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Context Several small studies have suggested that the gut microbiome might influence osteoporosis, but there is little evidence from human metabolomics studies to explain this association. Objective This study examined the association of gut microbiome dysbiosis with osteoporosis and explored the potential pathways through which this association occurs using fecal and serum metabolomics. Methods We analyzed the composition of the gut microbiota by 16S rRNA profiling and bone mineral density using dual-energy X-ray absorptiometry in 1776 community-based adults. Targeted metabolomics in feces (15 categories) and serum (12 categories) were further analyzed in 971 participants using ultra-high-performance liquid chromatography coupled to tandem mass spectrometry. Results This study showed that osteoporosis was related to the beta diversity, taxonomy, and functional composition of the gut microbiota. The relative abundance of Actinobacillus, Blautia, Oscillospira, Bacteroides, and Phascolarctobacterium was positively associated with osteoporosis. However, Veillonellaceae other, Collinsella, and Ruminococcaceae other were inversely associated with the presence of osteoporosis. The association between microbiota biomarkers and osteoporosis was related to levels of peptidases and transcription machinery in microbial function. Fecal and serum metabolomics analyses suggested that tyrosine and tryptophan metabolism and valine, leucine, and isoleucine degradation were significantly linked to the identified microbiota biomarkers and to osteoporosis, respectively. Conclusion This large population-based study provided robust evidence connecting gut dysbiosis, fecal metabolomics, and serum metabolomics with osteoporosis. Our results suggest that gut dysbiosis and amino acid metabolism could be targets for intervention in osteoporosis.

BACKGROUND Many studies have examined associations between dietary isoflavones and atherosclerosis, but few used objective biomarkers. OBJECTIVES We examined the associations of isoflavone biomarkers (primary analyses) and equol production (secondary analyses) with the progression of carotid intima-media thickness (cIMT), and whether inflammation, systolic blood pressure (SBP), blood lipids, and sex hormone-binding globulin (SHBG) mediated these associations, in Chinese adults. METHODS This 8.8-y prospective study included 2572 subjects (40-75 y old) from the GNHS (Guangzhou Nutrition and Health Study; 2008-2019). The concentrations of daidzein, genistein, and equol were assayed by an HPLC-tandem MS in serum (n = 2572) at baseline and in urine (n = 2220) at 3-y intervals. The cIMT of the common carotid artery (CCA) and bifurcation segment were measured by B-mode ultrasound every 3 y, and the progressions of cIMT ( ∆cIMT) were estimated using the regression method. RESULTS Multivariable linear mixed-effects models (LMEMs) and ANCOVA revealed that subjects with higher serum isoflavones tended to have lower increases of CCA-cIMT. The mean ± SEM differences in 8.8-y ∆CCA-cIMT between extreme tertiles of serum isoflavones were -17.1 ± 8.4, -20.6 ± 8.3, and -23.3 ± 10.4 μm for daidzein, total isoflavone, and equol (P-trends

Background This study aimed to develop mortality-prediction models for patients with coronavirus disease-2019 (COVID-19). Methods The training cohort included consecutive COVID-19 patients at the First People’s Hospital of Jiangxia District in Wuhan, China, from 7 January 2020 to 11 February 2020. We selected baseline data through the stepwise Akaike information criterion and ensemble XGBoost (extreme gradient boosting) model to build mortality-prediction models. We then validated these models by randomly collected COVID-19 patients in Union Hospital, Wuhan, from 1 January 2020 to 20 February 2020. Results A total of 296 COVID-19 patients were enrolled in the training cohort; 19 died during hospitalization and 277 discharged from the hospital. The clinical model developed using age, history of hypertension, and coronary heart disease showed area under the curve (AUC), 0.88 (95% confidence interval [CI], .80–.95); threshold, −2.6551; sensitivity, 92.31%; specificity, 77.44%; and negative predictive value (NPV), 99.34%. The laboratory model developed using age, high-sensitivity C-reactive protein, peripheral capillary oxygen saturation, neutrophil and lymphocyte count, d-dimer, aspartate aminotransferase, and glomerular filtration rate had a significantly stronger discriminatory power than the clinical model (P = .0157), with AUC, 0.98 (95% CI, .92–.99); threshold, −2.998; sensitivity, 100.00%; specificity, 92.82%; and NPV, 100.00%. In the subsequent validation cohort (N = 44), the AUC (95% CI) was 0.83 (.68–.93) and 0.88 (.75–.96) for the clinical model and laboratory model, respectively. Conclusions We developed 2 predictive models for the in-hospital mortality of patients with COVID-19 in Wuhan that were validated in patients from another center.

