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The relationship between albumin corrected anion gap (ACAG) and mortality in acute kidney injury (AKI) patients who received continuous renal replacement therapy (CRRT) has not been investigated in any previous studies. This study aimed to investigate the relationship between ACAG at CRRT initiation and all-cause mortality among these patients in the intensive care unit (ICU). Patients diagnosed with AKI and treated with CRRT in the ICU from the Medical Information Mart for Intensive Care-IV version 1.0 (MIMIC IV) database and Huzhou Central Hospital were retrospectively enrolled. Participants were divided into two groups: the normal ACAG group (12–20 mmol/L) and high ACAG group (> 20 mmol/L). The Kaplan–Meier method and log-rank test were used to compare the survival rate between the two groups. Restricted cubic spine (RCS) and Cox proportional-hazards models were utilized to analyze the relationship between ACAG at CRRT initiation and ICU all-cause mortality of these patients. A total of 708 patients met the inclusion criteria in the study. The all-cause mortality of these patients during ICU hospitalization was 41.95%. Patients in the high ACAG group exhibited significantly higher ICU all-cause mortality rate than patients in the normal ACAG group (all P χ12 = 13.620, χ22 = 12.460, both P 20 mmol/L) levels at the time of CRRT initiation in the MIMIC IV database and Huzhou Central Hospital were significantly correlated with ICU all-cause mortality after adjusting multiple potential confounding factors with hazard ratios of 2.852 (95% CI 1.718–4.734) and 2.637(95% CI 1.584–4.389), respectively. In critically AKI patients who undergo CRRT, higher ACAG (> 20 mmol/L) level at the initiation of CRRT was significantly correlated with ICU all-cause mortality. Therefore, clinicians should pay more attention to those patients with a higher ACAG value.

High-dose ascorbate confers tubular mitophagy responsible for septic acute kidney injury (AKI) amelioration, yet its biological roles in immune regulation remain poorly understood.

Ascorbate (Vitamin C) has been proposed as a promising therapeutic agent against sepsis in clinical trials, but there is little experimental evidence on its anti-septic efficacy. We report that Toll-like receptor 4 (TLR4) activation by LPS stimuli augments ascorbate uptake in murine and human tubular cells through upregulation of two ascorbate transporters SVCT-1 and -2 mediated by Fn14/SCFFbxw7α cascade. Ascorbate restriction, or knockout of SVCT-1 and -2, the circumstance reminiscent to blockade of ascorbate uptake, endows tubular cells more vulnerable to the LPS-inducible apoptosis, whereas exogenous administration of ascorbate overrides the ruin execution, for which the PINK1-PARK2, rather than BNIP3-NIX axis is required. Ascorbate increases, while SVCT-1 and -2 knockout or ascorbate restriction dampens tubular mitophagy upon LPS stimuli. Treatment of endotoxemic mice with high-dose ascorbate confers mitophagy and substantial protection against mortality and septic acute kidney injury (AKI). Our work provides a rationale for clinical management of septic AKI with high doses of ascorbate.

Background There is a scarcity of studies that covers the relationship between the red cell distribution width (RDW) and the prognosis of cardiac arrest (CA) patients. Moreover, the prognostic value of the changes in RDW during intensive care unit (ICU) hospitalization for CA patients is not investigated. This study focuses on the correlation between RDW measures at ICU admission and RDW changes during ICU hospitalization and the prognosis of CA patients. Methods A retrospective cohort study is used to collect clinical characteristics of CA patients (>18years) that are on their first admission to ICU with RDW data measured from the Medical Information Mart for Intensive Care-IV database. The primary outcomes are 30- and 90-day all-cause mortality. A multivariate Cox regression model is applied to test whether the RDW represents an independent risk factor that affects the all-cause mortality of these patients. Meanwhile, the dose-response relationship between the RDW and the mortality is described by the restricted cubic spine (RCS). Results A total of 1138 adult CA patients are included in this study. Compared to the survivor group, non-survivors show higher level of RDW. The Kaplan-Meier survival curve indicates that the cumulative survival rate of CA patients at 30 and 90 days decreases gradually as the RDW on ICU admission increases (log-rank test, χ 1 2 =46.460,χ 2 2 =47.210, both p-values=0.4%) is associated with decreased the 30 and 90 days cumulative survival rates (χ 1 2 =23.700,χ 2 2 =25.390, both p-values=0.4%) are independent risk factors for death at 30- and 90-day on CA patients. RCS illustrates that there is a non-linear relationship between the RDW on ICU admission and the increased risk of mortality of CA patients at 30 (χ 1 2 =11.990, p-value=0.007) and 90 days (χ 2 2 =12.340, p-value=0.006). Conclusions Elevated RDW levels on ICU admission and rising RDW during ICU hospitalization are powerful predictors of all-cause mortality for CA patients at 30 and 90 days, and they can be used as potential clinical biomarkers to predict the bad prognosis of these patients.

