A novel mitochondrial metabolism-related gene signature for predicting the prognosis of oesophageal squamous cell carcinoma.

Oesophageal squamous cell carcinoma (ESCC) is one of the most lethal cancers worldwide. Due to the important role of mitochondrial metabolism in cancer progression, a clinical prognostic model based on mitochondrial metabolism and clinical features was constructed in this study to predict the prognosis of ESCC. Firstly, the mitochondrial metabolism scores (MMs) were calculated based on 152 mitochondrial metabolism-related genes (MMRGs) by single sample gene set enrichment analysis (ssGSEA). Subsequently, univariate Cox regression and LASSO algorithm were used to identify prognosis-associated MMRG and risk-stratify patients. Functional enrichment, interaction network and immune-related analyses were performed to explore the features differences in patients at different risks. Finally, a prognostic nomogram incorporating clinical factors was constructed to assess the prognosis of ESCC. Our results found there were differences in clinical features between the MMs-high group and the MMs-low group in the TCGA-ESCC dataset (P<0.05). Afterwards, we identified 6 MMRGs (COX10, ACADVL, IDH3B, AKR1A1, LIAS, and NDUFB8) signature that could accurately distinguish high-risk and low-risk ESCC patients. A predictive nomogram that combined the 6 MMRGs with sex and N stage to predict the prognosis of ESCC was constructed, and the areas under the receiver operating characteristic (ROC) curve at 1, 2 and 3 years were 0.948, 0.927 and 0.848, respectively. Finally, we found that COX10, one of 6 MMRGs, could inhibit the malignant progression of ESCC in vitro. In summary, we constructed a clinical prognosis model based on 6 MMRGs and clinical features which can accurately predict the prognosis of ESCC patients.

The high-risk features and effect of postoperative radiotherapy on survival for patients with surgically treated stage IIIA-N2 non-small cell lung cancer.

OBJECTIVES: Although postoperative radiotherapy (PORT) could reduce the incidence of local recurrence in patients with IIIA-N2 non-small cell lung cancer (NSCLC), the role of PORT on survival in patients with surgically treated stage IIIA-N2 NSCLC remains controversial. Therefore, this study was designed to evaluate the effect of PORT on survival for patients with surgically treated stage IIIA-N2 NSCLC. MATERIALS AND METHODS: This study population was chosen from the Surveillance, Epidemiology, and End Results database. The Cox proportional hazards regression analysis was used to determine significant contributors to overall survival (OS) and cancer special survival (CSS) outcomes. To balance baseline characteristics between the non-PORT group and PORT group, propensity score matching (PSM) with 1:1 propensity nearest-neighbor match by 0.001 matching tolerance was conducted by R software. Furthermore, a Kaplan-Meier curve was used to visualize the OS and CSS between the PORT group and non-PORT group survival probability. RESULTS: Of all evaluated cases, 4511 with IIIA-N2 NSCLC were eligible for inclusion, of which 1920 were enrolled into the PORT group. On univariate analysis and multivariate analysis, sex, age, year of diagnosis, race, histologic type, T stage, PORT, use of chemotherapy, and positive regional nodes were significantly associated with OS and CSS in IIIA-N2 NSCLC (P < 0.05). However, PORT was not significantly associated with OS (univariate HR = 0.92, 95%CI 0.85-0.99, P = 0.02; multivariate HR = 1.01, 95%CI 0.93-1.08, P = 0.91) and CSS (univariate HR = 0.92, 95%CI 0.85-1.01, P = 0.06; multivariate HR = 1.103 95%CI 0.94-1.12, P = 0.56) in IIIA-N2 NSCLC. Meanwhile, after PSM, neither OS nor CSS did differ significantly between the non-PORT group and PORT group (OS HR = 1.08, 95%CI 0.98-1.19, P = 0.12; CSS HR = 1.10, 95%CI 0.99-1.23, P = 0.07). CONCLUSION: PORT did not contribute to a survival benefit in patients with surgically treated stage IIIA-N2 NSCLC.

Positive Chemotaxis of CREKA-Modified Ceria@Polydopamine Biomimetic Nanoswimmers for Enhanced Penetration and Chemo-photothermal Tumor Therapy.