The relationship of polyunsaturated fatty acids (PUFAs) with cardiovascular risk is still controversial. We aimed to determine whether erythrocyte n-3 and n-6 PUFAs are related to the risk of carotid atherosclerosis.From 2008 to 2019, baseline erythrocyte n-3 and n-6 PUFAs were determined in a cohort of 4040 Chinese adults (40-75 ys). The intima-media thickness (IMT) at the common carotid artery (CCA) and bifurcation of the carotid artery (BIF) and carotid plaque were assessed using ultrasonography at baseline and every 3 years.During a median follow-up of 8.8 years, we identified the following newly diagnosed cases: 535 cases of CCAIMT thickening, 654 cases of BIFIMT thickening, and 850 cases of carotid plaque. Higher erythrocyte docosahexaenoic acid (DHA) and arachidonic acid (ARA) and lower gamma-linolenic acid (GLA) were associated with decreased risks of BIFIMT thickening. N-3 eicosatrienoic acid (ETrA), docosapentaenoic acid (DPA), and n-6 dodecylthioacetic acid (DTA) presented a significant beneficial association with carotid IMT thickening in the short-term (2.8 y) follow-up (all p trend0.02), although the association was attenuated in the relatively long-term (8.8 y) follow-up. In addition, carotid plaque risk was found to be inversely associated with ETrA and DHA but positively associated with alpha-linolenic acid (ALA). N-6 linolenic acid (LA) and eicosadienoic acid (EDA) were not significantly associated with carotid atherosclerosis risk.Higher erythrocyte very-long-chain n-3 and n-6 PUFAs (especially DHA and ARA) and lower erythrocyte GLA are associated with lower carotid atherosclerosis risk, suggesting potential cardioprotective roles of very-long-chain PUFAs.

Presently, in the context of the novel coronavirus pneumonia epidemic, several antibiotics are overused in hospitals, causing heavy pressure on the hospital’s wastewater treatment process. Therefore, developing stable, safe, and efficient hospital wastewater treatment equipment is crucial. Herein, a bench-scale electrooxidation equipment for hospital wastewater was used to evaluate the removal effect of the main antibiotic levofloxacin (LVX) in hospital wastewater using response surface methodology (RSM). During the degradation process, the influence of the following five factors on total organic carbon (TOC) removal was discussed and the best reaction condition was obtained: current density, initial pH, flow rate, chloride ion concentration, and reaction time of 39.6 A/m2, 6.5, 50 mL/min, 4‰, and 120 min, respectively. The TOC removal could reach 41% after a reaction time of 120 min, which was consistent with the result predicted by the response surface (40.48%). Moreover, the morphology and properties of the electrode were analyzed. The degradation pathway of LVX was analyzed using high-performance liquid chromatography–mass spectrometry (LC–MS). Subsequently, the bench-scale electrooxidation equipment was changed into onboard-scale electrooxidation equipment, and the onboard-scale equipment was promoted to several hospitals in Dalian.

Background Several descriptive studies have reported that higher neutrophil count (NC) may be correlated with poor prognosis in patients with confirmed COVID‐19 infection. However, the findings from these studies are limited by methodology and data analysis. Methods This study is a cohort study. We non‐selectively and consecutively collected a total of 663 participants in a Chinese hospital from January 7 to February 28. Standardized and two‐piecewise Cox regression model were employed to evaluated the association between baseline neutrophil count (bNC), NC change rate (NCR), and death. Results bNC had a U‐shaped association with death. In the range of 0.1 to ≤1.49×109 /L (HR = 0.19, 95% CI = 0.05 to 0.66) and > 3.55×109 /L of bNC (HR = 2.82, 95% CI = 1.19 to 6.67), the trends on bNC with mortality were opposite. By recursive algorithm, the bNC at which the risk of the death was lower was range of >1.49 to ≤3.55×109 /L (HR=13.64, 95%CI=0.25 to 74.71). In addition, we find NCRs (NCR1 and NCR2) is not associated with COVID‐19‐related deaths. Conclusions Compared with NCR, bNC has the potential to be used for early risk stratification in patients with COVID‐19 infection. The relationship between bNC and mortality was U‐shaped. The safe range of bNC was 1.64 to 4.0 ×109 /L. Identifying the correlation may be helpful for early risk stratification and medical decision making. This article is protected by copyright. All rights reserved.

Background: Little is known about the interplay among dairy intake, gut microbiota and cardiometabolic health in human prospective cohort studies. Methods: The present study included 1780 participants from the Guangzhou Nutrition and Health Study. We examined the prospective association between habitual dairy consumption (total dairy, milk, yogurt) and gut microbial composition using linear regression after adjusting for socio-demographic, lifestyle and dietary factors. The cross-sectional association of dairy-associated microbial features with cardiometabolic risk factors was examined with a linear regression model, adjusting for potential confounders. Serum metabolomic profiles were analyzed by partial correlation analysis. Findings: There was a significant overall difference in gut microbial community structure (β-diversity) comparing the highest with the lowest category for each of total dairy, milk and yogurt (P < 0.05). We observed that dairy-associated microbes and α-diversity indices were inversely associated with blood triglycerides, while positively associated with high-density lipoprotein cholesterol. A follow-up metabolomics analysis revealed the association of targeted serum metabolites with dairy-microbial features and cardiometabolic traits. Specifically, 2-hydroxy-3-methylbutyric acid, 2-hydroxybutyric acid and L-alanine were inversely associated with dairy-microbial score, while positively associated with triglycerides (FDR-corrected P < 0.1). Interpretation: Dairy consumption is associated with the gut microbial composition and a higher α-diversity, which provides new insights into the understanding of dairy-gut microbiota interactions and their relationship with cardiometabolic health. Funding: This work was supported by the National Natural Science Foundation of China, Zhejiang Ten-thousand Talents Program, Westlake University and the 5010 Program for Clinical Researches of the Sun Yat-sen University.

