Rapid and accurate quantification of viable Bifidobacterium cells in milk powder with a propidium monoazide - antibiotic fluorescence in situ hybridization - flow cytometry method.

Due to its beneficial effects on human health, Bifidobacterium is commonly added to milk powder. Accurate quantification of viable Bifidobacterium is essential for assessing the therapeutic efficacy of milk powder. In this study, we introduced a novel propidium monoazide (PMA) - antibiotic fluorescence in situ hybridization (AFISH) - flow cytometry (FCM) method to rapidly and accurately quantify viable Bifidobacterium cells in milk powder. Briefly, Bifidobacterium cells were treated with chloramphenicol (CM) to increase their rRNA content, followed by staining with RNA-binding oligonucleotide probes, based on the AFISH technique. Then, the DNA-binding dye PMA was used to differentiate between viable and non-viable cells. The PMA-AFISH-FCM method, including sample pretreatment, CM treatment, dual staining, and FCM analysis, required around 2 h and was found to be better than the current methods. This is the first study to implement FCM combined with PMA and oligonucleotide probe for detecting Bifidobacterium.

Rapid and Accurate Quantification of Viable Lactobacillus Cells in Infant Formula by Flow Cytometry Combined with Propidium Monoazide and Signal-Enhanced Fluorescence In Situ Hybridization.

Lactobacillus is an important member of the probiotic bacterial family for regulating human intestinal microflora and preserving its normalcy, and it has been widely used in infant formula. An appropriate and feasible method to quantify viable Lactobacilli cells is urgently required to evaluate the quality of probiotic-fortified infant formula. This study presents a rapid and accurate method to count viable Lactobacilli cells in infant formula using flow cytometry (FCM). First, Lactobacillus cells were specifically and rapidly stained by oligonucleotide probes based on a signal-enhanced fluorescence in situ hybridization (SEFISH) technique. A DNA-binding fluorescent probe, propidium monoazide (PMA), was then used to accurately recognize viable Lactobacillus cells. The entire process of this newly developed PMA-SEFISH-FCM method was accomplished within 2.5 h, which included pretreatment, dual staining, and FCM analysis; thus, this method showed considerably shorter time-to-results than other rapid methods. This method also demonstrated a good linear correlation (R2 = 0.9994) with the traditional plate-based method with a bacterial recovery rate of 91.24%. To the best of our knowledge, the present study is the first report of FCM combined with PMA and FISH for the specific detection of viable bacterial cells.

Synergy of Front-Surface Energy-Level Gradient and Lattice Anchoring Effect for Enhancing Perovskite Solar Cell Performance.

A front surface gradient of the absorber valence band can effectively reduce the open-circuit voltage (VOC ) loss of perovskite solar cells by suppressing the minority carrier concentration near the front surface. However, the existing method is limited to the one-step fabrication process, resulting in underachieved photon harvesting and power conversion efficiency (PCE). To solve the problem, ZnCd-based alloy quantum dots (QDs) are utilized to create a valence-band-maximum gradient at the front surface of a two-step processed FAPbI3 absorber. This design significantly enhances VOC without requiring surface passivation. Furthermore, it is demonstrated that reducing the QD-perovskite lattice mismatch while maintaining QD's energy levels mitigates nonradiative recombination without compromising the front surface gradient effect. As a result, normal-structured perovskite solar cells achieve a VOC equivalent to 93% of the Schockley-Queisser limit and a PCE of 24.37%.

Multistage Anticoagulant Surfaces: A Synergistic Combination of Protein Resistance, Fibrinolysis, and Endothelialization.

