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The combination of chemotherapy and radiotherapy (chemoradiotherapy) is a promising strategy, extensively studied and applied clinically. Meanwhile, radiosensitizers play an important role in improving clinical radiotherapy therapeutic efficacy. There are still some disadvantages in practical applications, because radiosensitizers and drugs are difficult to deliver spatio-temporally to tumor sites and work simultaneously with low efficiency for DNA damage and repair inhibition, leading to an inferior synergistic effect. Herein, a suitable radiosensitizer of nano-enabled coordination platform (NP@PVP) with bismuth nitrate and cisplatin prodrug is developed by a simple synthetic route to improve the effectiveness of chemo-radiation synergistic therapy. When NP@PVP is internalized by a tumor cell, the bismuth in NP@PVP can sensitize radiation therapy (RT) by increasing the amount of reactive oxygen species generation to enhance DNA damage after X-ray radiation; meanwhile, the cisplatin in NP@PVP can inhibit DNA damage repair with spatio-temporal synchronization. NP@PVP is demonstrated to exhibit higher sensitization enhancement ratio (SER) of 2.29 and excellent tumor ablation capability upon irradiation in vivo in comparison with cisplatin (SER of 1.78). Our strategy demonstrates that the RT sensitization effect of bismuth and cisplatin based NP@PVP has great anticancer potential in chemo-radiation synergistic therapy, which is promising for clinical application.

Purpose: The present study was conducted to evaluate the pain-reducing efficacy and safety of the morphine and dexamethasone incorporated cocktail regimen in patients undergoing total hip arthroplasty (THA).Methods: The current study enrolled 75 patients and randomized them into three groups. The patients in group I were injected with morphine, dexamethasone, bupivacaine, flurbiprofen axetil, and normal saline. Patients assigned to group II were injected with dexamethasone, bupivacaine, flurbiprofen axetil, and normal saline. Patients in group III were given bupivacaine, flurbiprofen axetil, and normal saline. The visual analog scale (VAS) score and active and passive range of movement (ROM) were recorded and evaluated to compare the pain-controlling efficiency. The side effects of headache, dizziness, nausea, vomiting, wound leakage, and wound infection were monitored.Results: The patients in group I had the lowest VAS, and highest active ROM and passive ROM. The VAS reduced from day 1 to day 4, and the ROM increased conversely. The patients in group II presented a smaller reduction in VAS and a smaller increase in ROM, compared to the patients in Group III. The side effects of headache, dizziness, nausea, and vomiting were not recorded. Wound leakage was observed from 4 patients in group I (2 patients) and group II (2 patients). The was no statistical intergroup difference (p = 0.85). No wound infection symptoms were detected.Conclusions: Morphine and dexamethasone incorporated cocktail regimen efficiently reduced postoperative pain in patients undergoing primary total knee arthroplasty.Trial registration: Drug clinical trial registration system, CTR20181569. Registered 20 October 2018, http://www.chinadrugtrials.org.cn/clinicaltrials

This study evaluates the diagnostic performance of Doppler ultrasound in diagnosing fetal anemia. Data were taken from relevant study reports published in peer-reviewed journals identified after a literature search in electronic databases. Random effects meta-analyses were performed by pooling the effect sizes of diagnostic indices (sensitivity, specificity, positive/negative predictive values, and false-positive rate) or correlation coefficients reported by individual studies. As a result, 31 studies (1848 pregnancies; gestation age, 28.25 weeks [95% confidence interval {CI}, 26.87-29.63]) were included in the meta-analysis. Anemia was found in 63.7% (95% CI, 49.7-77.7) fetuses, and severe anemia was found in 36.7% (95% CI, 26.9-46.4) fetuses. Sensitivity and specificity of Doppler ultrasound for detecting fetal anemia in alloimmunized fetuses at middle cerebral artery peak systolic velocity cutoff of 1.5 multiple of median for gestation age were 83.42% (95% CI, 71.75-95.09) and 80.30% (95% CI, 73.58-87.02), respectively. Positive predictive value, negative predictive value, and false-positive rate were 76.35% (95% CI, 65.98-86.72), 80.0% (95% CI, 76.63-83.37), and 10.4% (95% CI, 5.9-14.9), respectively. Correlation coefficient between hematological anemia and Doppler ultrasound-measured blood flow velocity was -0.706 (95% CI, -0.765 to -0.635; P < 0.00001). In conclusion, Doppler ultrasound-measured middle cerebral artery peak systolic velocity at 1.5 multiple of median provides good diagnostic strength for the detection of alloimmunized fetal anemia. A strong correlation between Doppler velocimetric measures and hematological anemia is also observed.

