[Analysis of occurrence and treatment of perioperative complete atrioventricular block by transcatheter aortic valve implantation].

Objective: To retrospectively analyze the occurrence and treatment of perioperative complete atrioventricular block (CAVB) by transcatheter aortic valve implantation (TAVI). Methods: A total of 65 patients who underwent TAVI via femoral artery in the Heart Center of Henan People's Hospital from October 2017 to May 2021 were enrolled. Perioperative data of patients were recorded. The patients were divided into two groups according to whether complete atrioventricular block was occurred during TAVI: complete atrioventricular block group (Group CAVB) and non-complete atrioventricular block group (Group NCAVB). Multivariate logistic regression model was used to analyze the risk factors of complete atrioventricular block during transcatheter aortic valve implantation. The incidence of perioperative complications were recorded. Results: The patients age was (69.1±7.3) years old. and there were 35 males and 30 femals. There were 15 patients in group CAVB with complete atrioventricular block and 50 patients in group NCAVB. Multivariate analysis showed that preoperative right bundle branch block [OR (95%CI) vs 3.325 (2.132-13.061), P=0.005] and severe aortic valve calcification [OR (95%CI) vs 1.271 (1.052-3.326), P=0.030] were independent correlative factors for CAVB during TAVI perioperative period. The implantation rate of permanent pacemaker in group CAVB was 73.3% (11 cases), which was higher than 6.0% (3 cases) in group NCAVB (P<0.001). Conclusions: It indicated that preoperative right bundle branch block and severe aortic valve calcification are correlative factors for complete atrioventricular block for TAVI. The implantation rate of permanent pacemaker in complete atrioventricular block group increased significantly.

Neuroprotective effects of α-lipoic acid on long-term experimental autoimmune encephalomyelitis.

OBJECTIVE: Experimental autoimmune encephalomyelitis (EAE) is an animal model commonly used in research on the acute phase of multiple sclerosis (MS), but studies on the pathology and pathogenesis of EAE with a long disease course are seldom conducted. Besides its antioxidant properties, the comprehensive mechanisms through which α-lipoic acid (LA) affects EAE remain obscure. We here conducted the study to explore the possible mechanisms. MATERIALS AND METHODS: In this study, the following methods were used for investigating the effects of LA on long-term EAE: hematoxylin-eosin staining (HE) and electron microscopic examinations of pathological changes; Western blotting of ß-amyloid precursor protein (ß-APP) and myelin basic protein (MBP); Enzyme-linked immunosorbent assay (ELISA) of tumor necrosis factor-α (TNF-α), transforming growth factor-ß (TGF-ß), superoxide dismutase (SOD), malondialdehyde (MDA) as well as flow cytometry of CD4+CD25+FoxP3+ regulatory T cells (Tregs). RESULTS: The results showed: (1) diverse pathological features of long-term relapsing-remitting EAE; (2) relatively increased MBP and reduced ß-APP expression in LA recipients 180 days after onset; (3) down-regulated TNF-α and up-regulated TGF-ß levels in LA recipients 7 days after onset; (4) lower MDA and higher SOD levels in LA recipients 180 days after onset; (5) increased Treg levels in LA recipients 7 days after onset. CONCLUSIONS: Aside from oxidative stress, LA possessed anti-inflammatory and immunomodulatory effects on EAE. LA might be a promising candidate for MS treatment.

Polysaccharide of Danggui Buxue Tang, an Ancient Chinese Herbal Decoction, Induces Expression of Pro-inflammatory Cytokines Possibly Via Activation of NFκB Signaling in Cultured RAW 264.7 Cells.

Danggui Buxue Tang (DBT) is an ancient Chinese herbal decoction containing two herbs, Astragali Radix (AR) and Angelicae Sinensis Radix (ASR): this herbal decoction serves as dietary supplement for women during menopause. DBT has been known to modulate immune responses, and its polysaccharide is proposed to be one of the active components. However, the polysaccharide-induced signaling in immune activation is not revealed. Here, we are identifying that the immune activation, triggered by DBT, could be mediated by polysaccharide. In cultured macrophages (RAW 264.7 cells), the application of polysaccharide-enriched extract of DBT significantly increased the expressions of mRNA and protein levels of interleukin-1ß, interleukin-6 and tumor necrosis factor. The induction was much stronger than the polysaccharide extract generated singly from AR, or from ASR, or from their simple mixture. The induced cytokine release in cultured macrophage was revealed to be triggered by activation of nuclear factor-kappa B (NF-κB) signaling, including (i) degradation of IkBα; (ii) translocation of NF-κB p65 from cytosol to nuclei; and (iii) activation of NF-κB transcriptional elements. These results verified the possible role of DBT polysaccharide in modulating immune responses. Copyright © 2016 John Wiley & Sons, Ltd.

