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Due to advances in medical treatments, a substantial proportion of heart failure (HF) patients with reduced left ventricular ejection fraction (EF, HFrEF) have experienced partial or complete recovery of EF, termed HFrecEF, and markedly improved clinical outcomes. In the present study, we sought to investigate the relationship between glycemic control and the incidence of HFrecEF in hospitalized HFrEF patients with type 2 diabetes mellitus (T2DM).A total of 463 hospitalized T2DM patients with HFrEF were consecutively enrolled. Follow-up echocardiogram was performed after around 12 months. Patients who had an absolute EF improvement ≥10% and a second EF 40% were classified into HFrecEF, and those who did not meet these criteria were defined as persistent HFrEF.During the 12-month follow-up, 44.5% of T2DM patients developed HFrecEF. Patients with HFrecEF had significantly lower HbA1c level than those with persistent HFrEF (6.5% [IQR 5.8% ∼ 7.2%] vs. 6.7% [IQR 6.1% ∼ 7.8%], P = 0.003), especially in HF of an ischemic etiology. HbA1c levels were inversely correlated with changes in EF during follow-up. After multivariate adjustment, every 1% increase in HbA1c conferred a 17.4% (OR: 0.826 [95% CI 0.701-0.968]) lower likelihood of HFrecEF. Compared to patients with good glycemic control (HbA1c ≤ 6.2%), those with poor glycemic control (HbA1c 7.1%) had a 52.0% (OR: 0.480 [95% CI 0.281-0.811] decreased likelihood of HFrecEF.This study demonstrates that uncontrolled HbA1c level is associated with compromised development of HFrecEF in T2DM patients with HF, especially in those with an ischemic etiology.

Nanoparticle drug delivery systems have drawn considerable attention worldwide due to their unique characteristics and advantages in anticancer drug delivery. Herein, the curcumin (Cur) loaded nanomicelles with two-stage drug release behavior were developed. β-Cyclodextrin (β-CD) and cholesterol were conjugated onto both ends of the poly(ethylene glycol) (PEG) chain to obtain an amphiphilic β-CD-PEG-Chol. The Cur was loaded into the cavities of β-CD and nanomicelle when the β-CD-PEG-Chol self-assembled to the Cur@β-CD-PEG-Chol nanomicelles (Cur@CPC NMs). These Cur@CPC NMs are spherical particles with a particle size of 120.9 nm. The Cur drug loading capacity of Cur@CPC NMs are 61.6 ± 6.9 mg/g. The release behavior of Cur from Cur@CPC NMs conformed to a two-stage mode of "burst-release followed by sustained-release". The prepared Cur@CPC NMs possess high storage stability and excellent hemocompatibility. Moreover, these Cur@CPC NMs exhibit satisfactory antioxidant activity and anticancer activity, resulting in significant reduction in intracellular H

Anomalies as misalignment, microcrack are inevitable for large diameter high strength steel pipelines. To ensure the strain capacity of mismatched welding joint with misalignments of D 1,422 mm X80 steel pipeline, a comprehensive study via wide plate experiments and finite element model simulations was conducted. The full-scale tensile experiment of a X80 pipe wide plate with weld joint was conducted. Strain distributions on the plate was derived by DIC technic. Trends of CMOD at the precrack in the weld joint with tensile strains monitored. A FE model was established to inverse the wide plate experiment and prove the accuracy of numerical model’s prediction results for crack driving forces. Using the same modeling method, a parametrical 3D numerical simulation model for X80 line pipe with cracks in automatic welding joints was established. The double V-shaped groove type welding joint was precisely considered in the geometric model. Difference of the stress-strain relationships of yielding-to-tensile ratio of the BM, softening rate of the HAZ and strength matching coefficient of WM were considered in the material model. A CTOD extracting program coded was employed. Parametric analysis was performed to investigate the effects of load conditions, strength matching coefficient of WM, yielding-to-tensile ratio of BM and softening rate of HAZ on the strain capacity with a critical fracture toughness adopted in pipeline industry. Based on the derived results, mismatched ratio requirements of D 1,422 mm X80 pipes were listed, which provides guidance for the welding parameter design and safety evaluation of automatic welding joints.