SummaryResistance to apoptosis due to caspase deregulation is considered one of the main hallmarks of cancer. However, the discovery of novel non-apoptotic caspase functions has revealed unknown intricacies about the interplay between these enzymes and tumor progression. To investigate this biological problem, we capitalized on a Drosophila tumor model highly relevant for humans that relies on the concomitant upregulation of EGFR and the JAK/STAT signaling pathway. Our results indicate that widespread non-apoptotic activation of initiator caspases limits JNK signaling and facilitates cell fate commitment in these tumors, thus preventing the overgrowth and exacerbation of malignant features. Intriguingly, these caspase functions are strongly linked to the ability of these enzymes to control the recruitment and subsequent proliferation in situ of macrophage-like cells on the tumor. These findings assign novel tumor-suppressor activities to caspases independent of apoptosis, while providing highly relevant molecular details to understanding their diverse contribution during tumor progression.

Background Abnormal microRNAs (miRNAs) expression is closely related to the development and poor prognosis of pancreatic ductal adenocarcinoma (PDAC). We aimed to elucidate the invasive mechanism and clinical significance of miR‐10b in PDAC. Methods The RNA sequence data of pancreatic cancer were extracted from the TCGA database. R packages were performed to analyze the differential expression of RNAs. TargetScan, picTar, and miRanda were used to predict the target gene of miRNA. The expression level of the selected candidate was tested by western blot and RT‐PCR in PDAC cells and tissues. Scrape and Transwell assays were determined the effect of candidate molecules on cell migration and invasion. The gain of function and loss of function was achieved by co‐culture with mimics and vector. Luciferase reporters were generated based on the psiCHECK2 vector. The relative luciferase activity was measured with the Dual‐Luciferase Reporter Assay System and Infinate M200 PRO microplate reader. Results Based on the TCGA data and bioinformatics analysis, we obtained seven differentially expressed miRNAs. Both TCGA data and our center clinical date indicated that miR‐10b was contributed to the poor survival of PDAC. Based on the target gene prediction database, we found that E2F7 was a target mRNA of miR‐10b. In subsequent experiments in molecular biology, miR‐10b expression was downregulated in PDAC cells and tissues, while E2F7 was upregulated. Scrape and Transwell assay indicated that miR‐10b could inhibit the invasion and migration of PDAC. MiR‐10b was confirmed to be by the E2F7 targeting site by dual‐luciferase report. Moreover, rescue experiments prove that miR‐10b could inhibit the invasion and migration of PDAC cells by regulating E2F7 expression. Conclusion Our results suggest that miR‐10b could inhibit the progression of PDAC by regulating E2F7 expression and acts as an independent prognostic risk factor for PDAC., Acquired the miRNA sequencing dataset and corresponding clinical records of PDAC from TCGA. Differentially expressed miRNA analysis and survival analysis indicated miR‐10b was PDAC progression associated miRNA. And E2F7 was a potential target of miR‐10b. And miR‐10b may inhibit PDAC cell migration and invasion by targeting E2F7.

Resistance to apoptosis due to caspase deregulation is considered one of the main hallmarks of cancer. However, the discovery of novel non-apoptotic caspase functions has revealed unknown intricacies about the interplay between these enzymes and tumor progression. To investigate this biological problem, we capitalized on a Drosophila tumor model highly relevant for humans that relies on the concomitant upregulation of EGFR and the JAK/STAT signaling pathway. Our results indicate that widespread non-apoptotic activation of initiator caspases limits JNK signaling and facilitates cell fate commitment in these tumors, thus preventing the overgrowth and exacerbation of malignant features. Intriguingly, these caspase functions are strongly linked to the ability of these enzymes to control the recruitment and subsequent proliferation in situ of macrophage-like cells on the tumor. These findings assign novel tumor-suppressor activities to caspases independent of apoptosis, while providing highly relevant molecular details to understanding their diverse contribution during tumor progression.

