Search

Kidney is a primary target organ for mercuric chloride (HgCl 2 ) toxicity. Selenium (Se) can exert antagonistic effect on heavy metals-induced organ toxicity by regulating the expression of selenoproteins. The objective of this study was to investigate the effect of HgCl 2 on the gene expression of selenoproteins in chicken kidney. Sixty male Hyline brown chickens were randomly and evenly divided into two groups. After acclimatization for one week, chickens were provided with the standard diet as well as non-treated water (CON group), and standard diet as well as HgCl 2 -treated water (250 ppm, HgCl 2 group). After seven weeks, kidney tissues were collected to examine the mRNA expression levels of 25 selenoproteins genes and protein expression levels of 4 selenoproteins. Moreover, correlation analysis and principal component analysis (PCA) were used to analyze the expression patterns of 25 selenoproteins. The results showed that HgCl 2 exposure significantly decreased the mRNA expression of Glutathione peroxidase 1 (GPX1), GPX4, Thioredoxin reductase 2 (TXNRD2), Iodothyronine deiodinase 1 (DIO1), Methionine-Rsulfoxide reductase 1 (SELR), 15-kDa selenoprotein (SEP15), selenoprotein I (SELI), SELK, SELM, SELN, SELP, SELS, SELT, SELW, and SEPHS2. Meanwhile, HgCl 2 exposure significantly increased the mRNA expression of GPX3, TXNRD1, and SELU. Western blot analysis showed that the expression levels of GPX3, TXNRD1, SELK, and SELN were concordant with these mRNA expression levels. Analysis results of selenoproteins expression patterns showed that HgCl 2 -induced the main disorder expression of selenoproteins with antioxidant activity and endoplasmic reticulum resident selenoproteins. In conclusion, selenoproteins respond to HgCl 2 exposure in a characteristic manner in chicken kidney., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Mercuric chloride (HgCl 2 ) is a widely distributed environmental pollutant with multiorgan toxicity including immune organs such as spleen. Selenium (Se) is an essential trace element in animal nutrition and exerts biological activity to antagonize organ toxicity caused by heavy metals. The objective of this study was to explore the underlying mechanism of the protective effects of Se against spleen damage caused by HgCl 2 in chicken. Ninety male Hyline brown chicken were randomly divided into 3 groups namely Cont, HgCl 2 , and HgCl 2 +Se group. Chicken were provided with the standard diet and nontreated water, standard diet and HgCl 2 -treated water (250 ppm), and sodium selenite-treated diet (10 ppm) plus HgCl 2 -treated water (250 ppm), respectively. After being fed for 7 wk, the spleen tissues were collected, and spleen index, the microstructure of the spleen, and the indicators of oxidative stress, inflammation, apoptosis as well as heat shock proteins (HSP) were detected. First, the results of spleen index and pathological examination confirmed that Se exerted an antagonistic effect on the spleen injury induced by HgCl 2 . Second, Se ameliorated HgCl 2 -induced oxidative stress by decreasing the level of malondialdehyde and increasing the levels of glutathione, glutathione peroxidase, and total antioxidant capacity. Third, Se attenuated HgCl 2 -induced inflammation by decreasing the protein expression of nuclear factor kappa-B, inducible nitric oxide synthase, and cyclooxygenase-2, and the gene expression of interleukin (IL)-1β, IL-6, IL-8, IL-12β, IL-18 as well as tumor necrosis factor-α. Fourth, Se inhibited HgCl 2 -induced apoptosis by downregulating the protein expression of BCL2 antagonist/killer 1 and upregulating the protein expression of B-cell lymphoma-2. Finally, Se reversed HgCl 2 -triggered activation of HSP 60, 70, and 90. In conclusion, Se antagonized HgCl 2 -induced spleen damage in chicken, partially through the regulation of oxidative stress, inflammatory, and apoptotic signaling., (Copyright © 2020. Published by Elsevier Inc.)

Objectives of this study were to evaluate the alleviating effects of a commercial beta-1,3-glucan product (Aleta, containing 50% beta-1,3-glucan, Kemin Industries) on metabolic stress in transition Holstein cows as reflected by circulating metabolites and enzymes. Fifty-four multiparous Holstein cows were randomly allocated to three groups with 18 cows each. Cows in each group received a commercial basal diet or the basal diet supplemented with Aleta calculated to supply 5 or 10 g of Aleta per cow per day. Blood samples were collected at day -21, 1, and 21 relative to calving for determination of serum triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDLC), very low density lipoprotein (VLDL), glucose, insulin, β-hydroxybutyric acid (BHBA), aspartate aminotransferase (AST), alanine aminotransferase (ALT), glutamyl transpeptidase (GGT), and non-esterified fatty acid (NEFA). Supplementation with Aleta markedly elevated serum concentrations of TG, TC, HDLC, LDL-C and VLDL, implying its positive effect on lipid metabolism in transition dairy cows. Aleta treatment significantly decreased the serum concentrations of NEFA and BHBA, but markedly elevated the serum concentrations of glucose and insulin. Also, Aleta treatment significantly elevated the dry matter intake and milk production in postpartum cows, indicating the alleviating effect of Aleta on negative energy balance in transition cows. Moreover, Aleta treatment significantly reduced the serum activities of AST, ALT and GGT, indicating its hepatoprotective effect on transition cows. These results suggest that Aleta supplementation may help to improve fat metabolism disorder initiated by negative energy balance in transition dairy cows., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Liver resection for hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT) offers a chance of cure, although survival is often limited. The actual 3-year survival and its associated prognostic factors have not been reported., Methods: A nationwide database of HCC patients with PVTT who underwent liver resection with 'curative' intent was analyzed. The clinicopathologic characteristics, the perioperative, and survival outcomes for the actual long-term survivors were compared with the non-long-term survivors (patients who died within 3 years of surgery). Univariable and multivariable regression analyses were performed to identify predictive factors associated with long-term survival outcomes., Results: The study included 1590 patients with an actuarial 3-year survival of 16.6%, while the actual 3-year survival rate was 11.7%. There were 171 patients who survived for at least 3 years after surgery and 1290 who died within 3 years of surgery. Multivariable regression analysis revealed that total bilirubin > 17.1 μmol/l, AFP > 400 ng/ml, types of hepatectomy, extent of PVTT, intraoperative blood loss > 400 ml, tumor diameter > 5 cm, tumor encapsulation, R0 resection, liver cirrhosis, adjuvant TACE, postoperative early recurrence (< 1 year), and recurrence treatments were independent prognostic factors associated with actual long-term survival., Conclusion: One in nine HCC patients with PVTT reached the long-term survival milestone of 3 years after resection. Major hepatectomy, controlling intraoperative blood loss, R0 resection, adjuvant TACE, and 'curative' treatment for initial recurrence should be considered for patients to achieve better long-term survival outcomes.

Gemcitabine is widely used as an anticancer chemotherapy drug for a variety of solid tumors, and it has become the standard treatment option for locally advanced and metastatic pancreatic cancer. However, pancreatic cancer cells develop resistance to gemcitabine after a few weeks of treatment, resulting in poor therapeutic effects. Isocorydine (ICD) is a typical natural aporphine alkaloid, and ICD and its derivatives inhibit the proliferation of many types of cancer cells in vitro. In this study, ICD was found to synergistically inhibit cell viability with gemcitabine in pancreatic cancer cells. A microarray analysis showed that ICD can inhibit the upregulation of STAT3 and EMT in pancreatic cancer cells induced by gemcitabine. STAT3 is closely related to tumor EMT, migration and invasion. After knocking down the expression of STAT3 in pancreatic cancer cells, the combination index (CI) of ICD and gemcitabine decreased. ICD can reverse the increase in the expression of EMT-related transcription factors and proteins caused by gemcitabine, thereby inhibiting the enhanced cell migration and invasion ability caused by gemcitabine. Finally, the synergistic treatment effect of the combination treatment of ICD and gemcitabine in pancreatic cancer cells was confirmed in established xenograft models., Competing Interests: None., (AJTR Copyright © 2020.)

Neuropathic pain is difficult to treat and remains a major clinical challenge worldwide. While the mechanisms which underlie the development of neuropathic pain are incompletely understood, interferon signaling by the immune system is known to play a role. Here, we demonstrate a role for interferon β (IFNβ) in attenuating mechanical allodynia induced by the spared nerve injury in mice. The results show that intrathecal administration of IFNβ (dosages up to 5,000 U) produces significant, transient, and dose-dependent attenuation of mechanical allodynia without observable effects on motor activity or feeding behavior, as is common with IFN administration. This analgesic effect is mediated by the ubiquitin-like protein interferon-stimulated gene 15 (ISG15), which is potently induced within the spinal cord following intrathecal delivery of IFNβ. Both free and conjugated ISG15 are elevated following IFNβ treatment, and this effect is increased in UBP43 -/- mice lacking a key deconjugating enzyme. The IFNβ-mediated analgesia reduces MAPK signaling activation following nerve injury, and this effect requires induction of ISG15. These findings highlight a new role for IFNβ, ISG15, and MAPK signaling in immunomodulation of neuropathic pain and may lead to new therapeutic possibilities. PERSPECTIVE: Neuropathic pain is frequently intractable in a clinical setting, and new treatment options are needed. Characterizing the antinociceptive potential of IFNβ and the associated downstream signaling pathways in preclinical models may lead to the development of new therapeutic options for debilitating neuropathies., (Copyright © 2019. Published by Elsevier Inc.)