Tumor interstitial pressure represents the greatest barrier against drug diffusion into the depth of the tumor. Biometric nanomotors highlight the possibility of enhanced deep penetration and improve cellular uptake. However, control of their directionality remains difficult to achieve. Herein, we report cysteine-arginine-glutamic acid-lysine-alanine (CREKA)-modified ceria@polydopamine nanobowls as tumor microenvironment-fueled nanoscale motors for positive chemotaxis into the tumor depth or toward tumor cells. Upon laser irradiation, this nanoswimmer rapidly depletes the tumor microenvironment-specific hydrogen peroxide (H2O2) in the nanobowl, contributing to a self-generated gradient and subsequently propulsion (9.5 µm/s at 46 °C). Moreover, the asymmetrical modification of CREKA on nanobowls could automatically reconfigure the motion direction toward tumor depth or tumor cells in response to receptor-ligand interaction, leading to a deep penetration (70 µm in multicellular spheroids) and enhanced antitumor effects over conventional nanomedicine-induced chemo-photothermal therapy (tumor growth inhibition rate: 84.2% versus 56.9%). Thus, controlling the direction of nanomotors holds considerable potential for improved antitumor responses, especially in solid tumors with high tumor interstitial pressure.

A photo-activable nano-agonist for the two-signal model of T cell in vivo activation.

The two-signal model of T cell activation has helped shape our understanding of the adaptive immune response for over four decades. According to the model, activation of T cells requires a stimulus through the T cell receptor/CD3 complex (signal 1) and a costimulatory signal 2. Stimulation of activatory signals via T cell agonists has thus emerged. However, for a robust T cell activation, it necessitates not only the presence of both signal 1 and signal 2, but also a high signaling strength. Herein, we report a photo-activable nano-agonist for the two-signal model of T cell in vivo activation. A UV-crosslinkable polymer is coated onto upconversion nanoparticles with satisfactory NIR-to-UV light conversion efficiency. Then dual signal molecules, i.e., signal 1 and signal 2, are conjugated to the polymer end to yield the photo-activable T cell nano-agonist. In melanoma and breast cancer models, photo-activable nano-agonist could bind onto corresponding activatory receptors on the surface of T cells, but has limited activity without the application of NIR light (absence of photo-crosslinking of receptors and consequently a poor signaling strength). While when the NIR light is switched on locally, T cells in tumor are remarkably activated and kill tumor cells effectively. Moreover, we do not observe any detectable toxicities related to the photo-activable nano-agonist. We believe with two activatory signals being simultaneously strengthened by local photo-switched crosslinking, T cells realize a robust and selective activation in tumor and, consequently contribute to an enhanced and safe tumor immunotherapy.

Integrated transcriptome, proteome and single-cell sequencing uncover the prognostic and immunological features of colony-stimulating factor 3 receptor in pan-cancer.

BACKGROUND: Colony-stimulating factor 3 receptor (CSF3R) has been demonstrated to be associated with various hematological tumors, especially chronic neutrophilic leukemia; however, the detailed roles of CSF3R in other cancers remain to be explored. METHODS: In the present study, we systematically analyzed the expression profiles of CSF3R in pan-cancer by comprehensive bioinformatics databases, such as Tumor Immune Estimation Resource, version 2 (TIMER2.0), Gene Expression Profiling Interactive Analysis, version 2 (GEPIA2.0), etc. GEPIA2.0 was also used to analyze the relationship between CSF3R expression and patients' survival prognosis. RESULTS: We found that the high expression of CSF3R was associated with a poor prognosis in the brain tumor patients, such as brain lower grade glioma and glioblastoma multiforme. In addition, we further investigated the genetic mutation and DNA methylation level of CSF3R in multiple cancers. Immune infiltration analysis showed that CSF3R expression was positively correlated with a variety of tumor-infiltrating immune cells in most cancers. Single cell sequencing indicated that CSF3R levels were correlated with several cancer-associated pathways, such as DNA damage, cell invasion, and stemness. CONCLUSIONS: Taken together, the role of CSF3R in multiple cancers might reveal its potential as a novel prognostic biomarker and therapeutic target for cancer patients.

