions under hyperglycemic conditions. Conclusion: These results suggest that mogroside V inhibits hyperglycemia-induced lung cancer cells migration and invasion through reversing EMT and damaging cytoskeleton.

To explore the safety and feasibility of the combined medial and caudal approach in laparoscopic D3 lymphadenectomy plus complete mesocolic excision(CME) for right hemicolectomy in the treatment of right hemicolon cancer complicated with incomplete ileus.Clinical data of 65 patients with incomplete obstructive right-sided colon cancer (T1 to 4M0) diagnosed by abdominal CT enhanced scan or MRI and/or electric colonscope undergoing laparoscopic right hemicolectomy (D3 lymphadenectomy + CME) at Department of Emergency Medicine and Department of Gastrointestinal Surgery from June 2014 to June 2017 were retrospectively analyzed. Among them, 33 patients received the combined medial and caudal approach (combined medial and caudal approach group) and the other 32 patients received the cephalo medial-to-lateral approach (cephalo medial-to-lateral approach group). The operation highlights of the combined medial and caudal approach group were as follows: (1) The superior mesenteric vein (SMV) was first identified and exposed using the combined medial and caudal approach, and lymph node dissection along the anterior and right of SMV was performed. (2) With horizontal part of duodenum as landmarks, the dorsal mesenteric membrane of terminal ileum was opened by caudal-to-cranial approach, and right retroperitoneal space along the Toldt's space was separated. The anterior of pancreatic head and the right Toldt's space were then exposed. (3) Finally using medial-to-lateral approach, the roots of ileocolic vessels, middle colic vessel and right colic vessel were disconnected and ligated along the left border of SMV. The right branch of gastrocolic trunk of Henle was ligated and lymph node dissection along SMV was performed again. Patients in cephalo medial-to-lateral approach group underwent conventional operation. Baseline information, intraoperative blood loss, operation time, number of harvested lymph nodes, proportion of no less than 12 harvested lymph nodes per case, postoperative hospital stay and postoperative morbidity in both groups were analyzed and compared.Thirty-eight males and 27 females with age of 31 to 72 (56.8±11.7) years were enrolled in this study. There was no significant difference in baseline information between combined medial and caudal approach group and cephalo medial-to-lateral approach group(all P0.05). Intraoperative blood loss [(106.5±24.5) ml vs. (308.4±27.1) ml, t=-31.501, P=0.000] was significantly less, and operative time [(176.3 ± 18.0) minutes vs. (208.4 ± 47.3) minutes, t=-3.602, P=0.001] was significantly shorter in the combined medial and caudal approach group. The proportion of no less than 2 harvested lymph nodes per case [87.9%(29/33) vs. 84.4%(27/32)], the number of harvested lymph nodes (22.5±8.9 vs. 21.5± 7.6), postoperative morbidity of complication [6.1%(2/33) vs. 12.5%(4/32)] and postoperative hospital stay [(11.9±1.5) days vs. (13.4±4.4) days] were not significantly different between the two groups(all P0.05).The combined medial and caudal approach in laparoscopic right hemicolectomy (D3+CME) in the treatment of incomplete obstructive right-sided colon cancer is safe and feasible, and has advantages of less intraoperative blood loss and shorter operation time compared to the cephalo medial-to-lateral approach.

Apolipoprotein B plays a central role in lipoprotein metabolism. Many studies have evaluated the association between Apolipoprotein B gene polymorphisms (XbaI, EcoRI, SpIns/Del, MspI) and the risk for coronary artery disease and myocardial infarction. However, the results remain inconsistent, particularly among different populations. To more precisely determine the association between Apolipoprotein B gene polymorphisms and coronary artery disease/myocardial infarction risk, we performed a meta-analysis via a comprehensive search of electronic databases (up to February 1st, 2015), odds ratios (OR) and 95 % confidence intervals were calculated using a fixed or random effect model. A total of 47 studies, with 9411 coronary artery disease/myocardial infarction cases and 9082 controls, were included in this meta-analysis. The combined results revealed significant associations between an increased risk of coronary artery disease/myocardial infarction and EcoRI (AA vs GG: OR 1.511, 95 % confidence interval (CI) 1.098, 2.078) and SpIns/Del (DD vs II: OR 1.331, 95 % CI 1.064, 1.665) alleles in the general population. In a subgroup analysis stratified by ethnicity, the T allele of the XbaI variant was associated with a decreased risk in Caucasians, whereas it was associated with an increased risk among the East Asian population. No significant correlation was detected between the A allele of the MspI variant and the coronary artery disease/myocardial infarction risk in either the general population or any ethnic subgroup. The results of our study suggest that Apolipoprotein B gene polymorphisms may affect the coronary artery disease/myocardial infarction susceptibility and these effects may display notable discrepancies among different populations.