Expression of globular form acetylcholinesterase is not altered in P2Y1R knock-out mouse brain.

Adenosine 5'-triphosphate (ATP), a neurotransmitter and a neuromodulator, has been shown to be co-stored and co-released with acetylcholine (ACh) at the pre-synaptic vesicles in vertebrate neuromuscular junction (nmj). Several lines of studies demonstrated that binding of ATP to its corresponding P2Y1 receptors (P2Y1R) in muscle and neuron regulated the post-synaptic gene expressions. Indeed, the expression of acetylcholinesterase (AChE) in muscle was markedly decreased in P2Y1R-/- (P2Y1R knock-out) mice. In order to search for possible role of P2Y1R in cholinergic function of the brain, the expression of globular form AChE was determined in the brain of P2Y1R-/- mice. In contrast to that in muscle, the amounts of AChE activity, AChE catalytic subunit, structure subunit PRiMA and the amount of ACh, in the brain were not, significantly, altered, suggesting the role of P2Y1R in neuron could have different function as that in muscle. However, the expressions of a series of neuronal development markers, i.e. neurofilaments, were reduced in P2Y1R-/- mouse brain, indicating P2Y1R may be involved in neuronal development process.

Danggui Buxue Tang, Chinese Herbal Decoction Containing Astragali Radix and Angelicae Sinensis Radix, Induces Production of Nitric Oxide in Endothelial Cells: Signaling Mediated by Phosphorylation of Endothelial Nitric Oxide Synthase.

Danggui Buxue Tang, an ancient Chinese herbal decoction containing Astragali Radix and Angelicae Sinensis Radix at the weight ratio of 5:1, is used to mitigate menopausal syndromes in women. The pharmacological properties of Danggui Buxue Tang have been illustrated in bone development, blood enhancement, and immune stimulation. Here, we extended the possible pharmacological role of Danggui Buxue Tang in cardiovascular function. In cultured human umbilical vein endothelial cells, the application of Danggui Buxue Tang induced the release of nitric oxide and the phosphorylation of endothelial nitric oxide synthase and Akt kinase in time- and dose-dependent manners. The robust activation of nitric oxide signaling, however, required the boiling of Astragali Radix and Angelicae Sinensis Radix together, i.e., as Danggui Buxue Tang instead of other herbal extracts. The Danggui Buxue Tang-induced phosphorylation of endothelial nitric oxide synthase and Akt kinase in human umbilical vein endothelial cells were fully blocked by treatment with an endothelial nitric oxide synthase inhibitor (L-NAME), a PI3K/Akt inhibitor (LY294002), and a Ca(2+) chelator (BAPTA-AM). In parallel, the blockage of endothelial nitric oxide synthase and Akt activation subsequently fully abolished the Danggui Buxue Tang-induced nitric oxide production.

Analysis of Heart Rate Variability and Cardiac Autonomic Nerve Remodeling in Streptozotocin-induced Diabetic Rats.

BACKGROUND: Diabetes mellitus (DM) is associated with both cardiovascular and autonomic nervous system dysfunction. Spectral analysis of heart rate variability (HRV) can be used to monitor changes in response to autonomic innervation and stimulation of the heart. In this study, conducted in a rat model of diabetes, HRV and changes in associated neurotransmitters and neurotrophic factors in the right atrium (RA) were monitored. METHODS: Diabetes was induced by streptozotocin (STZ) (60 mg/kg) in male Wistar rats, and HRV data were collected for 10 weeks by telemetry. Time and frequency domains of HRV data were analyzed using established metrics. The levels of various neural enzymes in the RA were determined by enzyme-linked immunosorbent assay (ELISA) and immunofluorescence to characterize autonomic nerve remodeling. Insulin and methycobal were used to block the effects of STZ. RESULTS: HRV parameters reflecting parasympathetic tone (SDNN, RMSSD and HF domains) sharply decreased in the first 3 weeks after STZ administration; measures of sympathetic tone (SDANN) increased. After a series of adjustments, cardiac autonomic nerve innervation reached a new equilibrium, with a dominance of sympathetic tone. RA levels of tyrosine hydroxylase (TH) increased, and choline acetyltransferase (ChAT) decreased, indicating autonomic nerve remodeling. Levels of growth associated protein-43 (GAP43) and nerve growth factor (NGF) increased during the period of diabetes-induced cardiac-nerve damage; however, the level of ciliary neurotrophic factor (CNTF) decreased. The physical condition and indexes of rats were normalized in different degree after administration of the insulin and methycobal, but not completely recovered. CONCLUSION: STZ-induced diabetes was associated with cardiac autonomic nerve dysfunction at both the organ and molecular levels. Parasympathetic nerves exhibited severe damage and/or weak recovery; remodeling of sympathetic nerves predominated during 10-weeks of STZ-induced diabetes.