Tubular damage initiated by inflammatory response and ischemic/hypoxic stress is a hallmark of septic acute kidney injury (AKI), albeit the molecular mechanism coupling the two events remains unclear. We investigated the intrinsic nature of tubular damage with respect to inflammatory/hypoxic stress during septic AKI. Methods: The apoptotic response of tubular cells to LPS stimuli was analyzed before and after hypoxia exposure. Cellular ubiquitination, co-immunoprecipitation, GST-pulldown, in vitro protein kinase assay, immunofluorescence and CRISPR technology were adopted to determine the molecular mechanism underlying this process. In vivo characterization was performed in wild-type and DAPK1-/- mice models of cecal ligation and puncture (CLP). Results: We found that the MyD88-dependent inflammatory response couples to tubular damage during LPS stimuli under hypoxia in a Fn14/SCFFbxw7α-dispensable manner via recruitment of caspase-8 with TRIF-RIP1 signalosome mediated by DAPK1, which directly binds to and phosphorylates Pellino1 at Ser39, leading to Pellino1 poly-ubiquitination and turnover. Either pharmacological deactivation or genetic ablation of DAPK1 makes tubular cells refractory to the LPS-induced damage in the context of hypoxia, while kinase activity of DAPK1 is essential for ruin execution. Targeting DAPK1 effectively protects mice against septic AKI and potentiates the efficacy of a MyD88 homodimerization inhibitor, ST2825. Conclusion: Our findings provide a rationale for the mechanism whereby inflammation intersects with hypoxic tubular damage during septic AKI through a previously unappreciated role of DAPK1-inducible Ser39 phosphorylation in Pellino1 turnover and underscore that combined targeting DAPK1 and MyD88 might be a feasible strategy for septic AKI management.

Background Hypereosinophilia (HE) is a heterogeneous disease of unknown etiology in which tissue and organ injury is inflicted by excess numbers of circulating or infiltrating eosinophils. Herein, we describe a patient with rare organ damage due to HE and review the pertinent literature. Case summary A 43 year-old Chinese man with a 13-year history of eosinophilia and shortness of breath for 7 d presented to our hospital. During the course of his illness, the patient variably presented with gastrointestinal symptoms, eczema, vitiligo, mastitis, joint symptoms, nephrotic syndrome, and interstitial pneumonia. The chronic mastitis proved burdensome, necessitating bilateral mastectomy. HE was diagnosed by repeat bone marrow biopsy, and a kidney biopsy showed focal segmental glomerulosclerosis. Intermittent steroidal therapy is typically initiated to relieve such symptoms, although relapse and organ involvement often ensue once treatment is withdrawn. We administered methylprednisolone sodium succinate (40 mg/d) intravenously for 3 d, followed by oral tablets at the same dose. Subsequent computed tomography (CT) of the chest CT showed relative improvement of the interstitial pneumonia. The patient is currently on a continuous regimen of oral steroid, and his condition is stable. Conclusion HE is heterogeneous condition. This is the first reported case of bilateral mastectomy in a male patient with longstanding HE.

Pancreatic cancer (PC) is a great health burden to patients owing to its poor overall survival rate. Long noncoding RNAs (lncRNAs) interact with microRNAs (miRs) to participate in tumorigenesis. Therefore, we aim to uncover the role and related mechanism of LINC00473 in PC through the modulation of miR-195-5p and programmed death-ligand 1 (PD-L1). Increased LINC00473 and PD-L1 but declined miR-195-5p were determined in PC tissues and cell lines, and it was found that LINC00473 mainly situated in the cytoplasm. Also, miR-195-5p was verified to bind with both LINC00473 and PD-L1. Next, with the aim to examine the ability of LINC00473, miR-195-5p, and PD-L1 on the PC progression, the expression of LINC00473, miR-195-5p and PD-L1 were altered with mimics, inhibitors, overexpression vectors or siRNAs in PC cells and cocultured CD8+ T cells. It was demonstrated that LINC00473 sponged miR-195-5p to upregulate PD-L1 expression. More important, the obtained results revealed that LINC00473 silencing or miR-195-5p upregulation elevated the expression of Bcl-2 associated X protein (Bax), interferon (IFN)-γ, and interleukin (IL)-4 but reduced the expression of B-cell lymphoma-2 (Bcl-2), matrix metalloproteinase (MMP)-2, MMP-9, and IL-10, thus inducing the enhancement of the apoptosis as along with the inhibition of proliferation, invasion, and migration of the PC cells. LINC00473 silencing or miR-195-5p elevation activated the CD8+ T cells. Taken together, LINC00473 silencing blocked the PC progression through enhancing miR-195-5p-targeted downregulation of PD-L1. This finding offers new therapeutic options for treating this devastating disease.

