Traditional Chinese medicine for the prevention and treatment of presbycusis.

Background: Presbycusis/Age-related hearing loss is a sensorineural hearing loss caused by age-related deterioration of the auditory system that poses a risk to the physical and mental health of older people, including social and cognitive decline. It is also associated with frailty, falls and depression. There are currently no specific medications for the treatment of presbycusis, and early detection and intervention are key to its prevention and management. Traditional Chinese medicine interventions may offer opportunities in the prevention and treatment of presbycusis, but there is no relevant review. Methods: Literature searches was conducted using PubMed, Cochrane Library, Web of Science, and China National Knowledge Infrastructure (CNKI) databases for review articles, research articles, clinical trials, meta-analyses, and case studies in animal models and clinical trials. Results: We summarized the pathological mechanisms associated with presbycusis, related to genetic factors, environment, lifestyle, and molecular mechanisms related to oxidative stress, mitochondrial dysfunction, and inflammatory pathways. It is suggested that traditional Chinese medicine interventions may offer opportunities in the prevention and treatment of presbycusis using active ingredients of herbs or formulas, acupuncture, and exercise such as Tai Chi Chuan or Ba Duan Jin. The active ingredients of herbs or formulas may exert ear protection through Nrf2-mediated antioxidant pathways, NF-kB and NLRP3-related anti-inflammatory signaling, and regulation of autophagy. Conclusions: Here, we review the pathogenetic factors and pathological mechanisms involved in presbycusis, as well as traditional Chinese medicine interventions and treatments, with the aim of providing a new perspective for the prevention and treatment of hearing loss in the elderly and further improving their quality of life.

Curative effect of wrist-ankle acupuncture on postpartum abdominal pain and its influence on serum ß-EP level in puerpera. / è •è¸é’ˆæ²»ç–—äº§åŽè ¹ç—›çš„ä¸´åºŠç–—æ•ˆåŠå¯¹äº§å¦‡è¡€æ¸ ß-EP水平的影响.

OBJECTIVES: To observe the clinical effect of wrist-ankle acupuncture on postpartum abdominal pain and its influence on serum beta-endorphin (ß-EP) level in puerpera. METHODS: Seventy patients with postpartum abdominal pain were randomly divided into an acupuncture + herbal medication group (35 cases, 1 case dropped out) and a herbal medication group (35 cases, 2 cases dropped out). In the herbal medication group, 1 day after delivery, modified shenghua decoction was taken orally, one dose a day. In the acupuncture + herbal medication group, on the basis of herbal medication, wrist-ankle acupuncture was given at the Lower 1 and Lower 2 of the ankles, once daily. The duration of treatment was 3 days in the two groups. Before and after treatment, the score of visual analogue scale (VAS) for pain, serum ß-EP level, uterine fundus height, postpartum conditions of lochia and the uterine recovery at 42 days postpartum were compared in the patients of the two groups. RESULTS: At each time point after treatment (24 h, 48 h and 72 h after delivery), VAS scores and the uterine fundus height were reduced as compared with those before treatment (2 h after delivery) in the two groups (P<0.05); these indexes in the acupuncture + herbal medication group were lower than those in the herbal medication group (P<0.05). After treatment (72 h after delivery), ß-EP levels in the serum were increased when compared with those before treatment in the two groups (P<0.05), and the ß-EP level in the acupuncture + herbal medication group was higher than that in the herbal medication group (P<0.05). The volume of postpartum lochia discharge in the acupuncture + herbal medication group was higher than that in the herbal medication group (P<0.05), while the duration of postpartum lochia discharge and the total time of lochia discharge were shorter (P<0.05). Regarding the recovery of the uterus at 42 days postpartum, there was no statistical significance between the two groups (P>0.05). CONCLUSIONS: Wrist-ankle acupuncture obviously reduces the degree of postpartum abdominal pain and promotes the lochia discharge and the uterine recovery. The effect mechanism may be related to the up-regulation of serum ß-EP level and the increase of pain threshold so that analgesia is obtained.

