Dielectric and Magnetic Relaxations Exhibited in a 2D Parallel Interpenetrating Frustrated Star Net.

Constructing multiple functional geometric frustration magnets is a hot topic in solid state chemistry and material science. Herein, a two-dimensional (2D) parallel interpenetrating "star" net complex [HDMPDA][Fe6 (µ3 -O)2 (µ-O2 CH)15 ] (1) was obtained successfully with HDMPDA (DMPDA=N, N'-dimethyl-1,3-propanediamine) as charge balancer. The dipole reorientation of the rotator [HDMPDA]+ in the complex brings a structure transition which leads dielectric relaxation close to room temperature. Despite strong antiferromagnetic coupling existing between ions in the net, long-range order temperature TN of the complex is suppressed to 4.2 K by geometric frustration. Interestingly, below TN , a canted antiferromagnetic state, accompanied with slow magnetic relaxation, is detected due to the lack of enough magnetic coupling between 2D layers. Thus, 1 is a particular multifunctional magnetic frustration material containing two different types of relaxations.

NR4A1 counteracts JNK activation incurred by ER stress or ROS in pancreatic ß-cells for protection.

Sustained hyperglycaemia and hyperlipidaemia incur endoplasmic reticulum stress (ER stress) and reactive oxygen species (ROS) overproduction in pancreatic ß-cells. ER stress or ROS causes c-Jun N-terminal kinase (JNK) activation, and the activated JNK triggers apoptosis in different cells. Nuclear receptor subfamily 4 group A member 1 (NR4A1) is an inducible multi-stress response factor. The aim of this study was to explore the role of NR4A1 in counteracting JNK activation induced by ER stress or ROS and the related mechanism. qPCR, Western blotting, dual-luciferase reporter and ChIP assays were applied to detect gene expression or regulation by NR4A1. Immunofluorescence was used to detect a specific protein expression in ß-cells. Our data showed that NR4A1 reduced the phosphorylated JNK (p-JNK) in MIN6 cells encountering ER stress or ROS and reduced MKK4 protein in a proteasome-dependent manner. We found that NR4A1 increased the expression of cbl-b (an E3 ligase); knocking down cbl-b expression increased MKK4 and p-JNK levels under ER stress or ROS conditions. We elucidated that NR4A1 enhanced the transactivation of cbl-b promoter by physical association. We further confirmed that cbl-b expression in ß-cells was reduced in NR4A1-knockout mice compared with WT mice. NR4A1 down-regulates JNK activation by ER stress or ROS in ß-cells via enhancing cbl-b expression.

Endoscopic mucosal resection versus endoscopic submucosal dissection for colorectal laterally spreading tumors: a meta-analysis.

OBJECTIVE: to assess the efficacy and safety of endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) in the treatment of colorectal laterally spreading tumors (LSTs). METHODS: a systematic literature search was performed in PubMed, Embase, the Cochrane Library, CNKI and WANFANG databases. The related references were selected according to certain inclusion and exclusion criteria. The Cochrane Collaboration's Revman 5.3 software was used for data analysis. RESULTS: a total of 12 studies were included in the analysis. The total number of lesions was 3,062 (EMR: 1,906; ESD: 1,156). The en-bloc resection rate of ESD was 95 % (1,098/1,156), which was significantly higher than that of EMR (42.8 %, 815/1,906) (OR = 0.07, 95 % CI [0.02, 0.07], p < 0.00001). The complete resection rate of ESD was 93.2 % (109/117), which was significantly higher than that of EMR as well (71.9 %, 92/128) (OR = 0.12, 95 % CI [0.05, 0.29], p < 0.00001). The bleeding rate showed no significant difference between EMR and ESD (4.2 % vs 3.5 %) (OR = 1.04, 95 % CI [0.68, 1.60], p = 0.85). The perforation rates of EMR and ESD were 1.8 % and 2.4 %, respectively, which displayed a significant difference (OR = 0.56, 95 % CI [0.32, 0.97], p = 0.04). Nevertheless, the recurrence rate of EMR was significantly higher than that of ESD (15.9 % vs 0.5 %) (OR = 23.06, 95 % CI [11.11, 47.85], p < 0.00001). CONCLUSIONS: endoscopic resection of LSTs is safe and effective. As compared with EMR, ESD has higher en-bloc and complete resection rates but a lower recurrence rate. Therefore, ESD is highly recommended for the treatment of LSTs.