Poor cell viability after transplantation has restricted the therapeutic capacity of mesenchymal stem cells (MSCs) for cardiac dysfunction after myocardial infarction (MI). Growth arrest-specific gene 6 (Gas6) encodes a secreted γ-carboxyglutamic acid (Gla)-containing protein that functions in cell growth, adhesion, chemotaxis, mitogenesis and cell survival. In this study, we genetically modified MSCs with Gas6 and evaluated cell survival, cardiac function, and infarct size in a rat model of MI via intramyocardial delivery. Functional studies demonstrated that Gas6 transfer significantly reduced MSC apoptosis, increased survival of MSCs in vitro and in vivo, and that Gas6-engineered MSCs (MSCGas6)-treated animals had smaller infarct size and showed remarkably functional recovery as compared with control MSCs (MSCNull)-treated animals. Mechanistically, Gas6 could enhance phosphatidylinositol 3-kinase (PI3K)/Akt signaling and improve hypoxia-inducible factor-1 alpha (HIF-1α)-driven secretion of four major growth factors (VEGF, bFGF, SDF and IGF-1) in MSCs under hypoxia in an Axl-dependent autocrine manner. The paracrine action of MSCGas6 was further validated by coculture neonatal rat cardiomyocytes with conditioned medium from hypoxia-treated MSCGas6, as well as by pretreatment cardiomyocytes with the specific receptor inhibitors of VEGF, bFGF, SDF and IGF-1. Collectively, our data suggest that Gas6 may advance the efficacy of MSC therapy for post-infarcted heart failure via enhanced Gas6/Axl autocrine prosurvival signaling and paracrine cytoprotective action.

Objective Isoflavones and lignans are phytoestrogens present in plant-based foods, which have a potential preventive effect on breast carcinogenesis. The effects of phytoestrogens on breast cancer may differ according to the hormonal environment. This case-control study aimed to investigate the association between serum phytoestrogens and odds of breast cancer among Chinese pre- and postmenopausal women. Methods A total of 792 cases and 813 age-matched controls were included. Serum isoflavone (daidzein, genistein, glycitein, equol, and formononetin) and lignan (enterodiol and enterolactone) concentrations were measured using a liquid chromatography-tandem mass spectrometry method. Results Significant inverse associations were found between serum total soy isoflavone precursors, daidzein, genistein, formononetin, total lignans, enterodiol, enterolactone, and the odds of breast cancer in premenopausal but not postmenopausal women. For premenopausal women, the adjusted odds ratios (95% confidence intervals) for the highest versus the lowest serum concentration groups were 0.60 (0.41-0.87) for total soy isoflavones precursors, 0.64 (0.44-0.93) for daidzein, 0.62 (0.43-0.90) for genistein, 0.49 (0.35-0.68) for formononetin, 0.38 (0.25-0.57) for total lignans, 0.49 (0.33-0.73) for enterodiol, and 0.49 (0.33-0.74) for enterolactone. However, the interaction between serum phytoestrogens and menopausal status on odds of breast cancer was statistically significant only for daidzein. No significant association was found between serum equol or gycitein and the odds of breast cancer among either pre- or postmenopausal women. Conclusions Higher levels of certain serum isoflavones and lignans were associated with reduced odds of breast cancer in premenopausal women, but the interaction was statistically significant only for daidzein.

Background Little is known about the inter-relationship among fruit and vegetable intake, gut microbiota and metabolites, and type 2 diabetes (T2D) in human prospective cohort study. The aim of the present study was to investigate the prospective association of fruit and vegetable intake with human gut microbiota and to examine the relationship between fruit and vegetable-related gut microbiota and their related metabolites with type 2 diabetes (T2D) risk. Methods This study included 1879 middle-age elderly Chinese adults from Guangzhou Nutrition and Health Study (GNHS). Baseline dietary information was collected using a validated food frequency questionnaire (2008–2013). Fecal samples were collected at follow-up (2015–2019) and analyzed for 16S rRNA sequencing and targeted fecal metabolomics. Blood samples were collected and analyzed for glucose, insulin, and glycated hemoglobin. We used multivariable linear regression and logistic regression models to investigate the prospective associations of fruit and vegetable intake with gut microbiota and the association of the identified gut microbiota (fruit/vegetable-microbiota index) and their related fecal metabolites with T2D risk, respectively. Replications were performed in an independent cohort involving 6626 participants. Results In the GNHS, dietary fruit intake, but not vegetable, was prospectively associated with gut microbiota diversity and composition. The fruit-microbiota index (FMI, created from 31 identified microbial features) was positively associated with fruit intake (p p = 0.003) and the FMI-T2D association (OR 0.90, 95%CI 0.84–0.97) were both successfully replicated in the independent cohort. The FMI-positive associated metabolite sebacic acid was inversely associated with T2D risk (OR 0.67, 95%CI 0.51–0.86). The FMI-negative associated metabolites cholic acid (OR 1.35, 95%CI 1.13–1.62), 3-dehydrocholic acid (OR 1.30, 95%CI 1.09–1.54), oleylcarnitine (OR 1.77, 95%CI 1.45–2.20), linoleylcarnitine (OR 1.66, 95%CI 1.37–2.05), palmitoylcarnitine (OR 1.62, 95%CI 1.33–2.02), and 2-hydroglutaric acid (OR 1.47, 95%CI 1.25–1.72) were positively associated with T2D risk. Conclusions Higher fruit intake-associated gut microbiota and metabolic alteration were associated with a lower risk of T2D, supporting the public dietary recommendation of adopting high fruit intake for the T2D prevention.