Ferritin-Hijacking Nanoparticles Spatiotemporally Directing Endogenous Ferroptosis for Synergistic Anticancer Therapy.

Existing ferroptosis as an iron-dependent form of regulated cell death primarily relies on importing exogenous iron. However, the excessive employment of toxic materials may cause potential adverse effects on human health. Herein, a ferritin-hijacking nanoparticle (Ce6-PEG-HKN15 ) is fabricated, by conjugating the ferritin-homing peptide HKN15 with the photosensitizer chlorin e6 (Ce6) for endogenous ferroptosis without introducing Fenton-reactive metals. Once internalized, the designed Ce6-PEG-HKN15 NPs can specifically accumulate around ferritin. With laser irradiation, the activated Ce6 in nanoparticles potently generates reactive oxygen species (ROS) surrounding ferritin. Abundant ROS not only helps to destroy the iron storage protein and activate endogenous ferroptosis but also directly kill tumor cells. In turn, the released iron partially interacts with intracellular excess H2 O2 to produce O2 , thereby enhancing photodynamic therapy and further amplifying oxidative stress. Overall, this work highlights the possibility of endogenous ferroptosis via spatiotemporally destroying ferritin, offering a paradigm for synergistic ferroptosis-photodynamic antitumor therapy.

The Role of Problematic Smartphone Uses and Psychological Distress in the Relationship Between Sleep Quality and Disordered Eating Behaviors Among Chinese College Students.

Background: Sleep problems and eating disorders (EDs) are both serious public health concerns often seen in young adults. Yet, the underlying mechanisms for such associations are largely unknown. This study aims to examine potential serial multiple mediation effects of problematic smartphone use (PSU) and psychological distress (i.e., depressive and anxiety symptoms) in the relationship between sleep quality and disordered eating behaviors/attitudes (DEBs). Methods: A total of 4,325 students from two Tibet universities in China (2,657 females and 1,668 males) completed an online survey that included the following measurements: Eating Attitude Test-26 for disordered eating behaviors/attitudes, the Chinese Version of Pittsburgh Sleep Quality Index (CPSQI), Smartphone Addiction Scale-Short Version (SAS-SV) for problematic smartphone use, Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7) for psychological distress. Results: While the direct path linking sleep quality and DEBs was not found to be significant (Standardized ß = 0.006, 95% CI = -0.0667~0.0970), both PSU (Standardized ß = 0.016, 95% CI = 0.0256~0.0591) and anxiety symptoms (Standardized ß = 0.014, 95% CI = 0.0203~0.0526) may mediate a link between sleep quality and DEBs; serial multiple mediation analysis revealed that a serial indirect pathway of "sleep quality -> PSU -> anxiety symptoms -> DEBs" existed(Standardized ß = 0.001, 95% CI = 0.0002~0.0012). Similarly, while the direct path linking sleep quality and DEBs was not found to be significant (Standardized ß = 0.006, 95% CI = -0.0667~0.0970), both PSU (Standardized ß = 0.020, 95% CI = 0.0337~0.0692) and depressive symptoms (Standardized ß = 0.015, 95% CI = 0.0139~0.0652) may mediate a link between sleep quality and DEBs; serial multiple mediation analysis revealed that a serial indirect pathway of "sleep quality -> PSU -> depressive symptoms -> DEBs" existed (Standardized ß = 0.001, 95% CI = 0.0006~0.0038). Conclusions: Psychological and behavioral factors may comprehensively work together, leading to flow-on effects from sleep problems to disordered eating behaviors among university students. Appropriate interventions that target problematic smartphone use could thus potentially reduce anxiety and depression levels, which in turn will provide a buffer against the negative impact of poor sleep quality on eating disorder symptoms.

Biomimetic Melanosomes Promote Orientation-Selective Delivery and Melanocyte Pigmentation in the H2O2-Induced Vitiligo Mouse Model.