Acute kidney injury (AKI) initiated by sepsis remains a thorny problem despite recent advancements in its clinical management. Having been found to be activated during AKI, fibroblast growth factor-inducible molecule 14 (Fn14) may be a potential therapeutic target because of its involvement in the molecular basis of injury. Here, we report that LPS induces apoptosis of mouse cortical tubule cells mediated by Fn14, for which simultaneous Toll-like receptor (TLR)4 activation is required. Mechanistically, TLR4 activation by lipopolysaccharide, through disassociating E3 ligase SCFFbxw7α from Fn14, dismantles Lys48-linked polyubiquitination of Fn14 and stabilizes it. Pharmacological deactivation of Fn14 with monoclonal antibody ITEM-2 provides effective protection against lethal sepsis and AKI in mice. Our study underscores an adaptive mechanism whereby TLR4 regulates SCFFbxw7α-dependent Fn14 stabilization during inflammatory tubular damage and further supports investigation of targeting Fn14 in clinical trials of patients with septic AKI.

The immunosuppressive, inflammatory microenvironment orchestrated by neutrophil extracellular traps (NETs) plays a principal role in pathogenesis of sepsis. Fibroblast growth factor-inducible molecule 14 (Fn14) has been established as a potential target for septic acute kidney injury (AKI), making further therapeutic benefits from combined NETs and Fn14 blockade possible. Methods: The concurrence of NETs and Fn14 in mice and patients with septic AKI were assessed by immunofluorescence, immunohistochemistry, enzyme-linked immunosorbent assay (ELISA) and in silico studies. Survival, histopathological and biochemical analyses of wild-type and PAD4-deficient CMV-Cre; PAD4 fl/fl mice with septic AKI were applied to evaluate the efficacy of either pharmacological or genetic NETs interruption in combination with Fn14 blockade. Molecular mechanisms underlying such effects were determined by CRISPR technology, fluorescence-activated cell sorter analysis (FACS), cycloheximide (CHX) pulse-chase, luciferase reporter and chromatin immunoprecipitation (ChIP) assay. Results: NETs formation is concurred with Fn14 upregulation in murine AKI models of abdominal, endotoxemic, multidrug-resistant sepsis as well as in serum samples of patients with septic AKI. Pharmacological or genetic interruption of NETs formation synergizes with ITEM-2, a monoclonal antibody (mAb) of Fn14, to prolong mice survival and provide renal protection against abdominal sepsis, the effects that could be abrogated by elimination of macrophages. Interrupting NETs formation predominantly perpetuates infiltration and survival of efferocytic growth arrest-specific protein 6+ (GAS6+) macrophages in combination with ITEM-2 therapy and enhances transcription of tubular cell-intrinsic Fn14 in a DNA methyltransferase 3a (DNMT3a)-independent manner through dismantling the proteasomes-mediated turnover of homeobox protein Hox-A5 (HOXA5) upon abdominal sepsis challenge or LPS stimuli. Pharmacological NETs interruption potentiates the anti-septic AKI efficacy of ITEM-2 in murine models of endotoxemic and multidrug-resistant sepsis. Conclusion: Our preclinical data propose that interrupting NETs formation in combination with Fn14 mAb might be a feasible therapeutic strategy for septic AKI.

Jinou Wang,1 Chang Liu,1 Xiaoying Chang,1 Yafei Qi,1 Zhi Zhu,2 Xianghong Yang1 1Department of Pathology, Shengjing Hospital of China Medical University, Shenyang, China; 2Department of Surgical Oncology, The First Hospital of China Medical University, Shenyang, China Background: Peritoneal metastasis frequently occurs in patients with advanced ovarian cancer and is the main basis for a poor prognosis. The mechanism underlying preferential ovarian cancer spread to the peritoneum is not well understood. Methods: Herein, we investigated the significance and mechanism underlying fibrosis of mesothelial cells promoting peritoneal implantation of ovarian cancer. We have assessed themesothelial cell fibroblast transformation process in peritoneal tissues of omentum and fibrotic mesothelial cell release of chemokines to promote dissemination by scanning electron microscopy, ELISA, Western blot, and Transwell chamber assay. Results: We showed that the fibrosis of mesothelial cells exists in the peritoneum of ovarian cancer patients with peritoneal metastasis. Fibrosis of the mesothelial cells was induced by TGF-β1, which upregulates the CXCL12–CXCR4 and CXCL16–CXCR6 axes of mesothelial cells. Conclusion: CXCL12–CXCR4 and CXCL16–CXCR6 may be important signaling pathways closely involved in peritoneal metastasis of ovarian cancer that require further investigation. The findings may lead to developing alternative strategies aimed at preventing and treating the metastasis of ovarian cancer. Keywords: ovarian cancer, peritoneal, mesothelial cell, fibrosis