Errata: Increased Plasma Soluble Fractalkine in Patients with Chronic Heart Failure and Its Clinical Significance.

Errors appeared in the article entitled "Increased Plasma Soluble Fractalkine in Patients with Chronic Heart Failure and Its Clinical Significance" by Cui-Ling Ji, Adnan Nomi, Bin Li, Cheng Shen, Bing-Chun Song, and Jin-Guo Zhang (Vol. 60, No. 3, 701-707, 2019). The affiliations of the authors and the address for correspondence on the bottom of page 701 should be replaced by the following.From the 1Department of Cardiology II, Affiliated Hospital of Jining Medical University, Jining, China, 2Teaching and Research Section of International Students, Jining Medical University, Jining, China, and 3Department of Cardiology IV, Affiliated Hospital of Jining Medical University, Jining, China.Address for correspondence: Jin-Guo Zhang, MD, Department of Cardiology II, Affiliated Hospital of Jining Medical University, No. 89 Guhuai Road, Jining, Shandong 272100, China.

Increased Plasma Soluble Fractalkine in Patients with Chronic Heart Failure and Its Clinical Significance.

Fractalkine has been reported to play an important role in the pathophysiology of various cardiovascular disorders. This research aims to study the change of soluble fractalkine (sFKN) in plasma level of patients with chronic heart failure (CHF) and evaluate its prognostic value.A total of 96 patients with CHF and 45 healthy subjects were included in this study. The plasma levels of sFKN, brain natriuretic peptide (BNP), and Interleukin-18 (IL-18) were determined by ELISA kits when they were first admitted to the hospital. Left ventricular ejection fraction (LVEF) was measured by echocardiogram. Rehospitalization status within 1 year after the first hospitalization was also recorded.The plasma levels of sFKN, BNP, and IL-18 in patients with CHF were significantly higher than in the control group (P < 0.05). The concentrations of sFKN and BNP were increased with the severity of heart failure classified by NYHA classification (P < 0.05). There were no statistical differences among all CHF subgroups classified by etiology (P > 0.05). Plasma sFKN level in CHF group was positively correlated with BNP (r = 0.441, P < 0.001) and IL-18 (r = 0.592, P < 0.001). Receiver operating characteristic curve analysis showed that area under the curve values of FKN, BNP, and IL-18 were 0.885 (95%CI: 0.810 to 0.960, P < 0.001), 0.889 (95%CI: 0.842 to 0.956, P < 0.001), and 0.878 (95%CI: 0.801-0.954, P < 0.001), respectively. The concentrations of sFKN and BNP were increased in patients readmitted more than once within 1 year (P < 0.05).

NR4A1 retards adipocyte differentiation or maturation via enhancing GATA2 and p53 expression.

Nuclear receptor subfamily 4 group A member 1 (NR4A1) is an orphan nuclear receptor with diverse functions. It has been reported that NR4A1, as a transcriptional activator, is implicated in glucose and lipid metabolism. The aim of this study was to investigate the regulatory role of NR4A1 in adipogenesis and explore the underlying mechanisms. Quantitative real-time PCR and Western blotting were used to analyse the expression of genes involved in synthesis and mobilization of fats in vivo and in vitro. Dual-luciferase reporter assay was conducted to study the regulatory mechanisms of NR4A1. Our data from in vivo study confirmed that NR4A1 knockout (KO) mice fed with high-fat diet were more prone to obesity, and gene expression levels of PPARγ and FAS were increased in KO mice compared to controls; our data from in vitro study showed that NR4A1 overexpression in 3T3-L1 pre-adipocytes inhibited adipogenesis. Moreover, NR4A1 enhanced GATA binding protein 2 (GATA2) expression, which in turn inhibited peroxisome proliferator-activated receptor γ (PPARγ); NR4A1 inhibited sterol regulatory element binding transcription factor 1 (SREBP1) and its downstream gene fatty acid synthase (FAS) by up-regulating p53. NR4A1 inhibits the differentiation and lipid accumulation of adipocytes by enhancing the expression of GATA2 and p53.