Extremely limited drug retention and depigmentation represent the greatest barriers against vitiligo treatment advancement. Here, inspired by biological melanosomes, the primary melanin transporter, we developed biomimetic melanosomes to combat reactive oxygen species (ROS)-mediated melanocyte damage and depigmentation. Briefly, methylprednisolone (MPS) and melanin-mimicking polydopamine (PDA) were encapsulated inside lysine-proline-valine (KPV)-modified deformable liposomes (KPV-Lipos). Owing to their phospholipid bilayer flexibility and the specific affinity for melanocortin 1 receptor (MC1R), KPV-Lipos exhibited 1.43-fold greater skin deposition than traditional liposomes. The binding of KPV and its receptor also contributed to activating the cAMP-tyrosinase (TYR) signaling pathway, improving the endogenous melanin content. In addition, PDA mimicked melanosomes as it effectively increased the exogenous melanin content and scavenged ROS. Meanwhile, MPS inhibited inflammatory cytokine secretion, limiting the depigmented area. Ultimately, the biomimetic melanosomes affected the skin color of mice with H2O2-induced vitiligo. These melanosomes show potential as a universal platform for the self-supply of melanin by self-driven melanin synthesis with exogenous supplementation. Furthermore, this study offers ideas for the production of artificial packed melanosome substitutes for melanocyte-related diseases.

MicroRNA­93 inhibits the apoptosis and inflammatory response of tubular epithelial cells via the PTEN/AKT/mTOR pathway in acute kidney injury.

Renal tubular epithelial cell injury is the main cause of septic acute kidney injury (AKI), which is characterized by the excessive inflammatory response and apoptosis. Numerous studies have demonstrated that miRNAs are associated with inflammatory response and apoptosis in numerous diseases. The present study mainly focuses on investigating the association between microRNA (miRNA/miR) expression and inflammatory response and apoptosis in the pathogenesis of AKI. In vitro and in vivo models of AKI were simulated using Escherichia coli lipopolysaccharide (LPS)­administrated kidney epithelial cells and mice, respectively. The miRNA expression profile was examined using miRNA microarray in kidney tissues. Next, the effects of miR­93 upregulation on the apoptosis, cytokine expression and oxidative stress in the LPS­stimulated TCMK­1 were tested. The target genes of this miRNA were investigated, and the regulatory association between miR­93 and the AKT/mTOR pathway was investigated. The results demonstrated that miR­93 was the most downregulated miRNA in mice kidney. Furthermore, in LPS­induced renal tubular epithelial cells (TECs) injury model, that upregulation of miR­93 was found to attenuate the apoptosis and inflammatory response, as well as reactive oxygen species generation. Mechanistically, phosphatase and tensin homolog deleted on chromosome 10 (PTEN) was identified as a target of miR­93. Further experiments revealed that LPS­induced the decrease of phosphorylated (p)­AKT and p­mTOR protein expression in vitro are reversed by the overexpression of miR­93. The results of the present study suggested that the protective effect of miR­93 on AKI may be associated with the activation of PTEN/AKT/mTOR pathway. miR­93 may serve as a potential therapeutic target in sepsis­induced AKI.

A Decreased Level of Soluble Klotho Can Predict Cardiovascular Death in No or Mild Abdominal Aortic Calcification Hemodialysis Patients.

Background: Soluble Klotho plays an important role in cardiovascular disease and death in chronic kidney disease (CKD). We assessed the relationship between serum soluble Klotho (sKL) level and outcome in MHD patients. Methods: Soluble Klotho was detected by ELISA. Cox regression analysis and Kaplan-Meier analysis showed the relationship between sKL and cardiovascular disease (CVD) mortality in maintenance hemodialysis (MHD) patients. Results: There were 45 cases (35.2%) of all-cause death and 36 cases (28.1%) of CVD mortality. Multivariate linear regression analysis showed that Log[iPTH] (γ = -0.224, P = 0.015) was an independent predictor of sKL level. Cox regression showed that lower sKL was associated with higher CVD mortality rate [OR = 0.401, 95% CI (0.183-0.867), P = 0.022]. Kaplan-Meier analysis showed that the CVD mortality rate increased significantly in patients with low sKL (P = 0.006). Compared with high sKL patients, low sKL patients with no or mild vascular calcification [aortic calcification score (AACs) ≤ 4] had no significant difference in all-cause mortality rate. The CVD mortality rate was significantly lower in high sKL patients (P = 0.004) than in those with low sKL. In the severe calcification group (AACs ≥ 5), all-cause and CVD mortality rates were similar between different sKL groups (P = 0.706 and 0.488, respectively). The area under the receiver-operating characteristic curve (AUC) of soluble Klotho for predicting the CVD in MHD patients with AACs ≤ 4 was 0.796 (0.647-0.946, P = 0.017), sensitivity was 0.921, and specificity was 0.50 for a cutoff value of 307.69 pg/ml. Conclusions: Lower sKL was associated with higher CVD mortality rate. Lower sKL concentration in MHD patients with no or mild calcification can predict CVD mortality.

