Total paeony glycoside relieves neuroinflammation to exert antidepressant effect via the interplay between NLRP3 inflammasome, pyroptosis and autophagy.

BACKGROUND: Depression is a common mental illness characterised by abnormal and depressed emotions. Total paeony glycoside (TPG) is a naturally active saponin extracted from the traditional Chinese medicine Radix Paeoniae rubra. However, the antidepressant and neuroinflammatory effects of TPG have not been thoroughly studied. PURPOSE: To study the therapeutic potential of TGP in depression caused by neuronal injury and neuroinflammation and to explore the mechanism of TGP and the relationship between the NLRP3 inflammasome, pyroptosis, and autophagy. STUDY DESIGN: A chronic unpredictable mild stress (CUMS)-induced depression model and a cell model of corticosterone (CORT)-induced hippocampal neuron injury were established to evaluate the therapeutic effects of TPG. METHODS: The composition of TPG was analysed using high-performance liquid chromatography and mass spectrometry. The effects of TPG and fluoxetine on depression-like behaviour, neuronal injury, neuroinflammation, pyroptosis, and mitochondrial autophagy in the mice models were evaluated. RESULTS: TGP alleviated depression-like behaviours in mice and inhibited hippocampal neuronal apoptosis. The secretion of inflammatory cytokines was significantly reduced in CORT-induced hippocampal neuron cells and in the serum of a mouse model of CUMS-induced depression. In addition, TGP treatment reduced the levels of NLRP3 family pyrin structural domains, including NLRP3, pro-caspase-1, caspase-1, and IL-1ß, and the pyroptosis related proteins such as GSDMD-N. Importantly, TPG attenuated mitochondrial dysfunction, promoted the clearance of damaged mitochondria, and the activation of mitochondrial autophagy, which reduced ROS accumulation and NLRP3 inflammasome activation. An in-depth study observed that the regulatory effect of TPG on autophagy was attenuated by the autophagy inhibitor 3-methyladenine (3-MA) in vitro and in vivo. However, administration of the caspase-1 inhibitor Belnacasan (VX-765) successfully inhibited pyroptosis and showed a synergistic therapeutic effect with TPG. CONCLUSION: These results indicate that TPG can repair neuronal damage by activating autophagy, restoring mitochondrial function, and reducing inflammation-mediated pyroptosis, thereby playing an important role in the alleviation of neuroinflammation and depression. This study suggests new potential drugs and treatment strategies for neuroinflammation-related diseases and depression.

Structural characterisation of deer sinew peptides as calcium carriers, their promotion of MC3T3-E1 cell proliferation and their effect on bone deposition in mice.

Deer sinew as a by-product has high collagen and nutritional value. This study focuses on its hydrolysate being used as a calcium carrier to develop functional foods. The chelation mechanism was analyzed by SEM, EDS, UV-vis, FTIR, and fluorescence spectroscopy and zeta potential analysis after using peptide-sequenced deer sinew peptides for chelation with calcium ions. The results showed that the chelation of deer sinew peptides with calcium ions occurs mainly at the O and N atoms of carboxyl, amino and amide bonds. In vitro and in vivo studies revealed that deer sinew peptide-calcium chelate (DSPs-Ca) promoted the proliferation of MC3T3-E1 cells without toxic side effects and increased the alkaline phosphatase activity. The DSPs-Ca group improved the bone microstructure induced by low calcium, as well as up-regulated the expression of genes responsible for calcium uptake in the kidneys, as evidenced by serum markers, bone sections, bone parameters, and gene expression analyses in low-calcium-fed mice. From the above, it can be concluded that DSPs-Ca is expected to be a calcium supplement food for promoting bone health.

Research Progress on Effects of Ginsenoside Rg2 and Rh1 on Nervous System and Related Mechanisms.