Excess levels of chemical hepatotoxicants (alcohol, aflatoxin B1), oxidative drugs (acetaminophen) and some cytokines (ET-1, TGF-β1) can induce chronic or acute liver injury. After these, the severe hepatic disease, especially the liver fibrosis (LF) occurs without taking measures, which brings threat to human health. The dibenzocyclooctadiene lignans of S. chinensis (SCDLs) were found to act as the hepatoprotective components via blocking endothelin B receptor (ETBR). While study on its anti-LF mechanisms especially for its refined compound of schisantherin D (SC-D) is still a lack. So this study aims to investigate the anti-fibrosis effect of SC-D with in vitro and in vivo assays. Bioinformatics analysis revealed the close relations of ETBR to Smad2, Smad3, Nrf2, etc. in LF-related signaling pathways (such as TGF-β/Smad and Nrf2/ARE). Histopathological staining on livers showed the recovery trend in SC-D treated LF mice. SC-D also modulated expressions of ETBR and fibrosis or anti-oxidative related proteins (such as TIMP1, p-Smad2/3, Nrf2, Smad7, etc.) in LF mice livers. Serum levels of TNF-α, COLI, ALT, AST and LDH in SC-D treated mice were also downregulated compared with LF mice, and upregulated expression of GSH. In vitro studies, SC-D also modulated expressions of LF-related proteins to the normal tendency in LX-2 cell, while weakened its anti- LX-2 proliferation effect by transfections of si-Smad7 or si-Nrf2. Accordingly the anti-LF approach of SC-D showed relations with modulating ETBR linked fibrosis and anti-oxidative related signaling. Also, Smad7 and Nrf2 might be the key factors for SC-D mediated anti-LF effect.

Background. Left ventricular (LV) diastolic dysfunction (LVDD) is the defining feature of heart failure with preserved ejection fraction (HFpEF) and predicts subsequent incident heart failure (HF) and all-cause mortality. Mounting evidence reveals that cardiometabolic risk factors play critical roles in the development of LVDD. In this study, we sought to investigate the relation between serum uric acid (SUA) level and the progression of LVDD in apparently healthy patients. Methods. A total of 1082 apparently healthy subjects without diagnosed cardiovascular disease and LVDD were consecutively enrolled. SUA levels were measured, and repeat echocardiography and tissue Doppler imaging (TDI) were performed at baseline and during 1-year follow-up. Results. By dividing the study population based on quartiles of SUA, we found subjects in higher quartiles had greater increases in TDI-derived early diastolic velocity (e ′ ) and E (peak LV filling velocity)/e ′ ratios during 1-year follow-up. After multivariate adjustment, high SUA persisted to be an independent predictor for the subsequent worsening of LVDD (odds ratio: 1.351 [95% CI 1.125~1.625], per 100 μmol/L SUA). Subgroup analysis suggested that the association between SUA and LVDD development was more pronounced in subjects without other cardiometabolic risk factors involved. Factor analysis demonstrated that high SUA was the major cardiometabolic attribute in patients with LVDD progression. Conclusion. Our findings suggest that high SUA is an independent cardiometabolic risk factor for the progression of LVDD in apparently healthy subjects.

Background: Due to advances in medical treatments, a substantial proportion of heart failure (HF) patients with reduced left ventricular ejection fraction (EF, HFrEF) have experienced partial or complete recovery of EF, termed HFrecEF, and markedly improved clinical outcomes. In the present study, we sought to investigate the relationship between glycemic control and the incidence of HFrecEF in patients with type 2 diabetes mellitus (T2DM).Methods: A total of 385 T2DM patients with HFrEF were consecutively enrolled. Follow-up echocardiogram was performed after 6 to 12 months, which classified patients into HFrecEF or persistent HFrEF. Clinical outcomes of cardiovascular (CV) death and HF rehospitalization were analyzed during a mean of 3.3 years follow-up. Results: T2DM patients with HFrecEF had significantly lower HbA1c level than those with persistent HFrEF (6.4% [IQR 5.8%~7.1%] vs. 6.8% [IQR 6.1%~7.8%], P=0.001), especially in HF of ischemic etiology. After multivariate adjustment, every 1% increase in HbA1c conferred a 21.3% (OR: 0.787 [95% CI 0.658~0.933]) lower likelihood of HFrecEF. Compared to patients with good glycemic control (HbA1c≤6%), those with poor glycemic control (HbA1c > 8%) had higher risk of CV death or HF rehospitalization (HR: 2.778 [95% CI 1.470~5.251]). T2DM Patients with HFrecEF exhibited significantly better clinical outcomes than those with persistent HFrEF.Conclusions: This study demonstrates that T2DM patients with uncontrolled HbA1c levels were associated with compromised development of HFrecEF and worse clinical outcomes.

