PCSK9 dysregulates cholesterol homeostasis and triglyceride metabolism in olanzapine-induced hepatic steatosis via both receptor-dependent and receptor-independent pathways.

Schizophrenia, affecting approximately 1% of the global population, is often treated with olanzapine. Despite its efficacy, olanzapine's prolonged use has been associated with an increased risk of cardiovascular diseases and nonalcoholic fatty liver disease (NAFLD); however, the underlying mechanism remains unclear. Proprotein convertase subtilisin kexin type 9 (PCSK9) plays a crucial role in lipid metabolism and is involved in NAFLD pathogenesis via an unknown mechanism. This study aims to investigate the role of PCSK9 in olanzapine-induced NAFLD. C57BL/6J mice and HepG2 and AML12 cell lines were treated with varying concentrations of olanzapine to examine the effects of olanzapine on PCSK9 and lipid metabolism. PCSK9 levels were manipulated using recombinant proteins, plasmids, and small interfering RNAs in vitro, and the effects on hepatic lipid accumulation and gene expression related to lipid metabolism were assessed. Olanzapine treatment significantly increased PCSK9 levels in both animal and cell line models, correlating with elevated lipid accumulation. PCSK9 manipulation demonstrated its central role in mediating hepatic steatosis through both receptor-dependent pathways (impacting NPC1L1) and receptor-independent pathways (affecting lipid synthesis, uptake, and cholesterol biosynthesis). Interestingly, upregulation of SREBP-1c, rather than SREBP-2, was identified as a key driver of PCSK9 increase in olanzapine-induced NAFLD. Our findings establish PCSK9 as a pivotal factor in olanzapine-induced NAFLD, influencing both receptor-related and metabolic pathways. This highlights PCSK9 inhibitors as potential therapeutic agents for managing NAFLD in schizophrenia patients treated with olanzapine.

Osteopontin-integrin signaling positively regulates neuroplasticity through enhancing neural autophagy in the peri-infarct area after ischemic stroke.

OBJECTIVE: To investigate the role of Osteopontin (OPN) in mediating macroautophagy, autophagy, and neuroplasticity in the ipsilateral hemisphere after stroke. METHODS: Focal stroke was induced by photothrombosis in adult mice. Spatiotemporal expression of endogenous OPN and BECN1 was assessed by immunohistochemistry. Motor function was determined by the grid-walking and cylinder tasks. We also evaluated markers of neuroplasticity and autophagy using biochemical and histology analyses. RESULTS: Herein, we showed that endogenous OPN and beclin1 were increased in the peri-infarct area of stroked patients and mice. Intracerebral administration of OPN (0.1 mg/ml; 3 ml) significantly improved performance in motor behavioral tasks compared with non-OPN-treated stroke mice. Furthermore, the neural repair was induced in OPN-treated stroke mice. We found that OPN treatment resulted in a significantly higher density of a presynaptic marker (vesicular glutamate transporter 1, VgluT1) and synaptic plasticity marker (synaptophysin, SYN) within the peri-infarct region. OPN treatment in stroke mice not only increased protein levels of integrin ß1 but also promoted the expression of beclin1 and LC3, two autophagy-related proteins in the peri-infarct area. Additionally, OPN-induced neuroplasticity and autophagy were blocked by an integrin antagonist. CONCLUSION: Our findings indicate that OPN may enhance neuroplasticity via autophagy, providing a new therapeutic strategy for ischemic stroke.

Correlation of TET-2 Levels with Disease Evaluation in AMI Patients.

Objective: To investigate the expression levels of Ten-Eleven Translocation-2 (TET-2) in patients with acute myocardial infarction (AMI) and correlations of TET-2 levels with disease severity. Methods: A total of 150 patients with confirmed AMI were included in this study. According to the number of coronary artery lesions, the patients were divided into a single lesion group, two lesion group, and three lesion group. According to the Gensini scores, these patients were also assigned into three groups: the low-risk group, middle-risk group, and high-risk group. 150 patients without AMI confirmed by coronary angiography were included in the control group in the same period. TET-2 and cardiac troponin T (cTNT) levels were detected by ELISA analysis and compared among different groups. Pearson's correlation analysis was used to evaluate the correlations of TET-2 levels and cTNT levels/Gensini scores. The levels of TET-2 in AMI patients increased remarkably with the increase of disease severity. Patients in the single lesion group or low-risk group had the lowest levels of TET-2. Pearson correlation analysis indicated that TET-2 levels were positively associated with cTNT levels and Gensini scores, respectively (all P < 0.001). Conclusion: The levels of TET-2 were upregulated in AMI patients and positively correlated with cTNT levels or Gensini scores, suggesting that the examination of TET-2 expression levels could be exploited for predicting the disease severity.