Neurological-related disorders are diseases that affect the body's neurons or peripheral nerve tissue, such as Parkinson's disease (PD) and Alzheimer's disease (AD). The development of neurological disorders can cause serious harm to the quality of life and functioning of the patient. The use of traditional therapeutic agents such as dopamine-promoting drugs, anticholinergic drugs, cholinesterase inhibitors, and NMDA receptor antagonists is often accompanied by a series of side effects such as drug resistance, cardiac arrhythmia, liver function abnormalities, and blurred vision. Therefore, there is an urgent need to find a therapeutic drug with a high safety profile and few side effects. Herbal medicines are rich in active ingredients that are natural macromolecules. Ginsenoside is the main active ingredient of ginseng, which has a variety of pharmacological effects and is considered to have potential value in the treatment of human diseases. Modern pharmacological studies have shown that ginsenosides Rg2 and Rh1 have strong pharmacological activities in the nervous system, with protective effects on nerve cells, improved resistance to neuronal injury, modulation of neural activity, resistance to cerebral ischemia/reperfusion injury, improvement of brain damage after eclampsia hemorrhage, improvement of memory and cognitive deficits, treatment of AD and vascular dementia, alleviation of anxiety, pain, and inhibition of ionic-like behavior. In this article, we searched the pharmacological research literature of Rg2 and Rh1 in the field of neurological diseases, summarized the latest research progress of the two ginsenosides, and reviewed the pharmacological effects and mechanisms of Rg2 and Rh1, which provided a new way of thinking for the research of the active ingredients in ginseng anti-neurological diseases and the development of new drugs.

Arabidopsis 3ß-Hydroxysteroid Dehydrogenases/C4-Decarboxylases Are Essential for the Pollen and Embryonic Development.

The biosynthesis of C27-29 sterols from their C30 precursor squalene involves C24-alkylation and the removal of three methyl groups, including two at the C4 position. The two C4 demethylation reactions require a bifunctional enzyme known as 3ß-hydroxysteroid dehydrogenase/C4-decarboxylase (3ßHSD/D), which removes an oxidized methyl (carboxylic) group at C4 while simultaneously catalyzing the 3ß-hydroxyl→3-keto oxidation. Its loss-of-function mutations cause ergosterol-dependent growth in yeast and congenital hemidysplasia with ichthyosiform erythroderma and limb defect (CHILD) syndrome in humans. Although plant 3ßHSD/D enzymes were well studied enzymatically, their developmental functions remain unknown. Here we employed a CRISPR/Cas9-based genome-editing approach to generate knockout mutants for two Arabidopsis 3ßHSD/D genes, HSD1 and HSD2, and discovered the male gametophytic lethality for the hsd1 hsd2 double mutation. Pollen-specific expression of HSD2 in the heterozygous hsd1 hsd2/+ mutant not only rescued the pollen lethality but also revealed the critical roles of the two HSD genes in embryogenesis. Our study thus demonstrated the essential functions of the two Arabidopsis 3ßHSD/D genes in male gametogenesis and embryogenesis.

Neuroprotective effect of total flavonoids in stems and leaves of Glycyrrhiza uralensis Fisch. on oxidative stress in HT-22 cells and Caenorhabditis elegans.

The Glycyrrhiza uralensis Fisch. is a common traditional Chinese medicine. However, its aerial part is currently not widely studied and used. Therefore, we aimed to investigate the neuroprotective effects of total flavonoids in aerial stems and leaves of Glycyrrhiza uralensis Fisch. (GSF) by an in vitro LPS-induced HT-22 cell model and an in vivo Caenorhabditis elegans (C. elegans) model. In this study, cell apoptosis was evaluated by CCK-8 and Hoechst 33258 staining in LPS-induced HT-22 cells. Meanwhile, ROS level, mitochondrial membrane potential (MMP), and Ca2+ level were detected by the flow cytometer. In vivo, C. elegans was also investigated the effect of GSF on lifespan, spawning, and paralysis. Moreover, the survival of C. elegans to oxidative stimuli (juglone and H2O2), and the nuclear translocation of DAF-16 and SKN-1 were evaluated. The results showed that GSF could inhibit LPS-induced HT-22 cell apoptosis. Moreover, GSF decreased the levels of ROS, MMP, Ca2+, and malondialdehyde (MDA) and increased the activities of SOD and CAT in HT-22 cells. Furthermore, GSF did not affect the lifespan and laying of eggs of C. elegans N2. However, it delayed paralysis in C. elegans CL4176 in a dose-dependent manner. Meanwhile, GSF increased the survival rate of C. elegans CL2006 after juglone and H2O2 treatment, increased SOD and CAT, and decreased MDA levels. Importantly, GSF promoted the nuclear translocation of DAF-16 and SKN-1 in C. elegans TG356 and LC333, respectively. Taken together, GSF can play a protective role in neuronal cells by inhibiting oxidative stress.