Objective The current risk model for long-term prediction in coronary artery disease (CAD) is complicated, while a simple useful model is still lacking. We aim to investigate if CHADS2 and R2CHADS2 scores could predict long-term outcome for patients with CAD. Patients and methods We enrolled 3,700 patients with CAD between November 2010 and September 2014 at the Department of Cardiology from Chinese PLA General Hospital. The CHADS2 and R2CHADS2 scores were calculated. All cases were followed to track the incidence of composite end point consisting of cardiovascular (CV) death, myocardial infarction (MI), stroke, heart failure, and all-cause death. Results During a median 2.9-year follow-up, 443 patients experienced at least one element of the composite end point of CV death (n=168 [4.6%]), MI (n=59 [1.6%]), stroke (n=96 [2.6%]), heart failure (n=101 [2.8%]), and all-cause death (n=240 [6.6%]). Multivariate Cox regression analyses showed that the CHADS2 score (hazard ratio [HR]: 2.18, 95% CI: 2.00-2.38, p

Amyloid beta (Aβ) is the main component of the amyloid plaques that accumulate in the brains of Alzheimer patients. The present study was conducted to investigate whether the combined treatment with selenium (Se) and zinc (Zn) offers more beneficial effects than that provided by either of them alone in reversing Aβ25–35-induced neurotoxicity in PC12 cells. Cells were pretreated with 0.1 μmol/L of Se and Zn for 4 h, after treated with 10 mmol/L Aβ25–35 for 24 h. Cells were divided into control and five treated groups, and received either 10 mmol/L Aβ25–35,10 mmol/L Aβ25–35 + 0.1 μmol/L Se, 10 mmol/L Aβ25–35 + 0.1 μmol/L Zn, 10 mmol/LAβ25–35 + 0.1 μmol/L Se + 0.1 μmol/L Zn, or 0.1 μmol/L Se + 0.1 μmol/L Zn. The result showed that cell viability was decreased in MTT metabolic rate; LDH release and MDA, H2O2, and NO levels were increased and the GSK-3β and phosphorylated tau protein level were increased in Aβ25–35-treated group (P

Malignant melanoma is a highly aggressive neoplasia of melanocytic origin. In part because of the lack of effective treatment methods, the incidence and mortality rates of this disease continue to increase. Rapidly accumulating evidence suggests that dysregulation of epigenetic mechanisms, including DNA methylation/demethylation, chromatin modification, and remodeling, and diverse activities of noncoding RNAs, play a central role in the pathogenesis of melanoma. The epigenetic mark 5-hydroxymethylcytosine (5-hmC) has attracted interest since 2009, when it was shown that ten-eleven translocation proteins can enzymatically convert 5-methylcytosine into 5-hmC, a key intermediate of DNA demethylation. Factors that regulate DNA hydroxymethylation are frequently altered in cancer, leading to deregulation of 5-hmC levels. In this review, we will discuss the relationship between melanoma and DNA hydroxymethylation, the regulation of DNA hydroxymethylation, and defects in this pathway in melanoma.

Schisandrin A (Sch A) is a lignin extracted from the fruit of Schisandra chinensis, which has potential anti-inflammatory properties and is used for treating various inflammatory diseases. In this study, we aimed to evaluate the anti-inflammatory effects of Sch A and the underlying mechanisms in animal models of acute inflammation. First, the anti-inflammatory effects of Sch A were evaluated preliminarily in an animal model of xylene-induced ear edema. Sch A pretreatment significantly decreased the degree of edema and inhibited telangiectasia in the ear. Second, a mouse model of paw edema was used to investigate the anti-inflammatory effects and mechanisms of Sch A. Pretreatment with Sch A significantly inhibited carrageenan-induced paw edema in mice. Hematoxylin-eosin (HE) staining of paw tissues demonstrated that Sch A inhibited the infiltration of inflammatory cells in the mouse model of paw edema. Enzyme-linked immunosorbent assay (ELISA) results indicated that the levels of inflammatory factors decreased. The western blot and immunohistochemical assay results revealed that the toll-like receptor 4/nuclear factor kappa-B (TLR4/NF-κB) pathway could play a role in the anti-inflammatory functions of Sch A. The findings demonstrated that Sch A exerts anti-inflammatory effects and may provide possible strategies for the treatment of inflammatory diseases.