Yuemei Shan,1,2 Wei Cao,1 Tao Wang,1 Guiyang Jiang,3Yong Zhang,4 Xianghong Yang1 1Department of Pathology, ShengjingHospital of China MedicalUniversity, Shenyang, China; 2Department of Applied Technology, Instituteof Technology of China Medical University, Shenyang, China; 3Department of Pathology, First Affiliated Hospital and College ofBasic Medical Sciences, China MedicalUniversity, Shenyang, China; 4Department of Pathology, Cancer Hospital of China Medical University, Shenyang, China Background: Zinc finger protein 259 (ZNF259) is known to play essential roles in embryonic development and cell cycle regulation. However, its expression pattern and clinicopathological relevance remain unclear. Materials and methods: A total of 114 lung cancer specimens were collected. The ZNF259 expression was measured between the lung cancer tissues and the adjacent normal lung tissues by immunohistochemical staining and Western blotting. Moreover, the correlation of ZNF259 expression with clinicopathological features was analyzed in 114 cases of lung cancer. Additionally, ZNF259 was depleted in the lung cancer cells in order to analyze its effect in the lung cancer. Results: Immunohistochemical staining of 114 lung cancer specimens revealed significantly lower ZNF259 expression in lung cancer tissues than in adjacent normal lung tissues (53.5% vs 71.4%, P

The study was conducted for comparing the effects of 12 DNA damage response gene mutations (CHEK1, CHEK2, RAD51, BRCA1, BRCA2, MLH1, MSH2, ATM, ATR, MDC1, PARP1, and FANCF) on the overall survival (OS) of breast cancer (BC) patients. We searched the Cancer Genome Atlas (TCGA) database from inception to September 2016. Studies that investigated the association between 12 DNA damage responses related genes and BC consolidated into this Network meta-analysis, by comparing directly or indirectly to evaluate the hazard rate (HR) value and the surface under the cumulative sequence ranking curves (SUCRA). In total four articles were involved. Our results demonstrated 12 DNA damage response gene mutations were associated to the poor prognosis of BC patients (CHEK1: HR = 9.9, 95%CI = 3.6-26.0; CHEK2: HR = 6.9, 95%CI = 3.1-15.0; RAD51: HR = 5.8, 95%CI = 2.2-15.0; BRCA1: HR = 2.8, 95%CI = 1.3-6.1; BRCA2: HR = 3.9, 95%CI = 2.0-7.7; MLH1: HR = 11.0, 95%CI = 3.4-33.0; MSH2: HR = 6.5, 95%CI = 2.1-20.0; ATM: HR = 5.6, 95%CI = 2.6-12.0; ATR: HR = 2.9, 95%CI = 1.3-6.9; MDC1: HR = 15.0, 95%CI = 5.0-45.0; PARP1: HR = 3.4, 95%CI = 1.8-6.6; FANCF: HR = 6.0, 95%CI = 1.8-20.0). SUCRA results revealed that the mutation of MDC1 gene was related to the worst prognosis in patients with BC (SUCRA = 17.32%). DNA damage response gene mutations were associated to the poor prognosis in patients with BC and the BC patients with MDC1 gene mutation had the worst prognosis. J. Cell. Biochem. 118: 4728-4734, 2017. © 2017 Wiley Periodicals, Inc.

Fibroblast growth factor-inducible molecule 14 (Fn14) plays a principal role in triggering tubular damage during septic acute kidney injury (AKI). Here, we explore the mechanism underlying Fn14 deregulation in septic AKI. We identify Fn14 as a bona fide target of miR-19a, which directly binds to 3′ UTR of Fn14 for repression independent of cylindromatosis (CYLD), the deubiquitinase (DUB) downstream of miR-19a, and thereby antagonizes the LPS-induced tubular cell apoptosis. Genetic ablation of Fn14, but not of CYLD, abolishes the ability of miR-19a to antagonize the tubular apoptosis by lipopolysaccharide (LPS). In mice, systemic delivery of miR-19a confers protection against septic AKI. Our findings implicate that miR-19a may serve as a promising therapeutic candidate in the prevention of septic AKI.