Background and Purpose: Dopamine protects the duodenal mucosa. Here we have investigated the source of dopamine in gastric juice and the mechanism underlying the effects of luminal dopamine on duodenal bicarbonate secretion (DBS) in rodents., Experimental Approach: Immunofluorescence, UPLC-MS/MS, gastric incubation and perfusion were used to detect gastric-derived dopamine. Immunofluorescence and RT-PCR were used to examine the expression of dopamine receptors in the duodenal mucosa. Real-time pH titration and pH i measurement were performed to investigate DBS., Key Results: H + -K + -ATPase was co-localized with tyrosine hydroxylase and dopamine transporters in gastric parietal cells. Dopamine was increased in in vivo gastric perfusate after intravenous infusion of histamine and in gastric mucosa incubated, in vitro, with bethanechol chloride or tyrosine. D 2 receptors were the most abundant dopamine receptors in rat duodenum, mainly distributed on the apical membrane of epithelial cells. Luminal dopamine increased DBS in a concentration-dependent manner, an effect mimicked by a D 2 receptor agonist quinpirole and inhibited by the D 2 receptor antagonist L741,626, in vivo D 2 receptor siRNA and in D 2 receptor -/- mice. Dopamine and quinpirole raised the duodenal enterocyte pH i . Quinpirole-evoked DBS and PI3K/Akt activity were inhibited by calcium chelator BAPTA-AM or in D 2 receptor -/- mice., Conclusion and Implications: Dopamine in the gastric juice is derived from parietal cells and is secreted along with gastric acid. On arrival in the duodenal lumen, dopamine increased DBS via an apical D 2 receptor- and calcium-dependent pathway. Our data provide novel insights into the protective effects of dopamine on the duodenal mucosa., (© 2020 The British Pharmacological Society.)

EphrinB-EphB receptor tyrosine kinases have been demonstrated to play important roles in pain processing after peripheral nerve injury. We have previously reported that ephrinB-EphB receptor signaling can regulate excitability and plasticity of neurons in spinal dorsal horn, and thus contribute to spinal central sensitization in neuropathic pain. How EphB receptor activation influences excitability of primary neurons in dorsal root ganglion (DRG), however, remains unknown. Here, we report that EphB receptor activation facilitates calcium influx through N-methyl-D-aspartate receptor (NMDAR) dependent and independent manners. In cultured DRG cells from adult rats, EphB1 and EphB2 receptors were expressed in neurons, but not the glial cells. Bath application of EphB receptor agonist ephrinB2-Fc induced NMDAR-independent Ca influx, which was from the extracellular space rather than endoplasmic reticulum. EphB receptor activation also greatly enhanced NMDAR-dependent Ca influx and NR2B phosphorylation, which was prevented by pretreatment of Src kinase inhibitor PP2. In nerve-injured DRG neurons, elevated expression and activation of EphB1 and EphB2 receptors contributed to the increased intracellular Ca concentration and NMDA-induced Ca influx. Repetitive intrathecal administration of EphB2-Fc inhibited the increased phosphorylation of NR2B and Ca-dependent subsequent signals Src, ERK, and CaMKII as well as behaviorally expressed pain after nerve injury. These findings demonstrate that activation of EphB receptors can modulate DRG neuron excitability by facilitating Ca influx directly or through Src kinase activation-mediated NMDA receptor phosphorylation and that EphB receptor activation is critical to DRG neuron hyperexcitability, which has been considered critical to the subsequent spinal central sensitization and neuropathic pain.

Background: Hepatic vein tumour thrombus (HVTT) is a major determinant of survival outcomes for patients with hepatocellular carcinoma (HCC). An Eastern Hepatobiliary Surgery Hospital (EHBH)-HVTT model was established to predict the prognosis of patients with HCC and HVTT after liver resection, in order to identify optimal candidates for liver resection., Methods: Patients with HCC and HVTT from 15 hospitals in China were included. The EHBH-HVTT model with contour plot was developed using a non-linear model in the training cohort, and subsequently validated in internal and external cohorts., Results: Of 850 patients who met the inclusion criteria, there were 292 patients who had liver resection and 198 who did not in the training cohort, and 124 and 236 in the internal and external validation cohorts respectively. Contour plots for the EHBH-HVTT model were established to predict overall survival (OS) rates of patients visually, based on tumour diameter, number of tumours and portal vein tumour thrombus. This differentiated patients into low- and high-risk groups with distinct long-term prognoses in the liver resection cohort (median OS 34·7 versus 12·0 months; P < 0·001), internal validation cohort (32·8 versus 10·4 months; P = 0·002) and external validation cohort (15·2 versus 6·5 months; P = 0·006). On subgroup analysis, the model showed the same efficacy in differentiating patients with HVTT in peripheral and major hepatic veins, the inferior vena cava, or in patients with coexisting portal vein tumour thrombus., Conclusion: The EHBH-HVTT model was accurate in predicting prognosis in patients with HCC and HVTT after liver resection. It identified optimal candidates for liver resection among patients with HCC and HVTT, including tumour thrombus in the inferior vena cava, or coexisting portal vein tumour thrombus., (© 2020 BJS Society Ltd Published by John Wiley & Sons Ltd.)

Drug safety is a severe clinical pharmacology and toxicology problem that has caused immense medical and social burdens every year. Regretfully, a reproducible method to assess drug safety systematically and quantitatively is still missing. In this study, we developed an advanced machine learning model for de novo drug safety assessment by solving the multilayer drug-gene-adverse drug reaction (ADR) interaction network. For the first time, the drug safety was assessed in a broad landscape of 1,156 distinct ADRs. We also designed a parameter ToxicityScore to quantify the overall drug safety. Moreover, we determined association strength for every 3,807,631 gene-ADR interactions, which clues mechanistic exploration of ADRs. For convenience, we deployed the model as a web service ADRAlert-gene at http://www.bio-add.org/ADRAlert/. In summary, this study offers insights into prioritizing safe drug therapy. It helps reduce the attrition rate of new drug discovery by providing a reliable ADR profile in the early preclinical stage., (© 2019 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Aims: To investigate clinical characteristics and surgery outcomes of young children with focal cortical dysplasia (FCD) type II., Methods: Young children (onset age ≤6 years) with FCDII who underwent epileptic surgery in Children Epilepsy Center of Peking University First Hospital in 2014-2018 were followed up for at least 6 months after surgery., Results: One hundred and twelve children with FCDII were included, with median age of onset 0.9 years (0.01-5.9), who underwent surgery at 4.1 years old (0.8-16.2). Focal seizures were most frequent (90.2%) and epileptic spasms presented in 23 (20.5%) cases. Epileptic encephalopathy was not uncommon (12.5%), associated with earlier epilepsy onset and higher rate of bilateral onset on ictal EEG (OR = 0.213, 9.059; P = .041, .004). At the last follow-up, 88.4% achieved seizure-free. Before surgery, 49.1% showed moderate/severe developmental delay, associated with earlier seizure onset and higher rate of history of epileptic encephalopathy (OR = 0.740, 5.160, P = .023, .042). For 48 children with preoperatively moderate/severe developmental delay, DQ rank at 6 months postsurgery was improved in only four cases., Conclusion: For young children with FCDII, they tend to present with epileptic encephalopathies and show moderate/severe developmental delay before surgery. The seizure outcome was favorable after surgery. For children with preoperatively moderate/severe developmental delay, developmental outcome at 6 months after surgery was not satisfactory., (© 2019 The Authors. CNS Neuroscience & Therapeutics Published by John Wiley & Sons Ltd.)

Talaromyces marneffei is a common cause of infection in immunocompromised patients in Southeast Asia and Southern China. The pathogenicity of T. marneffei depends on the ability of the fungus to survive the cytotoxic processes of the host immune system and grow inside host macrophages. These mechanisms that allow T. marneffei to survive macrophage-induced death are poorly understood. In this study, we examined the role of a calcineurin homolog ( cnaA ) from T. marneffei during growth, morphogenesis and infection. Deletion of the cnaA gene in T. marneffei resulted in a strain with significant defects in conidiation, germination, morphogenesis, cell wall integrity, and resistance to various stressors. The Δ cnaA mutant showed a lower minimal inhibitory concentration (MIC) against caspofungin (16 μg/ml to 2 μg/ml) and micafungin (from 32 μg/ml to 4 μg/ml) compared with the wild-type. These results suggest that targeting calcineurin in combination with echinocandin treatment may be effective for life-threatening systemic T. marneffei infection. Importantly, the cnaA mutant was incapable of adapting to the macrophage environment in vitro and displayed virulence defects in a mouse model of invasive talaromycosis. For the first time, a role has been shown for cnaA in the morphology and pathogenicity of a dimorphic pathogenic filamentous fungus., (Copyright © 2020 Zheng, Pan, Latgé, Andrianopoulos, Luo, Yan, Wei, Huang and Cao.)

