Numerical simulations of elastic-plastic Richtmyer-Meshkov instability of multiple interfaces.

The elastic-plastic Richtmyer-Meshkov instability of multiple interfaces is investigated by numerical simulation using a multimaterial solid mechanics algorithm based on an Eulerian framework. This Richtmyer-Meshkov instability problem is realized by a copper layer that is flanked by vacuum and a copper block of different material strength. The research efforts are directed to reveal the influence of the layer thickness and material strength on the deformation of the perturbed solid-vacuum interface impacted by an initial shock. By varying the initial thickness (x_{I}) of the copper layer and the yield stress (σ_{Y2}) of the copper block, two deformation modes, which have been identified as the broken mode and the stable mode, are closely scrutinized. For a fixed x_{I} and a decreasing σ_{Y2}, the reflected rarefaction waves (RRWs), developing after the initial shock impacts the perturbed interface 1 (I1) between vacuum and the copper layer, become stronger after traveling across the interface 2 (I2). Subsequently, the velocity of I2 becomes larger, causing the width of I1 to grow larger. This width growth of I1 leads to a final separation of the spike from I1 and, consequently, the deformation mode changes from the stable mode to the broken mode. For a fixed σ_{Y2} and a decreasing x_{I}, the RRWs impact I2 at an earlier moment with a greater strength and thus the deformation mode changes from the stable mode to the broken mode. Meanwhile, the comparison of the spike width of cases whose deformation mode is the broken mode shows that there exists a maximum value of rescaled spike width, at which the deformation mode changes from the stable mode to the broken mode.

Turbulent Taylor-Couette flow of dilute polymeric solutions: a 10-year retrospective.

This retrospective aims to present a coherent history of important findings in direct numerical simulations and experiments in turbulent Taylor-Couette (TC) flow of dilute polymeric solutions in the last decade. Specifically, the sequence of flow transitions due to a continuous increase of fluid elasticity from classical Newtonian, to inertially and in turn to elastically dominated, and finally to the inertialess purely elastic turbulence, is presented. In each elastically modified flow state, the drag modification, coherent flow structures, velocity and elastic stress statistics, mechanism of turbulent kinetic energy production, spectral features as well as the self-sustaining cycles of turbulence, are discussed. Finally, to provide a broader perspective, an overview of important similarities and differences between elastically induced turbulence in prototypical curvilinear and rectilinear shear flows including the curvature-free limit of TC flow, namely, the spanwise-rotating plane Couette flow, is presented. This article is part of the theme issue 'Taylor-Couette and related flows on the centennial of Taylor's seminal Philosophical Transactions paper (part 1)'.

Knockdown of LncRNA MALAT1 Alleviates Coxsackievirus B3-Induced Acute Viral Myocarditis in Mice via Inhibiting Th17 Cells Differentiation.

Acute viral myocarditis (AVMC), most often caused by coxsackievirus B3 (CVB3) infection, is characterized by myocardial inflammation associated with high morbidity and mortality. A pathogenic role for T helper (Th) 17 cells in AVMC is well established. Long noncoding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been shown to play a key role in various inflammatory diseases. However, the expression of MALAT1 and its impact on Th17 cells differentiation in AVMC remain unclear. In the present study, we found that MALAT1 was highly expressed in mice with AVMC, and the expression was correlated positively with cardiac pathological scores, cardiac IL-17 mRNA expression, and the percentages of splenic Th17 cells. We further demonstrated that MALAT1 knockdown could significantly alleviate the severity of disease and inhibit the differentiation of Th17 cells, accompanying the reduced mRNA expression of RORγt and productions of Th17-related pro-inflammatory cytokines in vivo. Additionally, in vitro analysis showed that MALAT1 knockdown suppressed naïve CD4+ T cells differentiation towards Th17 cells. In conclusion, our results suggest that MALAT1 knockdown alleviates CVB3-induced AVMC in mice, which may be partially attributable to the decline in Th17 cells responses. MALAT1 may serve as a novel therapeutic option in AVMC.

Association between left ventricular diastolic dysfunction and septic acute kidney injury in severe sepsis and septic shock: A multicenter retrospective study.