ß-Carboline Alkaloids Resist the Aggregation and Cytotoxicity of Human Islet Amyloid Polypeptide.

ß-Carboline alkaloids have a variety of pharmacological activities, such as antitumor, antibiosis and antidiabetes. Harmine and harmol are two structurally similar ß-carbolines that occur in many medicinal plants. In this work, we chose harmine and harmol to impede the amyloid fibril formation of human islet amyloid polypeptide (hIAPP) associated with type 2 diabetes mellitus (T2DM), by a series of physicochemical and biochemical methods. The results indicate that harmine and harmol effectively prevent peptide fibril formation and alleviate toxic oligomer species. In addition, both small molecules exhibit strong binding affinities with hIAPP mainly through hydrophobic and hydrogen bonding interactions, thus reducing the cytotoxicity induced by hIAPP. Their distinct binding pattern with hIAPP is closely linked to the molecular configuration of the two small molecules, affecting their ability to impede peptide aggregation. The study is of great significance for the application and development of ß-carboline alkaloids against T2DM.

Banxia Xiexin decoction ameliorates dextran sulfate sodium (DSS)-induced ulcerative colitis via inhibiting serine-threonine protein kinase (Akt)/mitogen-activated protein kinase (MAPK) signaling pathway.

Banxia Xiexin decoction (BXD), a traditional Chinese medicine, was widely used in treating ulcerative colitis (UC). However, the active components of BXD and its mechanism in UC remain elusive. Therefore, we used network pharmacology in vivo experiments, molecular docking, and surface plasmon resonance strategy (SPR) to uncover BXD's potential mechanism. A UC rat model was established by orally administering 7% dextran sulfate sodium (DSS) in drinking water, BXD and palmatine were orally administered for 7 days. Network pharmacology was used to investigate the main bioactive components and crucial targets of BXD in treating UC. Molecular docking was used to investigate interactions between components and crucial targets, verifying the results by SPR. By network pharmacology predicting, 20 active components and 44 candidate anti-UC targets of BXD were identified, and the crucial proteins were screeded from PPI network, including extracellular regulated protein kinases (ERK), AKT1, and tumor necrosis factor-α (TNF). In addition, some key active components (palmatine, sexangularetin, and skullcapflavone II) were screened out from the active components-targets network. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment and in vivo experiments showed that protein-serine-threonine kinase (Akt)/MAPK pathway was involved in BXD treatment for UC; BXD and palmatine significantly ameliorated the severity of DSS-induced UC in rats. Our study might assist in further investigation of the active components in Chinese medicine.

[Effect of electroacupuncture combined with intradermal needling on simple obesity and serum intestinal lymphatic function-related factors].

OBJECTIVE: To assess the efficacy of the combined treatment with electroacupuncture (EA) and intradermal needling on simple obesity and explore its underlying effect mechanism. METHODS: A total number of 116 patients with simple obesity were randomized into an observation group (58 cases, 3 cases dropped off and 2 cases removed) and a control group (58 cases, 4 cases dropped off and 1 cases removed). Patients in the control group received EA at Zhongwan (CV 12), Quchi (LI 11), Zusanli (ST 36), Pishu (BL 20), Weishu (BL 21), etc., for 30 min each time. On the base of the intervention as the control group, the patients in the observation group received the intradermal needling at Tianshu (ST 25), Daheng (SP 15), Zusanli (ST 36), Shangjuxu (ST 37), Quchi (LI 11), Pishu (BL 20) and Weishu (BL 21). In each group, the intervention was given once every two days, 3 times a week, consecutively for 3 months. Before and after treatment, the obesity indexes (body mass [BW], body mass index [BMI], body fat percentage [F%], adiposity [A] and waist circumference [WC]), the serum intestinal lymphatic function-related factors (vascular endothelial growth factor C [VEGF-C], delta-like ligand 4 [DLL4], adrenomedullin [ADM]), blood lipid (total cholesterol [TC], triglyceride [TG] and low density lipoprotein-cholesterol [LDL-C]), and fasting plasma glucose (FPG), fasting insulin (FINS) and insulin resistance index (HOMA-IR) were observed in the patients of both groups; and the efficacy was assessed. RESULTS: The effective rate was 88.7% (47/53) in the observation group, higher than 71.7% (38/53) in the control group (P<0.05). After treatment, except FPG in the control group, BW, BMI, F%, A, WC, and the concentrations of serum VEGF-C, DLL4 and ADM, as well as TC, TG, LDL-C, FBG, FINS and HOMA-IR were all reduced compared with those before treatment in both groups (P<0.05). The reduction ranges of BW, BMI, F%, A, WC, and the concentrations of serum VEGF-C, DLL4 and ADM, and TC, LDL-C, FINS and HOMA-IR in the observation group were all larger than those in the control group (P<0.05). CONCLUSION: Electroacupuncture combined with intradermal needling can reduce body weight and lipid, and improve insulin resistance in treatment of simple obesity, which is achieved probably through inhibiting lymphangiogenesis and promoting lymphatic endothelial permeability.