Pathological analysis of extracapsular extension of metastatic lymph node and its potential impact on nodal clinical target volume in the radiotherapy of esophageal squamous cell carcinoma.

There is no consensus regarding the clinical target volume (CTV) margins which surround the gross tumor volume of metastatic lymph nodes (LN) in radiotherapy of esophageal squamous cell carcinoma (ESCC). This study retrospectively assessed the distance of extracapsular extension (ECE) of metastatic LN in thoracic ESCC and defined nodal CTV margins. Histological sections of metastatic LNs from 217 patients with thoracic ESCC were re-examined. The incidence and maximal distance of ECE of metastatic LNs were assessed. The relationships between ECE and clinicopathologic features were also investigated. The ECE was found in 37.3% of patients (81/217) and 23.1% of metastatic LN (159/689), and the incidences had a significant relationship with N stage and LN size. The median distance of ECE was 1.0 mm (range, 0.2-9.7 mm). The distance of ECE showed a positive correlation with LN size (Spearman's correlation coefficient = 0.419; p<0.001). The ECE distances of LN with <10 mm diameter were significantly smaller than LN with 10-30 mm diameter (p<0.001). The 95th percentiles of ECE distances for these two groups were 3 mm and 5 mm, respectively. For pathologic LN <10 mm in diameter, a 3-mm CTV margin appears to be adequate to encompass 95% of the microscopic ECE, and for LN 10-30 mm, a 5-mm CTV margin is recommended.

Wilson ratio of fermi gases in one dimension.

We calculate the Wilson ratio of the one-dimensional Fermi gas with spin imbalance. The Wilson ratio of attractively interacting fermions is solely determined by the density stiffness and sound velocity of pairs and of excess fermions for the two-component Tomonaga-Luttinger liquid phase. The ratio exhibits anomalous enhancement at the two critical points due to the sudden change in the density of states. Despite a breakdown of the quasiparticle description in one dimension, two important features of the Fermi liquid are retained; namely, the specific heat is linearly proportional to temperature, whereas the susceptibility is independent of temperature. In contrast to the phenomenological Tomonaga-Luttinger liquid parameter, the Wilson ratio provides a powerful parameter for testing universal quantum liquids of interacting fermions in one, two, and three dimensions.

Commensurate magnetic excitations induced by band splitting and Fermi surface topology in n-type cuprates.

The antiferromagnetic correlation plays an important role in high-Tc superconductors. Considering this effect, the magnetic excitations in n-type cuprates near the optimal doping are studied within the spin-density-wave description. The magnetic excitations are commensurate in the low-energy regime and further develop into spin-wave-like dispersion at higher energy, consistent with the inelastic neutron scattering measurements. We clearly demonstrate that the commensurability originates from the band splitting and Fermi surface topology. The commensurability is a normal state property and has nothing to do with d-wave superconductivity. Our results strongly suggest the essential role of antiferromagnetic correlations in the cuprates.

Electronic structure and magnetism of La4Ni3O8 from first principles.

The magnetic and electronic properties of La(4)Ni(3)O(8) are investigated by performing the full-potential linearized augmented plane wave method. The C-type antiferromagnetic spin ordering is preferred and a molecular correlated insulating state with high-spin Ni ions is found. Our results have proved that this insulating state is caused by a correlation effect and the strong interlayer interaction. Such strong interlayer coupling results from the high-spin occupation of Ni ions.

Structural, electronic, and dynamical properties of methane under high pressure.