Anticoagulant surface modification of blood-contacting materials has been shown to be effective in preventing thrombosis and reducing the dose of anticoagulant drugs that patients take. However, commercially available anticoagulant coatings, that is, both bioinert and bioactive coatings, are typically based on a single anticoagulation strategy. This puts the anticoagulation function of the coating at risk of failure during long-term use. Considering the several pathways of the human coagulation system, the synergy of multiple anticoagulation theories may provide separate, targeted effects at different stages of thrombosis. Based on this presumption, in this work, negatively charged poly(sodium p-styrenesulfonate-co-oligo(ethylene glycol) methyl ether methacrylate) and positively charged poly(lysine-co-1-adamantan-1-ylmethyl methacrylate) were synthesized to construct matrix layers on the substrate by electrostatic layer-by-layer self-assembly (LBL). Amino-functionalized ß-cyclodextrin (ß-CD-PEI) was subsequently immobilized on the surface by host-guest interactions, and heparin was grafted. By adjusting the content of poly(oligo(ethylene glycol) methyl ether methacrylate) (POEGMA), the interactions between modified surfaces and plasma proteins/cells were regulated. This multistage anticoagulant surface exhibits inertness at the initial stage of implantation, resisting nonspecific protein adsorption (POEGMA). When coagulation reactions occur, heparin exerts its active anticoagulant function in a timely manner, blocking the pathway of thrombosis. If thrombus formation is inevitable, lysine can play a fibrinolytic role in dissolving fibrin clots. Finally, during implantation, endothelial cells continue to adhere and proliferate on the surface, forming an endothelial layer, which meets the blood compatibility requirements. This method provides a new approach to construct a multistage anticoagulant surface for blood-contacting materials.

Transmembrane Protein 68 Functions as an MGAT and DGAT Enzyme for Triacylglycerol Biosynthesis.

Triacylglycerol (TG) biosynthesis is an important metabolic process for intracellular storage of surplus energy, intestinal dietary fat absorption, attenuation of lipotoxicity, lipid transportation, lactation and signal transduction in mammals. Transmembrane protein 68 (TMEM68) is an endoplasmic reticulum (ER)-anchored acyltransferase family member of unknown function. In the current study we show that overexpression of TMEM68 promotes TG accumulation and lipid droplet (LD) formation in a conserved active sites-dependent manner. Quantitative targeted lipidomic analysis showed that diacylglycerol (DG), free fatty acid (FFA) and TG levels were increased by TMEM68 expression. In addition, TMEM68 overexpression affected the levels of several glycerophospholipids, such as phosphatidylcholine, phosphatidylethanolamine and phosphatidylinositol, as well as sterol ester contents. TMEM68 exhibited monoacylglycerol acyltransferase (MGAT) and diacylglycerol acyltransferase (DGAT) activities dependent on the conserved active sites in an in vitro assay. The expression of lipogenesis genes, including DGATs, fatty acid synthesis-related genes and peroxisome proliferator-activated receptor γ was upregulated in TMEM68-overexpressing cells. These results together demonstrate for the first time that TMEM68 functions as an acyltransferase and affects lipogenic gene expression, glycerolipid metabolism and TG storage in mammalian cells.

The Patatin-Like Phospholipase Domain Containing Protein 7 Regulates Macrophage Classical Activation through SIRT1/NF-κB and p38 MAPK Pathways.

Lysophosphatidylcholine (LPC) is a bioactive lipid that modulates macrophage polarization during immune responses, inflammation, and tissue remodeling. Patatin-like phospholipase domain containing protein 7 (PNPLA7) is a lysophospholipase with a preference for LPC. However, the role of PNPLA7 in macrophage polarization as an LPC hydrolase has not been explored. In the current study, we found that PNPLA7 is highly expressed in naïve macrophages and downregulated upon lipopolysaccharide (LPS)-induced polarization towards the classically activated (M1) phenotype. Consistently, overexpression of PNPLA7 suppressed the expression of proinflammatory M1 marker genes, including interleukin 1ß (IL-1ß), IL-6, inducible nitric oxide synthase (iNOS), and tumor necrosis factor α (TNF-α), whereas knockdown of PNPLA7 augmented the inflammatory gene expression in LPS-challenged macrophages. PNPLA7 overexpression and knockdown increased and decreased Sirtuin1 (SIRT1) mRNA and protein levels, respectively, and affected the acetylation of the nuclear factor-kappa B (NF-κB) p65 subunit, a key transcription factor in M1 polarization. In addition, the levels of phosphorylated p38 mitogen-activated protein kinase (MAPK) were suppressed and enhanced by PNPLA7 overexpression and knockdown, respectively. Taken together, these findings suggest that PNPLA7 suppresses M1 polarization of LPS-challenged macrophages by modulating SIRT1/NF-κB- and p38 MAPK-dependent pathways.