Epithelial-mesenchymal transition (EMT) is one of the most important mechanisms in the initiation and promotion of cancer cell metastasis. The phosphoinositide 3-kinase (PI3K) signaling pathway has been demonstrated to be involved in TGF-β induced EMT, but the complicated TGF-β signaling network makes it challenging to dissect the important role of PI3K on regulation of EMT process. Here, we applied optogenetic controlled PI3K module (named ‘Opto-PI3K’), which based on CRY2 and the N-terminal of CIB1 (CIBN), to rapidly and reversibly control the endogenous PI3K activity in cancer cells with light. By precisely modulating the kinetics of PI3K activation, we found that E-cadherin is an important downstream target of PI3K signaling. Compared with TGF-β treatment, Opto-PI3K had more potent effect in down-regulation of E-cadherin expression, which was demonstrated to be regulated in a light dose-dependent manner. Surprisingly, sustained PI3K activation induced partial EMT state in A549 cells that is highly reversible. Furthermore, we demonstrated that Opto-PI3K only partially mimicked TGF-β effects on promotion of cell migration in vitro. These results reveal the importance of PI3K signaling in TGF-β induced EMT, suggesting other TGF-β regulated signaling pathways are necessary for the full and irreversible promotion of EMT in cancer cells. In addition, our study implicates the great promise of optogenetics in cancer research for mapping input-output relationships in oncogenic pathways.

Current in vivo selections for hematopoietic stem cell (HSC)-based gene therapy are drug dependent and not without risk of cytotoxicity or tumorigenesis. We developed a new in vivo selection system with the non-phosphorylatable Bcl2 mutant Bcl2

Objective We performed a prospective observational study to explore the prognostic value of plasma galectin-3, a biomarker for fibrosis and inflammation, in Chinese patients with heart failure (HF). Methods and results Galectin-3, N-terminal pro B-type natriuretic peptide (NT-proBNP) and other clinically related variables were measured in consecutive HF patients in Beijing Hospital. Specifically, galectin-3 was detected by an enzyme-linked immunosorbent assay. The primary end point was major adverse cardiac events (MACE), including all-cause mortality or readmission at the end of follow-up. The secondary end point was all-cause mortality. The adjusted hazard ratio (HR) was determined by COX regression model. In total, 272 patients were included in this study with a median age of 77 years, of whom 55.9% were male. During a median follow-up of 584 (415-813) days, 53 patients (19.5%) died and 103 patients (37.9%) died and/or required readmission. Plasma galectin-3 levels by tertiles were associated with an increased risk for the primary end point (P 0.001). Kaplan-Meier survival curves showed that the third tertile of galectin-3 was associated with an increased rate of MACE, compared with the first and second tertiles, with the log rank P 0.001 and P = 0.001, respectively. In addition, the multivariate COX regression model showed that the highest tertile of galectin-3 was associated with an increased risk for MACE (HR =2.13, 95% confidence interval: 1.24-3.68, P = 0.006), compared with the lowest tertile after adjustment for age, NT-proBNP, creatinine, uric acid, albumin, haemoglobin, and estimated glomerular filtration rate (eGFR). Conclusion Plasma galectin-3 is an independent predictor of all-cause mortality and/or readmission in Chinese patients with HF.

To explore the correlation between the clinical indicators of patients with advanced lung cancer and lung infectious agent, 370 cases (including 222 patients with Candida, 148 patients with Klebsiella) which have 21 clinical indicators was subjected to data mining in this paper. We used random forest-recursive feature selection (RF-RFE) algorithm to select features, and Random Forest (RF), Support Vector Machine (SVM) and Decision Tree (DT) were used to classify the two infections respectively, and the corresponding classification error was estimated by 10 times 10 fold cross-validation. The result of the experiment shows that the classification model has high specificity with Klebsiella and RF has a better performance on classification classifying Candida and Klebsiella.