Cadmium (Cd), as one of the most toxic heavy metals, has become a widespread environmental contaminant and threats the food quality and safety. The protective effect of selenium (Se) on Cd-induced tissue lesion and cytotoxicity in chicken has been extensively reported. The objective of this study was to investigate the antagonistic effect of Se on Cd-induced damage of chicken pectoral muscles via analyzing the trace elements and amino acids profiles. Firstly, 19 trace elements contents were analyzed by inductively coupled plasma mass spectrometry (ICP-MS). The results showed that under Cd exposure, the contents of Cd, lead (Pb), mercury (Hg), aluminum (Al), and lithium (Li) were significantly elevated, and the contents of Se, iron (Fe), and chromium (Cr) were significantly reduced. However, supplementing Se significantly reversed the effects induced by Cd. Secondly, the amino acids contents were detected by L-8900 automatic amino acid analyzer. The results showed that supplementing Se increased significantly Cd-induced decrease of valine (Val), leucine (Leu), arginine (Arg), and proline (Pro). Thirdly, the results of principal component analysis (PCA) showed that cobalt (Co), manganese (Mn), silicium (Si), and Pro may play special roles in response to the process of Se antagonizes Cd-induced damage of pectoral muscles in chickens. In summary, these results indicated that different trace elements and amino acids possessed and exhibited distinct responses to suffer from Se and/or Cd in chicken pectoral muscles. Notably, Se alleviated Cd-induced adverse effects by regulating trace elements and amino acids profiles in chicken pectoral muscles.

Cadmium (Cd) is a persistent environmental contaminant and induces neurotoxicity in animals. Trehalose (Tre) exhibits powerful neuroprotective effects in certain brain injury models. Herein, we revealed the specific molecular mechanism underlying the protective effects of Tre against Cd-induced brain damage in rats. Firstly, the results showed that Tre significantly ameliorated brain pathological injury induced by Cd. Secondly, Cd-induced down-regulation of total anti-oxidation capacity (T-AOC) and up-regulation of methane dicarboxylic aldehyde (MDA) in brain tissues were significantly reversed by Tre treatment. Importantly, the augmentation of nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) caused by Cd was significantly inhibited by Tre treatment. Thirdly, the levels of autophagy marker proteins were measured and the results showed that Tre significantly reversed the up-regulation of light chain 3II (LC-3II) and sequestosome 1 (SQSTM-1/p62) caused by Cd exposure. Finally, the apoptosis rate and the levels of apoptosis marker proteins including B cell leukemia/lymphoma 2 (Bcl2) and Bcl2-associated X protein (Bax) were also measured and the results showed that Cd-induced apoptosis was markedly inhibited by Tre treatment. Collectively, our data suggested that Tre exerted its neuroprotective effects by ameliorating oxidative stress, autophagy inhibition, and apoptosis induced by Cd in rat brains. In addition, the Nrf2 signaling pathway, which is continuously activated by Cd, may contribute to brain injury.

Purpos e. To determine whether the radiomic features of 18 F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) contribute to prognosis prediction in primary gastric diffuse large B-cell lymphoma (PG-DLBCL) patients. Methods . This retrospective study included 35 PG-DLBCL patients who underwent PET/CT scans at West China Hospital before curative treatment. The volume of interest (VOI) was drawn around the tumor, and radiomic analysis of the PET and CT images, within the same VOI, was conducted. The metabolic and textural features of PET and CT images were evaluated. Correlations of the extracted features with the overall survival (OS) and progression-free survival (PFS) were evaluated. Univariate and multivariate analyses were conducted to assess the prognostic value of the radiomic parameters. Results . In the univariate model, many of the textural features, including kurtosis and volume, extracted from the PET and CT datasets were significantly associated with survival (5 for OS and 7 for PFS (PET); 7 for OS and 14 for PFS (CT)). Multivariate analysis identified kurtosis (hazard ratio (HR): 28.685, 95% confidence interval (CI): 2.067-398.152, p =0.012), metabolic tumor volume (MTV) (HR: 26.152, 95% CI: 2.089-327.392, p =0.011), and gray-level nonuniformity (GLNU) (HR: 14.642, 95% CI: 2.661-80.549, p =0.002) in PET and sphericity (HR: 11.390, 95% CI: 1.360-95.371, p =0.025) and kurtosis (HR: 11.791, 95% CI: 1.583-87.808, p =0.016), gray-level nonuniformity (GLNU) (HR: 6.934, 95% CI: 1.069-44.981, p =0.042), and high gray-level zone emphasis (HGZE) (HR: 9.805, 95% CI: 1.359-70.747, p =0.024) in CT as independent prognostic factors. Conclusion . 18 F-FDG PET/CT radiomic features are potentially useful for survival prediction in PG-DLBCL patients. However, studies with larger cohorts are needed to confirm the clinical prognostication of these parameters., Competing Interests: All authors have no conflicts of interest to disclose., (Copyright © 2019 Yi Zhou et al.)

Cadmium (Cd), as a kind of ubiquitous and highly toxic heavy metal pollutants, has been known to result in immunotoxicity in animals. As a multifunctional bioactivity disaccharide, trehalose (Tre) is characterized by antioxidative, antiapoptotic, and accelerating autophagy. In this study, Sprague-Dawley (SD) rats were fed with cadmium chloride (CdCl 2 ) and/or Tre to explore the molecular mechanisms of Tre-protected against spleen injury caused by Cd exposure. Firstly, the results showed that Tre partially recovered splenic pathological changes induced by Cd exposure. Secondly, Tre dramatically declined the level of methane dicarboxylic aldehyde (MDA) and elevated the level of total antioxidant capacity (T-AOC) to weaken oxidative stress caused by Cd exposure in spleen tissue. Moreover, the results showed that Tre significantly suppressed Cd-induced the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and up-regulated the protein expression of nuclear Nrf2. Thirdly, Tre remarkably reduced the protein expression of sequestosome 1 (p62/SQSTM1) and microtubule-associated protein light chain 3II (LC-3II) to restore autophagy inhibition induced by Cd exposure. Finally, the results of TUNEL and the expression of apoptosis marker proteins showed that Tre significantly inhibited Cd-induced apoptosis in spleen tissue to exert its protective effects. In summary, the results indicated that Tre modulated Nrf2 signaling pathway, which interacted with apoptosis and autophagy to against Cd-induced spleen injury, providing potential therapeutic strategies for the prevention and treatment of Cd-related immune system diseases., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Cadmium (Cd) as a widespread toxic heavy metal accumulates in animal food including chicken meat through food chain enrichment and finally threatens human health. Selenium (Se) is an essential mineral and possesses antagonistic effects on Cd-induced multiple organs' toxicity in chickens. The objective of the present study was to reveal the antagonistic mechanisms of Se to Cd from the aspects of oxidative stress, inflammation, and meat quality in chicken breast muscles. Firstly, the results showed that Cd significantly elevated the levels of malondialdehyde (MDA), hydrogen peroxide (H 2 O 2 ), and protein carbonyl, and declined the levels of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and catalase (CAT) to trigger oxidative stress in chicken breast muscles. However, Se treatment significantly alleviated Cd-induced oxidative stress by increasing the levels of GSH-Px, SOD, and CAT, and decreasing the levels of MDA, H 2 O 2 , and protein carbonyl. Secondly, Se obviously inhibited the expressions of Cd-activated inflammation-related genes including tumor necrosis factor (TNF-α), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), inducible nitric oxide synthase (iNOS), prostaglandin-endoperoxide synthase 2 (COX-2), and prostaglandin E synthase (PTGEs) in chicken breast muscles. Thirdly, meat quality-related parameters including pH 45min , ultimate pH (pHu), and drip loss were also detected, and the results showed that Se markedly recovered Cd-induced dropt of pH 45min and increase of drip loss in chicken breast muscles. In brief, these findings demonstrated that Se significantly alleviated Cd-induced oxidative stress and inflammation, and declined meat quality of chicken breast muscles.