Role of the voltage-gated proton channel Hv1 in insulin secretion, glucose homeostasis, and obesity

Diabetes is characterized by an absolutely inadequate insulin secretion (type 1 diabetes mellitus) or a relative deficit in insulin secretion due to insulin resistance (type 2 diabetes mellitus), both of which result in elevated blood glucose. Understanding the molecular mechanisms underlying the pathophysiology of diabetes could lead to the development of new therapeutic approaches. The voltage-gated proton channel Hv1 is an ion channel with specific selectivity for protons, which is regulated by membrane potential and intracellular pH. Recently, our studies showed that Hv1 is expressed in β cells of the endocrine pancreas. Knockout of Hv1 reduces insulin secretion and results in hyperglycemia and glucose intolerance, but not insulin resistance. Furthermore, knockout of Hv1 leads to diet-induced obesity due to inflammation and hepatic steatosis. Increasing evidence suggests that Hv1 plays a pivotal role in glucose homeostasis and lipid metabolism. This review aims to summarize advances made so far in our understanding of the roles of Hv1 in the regulation of insulin secretion in β cells, glucose homeostasis, and obesity. (AU)

The Cognitive, Behavioral and Interpersonal Impacts of Virtual Practice with Short Health Videos on Chinese Ageing Women: A Discursive Approach.

In the digital era, the health information presented on virtual platforms plays a pivotal role in supporting people's active and healthy life. The ageing, especially ageing women, are more likely to seek and accept health information through online media platforms. The study shows that short health videos on social media platforms are extremely popular among ageing women in China for the accessing of virtual coaching. Adopting the qualitative methodology of in-depth interview and discourse analysis, the study investigates virtual coaching with short health video practice among 39 Chinese ageing women in different fields, who are all over sixty years old. Specifically, with the analytical tools of transitivity and generic structure analysis, the study explores the impacts of short health videos on Chinese ageing women's cognition, behavior and interpersonal relationships. The result shows that virtual practice and coaching via short health videos can build health awareness and a dynamic new lifestyle, and motivate women to positively practice physical activity and maintain positive interpersonal relationships. Factors affecting the effectiveness of short health videos are discussed for future research in the field of modeling and intervention.

Design of a genetically programmed barnacle-curli inspired living-cell bioadhesive.

In nature, barnacles and bacterial biofilms utilize self-assembly amyloid to achieve strong and robust interface adhesion. However, there is still a lack of sufficient research on the construction of macroscopic adhesives based on amyloid-like nanostructures through reasonable molecular design. Here, we report a genetically programmed self-assembly living-cell bioadhesive inspired by barnacle and curli system. Firstly, the encoding genes of two natural adhesion proteins (CsgA and cp19k) derived from E. coli curli and barnacle cement were fused and expressed as a fundamental building block of the bioadhesive. Utilizing the natural curli system of E. coli, fusion protein can be delivered to cell surface and self-assemble into an amyloid nanofibrous network. Then, the E. coli cells were incorporated into the molecular chain network of xanthan gum (XG) through covalent conjugation to produce a living-cell bioadhesive. The shear adhesive strength of the bioadhesive to the surface of the aluminum sheet reaches 278 â€‹kPa. Benefiting from living cells encapsulated inside, the bioadhesive can self-regenerate with adequate nutrients. This adhesive has low toxicity to organisms, strong resistance to the liquid environment in vivo, easy to pump, exhibiting potential application prospects in biomedical fields such as intestinal soft tissue repair.