Several small studies suggested gut microbiome might influence osteoporosis, but rare metabolomics evidence from human study had explained the link. This study examined the association of gut microbiome dysbiosis with osteoporosis and explored the potential pathways by using fecal and serum metabolomics. We analyzed gut microbiota compositions by 16S rRNA profiling and bone density (BMD) using a dual-energy X-ray absorptiometry in 1776 community-based adults. Targeted metabolomics in feces (15 categories) and serum (12 categories) were further analyzed in 971 participants with ultra-performance liquid chromatography coupled to tandem mass spectrometry. This study showed osteoporosis was related to gut microbiota beta diversity, taxonomy and functional composition. The relative abundance of Actinobacillus, Blautia, Oscillospira, Bacteroides and Phascolarctobacterium was positively, while Veillonellaceae other, Collinsella and Ruminococcaceae other were inversely, associated with the presence of osteoporosis, which related to higher levels of peptidases and transcription machinery in microbial function. Fecal and serum metabolomics analyses suggested that the tyrosine metabolism and the tryptophan metabolism in feces and the valine, leucine and isoleucine degradation in serum were significantly linked to the identified microbiota biomarkers and osteoporosis. This large population-based study provided the robust evidence connecting gut dysbiosis, fecal and serum metabolomics with osteoporosis. Our results suggested that gut dysbiosis and amino acid metabolism could be potential targets for the intervention of osteoporosis.

Saturated fatty acids with different chain lengths have different biological activities, but little is known about very-long-chain saturated fatty acids (VLCSFAs). This study investigated the associations between the circulating VLCSFAs and cardiovascular health. This community-based cohort study included 2198 adults without carotid artery plaques (CAPs) at baseline. The percentage of baseline erythrocyte VLCSFA (arachidic acid (C20:0), behenic acid (C22:0), and lignoceric acid (C24:0)) was measured by gas chromatography. The presence of CAPs was determined at baseline and every 3 years thereafter by ultrasound examination. A meta-analysis was conducted to summarize the pooled associations between circulating VLCSFAs and the risk of cardiovascular diseases (CVDs). During a median of 7.2 years of follow-up, 573 women (35.1%) and 281 men (49.6%) were identified as CAP incident cases. VLCSFAs were inversely related with CAP risk in women (all p-trend &lt, 0.05) but not in men. Multivariate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of CAPs for the highest (vs. lowest) quartile were 0.80 (0.63&ndash, 1.01) for C20:0, 0.71 (0.56&ndash, 0.89) for C22:0, 0.75 (0.59&ndash, 0.94) for C24:0, and 0.69 (0.55&ndash, 0.87) for total VLCSFAs in women. The pooled HRs (95% CIs) of CVDs for the highest (vs. lowest) circulating VLCSFAs from seven studies including 8592 participants and 3172 CVD events were 0.67 (0.57&ndash, 0.79) for C20:0, 0.66 (0.48&ndash, 0.90) for C22:0, and 0.57 (0.42&ndash, 0.79) for C24:0, respectively. Our findings suggested that circulating VLCSFAs were inversely associated with cardiovascular health.

In vitro and in vivo studies suggested that flavonols, flavones, flavanones and flavan-3-ols have preventive effects on breast carcinogenesis. Epidemiological evidence about the associations between these flavonoid biomarkers and breast cancer risk is limited. This study aimed to investigate the association between serum concentration of these flavonoids and breast cancer risk among Chinese women. This hospital-based case–control study recruited 792 breast cancer cases and 813 age frequency-matched (5-year interval) controls who provided eligible blood samples in Guangdong Province, China. Ultra-high-performance liquid chromatography–tandem mass spectrometry was used to measure flavonoids. Unconditional logistic regression was used to estimate the odds ratio (OR) and 95% confidence internal (CI). Higher concentrations of serum flavonols, isorhamnetin, kaempferol, flavanones and naringenin were significantly associated with lower breast cancer risk, with adjusted ORs (95% CIs) for the highest versus the lowest group of 0.66 (0.49–0.89) for flavonols, 0.52 (0.38–0.70) for isorhamnetin, 0.60 (0.45–0.80) for kaempferol, 0.65 (0.49–0.87) for flavanones and 0.45 (0.34–0.60) for naringenin, respectively. Significant positive associations were observed between serum flavan-3-ols, epigallocatechin, epigallocatechin-3-gallate and breast cancer risk. No significant associations were observed for serum quercetin, flavones, apigenin, luteolin, hesperetin, catechin, epicatechin and epicatechin-3-gallate with overall breast cancer risk. This study suggested that serum flavonols and flavanones were inversely associated with breast cancer risk and serum flavan-3-ols were positively associated with breast cancer risk. Serum flavones were not associated with overall breast cancer risk. These findings warrant further confirmation in prospective studies.

BACKGROUND Lumbar disc herniation (LDH) places a serious burden on the daily lives and socioeconomics of people. Although the pathogenesis of LDH is complex, genetic factors such as single nucleotide polymorphisms (SNPs) may affect the risk of developing LDH. In the present study, we aimed to elucidate the effect of RAB40C SNPs on the risk of LDH in the Chinese Han population. METHODS We investigated 508 LDH cases and 508 healthy controls for this case-control study. Three tag SNPs in RAB40C were selected and genotyped using the Agena MassARRAY platform (Agena Bioscience, San Diego, CA, USA). After adjusting for age and gender, odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using unconditional logistic regression. RESULTS In the allele model, we found rs62030917 and rs2269556 in RAB40C with a minor G allele significantly increased the risk of LDH (rs62030917: OR = 1.23, 95% CI = 1.00-1.50, p = 0.046; rs2269556: OR = 1.21, 95% CI = 1.02-1.45, p = 0.033). In genetic model analysis, rs2269556 was associated with an increased risk of LDH under both codominant (OR = 1.49, 95% CI = 1.03-2.15, p = 0.035) and log-additive models (OR = 1.21, 95% CI = 1.01-1.45, p = 0.035). rs62030917 of RAB40C was associated with an increased risk of LDH under codominant, recessive and log-additive models (p < 0.05) only among individuals younger than 49 years after stratification by age. CONCLUSIONS For the first time, our results suggest that rs62030917 and rs2269556 in the RAB40C gene influence genetic susceptibility to LDH.