Purpose: To investigate potential findings associated with cytokeratin 19 (CK19)-positive HCC, with special emphasis on MR texture analysis., Materials and Methods: Forty-eight patients with CK19-negative HCC and 38 patients with CK19-positive were retrospectively evaluated by texture analysis based on conventional MRI. Clinicalpathological characteristics, conventional MR imaging findings, and the MR texture analysis contained of 2415 texture features in the seven conventional sequences were compared. Significant features for differentiating were identified by univariate and multivariate analyses. Receiver operating characteristic analyses of the significant findings were performed and compared to evaluate their diagnostic performance., Results: There was no significant difference between the top1 texture feature (three-dimensional standard deviation separation of intensity on T2-weighted original images, abbreviated as: StdSeparation 3D) and the combined top1-6 feature in identifying CK19-positive HCC(P = 0.660). Univariate and multivariate analyses indicated that serum alpha-fetoprotein (AFP) level ≥400 ng/mL(P = 0.013), arterial rim enhancement(P = 0.005), and StdSeparation 3D texture character(P = 0.002) were independent variables associated with CK19-positive HCCs. The combination of the three indices showed a better performance than AFP level(P = 0.0028), arterial rim enhancement(P < 0.0001), and their combination(P = 0.0098); while no significantly better than the StdSeparation 3D texture character alone(P = 0.0788). An acceptable discrimination(AUC = 0.765) with both sensitivity and specificity greater than 75% was achieved for StdSeparation 3D texture character., Conclusion: Serum AFP level ≥400 ng/mL, arterial rim enhancement, and the StdSeparation 3D texture character were independently associated with CK19-positive HCC. The StdSeparation 3D texture character may be a reliable imaging biomarker which can improve the diagnostic performance., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objectives: To evaluate the diagnostic value of liver extracellular volume (ECV liver ) measurement by equilibrium MR in staging liver fibrosis in chronic hepatitis B (CHB) patients, and to compare its performance with serum fibrosis indices., Materials and Methods: 91 CHB patients were included and underwent gadopentetate dimeglumine-enhanced MRI with T1 mapping sequence before and 15-min after contrast. ECV liver , aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis index based on the four factors (FIB-4) were calculated and compared between fibrosis subgroups, and the correlations between the three indices and fibrosis stage or inflammatory activity were measured by Spearman correlation analysis and stepwise multiple regression analysis. Diagnostic performance in evaluating liver fibrosis stage was assessed and compared using receiver operating characteristic analysis., Results: Interobserver agreement showed an excellent interclass correlation coefficient of 0.895 for ECV liver . ECV liver , APRI and FIB-4 were different between fibrosis stages as a whole (F/H = 18.44-24.36, P ≤ 0.001). ECV liver had the strongest correlation with fibrosis stage (r = 0.727, P < 0.001), while APRI and FIB-4 had weak correlations (r = 0.466 and 0.440, P < 0.001). Multivariate analysis showed that only ECV liver was independently correlated with fibrosis stage (P < 0.001). The fibrosis stage was the only independent factor correlated with ECV liver comparing to inflammatory activity (P < 0.001). AUCs of ECV liver were larger than both APRI and FIB-4 in fibrosis staging, with significant differences in the diagnosis of advanced fibrosis (≥F3) and cirrhosis (F4) (P = 0.0024 to 0.0049)., Conclusion: MR ECV liver provides a promising noninvasive tool in staging liver fibrosis for CHB patients, superior to the fibrosis indices of APRI and FIB-4., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Microplastic pollution is an increasingly important environment problem. Many studies show the occurrence of microplastics in our environmental system. However, the freshwater system is less understood, especially in northwest China. We investigated the occurrence and characteristics of microplastics in the Wei River Basin, which is located in northwestern China. The Wei River is the largest tributary of the Yellow River and runs through three major provinces. In the Wei River, the concentration of microplastics in the surface waters varied from 3.67 to 10.7 items /L and in the sediments, the abundance of microplastics varied from 360 to 1320 items/kg. Fiber (50.1%)was the dominant types in water samples and sediments. The small size (<0.5 mm)(68.1%)were the main size of microplastics in Wei River. The types of microplastics were polyethylene, Polyvinyl chloride and polystyrene, as identified using a Fourier transform infrared spectrometer. This study could be a valuable reference for better understanding the microplastics pollution in inland northwestern China., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: To investigate clinical biomechanical principle of brace with stiletto needle therapy for scoliosis., Methods: Based on design ideas of teasing needle therapy, building an experimental mechanical model was built, seven specimens with scoliosis were chosen, and treated by brace therapy and then added to stiletto needle therapy., Results: The two experimental mechanical model methods could predict load of scoliosis by stiletto needle therapy, and was verified accuracy and effectiveness of model. The degree of initial scoliosis of 7 patients was (59.7±3.37)°, improved to (49.57±2.79)° by correction of brace, and (39.43±1.94)° by correction of brace with stiletto needle therapy, had significant differences( P <0.05). Lateral distraction force of thoracolumbar fossa from scoliosis as V, compressive force of scoliosis as T, brace with stiletto needle therapy could save effort for 45% to 46% than that of brace, while running torque Mw and compressive torque Mv could save effort about 45% to 47%, save effort of tension torque MT of muscle and ligament for 52%, and had statistical difference( P <0.05)., Conclusions: Experimental biomechanical model of teasing needle therapy confirmed that the therapy could significantly reduce Cobb angle, improve correction efficiency of brace and beneficial for correction effect. It is an effective treatment for scoliosis., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© 2019 by the China Journal of Orthopaedics and Traumatology Press.)

Lead (Pb) is a known nephrotoxicant that causes damage to proximal tubular cells. PERK pathway plays an important role in the pathogenesis of renal diseases, but its role in Pb-induced nephrotoxicity remains largely unknown. In this study, data showed that Pb could induce ER stress as shown by increased phosphorylation of PERK with subsequent activation of the eIF2α-ATF4-CHOP axis in primary rat proximal tubular (rPT) cells, indicating the activation of PERK-eIF2α-ATF4-CHOP pathway due to excessive ER stress. Pb-activated PERK pathway can be effectively inhibited by 4-phenylbutyric acid and PERK gene silencing, respectively; whereas continuously up-regulated by tunicamycin (TM) treatment. Moreover, Pb-induced apoptosis and inhibition of autophagic flux in rPT cells were significantly augmented and aggravated by co-treatment with TM, respectively. Pharmacological or genetic inhibition of the PERK pathway results in alleviation of apoptosis and restoration of autophagy inhibition in Pb-exposed rPT cells. Mechanistically, activation of PERK-eIF2α-ATF4-CHOP axis triggered by excessive ER stress in rPT cells leads to Pb-induced apoptosis and blockage of autophagic flux, resulting in nephrotoxicity., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Previous studies have shown that oxidative stress-induced inhibition of autophagy plays a pivotal role in cadmium (Cd)-mediated cytotoxicity in primary rat proximal tubular (rPT) cells. The objective of this study is to explore the protective effect of puerarin (PU), a potent antioxidant, on Cd-induced autophagy inhibition and oxidative stress in rPT cells. First, Cd-induced blockage of autophagic flux in rPT cells was obviously restored by PU treatment, evidenced by immunoblot analysis of autophagy marker proteins and tandem fluorescent-tagged LC3 method. Resultantly, Cd-induced autophagosome accumulation was significantly alleviated by PU treatment. Also, Cd-induced lysosomal alkalinization and impairment of lysosomal degradation capacity were obviously recovered by PU, demonstrating that PU can restore Cd-induced lysosomal dysfunction. Moreover, Cd-induced lysosomal membrane permeabilization (LMP) was effectively blocked by PU. Cd-stimulated Nrf2 nuclear translocation and subsequent elevated expression of Nrf2-downstream targets were significantly inhibited by PU treatment. Simultaneously, Cd-elevated protein levels of antioxidant enzymes and glutathione synthesis-related proteins in rPT cells were markedly downregulated by PU treatment. In conclusion, these observations indicate that PU alleviates Cd-induced cytotoxicity in rPT cells through restoring autophagy, blocking LMP and inhibiting Nrf2 pathway, which is intimately related with its antioxidant activity., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Cadmium (Cd) is a ubiquitously distributed environmental pollutant that is highly toxic to liver. Trehalose (Tr), a novel autophagy activator, has been shown to exert cytoprotective effect in numerous pathological processes. However, it is yet to be established whether Tr affords protection against Cd-induced hepatotoxicity. Here, we aimed to investigate the protective effect of Tr on Cd-induced hepatic injury in rats. First, Cd-elevated serum hepatic enzymes and liver pathological changes were significantly ameliorated by Tr treatment. Also, Tr remarkably improved Cd-mediated oxidative stress and antioxidant status in serum, indicating its anti-oxidant action for the whole body. Cd-stimulated nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear translocation and subsequent elevated expression of Nrf2-downstream targets in rat liver were significantly inhibited by Tr treatment. Simultaneously, Cd-elevated protein levels of hepatic antioxidant enzymes were markedly downregulated by administration with Tr. Moreover, Cd-induced autophagy inhibition in liver tissues was noticeably restored by Tr, evidenced by immunohistochemical analysis and immunoblot assays. Additionally, Tr treatment significantly mitigated Cd-induced apoptosis in hepatic tissues via inhibiting caspase-dependent apoptotic pathway. In conclusion, these observations demonstrate that Tr treatment alleviates Cd-induced liver injury by blocking Nrf2 pathway, restoring autophagy and inhibiting apoptosis., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: This retrospective study was to explore the value of whole lesion apparent diffusion coefficient (ADC) histogram in distinguishing invasive and noninvasive intraductal papillary neoplasms of the bile ducts (IPNBs)., Method and Materials: Fifty-two patients of IPNB underwent MRI at 1.5T with diffusion-weighted imaging (DWI, b = 500 s/mm 2 ) before surgical resections. ADC histogram metrics were generated by using the software MR OncoTreat. The mean, standard deviation, median, skewness, kurtosis as well as the 10th, 25th, 75th, and 90th percentiles were compared between pathologically defined invasive (n = 35) and noninvasive (n = 17) IPNBs. Such conventional imaging characters as lesion location, bile duct wall dilation, and mural nodularity were also assessed. Multivariate regression analysis as well as receiver operating characteristics (ROC) analysis were then conducted to determine the predictive factors and to evaluate potential diagnostic performances., Results: The inter-operator reliability was good to excellent (ICC: 0.693-979). Mean median, kurtosis, and the 10th, 25th, 75th, 90th percentiles were all greater in noninvasive group than invasive ones (P: 0.00-002). Skewness was lower in noninvasive group than invasive ones (- 1.0 ± 0.6 vs. - 0.3 ± 0.6, P = 0.00). After multivariate regression, skewness (AUC = 0.822, 95%CI 0.70-0.91) and mural nodularity (accuracy = 0.808) were the only two independent factors in predicting invasive IPNBs. The diagnostic performance improved (AUC = 0.867, 95%CI 0.742-0.946) when combining skewness and mural nodularity, however, the difference did not reach statistical significance (P = 0.16)., Conclusion: The ADC histogram has capability of distinguishing invasive and noninvasive IPNBs, in which skewness was an independent predictive factor.