The bs-YHEDA peptide protects the brains of senile mice and thus recovers intelligence by reducing iron and free radicals.

Iron accumulates in the brain with age and catalyzes free radical damage to neurons, thus playing a pathogenic role in Alzheimer's disease (AD). To decrease the incidence of AD, we synthesized the iron-affinitive peptide 5YHEDA to scavenge the excess iron in the senile brain. However, the blood-brain barrier (BBB) blocks the entrance of macromolecules into the brain, thus decreasing the therapeutic effects. To facilitate the entrance of the 5YHEDA peptide, we linked the low-density lipoprotein receptor (LDLR)-binding segment of ApoB-100 to 5YHEDA (named "bs-YHEDA"). The results of intravenous injections of bs-5YHEDA into senescent mice demonstrated that bs-YHEDA entered the brain, increased ferriportin levels, reduced iron and free radical levels, decreased the consequences of neuronal necrosis and ameliorated cognitive disfunction without kidney or liver damage. bs-5YHEDA is a safe iron and free radical remover that potentially alleviates aging and Alzheimer's disease.

Alterations in sorting and secretion of hepatic apoA5 induce hypertriglyceridemia due to short-term use of olanzapine.

Long-term use of olanzapine, an antipsychotic drug, induces hypertriglyceridemia, resulting in a higher risk of cardiovascular disease. However, the effects and underlying mechanisms of short-term use of olanzapine on circulating triglyceride levels remain poorly understood. Here, the role of apolipoprotein A5 (apoA5), a regulator of triglyceride metabolism, was investigated in olanzapine-induced hypertriglyceridemia. Our multi-center clinical study recruited 36 schizophrenia patients who received short-term (8 weeks) of olanzapine. Besides, female C57BL/6J mice were treated with olanzapine (3 mg/kg/day versus 6 mg/kg/day) for 6 weeks. We demonstrated that short-term use of olanzapine increased plasma triglyceride and decreased plasma apoA5 levels in the patients and mice, with a negative correlation between the two factors. However, no obesity was observed in the patients and mice. Interestingly, olanzapine increased hepatic apoA5 protein in the mice, without significant changes in hepatic Apoa5 mRNA. Consistently, in vitro studies indicated that olanzapine increased medium triglyceride levels and decreased medium apoA5 levels in a dose-dependent manner in human HepG2 cells and primary mouse hepatocytes. Whereas the olanzapine treatment increased hepatic apoA5 protein in vitro, without effects on hepatic APOA5 mRNA. Of note, olanzapine increased the co-localization between apoA5 protein and accumulated lipid droplets in hepatocytes, as opposed to at the hepatocellular plasma membrane, in mouse liver as demonstrated by fluorescence staining. Therefore, our study indicated that short-term use of olanzapine induced hypertriglyceridemia due to defects of sorting and secretion of hepatic apoA5.

Olanzapine causes non-alcoholic fatty liver disease via inhibiting the secretion of apolipoprotein A5. / 奥氮平通过抑制载脂蛋白A5åˆ†æ³Œå¯¼è‡´éžé ’ç²¾æ€§è„‚è‚ªæ€§è‚ç— .