BACKGROUND This study aimed to evaluate the biomechanical stress of the internal fixation screws and vertebral bodies after the full-segment, interval, key vertebral, and strategy pedicle screw fixations under 7 work conditions in a patient with adult degenerative scoliosis (ADS) using finite elements (FE) analysis. MATERIAL AND METHODS A patient with ADS underwent internal fixation by pedicle screws after posterior incision in combination with subtotal laminectomy decompression and bone graft fusion, and received thin-layer computed tomography (CT) spine scanning at T12-L5. The CT data were used to constitute three-dimensional FE full-segment, interval, key vertebral, and strategic pedicle screw models. The stress of each screw-rod system under different working conditions was evaluated. RESULTS Forward flexion, backward extension, lateral flexion, and rotation greatly increased the force of the pedicle screw systems. The maximum stress of the screw-rods was the lowest in the full-segment model under almost all the working conditions except for the upright situation. The maximum stress of the vertebral bodies was the minimum in the strategic model under all the 7 working conditions, followed by that in the key vertebra and full-segment models. CONCLUSIONS Collectively, the strategic and key vertebra pedicle screw schemes can decrease the biomechanical stress of screw-rod systems and vertebral bodies, which is close to the full-segment scheme. Our results may help explore the optimal surgical means for pedicle screw fixation for ADS patients, which can maximally reduce the risk of screws-related postoperative complications and simultaneously maintain a reasonable 3D orthopedic effect.

Background Changes in platelet count are common in COVID-19 patients. The platelet count reflects the thrombocyte turnover, acting as a sensitive indicator of illness severity that is of great clinical utility to monitor a quickly changing health condition of patients affected by aggressive viral infections. This study aims to investigate the significance of platelet count during the progression of the disease in COVID-19 patients. Methods A total of 532 COVID-19 patients were involved in the cohort study from the First People’s Hospital of Jiangxia District in Wuhan from January 7, 2020, to February 28, 2020. We collected the clinical characteristics and laboratory data of patients. Patients still hospitalized before February 29, 2020, died on admission, with malignant tumors, previous gastrointestinal surgery, missing baseline platelet count, or platelet count detected only once, were excluded. We used a generalized additive model and generalized additive mixed model to compare trends in platelet count over time among survivors and non-survivors, with an adjustment for potential confounders. Results During the follow-up, twenty-nine subjects died (mortality rate, 5.45%). The platelets among non-survivors decreased and among survivors increased gradually within 1 week after admission. In addition, the difference between the two groups showed an increasing trend during 1 week after admission. This difference increased by an average of 5.3 × 10^9/L daily. Conclusions In the early stage, platelet count can dynamically reflect the pathophysiological changes in COVID-19 patients. Early decrease in platelet count was associated with mortality in patients with COVID-19. Causality, however, cannot be deduced from our data.

Background: COVID-19 has caused a large number of deaths in a short period and lacks a specific treatment Early identification of poor prognosis patients may f

Background: Several descriptive studies have reported that higher neutrophil count (NC) may be correlated with poor prognosis in patients with confirmed COVID19

Loading of Au nanoparticles (AuNPs) onto environmentally sensitive polymer microgels is increasingly used to regulate their optical properties and catalytic activities. Herein, we synthesized composite polymer microgels composed of poly(N-isopropylacrylamide-co-3-methacryloxypropyltrimethoxysilane)/poly(acrylic acid) with a core–shell structure, and AuNPs were controllably loaded onto/into the network chains of the polymer microgels using seed-mediated growth. The prepared AuNPs composite materials possessed good pH sensitivity; the electromagnetic coupling between the AuNPs could thus be tuned via the swelling/deswelling of the polymer microgels under various acidic/alkaline conditions. More importantly, the coordination interaction between the carboxyl groups in the PAA chains and Cu2+ ions changed by varying the copper ion content under various pH conditions, thus enabling regulation of the localized surface plasmon resonance of the AuNPs. These structural features of the prepared composite microgels enabled to tailor the optical performance of the AuNPs by varying the pH of the surrounding medium.

Background Evolocumab (AMG 145), a PCSK9 inhibitor, has been shown to decrease low-density lipoprotein cholesterol (LDL-C) levels. Doses of 140 mg administered every 2 weeks (Q2W) and 420 mg administered every 4 weeks (Q4W) are widely used, and both dosing schedules were effective in clinical trials. However, some researchers have speculated that 140 mg Q2W administration has equal or even greater efficacy. This meta-analysis was performed to assess the differences in efficacy and safety between the two doses. Methods We searched the PubMed, EMBASE, and Web of Science databases to identify relevant clinical trials published before January 2016. A total of 2403 patients from 8 randomized controlled trials were identified and included in the analysis. Results Evolocumab administered at 140 mg Q2W resulted in a greater percent change from baseline in LDL-C concentration (− 7.27; 95% confidence interval (CI), − 10.36 to − 4.18) and had greater efficacy in achieving the treatment goal of LDL-C ≤ 1.8 mmol/L with an relative risk (RR) of 1.09 (95% CI, 1.00 to 1.18) compared with 420 mg Q4W in patients who were concomitantly treated with statins. These findings were not significantly different between the 140 mg Q2W and 420 mg Q4W groups when evolocumab was administered as monotherapy. There was no difference in the rate of occurrence of the main treatment-related adverse events between the two doses. Conclusions Evolocumab administered at 140 mg Q2W was more effective than the 420 mg Q4W dosage at lowering lipid concentrations, especially in patients who concomitantly received stable statin therapy.

