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The treatment of cardiovascular diseases and obesity, two diseases posing a major risk to human health, has been plagued by the scarcity of potent and effective medication with fewer side effects. To address this problem, numerous efforts, and some progress, have been made. Among possible treatments are some medicinal herbs; particularly promising is Alisma orientale (AO). In the last decade, an increasing amount of research has shown that AO has some desirable therapeutic effects on cardiovascular diseases and obesity. Because of its efficacy, natural origin, and minimal adverse effects, AO has aroused great attention. Based on this, this review provides an overview of the latest progress from the last decade regarding the pharmacological and therapeutic effects, molecular mechanisms, and related effective constituents of AO in the treatment of cardiovascular diseases and obesity. Results from the research currently available reveal that active constituents of AO, such as alisol B 23-acetate, alisol A 24-acetace, and alisol A, have been proven to be effective for treating cardiovascular diseases by modulating the lipid metabolism of macrophages, improving the biological behavior of vascular smooth muscle cells (VSMCs), and enhancing anti-inflammatory effects. Moreover, the active constituents of AO can also intervene in obesity by modulating abnormal glucose and lipid metabolism and fat decomposition of the body by activating the AMPK- and PPAR-related signaling pathways. In summation, based upon our research of available literature, this review reveals that AO and its active constituents have a great potential to be used as drugs for treating cardiovascular diseases and ameliorating obesity.

Acute kidney injury (AKI) after total aortic arch replacement (TAAR) is frequent and associated with adverse outcomes, whereas its early detection remains a challenge. Serum cystatin C (sCysC) and urinary N-acetyl-β-d-glucosaminidase (uNAG) are clinically available renal biomarkers, but their combination for AKI detection requires more evidence. This study aimed to assess the discriminative abilities of these biomarkers in AKI after TAAR.Patients undergoing TAAR were included in this prospective observational study. The AKI prediction model was developed and internal verificated, and the significance of each variable was analyzed by random forest (RF). Finally, the best predictive critical values of sCysC and uNAG were explored by the AUC-ROC curve.The AUC-ROC of the prediction model was substantially enhanced by adding sCysC and uNAG (0.909 vs 0.844, p 0.001), and the clinical utility and risk reclassification were significantly improved. Additionally, the RF showed that sCysC and uNAG ranked first and second. The AUC-ROC for each were 0.864 and 0.802 respectively, and the cut-off values were 1.395 mg/L and 31.90 U/g Cre respectively.The prediction model incorporating functional marker sCysC and tubular injury marker uNAG can improve the discriminative abilities of AKI after TAAR.

BACKGROUND: The modification of N(6)-methyladenosine (m(6)A) is a dynamic and reversible course that might play a role in cardiovascular disease. However, the mechanisms of m(6)A modification in myocardial ischemia/reperfusion injury (MIRI) remain unclear. METHODS: A mouse model of MIRI and a cell model of oxygen-glucose deprivation/reperfusion (OGD/R) HL-1 cells were employed. In an in vivo study, the total RNA m(6)A modification levels were determined by dot blot, and the key genes related to m(6)A modification were screened by real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot. In an in vitro study, the effects of AlkB homolog 5 (ALKBH5), an RNA demethylase, on cell proliferation, cell injury, and apoptosis were detected by the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay, lactate dehydrogenase (LDH) and cardiac troponin-I (cTnI) levels, and flow cytometry. Besides, the m(6)A modification-changed and differentially expressed messenger RNA (mRNA) were determined by methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA sequencing (RNA-seq) in ALKBH5-overexpressed HL-1 cells. Finally, the mRNA levels of the promising targeted gene were examined by RT-qPCR and its m(6)A modification levels were examined by MeRIP-qPCR. RESULTS: Our results showed that RNA m(6)A modification was involved in MIRI, in which ALKBH5 was downregulated. Functionally, by overexpressing or silencing ALKBH5 in experimental cells, we verified its protective properties on cell proliferation, cell injury, and apoptosis in the process of MIRI. Besides, we provided a mass of latent different mRNAs with m(6)A modification variation in ALKBH5-overexpressed HL-1 cells. Mechanistically, we further screened the most potential targeted mRNAs and suggested that triple functional domain (Trio) mRNA could be upregulated by ALKBH5 by reducing m(6)A level of Trio. CONCLUSIONS: This study demonstrated that the downregulated ALKBH5 might contribute to MIRI process by increasing the m(6)A modification of Trio mRNA and downregulating Trio.