Pharmacodynamic of cilostazol for anti-altitude hypoxia. / 西洛他唑抗高原缺氧的药效学评价.

OBJECTIVES: The plateau environment is characterized by low oxygen partial pressure, leading to the reduction of oxygen carrying capacity in alveoli and the reduction of available oxygen in tissues, and thus causing tissue damage. Cilostazol is a phosphodiesterase III inhibitor that has been reported to increase the oxygen release of hemoglobin (Hb) in tissues. This study aims to explore the anti-hypoxic activity of cilostazol and its anti-hypoxic effect. METHODS: A total of 40 male BALB/C mice were randomly divided into a low-dose cilostazol (6.5 mg/kg) group, a medium-dose (13 mg/kg) group, a high-dose (26 mg/kg) group, and a control group. The atmospheric airtight hypoxia experiment was used to investigate the anti-hypoxic activity of cilostazol and to screen the optimal dosage. Twenty-four male Wistar rats were randomly divided into a normoxia control group, a hypoxia model group, an acetazolamide (22.33 mg/kg) group, and a cilostazol (9 mg/kg) group. After 3 days of hypoxia in the 4 010 m high altitude, blood from the abdominal aorta was collected to determine blood gas indicators, the levels of IL-6 and TNF-α in plasma were determined by enzyme-linked immunosorbent assay, and the levels of malondialdehyde (MDA), superoxide dismutase (SOD), and glutataione (GSH) were measured. The degree of pathological damage for rat tissues was observed with HE staining. RESULTS: Compared with the control group, the survival time of mice in the low, medium, and high dose group of cilostazol was significantly prolonged, and the survival time of mice in the medium dose group was the longest, with an extension rate at 29.34%, so the medium dose was the best dose. Compared with the hypoxia model group, the P50 (oxygen partial pressure at Hb oxygen saturation of 50%) value of rats in the cilostazol group was significantly increased by 1.03%; Hb and Hct were significantly reduced by 8.46% and 8.43%, and the levels of IL-6 and TNF-α in plasma were reduced by 50.65% and 30.77%. The MDA contents in heart, brain, lung, liver, and kidney tissues were reduced by 37.12%, 29.55%, 25.00%, 39.34%, and 21.47%, respectively. The SOD activities were increased by 94.93%, 9.14%, 9.42%, 13.29%, and 20.80%, respectively. The GSH contents were increased by 95.24%, 28.62%, 28.57%, 20.80%, and 44.00%, respectively. The results of HE staining showed that compared with the hypoxia model group, cilostazol significantly improved the damage of heart, lung, and kidney tissues in rats after hypoxia. CONCLUSIONS: Cilostazol can significantly improve the oxidative stress and inflammatory reaction caused by rapid altitude hypoxia, and it has a significant protective effect on tissue damage caused by hypoxia, suggesting that it has obvious anti-hypoxic activity.