OBJECTIVES: Long-term treatment of olanzapine, the most widely-prescribed second-generation antipsychotic, remarkably increases the risk of non-alcoholic fatty liver disease (NAFLD), whereas the mechanism for olanzapine-induced NAFLD remains unknown. Excessive hepatic fat accumulation is the basis for the pathogenesis of NAFLD, which results from the disturbance of TG metabolism in the liver. Apolipoprotein A5 (ApoA5) is a key regulator for TG metabolism in vivo that promotes TG accumulation in hepatocytes, thereby resulting in the development of NAFLD. However, there are no data indicating the role of apoA5 in olanzapine-induced NAFLD. Therefore, this study aims to investigate the role of apoA5 in olanzapine-induced NAFLD. METHODS: This study was carried out via animal studies, cell experiment, and ApoA5 gene knockdown experiment. Six-week-old male C57BL/6J mice were randomized into a control group, a low-dose group, and a high-dose group, which were treated by 10% DMSO, 3 mg/(kg·d) olanzapine, and 6 mg/(kg·d) olanzapine, respectively for 8 weeks. The lipid levels in plasma, liver function indexes, and expression levels of ApoA5 were detected. HepG2 cells were treated with 0.1% DMSO (control group), 25 µmol/L olanzapine (low-dose group), 50 µmol/L olanzapine (medium-dose group), and 100 µmol/L olanzapine (high-dose group) for 24 h. HepG2 cells pretreated with 100 µmol/L olanzapine were transfected with siRNA and scrambled siRNA (negative control), respectively. We observed the changes in lipid droplets within liver tissues and cells using oil red O staining and fat deposition in liver tissues using HE staining. The mRNA and protein levels of ApoA5 were determined by real-time PCR and Western blotting, respectively. RESULTS: After intervention with 3 and 6 mg/(kg·d) olanzapine for 8 weeks, there was no significant difference in body weight among the 3 groups (P>0.05). Olanzapine dose-dependently increased the plasma TG, ALT and AST levels, and reduced plasma ApoA5 levels (all P<0.05), whereas there was no significant difference in plasma cholesterol (HDL-C, LDL-C, and TC) levels among the 3 groups (all P>0.05). Olanzapine dose-dependently up-regulated ApoA5 protein levels in liver tissues (all P<0.05), but there was no significant change in ApoA5 mRNA expression among groups (P>0.05). In the control group, the structure of liver tissues was intact, the morphology of liver cells was regular, and only a few scattered lipid droplets were found in the cells. In the olanzapine-treated group, there was a large amount of lipid deposition in hepatocytes, and cells were balloon-like and filled with lipid droplet vacuoles. The nucleus located at the edge of cell, and the number of lipid droplets was increased significantly, especially in the high-dose group. Likewise, when HepG2 cells were treated with olanzapine for 24 h, the number and size of lipid droplets were significantly elevated in a dose-dependent manner. Moreover, olanzapine dose-dependently up-regulated ApoA5 protein levels in HepG2 cells (all P<0.05), but there was no significant difference in ApoA5 mRNA expression among groups (P>0.05). Compared with the HepG2 cells transfected with scrambled siRNA, the number and size of lipid droplets in HepG2 cells transfected with ApoA5 siRNA were significantly reduced. CONCLUSIONS: The short-term intervention of olanzapine does not significantly increase body weight of mice, but it can directly induce hypertriglyceridemia and NAFLD in mice. Olanzapine inhibits hepatic apoA5 secretion but does not affect hepatic apoA5 synthesis, resulting in the pathogenesis of NAFLD. Inhibition of apoA5 secretion plays a key role in the development of olanzapine-related NAFLD, which may serve as an intervention target for this disease.

Case Report: A Mysterious Giant Thrombus in the Right Atrium in a Patient With Dilated Cardiomyopathy.

An isolated right atrial thrombus is a life-threatening entity that is extremely rare in patients with dilated cardiomyopathy (DCM), which is characterized by a reduced left ventricular function and consequent left ventricular thrombosis. Here, we present the case of a mysterious isolated giant right atrial thrombus in a male patient with DCM. The presence of deep vein thrombosis prompted us to investigate for other underlying diseases for his right atrial thrombus. Interestingly, the elevation of two tumor markers indicated the likelihood of cancer-associated thrombosis. Further, the computed tomography demonstrated a spiculated mass in the lower right lung that was confirmed by an endobronchial biopsy as lung squamous cell carcinoma. Consequently, the giant thrombus in the right atrium should be attributed principally to lung squamous cell carcinoma on the background of DCM. After 3 weeks of enoxaparin, the echocardiogram indicated partial resolution of the thrombus. However, the patient suffered sudden death due to pulmonary embolism.

A Rare Case of Isolated Right Ventricular Non-compaction With the Novel TTN Mutation.

Isolated right ventricular non-compaction (RVNC) is rare yet life-threatening if left untreated, especially when accompanied by ventricular tachycardia. We describe a rare case of isolated RVNC, presenting as a prominent and excessive trabeculation of the right ventricle (RV), with an abnormal electrocardiogram. The transthoracic echocardiography, computed tomography, and ventricular angiography results clearly demonstrated an isolated spongy RV, both anatomically and functionally. Genetic testing identified a missense mutation of TTN. Combined, the diagnosis of RVNC was established. The subsequent combination of heart failure therapy, antiarrhythmic, and anticoagulation therapy were effective with a favorable outcome. This case report describes the possible etiology, manifestation, characteristic images, and problematic diagnostic criteria of the isolated RVNC. This case also emphasizes the necessity for comprehensive cardiac screening in familial cardiomyopathy.