We describe a photoinduced copper-catalyzed asymmetric radical decarboxylative alkynylation of bench-stable N-hydroxyphthalimide(NHP)-type esters of racemic alkyl carboxylic acids with terminal alkynes, which provides a flexible platform for the construction of chiral C(sp3 )-C(sp) bonds. Critical to the success of this process are not only the use of the copper catalyst as a dual photo- and cross-coupling catalyst but also tuning of the NHP-type esters to inhibit the facile homodimerization of the alkyl radical and terminal alkyne, respectively. Owing to the use of stable and easily available NHP-type esters, the reaction features a broader substrate scope compared with reactions using the alkyl halide counterparts, covering (hetero)benzyl-, allyl-, and aminocarbonyl-substituted carboxylic acid derivatives, and (hetero)aryl and alkyl as well as silyl alkynes, thus providing a vital complementary approach to the previously reported method.

ObjectiveSerum N-terminal pro-B-type natriuretic peptide (NT-proBNP) and cystatin C (sCysC) are available clinically and beneficial in diagnosing acute kidney injury (AKI). Our purpose is to identify the performance of their combined diagnosis for AKI in critically ill patients.DesignA prospectively recruited, observational study was performed.SettingAdults admitted to the intensive care unit of a tertiary hospital in China.ParticipantsA total of 1222 critically ill patients were enrolled in the study.Main outcome measuresTo identify the performance of the combined diagnosis of serum NT-proBNP and sCysC for AKI in critically ill patients. The area under the receiver operating characteristic curve (AUC-ROC), category-free net reclassification index (NRI) and incremental discrimination improvement (IDI) were utilised for comparing the discriminative powers of a combined and single biomarker adjusted model of clinical variables enriched with NT-proBNP and sCysC for AKI.ResultsAKI was detected in 256 out of 1222 included patients (20.9%). AUC-ROC for NT-proBNP and sCysC to detect AKI had a significantly higher accuracy than any individual biomarker (pConclusionsIn critically ill individuals, serum NT-proBNP, sCysC and clinical risk factors combination improve the discriminative power for diagnosing AKI.

Backgrounds: The plasma colloid osmotic pressure (COP) values for predicting mortality are not well-estimated. A user-friendly nomogram could predict mortality by incorporating clinical factors and scoring systems to facilitate physicians modify decision-making when caring for patients with serious neurological conditions.Methods: Patients were prospectively recruited from March 2017 to September 2018 from a tertiary hospital to establish the development cohort for the internal test of the nomogram, while patients recruited from October 2018 to June 2019 from another tertiary hospital prospectively constituted the validation cohort for the external validation of the nomogram. A multivariate logistic regression analysis was performed in the development cohort using a backward stepwise method to determine the best-fit model for the nomogram. The nomogram was subsequently validated in an independent external validation cohort for discrimination and calibration. A decision-curve analysis was also performed to evaluate the net benefit of the insertion decision using the nomogram.Results: A total of 280 patients were enrolled in the development cohort, of whom 42 (15.0%) died, whereas 237 patients were enrolled in the validation cohort, of which 43 (18.1%) died. COP, neurological pathogenesis and Acute Physiology and Chronic Health Evaluation II (APACHE II) score were predictors in the prediction nomogram. The derived cohort demonstrated good discriminative ability, and the area under the receiver operating characteristic curve (AUC) was 0.895 [95% confidence interval (CI), 0.840–0.951], showing good correction ability. The application of this nomogram to the validation cohort also provided good discrimination, with an AUC of 0.934 (95% CI, 0.892–0.976) and good calibration. The decision-curve analysis of this nomogram showed a better net benefit.Conclusions : A prediction nomogram incorporating COP, neurological pathogenesis and APACHE II score could be convenient in predicting mortality for critically ill neurological patients.