Role of the voltage-gated proton channel Hv1 in insulin secretion, glucose homeostasis, and obesity.

Diabetes is characterized by an absolutely inadequate insulin secretion (type 1 diabetes mellitus) or a relative deficit in insulin secretion due to insulin resistance (type 2 diabetes mellitus), both of which result in elevated blood glucose. Understanding the molecular mechanisms underlying the pathophysiology of diabetes could lead to the development of new therapeutic approaches. The voltage-gated proton channel Hv1 is an ion channel with specific selectivity for protons, which is regulated by membrane potential and intracellular pH. Recently, our studies showed that Hv1 is expressed in ß cells of the endocrine pancreas. Knockout of Hv1 reduces insulin secretion and results in hyperglycemia and glucose intolerance, but not insulin resistance. Furthermore, knockout of Hv1 leads to diet-induced obesity due to inflammation and hepatic steatosis. Increasing evidence suggests that Hv1 plays a pivotal role in glucose homeostasis and lipid metabolism. This review aims to summarize advances made so far in our understanding of the roles of Hv1 in the regulation of insulin secretion in ß cells, glucose homeostasis, and obesity.

Heparin interacts with the main protease of SARS-CoV-2 and inhibits its activity.

The ability of SARS-CoV-2 to replicate in host cells is dependent on its main protease (Mpro, also called 3CLpro) that cut the viral precursor polyproteins and is a major target for antiviral drug design. Here, we showed that heparin interacts with the Mpro of SARS-CoV-2 and inhibits its activity. Protein fluorescence quenching showed that heparin strongly binds to the Mpro protein with dissociation constants KD of 16.66 and 31.60 µM at 25 and 35 °C, respectively. From thermodynamic parameters of the interaction, there are hydrophobic and hydrogen bond interactions between them. Fluorescence resonance energy transfer (FRET) assay demonstrated that heparin inhibits the proteolytic activity of Mpro with an inhibition constant Ki of 6.9 nM and a half maximal inhibitory concentrations (IC50) of 7.8 ± 2.6 nM. Furthermore, molecular docking analysis revealed that the recognition and binding groups of heparin within the active site of SARS-CoV-2 Mpro provide important new information for the characteristics of the interactions of heparin with the protease. Our finding suggested that heparin might have a potential role in inhibiting SARS-CoV-2 infection through inhibiting Mpro activity of SARS-CoV-2.

Mice lacking the proton channel Hv1 exhibit sex-specific differences in glucose homeostasis.

Sex as a physiologic factor has a strong association with the features of metabolic syndrome. Our previous study showed that loss of the voltage-gated proton channel Hv1 inhibits insulin secretion and leads to hyperglycemia and glucose intolerance in male mice. However, there are significant differences in blood glucose between male and female Hv1-knockout (KO) mice. Here, we investigated the differences in glucose metabolism and insulin sensitivity between male and female KO mice and how sex steroids contribute to these differences. We found that the fasting blood glucose in female KO mice was visibly lower than that in male KO mice, which was accompanied by hypotestosteronemia. KO mice in both sexes exhibited higher expression of gluconeogenesis-related genes in liver compared with WT mice. Also, the livers from KO males displayed a decrease in glycolysis-related gene expression and an increase in gluconeogenesis-related gene expression compared with KO females. Furthermore, exogenous testosterone supplementation decreased blood glucose levels in male KO mice, as well as enhancing insulin signaling. Taken together, our data demonstrate that knockout of Hv1 results in higher blood glucose levels in male than female mice, despite a decreased insulin secretion in both sexes. This sex-related difference in glucose homeostasis is associated with the glucose metabolism in liver tissue, likely due to the physiological levels of testosterone in KO male mice.

Inhibitory effects of chondroitin sulfate on alpha-amylase activity: A potential hypoglycemic agent.