Previous investigations have shown that changes in total prostate volume (TPV) are highly variable among aging men, and a considerable proportion of aging men have a stable or decreasing prostate size. Although there is an abundance of literature describing prostatic enlargement in association with benign prostatic hyperplasia, less is known about the appropriate age cut-off points for TPV growth rate. In this community-based cohort study, TPV was examined once a year in men who had consecutive health checkup, during a follow-up of 4 years. A total of 5058 men (age 18-92 years old) were included. We applied multiple regression analyses to estimate the correlation between TPV growth rate and age. Overall, 3232 (63.9%) men had prostate growth, and 1826 (36.1%) had a stable or decreased TPV during the study period. The TPV growth rate was correlated negatively with baseline TPV (r=-0.32, P

Spinal cord injury (SCI) comprises nerve and motor function disorders that may be caused by a variety of damaging factors and is challenging to treat. The aim of the present study was to investigate the regenerative effects of neural stem cell (NSC) transplantation combined with intraperitoneal injection of erythropoietin (EPO) on cross-sectional SCI in rats. A model of SCI was induced in 40 adult Wistar rats via the complete transection of the 10th thoracic vertebra (T10). The rats were allocated at random into 4 groups: Control, NSC, EPO and NSC + EPO groups (n=10 per group). Morphological alterations associated with axonal regeneration were detected using neurofilament (NF)-200 immunohistochemistry and immunofluorescence staining after 8 weeks. Basso, Beattie and Bresnahan (BBB) scoring was used to evaluate the recovery of hindlimb function. A total of 5 rats died following surgery, including 2 control rats and 1 rat each in the EPO, NSC and NSC + EPO groups. NSCs labeled with bromodeoxyuridine were observed to have survived and migrated in the spinal cord tissue after 8 weeks. Significant histomorphological differences were observed in the NSC and NSC + EPO groups compared with the EPO and control groups. Furthermore, the rats of the NSC + EPO group exhibited significantly enhanced axonal regeneration in the SCI area compared with the NSC group rats. The rats of the NSC and NSC + EPO groups exhibited significantly improved BBB scores compared with the EPO and control group rats at 7 days after treatment (P

The penetration paths of chloride ions in recycled aggregate concrete (RAC) are of significant interest and have not been well studied previously. This study used X-ray computed tomography (X-CT) as a novel approach to investigate chloride ion penetration paths in RAC. The results indicate that X-CT can be used for the constant monitoring of chloride ion penetration paths in RAC, and the influence of mix proportions on the chloride ion penetration can be understood through the X-CT visualization.

Background and aims Dyslipidemia contributes to the development and progression of renal disease. The objective of this study was to investigate whether an elevated non-HDL-cholesterol to HDL-cholesterol ratio (NonHDLc/HDLc) predicts new-onset chronic kidney disease (CKD). Methods and results We followed 1891 Chinese adults with normal or near-normal kidney function at baseline who participated in an annual health checkup program for the occurrence of new-onset CKD [defined as an estimated glomerular filtration rate (eGFR) of 2 (low eGFR) and/or proteinuria (defined as urinary protein ≥1 + on dipstick testing)] or low eGFR. Cox proportional hazards models were used to examine the independent relationship between the plasma NonHDLc/HDLc ratio and new-onset CKD. During a median follow-up period of 2.8 years, 3% ( n = 57) of participants developed new-onset CKD. Compared with patients in the lowest tertile, patients with NonHDLc/HDLc ratios in the highest tertile had a 1.45-fold higher risk of new-onset CKD (hazard ratio [HR], 2.45; 95% confidence interval [95% CI], 1.07 to 5.61; P = 0.035) after adjustment for potential confounders. There was a marginally significant association with low eGFR (tertile 3 versus tertile 1: HR, 2.94; 95% CI, 0.98 to 8.82; P = 0.054). Conclusions NonHDLc/HDLc ratio is an independent risk factor for the development of CKD. Assessment of NonHDLc/HDLc ratio may help identify high risk groups with chronic kidney disease.

A non-dipper pattern of high blood pressure is associated with increased risk of organ damage and cardiovascular disease in patients with hypertension. The aim of the study was to evaluate the left ventricular (LV) remodeling and function and arterial stiffness in a dipper/non-dipper pattern of high blood pressure in patients with hypertension. A total of 183 hypertensive patients with no history of adverse cardiovascular events were divided into two groups based on 24 hours ambulatory blood pressure monitoring (ABPM): 66 patients with a dipper pattern and 117 patients with non-dipper pattern. Detailed transthoracic echocardiogram was performed and analyzed with advance speckle tracking 3-orthogonal direction strain analysis to assess LV systolic function and tissue Doppler-derived E/E′ for LV diastolic function assessment. Cardio ankle vascular index (CAVI) was used to evaluate arterial stiffness. Compared with patients with dipper hypertension, those with non-dipper hypertension had increased LV mass index, higher prevalence of eccentric and concentric LV hypertrophy, more impaired LV diastolic and systolic function and peripheral arterial stiffness. Multivariable analysis revealed that a non-dipper pattern was independently associated with LV systolic dysfunction evaluated by speckle tracking-derived strain analysis. In conclusion, a non-dipper pattern of hypertension is an independent risk factor for LV systolic dysfunction. Treatment that could reverse this non-dipper pattern may reduce cardiac damage in these patients.

