Total saponins of Aralia elata (Miq.) Seem. alleviate myocardial ischemia-reperfusion injury by promoting NLRP3-inflammasome inactivation via PI3K/Akt signaling.

Total saponins of Aralia elata (Miq.) Seem. (TSAE) have been shown to play a significant role in cardiovascular protection, anti-tumor, liver protection, anti-oxidant stress, and anti-inflammation. However, the specific mechanisms of TSAE in myocardial ischemia-reperfusion injury (MIRI) remain largely elusive. Hearts from male Wistar rats were used to establish the isolated heart MIRI model. Using a multichannel physiological recorder, the whole course heart rate (HR), left ventricular development pressure (LVDP), and maximum rise/decrease rate of left ventricular pressure (±dp/dtmax ) were recorded. 2,3,5-triphenyl-2H-tetrazolium chloride staining observed the infarct area, while hematoxylin & eosin staining detected pathological changes in myocardial tissue. Creatine kinase, lactate dehydrogenase, total superoxide dismutase, and malondialdehyde concentrations were determined by enzyme-linked immunosorbent assay. Immunohistochemistry, quantitative PCR, and western blot assay were used to assess the amounts of IL-18 and IL-1ß, NLR family protein (NLRP3) inflammasome- and apoptosis-related proteins, respectively. Treatment with TSAE or MCC950 (NLRP3-specific inhibitor) significantly reduced the myocardial infarction area, alleviated pathological changes in myocardial tissues, enhanced LVDP and ±dp/dtmax levels, prevented myocardial oxidative damage, and inhibited NLRP3 inflammasome formation. In addition, TSAE enhanced Akt and GSK3ß phosphorylation, and LY29004 co-reperfusion markedly diminished the protective role of TSAE reperfusion on cardiac function, oxidative damage, and inflammatory responses. Collectively, TSAE treatment exhibited a protective effect on I/R-triggered inflammatory responses, cell necrosis, and oxidative stress injury by stimulating PI3K/Akt signaling-mediated NLRP3 inflammasome inhibition.

Investigation of the Cellular Pharmacological Mechanism and Clinical Evidence of the Multi-Herbal Antiarrhythmic Chinese Medicine Xin Su Ning.

Xin Su Ning (XSN), a China patented and certified multi-herbal medicine, has been available in China since 2005 for treating cardiac ventricular arrhythmia including arrhythmia induced by ischemic heart diseases and viral myocarditis, without adverse reactions being reported. It is vitally important to discover pharmacologically how XSN as a multicomponent medicine exerts its clinical efficacy, and whether the therapeutic effect of XSN can be verified by standard clinical trial studies. In this paper we report our discoveries in a cellular electrophysiological study and in a three-armed, randomized, double-blind, placebo-controlled, parallel-group, multicenter trial. Conventional electrophysiological techniques were used to study the cellular antiarrhythmic mechanism of XSN. Data was then modeled with computational simulation of human action potential (AP) of the cardiac ventricular myocytes. The clinical trial was conducted with a total of 861 eligible participants randomly assigned in a ratio of 2:2:1 to receive XSN, mexiletine, or the placebo for 4 weeks. The primary and secondary endpoint was the change of premature ventricular contraction (PVC) counts and PVC-related symptoms, respectively. This trial was registered in the Chinese Clinical Trial Register Center (ChiCTR-TRC-14004180). We found that XSN prolonged AP duration of the ventricular myocytes in a dose-dependent, reversible manner and blocked potassium channels. Patients in XSN group exhibited significant total effective responses in the reduction of PVCs compared to those in the placebo group (65.85% vs. 27.27%, P < 0.0001). No severe adverse effects attributable to XSN were observed. In conclusion, XSN is an effective multicomponent antiarrhythmic medicine to treat PVC without adverse effect in patients, which is convincingly supported by its class I & III pharmacological antiarrhythmic mechanism of blocking hERG potassium channels and hNaV1.5 sodium channel reported in our earlier publication and prolongs AP duration both in ventricular myocytes and with computational simulation of human AP presented in this report.

[Expert consensus statement on Diemailing~® Kudiezi Injection in clinical practice].