To explore the effect of interventional embolization treatment for hydrosalpinx on the outcome of in vitro fertilization and embryo transfer (IVF-ET).During the period from January 2013 to January 2015, a total of 129 patients with unilateral or bilateral hydrosalpinx were treated with IVF-ET and selected for retrospective analysis. Seventy-three patients (intervention group) with unilateral or bilateral hydrosalpinx were treated with fallopian tube embolization, which was followed by IVF-ET. During the same period, 56 patients (control group) with unilateral or bilateral hydrosalpinx directly received IVF-ET without receiving any treatment for hydrosalpinx.The clinical pregnancy rate of the control group was significantly lower than that of the intervention group (P < .05), while the abortion rate and ectopic pregnancy rate of the control group were strikingly higher than that of the intervention group (P < .05).Hydrosalpinx can decrease the clinical pregnancy rate of IVF-ET, and increase the incidence of abortion and ectopic pregnancy. The interventional embolization treatment for hydrosalpinx before IVF-ET can improve the clinical pregnancy rate and reduce adverse pregnancy outcome and which, with the advantages of a high success rate, convenient use, low cost, less pain, no anesthetic risk and no effect on the ovarian function it may further be developed for use in the clinic.

Objective: To investigate the diagnostic value of diffusion kurtosis imaging (DKI) histogram analysis in hepatic fibrosis staging., Materials and Methods: Thirty-six rats were divided into carbon tetrachloride-induced fibrosis groups (6 rats per group for 2, 4, 6, and 8 weeks) and a control group (n = 12). MRI was performed using a 3T scanner. Histograms of DKI were obtained for corrected apparent diffusion (D), kurtosis (K) and apparent diffusion coefficient (ADC). Mean, median, skewness, kurtosis and 25th and 75th percentiles were generated and compared according to the fibrosis stage and inflammatory activity., Results: A total of 35 rats were included, and 12, 5, 5, 6, and 7 rats were diagnosed as F0-F4. The mean, median, 25th and 75th percentiles, kurtosis of D map, median, 25th percentile, skewness of K map, and 75th percentile of ADC map demonstrated significant correlation with fibrosis stage ( r = -0.767 to 0.339, p < 0.001 to p = 0.039). The fibrosis score was the independent variable associated with histogram parameters compared with inflammatory activity grade ( p < 0.001 to p = 0.041), except the median of K map ( p = 0.185). Areas under the receiver operating characteristic curve of D were larger than K and ADC maps in fibrosis staging, although no significant differences existed in pairwise comparisons ( p = 0.0512 to p = 0.847)., Conclusion: Corrected apparent diffusion of DKI histogram analysis provides added value and better diagnostic performance to detect various liver fibrosis stages compared with ADC.

Selenoprotein K (SELENOK) is primarily observed in the endoplasmic reticulum, and serves to maintain the normal physiological functions of skeletal muscle. Skeletal muscle development and regeneration are associated with significant changes in the expression of specific microRNAs (miRNAs). Downregulated SELENOK expression is observed in chicken muscles deficient of Se. However, the mechanisms of miRNA regulation of SELENOK expression remain elusive. Here, deep sequencing was used to detect the miRNA profiles of muscle in Se deficient (-Se group) and normal (C group) chickens. A dual-luciferase reporter assay was adopted to verify the relationship between SELENOK and gga-let-7f-3p. In addition, gga-let-7f-3p was either overexpressed or knocked-down in chicken myoblasts. Furthermore, the cells were treated with N-acetyl-l-cysteine (NAC) or hydrogen peroxide (H2O2) in order to probe the factors involved in oxidative stress, endoplasmic reticulum stress (ERS) and apoptosis, respectively. Relative to the C group, there were 132 differentially expressed miRNAs (including 57 upregulated and 75 downregulated) in the muscles of the -Se group. The dual-luciferase reporter assay showed that SELENOK was a primary target of gga-let-7f-3p. It was also observed that the overexpression or knock-down of gga-let-7f-3p significantly influenced the SELENOK expression. Moreover, NAC blocked mimics of ga-let-7f-3p, thus inducing oxidative stress, ERS and apoptosis. Simultaneously, gga-let-7f-3p inhibitors blocked the stimulant effects caused by H2O2 in chicken myoblasts. Furthermore, Se deficiency downregulated the SELENOK protein expression and induced oxidative stress, ERS and apoptosis in chicken muscles. In conclusion, the gga-let-7f-3p-SELENOK pathway played a pivotal role in Se deficiency mediated muscle injuries through the induction of oxidative stress and ERS, ultimately promoting apoptosis.

Autophagy and apoptosis are two different biological processes that determine cell fates. We previously reported that autophagy inhibition and apoptosis induction are involved in lead(II)-induced cytotoxicity in primary rat proximal tubular (rPT) cells, but the interplay between them remains to be elucidated. Firstly, data showed that lead(II)-induced elevation of LC3-II protein levels can be significantly modulated by 3-methyladenine or rapamycin; moreover, protein levels of Autophagy-related protein 5 (Atg5) and Beclin-1 were markedly up-regulated by lead(II) treatment, demonstrating that lead(II) could promote the autophagosomes formation in rPT cells. Next, we applied three pharmacological agents and genetic method targeting the early stage of autophagy to validate that enhancement of autophagosomes formation can inhibit lead(II)-induced apoptotic cell death in rPT cells. Simultaneously, lead(II) inhibited the autophagic degradation of rPT cells, while the addition of autophagic degradation inhibitor bafilomycin A1 aggravated lead(II)-induced apoptotic death in rPT cells. Collectively, this study provided us a good model to know about the dynamic process of lead(II)-induced autophagy in rPT cells, and the interplay between autophagy and apoptosis highlights a new sight into the mechanism of lead(II)-induced nephrotoxicity., (Copyright © 2018. Published by Elsevier Inc.)

Background: To investigate the diagnostic value of diffusion kurtosis imaging (DKI) and diffusion-weighted imaging (DWI) in assessing liver regeneration after associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) compared with portal vein ligation (PVL)., Methods: Thirty rats were divided into the ALPPS, PVL, and control groups. DKI and DWI were performed before and 7 days after surgery. Corrected apparent diffusion (D), kurtosis (K) and apparent diffusion coefficient (ADC) were calculated and compared, radiologic-pathologic correlations were evaluated., Results: The volume of the right median lobe increased significantly after ALPPS. There were larger cellular diameters after ALPPS and PVL (P = 0.0003). The proliferative indexes of Ki-67 and hepatocyte growth factor were higher after ALPPS (P = 0.0024/0.0433). D, K and ADC values differed between the groups (P = 0.021/0.0015/0.0008). A significant correlation existed between D and the hepatocyte size (r = -0.523), no correlations existed in ADC and K (P = 0.159/0.111). The proliferative indexes showed moderate negative correlations with ADC (r = -0.484/-0.537) and no correlations with D and K (P = 0.100-0.877)., Discussion: Liver regeneration after ALPPS was effective and superior to PVL. DKI, especially the D map, may provide added value in evaluating the microstructure of liver regeneration after ALPPS, but this model alone may perform no better than the standard monoexponential model of DWI., (Copyright © 2017 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Coronary computed tomographic angiography is a robust non-invasive method to assess coronary artery disease (CAD) and analyze coronary plaque stability, especially for the non-calcified plaques. The aim of this study was to investigate the differential characteristics between the unstable coronary plaques and the stable coronary plaques using multi-slice computed tomography (MSCT)., Methods: Sixty patients with coronary heart disease (37 unstable plaques and 31 stable plaques) were included. The napkin ring thickness, napkin-ring sign, plaque CT attenuation and degree of lumen stenosis were retrospectively analyzed. The diagnostic performances of MSCT were determined to predict the unstable plaques. The difference was statistically significant if P<0.05., Results: The napkin ring thickness of the unstable plaques was thinner than that of the stable plaques (P<0.05). The napkin-ring sign was more frequently observed in the unstable group (89.2%) than the stable group (22.6%, P<0.05). The average CT value of the unstable plaques (26.8±17.8 HU) was lower than that of the stable plaques (68.5±25.5 HU, P<0.05). The unstable plaques had more severe lumen stenosis or occlusion (70.3%) than the stable plaques (41.9%, P<0.05). The measurable napkin ring thickness of the plaques with a cutoff value of 0.8 mm and an accuracy of 89.5% was one independent factor to predict unstable plaques. The optimal combined threshold of the napkin-ring sign and/or the plaque CT value of 53 HU with an accuracy of 80.9% was to predict unstable plaques., Conclusions: The optimal combined threshold of the napkin-ring sign and/or the plaque CT value ≤53 HU may be a good indicator to predict the unstable plaques in patients with CAD. The subgroup of measurable napkin ring thickness of the non-calcified plaques may also be an independent factor to predict the unstable plaques in patients with CAD., Competing Interests: Conflicts of Interest: An oral presentation was exhibited by Dr. Feng-xiang Song at the 2017 RSNA Annual Meeting.