Protective effects and mechanisms of high-dose vitamin C on sepsis-associated cognitive impairment in rats.

Sepsis survivors present long-term cognitive deficits. The present study was to investigate the effect of early administration of high-dose vitamin C on cognitive function in septic rats and explore its possible cerebral protective mechanism. Rat sepsis models were established by cecal ligation and puncture (CLP). Ten days after surgery, the Morris water maze test was performed to evaluate the behavior and cognitive function. Histopathologic changes in the hippocampus were evaluated by nissl staining. The inflammatory cytokines, activities of antioxidant enzymes (superoxide dismutase or SOD) and oxidative products (malondialdehyde or MDA) in the serum and hippocampus were tested 24 h after surgery. The activity of matrix metalloproteinase-9 (MMP-9) and expressions of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1(HO-1) in the hippocampus were measured 24 h after surgery. Compared with the sham group in the Morris water maze test, the escape latency of sepsis rats was significantly (P = 0.001) prolonged in the navigation test, whereas the frequency to cross the platform and the time spent in the target quadrant were significantly (P = 0.003) reduced. High-dose vitamin C significantly decreased the escape latency (P = 0.01), but increased the time spent in the target quadrant (P = 0.04) and the frequency to cross the platform (P = 0.19). In the CLP+ saline group, the pyramidal neurons were reduced and distributed sparsely and disorderly, the levels of inflammatory cytokines of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-10 in the serum and hippocampus were significantly increased (P = 0.000), the blood brain barrier (BBB) permeability in the hippocampus was significantly (P = 0.000) increased, the activities of SOD in the serum and hippocampus were significantly (P = 0.000 and P = 0.03, respectively) diminished while the levels of MDA in the serum and hippocampus were significantly (P = 0.007) increased. High-dose vitamin C mitigated hippocampus histopathologic changes, reduced systemic inflammation and neuroinflammation, attenuated BBB disruption, inhibited oxidative stress in brain tissue, and up-regulated the expression of nuclear and total Nrf2 and HO-1. High-dose vitamin C significantly (P < 0.05) decreased the levels of tumor necrosis factor- (TNF)-α, interleukin-6 (IL-6), MDA in the serum and hippocampus, and the activity of MMP-9 in the hippocampus, but significantly (P < 0.05) increased the levels of SOD, the anti-inflammatory cytokine (IL-10) in the serum and hippocampus, and nuclear and total Nrf2, and HO-1 in the hippocampus. In conclusion, high-dose vitamin C can improve cognition impairment in septic rats, and the possible protective mechanism may be related to inhibition of inflammatory factors, alleviation of oxidative stress, and activation of the Nrf2/HO-1 pathway.

Single-cell RNA sequencing reveals that targeting HSP90 suppresses PDAC progression by restraining mitochondrial bioenergetics.

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers, which lacks effective treatment strategies. There is an urgent need for the development of new strategies for PDAC therapy. The genetic and phenotypic heterogeneity of PDAC cancer cell populations poses further challenges in the clinical management of PDAC. In this study, we performed single-cell RNA sequencing to characterize PDAC tumors from KPC mice. Functional studies and clinical analysis showed that PDAC cluster 2 cells with highly Hsp90 expression is much more aggressive than the other clusters. Genetic and pharmacologic inhibition of Hsp90 impaired tumor cell growth both in vitro and in vivo. Further mechanistic study revealed that HSP90 inhibition disrupted the interaction between HSP90 and OPA1, leading to a reduction in mitochondrial cristae amount and mitochondrial energy production. Collectively, our study reveals that HSP90 might be a potential therapeutic target for PDAC.

Corrigendum to "Monitoring unbound warfarin in drug combination therapy by pharmacokinetics and fluorospectrometry" [Chinese Herbal Medicines 11 (2019) 92-97].

[This corrects the article DOI: 10.1016/j.chmed.2018.10.002.].

Airway relaxation mechanisms and structural basis of osthole for improving lung function in asthma.