Since the first case of human avian influenza A (H7N9) virus infection in 2013, five H7N9 epidemics have occurred in China, all of which caused severe diseases, including pneumonia and acute respiratory distress syndrome, and the fatality rates of these epidemics were as high as 30–40%. To control the prevalence of H7N9 influenza, an effective vaccine is urgently needed. In the present study, we used chitosan and recombinant human interleukin-2 as an adjuvant (JY) to promote the systemic and mucosal immune responses induced by the H7N9 vaccine. Mice were immunized intranasally with the inactivated split influenza A (H7N9) virus (A/Shanghai/02/2013) vaccine with or without JY. The hemagglutination inhibition (HI) titers of mice immunized with the JY-adjuvanted vaccine were significantly higher than those of mice immunized with the vaccine without adjuvant (21.11 ± 9.58 vs. 5.04 ± 3, P

The effect of the extremely low frequency magnetic field (ELF-MF) on biomass and mannatide production by α-hemolytic Streptococcus in liquid-state fermentation culture medium was studied during shake flask culture. Magnetic field (MF) inductions, exposure times, and exposure periods varied in a range of 0-1.5 mT, 0-16 h, and six periods of incubation time, respectively. Results showed both biomass and mannatide production increased significantly at MF induction 0.4, 0.6, and 0.9 mT and decreased at both 1.2 and 1.5 mT. Biomass increased by exposure for initial and middle stages of fermentation. Mannatide production increased significantly at 4-8, 8-12, and 17-21 h. Peak yield of biomass and mannatide production increased by 10.7% and 14.0% at 25 and 27 h of incubation at 0.6 mT MF induction and exposure to 8-12 h of incubation time, compared with the control experiment, respectively. ELF-MF could also enhance the growth rate and mannatide production rate of α-hemolytic Streptococcus. However, ELF-MF did not alter α-hemolytic Streptococcus cell growth and mannatide metabolizing regulation or fermentation pattern. Mannatide production was not associated with cellular growth but rather only partially associated. Bioelectromagnetics. 37:331-337, 2016. © 2016 Wiley Periodicals, Inc.

Glucagon-like peptide-1 (GLP-1) and GLP-1 receptor agonists are actively pursued as therapeutic agents for type 2 diabetes mellitus (T2DM). However, the therapeutic utility of GLP-1 is limited due to its rapid inactivation by dipeptidyl peptidase IV, and many GLP-1 receptor agonists suffer from innegligible adverse effects. In the present study, in order to develop long-acting GLP-1 derivatives with improved hypoglycemic activity, native GLP-1 (7-36)-NH2 was loaded into sterically stabilized phospholipid micelles (SSM), affording GLP-1-SSM. In vitro stability test and in vivo pharmacokinetic study demonstrated that the association of GLP-1 with SSM led to enhanced stability and drug utilization without affecting its insulinotropic and glucose-lowering activities. Single and multiple glucose tolerance tests confirmed that GLP-1-SSM was a long-acting antidiabetic agent comparable or even better than exendin-4. More importantly, preclinical studies found out that a chronic twice daily treatment of GLP-1-SSM in type 2 diabetic db/db mice suppressed body weight gain and food uptake, decreased HbA1c value, and restored the glucose tolerance ability. Collectively, our results suggest that GLP-1-SSM is a promising therapy for the treatment of T2DM and deserves further investigation.

Value and correlation analysis between ultrasound and mammography in the diagnosis and other risk factors related to breast cancer were explored. A total of 1,473 patients who underwent breast color ultrasonography and molybdenum target X-ray examination in Binzhou Medical University Hospital from March 2017 to August 2018 were collected, and the patient's ultrasound and mammography results were compared, also the pathological biopsy was used as the reference golden criteria to calculate the value of both test methods and the value of combined diagnosis in breast cancer. The risk factors associated with breast cancer were analyzed. Among the 1,473 patients, 387 breast cancer patients were detected by ultrasonography, 351 by mammography and 339 cases by combined diagnosis. A total of 314 cases were diagnosed as breast cancer after pathological biopsy. However, there were significant differences in tumor size, stages, and BI-RADS grades (P0.05), however, the diagnostic efficacy of ultrasonography combined with mammography was significantly better than the two single tests (P0.05). However, age, fertility status, and BMI were all risk factors related to breast cancer (OR>1; P