Identification of metabolic alterations is useful for elucidating the pathophysiology and mass spectrometry-aided metabolomic, which provides small molecule metabolites to understand underlying mechanisms of complex diseases. In this work, we developed a novel liquid chromatography coupled with tandem mass spectrometry-based metabolomics screen coupled with multivariate statistical analysis workflow to obtaining the metabolite annotation, visualization and rapid characterization of small molecular metabolites, then revealed the altered metabolic pathway in a rat model of alcohol-induced liver damage rats as case study. The ions were detected in both positive and negative mode, and the key biomarkers were selected through multivariate statistical screening analysis. We employed the enhanced mass spectrometry coverage method to comprehensive analysis of the metabolite data. Importantly, we further find these small molecule metabolites were associated with multiple metabolic pathways. The elucidation of these altered metabolic pathways should help identify new and specific therapeutic targets. In addition, this metabolomics workflow coupled to LC-MS/MS has been successfully applied to the identification of small molecule metabolites in this complex disease. We strongly believe that metabolomics studies will benefit from incorporating liquid chromatography coupled with tandem mass spectrometry strategies.

Down syndrome (DS), caused by trisomy of chromosome 21, occurs in 1 of every 800 live births. Early defects in cortical development likely account for the cognitive impairments in DS, although the underlying molecular mechanism remains elusive. Here, we performed histological assays and unbiased single-cell RNA-Seq (scRNA-Seq) analysis on cerebral organoids derived from 4 euploid cell lines and from induced pluripotent stem cells (iPSCs) from 3 individuals with trisomy 21 to explore cell-type–specific abnormalities associated with DS during early brain development. We found that neurogenesis was significantly affected, given the diminished proliferation and decreased expression of layer II and IV markers in cortical neurons in the subcortical regions; this may have been responsible for the reduced size of the organoids. Furthermore, suppression of the DSCAM/PAK1 pathway, which showed enhanced activity in DS, using CRISPR/Cas9, CRISPR interference (CRISPRi), or small-molecule inhibitor treatment reversed abnormal neurogenesis, thereby increasing the size of organoids derived from DS iPSCs. Our study demonstrates that 3D cortical organoids developed in vitro are a valuable model of DS and provide a direct link between dysregulation of the DSCAM/PAK1 pathway and developmental brain defects in DS.

The present study aimed to investigate the toxic effects of different amyloidogenic light-chains (LCs) on cardiomyocytes, and demonstrate the differentially expressed genes (DEGs) and signaling pathways that participate in this process. Cultured cardiomyocytes were treated with recombinant κ LC peptide (AL-09) or with serum from a patient diagnosed with multiple myeloma (λ LC) with cardiac involvement. The 6xHis peptide or serum from healthy patients was used as peptide control or serum control, respectively. Cell viability was determined using CCK-8 assay and apoptosis was analyzed by flow cytometry. The DEGs were detected by RNA sequencing (RNA-Seq), followed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Changes in gene expression levels were confirmed by reverse transcription-quantitative PCR. The cell viability in the AL-09 peptide-treated (0.2 mg/ml) and patient serum-treated (1:10 dilution) cardiomyocytes decreased to 42 and -72% of the corresponding control groups. The extent of cell apoptosis increased in AL-09-treated cardiomyocytes compared with the control group. RNA-Seq showed 256 DEGs co-existed in the two paired groups, including 127 upregulated and 88 downregulated genes. The KEGG pathways for upregulated expressed genes included the ‘TGF-β signaling pathway’, the ‘Hedgehog signaling pathway’, the ‘ErbB signaling pathway’ and ‘lysine degradation’. The higher mRNA expression of bone morphogenetic protein (Bmp) 4, Bmp6, prostaglandin G/H synthase (Ptgs)1, Ptgs2, epiregulin, Tgfa and procollagen-lysine,2-oxoglutarate 5-dioxygenase 2 were confirmed. The KEGG pathways of downregulated expressed genes included genes involved with the ‘p53 signaling pathway’ and the ‘cell cycle’. The mRNA expression levels of E3 ubiquitin-protein ligase CCNB1IP1 showed significant downregulation in the AL-09 peptide group compared with those in the 6xHis peptide group. In conclusion, cardiomyocytes treated with amyloidogenic λ and κ LCs presented with decreased cell viability compared with controls. Cell apoptosis increased in κ LC-treated cells compared with controls. The gene expression profiles associated with transforming growth factor-β-bone morphogenetic protein, the receptor tyrosine-protein kinase erbB-2 signaling pathways, prostaglandins, collagen production, the p53 signaling pathway and the cell cycle were altered in light-chain-treated cardiomyocytes.