Background: Due to advances in medical treatments, a substantial proportion of heart failure (HF) patients with reduced left ventricular ejection fraction (LVEF, HFrEF) have experienced partial or complete recovery of LVEF, termed HFrecEF, and markedly improved clinical outcomes. In the present study, we sought to investigate the relationship between glycemic control and the incidence of HFrecEF in patients with type 2 diabetes mellitus (T2DM).Methods: A total of 310 age- and sex-matched T2DM patients with HFrecEF and persistent HFrEF were retrospectively enrolled based on 12-month repeat echocardiograms. HFrecEF was defined as follow-up LVEF > 40% and absolute LVEF improvement ≥ 10% compared to the baseline. The relationship between HFrecEF and HbA1c levels was analyzed. Results: During the 12-month follow-up, LVEF recovered from 35.93% ± 5.62% to 51.11% ± 8.53% in the HFrecEF group (PP=0.238) in the HFrEF group. T2DM patients with HFrecEF had significantly lower HbA1c level than those with persistent HFrEF (6.4% [IQR 5.8%~7.1%] vs. 6.8% [IQR 6.3%~7.4%], PConclusions: This study demonstrates that HFrEF patients with T2DM are more likely to develop HFrecEF under optimal glycemic control valued by lower HbA1c level.

Background: Chromogranin B (CgB) is increased in heart failure and proportionate to disease severity. We investigated whether circulating CgB level is associated with left ventricular (LV) functional recovery potential after successful recanalization of chronic total occlusion (CTO).Methods: Serum levels of CgB were assayed in 53 patients with stable angina with LV functional recovery [an absolute increase in LV ejection fraction (EF) of ≥5%] and 53 age- and sex-matched non-recovery controls after successful recanalization of CTO during 12-month follow-up.Results: We found that CgB level was significantly lower in the recovery group than in the non-recovery group (593 [IQR 454–934] vs. 1,108 [IQR 696–2020] pg/ml, P < 0.001), and that it was inversely correlated with changes in LVEF (Spearman's r = −0.31, P = 0.001). Receiver operating characteristic (ROC) analysis showed that the area under the curve of CgB for predicting LVEF improvement was 0.76 (95% CI 0.664–0.856), and that the optimal cutoff value was 972.5 pg/ml. In multivariate analyses, after adjusting for confounding factors, high CgB level remained an independent determinant of impaired LV functional recovery after CTO recanalization. LV functional improvement appeared to be more responsive to CgB in patients with poor than with good coronary collaterals.Conclusions: Elevated circulating CgB level confers an increased risk of impaired LV functional recovery after successful recanalization of CTO in patients with stable coronary artery disease.

Objective: The purpose of this systematic review is to assess the therapeutic effect of Jianpi decoctions in Chinese herbal medicines (CHM) combined with chemotherapy on the postoperative treatment of colorectal cancer. Methods: Literatures were obtained from Wanfang database, CNKI, PubMed, Cqvip, MEDLINE, Cochrane, CBM, and Springer LINK as well as other conference papers and theses. The search included all documents in English or Chinese published before September 2018. We selected randomized controlled trials based on specific criteria and the most important criteria were that Jianpi decoction should be applied in combination with chemotherapy on the postoperative treatment of colorectal cancer. Results: Publications in eight electronic databases were extensively searched and 20 trials were included for analysis eventually. A total of 1652 patients in total were enrolled in these studies. Among them, 879 patients received CHM and Western medicine combination therapy and another 773 participants only got Western medicine therapy. Compared with those patients receiving Western medicine alone, the survival rate of 1-year (odds ratio [OR] = 2.35, 95% confidence limit [Cl] = 1.30–4.28,P < 0.05), 3-year (OR = 2.02, 95% Cl = 1.49–2.73,P < 0.001), and 5-year survival rate (OR = 2.32, 95% Cl = 1.56–3.45,P < 0.001) of patients in the group of Jianpi decoctions in CHM and chemotherapy combination has significantly increased. Moreover, results also showed positive effects on immunoregulation such as CD3+ (OR = 0.68, 95% confidence interval [CI] = 0.52–0.85,P < 0.0001), CD4+/CD8+ (OR = 0.77, 95% CI = 0.29–1.26,P < 0.05). Side effects caused by chemotherapy such as nausea (OR = 0.35, 95% CI = 0.25–0.50,P < 0.0001) and vomiting (OR = 0.32, 95% CI = 0.22–0.46,P < 0.0001), diarrhea (OR = 0.42, 95% CI = 0.30–0.60,P < 0.0001), as well as metastasis and recurrence (OR = 0.38, 95% CI = 0.24–0.61,P < 0.001) were remarkably reduced. The quality of life (OR = 4.40, 95% Cl = 2.86–6.77,P < 0.0001) has been improved. Moreover, there was no statistically significant bias in the overall studies. Conclusion: This systematic review suggests that Jianpi decoction in CHM can reduce the chemotherapy toxicity, enhance the patient's immunity, prolong their survival rate, improve their quality of life as well as prevent metastasis, and recurrence for patients in postoperative treatment of colorectal cancer.