Metformin Ameliorates Hepatic Steatosis induced by olanzapine through inhibiting LXRα/PCSK9 pathway.

Studies have confirmed that olanzapine, the mainstay treatment for schizophrenia, triggers metabolic diseases, including non-alcoholic fatty liver disease (NAFLD). However, the etiology of olanzapine-induced NAFLD is poorly understood. Proprotein convertase subtilisin kexin type 9 (PCSK9) is involved in NAFLD pathogenesis, and metformin can significantly decrease circulating PCSK9. The purpose of this study was to investigate the role of PCSK9 and explore the therapeutic effect of metformin for olanzapine-associated NAFLD. Olanzapine significantly upregulated PCSK9 and promoted lipid accumulation in mouse livers and HepG2 and AML12 cells. Metformin ameliorated these pathological alterations. PCSK9 upstream regulator liver X receptor α (LXRα) was significantly upregulated in olanzapine-induced NAFLD. LXRα antagonist treatment and LXRα overexpression resulted in a decrease and increase of PCSK9, respectively. Hepatic lipogenesis-associated genes FAS and SCD1 were significantly upregulated in olanzapine-induced NAFLD mice and HepG2 cells overexpressing PCSK9, and genes related to lipid ß-oxidation (SCAD and PPARα) were downregulated, while metformin reversed these changes. In addition, we found that LXRα overexpression compromised the effect of metformin on PCSK9 levels and intracellular lipid droplet formation. Taken together, our findings suggest that olanzapine enhances hepatic PCSK9 expression by upregulating LXRα, thereby increasing FAS and SCD1 expression as well as decreasing SCAD and PPARα, and promoting lipid accumulation, and, subsequently, NAFLD, which is ameliorated by metformin.

Sodium-glucose cotransporter protein-2 inhibitors and glucagon-like peptide-1 receptor agonists versus thiazolidinediones for non-alcoholic fatty liver disease: A network meta-analysis.

AIMS: Non-alcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disorders worldwide. Some hypoglycemic drugs can improve NAFLD. However, it is unclear which of these types of hypoglycemic drugs are more effective for NAFLD. Therefore, we conducted a network meta-analysis to determine the effect of thiazolidinediones (TZDs), sodium-glucose cotransporter 2 (SGLT2) inhibitors, and glucagon-like peptide-1 (GLP-1) receptor agonists on NAFLD patients. METHODS: A literature search of PubMed, EMBASE, the Cochrane Library, and Medline was conducted, and the literature from database inception up to April 30, 2021 was obtained. Liver function tests, lipid profiles, body mass index (BMI) and glycemic parameters were obtained from randomized controlled trials. Weighted mean differences (WMDs), relative risks and 95% confidence intervals (CIs) were calculated for continuous outcomes, and the I2 statistic was used to evaluate the heterogeneity of the studies. RESULTS: In total, 22 trials, including 1361 patients, were selected. In direct meta-analysis, GLP-1 receptor agonists were superior to TZDs in decreasing alanine aminotransferase (WMD, -0.40, 95% CI: -0.60 to -0.20), γ-glutamyl transferase (WMD, -5.00, 95% CI: -6.47 to -3.53), BMI (WMD, -4.10, 95%CI: -6.55 to -1.65) and triglycerides (WMD, - 0.50, 95% CI: -0.68 to -0.32). Based on Bayesian network meta-analysis, the effect of SGLT-2 inhibitors on weight loss was superior to that of TZDs (WMD, -1.80, 95%CI: -3.30 to -0.41). CONCLUSIONS: GLP-1 receptor agonists and SGLT-2 inhibitors improved liver enzymes, BMI, blood lipid, blood glucose and insulin resistance in NAFLD patients.

Xinshuitong Capsule extract attenuates doxorubicin-induced myocardial edema via regulation of cardiac aquaporins in the chronic heart failure rats.