The nationwide impact of injury-related deaths on average life expectancy in China.

To expand the evidence base to inform future public policy aimed at accident prevention, we investigated the impact of different categories of injury on average life expectancy in China. We used data from the National Death Cause Registration Information System and National Maternity and Children Health Surveillance databases, as well as 2010 population data from the National Bureau of Statistics. We then calculated the average life expectancy of the Chinese population, in addition to life expectancy after eliminating injury-related mortality. The average life expectancy of the Chinese population in 2010 was 74.93 years. After eliminating deaths due to injuries, the fourth leading cause of mortality in China, average life expectancy increased by 1.36 years. When this was broken down by population sub-groups, these gains were 1.76 and 0.79 years in men and women, 0.94 and 1.56 years in urban and rural residents, and 1.11, 1.30, and 1.67 years for residents in the Eastern, Central and Western regions respectively. After eliminating all categories of injury, the average life expectancy of the Chinese population was found to increase by 1.36 years. This figure was higher for males and residents of rural areas and Western China.

Effects of Xiaoyao San on exercise capacity and liver mitochondrial metabolomics in rat depression model.

Objective: This study aimed to investigate the therapeutic effects of Xiaoyao San (XYS), a herbal medicine formula, on exercise capacity and liver mitochondrial metabolomics in a rat model of depression induced by chronic unpredictable mild stress (CUMS). Methods: A total of 24 male SD rats were randomly divided into four groups: control group (C), CUMS control group (M), Venlafaxine positive treatment group (V), and XYS treatment group (X). Depressive behaviour and exercise capacity of rats were assessed by body weight, sugar-water preference test, open field test, pole test, and rotarod test. The liver mitochondria metabolomics were analyzed by using liquid chromatography-mass spectrometry (LC-MS) method. TCMSP database and GeneCards database were used to screen XYS for potential targets for depression, and GO and KEGG enrichment analyses were performed. Results: Compared with C group, rats in M group showed significantly lower body weight, sugar water preference rate, number of crossing and rearing in the open field test, climbing down time in the pole test, and retention time on the rotarod test (P < 0.01). The above behaviors and exercise capacity indices were significantly modulated in rats in V and X groups compared with M group (P < 0.05, 0.01). Compared with C group, a total of 18 different metabolites were changed in the liver mitochondria of rats in M group. Nine different metabolites and six metabolic pathways were regulated in the liver mitochondria of rats in X group compared with M group. The results of network pharmacology showed that 88 intersecting targets for depression and XYS were obtained, among which 15 key targets such as IL-1ß, IL-6, and TNF were predicted to be the main differential targets for the treatment of depression. Additionally, a total of 1 553 GO signaling pathways and 181 KEGG signaling pathways were identified, and the main biological pathways were AGE-RAGE signaling pathway, HIF-1 signaling pathway, and calcium signaling pathway. Conclusion: XYS treatment could improve depressive symptoms, enhance exercise capacity, positively regulate the changes of mitochondrial metabolites and improve energy metabolism in the liver of depressed rats. These findings suggest that XYS exerts antidepressant effects through multi-target and multi-pathway.

A unique insight for Xiaoyao San exerts antidepressant effects by modulating hippocampal glucose catabolism using stable isotope-resolved metabolomics.