Ferroptosis is a newly discovered type of cell death triggered by intracellular phospholipid peroxidation that is morphologically, biologically and genetically distinct from other types of cell death. Ferroptosis is classified as regulated necrosis and is more immunogenic than apoptosis. To date, compelling evidence indicates that ferroptosis plays an important role in inflammation, and several antioxidants functioning as ferroptosis inhibitors have been shown to exert anti-inflammatory effects in experimental models of certain diseases. Our review provides an overview of the link between ferroptosis and inflammation; a better understanding of the mechanisms underlying ferroptosis and inflammation may hasten the development of promising therapeutic strategies involving ferroptosis inhibitors to address inflammation.

ObjectiveChanges in thyroid function will be accompanied by changes in urinary N-acetyl-β-D-glucosaminidase (uNAG) levels. Therefore, whether thyroid hormones interfere the ability of uNAG in detecting acute kidney injury (AKI) has raised concern in patients with critical illness.DesignA prospectively recruited, observational study was performed.SettingAdults admitted to the intensive care unit of a grade A tertiary hospital in China.ParticipantsA total of 1919 critically ill patients were enrolled in the study.Main outcome measuresTo investigate the variations of the ability of uNAG to detect AKI in patients with critical illness under different thyroid hormones levels (differences in area under the curve (AUC) for uNAG diagnosis and prediction of AKI with different thyroid hormones levels).ResultsThe bivariate correlation analysis revealed that FT3 and TT3 levels were independently associated with uNAG levels (p0.05).ConclusionsEven if uNAG levels varied with FT3 and TT3 levels, these hormones did not interfere with uNAG’s ability to detect AKI in patients with critical illness.

Firms often look for ways to improve the return on investment that they earn from costly environmental innovation. Drawing from customer-based brand equity perspective, this article investigates license effect, a previously unexplored benefit associated with brands’ environmental innovation. License effect refers that high level of environmental innovation grants brands the license to employ atypical marketing strategy without penalty (in the form of impaired attitudes). We confirm the existence of license effect at product attribute level and brand level in study 1 and 2. Study 3 further investigated whether license effect was contingent on important contextual factors. Our results reveal that license takes effect on price strategy at both product attribute level and brand level. Moreover, license effect disappears in recycle phase. We conclude that license comes into effect only when customers construe atypical marketing strategies as behaviors that associated with personal benefit. By introducing license effect, we bridge innovation literature and customer-based brand equity theory to explore firms’ benefit from consumers’ evaluations. Furthermore, our findings remind managers of a new approach to improve return from environmental innovation investment.

Tubular arch bridges are susceptible to fatigue problems due to stress concentrations, welding imperfections and tensile residual weld stresses. These bridges are composed of circular hollow section profiles welded together in tubular joints. This paper describes the determination of residual weld stresses in T-joints with the incremental hole-drilling method. The residual stress distribution can be used to determine fatigue crack behavior and fatigue lifetime more precisely. The incremental hole-drilling method is used to measure residual welding stresses on two similar T-joints. Experimental residual stress measurements were performed with the aid of the RS-200 milling guide. Strain gauge rosettes are attached to the test surface and with the milling guide, a small hole is drilled through the center of the strain gauge rosette. Strains at incremental depths are measured and the residual stresses are calculated according to ASTM E837-13a. A comparison is made between residual stress distributions obtained with finite element simulation and the experimental measurements. The distributions from finite element simulation show tensile yield stresses close to the weld while the experimental measurements indicate tensile yield stresses only in the axial direction of the primary tube. In all other cases, the residual stresses are tensile within 50% of yield stress or even compressional. However, more measurements on similar test specimens are necessary for a reliable residual stress distribution. Knowledge of the residual stress distribution is essential to accurately estimate the crack development under fatigue loads. In future research, the residual stresses can be used to study the influence of residual weld stresses on the fatigue lifetime and improve the design of steel tubular joints in arch bridges.

Background The objective of this study is to assess the efficacy of electrical stimulation (ES) for the treatment of patients with migraine. Methods MEDLINE, EMBASE, Cochrane Library, CINAHL, PsycINFO, Scopus, Web of Science, Allied and Complementary Medicine Database, ProQuest Nursing and Allied Health, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure will be searched for eligible studies. All electronic databases will be searched from inception to the present with no language restriction. Two authors will independently carry out study selection, data collection, and study quality assessment, respectively. RevMan 5. 3 software will be used for statistical analysis. Results This study will summarize high quality evidence on the efficacy and safety of ES for the treatment of migraine. Conclusion This study will establish the accurate results of ES for migraine to facilitate the clinical practice and guideline development. Prospero registration number PROSPERO CRD42019147480.