Acute kidney injury (AKI) initiated by sepsis remains a thorny problem despite recent advancements in its clinical management. Having been found to be activated during AKI, fibroblast growth factor-inducible molecule 14 (Fn14) may be a potential therapeutic target because of its involvement in the molecular basis of injury. Here, we report that LPS induces apoptosis of mouse cortical tubule cells mediated by Fn14, for which simultaneous Toll-like receptor (TLR)4 activation is required. Mechanistically, TLR4 activation by lipopolysaccharide, through disassociating E3 ligase SCF

Apoptosis of neural cells is one of the main pathological features in hypoxic/ischemic brain injury. Nuclear factor-κB (NF-κB) might be a potential therapeutic target for hypoxic/ischemic brain injury since NF-κB has been found to be inactivated after hypoxia exposure, yet the underlying molecular mechanisms of NF-κB inactivation are largely unknown. Here we report that epidermal growth factor receptor (EGFR) activation prevents neuron-like PC12 cells apoptosis in response to hypoxia via restoring NF-κB-dependent transcriptional upregulation of cyclin D1. Functionally, EGFR activation by EGF stimulation mitigates hypoxia-induced PC12 cells apoptosis in both dose- and time-dependent manner. Of note, EGFR activation elevates IKKβ phosphorylation, increases IκBα ubiquitination, promotes P65 nuclear translocation and recruitment at cyclin D1 gene promoter as well as upregulates cyclin D1 expression. EGFR activation also abrogates the decrease of IKKβ phosphorylation, reduction of IκBα ubiquitination, blockade of P65 nuclear translocation and recruitment at cyclin D1 gene promoter as well as downregulation of cyclin D1 expression induced by hypoxia. Furthermore, NF-κB-dependent upregulation of cyclin D1 is instrumental for the EGFR-mediated cytoprotection against hypoxic apoptosis. In addition, the dephosphorylation of EGFR induced by either EGF siRNA transfection or anti-HB-EGF neutralization antibody treatment enhances hypoxic cytotoxicity, which are attenuated by EGF administration. Our results highlight the essential role of NF-κB-dependent transcriptional upregulation of cyclin D1 in EGFR-mediated cytoprotective effects under hypoxic preconditioning and support further investigation of EGF in clinical trials of patients with hypoxic/ischemic brain injury.

Background Although aberrant DNA methyltransferase 3a (DNMT3a) expression is important to the tumorigenesis of pancreatic ductal adenocarcinoma (PDAC), the role of DNMT3a in PDAC prognosis is not clarified yet due to the limited studies and lacking of underlying molecular mechanism. Methods The expression of DNMT3a was examined by immunohistochemistry in PDAC tissues. Gene expression profiles assays were conducted to explore the impact of DNMT3a on biological processes and signal pathways. Cell cycle and apoptosis were measured by flow cytometry. Western blotting and real-time qPCR assays were used to explore the impact of DNMT3a on expression of protein and mRNA related to cell cycle, STAT3 signaling pathway and apoptosis. Results DNMT3a was overexpressed and closely associated with poor outcomes of PDAC. DNMT3a knockdown restrained PDAC cell proliferation, induced cell cycle arrest and promoted apoptosis in vitro. Affymetrix GeneChip Human Transcriptome Array identified that the cell cycle-related process was most significantly associated with DNMT3a. DNMT3a knockdown induced G1-S phase transition arrest by decreasing the expression of cyclin D1, which was mediated by the reduction of IL8 and the subsequent inactivation of STAT3 signaling pathway. Furthermore, exogenous apoptosis was also promoted after DNMT3a knockdown, probably via up-regulation of DNA transcription and expression in CASP8. Conclusion These findings indicate that DNMT3a plays an important role in PDAC progression. DNMT3a may serve as a prognostic biomarker and a therapeutic strategy candidate in PDAC.