Network pharmacology and molecular docking analysis on the mechanism of Cordyceps militaris polysaccharide regulating immunity through TLR4/TNF-α pathwayss.

The role of polysaccharide components in the immune system, especially immunomodulatory effects, has received increasing attention. In this context, in this study, network pharmacology was adopted to explore the hypothesis of a multitarget mechanism for immune modulation by Chrysalis polysaccharides. A total of 174 common targets were screened by network pharmacology, with the main ones being TNF, MAPK3, CASP3, VEGFA, and STAT3, mostly enriched in the Toll pathway. The molecular docking results showed that the polysaccharide fraction of Chrysalis binds well to TNF proteins. Besides, in vitro cellular assays were performed to verify the ability of Chrysalis polysaccharides to regulate macrophage polarization and to screen for macrophage surface receptors. Furthermore, in vivo experiments were conducted to prove the activation of TLR4 and TNF-α protein expression in mice by Chrysalis polysaccharide.

Ecological stoichiometry of soil and microbial biomass carbon, nitrogen and phosphorus in tea plantations with different ages.

The implementation of ecological engineering projects such as "Green for Grain" causes great changes in the cycling and stoichiometry of soil carbon (C), nitrogen (N), and phosphorus (P), with consequences on soil microbial biomass stoichiometric characteristics. However, the temporal dynamics and coordination of soil-microbial C:N:P stoichiometry are still unclear. In this study, we examined the variations of soil-microbial biomass C, N, and P with the tea plantation ages (<5 a, 5-10 a, 10-20 a, 20-30 a, and >30 a) in a small watershed in the Three Gorges Reservoir Area. We analyzed the relationships between their stoichiometric ratios, microbial entropy (qMBC, qMBN, qMBP), and stoichiometric imbalance (ratios of soil C, N, P stoichiometry to microbial biomass C, N, P stoichiometry). The results showed that with the increases of tea plantation ages, soil and microbial biomass C, N, P contents, soil C:N and C:P significantly increased, while soil N:P declined; the microbial biomass C:P and N:P increased first and then decreased, but microbial biomass C:N did not change. Tea plantation ages significantly affected soil microbial entropy and soil-microbial stoichiometry imbalance (C:Nimb, C:Pimb, N:Pimb). With the increases of tea plantation ages, qMBC first decreased and then increased, while qMBN and qMBP went up in a fluctuating pattern. The C-N stoichiometry imbalance (C:Nimb) and C-P stoichiometry imbalance (C:Pimb) increased significantly, while the N-P stoichiometry imbalance (N:Pimb) showed a fluctuating rise. Results of the redundancy analysis showed that qMBC was positively correlated with soil N:P and microbial biomass C:N:P, but negatively correlated with microbial stoichiometric imbalance and soil C:N, C:P; whereas qMBN and qMBP showed the opposite situation. The microbial biomass C:P was most closely related to qMBC, while C:Nimb and C:Pimb had greater effects on qMBN and qMBP.

Analysis of Potential Mechanism of Herbal Formula Taohong Siwu Decoction against Vascular Dementia Based on Network Pharmacology and Molecular Docking.