Amyloid precursor proteins (APPs) are processed by β-, γ-, and e-secretases and caspase-3 to generate C-terminal fragments of APP (APP-CTFs), which may contribute to the pathology of Alzheimer's disease (AD). In addition to amyloid plaques and neurofibrillary tangles, AD brains contain Hirano bodies, which are rod-like structures mostly composed of actin and the actin-binding protein, cofilin. However, the mechanisms underlying the formation of cofilin-actin rods are still unknown. In this study, we aim to elucidate the effects of APP-CTFs on the actin-depolymerizing factor [(ADF)/cofilin]. Our data indicate that transfection with APP-CT99 and APP-CT57 may increase the phosphorylation level of Ser3 of ADF/cofilin and Thr508 of LIM-kinase 1 in rat primary cortical neuronal cultures. S3 peptide, a synthetic peptide competitor of LIM-kinase 1 for ADF/cofilin phosphorylation and an inhibitor of APP-CTFs, induced ADF/cofilin phosphorylation. In comparison with the wild-type mouse, the APP-CT transgenic mouse showed increased immunoreactivity of phosphorylated cofilin (p-cofilin) in the brain. Treatment with DAPT, an inhibitor of γ-secretase, resulted in a decrease in p-cofilin protein level in the group transfected with full-length APP-695. Transfection with the mutant APP-CTF with a deleted YENPTY domain resulted in no significant increase in p-cofilin level. Thus, APP-CTFs induced cofilin phosphorylation to facilitate nuclear translocation. These results suggest a relationship between APP-CTFs and ADF/cofilin that may be suggestive of a new toxic pathway in the pathology of AD.

Background Many tripartite motif (TRIM) family proteins have been reported to be of great importance in the initiation and progression in hepatocellular carcinoma (HCC). However, the biological role and regulatory mechanism of tripartite motif containing 52 (TRIM52) in HCC development and progression are poorly defined. Methods Immunohistochemistry (IHC), quantitative real-time PCR (qRT-PCR) or Western blot analysis was used to detect TRIM52, p21, matrix metalloproteinase 2 (MMP2), protein phosphatase, Mg2+/Mn2+ dependent 1A (PPM1A), p-Smad2/3 and Smad2/3 levels in HCC tissues and cell lines. HCC cell proliferation and cell cycle were measured by Cell Counting Kit-8 (CCK-8) and flow cytometry analysis, respectively. HCC cell migration and invasion were measured by Transwell assay. Tumor growth of HCC cells in vivo was measured using the nude mouse xenograft model. The correlation between TRIM52 and PPM1A was measured by co-immunoprecipitation (Co-IP) and ubiquitination analysis in vitro. Results TRIM52 was significantly up-regulated in the HCC tissues in comparison with the adjacent non-tumor hepatic tissues. TRIM52 was also up-regulated in HCC cell lines (MHCC-97H and MHCC-97L cells) compared with normal human liver cell line LO2. TRIM52 down-regulation by RNA interfering in MHCC-97H cells enhanced inhibition of cell proliferation, migration and invasion. TRIM52 down-regulation also induced MHCC-97H cells arrest in G0-G1 phase cell cycle and inhibited MHCC-97H cell growth in the nude mice. However, TRIM52 up-regulation in MHCC-97L cells promoted cell proliferation, migration and invasion. Furthermore, TRIM52 down-regulation significantly increased p21 and PPM1A expression, but inhibited MMP2 expression and induced Smad2/3 dephosphorylation in MHCC-97H cells, which were reversed by TRIM52 up-regulation in MHCC-97L cells. TRIM52 was found interacted with PPM1A and TRIM52 down-regulation inhibited the ubiquitination of PPM1A. Importantly, PPM1A up-regulation in MHCC-97L cells significantly suppressed TRIM52-mediated enhancement on cell proliferation, invasion and migration. Conclusions Our findings suggest that TRIM52 up-regulation promotes proliferation, migration and invasion of HCC cells through the ubiquitination of PPM1A.