Purpose: To investigate the value of diffusion kurtosis imaging (DKI) histogram analysis in assessing liver regeneration and the microstructure basis after associating liver partition and portal vein ligation for staged hepatectomy (ALPPS), in comparison with portal vein ligation (PVL)., Materials and Methods: Thirty rats were divided into the ALPPS, PVL, and control groups. Histograms of DKI using a 3T magnetic resonance imaging (MRI) scanner were performed for corrected apparent diffusion (D), kurtosis (K), and apparent diffusion coefficient (ADC). Mean, median, skewness, kurtosis, and the percentiles (5 th , 25 th , 50 th , 75 th , and 95 th ) were generated and compared, and radiologic-pathologic correlations were evaluated., Results: There were more significant volume increases of the right median lobe after ALPPS than PVL (P = 0.0304/0.0017). The ALPPS group had larger hepatocyte size (P = 0.009/0.000), higher Ki-67 and hepatocyte growth factor expression (P = 0.001-0.036) compared with both PVL and control groups. Mean, median, 5 th , 25 th , 50 th , 75 th percentiles of D map in ALPPS were lower than the control group (P = 0.001-0.022). Skewness and 75 th , 95 th percentiles of K map in ALPPS were higher than the PVL group (P = 0.011-0.042). No differences existed in the ADC map between groups (P = 0.073-0.291). Mean, median, 5 th , 25 th , 50 th percentiles of D map, and 5 th percentile of K map showed significant correlations with hepatocyte size (r = -0.582 to -0.426); no significant correlations were found in ADC parameters (P = 0.460-0.934)., Conclusion: ALPPS induced true accelerated liver hypertrophy, superior to that seen with PVL. Histogram analysis of diffusion kurtosis indices may provide added values in evaluating liver regeneration and the intrinsic microstructure basis after ALPPS in comparison with the standard monoexponential ADC., Level of Evidence: 3 Technical Efficacy Stage: Stage 2 J. Magn. Reson. Imaging 2018;47:729-736., (© 2017 International Society for Magnetic Resonance in Medicine.)

Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that regulates a cluster of oxidative stress-inducible genes in cells. Here, we aimed to investigate whether trehalose (Tre) protects primary rat proximal tubular (rPT) cells against cadmium (Cd)-induced oxidative stress via Nrf2 antioxidant pathway. Data showed that Tre treatment inhibited Nrf2 nuclear translocation and restored the decline in Kelch-like ECH-associated protein 1 (Keap1) protein level in Cd-exposed rPT cells. Moreover, Cd-activated Nrf2 target genes, including phase II detoxifying enzymes, that is, NAD(P)H quinone oxidoreductase 1 and heme oxygenase-1, direct antioxidant proteins, that is, glutathione peroxidase, superoxide dismutase, catalase, and glutathione biosynthesis-related proteins, that is, glutamatecysteine ligase catalytic subunit, glutamate cysteine ligase modifier subunit, and glutathione reductase, were all downregulated by co-treatment with Tre. Collectively, these findings demonstrate that Tre treatment alleviates Cd-induced oxidative stress in rPT cells by inhibiting the Nrf2-Keap1 signaling pathway., (© 2017 Wiley Periodicals, Inc.)

Background: Hepatic inflammatory pseudotumor (IPT) is classified into 2 types based on IgG4 stain: IgG4-related and non-IgG4-related; the two types differ not only in their pathological characteristics, but also in the clinical features. This study aimed to investigate the MR character of hepatic IPT, and differentiate the IgG4-related IPT from the non-IgG4-related IPT., Methods: Twenty-five patients with 27 histologically proven hepatic IPTs were retrospectively analyzed. Ten lesions were diagnosed as IgG4-related IPT, and the other 17 as non-IgG4-related IPT. The MR signal features on T1, T2-weighted, dynamic-enhanced, and diffusion-weighted imaging were evaluated and compared., Results: The dominant lesions were subcapsularly distributed (n=17, 63.0%) with clear boundary (n=20, 74.1%), and showed progressive enhancement pattern (n=21, 77.8%) with diffuse homogeneous (n=12, 44.4%) or heterogeneous (n=8, 29.6%) hyperintensity, accompanied by delayed capsule-like enhancement (n=17, 63.0%) and central nonenhanced areas (n=18, 66.7%). Morphological features (P>0.05) were not sufficient to differentiate IgG4-related IPT from non-IgG4-related IPT; the wash-out pattern was only found in 2 IgG4-related IPT, while the progressive enhancement pattern was more common in the non-IgG4-related lesions (n=16) (P=0.022). During portal and delayed phases, iso-/hypoenhanced lesions were only seen in 3 IgG4-related IPT, and circular-enhanced lesions (n=5) existed exceptionally in the non-IgG4-related group with significant differences (P=0.029 and 0.027). Most IgG4-related IPTs had lower apparent diffusion coefficient compared with the liver parenchyma (n=6), while most non-IgG4-related IPTs had higher apparent diffusion coefficient value (n=13) (P=0.046)., Conclusions: Although MR images of hepatic IPT have certain characteristics, they are not enough to differentiate IgG4-related IPT from non-IgG4-related IPT. The enhancement pattern, signal features on portal and delayed phases, and the apparent diffusion coefficient value of the lesion may be helpful for the diagnosis., (Copyright © 2017 The Editorial Board of Hepatobiliary & Pancreatic Diseases International. Published by Elsevier B.V. All rights reserved.)

Recent studies have shown that radiofrequency (RF) ablation therapy is a safe, feasible, and effective procedure for hepatic hemangiomas, even huge hepatic hemangiomas. RF ablation has the following advantages in the treatment of hepatic hemangiomas: minimal invasiveness, definite efficacy, high safety, fast recovery, relatively simple operation, and wide applicability. It is necessary to formulate a widely accepted consensus among the experts in China who have extensive expertise and experience in the treatment of hepatic hemangiomas using RF ablation, which is important to standardize the application of RF ablation for the management of hepatic hemangiomas, regarding the selection of patients with suitable indications to receive RF ablation treatment, the technical details of the techniques, therapeutic effect evaluations, management of complications, etc . A final consensus by a Chinese panel of experts who have the expertise of using RF ablation to treat hepatic hemangiomas was reached by means of literature review, comprehensive discussion, and draft approval., Competing Interests: Conflict-of-interest statement: The authors have no conflicts of interest to declare.

The development of targeted tyrosine kinase inhibitors (TKIs) has succeeded in altering the course of chronic myeloid leukemia (CML). However, a number of patients have failed to respond or experienced disease relapse following TKI treatment. Proviral integration site for moloney murine leukemia virus‑1 (PIM‑1) is a serine/threonine kinase that participates in regulating apoptosis, cell cycle, signal transduction and transcriptional pathways, which are associated with tumor progression, and poor prognosis. SMI‑4a is a selective PIM‑1 kinase inhibitor that inhibits PIM‑1 kinase activity in vivo and in vitro. The present study aimed to explore the mechanism underlying the antitumor effect of SMI‑4a in K562 and imatinib‑resistant K562 (K562/G) cell lines. It was demonstrated that SMI‑4a inhibited the proliferation of K562 and K562/G cells using a WST‑8 assay. The Annexin V‑propidium iodide assay demonstrated that SMI‑4a induced apoptosis of K562 and K562/G cells in a dose‑, and time‑dependent manner. Furthermore, Hoechst 33342 staining was used to verify the apoptosis rate. The clone formation assay revealed that SMI‑4a significantly inhibited the colony formation capacity of K562 and K562/G cells. Western blot analysis demonstrated that SMI‑4a decreased phosphorylated (p)‑Ser9‑glycogen synthase kinase (GSK) 3β/pGSK3β and inhibited the translocation of β‑catenin. In addition, the downstream gene expression of apoptosis regulator Bax and poly(ADP‑ribose) polymerase‑1 was upregulated, and apoptosis regulator Bcl‑2 and Myc proto‑oncogene protein expression levels were downregulated. Immunofluorescence results demonstrated changes in the expression level of β‑catenin in the plasma and nucleus. The results of the present study suggest that SMI‑4a is an effective drug to use in combination with current chemotherapeutics for the treatment of imatinib-resistant CML.