Objective: The objective of the study is to explore the traditional Chinese medicine (TCM) syndrome distribution in colorectal cancer (CRC) and its correlation with treatment methods and clinical laboratory indicators. Materials and Methods: Using the CRC cases report form of TCM, 760 CRC patients with TCM four diagnosis information, western medicine treatment information and clinical laboratory indicators were collected, and TCM syndromes distribution in CRC were summarized. The correlation between TCM syndrome type and western medicine treatments, clinical laboratory indicators such as liver and kidney function, immune function, and tumor biomarkers was analyzed. Results: In 760 cases of CRC, Spleen deficiency syndrome (SDS, 25%), liver and kidney Yin deficiency syndrome (LKYDS, 13%), LKYDS-SDS, 12%, spleen deficient Qi stagnation syndrome (SDQSS, 10%), and damp heat syndrome (DHS, 9%) were more common TCM syndrome types. LKYDS, SDS, LKYDS-SDS, and SDQSS were significantly distributed under different treatment methods (P < 0.001). There was no statistically significant difference in the distribution of immune function and cytokine among the five TCM syndromes (P > 0.05), but there was statistically significant difference in the distribution of blood routine, liver and kidney function, and tumor biomarkers (P < 0.05). Conclusion: LKYDS, SDS, LKYDS-SDS, SDQSS, and DHS were the first five TCM syndromes in CRC. There were the significant correlations between the distribution of TCM syndrome and the clinical laboratory indicators, and the distribution of TCM syndromes was affected by surgery, radiotherapy, and chemotherapy.

Triple-negative breast cancer (TNBC) is a refractory type of breast cancer that does not yet have clinically effective drugs. The aim of this study is to investigate the synergistic effects and mechanisms of resveratrol combined with cisplatin on human breast cancer MDA-MB-231 (MDA231) cell viability, migration, and invasion in vivo and in vitro. In vitro, MTS assays showed that resveratrol combined with cisplatin inhibits cell viability as a concentration-dependent manner, and produced synergistic effects (CI &lt, 1). Transwell assay showed that the combined treatment inhibits TGF-β1-induced cell migration and invasion. Immunofluorescence assays confirmed that resveratrol upregulated E-cadherin expression and downregulated vimentin expression. Western blot assay demonstrated that resveratrol combined with cisplatin significantly reduced the expression of fibronectin, vimentin, P-AKT, P-PI3K, P-JNK, P-ERK, Sma2, and Smad3 induced by TGF-β1 (p &lt, 0.05), and increased the expression of E-cadherin (p &lt, 0.05), respectively. In vivo, resveratrol enhanced tumor growth inhibition and reduced body weight loss and kidney function impairment by cisplatin in MDA231 xenografts, and significantly reduced the expressions of P-AKT, P-PI3K, Smad2, Smad3, P-JNK, P-ERK, and NF-κB in tumor tissues (p &lt, 0.05). These results indicated that resveratrol combined with cisplatin inhibits the viability of breast cancer MDA231 cells synergistically, and inhibits MDA231 cells invasion and migration through Epithelial-mesenchymal transition (EMT) approach, and resveratrol enhanced anti-tumor effect and reduced side of cisplatin in MDA231 xenografts. The mechanism may be involved in the regulations of PI3K/AKT, JNK, ERK and NF-κB expressions.

Non-negative matrix factorization (NMF), as a type of matrix factorization, has been widely used in the field of hyperspectral unmixing. Sparse concept coding (SCC) is another matrix factorization method that has emerged in recent years. A hyperspectral unmixing method based on SCC is presented. In this approach, SCC first learns a set of basis vectors that can capture the intrinsic geometric structure of the data as endmembers; and then this set of basis vectors is used as a dictionary for sparse representation learning; the sparse coefficients obtained is the abundances, which meets the requirement of abundance sparsity. SCC avoids the addition of manifold regularization on the endmembers and sparse constraints on the abundances, which reduces the complexity of the unmixing process. The presented algorithm is applied on synthetic and real data sets. Experimental results show that SCC improves unmixing accuracy compared with original NMF, L1/2-NMF and L1-NMF.