The ease of genetic manipulation, as well as the evolutionary conservation of gene function, has placedDrosophila melanogasteras one of the leading model organisms used to understand the implication of many proteins with disease development, including caspases and their relation to cancer. The family of proteases referred to as caspases have been studied over the years as the major regulators of apoptosis: the most common cellular mechanism involved in eliminating unwanted or defective cells, such as cancerous cells. Indeed, the evasion of the apoptotic programme resulting from caspase downregulation is considered one of the hallmarks of cancer. Recent investigations have also shown an instrumental role for caspases in non-lethal biological processes, such as cell proliferation, cell differentiation, intercellular communication, and cell migration. Importantly, malfunction of these essential biological tasks can deeply impact the initiation and progression of cancer. Here, we provide an extensive review of the literature surrounding caspase biology and its interplay with many aspects of cancer, emphasising some of the key findings obtained fromDrosophilastudies. We also briefly describe the therapeutic potential of caspase modulation in relation to cancer, highlighting shortcomings and hopeful promises.

At present, fostering and promoting empathy, an important humanistic quality, are believed ethical imperatives, and should be carried through the pharmacy education to facilitate the interpersonal and philosophical development of healthcare students. A cross-sectional study used the JSE-HPS (Jefferson Scale of Empathy-Health Profession Student version) to assess 263 Chinese pharmacy undergraduates from 1 st to 4 th year at Wuhan University of Science and Technology. Attached to the scale was a survey containing questions on demographics and favorite implementation model of humanistic education. Mean score of JSE-HPS was 112.58. Cronbach’s alpha coefficient was 0.81. Three factors emerging in the factor analysis of JSE-HPS are “perspective taking”, “compassionate care” and “ability to stand in patients’ shoes”. And empathy score of 4 th -year students was highest. In addition, the three most popular implementation models were “Social activities”, “Extracurricular activity on pharmacy humanistic education”, and “Humanistic education should be infiltrated and integrated within the existing professional curriculum”, respectively. Our study findings indicate that humanistic education in the foundations courses for 1 st to 3 rd academic year pharmacy students need to be focus on. For successful practice, humanistic education that promotes empathy has to be integrated within the existing training programs for pharmacy undergraduate students in a vivid way.

Accurate risk stratification is crucial for the evaluation of patients with coronary artery disease (CAD). We evaluated 8 biomarkers representing inflammation (growth differentiation factor [GDF]-15, fibrinogen), renal function (estimated glomerular filtration rate [eGFR]), endothelial activation (

Aeruginosins are a class of cyanobacteria-derived bioactive linear tetrapeptides composed of nonproteinogenic amino-acid residues, such as the 2-carboxy-6-hydroxyoctahydroindole (Choi) moiety, which is the hallmark of aeruginosin. The biosynthetic pathway of the Choi moiety remains elusive. Previous studies have suggested that AerE, a protein that possesses two cupin domains, participates in the biosynthesis of the Choi moiety. In this study, recombinant AerE fromMicrocystis aeruginosa, which was overexpressed inEscherichia coliand purified by Ni2+-chelating affinity and gel-filtration chromatography, was successfully crystallized and X-ray diffraction analysis was performed. The crystal belonged to the orthorhombic space groupP212121, with unit-cell parametersa= 34.770,b= 62.133,c= 87.401 Å. The diffraction data from the crystal were scaled to a maximum resolution of 1.60 Å. The calculated Matthews coefficient of the crystal is 1.93 Å3 Da−1, suggesting that there is one molecule in the asymmetric unit.

This study aimed to explore the assessment value of virtual touch quantization (VTQ) for the clinicopathological typing of renal fibrosis. The quantitative detection of 76 patients with nephropathy was performed using acoustic radiation force impulse imaging (ARFI). The extent of the renal fibrosis in each patient was confirmed using ultrasound-guided biopsy pathology. The VTQ values were compared with the degree of renal fibrosis in order to analyze the correlation between them. Patients were divided pathologically into four groups, as follows: non-fibrosis (n=14), mild fibrosis (n=40), moderate fibrosis (n=21) and severe fibrosis (n=1). Compared with the non-fibrosis group, the VTQ values of the mild and moderate fibrosis groups were significantly increased (P0.05). According to the receiver operating characteristic (ROC) curve, a VTQ value of renal parenchyma of >1.67 m/sec was determined to be an indicator of renal fibrosis, with a sensitivity of 86.3% and a specificity of 83.3%. VTQ technology may be significant in the assessment of the extent of renal fibrosis.