Doxorubicin (Dox), an effective antineoplastic drug, was limited use for cardiotoxicity. Xinshuitong Capsule (XST), a patented herbal formula, showed desirable beneficial effects in the treatment of chronic heart failure (CHF) patients. However, the drug on Dox-induced cardiotoxicity remains unclear. Ninety male Sprague-Dawley rats were randomized into two groups: 15 rats were selected as the normal group and 75 rats were injected intraperitoneally with Dox to establish CHF rat models, the success ones were randomly divided into five groups: low XST (LXST), medium XST (MXST) or high XST (HXST) (4.9, 9.8, or 19.6 g/kg d) administrated intragastrically twice a day for 4 weeks, with the captopril-treated group and the model group as comparison. The model group showed the cardiac functions generally impaired, and CHF mortality rate higher (47%) than those in the XST-treated groups (averaged 24%, P < 0.05). Compared with XST-treated groups, myocardial remodeling, inflammation and desarcomerization, and higher water content more severe in the cardiac tissue in the model group (P < 0.05), which was associated with higher expressions of mRNA or protein levels of AQP1, 4 and 7. Dox-impaired cardiac functions, cardiac remodeling and myocardial edema could be dose-dependently reverted by XST treatment. XST could inhibit AQP1, 4 and 7 at mRNA levels or at protein levels, which was associated with the attenuation of myocardial edema and cardiac remodeling, decreasing the ventricular stiffness and improving the cardiac functions and rats' survival. AQPs is involved in cardiac edema composed one of the mechanisms of Dox-induced cardiotoxicity, XSTvia inhibition of AQPs relieved the Dox-induced side effects.

H2O2 gel bleaching induces cytotoxicity and pain conduction in dental pulp stem cells via intracellular reactive oxygen species on enamel/dentin disc.

BACKGROUND: Bleaching is widely accepted for improving the appearance of discolored teeth; however, patient compliance is affected by bleaching-related complications, especially bleaching sensitivity. This study aimed to investigate the role of reactive oxygen species (ROS) in cytotoxicity and pain conduction activated by experimental tooth bleaching. METHODS: Dental pulp stem cells with or without N-acetyl-L-cysteine (NAC), an ROS scavenger, were cultured on the dentin side of the enamel/dentin disc. Subsequently, 15% (90 min) and 40% (30 min) bleaching gels were painted on the enamel surface. Cell viability, intracellular ROS, Ca2+, adenosine triphosphate (ATP), and extracellular ATP levels were evaluated using the Cell Counting Kit-8 assay, 2',7'-dichlorodihydrofluorescein diacetate, CellROX, fura-3AM fluorescence assay, and ATP measurement kit. The rat incisor model was used to evaluate in vivo effects after 0, 1, 3, 7, and 30 days of bleaching. Changes in gene and protein expression of interleukin 6 (IL-6), tumor necrosis factor-alpha (TNFα), transient receptor potential ankyrin 1 (TRPA1), and Pannexin1 (PANX1) in dental pulp stem cells and pulp tissue were detected through RT-PCR, western blotting, and immunofluorescence. RESULTS: The bleaching gel suppressed dental pulp stem cell viability and extracellular ATP levels and increased intracellular ROS, Ca2+, and intracellular ATP levels. The mRNA and protein expression of IL-6, TNFα, TRPA1, and PANX1 were up-regulated in vitro and in vivo. Furthermore, the 40% gel had a stronger effect than the 15% gel, and NAC ameliorated the gel effects. CONCLUSIONS: Our findings suggest that bleaching gels induce cytotoxicity and pain conduction in dental pulp stem cells via intracellular ROS, which may provide a potential therapeutic target for alleviating tooth bleaching nociception.

TRPA1 triggers hyperalgesia and inflammation after tooth bleaching.

Hyperalgesia has become a major problem restricting the clinical application of tooth bleaching. We hypothesized that transient receptor potential ankyrin 1 (TRPA1), a pain conduction tunnel, plays a role in tooth hyperalgesia and inflammation after bleaching. Dental pulp stem cells were seeded on the dentin side of the disc, which was cut from the premolar buccal tissue, with 15% (90 min) or 40% (3 × 15 min) bleaching gel applied on the enamel side, and treated with or without a TRPA1 inhibitor. The bleaching gel stimulated intracellular reactive oxygen species, Ca2+, ATP, and extracellular ATP in a dose-dependent manner, and increased the mRNA and protein levels of hyperalgesia (TRPA1 and PANX1) and inflammation (TNFα and IL6) factors. This increment was adversely affected by TRPA1 inhibitor. In animal study, the protein levels of TRPA1 (P = 0.0006), PANX1 (P < 0.0001), and proliferation factors [PCNA (P < 0.0001) and Caspase 3 (P = 0.0066)] increased significantly after treated rat incisors with 15% and 40% bleaching gels as detected by immunohistochemistry. These results show that TRPA1 plays a critical role in sensitivity and inflammation after tooth bleaching, providing a solid foundation for further research on reducing the complications of tooth bleaching.