Overuse of ß2-adrenoceptor agonist bronchodilators evokes receptor desensitization, decreased efficacy, and an increased risk of death in asthma patients. Bronchodilators that do not target ß2-adrenoceptors represent a critical unmet need for asthma management. Here, we characterize the utility of osthole, a coumarin derived from a traditional Chinese medicine, in preclinical models of asthma. In mouse precision-cut lung slices, osthole relaxed preconstricted airways, irrespective of ß2-adrenoceptor desensitization. Osthole administered in murine asthma models attenuated airway hyperresponsiveness, a hallmark of asthma. Osthole inhibited phosphodiesterase 4D (PDE4D) activity to amplify autocrine prostaglandin E2 signaling in airway smooth muscle cells that eventually triggered cAMP/PKA-dependent relaxation of airways. The crystal structure of the PDE4D complexed with osthole revealed that osthole bound to the catalytic site to prevent cAMP binding and hydrolysis. Together, our studies elucidate a specific molecular target and mechanism by which osthole induces airway relaxation. Identification of osthole binding sites on PDE4D will guide further development of bronchodilators that are not subject to tachyphylaxis and would thus avoid ß2-adrenoceptor agonist resistance.

Huangjinya Black Tea Alleviates Obesity and Insulin Resistance via Modulating Fecal Metabolome in High-Fat Diet-Fed Mice.

SCOPE: Huangjinya is a light-sensitive tea mutant containing low levels of tea polyphenols. Currently, most studies focused on characteristics formation, free amino acid metabolism and phytochemical purification. The biological activity of Huangjinya black tea (HJBT) on metabolic syndrome regarding fecal metabolome modulation is unavailable and is studied herein. METHODS AND RESULTS: High-fat diet (HFD)-fed mice are treated with HJBT for 9 weeks, various metabolic biomarkers and fecal metabolites are determined. HJBT reduces adipogenic and lipogenic gene expression, enhances lipolytic gene expression, decreases adipocyte expansion, and prevents the development of obesity. HJBT reduces lipogenic gene expression, increases fatty acid oxidation-related genes expression, which alleviates liver steatosis. HJBT enhances glucose/insulin tolerance, increases insulin/Akt signaling, attenuates hyperlipidemia and hyperglycemia, prevents the onset of insulin resistance. HJBT modulates bile acid metabolism, promotes secondary/primary bile acid ratio; increases short-chain fatty acids production, promotes saturated and polyunsaturated fatty acids content; reduces carnitines and phosphocholines, but increases myo-inositol content; decreases branched-chain and aromatic amino acids content; increases the metabolite content related to pentose phosphate pathway. CONCLUSION: This study reported the association between fecal metabolome modulation and metabolism improvement due to HJBT administration, proposes HJBT as a dietary intervention for preventing obesity and metabolic disorders.

Comparative analysis of fecal metabolite profiles in HFD-induced obese mice after oral administration of huangjinya green tea extract.

To explore the impact of Huangjinya on metabolic disorders and host endogenous metabolite profiles, high-fat diet (HFD)-fed mice were administrated with Huangjinya green tea extract (HGT) at the dose of 150 or 300 mg/kg for 9 weeks. Epigallocatechin gallate was the main catechin derivative, followed by epigallocatechin and catechin presented in HGT, which contained high levels of free amino acids (50.30 ± 0.60 mg/g). HGT significantly alleviated glucose and insulin intolerance, reduced hepatic lipid accumulation and liver steatosis, and prevented white adipose tissue expansion in HFD-fed mice. Untargeted mass spectrometry-based metabolomics analysis revealed that HGT reduced the abundance of fecal branched-chain amino acids, aromatic amino acids, sphingolipids, and most acyl cholines, modulated bile acid metabolism by increasing chenodeoxycholate and reducing cholic acid content, and increased unsaturated fatty acids content. Fatherly, HGT activated insulin/PI3K/Akt and AMPK signaling pathways in the liver, reduced adipogenic and lipogenic genes expression, and promoted the genes expression related to lipolysis and adipocyte browning in white adipose tissue, contributed to improving metabolic syndrome in HFD-fed mice. The current study reported the impact of HGT supplementation on endogenous metabolite profiles, and highlights the positive roles of HGT in preventing diet-induced obesity and the related metabolic disorders.