Body mass index combined with waist circumference can predict moderate chronic kidney disease: A retrospective study.

ABSTRACT: Overweight and obesity may be associated with poor clinical outcome, including chronic kidney disease (CKD). However, whether body mass index (BMI), waist-to-hip ratio (WHR), and waist circumference (WC) are related to CKD is yet to be elucidated.A total of 7593 adults were divided into 4 groups based on the estimated glomerular filtration rate (eGFR) quartile. The eGFR was calculated with the CKD Epidemiology Collaboration. Multiple linear regression analyzed the association between eGFR and WHR, BMI, and WC. Logistic regression analysis determined whether the CKD patients were associated with WHR, BMI, and WC after adjusting for other variables.The mean age of the cohort was 72.34 ±â€Š7.30 years. Multiple linear regression analysis showed that WC (P = .006) was associated with eGFR, although adjusted by lifestyle factor and biochemical indicators. The individuals in the underweight, overweight, and obese groups had significantly lower eGFR value than those in the healthy weight group in moderate CKD. The eGFR in the overweight group with WHR ≤0.894 was higher than in the healthy weight group with WHR >0.894 group (P = .036). Overweight with WHR ≤0.894 group had a longer WC with a pronounced increase in the hip circumference. Logistic regression analysis showed that the WC (OR = 1.362, P < .001) and BMI (OR = 1.227, P = .031) were independent risk factors for moderate CKD patients. Each standard deviation (SD) of high BMI and WC level was associated with 23.0% and 17.3% higher odds of moderate CKD (OR = 1.230, P = .017 and OR = 1.173, P = .021, respectively).WC is an independent risk factor for eGFR. Combined BMI and WC are important factors that would predict moderate CKD patients.

The pathophysiological mechanism of ischemic stroke after hypobaric hypoxia simulation at high altitude.

Tibet is an area in China with a high incidence of stroke, typically attributed to hypobaric hypoxia. The present study aimed to observe the neuronal injury of ischemic stroke after hypobaric hypoxia and explore the mechanism by which N-methyl-D-aspartate receptor (NMDAR) and its downstream pathways are involved. This study employed a hypobaric chamber to imitate high altitude at 4000 m. After hypoxia, the middle cerebral artery occlusion (MCAO) model was used to mimic ischemic stroke. Behavioral tests and measurements of infarct area were used to observe neuronal injuries. The expression of NMDAR, Ca2+/calmodulin-dependent protein kinase II (CaMKII) and phosphorylated CaMKII (Threonine 286) (P-CaMKII) was tested by western blot, and hematological tests were used to count the number of red blood cells (RBCs) and hemoglobin. Compared with the plain+MCAO group, the neurological deficit scores and infarct area of rats in the 4000 m + MCAO group were all decreased, and the protein expression of NMDAR, CaMKII and P-CaMKII was reduced. Compared with the plain group, the numbers of RBCs, hemoglobin and hematocrit were increased in the 4000 m group; compared with the 4000 m groups, the three indexes were increased in the 4000 m + MCAO groups. The neuronal injuries after hypoxia were not more serious than those in rats enduring ischemia and reperfusion in plain. The underlying mechanisms were related to the decreased expression of NMDAR and CaMKII; furthermore, the increased numbers of RBCs and hemoglobin may be crucial mechanisms for the incidence and development of ischemic stroke at high altitude.

Sialic acid-engineered mesoporous polydopamine nanoparticles loaded with SPIO and Fe3+ as a novel theranostic agent for T1/T2 dual-mode MRI-guided combined chemo-photothermal treatment of hepatic cancer.