Inhibiting the activity of the intestinal enzyme α-amylase that catalyzes the degradation of starch into glucose can control blood glucose and provide an essential way for the treatment of Type-II diabetes mellitus (T2DM). Here, we compared the structural information of chondroitin sulfate (CS) from different origins and the effects on activity of α-amylase and blood glucose have been investigated. The inhibitory effects of shark and porcine CSs against α-amylase activity is obvious with IC50 values of 11.97 and 14.42 mg/ml, respectively, but the bovine CS almost no effect. From the data of fluorescence spectroscopic analyses, CSs from shark and pig quench Try fluorescence intensity of the enzyme, whereas bovine CS induces an increase. In vivo, oral administration of shark and porcine CSs efficiently suppresses postprandial blood glucose levels in normal and diabetic mice. Our study found that CSs from different sources showed different biological functions even if both molecular weight and disaccharide subunit composition are almost the same, and demonstrated that the CSs from shark and pig as α-amylase inhibitors could be regarded as a novel functional food ingredient in T2DM management.

Deficiency of voltage-gated proton channel Hv1 aggravates ovalbumin-induced allergic lung asthma in mice.

Asthma is a chronic airway inflammation that caused by many factors. The voltage-gated proton channel Hv1 has been proposed to extrude excessive protons produced by NADPH oxidase (NOX) from cytosol to maintain its activity during respiratory bursts. Here, we showed that loss of Hv1 aggravates ovalbumin (OVA)-induced allergic lung asthma in mice. The numbers of total cells, eosinophils and neutrophils in bronchoalveolar lavage fluid (BALF) of Hv1-deficiency (KO) mice are obviously increased after OVA challenge compared with that of wild-type (WT) mice. Histopathological staining reveals that Hv1-deficiency aggravates OVA-induced inflammatory cell infiltration and goblet cell hyperplasia in lung tissues. The expression of IL-4, IL-5 and IL-13 are markedly increased in lung tissues of OVA-challenged KO mice compared with that of WT mice. Furthermore, the expression levels of NOX2, NOX4 and DUOX1 are dramatically increased, while the expression levels of SOD2 and catalase are significantly reduced in lung tissues of OVA-challenged KO mice compared with that of WT mice. The production of ROS in lung tissues of KO mice is significantly higher than that of WT mice after OVA challenge. Our data suggest that Hv1-deficiency might aggravate the development of allergic asthma through increasing ROS production.

Design of a Genetically Programmed Biomimetic Lipase Nanoreactor.

Alternative to the traditionally independent production of lipase, chemical synthesis of nano-carriers, and then preparing nanoimmobilized enzymes, we exploit a yeast genetically programmed virus biomimetic lipase nanoreactor in a sustainable manner. The nanoreactor biogenesis process integrated lipase production, protein component (coat-protein subunit and scaffold protein) production, self-assembly of protein components, and the encapsulation of lipase into protein nanocages using a simple process. It included overexpression of nanocage components, coat-protein subunits, and fused lipase-scaffold proteins and subsequent spontaneous self-assembly and encapsulation based on the specific interaction between the coat-protein subunit and the scaffold protein fused in the target lipase enzyme. The genetically programmable lipase nanoreactor showed improved stability under various harsh conditions, and was validated in fatty acid methyl ester synthesis with 86% yield at a high concentration of waste cooking oil (200 mM), which demonstrates the robustness and feasibility of the lipase nanoreactor in biodiesel production.

Loss of voltage-gated proton channel Hv1 leads to diet-induced obesity in mice.