Olanzapine leads to nonalcoholic fatty liver disease through the apolipoprotein A5 pathway.

The antipsychotic drug olanzapine was reported to induce nonalcoholic fatty liver disease (NAFLD), whereas the underlying mechanism remains incompletely understood. This study investigated whether apolipoprotein A5 (apoA5) and sortilin, two interactive factors involved in NAFLD pathogenesis, are implicated in olanzapine-induced NAFLD. In our study, at week 8, olanzapine treatment successfully induced hepatic steatosis in female C57 BL/6 J mice, which was independent of body weight gain. Likewise, olanzapine effectively mediated hepatocyte steatosis in HepG2 cells characterized by substantially elevated intracellular lipid droplets. Increased plasma triglyceride concentration and decreased plasma apoA5 levels were observed in mice treated with 8-week olanzapine. Surprisingly, olanzapine markedly enhanced hepatic apoA5 protein levels in mice, without a significant effect on rodent hepatic ApoA5 mRNA. Our in vitro study showed that olanzapine reduced apoA5 protein levels in the medium and enhanced apoA5 protein levels in hepatocytes, whereas this drug exerted no effect on hepatocyte APOA5 mRNA. By transfecting APOA5 siRNA into HepG2 cells, it was demonstrated that APOA5 knockdown effectively reversed olanzapine-induced hepatocyte steatosis in vitro. In addition, olanzapine drastically increased sortilin mRNA and protein levels in vivo and in vitro. Interestingly, SORT1 knockdown reduced intracellular apoA5 protein levels and increased medium apoA5 protein levels in vitro, without affecting intracellular APOA5 mRNA levels. Furthermore, SORT1 knockdown greatly ameliorated hepatocyte steatosis in vitro. This study provides the first evidence that sortilin inhibits the hepatic apoA5 secretion that is attributable to olanzapine-induced NAFLD, which provides new insight into effective strategies against NAFLD for patients with schizophrenia administered olanzapine.

Effects of olanzapine treatment on lipid profiles in patients with schizophrenia: a systematic review and meta-analysis.

Olanzapine-induced dyslipidemia significantly increases the risk of cardiovascular disease in patients with schizophrenia. However, the clinical features of olanzapine-induced dyslipidemia remain hitherto unclear because of inconsistencies in the literature. This meta-analysis thus investigated the effects of olanzapine treatment on lipid profiles among patients with schizophrenia. Studies of the effects of olanzapine on lipids were obtained through the PubMed, Web of science, The Cochrane Library and Embase databases (up to January 1, 2020). Twenty-one studies and 1790 schizophrenia patients who received olanzapine therapy were included in our analysis. An olanzapine-induced increase was observed in plasma triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) levels in patients with schizophrenia (all P < 0.05). Moreover, the time points analyzed included the following: baseline, 4 weeks, 6 weeks, 8 weeks, 12 weeks, and ≥ 24 weeks (data of ≥ 24 weeks were integrated). The significant elevation of TG, TC, and LDL-C was observed in patients with schizophrenia already by 4 weeks of olanzapine therapy (all P < 0.05), with no obvious changes observed in high-density lipoprotein cholesterol (HDL-C) (P > 0.05). In conclusion, olanzapine-induced dyslipidemia, characterized by increased TG, TC, and LDL-C levels, was observed in patients with schizophrenia already by 4 weeks of olanzapine treatment.

Heat map visualization for electrocardiogram data analysis.