INTRODUCTION: Left ventricular diastolic dysfunction (LVDD) adversely impacts renal function, and E/e' is a significant predictor of adverse kidney events under different clinical conditions. However, no studies have evaluated the association between LVDD and septic acute kidney injury (AKI) among patients with severe sepsis and septic shock. METHODS: This multicenter retrospective study evaluated adult patients with severe sepsis or septic shock between January 1, 2013, and December 31, 2019, who underwent echocardiography within 24 hours after admission to an intensive care unit. RESULTS: A total of 495 adult patients were enrolled in the study. LVDD grades II and III were associated with severe (stage 3) AKI (p < 0.001, p for trend < 0.001). E/e' and e' were risk factors for septic AKI (OR, 1.155; 95% CI, 1.088-1.226, p < 0.001; and OR, 7.218; 95% CI, 2.942-17.712, p < 0.001, respectively) in the multivariate logistic regression analysis. The area under the receiver operating characteristic curve of E/e' and e' was 0.728 (95% CI, 0.680-0.777, p < 0.001) and 0.715 (95% CI, 0.665-0.764, p < 0.001), respectively. CONCLUSIONS: LVDD was associated with septic AKI, and E/e' and e' are useful predictors of septic AKI among patients with severe sepsis or septic shock. TRIAL REGISTRATION: The study was registered at the Chinese Clinical Trial Registry (Protocol No. ChiCTR2000033083).

Higher Teicoplanin Blood Level Needed in Elderly Critically Ill Patients.

BACKGROUND: Significant changes in the pathophysiology of older critically ill patients may affect the pharmacokinetics and pharmacodynamics of teicoplanin. This study aimed to determine the optimal teicoplanin blood level in this patient population. METHODS: 128 older critically ill and 86 older non-critically ill patients were involved and analyzed. RESULTS: The target thresholds of teicoplanin blood concentrations in older critically ill patients and non-critically ill patients should be 31.4mg/L and 15.3mg/L, respectively. The dose of teicoplanin in older critically ill patients should be greater than 800 mg to achieve the target blood level. CONCLUSION: An individualized dosing approach of teicoplanin based on therapeutic drug monitoring is necessary for older critically ill patients.

Neutralization of interleukin-38 exacerbates coxsackievirus B3-induced acute myocarditis in mice.

BACKGROUND: Interleukin (IL)-38, a novel member of the IL-1 family, has been reported to be involved in several diseases associated with viral infection. However, the expression and functional role of IL-38 in acute viral myocarditis (AVMC) have not been investigated. METHODS: Male BALB/c mice were treated with intraperitoneal (i.p.) injection of coxsackievirus B3 (CVB3) for establishing AVMC models. On day 7 post-injection, the expression of IL-38 and IL-36R (IL-36 receptor) were measured. Mice were then treated with i.p. injection of mouse Anti-IL-38 Antibodies (Abs) for neutralization of IL-38. The survival, bodyweight loss, cardiac function, and myocarditis severity of mice were recorded. The percentages of splenic Th1 and Th17 cells, the expression levels of Th1/Th17-related master transcription factors (T-bet and RORγt) and cytokines were determined by flow cytometry, RT-qPCR, and ELISA, respectively. Cardiac viral replication was further detected. RESULTS: The mRNA and protein expression levels of IL-38 in myocardium and serum, as well as cardiac IL-36R mRNA levels were significantly elevated in mice with AVMC. Increased IL-38 levels were negatively correlated with the severity of AVMC. Neutralization of IL-38 exacerbated CVB3-induced AVMC, as verified by the lower survival rate, impaired cardiac function, continuous bodyweight loss, and higher values of HW/BW and cardiac pathological scores. In addition, neutralization of IL-38 suppressed Th1 cells differentiation while promoted Th17 cells differentiation, accompanied by decreased T-bet mRNA expression and increased RORγt expression. Down-regulation of IFN-γ and up-regulation of IL-17, TNF-α, and IL-6 mRNA and protein expression levels in myocardium and serum were also observed in the IL-38 neutralization group. Furthermore, neutralization of IL-38 markedly promoted cardiac viral replication. CONCLUSIONS: Neutralization of IL-38 exacerbates CVB3-induced AVMC in mice, which may be attributable to the imbalance of Th1/Th17 cells and increased CVB3 replication. Thus, IL-38 can be considered as a potential therapeutic target for AVMC.

In Vitro Differentiation of Human Placenta-Derived Multipotent Cells into Schwann-Like Cells.