pH-Responsive nanoparticles (NPs) have emerged as an effective antitumor drug delivery system, promoting the drugs accumulation in the tumor and selectively releasing drugs in tumoral acidic microenvironment. Herein, we developed a new amphiphilic modified hydroxyethyl starch (HES) based pH-sensitive nanocarrier of antitumor drug delivery. HES was first modified by hydrophilic imidazole and hydrophobic cholesterol to obtain an amphiphilic polymer (IHC). Then IHC can self-assemble to encapsulate doxorubicin (DOX) and form doxorubicin-loaded nanoparticles (DOX/IHC NPs), which displayed good stability for one week storage and acidic sensitive long-term sustained release of DOX. As a result, cancer cell endocytosed DOX/IHC NPs could continuously release doxorubicin into cytoplasm and nucleus to effectively kill cancer cells. Additionally, DOX/IHC NPs could be effectively enriched in the tumor tissue, showing enhanced tumor growth inhibition effect compared to free doxorubicin. Overall, our amphiphilic modified HES-based NPs possess a great potential as drug delivery system for cancer chemotherapy.

Background Patients with type 2 diabetes are under substantially higher risk of in-stent restenosis (ISR) after coronary stent implantation. We sought to investigate whether visit-to-visit HbA1c variability is a potential predictor of ISR in diabetic patients after stent implantation. Methods We consecutively enrolled type 2 diabetic patients who underwent successful elective percutaneous coronary intervention and performed follow-up coronary angiography after around 12 months. The incidence of ISR and its relationship with visit-to-visit HbA1c variability, expressed as coefficient of variation (CV), standard deviation (SD) and variability independent of the mean (VIM), were studied. Multivariable Cox proportional hazards models were constructed to analyze the predictive value of HbA1c variability for ISR. Results From September 2014 to July 2018 in Ruijin Hospital, a total of 420 diabetic patients (688 lesions) after stent implantation were included in the final analysis. During a mean follow-up of 12.8 ± 1.3 months, the incidence of ISR was 8.6%, which was significantly increased in patients with higher CV of HbA1c (P = 0.001). The mean diameter stenosis (DS), net luminal loss and net luminal gain were 22.9 ± 16.8%, 0.42 ± 0.88 mm and 1.66 ± 0.83 mm, respectively. Greater DS was observed in subjects with higher tertiles of CV of HbA1c (P 1c ≤ 7%) in the baseline. In multivariate analysis, HbA1c variability was independently associated with incidence of ISR after adjustment for traditional risk factors and mean HbA1c (HR: 3.00 [95% CI 1.14–7.92] for highest vs. lowest tertile). Inclusion of CV of HbA1c led to a better risk stratification accuracy. Assessing HbA1c variability by SD or VIM yielded similar findings. Conclusions This study suggests that visit-to-visit HbA1c variability is an independent predictor of incidence of ISR in patients with type 2 diabetes after stent implantation. Trial registration NCT02089360: NCT

Background Patients with type 2 diabetes mellitus (T2DM) are predisposed to poor cardiovascular outcomes after ST-segment elevation myocardial infarction (STEMI). Left ventricular adverse remodeling (LVAR) triggered upon myocardial infarction is recognized as the predominant pathological process in the development of heart failure. In the present study, we sought to investigate whether visit-to-visit fasting plasma glucose (FPG) variability is a potential predictor of LVAR in T2DM patients after STEMI. Methods From January 2014 to December 2018 in Ruijin Hospital, T2DM patients with STEMI who underwent primary percutaneous coronary intervention were consecutively enrolled and followed up for ~ 12 months. The changes in left ventricular geometric and functional parameters between baseline and 12-month follow-up were assessed by echocardiography. The incidence of LVAR, defined as 20% increase in indexed left ventricular end-diastolic volume (LVEDV), and its relationship with visit-to-visit FPG variability were analyzed. Multivariate regression models were constructed to test the predictive value of FPG variability for post-infarction LVAR. Results A total of 437 patients with type 2 diabetes and STEMI were included in the final analysis. During a mean follow-up of 12.4 ± 1.1 months, the incidence of LVAR was 20.6% and mean enlargement of indexed LVEDV was 3.31 ± 14.4 mL/m2, which was significantly increased in patients with higher coefficient variance (CV) of FPG (P = 0.002) irrespective of baseline glycemic levels. In multivariate analysis, FPG variability was independently associated with incidence of post-infarction LVAR after adjustment for traditional risk factors, baseline HbA1c as well as mean FPG during follow-up (OR: 3.021 [95% CI 1.081–8.764] for highest vs. lowest tertile of CV of FPG). Assessing FPG variability by other two measures, including standard deviation (SD) and variability independent of the mean (VIM), yielded similar findings. Conclusions This study suggests that visit-to-visit FPG variability is an independent predictor of incidence of LVAR in T2DM patients with STEMI. Trial registration Trials number, NCT02089360; registered on March 17,2014.