OBJECTIVE: The voltage-gated proton channel Hv1 has been proposed to mediate NADPH oxidase (NOX) function by regulating intracellular pH during respiratory bursts. In our previous work, we showed that Hv1 is expressed in pancreatic ß cells and positively regulates insulin secretion. Here, we investigated the role of Hv1 in adipose tissue differentiation, metabolic homeostasis and insulin sensitivity using Hv1 knockout (KO) mice. DESIGN: Mice with genetic deletion of Hv1 are treated with high-fat diet (HFD) similar to wild-type (WT) mice. Body weight gain, adiposity, insulin sensitivity and gene expressions in both adipose tissue and liver were analyzed. RESULTS: Mice with genetic deletion of Hv1 display overt obesity with higher body weight gain and accumulation of adipose tissue compared with similarly HFD-treated WT. Hv1-deficient mice develop more glucose intolerance than WT, but no significant difference in insulin resistance, after fed with HFD. Deficiency of Hv1 results in a remarkable increase in epididymal adipocyte weight and size, while the gene expressions of proinflammatory factors and cytokines are obviously enhanced in the HFD-fed mice. Furthermore, the gene expression of Hv1 is increased in the HFD-fed mice, which is accompanied by the increase of NOX2 and NOX4. In addition, there is more severely diet-induced steatosis and inflammation in liver in KO mice. CONCLUSION: Our data demonstrated that lacking of Hv1 results in diet-induced obesity in mice through inflammation and hepatic steatosis. This study suggested that Hv1 acts as a positive regulator of metabolic homeostasis and a potential target for antiobesity drugs in therapy and may serve as an adaptive mechanism in cooperating with NOX to mediate reactive oxygen species for adipogenesis and insulin sensitivity.

Loss of the voltage-gated proton channel Hv1 decreases insulin secretion and leads to hyperglycemia and glucose intolerance in mice.

Insulin secretion by pancreatic islet ß-cells is regulated by glucose levels and is accompanied by proton generation. The voltage-gated proton channel Hv1 is present in pancreatic ß-cells and extremely selective for protons. However, whether Hv1 is involved in insulin secretion is unclear. Here we demonstrate that Hv1 promotes insulin secretion of pancreatic ß-cells and glucose homeostasis. Hv1-deficient mice displayed hyperglycemia and glucose intolerance because of reduced insulin secretion but retained normal peripheral insulin sensitivity. Moreover, Hv1 loss contributed much more to severe glucose intolerance as the mice got older. Islets of Hv1-deficient and heterozygous mice were markedly deficient in glucose- and K+-induced insulin secretion. In perifusion assays, Hv1 deletion dramatically reduced the first and second phase of glucose-stimulated insulin secretion. Islet insulin and proinsulin content was reduced, and histological analysis of pancreas slices revealed an accompanying modest reduction of ß-cell mass in Hv1 knockout mice. EM observations also indicated a reduction in insulin granule size, but not granule number or granule docking, in Hv1-deficient mice. Mechanistically, Hv1 loss limited the capacity for glucose-induced membrane depolarization, accompanied by a reduced ability of glucose to raise Ca2+ levels in islets, as evidenced by decreased durations of individual calcium oscillations. Moreover, Hv1 expression was significantly reduced in pancreatic ß-cells from streptozotocin-induced diabetic mice, indicating that Hv1 deficiency is associated with ß-cell dysfunction and diabetes. We conclude that Hv1 regulates insulin secretion and glucose homeostasis through a mechanism that depends on intracellular Ca2+ levels and membrane depolarization.

Population Pharmacokinetic/Pharmacodynamics Modeling of Ibutilide in Chinese Healthy Volunteers and Patients With Atrial Fibrillation (AF) and/or Atrial Flutter (AFL).

PURPOSE: The goal of this study was to develop a population pharmacokinetic (PK) and PK/pharmacodynamics (PD) model for ibutilide, to evaluate the time course of its effect on QT interval in Chinese. METHODS: The population PK and PK/PD model were developed using data from 40 Chinese healthy volunteers using nonlinear mixed-effects modeling, and the final population PK/PD model was applied on 100 patients with atrial fibrillation (AF) and/or atrial flutter (AFL). FINDINGS: The PK parameters of ibutilide were best described by a 3-compartment model with first-order elimination. No statistically significant covariate was found for each PK model parameter. Individualized QT interval correction, by heart rate, was performed by a power model, and the circadian rhythm of QT intervals was described by 2 mixed-effect cosine functions. The QT interval data of ibutilide was well characterized by a sigmoid Emax model (E(C)=Emaxγ×Cγ/(EC50γ+Cγ)) with an effect compartment. The final PK/PD model was used to estimate individual parameters of patient data and found good predictions compared with healthy volunteers; AF and/or AFL patients had lower Emax and higher EC50. IMPLICATIONS: A population PK and PK/PD model for ibutilide in healthy volunteers was developed and could well capture ibutilide's PK/PD characteristics. The final PK/PD model was applied on patients with AF and/or AFL successfully.