Vascular dementia (VaD) is the second most prevalent dementia, which is attributable to neurovascular dysfunction. Currently, no approved pharmaceuticals are available. Taohong Siwu decoction (TSD) is a traditional Chinese medicine prescription with powerful antiapoptosis and anti-inflammatory properties. In this study, a network pharmacology approach together with molecular docking validation was used to explore the probable mechanism of action of TSD against VaD. A total of 44 active components, 202 potential targets of components, and 3,613 VaD-related targets including 161 intersecting were obtained. The potential chemical components including kaempferol, baicalein, beta-carotene, luteolin, quercetin, and beta-sitosterol involved in the inflammatory response, oxidative stress, and apoptosis might have potential therapeutic effects on the treatment of VaD. The potential core targets including AKT1, CASP3, IL1ß, JUN, and TP53 associated with cell apoptosis and inflammatory might account for the essential therapeutic effects of TSD in VaD. The results indicated that TSD protected against VaD through multicomponent and multitarget modes. Though the detailed mechanism of action of various active ingredients needs to be further illustrated, TSD still showed a promising therapeutic agent for VaD due to its biological activity.

[Effects of moss biocrusts on soil-microbe-ectoenzyme stoichiometric characteristics in a subtropical area]. / 亚热带苔藓结皮对土壤-微生物-èƒžå¤–é ¶åŒ–å­¦è®¡é‡ç‰¹å¾çš„å½±å“.

The formation and development of biological soil crusts (biocrusts) potentially affect the cycles and stoichiometric characteristics of soil carbon (C), nitrogen (N), and phosphorus (P). However, it is still unclear how soil microbes adapt to such changes. In this study, we examined the effects of moss-dominated biocrusts coverage (0, 1%-20%, 20%-40%, 40%-60%, 60%-80%, and 80%-100%) on soil physicochemical properties, soil microbial biomass, and ectoenzyme activities [ß-1, 4-glucosidase (BG), ß-1, 4-N-acetyl glucosidase (NAG), acid phosphatase (AP)] in two soil layers (0-5 and 5-10 cm) in the Three Gorges Reservoir area, as well as the covariations of soil-microbe-ectoenzyme C:N:P stoichiometry. The results showed that biocrust development significantly increased soil clay content, water stable aggregates, soil C, N, P contents, and significantly decreased soil bulk density and sand content. Microbial biomass C, N, P and ectoenzyme activities were significantly increased with increasing biocrust coverage. Soil depth did not affect soil physicochemical properties and C:N:P, but significantly affected microbial biomass, ectoenzyme activities, BG:AP and NAG:AP. Soil C, N and P contents were significantly positively correlated with microbial biomass and ectoenzyme activities, negatively correlated with BG:NAG, while positively correlated with NAG:AP, but had no significant correlation with microbial biomass C:N:P. There was no significant correlation between soil-microbe and microbial-ectoenzyme C:N:P. BG:NAG:AP decreased gradually with the increase of C:N:P stoichiometric imbalance between microbe and soil. This study indicated that the microbial metabolism was co-limited by N and P and with stronger P limitation. Microbes could maintain homeostasis by adjusting their own biomass and ectoenzyme C:N:P to adapt to changes in soil ecological stoichiometry driven by biocrust development.

[Study on antidepressant effect of total alkaloids of Fibraurea recisa].