Hepatic cancer is a serious disease with high morbidity and mortality. Theranostic agents with effective diagnostic and therapeutic capability are highly needed for the treatment of hepatic cancer. Herein, we aimed to develop a novel mesoporous polydopamine (MPDA)-based theranostic agent for T1/T2 dual magnetic resonance imaging (MRI)-guided cancer chemo-photothermal therapy. Superparamagnetic iron oxide (SPIO)-loaded MPDA NPs (MPDA@SPIO) was firstly prepared, followed by modifying with a targeted molecule of sialic acid (SA) and chelating with Fe3+ (SA-MPDA@SPIO/Fe3+ NPs). After that, doxorubicin (DOX)-loaded SA-MPDA@SPIO/Fe3+ NPs (SA-MPDA@SPIO/DOX/Fe3+) was prepared for tumor theranostics. The prepared SAPEG-MPDA@SPIO/Fe3+ NPs were water-dispersible and biocompatible as evidenced by MTT assay. In vitro photothermal and relaxivity property suggested that the novel theranostic agent possessed excellent photothermal conversion capability and photostability, with relaxivity of being r1 = 4.29 mM-1s-1 and r2 = 105.53 mM-1s-1, respectively. SAPEG-MPDA@SPIO/Fe3+ NPs could effectively encapsulate the DOX, showing dual pH- and thermal-triggered drug release behavior. In vitro and in vivo studies revealed that SA-MPDA@SPIO/DOX/Fe3+ NPs could effectively target to the hepatic tumor tissue, which was possibly due to the specific interaction between SA and the overexpressed E-selectin. This behavior also endowed SA-MPDA@SPIO/DOX/Fe3+ NPs with a more precise T1-T2 dual mode contrast imaging effect than the one without SA modification. In addition, SAPEG-MPDA@SPIO/DOX/Fe3+ NPs displayed a superior therapeutic effect, which was due to its active targeting ability and combined effects of chemotherapy and photothermal therapy. These results demonstrated that SAPEG-MPDA@SPIO/DOX/Fe3+ NPs is an effective targeted nanoplatform for tumor theranostics, having potential value in the effective treatment of hepatic cancer.

ROS-responsive chitosan-SS31 prodrug for AKI therapy via rapid distribution in the kidney and long-term retention in the renal tubule.

The development of drugs with rapid distribution in the kidney and long-term retention in the renal tubule is a breakthrough for enhanced treatment of acute kidney injury (AKI). Here, l-serine-modified chitosan (SC) was synthesized as a potential AKI kidney-targeting agent due to the native cationic property of chitosan and specific interaction between kidney injury molecule-1 (Kim-1) and serine. Results indicated that SC was rapidly accumulated and long-term retained in ischemia-reperfusion-induced AKI kidneys, especially in renal tubules, which was possibly due to the specific interactions between SC and Kim-1. SC-TK-SS31 was then prepared by conjugating SS31, a mitochondria-targeted antioxidant, to SC via reactive oxygen species (ROS)-sensitive thioketal linker. Because of the effective renal distribution combined with ROS-responsive drug release behavior, the administration of SC-TK-SS31 led to an enhanced therapeutic effect of SS31 by protecting mitochondria from damage and reducing the oxidative stress, inflammation, and cell apoptosis.

NIR-Triggered Sequentially Responsive Nanocarriers Amplified Cascade Synergistic Effect of Chemo-Photodynamic Therapy with Inspired Antitumor Immunity.

A desirable cancer therapeutic strategy is supposed to have effective ability to not only exert maximum anticancer ability but also inspire antitumor immunity for preventing tumor relapse and metastasis. During this research, multifunctional upconversion nanoparticles (UCNPs) coated by ROS-responsive micelles are prepared for tumor targeting and near-infrared (NIR)-triggered photodynamic therapy (PDT)-combined synergistic effect of chemotherapy. Moreover, both PDT and chemotherapy agents could activate antitumor immunity via inducing immunogenic cell death with CD8+ and CD4+ T cells infiltrating in tumors. Through the experiments, intravenous administration of multifunctional nanocarriers with noninvasive NIR irradiation destroys the orthotopic tumors and efficiently suppresses lung metastasis in a metastatic triple-negative breast cancer model by cascade-amplifying chemo-PDT and systemic antitumor immunity. In conclusion, this study provides prospective chemo-PDT with inspired antitumor immunity for metastatic cancer treatment.