Pancreatic cancer is a serious malignancy accompanied by a well-documented poor prognosis. Accumulating studies have indicated the crucial roles played by long non-coding RNAs (lncRNAs) in proliferation, apoptosis and invasion of cancer cells. The aim of the current study was to investigate the role of lncRNA LINC01207 in autophagy and apoptosis of pancreatic cancer cells and its regulatory mechanism interacting with miR-143-5p. Initially, expression profiles of lncRNAs and genes associated with pancreatic cancer were identified. The expression patterns of LINC01207, miR-143-5p and AGR2 in both pancreatic cancer and adjacent tissues were then determined. The binding relationship of LINC01207 to miR-143-5p and targeting relationship of miR-143-5p to AGR2 were subsequently verified. Silencing of LINC01207, or up-regulation or down-regulation of miR-143-5p was introduced into the pancreatic cancer cells, so as to analyze their effects on the cell growth, apoptosis and autophagy. Besides, these regulatory effects were further explored with the determination of the autophagy- and apoptosis-related gene or proteins. LINC01207 and AGR2 were highly expressed while miR-143-5p was poorly expressed in pancreatic cancer. Functionally, LINC01207 can bind to miR-143-5p, and AGR2 was a target gene of miR-143-5p. Importantly, silencing of LINC01207 down-regulated the expression of AGR2 by up-regulating miR-143-5p. Moreover, silencing of LINC01207 and up-regulation of miR-143-5p promoted cell apoptosis and autophagy, corresponding to increased expression of autophagy- and apoptosis-related proteins, in addition to inhibited cell growth. Taken together, silencing of LINC01207 prevents the progression of pancreatic cancer by impairing miR-143-5p-targeted AGR2 expression, providing a potential target for pancreatic cancer treatment.

An integrated pressure and magnetic field sensor based on piezoresistance effect is proposedin this paper. The integrated sensor is composed of a C-type silicon cup, ferromagnetic materialand Wheatstone bridge constructed by four metal oxide semiconductor field effect transistors(MOSFETs) channel resistances as piezoresistances. Based on the piezoresistance effect of channelresistances, the measurement to the external pressure P and magnetic field B can be achieved by thesensor. Through using complementary metal oxide semiconductor (CMOS) technology and microelectromechnicalsystem (MEMS) technology, the sensor chip was designed and fabricated on orientation silicon substrates, locating the ferromagnetic material on its squared silicon membranecenter. The experimental results show that when supply voltage of the sensor is 2.0 V, the pressuresensitivity of sensor is 0.39 mV/kPa (B=0 T), and the magnetic field sensitivity of sensor is 1.48 mV/T(P=0 kPa).

To evaluate the significance of hepatic functional reserve for the operation of liver cancer complicated with cirrhosis.Fifty-six patients suffering from liver cancer complicated with cirrhosis were divided into three levels, A, B and C, according to Child-Pugh grading system. Based on indocyanine green retention rate at 15 min (ICGR15) value, patients were divided into three intervals, ≤15%, 15-25% and ≥25%. According to the existence of complications, patients were divided into the complication group and the no complication group.Child-Pugh grading included 50 cases of level A, 45 cases of B and 29 cases of C. ICGR15 value included 47 cases of ≤15% interval, 47 cases of 15-25% and 30 cases of ≥25%. As the IGCR15 value increased, the levels of all indicators were obviously increased. Among the 124 patients, 35 cases (28.23%) suffered complications The median follow-up time was 25.0 months. The survival rate of the complication group was 60.00% (21 cases), significantly lower than that of the no complication group (84.27%). Child-Pugh grading of the complication group included 4 cases of level A, 12 cases of B and 19 cases of C. ICGR15 value included 15 cases of 15~25% interval and 20 cases of ≥25%.Child-Pugh grading and ICGR15 value can both reflect hepatic functional reserve and are of great clinical significance for complication and survival. There is a fairly good relevance between ICGR15 and levels of AFP, ALT and indicators of liver fibrosis.

This paper studies the solution to combat aircrafts path planning problem in confrontational battle space. First of all, according to the dynamic movement characteristics of emergent threats, a path planning target function model is built based on dynamic threat; then based on the defects of basic genetic algorithm, a kind of improved genetic algorithm based on predatory search strategies is further designed; finally the model and the algorithm are tested effective by simulation verification.

To investigate the mechanisms underlying the protective effects of sodium tanshinone IIA sulfonate (STS) in an ischemia-reperfusion (I/R)-induced rat myocardial injury model.Male SD rats were iv injected with STS, STS+LY294002 or saline (NS) for 15 d. Then the hearts were subjected to 30 min of global ischemia followed by 2 h of reperfusion. Cardiac function, infarction size and area at risk were assessed. Cell apoptosis was evaluated with TUNEL staining, DNA laddering and measuring caspase-3 activity. In addition, isolated cardiomyocytes of neonatal rats were pretreated with the above drugs, then exposed to H2O2 (200 mol/L) for 1 h. Cell apoptosis was detected using flow cytometric assay. The levels of p-Akt, p-FOXO3A and Bim were examined with immunoblotting.Compared to NS group, administration of STS (20 mg/kg) significantly reduced myocardial infarct size (40.28%±5.36% in STS group vs 59.52%±7.28% in NS group), and improved the myocardial function as demonstrated by the increased values of dp/dtmax, LVDP and coronary flow at different reperfusion time stages. Furthermore, STS significantly decreased the rate of apoptotic cells (15.11%±3.71% in STS group vs 38.21%±7.83% in NS group), and reduced caspase-3 activity to nearly a quarter of that in NS group. Moreover, STS significantly increased the phosphorylation of Akt and its downstream target FOXO3A, and decreased the expression of pro-apoptotic gene Bim. Co-treatment with the PI3K inhibitor LY294002 (40 mg/kg) partially countered the protective effects induced by STS treatment. In isolated cardiomyocytes, STS exerted similar protective effects as shown in the ex vivo I/R model.STS pretreatment reduces infarct size and improves cardiac function in an I/R-induced rat myocardial injury model via activation of Akt/FOXO3A/Bim-mediated signal pathway.