This study aimed to investigate the antidepressant effects of total alkaloids of Fibraurea recisa in HT22 cells damaged by corticosterone (CORT) in vitro and in a mouse model of chronic unpredictable mild stress (CUMS) as well as the underlying mechanisms.In cellular experiments,the viability of CORT-damaged HT22 cells was detected using cell counting kit-8 (CCK-8),and the cell apoptosis was detected by Hoechst 33258 staining.In animal experiments,C57BL/6N mice were randomly divided into the control group,model group,low (100 mg·kg~(-1)),medium (200 mg·kg~(-1)) and high (400 mg·kg~(-1))-dose of total alkaloids of F.recisa groups,and positive control group.After 21 days of CUMS exposure,their depressive behaviors were observed in behavioral and Morris water maze tests.The serum levels of 5-hydroxytryptamine (5-HT),dopamine (DA),and norepinephrine (NE) were assessed by ELISA.The expression levels of apoptosis-related proteins Bcl-2,Bax and cleaved caspase-3 in HT22 cells and mouse hippocampus were detected by Western blot.The results suggested that total alkaloids of F.recisa alleviated the damage of HT22 cells induced by CORT in a dose-dependent manner.The Hoechst 33258 staining uncovered that total alkaloids of F.recisa better reduced the blue spots and inhibited cell apoptosis.The results of animal experiments showed that total alkaloids of F.recisa significantly improved the depression-like behaviors of mice and increased the serum levels of 5-HT,DA and NE as compared with those in the model group.The Western blot assays revealed a significant up-regulation of Bcl-2 protein expression,but an obvious reduction in Bax and cleaved caspase-3protein expression in the total alkaloids of F.recisa group.In conclusion,total alkaloids of F.recisa inhibited depression possibly by regulating the apoptosis-related protein expression or elevating the monoamine neurotransmitter levels in the brain.

A Novel Review of Homocysteine and Pregnancy Complications.

Homocysteine (Hct) is a substance produced in the metabolism of methionine. It is an essential type of amino acid gained from the daily diet. Methylenetetrahydrofolate reductase (MTHFR) gene mutation is related to elevated total homocysteine (tHct) expressions, in particular, among women with low folate intake. Hyperhomocysteinemia (HHct) is caused by numerous factors, such as genetic defects, lack of folic acid, vitamin B6 and B12 deficiency, hypothyroidism, drugs, aging, and renal dysfunction. Increased Hct in peripheral blood may lead to vascular illnesses, coronary artery dysfunction, atherosclerotic changes, and embolic diseases. Compared to nonpregnant women, the Hct level is lower in normal pregnancies. Recent studies have reported that HHct was associated with numerous pregnancy complications, including recurrent pregnancy loss (RPL), preeclampsia (PE), preterm delivery, placental abruption, fetal growth restriction (FGR), and gestational diabetes mellitus (GDM). Besides, it was discovered that neonatal birth weight and maternal Hct levels were negatively correlated. However, a number of these findings lack consistency. In this review, we summarized the metabolic process of Hct in the human body, the levels of Hct in different stages of normal pregnancy reported in previous studies, and the relationship between Hct and pregnancy complications. The work done is helpful for obstetricians to improve the likelihood of a positive outcome during pregnancy complications. Reducing the Hct level with a high dosage of folic acid supplements during the next pregnancy could be helpful for females who have suffered pregnancy complications due to HHct.

Protective Effects of 3,4-Seco-Lupane Triterpenes from Food Raw Materials of the Leaves of Eleutherococcus Senticosus and Eleutherococcus Sessiliflorus on Arrhythmia Induced by Barium Chloride.

As a traditional wild vegetable and food raw material, the leaves of Eleutherococcus senticosus and Eleutherococcus sessiliflorus are rich in 3,4-seco-lupane triterpenes, including chiisanoside (CSS), divaroside (DVS), sessiloside-A (SSA), and chiisanogenin (CSG). This study was conducted to evaluate the anti-arrhythmic effects of these 3,4-seco-lupane triterpenes. Evaluation of the cytotoxicity of compounds was performed by measuring cell viability and apoptosis with the CCK-8 assay. In vivo, arrhythmia was induced by rapid injection of BaCl2 via rat caudal vein. The occurrence time and duration of arrhythmias in rats were studied. The levels of SOD and MDA in serum, and Na+ -K+ -ATPase and Ca2+ -Mg2+ -ATPase in myocardial homogenate were detected by ELISA. The histopathological changes of rats myocardial were observed by HE staining. Changes in the expression of PKA and related proteins were detected by Western blot. The 3,4-seco-lupane triterpenes interactions with protein kinase A were analyzed by molecular docking. In the present study, we found that 3,4-seco-lupane triterpenes exhibited powerful anti-arrhythmic activity, especially DVS completely relieved the ventricular arrhythmia induced by BaCl2 . This study suggests that the leaves of E. senticosus and E. sessiliflorus might be used as functional food materials to prevent arrhythmia, and DVS can potentially be further developed as an anti-arrhythmic drug.