Active angiogenesis is the basic pathological feature of glioma. Tumor angiogenesis is involved in vascular endothelial cell migration to the tumor tissue and in the formation of tube-like structures. The present study aimed to investigate the role of leucine-rich repeats and immunoglobulin-like domains 2 (LRIG2) in glioma angiogenesis. Glioma (n=50) and normal brain (n=20) tissue samples were collected from patients to detect the expression of LRIG2, epidermal growth factor receptor (EGFR), vascular endothelial growth factor A (VEGF-A), and cluster of differentiation 31 (CD31) using immunohistochemistry. In addition, the association between the expression of LRIG2 in glioma tissue and the microvessel density (MVD) was analyzed. In vitro , the expression of LRIG2 in human glioma U87 and U251 cell lines was knocked down. Subsequently, cell migration and tube formation assays of human umbilical vein endothelial cells (HUVECs) were performed using a coculture system. The protein expression levels of LRIG2, EGFR, phosphorylated-EGFR and VEGF-A were determined using western blotting. The results demonstrated that the expression levels of LRIG2, EGFR, VEGF-A and CD31 were highly upregulated in glioma tissue samples. Furthermore, LRIG2 expression in glioma tissue samples was significantly correlated with the MVD. In vitro , the downregulation of LRIG2 inhibited HUVEC migration and tube formation induced by coculture with glioma cells. The downregulation of LRIG2 resulted in decreased expression of EGFR and VEGF-A. The effects of the LRIG2 knockdown were reversed following EGF treatment. These findings suggest that LRIG2 is a potential target for the inhibition of glioma angiogenesis, which is possibly mediated via the EGFR/VEGF-A signaling pathway.

The purpose of this study was to objectively assess the morbidity of post-thrombotic syndrome (PTS) in iliofemoral vein thrombosis treated with catheter-directed thrombolysis (CDT) and stenting under the protection of inferior vena cava (IVC) filter. All patients with an unprovoked episode of iliofemoral vein thrombosis combined with iliac vein compression syndrome (IVCS) during January 2011 and January 2015 were enrolled. Clinical records of all patients were evaluated. Firstly, cox regression was performed to find out the factors impacted the incidence of PTS. Then, Kaplan Meier analysis was conducted to verify the roles of these factors in PTS. A total of 247 patients who underwent CDT and IVC filter insertion for iliofemoral vein thrombosis and were found stenosis in the iliac vein after CDT were included in this study. Among them, 74 patients suffered PTS diagnosed via Villalta scale. Comparison with patients without stent implantation and filter withdrawal, patients with stent implantation and filter withdrawal had a less risk of PTS, but patients with a lesion in the left or bilateral proximal deep vein had a more risk of PTS. Cox regression found that stent implantation was a preventive measure to prevent PTS (OR 0.541, 95% CI 0.334-0.876, p = 0.012). The Kaplan-Meier curve found that patients with stent implantation had a less ratio of PTS occurrence (P = 0.008). In patients with iliofemoral vein thrombosis and IVCS, stent implantation to solve the residual obstruction after CDT might play an important role in preventing PTS.

Herein, we report a novel thermal/photoresponsive shape-memory polyurethane network with a pendant azobenzene group by utilizing its anisotropic-isotropic phase transitions and photoresponsive feature concurrently. To achieve this goal, the side-chain liquid crystalline polyurethane networks based on the pendant azobenzene group [SCLCPU(AZO)-Ns] were developed in a well-defined architecture. The smectic C nature of an LC phase in the polyurethane networks was confirmed by differential scanning calorimetry, polarized optical microscopy, and one-dimensional and two-dimensional wide-angle X-ray diffraction. The well-defined architecture-made SCLCPU(AZO)-N displays two distinct transition temperatures (T trans ) (T g and T cl ), with a difference of about 40 °C. Consequently, the excellent triple-shape-memory effect in this network was demonstrated by cyclic thermomechanical analysis. By making full use of the trans-cis photoisomerization of azobenzene, the reversible bending and unbending behaviors were realized under the light irradiation with wavelengths of 450 and 550 nm, respectively.

Background: Few studies have investigated the value of Gd-EOB-DTPA-enhanced T1 mapping in exact fibrosis staging, especially its correlation with hepatic molecular transporters., Aims: To investigate the diagnostic value of Gd-EOB-DTPA-enhanced T1 mapping in staging liver fibrosis and its relationship with hepatic molecular transporters., Methods: Thirty rats were divided into the carbon tetrachloride-induced fibrosis groups and a control group. T1-mapping was performed before and 20min after administration of Gd-EOB-DTPA. The T1 relaxation time and reduction rate (Δ%) were calculated, and their correlations with the degree of fibrosis, necroinflammatory activity, iron load and hepatic molecular transporters were assessed and compared., Results: Hepatobiliary phase T1 relaxation time (HBP) and Δ% were different between each adjacent fibrosis subgroups(P=0.000-0.042). Very strong correlations existed between fibrosis and both HBP and Δ% (r=0.960/-0.952), and multivariate analyses revealed that fibrosis was the only factor independently predicted by HBP (P=0.000) and Δ% (P=0.001), comparing to necroinflammatory activity and iron load. The expression of the organic anion transporting polypeptide1a1 (Oatp1a1) was significantly correlated with HBP and Δ% at both mRNA (r=-0.741/0.697) and protein (r=-0.577/0.602) levels. Weaker correlations were found for multidrug resistance associated protein2 (Mrp2). Generally, both transporters showed decreasing levels with increasing degrees of fibrosis., Conclusion: Gd-EOB-DTPA-enhanced T1 mapping may provide a reliable diagnostic tool in staging liver fibrosis, and can be regarded as a useful imaging biomarker of hepatocyte transporter function., (Copyright © 2017 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Aim: The intestinal barrier is made up of epithelial cells and intercellular junctional complexes to regulate epithelial ion transport and permeability. Dopamine (DA) is able to promote duodenal epithelial ion transport through D1-like receptors, which includes subtypes of D 1 (D 1 R) and D 5 (D 5 R), but whether D1-like receptors influence the duodenal permeability is unclear., Methods: FITC-dextran permeability, short-circuit current (I SC ), Western blot, immunohistochemistry and ELISA were used in human D 5 R transgenic mice and hyperendogenous enteric DA (HEnD) rats in this study., Results: Dopamine induced a downward deflection in I SC and an increase in FITC-dextran permeability of control rat duodenum, which were inhibited by the D1-like receptor antagonist, SCH-23390. However, DA decreased duodenal transepithelial resistance (TER), an effect also reversed by SCH-23390. A strong immunofluorescence signal for D 5 R, but not D 1 R, was observed in the duodenum of control rat. In human D 5 R knock-in transgenic mice, duodenal mucosa displayed an increased basal I SC with high FITC-dextran permeability and decreased TER with a lowered expression of tight junction proteins, suggesting attenuated duodenal barrier function in these transgenic mice. D 5 R knock-down transgenic mice manifested a decreased basal I SC with lowered FITC-dextran permeability. Moreover, an increased FITC-dextran permeability combined with decreased TER and tight junction protein expression in duodenal mucosa were also observed in HEnD rats., Conclusion: This study demonstrates, for the first time, that DA enhances duodenal permeability of control rat via D 5 R, which provides new experimental and theoretical evidence for the influence of DA on duodenal epithelial barrier function., (© 2016 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.)

Purpose: To investigate and compare the diagnostic value of diffusion kurtosis imaging (DKI) with diffusion-weighted imaging (DWI) in assessing and quantifying hepatic fibrosis., Methods: Thirty rats were divided into the control group (n = 6) and the fibrosis experimental groups (n = 6 per group) with CCl 4 administration for 2, 4, 6, and 8 weeks. Liver fibrosis stage (S) and necroinflammatory activity grade (G) were histopathologically determined. DKI and DWI were performed; mean apparent diffusion (MD), mean kurtosis (MK), and apparent diffusion coefficient (ADC) values were calculated. DKI parameters were compared with ADC values according to G/S scores., Results: Strong inverse correlations were found between the degree of fibrosis and both MD and ADC (r = -0.840 and r = -0.760), while only weak correlation existed in MK (r = 0.405). ROC analyses demonstrated the AUC in MD, MK, and ADC of 0.862, 0.684, 0.817 for identifying mild and severe fibrosis, and 0.757, 0.675, 0.733 for non-cirrhosis and cirrhosis, respectively. The degree of fibrosis was significantly correlated with α-smooth muscle actin (α-SMA) (P < 0.0001); α-SMA had strong inverse correlation with MD (r = -0.723), moderate inverse correlation with ADC (r = -0.613), and very weak correlation with MK (r = 0.175). Additionally, MD was strongly correlated with the necroinflammatory activity (r = -0.758), ADC was moderately correlated (r = -0.492), and MK was weakly correlated (r = 0.254)., Conclusion: DKI may provide added information and serve as a valuable tool for the characterization and surveillance of liver fibrosis in a non-invasive manner.