Diemailing~® Kudiezi Injection( DKI) is widely used in the treatment of cerebral infarction,coronary heart disease and angina pectoris. Long-term clinical application and related research evidence showed that DKI has a good effect in improving the clinical symptoms of cardiovascular and cerebrovascular diseases. However,this injection has not been included in any clinical practice guideline. It has been found that the use of DKI is in wrong way in clinical practice in recent years. Therefore,clinical experts from the field of cardiovascular and cerebrovascular diseases nationwide are invited to compile this expert consensus in order to guide clinicians.GRADE system is used to grade the quality of evidence according to different outcomes according to degrading factors. Then it forms the recommendation or consensus suggestion through the nominal group method. The formation of expert consensus mainly considers six factors: quality of evidence,economy,efficacy,adverse reactions,patient acceptability and others. Based on these six aspects,if the evidence is sufficient,a " recommendation" supported by evidence is formed,and GRADE grid voting rule is adopted. If the evidence is insufficient,a " consensus suggestions" will be formed,using the majority voting rule. In this consensus,the clinical indications,efficacy,safety evidences and related preliminary data of DKI were systematically and comprehensively summarized in a concise and clear format,which could provide valuable reference for the clinical use of DKI. This consensus has been approved by China association of Chinese medicine which is numbered GS/CACM 202-2019.

The Prognostic Significance of Beta2 Microglobulin in Patients with Hemophagocytic Lymphohistiocytosis.

OBJECTIVE: To determine the prognostic significance of beta2 microglobulin (ß2-m) concentrations in patients with hemophagocytic lymphohistiocytosis (HLH), a rare disorder caused by pathologic activation of the immune system. PATIENTS AND METHODS: The study population consisted of 74 patients diagnosed with HLH and 35 healthy controls. Serum ß2-m levels were measured using a latex agglutination photometric immunoassay. RESULTS: Median serum ß2-m levels were significantly higher in HLH patients than in healthy controls (4.05 versus 1.5 mg/L; P < 0.001) and were significantly higher in patients with lymphoma associated hemophagocytic syndrome (LAHS) than in patients with benign disease-associated HLH (4.2 versus 3.3 mg/L; P < 0.001). Higher serum ß2-m levels were positively correlated with LAHS (P = 0.005), abnormal lactate dehydrogenase concentrations (P = 0.009), and hypoalbuminemia (P = 0.003). ROC analysis showed that overall survival (OS) was significantly shorter in LAHS patients with serum ß2-m levels ≥4.03 mg/L compared to <4.03 mg/L (P < 0.001). Moreover, multivariate analysis showed that serum ß2-m level was an independent prognostic of OS (P = 0.034) in patients with LAHS. CONCLUSION: High serum ß2-m levels and LAHS were associated with markedly poorer OS in patients with HLH. Serum ß2-m concentration was a powerful and independent prognostic factor for OS in patients with LAHS.

[Relationship of Chinese medicine syndrome pattern with heart function and brain natriuretic peptide in patients with heart failure].

OBJECTIVE: To observe the relationship of Chinese medicine (CM) syndrome pattern with heart function detected by ultrasonic cardiography and brain natriuretic peptide (BNP) level in patients with heart failure (HF). METHODS: One hundred and sixteen inpatients of HF hospitalized in Dongfang Hospital from January, 2007 to January, 2009 were assigned to three groups according to their CM syndrome pattern differentiated, the qi-yin deficiency group (QYD), the qi-deficiency and blood-stasis group (QDBS) and the yang-deficiency with water overflowing group (YDWO). Ultrasonic cardiographic (USCG) parameters, including left ventricular end-systolic diameter (LVEDs), left ventricular end-diastolic diameter (LVEDd) and left ventricular ejection fraction (LVEF) were detected, and blood level of BNP was measured. RESULTS: LVEF was decreased while BNP was increased in patients with syndrome patterns in the order of QYD --> QDBS --> YDWO, and showed significant difference between groups (P < 0.01); CM syndrome patterns was related with all the USCG parameters and BNP level, especially the BNP (r = 0.71, P < 0.05) and LVEF (r = -0.34, P < 0.05). CONCLUSION: LVEF and BNP can reflect the severity of heart failure, and they could be taken as the beneficial objective and quantitative indices for syndrome pattern differentiation.

A dynamic micromixer for arbitrary control of disguised chemical selectivity.

A new type of dynamic micromixer combining the concepts of parallel multi-lamination and hydrodynamic focusing was developed for arbitrary control of disguised chemical selectivity.

Individually addressable crystalline conducting polymer nanowires in a microelectrode sensor array.