Mapping Functional Connectivity from the Dorsal Cortex to the Thalamus.

Neural activity in the corticothalamic network is crucial for sensation, memory, decision, and action. Nevertheless, a systematic characterization of corticothalamic functional connectivity has not been achieved. Here, we developed a high throughput method to systematically map functional connections from the dorsal cortex to the thalamus in awake mice by combing optogenetic inactivation with multi-channel recording. Cortical inactivation resulted in a rapid reduction of thalamic activity, revealing topographically organized corticothalamic excitatory inputs. Cluster analysis showed that groups of neurons within individual thalamic nuclei exhibited distinct dynamics. The effects of inactivation evolved with time and were modulated by behavioral states. Furthermore, we found that a subset of thalamic neurons received convergent inputs from widespread cortical regions. Our results present a framework for collecting, analyzing, and presenting large electrophysiological datasets with region-specific optogenetic perturbations and serve as a foundation for further investigation of information processing in the corticothalamic pathway.

Electrophysiological findings during atrial fibrillation reablation: Extending from pulmonary vein reconnection to sequential bipolar voltage map information.

BACKGROUND: Left atrial substrate modification targeting low voltage zones (LVZ) is an ablation strategy that-in addition to pulmonary vein (PV) isolation-tries to eliminate arrhythmogenic mechanisms harbored in such tissue. Electrophysiological findings at reablation include (a) PV reconnection, (b) reconnection over previous substrate ablation, and (c) de-novo LVZ. OBJECTIVE: To study, prevalence and contribution of these arrhythmogenic electrophysiological entities in patients with atrial fibrillation (AF) recurrences. METHODS: Consecutive patients with highly symptomatic AF undergoing index and reablation were included (n = 113). In all patients' PV reconnection, reconnection over previous substrate ablation and spontaneous de-novo LVZ were quantitatively assessed and integrated into an individual reablation strategy. Follow-up was based on continuous device monitoring. RESULTS: At re-do procedure, 45 out of 113 (39.8%) patients showed PV reconnection as the only electrophysiological abnormality. Reconduction over previous lines was the only electrophysiological abnormality in 8 out of 113 (7.1%) patients. Spontaneous de-novo LVZ was the only electrophysiological abnormality in 12 out of 113 (10.6%) patients. Combined findings of PV reconnection, line reconduction, and/or spontaneous de-novo LVZ were seen in 40 out of 113 (35.4%) patients. No detectable electrophysiological abnormality was observed in 8 out of 113 (7.1%) patients. In univariate analysis, none of the tested electrophysiological characteristics independently predicted the outcome after re-do. CONCLUSIONS: In patients undergoing reablation, we could show that reconduction over previous substrate ablation as well as the development of new low voltage areas are frequent findings besides classical PV reconnection-without a clear leading cause for recurrences. These findings impact reablation strategies as well as the strategic focus during index procedures.

Role of inducibility and its dynamic change in the outcome of catheter ablation of atrial fibrillation: a single center prospective study.