Background:Patients with type 2 diabetes are under substantially higher risk of in-stent restenosis (ISR) after coronary stent implantation. We sought to investigate whether visit-to-visit glycemic variability is a potential predictor of ISR in diabetic patients after stent implantation.Methods:Type 2 diabetic patients underwent elective percutaneous coronary intervention were consecutively enrolled and 1-year follow-up coronary angiography was performed. The incidence of ISR and its relationship with visit-to-visit HbA1c variability, expressed as coefficient of variation (CV), standard deviation (SD) and variability independent of the mean (VIM), were studied. Multivariable Cox proportional hazards models were constructed to analyze the predictive value of glycemic variability for ISR.Results:From September 2014 to July 2018 in Ruijin Hospital, a total of 420 diabetic patients (688 lesions) after stent implantation were included in the final analysis. During a mean follow-up of 12.8 ± 1.3 months, the incidence of ISR was 8.6%, which was significantly increased in patients with higher CV of HbA1c (P = 0.001). The mean diameter stenosis (DS), net luminal loss and net luminal gain were 22.9 ± 16.8%, 0.42 ± 0.88 mm and 1.66 ± 0.83 mm, respectively. Greater DS was observed in subjects with higher tertiles of CV of HbA1c (P 1c ≤ 7%). In multivariate analysis, HbA1c variability was independently associated with incidence of ISR after adjustment for traditional risk factors and mean HbA1c (HR: 3.00 [95% CI:1.14 ~ 7.92] for highest vs. lowest tertile). Inclusion of CV of HbA1c led to a better risk stratification accuracy. Assessing glycemic variability by SD or VIM yielded similar findings.Conclusions:This study suggests that visit-to-visit HbA1c variability is an independent predictor of incidence of ISR in patients with type 2 diabetes after stent implantation.

Lung cancer has high incidence and mortality rates, in which lung squamous cell carcinoma (LUSC) is a primary type of non-small cell lung carcinoma (NSCLC). The aim of our study was to discover long non-coding RNAs (lncRNAs) associated with diagnose and prognosis for LUSC. RNA sequencing data obtained from LUSC samples were extracted from The Cancer Genome Atlas database (TCGA). Two prognosis-associated lncRNAs (including SFTA1P and LINC00519) were selected from LUSC samples, and the expression levels were also verified to be associated abnormal in LUSC clinical samples. Our findings demonstrate that lncRNAs SFTA1P and LINC00519 exert important functions in human LUSC and may serve as new targets for LUSC diagnosis and therapy.

Acid mine drainage (AMD) is the most significant environmental pollution problem associated with the mining industry. Case-specific testing is widely applied and established in the mining and consulting businesses for AMD prediction, and any improvements in its efficiency, while reducing its environmental impact, are of utmost societal importance. In this study, we develop a microfluidic screening method as a useful tool in the prediction and, potentially, prevention and remediation of AMD. The new approach offers key advantages including high throughput screening of reaction conditions, better spatiotemporal control over the process, and ability to conduct field-based measurements, which will account for specific interactions between mineral ores and their environment. Reagent and sample consumptions are greatly reduced to mL and mg levels, compared with those in conventional bulk-scale screening. Parallel (multichip) screening of ferric ion concentration gradients (0–40 mM) and temperature (23–75 °C) is demonstrated here, showing that the dissolution rate of pyrite significantly changes with the pH, temperature, and the ferric ion concentration, consistent with previous bulk-scale studies. To verify the robustness of the method, a mine waste rock was also tested in the microchip with natural waters. This study demonstrates the application of microfluidic screening to the challenging issue of AMD and, more generally, forecasting and optimization of mineral leaching in industry. Refereed/Peer-reviewed