ETHNOPHARMACOLOGICAL RELEVANCE: In traditional Chinese medicine (TCM) theory, depression is an emotional disease, which is thought to be related to stagnation of liver qi and dysfunction of the spleen in transport. Xiaoyao San (XYS) is considered to have the effects of soothing liver-qi stagnation and invigorating the spleen. The spleen has the function to transport and transform nutrients. The liver has also termed the center of energy metabolism in the body. Therefore, exploring the antidepressant effects of XYS from the perspective of energy metabolism may reveal new findings. AIM OF THE STUDY: Glucose catabolism is an important part of energy metabolism. In recent years, several researchers have found that XYS can exert antidepressant effects by modulating abnormalities in glucose catabolism-related metabolites. The previous research of our research group found that the hippocampus glucose catabolism was disordered in depression. However, the antidepressant potential of XYS through modulating the disorders of hippocampal glucose catabolism and the specific metabolic pathways and targets of XYS action were still unknown. The aim of this study was to address the above scientific questions. MATERIALS AND METHODS: In this research, the CUMS (chronic unpredictable mild stress) model was used as the animal model of depression. The antidepressant effect of XYS was evaluated by behavioral indicators. The specific pathways and targets of XYS modulating the disorders of glucose catabolism in the hippocampus of CUMS rats were obtained by stable isotope-resolved metabolomics. Further, the isotope tracing results were also verified by molecular biology and electron transmission electron microscopy. RESULTS: The results demonstrated that XYS pretreatment could significantly improve the depressive symptoms induced by CUMS. More importantly, it was found that XYS could modulate the disorders of glucose catabolism in the hippocampus of CUMS rats. Stable isotope-resolved metabolomics and enzyme activity tests showed that Lactate dehydrogenase (LDH), Pyruvate carboxylase (PC), and Pyruvate dehydrogenase (PDH) were targets of XYS for modulating the disorders of glucose catabolism in the hippocampus of CUMS rats. The Succinate dehydrogenase (SDH) and mitochondrial respiratory chain complex V (MRCC-Ⅴ) were targets of XYS to improve abnormal mitochondrial oxidative phosphorylation in the hippocampus of CUMS rats. XYS was also found to have the ability to improve the structural damage of mitochondria and nuclei in the hippocampal caused by CUMS. CONCLUSIONS: This study was to explore the antidepressant effect of XYS from the perspective of glucose catabolism based on a strategy combining stable isotope tracing, molecular biology techniques, and transmission electron microscopy. We not only obtained the specific pathways and targets of XYS to improve the disorders of glucose catabolism in the hippocampus of CUMS rats, but also revealed the specific targets of the pathways of XYS compared with VLF.

Prognosis-related metabolic genes in the development of colorectal cancer progress and perspective.

Colorectal cancer (CRC) is one of the most commonplace malignant tumors in the world. The occurrence and development of CRC are involved in numerous events. Metabolic reprogramming is one of the hallmarks of cancer and is convoluted and associated with carcinogenesis. Lots of metabolic genes are involved in the occurrence and progression of CRC. Study methods combining tumor genomics and metabolomics are more likely to explore this field in depth. In this mini-review, we make the latest progress and future prospects into the different molecular mechanisms of seven prognosis-related metabolic genes, we screened out in previous research, involved in the occurrence and development of CRC.

A bibliometric analysis of ferroptosis, necroptosis, pyroptosis, and cuproptosis in cancer from 2012 to 2022.

This study aims to visualize research hotspots and trends of "ferroptosis in cancer", "necroptosis in cancer", "pyroptosis in cancer", and "cuproptosis in cancer" through a bibliometric analysis to facilitate understanding of future developments in basic and clinical research and to provide a new perspective on cancer treatment. From January 1, 2012 to October 31, 2022, in the field of "ferroptosis in cancer", a total of 2467 organizations from 79 different countries published 3302 articles. 2274 organizations from 72 different countries published 2233 articles in the field of " necroptosis in cancer". 1366 institutions from 58 different countries contributed 1445 publications in the field of "pyroptosis in cancer". In the field of " cuproptosis in cancer", the number of articles published in the last 10 years is relatively low, with a total of 109 articles published by 116 institutions from four different countries. In the field of "ferroptosis in cancer", Tang Daolin had published 66 documents, ranked the first, while Dixon SJ is the most cited author, cited 3148 times; In the fields of "necroptosis in cancer", Vandenabeele peter had published 35 papers and Degterev had been cited 995 times, ranked the first, respectively; Kanneganti thirumala-devi had published 24 papers, is the highest number of publications in the fields of "pyroptosis in cancer", while Shi JJ was the most cited author with being cited 508 times. Both Huang Yan and Wang Tao published three papers and tied for first place and Tsvetkov p ranks first with being cited 107 times in "cuproptosis in cancer". "Cell", "Cell", "Nature", and "Science" was the most frequently co-cited journal on "ferroptosis in cancer", "necroptosis in cancer", "pyroptosis in cancer", and "cuproptosis in cancer", respectively. Further exploration of inhibitors of different Programmed cell death (PCD) and their targeted therapies are potential treatment options for cancer, but more direct clinical evidence as well as higher level clinical trials remain to be explored. Further clarification of the mechanisms of crosstalk between these PCDs may provide effective cancer treatments. And the role of different types of PCDs, especially the novel ones discovered, in cancer can be expected to remain a hot topic of research in the cancer field for quite some time to come.