Background It is demonstrated that elevated serum levels of alkaline phosphatase (ALP) and phosphate indicate a higher risks of cardiovascular disease (CVD) and total mortality in population with chronic kidney disease (CKD), but it remains unclear whether this association exists in people with normal or preserved renal function. Method Clinical trials were searched from Embase and PubMed from inception to 2013 December using the keywords “ALP”, “phosphate”, “CVD”, “mortality” and so on, and finally 24 trials with a total of 147634 patients were included in this study. Dose-response and semi-parametric meta-analyses were performed. Results A linear association of serum levels of ALP and phosphate with risks of coronary heart disease (CHD) events, CVD events and deaths was identified. The relative risk(RR)of ALP for CVD deaths was 1.02 (95% confidence interval [CI], 1.01–1.04). The RR of phosphate for CVD deaths and events was 1.05 (95% CI, 1.02–1.09) and 1.04 (95% CI: 1.03–1.06), respectively. A non-linear association of ALP and phosphate with total mortality was identified. Compared with the reference category of ALP and phosphate, the pooled RR of ALP for total mortality was 1.57 (95% CI, 1.27–1.95) for the high ALP group, while the RR of phosphate for total mortality was 1.33 (95% CI, 1.21–1.46) for the high phosphate group. It was observed in subgroup analysis that higher levels of serum ALP and phosphate seemed to indicate a higher mortality rate in diabetic patients and those having previous CVD. The higher total mortality rate was more obvious in the men and Asians with high ALP. Conclusion A non-linear relationship exists between serum levels of ALP and phosphate and risk of total mortality. There appears to be a positive association of serum levels of ALP/phosphate with total mortality in people with normal or preserved renal function, while the relationship between ALP and CVD is still ambiguous.

Elevated serum phosphate is associated with cardiovascular and total mortality in patients with kidney diseases and healthy individuals. But whether serum phosphate is associated with stroke is controversial. We searched PubMed and Embase from January 1, 1970 to May 9, 2014 with keywords such as “serum phosphate”, “serum phosphorus”, and “stroke”. Dose–response meta-analysis was conducted. A restricted cubic spline model was used, and then we estimated pooled RR using generalized least square regression taking into account the correlation among categories of each study. Five studies with a total of 32,608 patients were included. We identified a linear relationship between serum phosphate and risk of stroke (P for non-linearity = 0.5258). The RR of phosphate (1 mg/dL) for stroke was 1.00 (95 % CI 0.97–1.05), similar results were observed in subgroup analysis. A linear relationship between serum phosphate and risk of stroke is identified. There is no association between serum level of phosphate and stroke.

AIM: To investigate the protective effect of glutamine (Gln) on intestinal injury and the bacterial community in rats exposed to hypobaric hypoxia environment. METHODS: Sprague-Dawley rats were divided into control, hypobaric hypoxia (HH), and hypobaric hypoxia + Gln (5.0 g/kg BW·d) (HG) groups. On the first 3 d, all rats were placed in a normal environment. After the third day, the HH and HG groups were transferred into a hypobaric chamber at a simulated elevation of 7000 m for 5 d. The rats in the HG group were given Gln by gavage daily for 8 d. The rats in the control and HH groups were treated with the same volume of saline. The intestinal morphology, serum levels of malondialdehyde (MDA), superoxide dismutase (SOD), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interferon-gamma (IFN-γ) and diamino oxidase (DAO) were examined. We also evaluated the expression levels of occludin, toll-like receptor 4 (TLR4), nuclear factor-κB p65 (NF-κB p65) and myeloid differentiation factor 88 (MyD88), and examined the bacterial community in caecal contents. RESULTS: Hypobaric hypoxia induced the enlargement of the heart, liver, lung and kidney, and caused spleen atrophy. Intestinal villi damage was also observed in the HH group. Supplementation with Gln significantly alleviated hypobaric-induced damage to main organs including the intestine, increased serum SOD (1.14 ± 0.03 vs 0.88 ± 0.04, P < 0.05) and MDA (8.35 ± 1.60, P < 0.01) levels and decreased serum IL-6 (1172.13±30.49 vs 1407.05 ± 34.36, P < 0.05), TNF-α (77.46 ± 0.78 vs 123.70 ± 3.03, P < 0.001), IFN-γ (1355.42 ± 72.80 vs 1830.16 ± 42.07, P < 0.01) and DAO (629.30 ± 9.15 vs 524.10 ± 13.34, P < 0.001) levels. Moreover, Gln significantly increased occludin (0.72 ± 0.05 vs 0.09 ± 0.01, P < 0.001), TLR4 (0.15 ± 0.05 vs 0.30 ±0.09, P < 0.05), MyD88 (0.32 ± 0.08 vs 0.71 ± 0.06, P < 0.01), and NF-κB p65 (0.16 ± 0.04 vs 0.44 ± 0.03, P < 0.01) expression levels and improved the intestinal bacterial community. CONCLUSION: Gln treatment protects from intestinal injury and regulates the gut flora imbalance in hypoxia environment. These effects may be related to the TLR4/MyD88/NF-κB signaling pathway.