Yinchenhao decoction (YCHD), comprising Yinchenhao (Artemisiae Scopariae Herba), Zhizi (Gardeniae Fructus) and Dahuang (Radix Rhei et Rhizoma), is widely used for treating various diseases. We aimed to investigate the bile acid metabolic mechanism of YCHD in dimethylnitrosamine (DMN)-induced liver fibrosis model. Rats received DMN (10 mg/kg, intraperitoneally) for four successive weeks for liver fibrosis induction and were treated with YCHD for the last 2 weeks. Histopathological analysis showed that YCHD prevented DMN-induced histopathological changes in liver tissues. Serum liver function in YCHD group improved. Ultraperformance liquid chromatography-mass spectrometry analysis showed that YCHD significantly restored both free and conjugated bile acid levels increased by DMN, to normal levels. RT-qPCR results showed that YCHD treatment upregulated the expression of genes related to bile acid synthesis, reabsorption, and excretion. Western blotting analysis showed that YCHD downregulated α-SMA, TGF-β1, p-Smad3, and p-ERK1/2 expression in chenodeoxycholic acid (CDCA)-activated hepatic stellate cells (HSCs). The viability of CDCA-activated HSCs significantly increased after treatment with YCHD and PD98059 (an ERK inhibitor) compared to YCHD treatment alone. Our findings suggest that YCHD alleviated DMN-induced liver fibrosis by regulating enzymes responsible for bile acid metabolism. Additionally, it inhibits CDCA-induced HSC proliferation and activation via TGF-β1/Smad/ERK signalling pathway.

Carvedilol, the third generation of vasodilators; serves as the blocker of non-selective beta-adrenergic receptor and alpha1 adrenergic receptor. It could protect the cardiovascular system of patients receiving dialysis treatment. However, current clinical trials discussing the therapeutic benefit of carvedilol on patients receiving dialysis treatment remain inconsistent. Consequently, we decided to perform a meta-analysis to evaluate the clinical efficacy of carvedilol on patients receiving dialysis treatment. A search was conducted using EMBASE, Pubmed, Cochrane Central Register of Controlled Trials, Wanfang database, Chinese National Knowledge Infrastructure (CNKI), and VIP information database up to February 2020. We research publications (include English and Chinese language) that discuss the effects of carvedilol on cardiovascular events, all-cause mortality, hospitalizations or left ventricular ejection fraction (LVEF) in dialysis population. Our analysis included 4 randomized control trials and 2 observational studies. We discussed the therapeutical effects of carvedilol on all-cause mortality, cardiovascular events, hospitalizations, and LVEF of patients receiving dialysis treatment. Totally, this analysis reported 2998 hemodialysis (HD) patients. We found a significant association between carvedilol and reduced incidence of all-cause mortality, cardiovascular events and hospitalizations in HD patients. In addition, carvedilol significantly improves LVEF (n = 241; WMD = 6.95; 95% CI, 0.54 to 13.36; I2 = 90%) in HD population. Our systematic review and meta-analysis demonstrates that carvedilol is associated with a reduced incidence of cardiovascular events, all-cause mortality and hospitalizations in patients on HD. Besides; carvedilol significantly improves LVEF in HD population. Nevertheless, high-quality and well-powered evidence is still needed, so as to further confirm the impacts of carvedilol on HD patients.

The present work focuses on in situ studying the transformation process of collagen molecules and fibrils in pigskin along with hydrothermal shrinkage. The results indicate that the triple helix of collagen molecules is firstly destabilized by hydrothermal treatment and more water molecules enter the space of three polypeptide chains of collagen molecules to slight increase the diameter of collagen fibrils. Then, the thermally labile domain of collagen molecules unfolds first to form tiny nodules. The nodules are shrinkage foci, which enlarge further and finally coalesce resulting in the shrinkage of pigskin. During the shrinkage process, the diameter of fibrils increases sharply. The spaces between collagen fibrils and fibers are compressed to form a more compact space arrangement than original extended forms, resulting in extrusion of water molecules. After shrinkage, partial fibrils structure was still observed and retained their characteristic banding patterns. Subsequently, the residual fibrils structure gradually disappeared and degraded.

Background Adverse cardiac remodeling after ST-segment elevation myocardial infarction (STEMI) is a major cause for poor cardiovascular outcomes such as heart failure. The predisposing factors and underlying mechanisms remain not fully understood. This study investigates the association of insulin resistance and dysglycemia with left ventricular (LV) remodeling after STEMI in non-diabetic patients. Methods A total of 485 non-diabetic subjects with STEMI who underwent primary percutaneous coronary intervention were consecutively enrolled and followed up for 12 months. Relation of homeostasis model assessment-estimated insulin resistance (HOMA-IR) and glucose levels to changes in echocardiography parameters was studied. Results Left ventricular dilation was detected in 49.1% of subjects at 12-month follow-up after STEMI, and was more severe in subjects with impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and high HOMA-IR levels. HOMA-IR remained correlated to changes in LV dimensions after adjusting for confounding risk factors. Multivariate regression analysis demonstrated that higher HOMA-IR was independently associated with greater LV dilation after STEMI. A significant interaction term was present between HOMA-IR and IGT in the model (P = 0.001). Conclusions Our study reveals that insulin resistance and dysglycemia are prevalent in non-diabetic patients with STEMI and are predictors of the post-infarction LV dilation. Trial registration Trials number, NCT02089360; registered on March 17, 2014