High-throughput metabolomics can clarify the underlying molecular mechanism of diseases via the qualitative and quantitative analysis of metabolites. This study used the established Yang Huang syndrome (YHS) mouse model to evaluate the efficacy of geniposide (GEN). Urine metabolic data were quantified by ultraperformance liquid chromatography-tandem mass spectrometry. The non-target screening of the massive biological information dataset was performed, and a total of 33 metabolites, including tyramine glucuronide, aurine, and L-cysteine, were identified relating to YHS. These differential metabolites directly participated in the disturbance of phase I reaction and hydrophilic transformation of bilirubin. Interestingly, they were completely reversed by GEN. While, as the auxiliary technical means, we also focused on the molecular prediction and docking results in network pharmacological and integrated analysis part. We used integrated analysis to communicate the multiple results of metabolomics and network pharmacology. This study is the first to report that GEN indirectly regulates the metabolite "tyramine glucuronide" through its direct effect on the target heme oxygenase 1 in vivo. Meanwhile, heme oxygenase-1, a prediction of network pharmacology, was the confirmed metabolic enzyme of phase I reaction in hepatocytes. Our study indicated that the combination of high-throughput metabolomics and network pharmacology is a robust combination for deciphering the pathogenesis of the traditional Chinese medicine (TCM) syndrome.

The accumulation of arsenic in rice has become a worldwide concern. In this study, dose-dependency in tissues (intestine, liver and kidney) and blood distribution of inorganic arsenicals and their methylated metabolites were investigated in male C57BL/6 mice exposed to four arsenic species (arsenite [iAs]III, arsenate [iAs]V, monomethylarsonate [MMA]V, and dimethylarsinate [DMA]V) at four doses (control [C]: 0 μg/g, simulation [S]: 0.91 μg/g, medium [M]: 9.1 μg/g and high [H]: 30 μg/g) according to the arsenical composition in rice for 8 and 16 weeks. No adverse effects were observed, while body weight gain decreased in group H. Increases in total arsenic concentrations (CtAs) and histopathological changes in the tissues occurred in all of the test groups. CtAs presented a tendency of kidney > intestine > liver > blood and were time-/dose-dependent in the liver and kidney in groups M and H. In the intestine and blood, abundant iAs (23%–28% in blood and 36%–49% in intestine) was detected in groups M and H, and CtAs decreased in group H from the 8th week to the 16th week. PMI decreased in the liver and SMI decreased in the kidney. These results indicate that the three tissues are injured through food arsenic. The intestine can also accumulate food arsenic, and the high arsenic dose will cause a deficiency in the absorbing function of the intestine. Thus, long-term exposure to arsenic-contaminated rice should be taken seriously attention.

Human GABAergic interneurons (GIN) are implicated in normal brain function and in numerous mental disorders. However, the generation of functional human GIN subtypes from human pluripotent stem cells (hPSCs) has not been established. By expressing LHX6, a transcriptional factor that is critical for GIN development, we induced hPSCs to form GINs, including somatostatin (SST, 29%) and parvalbumin (PV, 21%) neurons. Our RNAseq results also confirmed the alteration of GIN identity with the overexpression of LHX6. Five months after transplantation into the mouse brain, the human GABA precursors generated increased population of SST and PV neurons by overexpressing LHX6. Importantly, the grafted human GINs exhibited functional electrophysiological properties and even fast-spiking-like action potentials. Thus, expression of the single transcription factor LHX6 under our GIN differentiation condition is sufficient to robustly induce human PV and SST subtypes.