The study was conducted to investigate the role of vitamin E in the high altitude hypoxia-induced damage to the intestinal barrier in rats. Sprague-Dawley rats were divided into control (Control), high altitude hypoxia (HH), and high altitude hypoxia+vitamin E (250 mg/kg BW*d) (HV) groups. After the third day, the HH and HV groups were placed in a hypobaric chamber at a stimulated elevation of 7000 m for 5 days. The rats in the HV group were given vitamin E by gavage daily for 8 days. The other rats were given equal volume saline. The results showed that high altitude hypoxia caused the enlargement of heart, liver, lung and kidney, and intestinal villi damage. Supplementation with vitamin E significantly alleviated hypoxia-caused damage to the main organs including intestine, increased the serum superoxide dismutase (SOD) (p< 0.05), diamino oxidase (DAO) (p< 0.01) levels, and decreased the serum levels of interleukin-2 (IL-2) (p< 0.01), interleukin-4 (IL-4) (p

Lingyao Qi, Hanxiong Liu, Lianchao Cheng, Caiyan Cui, Xu Chen, Siqi Yang, Lin Cai Department of Cardiology, Affiliated Hospital of Southwest Jiaotong University, The Third People’s Hospital of Chengdu, Chengdu, Sichuan, People’s Republic of ChinaCorrespondence: Lin CaiDepartment of Cardiology, Affiliated Hospital of Southwest Jiaotong University, The Third People’s Hospital of Chengdu, Chengdu, Sichuan, People’s Republic of ChinaTel/Fax +86 28-67575956Email clin63@hotmail.comPurpose: Chronic kidney disease (CKD) is common in patients admitted with acute coronary syndrome (ACS), and it is associated with poor outcomes. However, data are limited. Hence, we examined the long-term prognostic significance of estimated glomerular filtration rate (eGFR) among Chinese patients hospitalized with ACS.Patients and Methods: This is a multicenter, observational study that included 1860 ACS patients enrolled between March 2014 and June 2019 from 11 hospitals in Chengdu. CKD-EPI equation was used to calculate the baseline eGFR. Patients were divided into three groups: eGFR ≥ 90 mL/min (normal renal function), eGFR 60 to < 90 mL/min (mild impaired renal function), and eGFR < 60 mL/min (moderate or severe renal dysfunction). The endpoint was all-cause death during follow-up.Results: At baseline, 714 patients had normal renal function, while 746 patients had mild impaired renal function, and 400 patients had moderate or severe renal dysfunction. In the follow-up of 15 months (10 months, 22 months), 261 (14.0%) patients died;, 139 (34.8%) in the moderate or severe renal dysfunction group, 94 (12.6%) in the mild impaired renal function group, and 28 (3.9%) in the normal renal function group (log-rank p-value from Kaplan–Meier analysis < 0.001). In multivariable Cox Proportional hazard analysis, age, systolic blood pressure (SBP), heart rate, eGFR, ST-elevation myocardial infarction (STEMI), and percutaneous coronary intervention (PCI) were independent predictors of all-cause death.Conclusion: In this study, among Chinese patients with ACS, renal insufficiency was associated with unfavorable long-term prognosis. Age, SBP, heart rate, eGFR, STEMI, and PCI could identify those at risk.Keywords: renal insufficiency, acute coronary syndrome, long-term prognosis, retrospective study