Human placenta-derived multipotent stem cells (PDMCs) resembling embryonic stem cells can differentiate into three germ layer cells, including ectodermal lineage cells, such as neurons, astrocytes, and oligodendrocytes. The favorable characteristics of noninvasive cell harvesting include fewer ethical, religious, and legal considerations as well as accessible and limitless supply. Thus, PDMCs are attractive for cell-based therapy. The Schwann cell (SC) is the most common cell type used for tissue engineering such as nerve regeneration. However, the differentiation potential of human PDMCs into SCs has not been demonstrated until now. In this study, we evaluated the potential of PDMCs to differentiate into SC-like cells in a differentiation medium. After induction, PDMCs not only exhibited typical SC spindle-shaped morphology but also expressed SC markers, including S100, GFAP, p75, MBP, and Sox 10, as revealed by immunocytochemistry. Moreover, a reverse transcription-quantitative polymerase chain reaction analysis revealed the elevated gene expression of S100, GFAP, p75, MBP, Sox-10, and Krox-20 after SC induction. A neuroblastoma cell line, SH-SY5Y, was cultured in the conditioned medium (CM) collected from PDMC-differentiated SCs. The growth rate of the SH-SY5Y increased in the CM, indicating the function of PDMC-induced SCs. In conclusion, human PDMCs can be differentiated into SC-like cells and thus are an attractive alternative to SCs for cell-based therapy in the future.

[A clinical study of the evaluation of hemodynamic status in mechanically ventilated critically ill patients by continuous non-invasive arterial pressure monitor].

OBJECTIVE: To evaluate the difference and correlation between continuous non-invasive arterial pressure (CNAP) monitor and pulse indicated continuous cardiac output (PiCCO) monitor on determination of hemodynamic parameters in mechanically ventilated critically ill patients, and to assess the feasibility of non-invasive monitoring of hemodynamics with CNAP. METHODS: A prospective observation self-control study was conducted.The critically ill patients with mechanical ventilation who needed hemodynamics monitoring, and admitted to the fourth department of intensive care unit (ICU) of Fujian Provincial Hospital from June 2018 to March 2019 were enrolled. PiCCO catheter were inserted immediately after admission, the hemodynamic indexes were measured by thermodilution method, and mean arterial pressure (MAPPiCCO), cardiac index (CIPiCCO), pulse pressure variation rate (PPVPiCCO) and systemic vascular resistance index (SVRIPiCCO) were obtained at 0 hour and 24 hours respectively. Meanwhile, the above indexes (MAPCNAP, CICNAP, PPVCNAP and SVRICNAP) were measured with CNAP. All measurements were repeated thrice and average values were reported. The differences in above parameters between the two methods were evaluated. Pearson test was used for the correlation analysis and Bland-Altman analysis method was used for consistency test. RESULTS: Thirty-eight patients were enrolled into this study. One patient died within 24 hours was excluded, 2 patients were excluded due to withdrawing treatment within 24 hours, 2 patients were excluded because of atrial fibrillation, and 1 patient's data was lost due to technical problems. Thus, data from 32 patients were available for final analysis. There were 12 females and 20 males, aging 26-84 years old with the mean of (66.8±19.1) years old, body mass index (BMI) of (23.7±3.9) kg/m2, acute physiology and chronic health evaluation II (APACHE II) score of 19.5±5.3, sepsis-related organ failure assessment (SOFA) score of 9.7±4.1. There were no significant differences in CI or PPV between CNAP and PiCCO groups [CI (mL×s-1×m-2): 59.8±12.6 vs. 58.5±14.2, PPV: (14.7±6.8)% vs. (14.0±6.8)%, both P > 0.05]. MAP and SVRI measured by CNAP were significantly higher than those measured by PiCCO [MAP (mmHg, 1 mmHg = 0.133 kPa): 65.6±9.4 vs. 60.1±9.2, SVRI (kPa×s×L-1×m-2): 206.2±53.9 vs. 179.5±57.8, both P < 0.01]. The correlation analysis showed that MAP, CI, PPV and SVRI measured by the two methods were significantly positively correlated (r value was 0.624, 0.864, 0.835 and 0.655 respectively, all P < 0.05). Bland-Altman analysis showed that CNAP and PiCCO had a good consistency for the measurement of CI and PPV, the average differences were 1.2 mL×s-1×m-2 and 0.5% respectively, while the 95% confidence interval (95%CI) were -12.8-15.3 mL×s-1×m-2 and -7.1%-8.2% respectively. However, the consistency of MAP and SVRI measured by those two methods was poor, the average differences were 5.5 mmHg and 26.8 kPa×s×L-1×m-2 respectively, while the 95%CI was -10.4-21.3 mmHg and -64.5-118.0 kPa×s×L-1×m-2 respectively. CONCLUSIONS: CNAP was comparable with PiCCO when monitoring CI and PPV in mechanically ventilated critically ill patients; while the results of MAP and SVRI might be inaccurate, which should be interpreted correctly and carefully.