Angiotensin II (Ang II)-induced mitochondrial dysfunction is a prominent characteristic of the majority of cardiovascular diseases. Astragaloside IV (As-IV), the major active ingredient of Astragalus membranaceus (Fisch.) Bge. (a traditional Chinese herbal medicine), possesses antioxidant properties. The present study was carried out to examine whether As-IV can reverse Ang II-induced mitochondrial dysfunction in vascular smooth muscle cells (VSMCs) and to elucidate the underlying molecular mechanisms. Cultured rat aortic VSMCs treated with Ang II (1 µM) for 24 h exhibited mitochondrial dysfunction, including a decrease in mitochondrial oxygen consumption rates (OCRs), adenosine triphosphate (ATP) production and mitochondrial DNA (mtDNA) levels, as well as the disruption of mitochondrial structural integrity. Following treatment with Ang II, As-IV (50 µg/ml) was added to the culture medium followed by incubation for a further 24 h. The administration of As-IV significantly increased the mitochondrial OCRs, ATP production and the mtDNA levels, and reversed the mitochondrial morphological changes which occurred in the VSMCs. Treatment with As-IV also reversed the Ang II-induced increase in the production of reactive oxygen species (ROS), the increase in NADPH oxidase and xanthine oxidase activity, as well as the decrease in mitochondrial membrane potential (ΔΨm) and manganese superoxide dismutase (Mn-SOD) activity. Furthermore, treatment with As-IV led to an increase in the mRNA expression of peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α) and mitochondrial transcription factor A (Tfam), and in the protein expression of PGC-1α, parkin and dynamin 1-like protein 1 (Drp1) in the VSMCs. These results indicate that As-IV exerts beneficial effects on Ang II-induced mitochondrial dysfunction in rat VSMCs and that these effects are mediated through the inhibition of ROS overproduction, as well as the promotion of mitochondrial autophagy and mitochondrial biogenesis. These data demonstrate the antioxidant properties of As-IV.

Yin-Chen-Hao-Tang (YCHT), the classic formulae of traditional Chinese medicine (TCM), is widely used to treat dampness-heat jaundice syndrome (DHJS) and various liver diseases. However, the therapeutic mechanism of YCHT is yet to have an integrated biological interpretation. In this work, we used metabolomics technology to reveal the adjustment of small molecule metabolites in body during the treatment of YCHT. Aim to discover the serum biomarkers which are associated with the treatment of DHJS against YCHT. Pathological results and biochemical indicators showed that the hepatic injury and liver index abnormalities caused by DHJS was effectively improve after treatment with YCHT. On the basis of effective treatment, ultra-high performance liquid chromatography (UPLC-G2Si-HDMS) combined with the multivariate statistical analysis method was utilized to analyze the serum samples. Finally, 22 biomarkers were identified by using mass spectrometry and illuminated the correlative metabolic pathways which play a significant role and as therapeutic targets in the treatment of DHJS. This work demonstrated that mass spectrometry metabolomics provides a new insight to elucidate the action mechanism of formulae.

The article using Brusselator model analyses the evolution mechanism of industrial clusters. The study found, the formation of industrial clusters is an inner reinforcing cycle accumulation process, the competing interaction is an important condition for the evolution of industrial clusters, and cluster innovation driving the system to the state development more orderly, form the new dissipative structure, promote the evolution of industrial cluster.

Objective To explore protective effect of rosiglitazone on myocardial ischemia reperfusion injury. Methods A total of 48 male SD rats were randomly divided into control group (A), I/R group(B), high dose of rosiglitazone (C), low dose of rosiglitazone (D). Plasm concentration of creatine kinase (CK), CK-MB, hsCRP, Superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), nitric oxide (NO) and endothelin (ET) were measured 1 h later after I/R. 24 h after I/R hearts were harvested to observe pathological and ultrastructural changes. Immunohistochemistry and western blotting was used to test CD40 expression in myocardial tissue. Area of myocardial infarction were tested, arrhythmia rate during I/R was recorded. Results Plasm concentration of creatine kinase (CK), CK-MB, hsCRP, NO, MDA and ET were decreased in group C, D compared with group B. Plasm concentration of T-SOD and GSH-Px was increased significantly in group C, D compared with group B. Compared with group B, pathological and ultrastructural changes in group C, D were slightly. Myocardial infarction area and arrhythmia rate were lower in group C, D compare with group B. Conclusions Rosiglitazone can protect myocardium from I/R injury by enhancing T-SOD and GSH-Px concentration, inhibit inflammatory reaction, improve endothelial function, reduce oxidative stress and calcium overload.