Serum Fibroblast Growth Factor 19 and Total Bile Acid Concentrations Are Potential Biomarkers of Hepatocellular Carcinoma in Patients with Type 2 Diabetes Mellitus.

PURPOSE: Type 2 diabetes mellitus (T2DM) carries a high risk of hepatocellular carcinoma (HCC). Both serum fibroblast growth factor 19 (FGF19) and bile acid concentrations are associated with T2DM and HCC. We aimed at evaluating the relationships between FGF19 and bile acid concentrations and HCC in patients with T2DM. METHODS: Twenty-seven healthy volunteers (control group), 27 patients with T2DM (T2DM group), 16 patients with newly diagnosed HCC (HCC group), and 10 T2DM patients with newly diagnosed HCC (T2DM-HCC group) were studied at the Affiliated Hospital of Nantong University between June 2016 and June 2017. The serum concentrations of serum FGF19 and total bile acids (TBA) were measured in all the participants. Correlation analysis and multiple stepwise regression analysis of the FGF19 and TBA concentrations were performed in all the participants and in the four groups. RESULTS: The concentrations of FGF19 were 220.5 pg/ml, 185.1 pg/ml, 115.8 pg/ml, and 70.4 pg/ml in the HCC, T2DM-HCC, control, and T2DM groups, respectively (p < 0.001), and the TBA concentrations were 21.75 µmol/l, 14.25 µmol/l, 14.25 µmol/l, 14.25 µmol/l, 14.25 p < 0.001), and the TBA concentrations were 21.75 r = 0.777; p < 0.001), and the TBA concentrations were 21.75 r = 0.777; p < 0.001), and the TBA concentrations were 21.75 r = 0.777; p < 0.001), and the TBA concentrations were 21.75 r = 0.777; p < 0.001), and the TBA concentrations were 21.75 r = 0.777; p < 0.001), and the TBA concentrations were 21.75 . CONCLUSIONS: Simultaneous increase of serum FGF19 and TBA levels may be used as indicators of HCC screening at early stage in patients with T2DM.

Association of abdominal aortic calcification estimated by plain radiography with outcomes in haemodialysis patients: A 6-year follow-up study.

AIM: Vascular calcification has played a vital role in increasing the prevalence of cardiovascular disease (CVD) and mortality in maintenance haemodialysis (MHD) patients. This study is aimed at exploring the prognostic value of abdominal aortic calcification (AAC) estimated by plain lateral abdominal radiography in MHD patients. METHODS: Lateral abdominal radiography was used to determine the abdominal aortic calcification score (AACS). The serum level of fibroblast growth factor-23 was tested by enzyme-linked immunosorbent assay. Patients were divided into two groups: no or minor calcification group (AACS < 5) and moderate to severe calcification group (AACS ≥ 5). All patients were followed up to death or the end of the study (30 November 2016). RESULTS: A total of 114 patients were enrolled in this study, including 64 males (56.1%), and the mean age was 57.42 ± 13.48 years. Seventy-six patients (66.7%) exhibited AAC. Independent predictors for moderate to severe calcification were older age (odds ratio (OR) 1.06 (1.02-1.10), P = 0.003), longer dialysis vintage (OR 1.01 (1.00-1.02), P = 0.039), presence of smoking (OR 3.01 (1.18-7.70), P = 0.021) and higher Log fibroblast growth factor-23 serum levels (OR 2.83 (1.01-7.94), P = 0.048). During a median follow-up of 6.0 (5.6, 6.1) years, 22 patients (19.3%) died of all-cause death, and 17 cases (14.9%) died of CVD. Kaplan-Meier survival curves showed that patients in the moderate to severe calcification group had significantly higher all-cause (28.3 vs 11.5%, P = 0.028) and CVD mortality (22.6 vs 8.2%, P = 0.035) than that in the no or minor calcification group. A multivariate Cox regression showed that AACS (hazard ratio 1.08 (1.01-1.15), P = 0.022) was an independent predictor of CVD mortality. Compared with the no or minor calcification group, the risk of CVD mortality was increased by a factor of 3.14 in patients in the moderate to severe calcification group (hazard ratio 3.14 (1.04-9.44), P = 0.042). CONCLUSION: Our data suggest that AAC is prevalent in MHD patients and could provide potential predictive information for CVD mortality. Plain lateral abdominal radiography, which is simple and cheap and involves lower radiation, might represent an appropriate screening method for evaluating vascular calcification in daily clinical practice.