The electronic structure and lattice dynamical properties of solid methane under high pressure have been studied based on density functional theory. We identify a cubic structure with space group of I43m below 14 GPa, the Pmn2(1) structure in the range of 14-21 GPa, and the P2(1)/c structure from 21 to 65 GPa. Our obtained Raman spectra of the P2(1)/c structure agree well with the typical Raman active modes in the available experimental data. At 65 GPa, methane undergoes a phase transition from P2(1)/c to Pnma. The structures with P2(1)/c and Pnma symmetries are insulating, and under any pressure studied methane always remains in molecular form. For Pnma phase, the orientational ordering of CH(4) molecules varies significantly at 79, 88, and 92 GPa, and by further increasing pressure the rotation of the molecules freezes and orientational ordering remains unchanged.

Anti-acetylcholinesterase activities of traditional Chinese medicine for treating Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive memory loss and cognitive impairment. It is the most common type of dementia in the ageing population due to a severe loss of cholinergic neurons in selected brain area. At present, acetylcholinesterase inhibitors (AChEI) are the first group of drugs approved by the FDA to treat mild to moderate Alzheimer's disease. Most of these drugs such as huperzine and galanthamine are originally isolated from plants. In this study, the AChE inhibitory activities from extracts of Chinese medicinal herbs that have traditionally been prescribed to treat insomnia and brain function disorders were examined in a 96-well plate assay based on Ellman's method. Both ethanol and aqueous extracts of 26 traditional Chinese medicinal herbs were tested. Inhibitory effects were expressed as the percentage of inhibition. For the herbal extracts that were shown to exert a significant inhibition, dose-dependent inhibitory assays were also performed. Ethanol and aqueous extracts of six herbs were found to have high AChE inhibitory activities in a dose-dependent manner. The IC(50) of these herbal extracts on inhibition of AChE are at around 5-85 microm/ml. The results of this study indicate that there is a great potential to search for novel usage of these medicinal herbs for the treatment of AD.

Intermediate coupling theory of electronic ferroelectricity.

We calculate the quantum phase diagram of an extended Falicov-Kimball model for one- and two-dimensional systems in the intermediate coupling regime. Even though some features of the phase diagram are obtained analytically, the main results are calculated with a constrained path Monte Carlo technique. We find that this regime is dominated by a Bose-Einstein condensation of excitons with a built-in electric polarization. The inclusion of a finite hybridization between the bands removes the condensate but reinforces the ferroelectricity.

Single hole motion in LaMnO3.

We study single hole motion in LaMnO3 using the classical approximation for Jahn-Teller lattice distortions, a modified Lang-Firsov approximation for dynamical breathing-mode phonons, and the self-consistent Born approximation (verified by exact diagonalization) for hole-orbital-excitation scattering. We show that in the realistic parameter space for LaMnO3, quantum effects of electron-phonon interaction are small. The quasiparticle bandwidth is about 2.2J in the purely orbital t-J model. It is strikingly broadened to be of order t by strong static Jahn-Teller lattice distortions even when the polaronic band narrowing is taken into account.

Chiral derivatives of 2-cyclohexylideneperhydro-4,7-methanoindenes, a novel class of nonsteroidal androgen receptor ligand: synthesis, X-ray analysis, and biological activity.

A series of 2-cyclohexylideneperhydro-4,7-methanoindene derivatives was synthesized as novel androgen receptor ligands. Asymmetric hydroboration of key intermediate 2 afforded single enantiomer alcohol derivatives (3aR)-3 and (3aS)-3 which could be further transformed to give 12 variously substituted keto alcohol target compounds. X-ray crystallography of the 4-bromobenzenesulfonyl ester (3aS)-13 was used to establish their absolute configuration. The binding of these compounds to the rat ventral prostate androgen receptor showed moderate affinity with IC(50) values of 1.2 microM and above but with substantial enantiomeric dependencies which varied in accordance to Pfieffer's rule. Surprisingly, the (3aS)-5alpha-alcohols displayed similar affinity to the (3aR)-5beta-alcohols, and molecular modeling suggested an alternative mode of binding for the (3aS) series. The three compounds with the best androgen receptor affinity were assayed in vivo for antiandrogenic and androgenic effects on sex accessory organ growth in castrated immature rats and were found to be ineffective.

The anxiogenic-like and anxiolytic-like effects of MDMA on mice in the elevated plus-maze: a comparison with amphetamine.