[Clinical research of target guided treatment of patients with severe heart failure under the guidance of pulse indicator continuous cardiac output].

OBJECTIVE: To investigate the value of pulse indicator continuous cardiac output (PiCCO) monitoring in the treatment management of patients with severe heart failure. METHODS: Sixty patients of severe heart failure admitted to intensive care unit (ICU) of Fujian Provincial Hospital from August 2017 to February 2019 were enrolled, and they were divided into control group and treatment group according to random number table method, with 30 in each group. The treatment group used bedside PiCCO to carry out minimally invasive hemodynamics monitoring, according to the monitoring data target guidance for vasoactive drugs and liquid management. The control group was based only on traditional electrocardiogram (ECG) monitoring and lung sound, urine volume of vasoactive drugs and liquid management. The changes of cardiac index (CI), global end diastolic volume index (GEDVI), extravascular lung water index (EVLWI), systemic vascular resistance index (SVRI), invasive mean arterial pressure (MAP) and central venous pressure (CVP) were observed before and 72 hours after treatment in the treatment group. The 7-day total effective rate, the length of ICU stay and 28-day mortality were compared between the two groups. RESULTS: Compared with before treatment, CI and MAP in the treatment group were significantly increased after treatment [CI (mL×s-1×m-2): 53.34±16.67 vs. 35.01±13.34, MAP (mmHg, 1 mmHg = 0.133 kPa): 72.6±10.6 vs. 62.5±10.3, both P < 0.05], GEDVI, EVLWI, SVRI, CVP were significantly decreased [GEDVI (mL/m2): 760.3±90.2 vs. 960.2±110.3, EVLWI (mL/kg): 6.5±1.3 vs. 12.5±6.2, SVRI (kPa×s×L-1×m-2): 297.3±35.1 vs. 434.1±58.8, CVP (mmHg): 10.1±2.6 vs. 12.2±3.4, all P < 0.05]. Compared with the control group, the 7-day total effective rate of the treatment group was significantly higher (90.0% vs. 80.0%), the length of ICU stay was significantly shorter (days: 8.2±4.5 vs. 10.3±2.5), and the 28-day mortality was significantly lower, with statistically significant difference (all P < 0.05). CONCLUSIONS: PiCCO monitoring is a goal-oriented treatment management for patients with severe heart failure, which is helpful to individualized accurate treatment, shorten the length of ICU stay and improve short-term prognosis.

Pharmacokinetics of multiple doses of teicoplanin in Chinese elderly critical patients.

BACKGROUND: The dose-effect relationship of teicoplanin has been a hot topic of clinical concern, but there was lack of the evidence of Chinese patients to optimize dosage, especially in elderly critical patients, whose plasma protein, liver and kidney function are greatly different from ordinary patients. METHODS: Elderly critical patients were divided into high-dose(800mg), medium-dose (600mg) and low-dose (400mg) groups, which consisted of 6 cases of each group. Three groups were taken intravenous blood at different times after the last administration of teicoplanin to measure teicoplanin plasma concentration. RESULTS: The t1/2 of high-dose, middle-dose and low-dose groups were 70.76 ± 11.72h, 73.60 ± 9.48h, 80.24 ± 6.75h, respectively; CL were 0.14 ± 0.09mL ∙ h-1 ∙ kg-1, 0.11 ± 0,05mL ∙ h-1 ∙ kg-1, 0.12 ± 0.06mL ∙ h-1 ∙ kg-1 respectively. The Cmax and AUC0-t of the three dose groups were linearly correlated with the dose. CONCLUSIONS: In Chinese elderly critical patients, t1/2 of teicoplanin was consistent with that of literatures published, however, CL were higher. The pharmacokinetics of teicoplanin at the range of 400 ~ 800mg is linear pharmacokinetics, indicating that the dosage regimens for patients were more simply and accurately adjusted according to therapeutic drug monitoring.

Associations between age at menarche and menopause with cardiovascular disease, diabetes, and osteoporosis in Chinese women.