A novel insight for high-rate and low-efficiency glucose metabolism in depression through stable isotope-resolved metabolomics in CUMS-induced rats.

BACKGROUND: Existing research has suggested that depression results in disorders of glucose metabolism in the organism which causing insufficient energy supply. However, the overall changes in glucose metabolism that arise from depression have not been clarified. METHODS: In this study, the depression-like behavior in chronically unpredictable mild stressed rats was investigated, and the fate of glucose was tracked through isotope tracing and mass spectrometry, with a focus on metabolite changes in cecal contents. RESULTS: As indicated by the results, the isotopic results of cecal contents can indicate the metabolic end of the organism. Moreover, the TCA cycle activity was notably reduced, and the gluconeogenesis pathway was abnormally up-regulated in the CUMS-induced rats. The organism expedited other glucose metabolism pathways to make up for the insufficiency of energy. As a result, the activity of the inefficient glycolysis pathway was increased. LIMITATIONS: Existing research has only investigated the metabolism of 13C-glucose, and lipids and proteins have been rarely explored. CONCLUSIONS: The chronic unpredictable mild stress can inhibit the entry of pyruvate into mitochondria in SD rats, such that the activity of TCA is reduced, and insufficient energy supply is caused. The organism is capable of expediting other glucose metabolism rate pathways to make up for the insufficiency of energy, whereas it still cannot compensate for the loss of energy. As a result, CUMS-induced rats exhibited high-rate and low-efficiency glucose metabolism.

Serum metabolomic responses to aerobic exercise in rats under chronic unpredictable mild stress.

This study analyzed the effects of aerobic exercise on endogenous serum metabolites in response to chronic unpredictable mild stress (CUMS) using a rat model, aiming to identify the metabolic regulatory pathways involved in the antidepressant effect resulted from a 28-day treadmill aerobic exercise intervention. The animals were randomly divided into four groups (n = 8): normal control, normal with aerobic exercise, CUMS control, and CUMS with aerobic exercise. Body weight, sucrose preference and open field tests were performed weekly during the intervention period for changes in depressant symptoms. Serum metabolic profiles obtained by using the LC-MS/MS metabolomics were analyzed to explore the regulatory mechanism for the effect of the aerobic exercise on depression. Behavior tests showed that the aerobic exercise resulted in a significant improvement in depression-like behavior in the CUMS rats. A total of 21 differential metabolites were identified as being associated with depression in serum metabolic profile, of which the aerobic exercise significantly modulated 15, mainly related to amino acid metabolism and energy metabolism. Collectively, this is the first study that LC-MS/MS techniques were used to reveal the modulatory effects of aerobic exercise on the serum metabolic profile of depressed rats and the findings further enriched our understanding of potential mechanisms of aerobic exercise interventions on depression.

New perspectives on chinese herbal medicine (zhong-yao) research and development.

Synthetic chemical drugs, while being efficacious in the clinical management of many diseases, are often associated with undesirable side effects in patients. It is now clear that the need of therapeutic intervention in many clinical conditions cannot be satisfactorily met by synthetic chemical drugs. Since the research and development of new chemical drugs remain time-consuming, capital-intensive and risky, much effort has been put in the search for alternative routes for drug discovery in China. This narrative review illustrates various approaches to the research and drug discovery in Chinese herbal medicine. Although this article focuses on Chinese traditional drugs, it is also conducive to the development of other traditional remedies and innovative drug discovery.

Case Report: Successful Outcome for Refractory Diabetic Peripheral Neuropathy in Patients With Ultrasound-Guided Injection Treatment.