We investigate the relationship of SNPs in XRCC1, ERCC1 and ERCC2 to methotrexate intravenous adriamycin and intra-arterial cisplatin chemotherapy response and survival in bone cancer patients. 281 consecutive patients diagnosed with bone tumor between January 2003 to January 2005, and they were followed up until the end of January 2010. Polymorphisms in XRCC1Arg280His, XRCC1Arg399Gln, ERCC1 Asn118Asn, ERCC1 Gln504Lys, ERCC2 Asp312Asn and ERCC2 Lys751Gln were detected based upon Sequenom MassARRAY platform. All 281 patients were followed up until the end of January 2010. The median follow-up time was about 43.9 months. Our study showed a longer survival rate in XRCC1 399 Arg/Arg genotype than Gln/ Gln, and with a significant increased death risk (HR=0.46, 95%CI=0.31-0.96). For ERCC1 Asn118Asn, the variant genotype T/T was strongly significantly associated with a higher event free survival when compared with the wide-type C/C, with the adjusted OR (95% CI) of 0.33(0.15-0.97). ERCC2 751 A/A genotype showed increased the event free survival of osteosarcoma (HR=0.45; 95%CI=0.15-0.91), and T allele genotype of ERCC2 Lys751Gln was significantly associated with low risk of death from osteosarcoma (HR=0.53, 95%CI= 0.28-0.95). This study is the first time to report the ERCC1 and ERCC2 gene polymorphisms might well be useful as a surrogate marker of clinical outcome in bone cancer. Key words: DNA repaired gene, polymorphisms, osteosarcoma, chemotherapy, response.

We investigated the effect of neural stem cells (NSC) and erythropoietin (EPO) on axon regeneration in adult rats with transected spinal cord injury, and provided an experimental basis for clinical treatment. Forty Wistar rats with T10-transected spinal cord injury were randomly divided into four groups of ten rats: a control group (group A), an NSC-transplant group (group B), an NSC-transplant and EPO group (group C), and an EPO group (group D). Biotinylated dextran amines (BDA) anterograde corticospinal cord neuronal tracing and Fluoro-Gold (FG) retrograde tracing were carried out at the 8th week after operation to observe the regeneration of nerve fibers. The Basso, Beattie, and Bresnahan (BBB) locomotor score was used to evaluate restoration. 1) BDA and FG immunofluorescence staining: in group C, a large number of regenerated axons were observed and some penetrated the injured area. In group B, only a small number of regenerated axons were observed and none penetrated the injured area. In group D, only sporadic regenerated nerve fibers were observed occasionally, while in group A, no axonal regeneration was observed. In group C, a small number of cones and axons emitted yellow fluorescence, and no FG-labeled cells were observed in the other groups. 2) The BBB scores for group C were higher than those for the other groups, and the differences were statistically significance (P < 0.05). NSC transplantation combined with EPO intraperitoneal injection may benefit axon regeneration in rats with transected spinal cord injury, and accelerate the functional recovery of the hindlimb locomotor.

The part-through circumferential crack is a typical crack form in pipe structure, which often lead to the structure failure. Firstly, the local flexibility equations of a pipe with a part-through circumferential crack are derived by using linearly elastic fracture mechanics. Secondly, an adaptive Simpson quadrature-revisted was used to numerically calculate the local flexibility coefficients. Finally, the model test were performed to validate the local flexibility for a part-through circumferentially cracked pipe. The results show that the natural frequencies of cracked pipe obtained by the model test agree well with the theoretical values from the proposed equations of the local flexibility. It is demonstrated the feasibility of the proposed method for vibtaion analysis and damage identification of a cracked pipe.

Background Morbidities related to atherosclerosis, such as acute coronary syndrome (ACS), remain the leading cause of mortality. Axl is a receptor tyrosine kinase that is expressed in mammalian vascular and immune cells. Axl signaling is involved in the regulation of the inflammatory response. A considerable amount of evidence indicates that inflammation is responsible for the development of atherosclerosis in patients with ACS. Methods To assess the relation of Axl and ACS, we recruited 64 patients with coronary heart disease: 34 with ACS, 30 with stable coronary heart disease, and 24 apparently healthy controls. Serum concentrations of soluble Axl (sAxl) were quantified by enzyme-linked immunosorbent assay. High-sensitivity C-reactive protein, tumor necrosis factor alpha, troponin i, and other routine biochemical markers were also measured. Results The levels of sAxl were significantly higher in patients with ACS than in the controls ( P = 0.005). Furthermore, correlation analysis indicated that sAxl was significantly associated with serum levels of high-sensitivity C-reactive protein (r = 0.283, P = 0.008), tumor necrosis factor alpha (r = 0.565, P 0.001), and troponin I (r = 0.264, P = 0.013). Logistic regression analysis (odds ratio = 1.038, 95% confidence interval, 1.008–1.069, P = 0.012) indicated a significant association between sAxl and ACS. Conclusions Serum levels of sAxl correlate to inflammatory biochemical markers. These findings demonstrate for the first time that sAxl does have a role in ACS, presumably connected to the inflammation.