BACKGROUND: The role of atrial arrhythmia inducibility as an endpoint of catheter ablation of atrial fibrillation (AF) has been a controversial subject in many studies. Our goal is to evaluate the significance of inducibility, the impact of multiple sites or protocols of stimulation or the change in inducibility status in a prospective study including patients with AF undergoing first catheter ablation. METHODS: We studied 170 consecutive patients with AF (62.9% paroxysmal) undergoing catheter ablation. All patients underwent two separate stimulation protocols before and after the ablation from the coronary sinus ostium and the left atrial appendage: burst pacing at 300, 250, 200 milliseconds (or until refractoriness) for 10 seconds and ramp decrementing from 300 to 200 milliseconds in increments of 10 milliseconds every three beats for 10 seconds. Inducibility was defined as any sustained AF or organized atrial tachycardia (AT) lasting >30 seconds. RESULTS: We had AF/AT inducibility in 55 patients at baseline compared to 36 following ablation. After a mean of 41, 3 months follow-up, 115 patients were free of AF. Inducibility before or after the ablation or change in inducibility status did not influence AF recurrence. There were no significant differences regarding paroxysmal or persistent patients with AF. CONCLUSIONS: Non-inducibility of atrial arrhythmia or change in inducibility status following pulmonary vein (PV) isolation and substrate modification are not associated with long-term freedom from recurrent arrhythmia. Therefore, the use of induction of an endpoint in AF ablation is limited.

Characterizing left ventricular mechanical and electrical activation in patients with normal and impaired systolic function using a non-fluoroscopic cardiovascular navigation system.

PURPOSE: Cardiac disease frequently has a degenerative effect on cardiac pump function and regional myocardial contraction. Therefore, an accurate assessment of regional wall motion is a measure of the extent and severity of the disease. We sought to further validate an intra-operative, sensor-based technology for measuring wall motion and strain by characterizing left ventricular (LV) mechanical and electrical activation patterns in patients with normal (NSF) and impaired systolic function (ISF). METHODS: NSF (n = 10; ejection fraction = 62.9 ± 6.1%) and ISF (n = 18; ejection fraction = 35.1 ± 13.6%) patients underwent simultaneous electrical and motion mapping of the LV endocardium using electroanatomical mapping and navigational systems (EnSite™ NavX™ and MediGuide™, Abbott). Motion trajectories, strain profiles, and activation times were calculated over the six standard LV walls. RESULTS: NSF patients had significantly greater motion and systolic strains across all LV walls than ISF patients. LV walls with low-voltage areas showed less motion and systolic strain than walls with normal voltage. LV electrical dyssynchrony was significantly smaller in NSF and ISF patients with narrow-QRS complexes than ISF patients with wide-QRS complexes, but mechanical dyssynchrony was larger in all ISF patients than NSF patients. The latest mechanical activation was most often the lateral/posterior walls in NSF and wide-QRS ISF patients but varied in narrow-QRS ISF patients. CONCLUSIONS: This intra-operative technique can be used to characterize LV wall motion and strain in patients with impaired systolic function. This technique may be utilized clinically to provide individually tailored LV lead positioning at the region of latest mechanical activation for patients undergoing cardiac resynchronization therapy. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov . Unique identifier: NCT01629160.

Prevalence and predictors of low voltage zones in the left atrium in patients with atrial fibrillation.

Aims: To describe the extent and distribution of low voltage zones (LVZ) in a large cohort of patients undergoing ablation for paroxysmal and persistent atrial fibrillation (AF), and to explore baseline predictors of LVZ in these patients. Methods and results: Consecutive patients who underwent a bipolar voltage map guided AF ablation, were enrolled. Voltage maps were conducted for each patient using 3-dimensional electroanatomical mapping system and LVZ were defined as areas of bipolar voltage < 0.5 mV. A total of 539 patients (309 male, age 65 ± 10 years) were included. Low voltage zones was present in 58 out of 292 patients with paroxysmal and 134 out of 247 persistent AF (P < 0.001). The area of LVZ was larger in patients with persistent as compare to paroxysmal AF, 5 cm2 (IQR 3-18.6) vs. 12.1 cm2 (IQR 3.6-28.5), P = 0.026, respectively. In the multivariate analysis age (OR 1.07, 95%CI 1.05-1.10, P < 0.001), female gender (OR 2.18, 95%CI 1.38-3.43, P = 0.001), sinoatrial node dysfunction (OR 3.90, 95%CI 1.24-12.21, P = 0.020), larger surface area of left atrium pr. cm2 (OR 1.01, 95%CI 1.00-1.02, P = 0.016), and persistent AF (OR 5.03, 95%CI 3.20-7.90, P<0.001) were associated with presence of LVZ. Conclusion: In a large cohort of patients undergoing ablation for AF, the prevalence of LVZ was higher and LVZ areas larger in patients with persistent as compared with paroxysmal AF. The most frequent localization of LVZ was anterior wall, septum and posterior wall. Presence of LVZ was associated with higher age, female gender, larger LA surface area, and sinoatrial node dysfunction.