An efficient, site-specific and scalable approach has been developed to produce high-quality and individually addressable conducting polymer nanowire electrode junctions (CPNEJs) in a parallel-oriented array. Polypyrrole and PEDOT conducting polymer nanowires (CPNWs) with uniform diameters (ca. 60-150 nm) were introduced into the desired electrode junctions in a precise manner by performing a three-step constant-current electrochemical process at a low current density and a low concentration of monomers. A low scan rate, cyclic voltammetric method was also employed and gave similar results. These CPNEJ arrays function as a miniaturized sensor for the parallel and real-time detection of gas and organic vapour. The electrochemical approaches utilized allow the conducting polymer chains to self-organize in the CPNWs to form novel polycrystalline structures, observed by high resolution TEM. The weak diffraction rings at 4.88 Å and 4.60 Å were observed for PEDOT and polypyrrole CPNWs, respectively.

Solution-phase surface modification in intact poly(dimethylsiloxane) microfluidic channels.

An improved approach composed of an oxidation reaction in acidic H2O2 solution and a sequential silanization reaction using neat silane reagents for surface modification of poly(dimethylsiloxane) (PDMS) substrates was developed. This solution-phase approach is simple and convenient for some routine analytical applications in chemistry and biology laboratories and is designed for intact PDMS-based microfluidic devices, with no device postassembly required. Using this improved approach, two different functional groups, poly(ethylene glycol) (PEG) and amine (NH2), were introduced onto PDMS surfaces for passivation of nonspecific protein absorption and attachment of biomolecules, respectively. X-ray electron spectroscopy and temporal contact angle experiments were employed to monitor functional group transformation and dynamic characteristics of the PEG-grafted PDMS substrates; fluorescent protein solutions were introduced into the PEG-grafted PDMS microchannels to test their protein repelling characteristics. These analytical data indicate that the PEG-grafted PDMS surfaces exhibit improved short-term surface dynamics and robust long-term stability. The amino-grafted PDMS microchannels are also relatively stable and can be further activated for modifications with peptide, DNA, and protein on the surfaces of microfluidic channels. The resulting biomolecule-grafted PDMS microchannels can be utilized for cell immobilization and incubation, semiquantitative DNA hybridization, and immunoassay.

A soliton phenomenon in langmuir monolayers of amphiphilic bistable rotaxanes.

Surface pressure-area isotherms, light scattering microscopy, and atomic force microscopy have all been used to provide information about the stabilities and dynamics of Langmuir monolayers composed of amphiphilic bistable [2]rotaxane molecules. Superstructures that have the appearance of localized mobile solitons are formed during the compression of monolayers of the [2]rotaxanes below their collapse pressures. Solitons move solely in a linear trajectory in both directions across the film, perpendicular to the compression direction, without any apparent broadening or change in their shape.

Folding Langmuir monolayers.

The maximum pressure a two-dimensional surfactant monolayer is able to withstand is limited by the collapse instability towards formation of three-dimensional material. We propose a new description for reversible collapse based on a mathematical analogy between the formation of folds in surfactant monolayers and the formation of Griffith Cracks in solid plates under stress. The description, which is tested in a combined microscopy and rheology study of the collapse of a single-phase Langmuir monolayer (LM) of 2-hydroxy-tetracosanoic acid (2-OH TCA), provides a connection between the in-plane rheology of LMs and reversible folding.

A clinical and experimental study on the protective effects of jiangzhi tongmai fang on endothelial injury.

31 cases of atherosclerosis (AS) were treated with Jiang Zhi Tong Mai Fang ([symbol: see text], formula of JZTMF), and its effect was compared with 30 cases treated with lovastatin in the control group. Clinically, the JZTMF formula showed an effect of regulating blood lipids, and therefore it was antiatherosclerotic. The mechanism is, probably, restoration of the function of endothelial cells (EC) by increasing the synthesis of 6-keto-PGF1 alpha and decreasing the release of endothelin (ET) as evidenced in the experimental study.

[Fabrication of Y2O3-doped CeO2 ultrathin film by newly developed component-controllable Langmuir-Blodgett method].

A fabrication technique of component-controllable multi-component ultrathin ceramic films has been developed by a promising LB method. The precursor of Y2O3-doped CeO2 (YDC) ultrathin film was prepared with cerium IV 2,2,6,6-tetramethyl-heptanedionate (Ce(tmhd)4) and yttrium 2,2,6,6-tetramethylheptanedionate (Y(tmRd)3) as "surface ions" on subphase surface instead of traditional "subphase ions". The YDC film was successfully fabricated after ultraviolet/ozone treatment and annealing in oxygen ambience with the precursor. XPS results proved that the surface of the fired film contained mainly Ce, O and Y and that the elemental ratio of Y/Ce was well controlled.