Diagnostic analysis of new quantitative parameters of low-dose dynamic myocardial perfusion imaging with CZT SPECT in the detection of suspected or known coronary artery disease.

The goal of this study is to explore and evaluate the diagnostic values of myocardial blood flow (MBF), myocardial flow reserve (MFR) and relative flow reserve (RFR) obtained with low-dose dynamic CZT SPECT for patients with suspected or known coronary artery disease (CAD). Fifty-seven consecutive patients who underwent low-dose dynamic CZT SPECT and CAG were enrolled. MBF, MFR and RFR were calculated on the vessel level with dedicated quantitative software, and the difference and correlation of each parameter was compared according to the reference standard of stenosis ≥ 50% or ≥ 75% on CAG, respectively. ROC curves were made by stress MBF (sMBF), rest MBF (rMBF), MFR and RFR. The optimal cut-off values and corresponding diagnostic efficacy were obtained and compared with each other. Results indicated that when stenosis ≥ 50% or ≥ 75% on CAG was used as the reference standard at the vessel level, there was no statistically significant difference in rMBF between the negative group and the positive group (P > 0.05), and the sMBF and MFR in positive groups were significantly lower than that in the negative group (all P < 0.05). There was a moderate to significant correlation between sMBF and MFR, sMBF and RFR, MFR and RFR (all P < 0.0001). These results indicate that low-dose dynamic CZT SPECT imaging can easily obtain the sMBF, MFR and RFR, and there is a good correlation among the three parameters, which has a certain diagnostic value for patients with suspected or known CAD, and is a useful supplement to the conventional qualitative or semi-quantitative diagnostic methods.

Cognitive-enhancing effects of fibrauretine on Aß1-42-induced Alzheimer's disease by compatibilization with ginsenosides.

Fibrauretine is the main active ingredient in rattan stems of Fibraurea recisa Pierre. The aim of this study was to evaluate the cognitive-enhancing effects and underlying molecular mechanisms of fibrauretine compatibilized with ginsenosides on Alzheimer's disease (AD) induced in mice with amyloid ß-protein (Aß1-42). The results showed that the spatial learning and memory abilities of AD mice were significantly enhanced after combined treatment with fibrauretine and ginsenosides using the Morris water maze test. The levels of acetylcholinesterase (AChE) and phosphorylated Tau protein (p-Tau) in brain tissue and the levels of nitric oxide (NO), malondialdehyde (MDA), and N-terminal pro-brain natriuretic peptide (NT-proBNP) in plasma were significantly increased in Aß1-42-induced AD mice, and these effects were reversed after combined treatment with fibrauretine and ginsenosides. By contrast, a significant increase in the levels of catalase (CAT), superoxide dismutase (SOD), choline acetyltransferase (ChAT) and glutathione peroxidase (GSH-Px) was observed in the combined treatment group. The results of haematoxylin and eosin (H&E) staining, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labelling (TUNEL) analysis, immunohistochemistry (IHC) and Western blot analysis showed that the apoptosis rate, Bax, nuclear factor kappa-B p65 (NF-κBp65), cleaved caspase-3 and cleaved caspase-9 expression levels were obviously decreased and that the Bcl-2 expression levels were significantly increased in the hippocampi of mice treated with fibrauretine and ginsenosides. The results of this study show that the ameliorative effect of fibrauretine against AD can be significantly enhanced by compatibilization with ginsenosides. The underlying molecular mechanisms of fibrauretine may be related to antioxidation and anti-apoptosis.