Yinchenhao decoction (YCHD) is a classical Traditional Chinese Medicine (TCM) formula that has been widely used in the treatment of liver fibrosis caused by chronic hepatitis B and jaundice for more than 1800 years. The purpose of this study was to investigate the apoptosis regulation mechanisms of YCHD and its active components suppresses liver fibrosis. The active components and putative targets of YCHD were predicted by network pharmacology approach. Functional and pathway enrichment analysis were presented in the present study by using clusterProfiler. Further, experimental validation was done by using terminal deoxynucleotidyl transferase (TDT) dUTP nick end labelling (TUNEL) assay and western blotting in dimethylnitrosamine (DMN)-induced liver fibrosis rats, and cell proliferation assay, apoptosis assay, and western blotting in human hepatic L02 cells and LX2 cells. 45 active compounds in YCHD formula, 592 potential target proteins and 1191 liver fibrosis-related human genes were identified. Functional and pathway enrichment analysis indicated that YCHD obviously influenced TNF, PI3K-Akt signaling pathways. Further, In vivo experiment indicated that YCHD treatment not only attenuated the symptoms of liver fibrosis, but also decrease the apoptosis of hepatic parenchyma cells. Moreover, in vitro experiments showed that rhein, kaempferol and quercetin treatments remarkably decreased the protein levels of cleaved caspase-3 and increased p-ERK1/2, PI3K and Bcl-XL protein expression in TNF-α-stimulated L02 cells. On the contrary, rhein, kaempferol, aloe-emodin and quercetin inhibited the proliferation of LX2 cells and up-regulated the protein levels of Bax and cleaved caspase-8. In conclusion, 45 active components and 296 potential targets of YCHD against liver fibrosis were identified by the analysis of network pharmacology and transcriptomics combination. The mechanisms of YCHD against liver fibrosis were involved in the regulation of multiple targets, especially affecting the apoptosis-related signaling pathways.

This paper reports on an ore-on-a-chip that enables efficient investigations of mineral leaching using real ore samples. Here, chalcopyrite (CuFeS2) ore samples are cut, polished flat, and sealed against a polydimethylsiloxane microchannel. The leach solution is collected for analysis, and the ore sample is then recovered for surface analysis. Compared to conventional bulk-scale leach tests, the ore-on-a-chip allows for faster, more efficient screening of leach parameters using real ore samples obtained from mine sites. Insight and optimization of leach conditions is demonstrated here for chalcopyrite, which has been extensively studied, yet leach performance is still strongly dependent on the origin of the ore. Two grades of chalcopyrite were chosen for this study (moderate and high purity), and the effect of ferric ion concentration and pH was studied in moderate and high purity chalcopyrite ores, respectively. The leach rate of Cu was faster in the presence of ore impurities (moderate grade) compared to the higher purity ore under the same conditions. The results also suggest that Fe is preferentially leached in the early stages to form an iron-deficient sulfide, according to X-ray photoelectron spectroscopy. Longer leach studies (48 h) reported no measurable surface passivation for the conditions studied. The ore-on-a-chip offers a new approach of case specific leach studies, which will enable rapid and tailored optimization of leach strategies for mineral processing Refereed/Peer-reviewed

To investigate the mechanism of a Bushen-Jianpi decoction (BSJPD) in liver cancer (LC) treatment, we analyzed clinical therapy data, conducted network pharmacology analysis, and performed pharmacological experimental verificationin vitroandin vivo. The univariate analysis of clinical therapy showed that the BSJPD was protective factor (p< 0.05). The network pharmacology analysis showed that 9 compounds were important nodes of BSJPD-LC therapy network. In experimental verification, the rate of apoptosis increased in the liver tumors of mice treated with the BSJPD (p< 0.05); drug serum with 20 % BSJPD inhibited cell viability (p< 0.05) and reduced the expression of PI3K, the Bcl-xL/BAD ratio, and the levels of p53 and p-Akt in HepG2 cells. Moreover, licochalcone A, alisol B, and hederagenin inhibited cell viability (p< 0.05), induced cell apoptosis (p< 0.01), reduced p-Akt levels, and increased cleaved-CASP3 (p< 0.05) and p53 expression levels in HepG2 cells. These data suggest that the BSJPD prolongs the survival of LC patients and induces apoptosis and that it may be associated with the regulation of PI3K, Akt, p53, CASP3, and Bcl-xL/BAD expression.