To investigate the efficacy and mechanism of mandibular advancement device (MAD) treatment on obstructive sleep apnea syndrome (OSAS) patients.Eighty OSAS patients treated with a mandibular protraction appliance were included in the study. Three-dimensional reconstruction technique was used as to measure the changes of upper airway structure and volume before and after MAD treatment. The data was analyzed using SPSS 17.0 software package.The anatomic structure and the reinforcement of soft tissue's collapse in the upper airway changed after application of MAD in OSAS patients; velopharyngeal and laryngopharynx configuration was significantly increased (P0.01), while oropharyngeal configuration was significantly decreased (P0.05).This study demonstrated that pathogeny of OSAS based on morphological characteristics may be removed by mandibular advancement device, the mechanism of efficacy of MAD treatment can be the reduction of airway internal fluctuation and vortex of air.

The harmonic gear cold rolling process is an effective method to solve mass production. However, tooth profile quality problems greatly hinder the development of the process. Based on engagement theory, the dynamic characteristics of the rolling process and flexible wheel rolling tooth profile errors caused by the changes of the number of contact points were analyzed and studied, and the process methods were put forward to eliminate or reduce tooth profile errors in this paper, which has an important significance in analysis of rolling tooth profile errors, modification shape of the rolling wheel, optimization of process parameters and improvement of gear rolling quality.

Medulloblastoma is a primitive neuroectodermal tumor, which originates in the cerebellum, presumably due to the alterations of some neurogenetic elements. Sirtuin 1 (SIRT1), a class III histone deacetylase (HDAC), regulates differentiation of neuronal stem cells but its status in medulloblastomas remains largely unknown. The current study aimed to address this issue by checking SIRT1 expression in noncancerous cerebellar tissues, medulloblastoma tissues and established cell lines. The roles of SIRT1 in proliferation and survival of UW228-3 medulloblastoma cells were analyzed by SIRT1 small interfering RNA (siRNA) transfection and SIRT1 inhibitor nicotinamide treatment. The results revealed that the frequency of SIRT1 expression in medulloblastoma tissues was 64.17% (77/120), while only one out of seven tumor-surrounding noncancerous cerebellar tissues showed restricted SIRT1 expression in the cells within the granule layer. Of the three morphological subtypes, the rates of SIRT1 detection in the large cell/anaplastic cell (79.07%; 34/43) and the classic medulloblastomas (60.29%; 41/68) are higher than that (22.22%; 2/9) in nodular/desmoplastic medulloblastomas (P

A 9-month-old infant with left ovarian Sertoli Leydig cell tumors (SLCTs) was reported and the special histological pattern was that the main components of the tumor were leydig cells. She was the youngest reported case of the tumor. The patient had increased serum estradiol and A-Fetoprofein (AFP) and a left oophorectomy was performed. After surgery, the patient has not received any treatment. So far, the patient has been well and survived without recurrence for 40 months.

Medulloblastoma cells exhibit varied responses to therapy by all‐trans retinoic acid (RA). The underlying mechanism for such diverse effects however remains largely unclear. In this study, we attempted to elucidate the molecular basis of RA resistance through the study of RA signaling components in both RA‐sensitive (Med‐3) and RA‐resistant (UW228‐2 and UW228‐3) medulloblastoma cells. The results revealed that RARα/β/γ and RXRα/β/γ were found in the three cell lines. Expression of CRABP‐I and CRABP‐II was seen in Med‐3 cells, up‐regulated when treated with RA, but was absent in UW228‐2 and UW228‐3 cells regardless of RA treatment. Bisulfite sequencing revealed 8 methylated CG sites at the promoter region of CRABP‐II in UW228‐2 and UW228‐3 but not in Med‐3 cells. Demethylation by 5‐aza‐2′‐deoxycytidine recovered CRABP‐II expression. Upon restoration of CRABP‐II expression, both UW228‐2 and UW228‐3 cells responded to RA treatment by forming neuronal‐like differentiation, synaptophysin expression, β‐III tubulin upregulation, and apoptosis. Furthermore, CRABP‐II specific siRNA reduced RA sensitivity in Med‐3 cells. Tissue microarray‐based immunohistochemical staining showed variable CRABP‐II expression patterns among 104 medulloblastoma cases, ranging from negative (42.3%), partly positive (14.4%) to positive (43.3%). CRABP‐II expression was positively correlated with synaptophysin (rs = 0.317; p = 0.001) but not with CRABP‐I expression (p > 0.05). In conclusion, aberrant methylation in CRABP‐II reduces the expression of CRABP‐II that in turn confers RA resistance in medulloblastoma cells. Determination of CRABP‐II expression or methylation status may enable a personalized RA therapy in patients with medulloblastomas and other types of cancers.