[Study advances in regulation effect of Tripterygium wilfordii and its extracts on innate immune system in rheumatoid arthritis cases].

Rheumatoid arthritis( RA) is an autoimmune disease characterized by chronic and aggressive polyarthritis. The innate immunity mechanism plays a key role in the pathogenesis of RA. Tripterygium wilfordii and its extracts have regulatory effects on innate immune cells including macrophages,dendritic cells,neutrophils,mast cells,NK cells,NKT cells,etc.,as well as a variety of innate immune molecules including cytokines,adhesion molecules,patterns recognition receptor( PRR) and the complement molecules,showing a regulatory effect in the pathogenesis of RA innate immunity. In this paper,the recent domestic and foreign researches on the pathogenesis of RA with innate immunity involved were reviewed and the research status of T. wilfordii and its extracts on the regulation of innate immunity involved in RA was summarized.

Weak direct current (DC) electric fields as a therapy for spinal cord injuries: review and advancement of the oscillating field stimulator (OFS).

Traumatic injury to the spinal cord remains a catastrophic event that has lifelong consequences. While decades of research have elucidated much of the pathophysiology associated with spinal cord injury (SCI), there still remains no clinically approved treatments for restoring lost sensorimotor function. The traditional dogma suggests central nervous system (CNS) neurons do not regenerate after injury but active areas of research aim to overcome this biological bottleneck. One particular approach using low-level direct current electric fields (DC EFs) appears especially promising based on a rich set of experimental data. This review highlights the biological basis for EF-induced regeneration and discusses the pre-clinical and clinical trials using the oscillating field stimulator (OFS)-a medical device designed to deliver DC EFs in vivo. I further report ongoing developments in our laboratory that refreshes the OFS concept with the hope of renewing interest in conducting additional clinical trials.

Electrophysiological characteristics and radiofrequency ablation of sustained monomorphic ventricular tachycardia in adult patients with isolated ventricular noncompaction.

PURPOSE: This study examined electrophysiological characteristics and outcomes of patients with sustained ventricular tachycardia (VT) in the setting of isolated ventricular noncompaction (IVNC). BACKGROUND: In patients with IVNC, VT has been associated with sudden cardiac death. However, the electrophysiological characteristics and optimal management of these VTs are only incompletely understood. METHODS: This retrospective cohort study assessed arrhythmia characteristics and outcomes in IVNC patients with sustained monomorphic VTs. Data were obtained from five academic centers covering the time period from January 1, 2006, to December 31, 2016, with a median follow-up of 40 months. RESULTS: Eighteen consecutive IVNC patients with sustained VTs (12 males [66%], mean age of 44.4 ± 16.9 years) were enrolled. Seven (39%) patients underwent VT ablation (five males, mean age of 43.3 ± 15.5 years) and nine (50%) patients received ICD therapy. Six of 18 patients (33%) died during a median follow-up of 40 months. Of these, three had ICDs, two had undergone VT ablation, and one had received only antiarrhythmic drugs. Among the seven patients with prior VT ablation, five VTs in the RV (three RVOT and one tricuspid annulus) and two LV VTs (one anterolateral papillary muscle and one inferolateral wall) were localized by 3-D mapping and successfully ablated. In six of seven ablation cases (85.7%), the VTs were distant from the noncompaction zone. VTs appeared to be focal in 57% (4/7) and macro-reentry in 43% (3/7) of patients based on 3-D mapping and entrainment studies. The success rate of VT ablation was 85.7% with one VT recurrence and two deaths during the mean follow-up of 54 (28-115) months. CONCLUSIONS: IVNC Patients with sustained VTs appear to have a poor prognosis despite receiving ICD or apparently successful VT ablation therapy. Further, most VTs appear to arise remote from the noncompaction zone. Whether these VTs were "idiopathic" or related to IVNC was uncertain.