Many abused substances have been found to possess anxiogenic-like or/and anxiolytic-like properties. Discrepancies about the effects of MDMA, one of the most popular recreational drugs in recent years, on anxiety have been seen in the literature, and almost all of the data in this respect were derived from retrospective studies. The present study was thus designed to examine the drug's actions by using an animal model of anxiety, the elevated plus-maze test in male mice. Intraperitoneal MDMA at 1 mg/kg was ineffective, at 4 mg/kg decreased the percent of open arm entries (p < 0.01), and increased enclosed entries (p < 0.05), at 12 mg/kg had no significant effect, and at 20 mg/kg induced an increase of percent of open time (p < 0.01). As control drugs, amphetamine (0.5-4 mg/kg, i.p.) produced a dose-dependent, anxiogenic-like effect and diazepam (1 mg/kg, i.p.) induced an anxiolytic-like effect in the test. The results indicate that MDMA has anxiogenic-like properties at lower doses and anxiolytic-like at higher doses. The effects of MDMA and amphetamine on the mouse's responses to the plus-maze are compared. These findings provide a possible explanation for the controversies over MDMA's effects on anxiety in the literature.

Propylene glycol elicits anxiolytic-like responses to the elevated plus-maze in male mice.

Propylene glycol is a common solvent often contained in injectable solutions of anxiolytics of low water-solubility, such as diazepam (Valium) and pentobarbital (Nembutal). Several studies have shown that propylene glycol can have an inhibitory effect on the central nervous system. This study, using ethanol for comparison, further examined whether propylene glycol has anti-anxiety properties. Use of the elevated plus-maze test with male mice revealed that propylene glycol at doses (27 or 41 mmol kg-1, i.p.) which did not affect general activity, increased the number of entries into open arms and of head dips over open arm edges, indicative of an anxiolytic effect. In parallel, ethanol (14 and 27 mmol kg-1, i.p.) caused an increase in the amount of time spent on open arms and number of entries into open arms, accompanied by reduction of returns into closed arms. These doses of ethanol had no significant effect on motor ability. The results suggest that propylene glycol can act as an anxiolytic agent and that its anxiolytic potency is weaker than that of ethanol. In addition to previous warnings about the pharmacological effects of propylene glycol, the findings of this study alert investigators to the anxiolytic properties of the compound when it is employed as a solvent in anxiety or anxiety-related studies.

Serotonergic modulation of 3,4-methylenedioxymethamphetamine (MDMA)-elicited reduction of response rate but not rewarding threshold in accumbal self-stimulation.

In a fixed interval 5-s rate-frequency function paradigm with rats, 3,4-methylenedioxymethamphetamine (MDMA; 0.5, 2 and 4 mg/kg) dose-dependently decreased response rate for nucleus accumbens self-stimulation while both D-amphetamine (0.3 and 1 mg/kg) and cocaine (5 and 15 mg /kg) increased response rates. The highest doses of MDMA caused a cessation of responding in many of the rats tested, but in those rats that continued to respond a significant reduction in frequency threshold for self-stimulation was seen. Cocaine and amphetamine dose-dependently reduced frequency threshold in all rats tested. The non-specific serotonin antagonist, methysergide (5 mg/kg), reversed the inhibitory effects of MDMA on response rates and caused all rats to respond following MDMA (4 mg/kg). Methysergide did not affect MDMA's threshold-lowering properties and when administered alone methysergide had not effect on self-stimulation. These results suggest serotonergic involvement in the performance but not reinforcement-modulating effect of MDMA in the self-stimulation paradigm.

Contrasting effects of dopaminergic blockade on MDMA and d-amphetamine conditioned taste aversions.

A series of experiments examined the role of dopamine in the conditioned taste aversion (CTA) produced by 3,4-methylenedioxymethamphetamine (MDMA) and d-amphetamine in rats. The CTA induced by MDMA (1.0 mg/kg) was unaffected by the D1 dopamine receptor antagonist SCH23390 (0.3 or 0.6 mg/kg), the D2 receptor antagonist raclopride (0.3 or 0.6 mg/kg), SCH23390 and raclopride combined (both 0.3 or 0.6 mg/kg), or the D1/D2 receptor antagonist haloperidol (0.4 mg/kg). In contrast, the CTA produced by d-amphetamine (0.5 mg/kg) was attenuated by SCH23390 and raclopride combined (both 0.3 mg/kg) as well as haloperidol (0.4 mg/kg), but not by SCH23390 (0.3 or 0.6 mg/kg) or raclopride (0.3 or 0.6 mg/kg) alone. These results suggest that dopamine plays different roles in MDMA and amphetamine CTAs, and that the D1 and D2 receptors independently mediate the aversive effect of amphetamine in CTA.