BACKGROUND: Most electrocardiogram (ECG) studies still take advantage of traditional statistical functions, and the results are mostly presented in tables, histograms, and curves. Few papers display ECG data by visual means. The aim of this study was to analyze and show data for electrocardiographic left ventricular hypertrophy (LVH) with ST-segment elevation (STE) by a heat map in order to explore the feasibility and clinical value of heat mapping for ECG data visualization. METHODS: We sequentially collected the electrocardiograms of inpatients in the First Affiliated Hospital of Shantou University Medical College from July 2015 to December 2015 in order to screen cases of LVH with STE. HemI 1.0 software was used to draw heat maps to display the STE of each lead of each collected ECG. Cluster analysis was carried out based on the heat map and the results were drawn as tree maps (pedigree maps) in the heat map. RESULTS: In total, 60 cases of electrocardiographic LVH with STE were screened and analyzed. STE leads were mainly in the V1, V2 and V3 leads. The ST-segment shifts of each lead of each collected ECG could be conveniently visualized in the heat map. According to cluster analysis in the heat map, STE leads were clustered into two categories, comprising of the right precordial leads (V1, V2, V3) and others (V4, V5, V6, I, II, III, aVF, aVL, aVR). Moreover, the STE amplitude in 40% (24 out of 60) of cases reached the threshold specified in the STEMI guideline. These cases also could be fully displayed and visualized in the heat map. Cluster analysis in the heat map showed that the III, aVF and aVR leads could be clustered together, the V1, V2, V3 and V4 leads could be clustered together, and the V5, V6, I and aVL leads could be clustered together. CONCLUSION: Heat maps and cluster analysis can be used to fully display every lead of each electrocardiogram and provide relatively comprehensive information.

Effect of Betahistine and Metformin on Antipsychotic-Induced Weight Gain: An Analysis of Two Clinical Trials.

Antipsychotic-induced weight gain is one of the most common adverse effects of antipsychotic treatment. However, there are no well-established interventions for the weight gain yet. In this study, we pooled the data from two clinical trials, which were originally examining the efficacy of betahistine and the efficacy of metformin in treating antipsychotic-induced weight gain and insulin resistance. A total of 67 people with schizophrenia or bipolar disorder treated with antipsychotics were assigned to 36 mg day-1 betahistine (n = 13) or 1,000 mg day-1 metformin (n = 25) or placebo (n = 29) treatment for 12 weeks, with evaluation at baseline and week 12. The primary outcome was the body mass index (BMI). After treatment, metformin group had a mean decrease in BMI of 1.46 ± 0.14 (p < 0.001) and insulin resistance index (IRI) of 4.30 ± 2.02 (p < 0.001). The betahistine group had no significant alteration in BMI or IRI. However, placebo group had a mean increase in BMI of 1.27 ± 0.77 (p < 0.001) and IRI of 0.45 ± 0.86 (p < 0.001). Between the two treatment groups, metformin significantly decreased weight, BMI, fasting glucose, insulin level, and IRI but not waist circumference when compared with betahistine. Moreover, metformin significantly decreased weight, BMI, waist circumference, fasting glucose, insulin level, and IRI when compared with placebo, whereas betahistine significantly decreased body weight, waist circumference, BMI, insulin level, and IRI but not fasting glucose when compared with placebo. In this study, we found that both metformin treatment and betahistine treatment were efficacious in improving antipsychotic-induced weight gain and insulin resistance, and metformin was more efficacious in preventing and revising the weight gain induced by antipsychotics. Clinical Trial Registration: www.ClinicalTrials.gov, NCT00451399(Study 1), NCT00709202(Study 2).

[Remineralization of demineralized dentin induced by bioactive glass NovaMin].

OBJECTIVE: To explore the remineralization effect of bioactive glass NovaMin on demineralized dentin specimens, and to study the physical and chemical properties of formed structure at dentin surface.
 Methods: One mm-thickness coronal dentin slices were soaked in ethylene diamine tetraacetic acid (EDTA) for 48 h to prepare the completely demineralized dentin specimens and they were divided into 2 groups: an artificial saliva group (control group) and a NovaMin powder group. The specimens were treated with artificial saliva or NovaMin powder for 2 min (2 times every day), and the interval was 8 hours. Then, the specimens were soaked in the remineralization solution. After 7 days, the scanning electron microscope (SEM), energy dispersive X-ray (EDX), attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) and X-ray diffraction (XRD) were used to detect dentin morphology, the physical and chemical properties of the formed structure at dentin surface.
 Results: The results of SEM showed that a defined surface layer in the NovaMin powder group could be observed in the SEM imaging at the 7th day, which completely occluded dentinal tubules; the EDX, ATR-FTIR and XRD analysis found that the mineralized layer formed at dentin surface was mainly composed of calcium and phosphate elements, which was similar to the hydroxyapatite-like crystal. However, there were no materials formed at the dentin surface in the control group, and the dentinal tubules were still open.
 Conclusion: NovaMin can remineralize the demineralized dentin specimens and occlude the dentinal tubules in hydroxyapatite-like crystal structure.