CONTEXT: Ages at menarche and menopause are associated with cardiovascular disease (CVD), diabetes, and osteoporosis in Caucasian women, but associations remain unexplored in Chinese women. OBJECTIVE: The purpose of this study was to assess associations between age at menarche and menopause with CVD, diabetes, and osteoporosis in Chinese women. DESIGN AND SETTING: A cross-sectional, population-based study was conducted in Fujian, China, from June 2011 to January 2012. PARTICIPANTS: Among 6242 women aged 21 to 92 years, 3304 postmenopausal women were enrolled, excluding premenopausal women (n = 2527), those with unreported ages at menarche and menopause (n = 138), those with unrecorded physical measurements (n = 203), and those with menarche age <8 years or >20 years (n = 70). MAIN OUTCOME MEASURES: An oral glucose tolerance test, a 12-lead resting electrocardiogram, and calcaneus quantitative ultrasound were performed. RESULTS: No significant associations were found between menarche age, diabetes, and osteoporosis (both P > .05); later menarche (>18 years) was significantly associated with lower CVD risk (odds ratio = 0.71, 95% confidence interval, 0.57-0.89; P = .002). Menopause age was not associated with diabetes; higher menopause age was associated with decreasing CVD risk (P for trend = .020) and earlier menopause (≤46 years) with significantly higher osteoporosis risk (odds ratio = 1.59, 95% confidence interval, 1.07-2.36; P = .023). CONCLUSIONS: In China, ages at menarche and menopause are not associated with diabetes. Later menarche and menopause are associated with decreasing CVD risk and earlier menopause with higher osteoporosis risk. Menarche and menopause history may help identify women with increased risk of developing CVD and osteoporosis.

Construction of NF-κB-targeting RNAi adenovirus vector and the effect of NF-κB pathway on proliferation and apoptosis of vascular endothelial cells.

To construct a recombinant adenovirus vector expressing a RNAi for the Nuclear Factor kappa B (NF-κB)/p65 gene and use it to explore the role of the NF-κB pathway on the regulation of proliferation and apoptosis of vascular endothelial cells. A recombinant adenovirus containing a RNAi cassette targeting the p65 gene was constructed, and its silencing effect on p65 was detected by Western blot analysis in ECV304 cells. Expression of the p65 protein in ECV304 cells was efficiently down-regulated by the RNAi adenovirus for more than 6 days. ECV304 cells proliferation and apoptosis were measured using the MTT assay and flow cytometry, respectively. Blocking the NF-κB pathway with the RNAi adenovirus substantially decreased the proliferation of ECV304 cells, but only slightly affected cell apoptosis. We used a NF-κB/p65-targeting RNAi adenovirus to demonstrate the role of the NF-κB pathway in the regulation of ECV304 cell proliferation. This adenovirus may serve as an important tool to study the NF-κB pathway.

Fabricating scaffolds by microfluidics.

In this paper, we demonstrate for the first time the technique to using microfluidics to fabricate tissue engineering scaffolds with uniform pore sizes. We investigate both the bubble generation of the microfluidic device and the application of foam as a tissue engineering scaffold. Our microfluidic device consists of two concentric tapered channels, which are made by micropipettes. Nitrogen gas and aqueous alginate solution with Pluronic((R)) F127 surfactant are pumped through the inner and the outer channels, respectively. We observe rich dynamic patterns of bubbles encapsulated in the liquid droplets. The size of the bubble depends linearly on the gas pressure and inversely on the liquid flow rate. In addition, monodisperse bubbles self-assemble into crystalline structures. The liquid crystalline foams are further processed into open-cell solid foams. The novel foam gel was used as a scaffold to culture chondrocytes.

Ablation of NF-kappaB expression by small interference RNA prevents the dysfunction of human umbilical vein endothelial cells induced by high glucose.

Diabetes is a major independent risk factor for cardiovascular disease and stroke. High glucose (HG) reduces endothelial cell (EC) proliferation with a concomitant increase in apoptosis. HG also induces the translocation of nuclear factor (NF)-kappaB in human umbilical vein endothelial cells (HUVECs). However, data regarding the relationship between NF-kappaB signaling and HG-induced endothelial dysfunction are limited. In the present study, we constructed an NF-kappaB-targeting RNA interference (RNAi) adenovirus vector and cultured HUVECs in 5.5, 20.5, or 30.5 mM D: -glucose or in daily alternating 5.5 or 30.5 mM D: -glucose. We assessed the effects of the NF-kappaB pathway on proliferation under HG conditions by measuring bromodeoxyuridine incorporation and conducting methyl thiazolyltetrazolium assays. We also tested apoptosis by performing flow cytometry and terminal deoxynucleotidyl transferase nick-end labeling assay. The RNAi adenovirus effectively downregulated expression of the p65 protein in HUVECs for more than 6 days. Blockage of the NF-kappaB pathway with the RNAi adenovirus substantially protected HUVECs from decreased proliferation and reduced cellular apoptosis in HG conditions. These findings may explain how hyperglycemia promotes dysfunction of ECs and could elucidate a potential new target for therapeutic interventions.