Objective: To investigate the clinical features and surgical strategy for pediatric intractable epilepsy due to posterior quadrantic cortical dysplasia and to assess the surgical outcomes., Methods: The clinical features and preoperative evaluation results of 14 children with intractable epilepsy due to posterior quadrantic cortical dysplasia were retrospectively analyzed. The localization values of video-electroencephalography and intraoperative monitoring and the indications, advantages and disadvantages of temporoparietooccipital disconnection were evaluated., Results: The 14 children had different seizure types, of which spasm was the most common one. The lesions of cortical dysplasia involved the central cerebral region in 2 cases. After temporoparietooccipital disconnection in 14 patients, 13 cases were seizure-free; only one case still had seizures, but the frequency dropped by more than 50%., Conclusions: Temporoparietooccipital disconnection is a safe and effective surgical procedure for children with intractable epilepsy due to posterior quadrantic cortical dysplasia.

Celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, has been demonstrated to exert antitumor activity in a variety of cancer cells. The underlying mechanism involves inhibition of cell cycle progression and induction of apoptosis. Besides, celecoxib has also been found to induce autophagy in some solid tumor cells. The aim of this study was to investigate the effect of celecoxib on cell proliferation in HL-60 human acute leukemia cells and to explore the potential mechanism. HL-60 cells were exposed to various concentrations of celecoxib and cell viability was evaluated by the MTT assay. Apoptosis was analyzed with flow cytometry and the amount of autophagosome was evaluated by LysoTracker probe labelling. The expression of apoptosis- and autophagy-related proteins was assayed by Western blot and LysoSensor probe labelling was used to detect the effect of celecoxib on the lysosomal functions. The results of this study indicated that celecoxib inhibited cell proliferation in a time- and dose-dependent fashion. The flow cytometry analysis showed that celecoxib induced apoptosis at low concentrations and mainly cell necrosis at high concentrations. The Western blot test confirmed the induction of apoptosis by the upregulation of apoptosis-related proteins cleaved caspase-3 and cleaved PARP. Furthermore, this study demonstrated that celecoxib prevented the autophagic flux by inhibiting lysosome function; the fluorescence intensity of the LysoTracker probe and the level of autophagy-related proteins LC3-II and p62 were increased, but the fluorescence intensity of the LysoSensor probe was weakened. These findings show that celecoxib is an autophagy suppresser and has antitumor effects in HL-60 cells by inducing cell apoptosis and necrosis., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Zoledronic acid (ZOL), a nitrogen‑containing bisphosphonate, is widely used in metastatic bone disease. Previous studies indicate that ZOL has marked anti‑leukemia activity, however, the underlying mechanism of action remains to be elucidated. The present study aimed to explore the mechanism of the anti‑leukemia effect of ZOL in leukemia cells. It was observed that ZOL inhibited the proliferation of HL‑60 and adriamycin‑resistant HL‑60 (HL‑60/A) cells using a WST‑8 assay. An Annexin V‑propidium iodide indicated that ZOL induced apoptosis of the two cell types in a dose‑ and time‑dependent manner. Hoechst 33342 staining was also used to verify the levels of apoptosis. The colony formation assay demonstrated that ZOL significantly inhibited colony formation capacity in acute myeloid leukemia (AML) cells. This was achieved by the induction of S‑phase cell cycle arrest, downregulation of B‑cell lymphoma 2 (Bcl‑2) and upregulation of Bcl‑2 associated X protein and cleaved poly (ADP‑ribose) polymerase. The results indicate that ZOL inhibited cell proliferation by inducing apoptosis via the mitochondrial apoptotic pathway and this anti‑leukemic activity appeared notably enhanced in HL‑60/A cells. As ZOL is already available for clinical use, these results indicate that it may be an effective addition to the chemotherapeutic strategies for AML.

Purpose: To compare MR imaging features of combined hepatocellular-cholangiocarcinoma (cHCC-CC) in normal, fibrotic, and cirrhotic livers., Methods: A total of 64 patients with 67 pathologically proven cHCC-CCs were retrospectively analyzed. Patients were classified into three groups according to the patients' liver condition: patients with normal liver (F0, group 1), fibrosis without cirrhosis (F1-3, group 2), and cirrhosis (F4, group 3). The morphological and MR signal features on T1- and T2-weighted, dynamic contrast-enhanced, diffusion-weighted imaging, as well as the accompanying imaging findings, were evaluated and compared., Results: There were 12, 19, and 33 patients in groups 1, 2, and 3, respectively. Tumors in the fibrotic and cirrhotic livers were smaller than those in the normal liver, and tumors with cirrhosis had the smallest size (P = 0.0326). No statistical difference was found when comparing the signal intensity on T2-weighted imaging (P = 0.496), but iso- or hypointense lesions were only found in the fibrosis (n = 2) or cirrhosis group (n = 2). Enhancement pattern was different between groups, the washout pattern was more often seen in the cirrhosis group (P = 0.049), and the accompanying mosaic architecture was also more commonly seen in the cirrhosis group (P = 0.048). The ADC values of the lesions were not different among the three groups (P = 0.899)., Conclusion: MRI may provide valuable information for the diagnosis and differential diagnosis of cHCC-CC in normal, fibrotic, and cirrhotic livers. The nodule size, enhancement pattern, and the presence of mosaic architecture in cHCC-CC differ between different degrees of background liver disease.

The interaction between bone marrow stromal cells and leukemia cells is critical for the persistence and progression of leukemia, and this interaction may account for residual disease. However, the link between leukemia cells and their environment is still poorly understood. In our study, runt‑related transcription factor 3 (RUNX3) was identified as a novel target gene affected by As2O3 and involved in mesenchymal stem cell (MSC)‑mediated protection of leukemia cells from As2O3‑induced apoptosis. We observed induction of RUNX3 expression and the translocation of RUNX3 into the nucleus after As2O3 treatment in leukemia cells. In K562 chronic myeloid leukemia cells, downregulation of endogenous RUNX3 compromised As2O3‑induced growth inhibition, cell cycle arrest, and apoptosis. In the presence of MSC, As2O3‑induced expression of RUNX3 was reduced significantly and this reduction was modulated by CXCL12/CXCR4 signaling. Furthermore, overexpression of RUNX3 restored, at least in part, the sensitivity of leukemic cells to As2O3. We conclude that RUNX3 plays an important role in As2O3‑induced cellular responses and allows cells to overcome MSC‑mediated drug resistance. Therefore, RUNX3 is a promising target for therapeutic approaches to overcome MSC‑mediated drug resistance.

An acrylic monomer bearing xanthene group, N-oxethyl acrylate-N'-rhodamine B hydrazide (ARBHE) was synthesized from N-hydroxyl ethyl-N'-rhodamine hydrazide (RBHE) and acryloyl chloride (Ac) in the presence of triethylamine in dry dichloromethane (CH2Cl2) at room temperature. The synthesized ARBHE was identified by FTIR, (1)H NMR spectra and elementary analysis. Copolymer poly(AM-ARBHE) of ARBHE and AM was synthesized with thermal initiator by free radical precipitation polymerization and it was characterized by the method of FTIR and (1)H NMR. Its molecular weights (Mη) was 7.03 × 10(3) g mol(-1) and the content of rhodamine units in the polymer chains was 1.44 % in mole fraction. The ability of the poly(AM-ARBHE) to detect different metal cations (Ag(+), Ba(2+), Cd(2+) Co(2+), Cr(3+), Cu(2+), Co(2+) K(+), La(3+), Mg(2+), Na(+), Ni(2+), Pb(2+), Fe(2+), Fe(3+), Hg(2+) and Zn(2+)) in water was investigated. Upon addition of Cr(3+), Fe(3+) or Hg(2+) ions to the aqueous solution, visual color change and fluorescence enhancement were observed. Moreover, other metal ions did not induce obvious changes to the fluorescence spectra except to Fe(2+). The detection limit of poly(AM-ARBHE) was less than 1 × 10(-11) M. The results suggest that this copolymer may offer potential as a polymeric sensor for Cr(3+), Fe(3+) and Hg(2+) ions in water.

Objective: To investigate the effect of low-intensity anticoagulation therapy for Chinese population with heart valve replacement., Methods: From January 2011 to March 2012, 3 000 patients with heart valve replacement in Fuwai Hospital and West China Hospital were followed-up for 1 year, the method and intensity of postoperative anticoagulation, as well as the complications were studied and analyzed., Results: The rate of follow-up was 88.57%, and the cumulative follow-up was 1 726.1 patient-years (Pty). The mean oral warfarin dosage was (2.68 ± 6.45) mg/d, and the mean INR values of the patients treated in Fuwai Hospital and West China Hospital were 2.01 ± 1.10 and 186 ± 0.69 respectively (total 54 379 samples). The total rates of anticoagulation complication and mortality were 5.79% Pty and 0.12% Pty respectively, among which the morbidity and mortality of hemorrhage were 3.59% Pty and 0.12% Pty respectively, while the morbidity and mortality of thromboembolism were 2.03% Pty and 0.00% Pty respectively. There are no significant differences of actual anticoagulation intensity (P = 0.28)and the complication rates between the two hospitals ., Conclusion: The optimal intensity scope (INR) of 1.5-2.5 (mean 1.8-2.0) is safe and efficient for Chinese patients with prosthetic heart valves, and no significant regional difference in the intensity of anticoagulation therapy required.