Welding parameters have important affect on welding quality. In this paper, temperature field and residual stress field simulation of thin 316L stainless steel plate are performed by finite element method. The welding process is multi-pass butt TIG(Tungsten Inert Gas) welding. Simulation model are established by SYSWELD code with multi-pass bead. A Gaussian heat source representing the arc energy is verified and the temperature distribution in multilayer welding process is simulated. Then the results are compared with test results measured by thermal-couples. Effects of welding speed and interpass cooling time during multi-pass on temperature field and stress field are studied. The results show that the faster the welding speed and the longer the cooling time, the higher the residual stress will be.

Background: Astragaloside IV (As-IV) exerts beneficial effects on hypoxia/reoxygenation (H/R)-induced cardiomyocyte injury, possibly through normalization of sarcoplasmic reticulum Ca2+ ATPase (SERCA2a) function. The exact mechanisms remain unknown. This study was designed to investigate the role of protein kinase A (PKA) in the protective effect of As-IV on SERCA2a function. Methods: Cultured cardiomyocytes from neonatal rats were exposed to 6 h of hypoxia followed by 3 h of reoxygenation (H/R) with or without As-IV treatment. Myocyte injury was determined by the creatine kinase (CK)-MB fraction in supernatant. Myocardial SERCA2a activity and PKA kinase activity were assessed. PKA subunit mRNA expression and Ser16 phosphorylated phospholamban (Ser16-PLN) protein expression were detected by real-time PCR and Western blot, respectively. Results: The administration of As-IV significantly decreased CK-MB release and restored SERCA2a activity in H/R cardiomyocytes. The mRNAs of PKA subunits, PKA-RIα, PKA-RIIα, PKA-RIIβ, PKA-Cα and PKA-Cβ, were downregulated in H/R cardiomyocytes. However, PKA-Cα mRNA expression was significantly increased after As-IV treatment. Meanwhile, there was a tendency to recovery of the H/R-induced PKA kinase activity decrease after As-IV treatment. The expression of Ser16-PLN protein, which is specifically phosphorylated by PKA, was upregulated in As-IV-treated H/R cardiomyocytes. Conclusions: These results suggest that the cardioprotection of As-IV may be through the upregulation of PKA and Ser16-PLN, thereby restoring SERCA2a function in H/R injury.

α-Solanine, a naturally occurring steroidal glycoalkaloid in potato sprouts, was found to possess anti-carcinogenic properties, such as inhibiting proliferation and inducing apoptosis of tumor cells. However, the effect of α-solanine on cancer metastasis remains unclear. In the present study, we examined the effect of α-solanine on metastasis in vitro. Data demonstrated that α-solanine inhibited proliferation of human melanoma cell line A2058 in a dose-dependent manner. When treated with non-toxic doses of α-solanine, cell migration and invasion were markedly suppressed. Furthermore, α-solanine reduced the activity of matrix metalloproteinase-2 (MMP-2) and MMP-9, which are involved in the migration and invasion of cancer cells. Our biochemical assays indicated that α-solanine potently suppressed the phosphorylation of c-Jun N-terminal kinase (JNK), phosphatidylinositide-3 kinase (PI3K) and Akt, while it did not affect phosphorylation of extracellular signal regulating kinase (ERK). In addition, α-solanine significantly decreased the nuclear level of nuclear factor kappa B (NF-κB), suggesting that α-solanine inhibited NF-κB activity. Taken together, the results suggested that α-solanine inhibited migration and invasion of A2058 cells by reducing MMP-2/9 activities. It also inhibited JNK and PI3K/Akt signaling pathways as well as NF-κB activity. These findings reveal new therapeutic potential for α-solanine in anti-metastatic therapy.