Background: Growth differentiation factor-15 (GDF-15), a biomarker associated with remodeling, oxidative stress and inflammation, has been used to stratify heart failure (HF) patients. However, its prognostic value in Chinese HF patients is still unknown. Methods: GDF-15 levels were examined on admission in 272 consecutive HF patients in Beijing Hospital (a Chinese tertiary medical center) by a commercial enzyme-linked immunosorbent assay. We recorded the incidence of all-cause mortality and/or readmission for HF during a median follow-up period of 558 days. Patients were stratified according to the tertiles of GDF-15. Results: Fifty-three (19.5%) patients died and 103 (37.9%) patients had major adverse cardiac events (MACE) which included the composite outcome of all-cause mortality or readmission for HF at the end of follow-up. Kaplan-Meier survival curves showed that the third tertile of GDF-15 was associated with increased rate of all-cause mortality (compared with the first and second tertiles, log rank p = 0.001 and 0.001, respectively) or MACE (compared with the first and second tertiles, log rank p = 0.002 and p < 0.001, respectively). In addition, multivariate Cox regression model showed that the highest tertile of GDF-15 was independently associated with increased risk of all-cause death (hazard ratio = 5.95, 95% confidence interval 1.88–18.78, p = 0.002) compared with the lowest tertile after adjustment for related clinical variables such as age, renal function or N-terminal pro-B-type natriuretic peptide. Conclusions: Plasma GDF-15 is an independent predictor of all-cause mortality in Chinese patients with HF. It may potentially be used to stratify and prognosticate HF patients.

The present study aimed to determine the levels of cathepsin B (cath B), cathepsin L (cath L), cystatin C, urokinase plasminogen activator (u-PA) and urokinase plasminogen activator receptor (u-PAR) in the sera of patients with lung cancer compared to healthy controls using ELISA. Concomitantly, the relationship between the components and clinicopathological prognosis was analyzed. The study included 30 healthy volunteers and 105 lung cancer patients. Blood samples were collected and cath B, cath L, cystatin C, u-PA and u-PAR measurements were made using ELISA. Results showed that the levels of cath B, cath L, cystatin C, u-PA and u-PAR were significantly higher in the patient group compared to the healthy controls. The significance was marked for cath B and mild for u-PAR in correlation with lymph node metastasis. There was no significance for other parameters. Notably, patients with a combination of high cystatin C and high cath B levels had significantly lower survival probability as compared to those with cystatin C(+)/cath B(-) or with cystatin C(-)/cath B(-). Similarly, patients with a combination of high u-PA and u-PAR experienced significantly shorter survival. Furthermore, the univariate analysis revealed that cath B, u-PAR, lymph node metastases, stage and grade were related to survival. However, findings of the multivariate Cox analysis indicated that the sera levels of cath B, u-PAR and lymph node metastases may serve as independent prognostic variables in patients with lung cancer.

Rationale: About 50% of patients with a diagnosis of nonsmall cell lung carcinoma exhibit metastatic disease at the time of diagnosis. The preferential sites of extrapulmonary spread are the lymph nodes, liver, brain, adrenal glands, and bones; gastrointestinal tract perforation secondary to metastatic lung cancer is extremely rare. Patient concerns: A 60-year-old male nonsmoker patient presented with a 20-day history of facial, neck, and right upper limb edema. Physical examination revealed a 3.5 cm mass in his right chest. Computed tomography (CT) revealed a 4 cm mass near the right lung hilum. Diagnosis: Biopsy of the right chest wall mass revealed low differentiated lung adenocarcinoma. Additionally, retroperitoneal lymphadenopathy, pericardial effusion, metastases in the mediastinum, bilateral adrenal gland, and right thoracic wall nodule, as well as multiple bone metastases were also found. Interventions: Since the patient was diagnosed with multiple metastatic lung cancer, chemotherapy was started. One week after chemotherapy, he experienced a sudden acute abdominal pain. Abdominal CT examination indicated the possibility of intestinal perforation. Hence, the patient underwent an emergency operation. During the surgical procedure, 2 perforations of size 1×1 cm2 were discovered at 110 cm and 140 cm of the jejunum from Treitz's ligament. Then, an intestinal resection and end-to-end anastomosis were performed. The pathological diagnosis of the resected specimen revealed that it was a metastatic lung adenocarcinoma of small intestine. Outcomes: The patient died 10 days after operation and 19 days following the cancer diagnosis due to septic shock. Lessons: Gastrointestinal tract metastasis from the lung is uncommon, but the survival rate is extremely low; therefore, it should be considered as a possibility in patients who present with any of the gastrointestinal symptoms.