Effect of acute exposure to hypobaric hypoxia on learning and memory in adult Sprague-Dawley rats.

The present study aimed to observe the effects of acute exposure to hypobaric hypoxia on learning and memory in adult Sprague-Dawley (SD) rats as well as the changes in N-methyl-D-aspartate receptor (NMDAR) subunits. Learning and memory abilities were evaluated with Morris water maze following simulated hypoxia at 5000 m or 7000 m for 2, 4 or 6 days. The number of red blood cells, the level of hemoglobin, oxidative stress markers, the extent of neuronal damage in the hippocampal CA1, and the expression of NMDAR subunits were all measured. In place navigation test, the escape latency significantly increased only in the 5000 M 6Day (P < 0.05) group than the latency in the plain group on the fourth day. In the spatial probe test, the times of platform passing showed no significant difference between the hypoxia and plain groups. Polycythemia, an increased ratio of superoxide dismutase/malondialdehyde and degeneration of neurons appeared in an elevation-dependent and duration-dependent manner in those hypoxia groups. Furthermore, the protein expression of NR1 increased and the protein expression levels of NR2A, NR2B, and NR3A were all decreased in the 5000M 6Day and 7000M 6Day groups. In summary, the feeble effect of acute exposure to simulated hypobaric hypoxia on learning and memory in adult SD rats may be attributed to increased antioxidative capacities and decreased expression of NR3A. And moreover, differences in the expressions of NMDAR subunits were closely related to the altitude and duration.

Variability of serum phosphorus and its association with mortality among hemodialysis patients
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OBJECTIVE: To determine the relationship between the variability of serum phosphorus and mortality among maintenance hemodialysis (MHD) patients. MATERIALS AND METHODS: A total of 502 MHD cases were studied from the Shanghai Renal Registry Network. Serum phosphorus variability was indicated by a coefficient of variation (CV). According to the CV median of serum phosphorus, patients were divided into two groups: a high-variability group (CV ≥ 0.226 mmol/L) and a low-variability group (CV < 0.226 mmol/L). Average phosphorus ≤ 1.78 mmol/L was defined as the standard phosphorus group and serum phosphorus > 1.78 mmol/L was defined as the non-standard phosphorus group. The relationship between serum phosphorus variability and all-cause and cardiovascular disease (CVD) mortality was assessed. RESULTS: In the 502 MHD cases, the average age of patients was 63.9 ± 14.60 years, and dialysis vintage was 82.0 (43.0 - 139.0) months. 118 patients (23.5%) died, succumbing to all-cause mortality, while 64 patients (14.3%) died from CVD. The high-variability group had increased all-cause mortality (27.7% vs. 19.3%, p = 0.028). Death from CVD was increased in the high-variability group, but had no statistical significance (15.4% vs. 10.0%, p = 0.082). Cox regression analysis showed that older age, low hemoglobin levels, a higher phosphorus CV, and low serum albumin were independent risk factors for all-cause and CVD mortality. The standard group with low-phosphorus variability had a decreased mortality compared with the non-standard group with high variability (15.3 vs. 29.2%, p = 0.047 and 6.0 vs. 15.0%, p = 0.033, respectively). The Kaplan-Meier method revealed that patients with low phosphorus variability had a decreased all-cause and CVD mortality (p = 0.023 and p = 0.047, respectively) compared with high phosphorus variability patients. CONCLUSION: Higher phosphorus CV was independently correlated with all-cause and CVD mortality. Low phosphorus variability with on-target levels resulted in decreased patient mortality. Thus, stable serum phosphorus levels may improve survival in MHD patients.
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