[Clinical analysis of 160 cases of statin-induced myopathy].

OBJECTIVE: To analyze the clinical features of statin-induced myopathy. METHOD: The statin-induced myopathy case reported as adverse drug reaction (ADR) to the Beijing Center for ADR Monitoring during January 2007 to December 2012 was summarized, patients were divided to myopathy group and rhabdomyolysis group, according to the absence or presence of rhabdomylysis. The clinical characteristics, medication history and outcome were compared between the two groups. RESULTS: A total of 160 statin-induced myopathy cases (54 in rhabdomyolysis group (33.8%) and 106 cases in myopathy group (66.3%)) were collected from the database (mean age: (64.22 ± 13.55) years old, 51.2% male, n = 82). The ADR occurred immediately after the first medication and up to 4 years after medication. Observed clinical features were myalgia, myositis, asymptommatic creatine kinase (CK) elevation or rhabdomyolysis. The average age were (68.54 ± 15.41) years old in rhabdomylysis group and (62.02 ± 12.41) years old in myopathy group (P = 0.004). There was no gender difference between the rhabdomylysis group and myopathy group (P = 0.406) . Twenty-four cases (44.4%) in rhabdomyolysis group and 26 cases (16.5%) in myopathy group were treated with high dose statin (P < 0.001). Percent of simvastatin treatment was significantly higher in rhabdomyolysis group (70.4% (38/54) ) than in myopathy group (32.1% (34/106), P < 0.001). Spearman correlation analysis showed that age, high-dose statin treatment and simvastatin use were all positively correlated with rhabdomylysis (P < 0.001), and the correlation coefficients (r value) were 0.305, 0.290 and 0.364, respectively. Four patients (aged from 71 to 85 years) died because of ADR and all 4 cases received high-dose statin treatment, 3 of them suffered from complex combined diseases, acute disease progression and complex multiple drug use history. CONCLUSIONS: Severe statin-induced myopathy, like rhabdomyolysis, is more likely to occur in old patients, in patients taking high-dose statin, especially simvastatin.

Efficacy and safety of aranidipine enteric-coated tablets compared with amlodipine in Chinese patients with mild to moderate essential hypertension: a multicenter, randomized, double-blind, parallel-controlled clinical trial.

This is a multicenter, randomized, double-blind, parallel-controlled study, conducted in Chinese patients with mild to moderate essential hypertension. After a 2-week washout period, 236 eligible patients were randomly to receive aranidipine 5-10 mg/d (n = 118) or amlodipine 5-10 mg/d (n = 118) for 10 weeks. The blood pressure and heart rate were evaluated in outpatient clinics, and ambulatory blood pressure monitoring was performed in 24 patients in each group. The blood pressure was significantly decreased in both groups. Compared with amlodipine, the patients who received aranidipine had less response in blood pressure (P < 0.01). The trough/peak ratios of diastolic blood pressure in aranidipine and amlodipine groups were 0.57 ± 0.20 and 0.68 ± 0.19, respectively (P = 0.119). Adverse events occurred at 11.86% and 7.63% in the aranidipine and amlodipine groups, respectively (P = 0.348). Headache was observed at an incidence of >3.0% in both groups, and the serum glucose and lipid profile had no significant change in the amlodipine group. In conclusion, once-daily administration of aranidipine (5-10 mg) effectively controlled blood pressure, and the short-term treatment might result in it being less effective than amlodipine. It had a stable action over 24-hour period, and the mechanism of that is not yet clear. Aranidipine had a good safety similar to that of amlodipine.