Neuronal apoptosis is a contributing cause of disability and death in cerebral ischemia. Nuclear factor-κB (NF-κB) may become a potential therapeutic target for hypoxic/ischemic neuron damage because NF-κB is inactivated after hypoxia exposure. Vascular endothelial growth factor (VEGF) has been found to improve neurological function recovery in cerebral ischemic injury although the exact molecular mechanisms that underlie the neuroprotective function of VEGF remain largely unknown. Here we defined the mechanism by which VEGF antagonized neuron-like PC12 cells apoptosis induced by hypoxia mimetic agent cobalt chloride (CoCl2) is through restoration of NF-κB activity. Depletion of VEGF with small interfering RNA (siRNA) in PC12 cells conferred CoCl2-induced cytotoxicity which was mitigated by VEGF administration. Treatment of PC12 cells with VEGF attenuated the CoCl2-induced cytotoxicity in both dose- and time-dependent manner. Mechanistically, VEGF increased IκBα phosphorylation and ubiquitination, promoted P65 nuclear translocation as well as upregulated XIAP and CCND1 expression. Meanwhile, VEGF administration reversed the dysregulation of IκBα phosphorylation and ubiquitination, P65 nuclear translocation as well as XIAP and CCND1 expression induced by CoCl2. Notably, the VEGF-dependent cytoprotection was abolished by pretreatment with BAY 11-7085, a specific inhibitor of NF-κB. Our data suggest that VEGF/NF-κB signalling pathway represents an adaptive mechanism that protects neural cells against hypoxic damage.

To evaluate the feasibility of endometrial sampler Pipelle for endometrial histologic diagnosis.Using prospective and self-control methods, 200 patients with endometrial biopsy firstly used Pipelle endometrial sampler for endometrial tissue, then followed by diagnostic curettage, the same pathologist evaluated the specimen quality and made the histologic diagnosis.Totally 200 patients completed the observation, the specimen satisfaction of Pipelle was 93.0% (in this 200 cases, 186 cases were satisfactory), its pathological accuracy was 85.0% (in this 200 cases, 170 cases' pathological results are highly consistent with diagnostic curettage). There was no significant difference between two kinds of endometrial sampling (P0.05). There was no pain for patients during the Pipelle using process.Pipelle could obtain satisfactory samples used for histological diagnosis in normal endometrium, simple hyperplasia, complex hyperplasia, atypical hyperplasia and endometrial cancer disease, because its pathological accuracy is so close to the diagnostic curettage, which may be used as a routine screening tool of endometrial diseases.

Tanshinone IIA is a lipophilic abietane diterpene compound, which exhibits protective effects against ischaemia/reperfusion injury; however, the pathways responsible for the myocardial protective activities of tanshinone IIA remain to be elucidated. The aim of the present study was to investigate the effect of tanshinone IIA on the Janus‑activated kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway, which is associated with cardiac dysfunction during ischemia/reperfusion. The results demonstrated that tanshinone IIA protected myocardial cells from hypoxia/ischemia‑induced injury in vitro and recovered decreased cell viability due to activation of the JAK2/STAT3 pathway, with 10 µM tanshinone IIA exhibiting the most potent protective effects. Flow cytometric analysis revealed that tanshinone IIA reversed the apoptotic aggravation induced by JAK2/STAT3 inhibitors following hypoxic ischemia. However, JAK2 inhibitors promoted the myocardial protective effect of tanshinone IIA from hypoxic‑ischemic injury. Furthermore, tanshinone IIA and JAK2/STAT3 inhibitors in combination augmented the protection of myocardial cells from apoptosis induced by ischemia/reperfusion preconditioning in vivo. In conclusion, the results of the present study indicated that JAK2/STAT3 inhibitors may enhance the protective effect of tanshinone IIA on cardiac myocytes from hypoxic ischemia-induced injury, therefore suggesting that JAK2/STAT3 inhibitors may have a potential application in combination therapies with tanshinone IIA.