A combination of extrinsic hematopoietic growth regulators, such as stem cell factor (SCF), interleukin (IL)-3 and IL-6, can induce division of quiescent hematopoietic stem cells (HSCs), but it usually impairs HSCs' self-renewal ability. However, intrinsic negative cell cycle regulators, such as p18INK4c (p18) p27Kip1 (p27) and MAD1, can regulate the self-renewal of HSCs. It is unknown whether the removal of some extrinsic regulators and the knockdown of intrinsic negative cell cycle regulators via RNA interference (RNAi) induce ex vivo expansion of the HSCs. To address this question, a lentiviral vector-based RNAi tool was developed to produce two copies of small RNA that target multiple genes to knockdown the intrinsic negative cell cycle regulators pl8, p27 and MAD1. Colony-forming cells, long-term culture-initiating cells (LTC-IC) and engraftment assays were used to evaluate the effects of extrinsic and intrinsic regulators. Results showed that the medium with only SCF, but without IL-3 and IL-6, could maintain the sca-1+c-kit+ bone marrow cells with high LTC-IC frequency and low cell division. However, when the sca-1+c-kit+ bone marrow cells were cultured in a medium with only SCF and simultaneously knocked down the expression of pl8, p27 and MAD1 via the lentiviral vector-based RNAi, the cells exhibited both high LTC-IC frequency and high cell division, though engraftment failed. Thus, the simultaneous knockdown of pl8, p27 and MAD1 with a medium of only SCF can induce LTC-IC expansion despite the loss of engraftment ability.

Background: Human adenovirus type 7 (HAdV7) is globally attracting great concern as its high morbidity and severity in respiratory diseases, especially in Asia. Objective: To investigate the clinical and epidemiologic characteristics of HAdV7 infection outbreak in East China. Methods: The clinical samples were collected from the patients of an ARD outbreak in East Chinafor the detection of causative pathogens by multiplex PCR. The molecular type of human adenovirus isolates were identified by sequencing and homologous comparison based on their hexon genes. The spatiotemporal dynamics of global HAdV7 was investigated using the phylogenetic and phylogeographic analyses. Total 67 referenced HAdV7 hexon sequences (>800 bp) from GenBank were selected for constructing the maximum likelihood tree by MEGA 5.1.0, grouped according to the tree topology for the further migration analysis by PAUP* 4.0 and MigraPhyla 1.0 b to understand the transmission patterns of HAdV7 in global epidemics. Results: The results showed HAdV7 as the causative pathogen in this outbreak, and the outbreak strains had the hexon sequences highly identical with the isolates in Shaanxi (2012). The origin of HAdV7 was inferred as California, meanwhile a total of 21 migration routes were acquired. HAdV7 in this outbreak was statistically proven dispersed from Shaanxi province (2012). Conclusions: The analyses of epidemiology and transmission pattern of HAdV7 would not only enrich the molecular biological basic database but also provide theoretical basis for HAdV7 prevention and control strategy.

To fabricate an innovative scaffold for lung cancer cell culture and establish a three-dimensional lung cancer model in vitro, and to reveal the differences in biological functions of lung cancer cells under the two-dimensional and three-dimensional culture conditions.We chose agarose and alginate as the scaffold materials, and 3D printing technique was applied to construct cell culture scaffold. 95D cells were co-cultured with this scaffold. The differences of cell morphology, proliferation ability, protein expression, etc. in the cells cultured under 2D and 3D cultural conditions were evaluated by light microscopy using HE staining, MTT assay, scanning electron microscopy, and Western blot analysis.Cells cultured in 2D wells displayed a spindle and polygonal morphology, whereas those grown in the 3D culture aggregated into spheroids, which invaded, migrated and disseminated into the surrounding scaffold. MTT assay showed that the proliferation rates of the 3D-cultured cells for 2-6 days were significantly lower than, but those cultured for 8-9 days were significantly higher than that of the 2D-cultured cells, indicating that proliferative activity of the cells grown in 2D cultures for 8-9 days was inhibited. In contrast, cells grown on 3D scaffolds still maintained a higher proliferation. The Western blot assay showed that the expression of Cdc42, p53, mTOR were significantly down-regulated in 3D scaffold-cultured group (0.529±0.103, 0.820±0.038 vs. 1.967±0.066), compared with that of the 2D-cultured group (3.063±0.139, 1.738±0.122 vs. 2.472±0.151) (P0.05 for all), while the expression of MMP-2 was up-regulated in the 3D-cultured cells (1.110±0.029), significantly higher than that of the 2D-cultured cells (0.017±0.001) (P0.05).The cell morphology, proliferation and associated protein expression of lung cancer cells in 3D-culture systems are distinctively different as compared to those of the 2D-cultural cells. 3D-bioprinted agarose-alginate scaffold can better mimic the growth microenvironment of lung cancer in vivo and may provide a promising model for lung cancer research in vitro.