Diabetic peripheral neuropathy is the most prevalent chronic complication of diabetes and is based on sensory and autonomic nerve symptoms. Generally, intensive glucose control and nerve nourishment are the main treatments. However, it is difficult to improve the symptoms for some patients; such cases are defined as refractory diabetic peripheral neuropathy (RDPN). In this paper, we present five patients treated with saline and mecobalamin by ultrasound-guided injection. The Visual Analog Scale and Toronto Clinical Scoring System were used to evaluate the symptoms, and the neuro-ultrasound scoring system and electrophysiological severity scale were evaluated by ultrasound and electrophysiological examination. In brief, ultrasound-guided hydrodissection may be a safe way to treat RDPN.

A Study of Antidepressant Effect and Mechanism on Intranasal Delivery of BDNF-HA2TAT/AAV to Rats with Post-Stroke Depression.

AIM: Post-stroke depression (PSD) is one of the most frequent neuropsychiatric disorders associated with stroke characterized by depression. The neuroplasticity hypothesis postulates that loss of brain-derived neurotrophic factor (BDNF) plays a major role in pathophysiology of PSD, and restoration of it may represent a critical mechanism underlying antidepressant efficacy. METHODS: In previous studies, we designed a new fusion gene, HA2TAT-BDNF, and cloned it into adenovirus associated virus (AAV) to construct the BDNF-HA2TAT/AAV for the delivery of BDNF to central nervous system (CNS) via nose-brain pathway. In this study, we used it to explore the antidepressant effects on PSD rats through behavioral and various histological methods, and try to find out its specific mechanism. RESULTS: Compared with the control group, the PSD+AAV group showed decreased sucrose consumption percentage in the sucrose preference test (SPT) (P < 0.001) and prolonged immobility in the forced swimming test (FST) (P=0.000). However, the nasal administration of BDNF-HA2TAT/AAV reversed results of these two behavioral tests (P>0.05, P >0.05), showing an adequate antidepressant effect. Compared with the control group, the concentrations of BDNF mRNA and protein in the hippocampus (P< 0.05, P < 0.01) and prefrontal cortex (P < 0.01, P < 0.01) of PSD rats both decreased. Increased BDNF mRNA and protein expression was observed in the prefrontal cortex (P > 0.05, P < 0.05), without notable change in the hippocampus (P < 0.05, P < 0.001) of PSD+BDNF rats. CONCLUSION: These results suggest that BDNF reductions in the prefrontal cortex and hippocampus are associated with the development of post-stroke depression, and that increased levels of BDNF in the prefrontal cortex could be used as a therapeutic target to treat PSD. However, the exact mechanism of BDNF action remains unclear in this regard, hindering the wider application of our method. We expect that our research could facilitate the exploration of pathogenesis and the new treatment method of PSD.

Impact of an educational program on reducing health care-associated meningitis or ventriculitis in the neurosurgical intensive care unit.

BACKGROUND: Health care-associated meningitis or ventriculitis (HCAMV) is a serious complication in different neurosurgical procedures and is associated with significant morbidity and mortality. We aimed to investigate whether an educational intervention program could reduce the HCAMV incidence in patients undergoing postsurgery external ventricular drainage and wound management. METHODS: We enrolled 2,904 patients from the neurosurgery intensive care unit between January 1, 2016 and December 31, 2018. The medical staff undertook an educational program developed by a multidisciplinary team on correct external ventricular drainage insertion and maintenance. The program included a 9-page self-learning module on the HCAMV risk factors and operational improvements. Each participant completed a pre- and posttest on their HCAMV knowledge. RESULTS: We found that 38 of 693 (5.48%) patients presented with infection in the preintervention 9-month period. In the 27-month postintervention period, the proportion of HCAMV incidence dropped by 52.19% (P < .0001) to 58 of 2,211 (2.62%) patients. CONCLUSIONS: Educational intervention aimed at the neurosurgery intensive care unit staff could significantly reduce the HCAMV rate, leading to a significant decline in the cost, morbidity, and mortality caused by neurosurgical procedures.

[Causes of death analysis in 133 congestive heart failure patients].