[Advance in studies on pharmacokinetics of baicalin].

Scutellariae baicalensis is one of the most important traditional Chinese medicinal herbs, mainly distributed in Shandong and Hebei provinces. It has significant pharmacological effects such as antimicrobial activity, anti-inflammatory and antioxidation. Baicalin is one of its main effective components. However, baicalin's low bioavailability has restricted its clinical application. In recent decades, extensive studies have been carried out on the metabolism of baicalin in vivo at home and abroad. In order to provide scientific references for baicalin's further studies, this paper would not only review the advances in pharmacokinetics research of baicalin and Chinese herbal preparations containing baicalin, but also make a summary on research status of baicalin.

Effects of triptolide on hippocampal microglial cells and astrocytes in the APP/PS1 double transgenic mouse model of Alzheimer's disease.

The principal pathology of Alzheimer's disease includes neuronal extracellular deposition of amyloid-beta peptides and formation of senile plaques, which in turn induce neuroinflammation in the brain. Triptolide, a natural extract from the vine-like herb Tripterygium wilfordii Hook F, has potent anti-inflammatory and immunosuppressive efficacy. Therefore, we determined if triptolide can inhibit activation and proliferation of microglial cells and astrocytes in the APP/PS1 double transgenic mouse model of Alzheimer's disease. We used 1 or 5 µg/kg/d triptolide to treat APP/PS1 double transgenic mice (aged 4-4.5 months) for 45 days. Unbiased stereology analysis found that triptolide dose-dependently reduced the total number of microglial cells, and transformed microglial cells into the resting state. Further, triptolide (5 µg/kg/d) also reduced the total number of hippocampal astrocytes. Our in vivo test results indicate that triptolide suppresses activation and proliferation of microglial cells and astrocytes in the hippocampus of APP/PS1 double transgenic mice with Alzheimer's disease.

Current-distance relationships for peripheral nerve stimulation localization.

BACKGROUND: Successful peripheral nerve blocks require accurate placement of the injection needle tip before local anesthetic application. In this investigation, we experimentally reconstructed polarity-dependent (anode and cathode) stimulation maps using ex vivo and in vivo animal models. METHODS: A novel ex vivo configuration (muscle-nerve composite) was first used to probe both cathodic and anodic stimulation characteristics. The electrophysiology (compound nerve action potential, CAP) of rat sciatic nerve was recorded at varying stimulation (monopolar electrode) distances and intensities. We repeated this methodology with an open dissection rat model that was more analogous to the clinical setting. Resultant data from the current sweeps were plotted as a 3-dimensional distance-stimulus-CAP map. These plots depict the minimum stimulation currents required for nerve activation and describe the expected electrophysiological outcomes as a function of distance and input stimulus intensity. The stimulation maps provide positional information relevant to clinical procedures such as nerve localization during regional anesthesia. RESULTS: Cathodic stimulation produced a complex biphasic electrophysiological response. The CAP amplitude (with fixed current) increased as the electrode moved closer towards the nerve, but decreased upon close proximity or nerve contact. This phenomenon was dependent upon stimulation intensity and was observed in both ex vivo and in vivo models. Anodic stimulation produced a monotonic relationship, with the CAP increasing with closer electrode-to-nerve distances. Minimum extraneural activation thresholds were found to be 0.34 ± 0.11 mA (mean ± sd) and 0.63 ± 0.12 mA for cathode and anode stimulation, respectively. Intraneural thresholds were substantially lower, 0.12 ± 0.03 mA and 0.32 ± 0.09 mA, for cathode and anode, respectively. CONCLUSION: Cathodic stimulation may produce conduction block at close tip-to-nerve distances. In contrast, anodic stimulation elicited output characteristics that were predictable and more suitable for nerve localization. We believe anodic stimulation is a viable option at near-nerve distances, despite the increased current requirements. This hypothesis is a paradigm shift in stimulation nerve localization, which conventionally has been cathode based. The hypothesis should be clinically validated.