Differential expressed analysis of Tripterygium wilfordii unigenes involved in terpenoid backbone biosynthesis.

Tripterygium wilfordii Hook. f. is the traditional medicinal plants in China. Triptolide, wilforgine, and wilforine are the bioactive compounds in T. wilfordii. In this study, the contents of three metabolites and transcription levels of 21 genes involved in three metabolites biosynthesis in T. wilfordii were examined using high-performance liquid chromatography and reverse transcription PCR after application of methyl jasmonate (MeJA) on hairy roots in time course experiment (3-24 h). The results indicated that application of MeJA inhibited triptolide accumulation and promoted wilforgine and wilforine metabolites biosynthesis. In hairy roots, wilforgine content reached 693.36 µg/g at 6 h after adding MeJA, which was 2.23-fold higher than control. The accumulation of triptolide and wilforine in hairy roots increased the maximum at 9 h, which was 1.3- and 1.6-folds more than the control. Most of the triptolide secretes into the medium, but wilforgine and wilforine cannot secrete into the medium. The expression levels of unigenes which involved terpenoid backbone biosynthesis exist the correlation with marker metabolites (triptolide, wilforgine and wilforine) after induction by MeJA, and can be then used to infer flux bottlenecks in T. wilfordii secondary metabolites accumulation. These results showed that these genes may have potential applications in the metabolic engineering of T. wilfordii metabolites production.

Mapping-guided characterization of mechanical and electrical activation patterns in patients with normal systolic function using a sensor-based tracking technology.

AIMS: In times of evolving cardiac resynchronization therapy, intra-procedural characterization of left ventricular (LV) mechanical activation patterns is desired but technically challenging with currently available technologies. In patients with normal systolic function, we evaluated the feasibility of characterizing LV wall motion using a novel sensor-based, real-time tracking technology. METHODS AND RESULTS: Ten patients underwent simultaneous motion and electrical mapping of the LV endocardium during sinus rhythm using electroanatomical mapping and navigational systems (EnSite™ NavX™ and MediGuide™, SJM). Epicardial motion data were also collected simultaneously at corresponding locations from accessible coronary sinus branches. Displacements at each mapping point and times of electrical and mechanical activation were combined over each of the six standard LV wall segments. Mechanical activation timing was compared with that from electrical activation and preoperative 2D speckle tracking echocardiography (echo). MediGuide-based displacement data were further analysed to estimate LV chamber volumes that were compared with echo and magnetic resonance imaging (MRI). The lateral and septal walls exhibited the largest (12.5 [11.6-15.0] mm) and smallest (10.2 [9.0-11.3] mm) displacement, respectively. Radial displacement was significantly larger endocardially than epicardially (endo: 6.7 [5.0-9.1] mm; epi: 3.8 [2.4-5.6] mm), while longitudinal displacement was significantly larger epicardially (endo: 8.0 [5.0-10.6] mm; epi: 10.3 [7.4-13.8] mm). Most often, the anteroseptal/anterior and lateral walls showed the earliest and latest mechanical activations, respectively. 9/10 patients had concordant or adjacent wall segments of latest mechanical and electrical activation, and 6/10 patients had concordant or adjacent wall segments of latest mechanical activation as measured by MediGuide and echo. MediGuide's LV chamber volumes were significantly correlated with MRI (R2= 0.73, P < 0.01) and echo (R2= 0.75, P < 0.001). CONCLUSION: The feasibility of mapping-guided intra-procedural characterization of LV wall motion was established. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov; Unique identifier: CT01629160.