C-reactive protein (CRP) is an important predictive factor for cardiac disorders including acute myocardial infarction. Therapeutic inhibition of CRP has been shown to be a promising new approach to cardioprotection in acute myocardial infarction in rat models, but the direct effects of CRP on cardiac myocytes are poorly defined. In this study, we investigated the effects of CRP on cardiac myocytes and its molecular mechanism involved. Neonatal rat cardiac myocytes were exposed to hypoxia for 8 h. Hypoxia induced myocyte apoptosis under serum-deprived conditions, which was accompanied by cytochrome c release from mitochondria into cytosol, as well as activation of Caspase-9, Caspase-3. Hypoxia also increased Bax and decreased Bcl-2 mRNA and protein expression, thereby significantly increasing Bax/Bcl-2 ratio. Cotreatment of CRP (100 mug/ml) under hypoxia significantly increased the percentage of apoptotic myocytes, translocation of cytochrome c, Bax/Bcl-2 ratio, and the activity of Caspase-9 and Caspase-3. However, no effects were observed on myocyte apoptosis when cotreatment of CRP under normoxia. Furthermore, Bcl-2 overexpression significantly improved cellular viability through inhibition of hypoxia or cotreatment with CRP induced Bax/Bcl-2 ratio changes and cytochrome c release from mitochondria to cytosol, and significantly blocked the activity of Caspase-9 and Caspase-3. The present study demonstrates that CRP could enhance apoptosis in hypoxia-stimulated myocytes through the mitochondrion-dependent pathway but CRP alone has no effects on neonatal rat cardiac myocytes under normoxia. Bcl-2 overexpression might prevent CRP-induced apoptosis by inhibiting cytochrome c release from the mitochondria and block activation of Caspase-9 and Caspase-3.

Background To investigate the drug resistant gene profiles and molecular typing of Acinetobacter baumannii isolates collected from clinical specimens in a comprehensive hospital, Jiangsu province. Methods This study included 120 patients in a comprehensive hospital with drug-resistant A. baumannii infections on clinical specimens from October 2011 to December 2013. Antibiotic susceptibility test was determined by Vitek 2 Compact system. OXA-51, OXA-23, OXA-24, OXA-58, VIM, IMP, SHV, GES, TEM, AmpC, qacEΔ1-sul1, intI l, CarO, aac(6′)-Ib, and aac(6′)-II were analyzed by PCR. The analysis of molecular typing for 50 multidrug resistant A. baumannii isolates was performed by PFGE. Results A total of 64(53%) isolates were multidrug-resistant A.baumannii. The antibiotic susceptibility tests showed that the resistant rates to common antibiotics of mutidrug-resistant A. baumannii were extremely high, most of which over 60%. One hundred and ten isolates harbored OXA-51 (91.7%), 100 for OXA-23(83.3%), 103 for VIM-1(85.8%), 90 for AmpC(75.00%), 50 for aac(6′)-Ib(41.7%), 77 for the loss of CarO (64.2%), 85 for intl1(70.8%), and 64 for qacEΔ1-sul1(53.33%), while OXA-24 was undetected. Fifty multidrug-resistant A. baumannii isolates belong to 14 clones according to the PFGE DNA patterns. Main clone A includes 24 isolates, while clone B and clone C includes 6 and 9 isolates, respectively and others with no common source identified. Conclusion There is high morbidity of A. baumannii infections in the hospital, especially in ICU and sputum is the most common sample type.The mainly drug-resistant genes of A. baumannii are OXA-51, OXA-23, and VIM-1 in the hospital. Clonal dissemination provides evidence for the prevalence of multidrug-resistant A. baumannii among clinical isolates. It is suggested that there is an urgent need for effective control and prevention measures.

Cases with loss of articular cartilage or lowering of articular lubricant performance are frequent among patients afflicted by various gonarthropathies or those fitted with prosthetic joints. The management of such cases has necessitated evaluation studies on the clinical efficacy of using high molecular weight hyaluronic acid as an artificial synovial fluid with a view to improving articular lubricant performance. The proper implementation of such evaluation studies on lubrication performance requires testing methods capable of assessing basic lubricant performance not ouly with respect to articular cartilage alone but also with respect to various other combinations of materials, i.e., lubrication between articular bone and artificial joints, etc. In the present study, first, a simple standard lubricant performance test using several small readily procurable test specimens was de­ vised. Then, this test was employed to evaluate the basic lubricant properties of hyaluronic acid intended for use as artificial synovial fluid. Key Words-mechanical testing, pendulum type friction tester, skeletal joint, hyaluronic acid, lubrication, molecular weight, viscosity

The solubilities of the K2Cr2O7 + CrO3 + KNO3 + HNO3 + H2O system at 0 °C, 25 °C, and 45 °C were determined, and the phase diagrams were constructed. Furthermore, analyses and discussions are made on the crystalline areas in the phase diagrams. Based on the solubility data, the technique of a new cleaner process for manufacturing chromium trioxide and potassium nitrate simultaneously by decomposing potassium dichromate with nitric acid was evaluated.