OBJECTIVE: To analyze the causes of death in patients with heart failure. METHODS: A total of 133 heart failure patients died during hospitalization in our hospital between January 2005 and December 2008 were enrolled in this study. Patients were divided to two groups: sudden death (group A, n = 73, 54.9%), chronic end-stage pump failure (group B, n = 55, 41.4%). The remaining 5 cases died of other causes were excluded from the final analysis. Clinical data (medical history, blood pressure, clinical manifestation, NYHA cardiac function class, left ventricular diameter of diastole, left ventricular ejection fraction, ventricular arrhythmias, drug therapy) of group A and B were analyzed. RESULTS: There were no significant differences in terms of medical history (including hypertension and diabetes), blood pressure, heart rate and the incidence of ventricular arrhythmia between the two groups. In group A, the NYHA functional class was mostly II or III grade, and LVEF value was significantly higher than that of group B. The incidence of angina pectoris was significantly higher in group A compared to group B. beta-blocker and angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker use was also significantly higher in group A than in group B, however, the treatment dose was significantly lower and therapy duration was significantly shorter in group A than in group B. There were significantly less patients received statins and anti-platelet aggregation drugs in group A compared to group B. CONCLUSION: In our patient cohort, sudden cardiac death often occurred in heart failure patients with NYHA cardiac function II to III grade, angina pectoris, probably due to the unstable coronary plaque and less statins and anti-platelet drug use in these patients.

[Effects of zearalenone on the proliferation of SK-N-SH human neuroblastoma cells].

OBJECTIVE: To investigate effects of zearalenone (ZEA) on the proliferation of SK-N-SH human neuroblastoma cells in vitro and its possible mechanism. METHODS: SK-N-SH cells were cultured in estrogen-free improved minimum essential medium and divided into 5 groups based on different treatments: group 1, without treatment; group 2, treated with 17beta-estradiol (E(2)); group 3, treated with ZEA; group 4, treated with both E(2) and ICI 182780; group 5, treated with both ZEA and ICI 182780. Absorbance value (AV) was determined at the time point of 0, 24, 48 and 72 hours, and DNA proliferation index (PI) at 72 hours. Flow cytometer, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) were employed to monitor cell apoptosis. RESULTS: At 24, 48 and 72 hours, the AV of group 3 were 1.39, 1.32, and 1.22 times to those of group 1, respectively. PI in group 3 was 1.43 times of that in group 1 at 72 hours. The results of group 2 were similar to those in group 3. At the same time, the growth of cells was inhibited by ICI 182780 despite the presence of E(2) and ZEA. Apoptosis cells were abundant in group 1 and ICI 182780 groups, but little in E(2) and ZEA groups. CONCLUSION: ZEA might promote the proliferation of SK-N-SH cells to a level similar to that of E(2), which might probably be brought about via estrogen receptor pathways and depressing apoptosis.

Increased methylation of glucocorticoid receptor gene promoter 1F in peripheral blood of patients with generalized anxiety disorder.

Previous findings on the dysfunction of hypothalamic-pituitary-adrenal (HPA) axis in generalized anxiety disorder (GAD) are controversial, and the molecular mechanisms underlying such dysfunction remain unclear. We analyzed the methylation status of the NR3C1 1F promoter and the expression of glucocorticoid receptor-α isoform (GRα) in peripheral blood mononuclear cells (PMBCs), the basal cortisol level in serum, and a functional neuroendocrine marker for GR sensitivity in the PMBCs in 64 patients with current GAD and 85 healthy controls. We found that patients with GAD had significantly elevated levels of morning basal serum cortisol (P < 0.0001) and diminished GR sensitivity in the PBMCs (P < 0.0001) compared with healthy controls. The overall methylation levels across NR3C1 1F promoter (P < 0.0001) and percent methylation at each of the 5 CpG sites including CpG12, 21, 30, 31, and 32 (P < 0.001) significantly increased. Accordingly, the mRNA levels of GRα significantly decreased (P < 0.0001) in the PBMCs in patients with GAD compared with healthy controls, with the effects specific in patients without childhood traumatic experience. Moreover, both serum basal cortisol levels and GR sensitivity in the PBMCs were negatively correlated with the overall methylation levels of the NR3C1 1F promoter (P < 0.0001) and positively correlated with GRα mRNA levels (P = 0.007) in the PBMCs. In sum, our study revealed the increased activity of the HPA axis and diminished peripheral glucocorticoid responsiveness of GR underlying episodes of GAD. Furthermore, such dysfunction of the HPA axis is associated with both increased DNA methylation of NR3C1 1F promoter and decreased GRα expression.