Arterial ischemia and hemorrhage are associated with bevacizumab, an inhibitor of vascular endothelial growth factor that is widely used to treat many types of cancers. As specific types of arterial ischemia and hemorrhage, cerebrovascular events such as central nervous system (CNS) ischemic events and CNS hemorrhage are serious adverse events. However, increased cerebrovascular events have not been uniformly reported by previous studies. New randomized controlled trials (RCTs) have been reported in recent years and we therefore conducted an up-to-date meta-analysis of RCTs to fully characterize the risk of cerebrovascular events with bevacizumab. We searched the databases of PubMed, Web of Science, and the American Society of Clinical Oncology conferences to identify relevant clinical trials up to February 2014. Eligible studies included prospective RCTs that directly compared patients with cancer treated with and without bevacizumab. A total of 12,917 patients from 17 RCTs were included in our analysis. Patients treated with bevacizumab had a significantly increased risk of cerebrovascular events compared with patients treated with control medication, with a relative risk of 3.28 (95% CI, 1.97-5.48). The risks of CNS ischemic events and CNS hemorrhage were increased compared with control, with RRs of 3.22 (95% CI, 1.71-6.07) and 3.09 (95% CI, 1.36-6.99), respectively. Risk varied with the bevacizumab dose, with RRs of 3.97 (95% CI, 2.15-7.36) and 1.96 (95% CI, 0.76-5.06) at 5 and 2.5 mg/kg/week, respectively. Higher risks were observed in patients with metastatic colorectal cancer (RR, 6.42; 95% CI, 1.76-35.57), and no significant risk was observed in other types of tumors. In conclusion, the addition of bevacizumab significantly increased the risk of cerebrovascular events compared with controls, including CNS ischemic events and CNS hemorrhage. The risk may vary with bevacizumab dose and tumor type.

Prolonged use of glucocorticoids (GCs) for the treatment of chronic inflammatory and autoimmune diseases commonly exerts various side-effects, including impairment of skeletal development. However, the effect of GCs on chondrocytes, which play a key role in skeletal development, has been rarely reported. In the present study, autophagy was induced in the ATDC5 chondrocyte cell line following treatment with dexamethasone (Dex) at doses of 1‑100 µM, and that this effect can be inhibited by RU486, a GC antagonist. Autophagy induced by the highest Dex dose (100 µM) was associated with a reduction in ATDC5 cell viability. We conclude that high doses of GC can reduce ATDC5 chondrocyte cell viability by inducing autophagy.

Concerns have arisen regarding the risk of ischemic heart disease with the novel antiangiogenic agent bevacizumab, a recombinant humanised monoclonal antibody to the vascular endothelial growth factor that is widely used in cancer treatment. Currently, the role of bevacizumab in ischemic heart disease is controversial. This meta-analysis was therefore performed to assess the overall risk of ischemic heart disease associated with the use of bevacizumab. The databases of PubMed, EMBASE and Web of Science were searched for English language studies of randomised controlled trials comparing bevacizumab with control therapy published through October 25, 2012. Summary incidence rates, relative risks (RRs) and 95% confidence intervals (CIs) were calculated using random-effects or fixed-effects models based on the heterogeneity of the included studies. A total of 4,617 patients from 7 randomised controlled trials were identified and included for analysis. Among those patients receiving bevacizumab, the summary incidence of ischemic heart disease was 1.0% (95% CI, 0.6%–1.4%). Patients treated with bevacizumab had a significantly increased risk of ischemic heart disease with an RR of 2.49 (95% CI, 1.37–4.52) compared with controls. In addition, both high doses and low doses of bevacizumab increased the risk of cardiac ischemia (low dose at 2.5 mg/kg per week: RR, 2.14 [95% CI, 1.09–4.19]; high dose at 5 mg/kg per week: RR, 4.81 [95% CI, 1.03–22.42]). Bevacizumab was also found to significantly increase the risk of cardiac ischemia in patients with colorectal cancer (RR, 2.13; 95% CI, 1.11–4.06) compared with controls. This meta-analysis shows the use of bevacizumab was associated with an increased risk of developing ischemic heart disease in colorectal cancer patients receiving this drug. Our conclusions are limited by the available data. Further evaluations of high-quality RCTs are needed.

Abstract 4819 The Eph receptors are found in a wide range of cancers and correlate with metastasis. However, their precise role in cancer has only started to be addressed. In this study, we investigated the role of Eph-A4 receptor in metastasis and invasive activity of myeloid leukemia cells. We fisr tested the expression of Eph-A4 in eight primary myeloid leukemias imclulding four with extramedullary metastasis and four without it, and leukemia cell line K562 by Real-time PCR and western blotting, then found that Eph- A4 was wildly expressed in myeloid Leukemia cells, especially in myeloid leukemia cells with high invasive activity. To further clarified the question, the stable over-expressing Eph-A4 cell line (K562-EphA4) based the wild K562 cell and pGC lentivirus vector were established to declare the metastasis and invasive activity in myeloid leukemia cells in vitro by trans-well migration assay. The results indicated that the mRNA level and protein expression of Eph-A4 were significantly increased in myeloid leukemias with extramedullary metastasis and K562 cells compared to those without it (P Disclosures: No relevant conflicts of interest to declare.