Crosstalk between autophagy and the Keap1-Nrf2-ARE pathway regulates realgar-induced neurotoxicity.

ETHNOPHARMACOLOGICAL RELEVANCE: Realgar, the main component of which is As2S2 or As4S4 (≥90%), is a traditional Chinese natural medicine that has been used to treat carbuncles, furuncles, snake and insect bites, abdominal pain caused by parasitic worms, and epilepsy in China for many years. Because realgar contains arsenic, chronic or excessive use of single-flavor realgar and realgar-containing Chinese patent medicine can lead to drug-induced arsenic poisoning, but the exact mechanism underlying its toxicity to the central nervous system is unclear. AIM OF THE STUDY: The aim of this study was to clarify the mechanism of realgar-induced neurotoxicity and to investigate the effects of realgar on autophagy and the Keap1-Nrf2-ARE pathway. MATERIALS AND METHODS: We used rats treated with the autophagy inhibitor 3-methyladenine (3-MA) or adeno-associated virus (AAV2/9-r-shRNA-Sqstm1, sh-p62) to investigate realgar-induced neurotoxicity and explore the specific relationship between autophagy and the Keap1-Nrf2-ARE pathway (the Nrf2 pathway) in the cerebral cortex. Molecular docking analysis was used to assess the interactions among the Nrf2, p62 and Keap1 proteins. RESULTS: Our results showed that arsenic from realgar accumulated in the brain and blood to cause neuronal and synaptic damage, decrease exploratory behavior and spontaneous movement, and impair memory ability in rats. The mechanism may have involved realgar-mediated autophagy impairment and continuous activation of the Nrf2 pathway via the LC3-p62-Keap1-Nrf2 axis. However, because this activation of the Nrf2 pathway was not sufficient to counteract oxidative damage, apoptosis was aggravated in the cerebral cortex. CONCLUSIONS: This study revealed that autophagy, the Nrf2 pathway, and apoptosis are involved in realgar-induced central nervous system toxicity and identified p62 as the hub of the LC3-p62-Keap1-Nrf2 axis in the regulation of autophagy, the Nrf2 pathway, and apoptosis.

Clinical Efficacy of Wumeiwan Combined with Bazhentang in Treatment of Obese of Type 2 Diabetes Mellitus Patients with Qi and Yin Deficiencies, Phlegm and Stasis / 中国实验方剂学杂志

Objective: To observe the clinical efficacy of Wumeiwan combined with Bazhentang in the treatment of obesity type 2 diabetes with Qi and Yin deficiencies, phlegm and stasis. Method: Totally 60 patients with type 2 diabetes mellitus were randomly divided into observation group and control group, with 30 cases in each group. Observation group was given Wumeiwan combined with modified Bazhentang in addition to Western medicine (metformin hydrochloride). The control group was treated with traditional Western medicine (metformin hydrochloride). The course of treatment is eight weeks. Fasting blood sugar (FPG),2 hPG (2 hPG),glycosylated hemoglobin (HbA1c),total cholesterol (TC),triglycerin (TG),body mass index (BMI),safety indicators (three major routine,liver and kidney functions) and clinical symptoms before and after treatment between two groups were compared. The clinical efficacy of two groups was evaluated. Result: The observation group had an effective rate of 93.3% (28/30),which was significantly higher than 73.3% (22/30) of the control group,with statistically significant differences (PPPPConclusion: Modified Wumeiwan combined with Bazhentang is safe and effective in treating patients with type 2 diabetes mellitus with Qi and Yin deficiencies, phlegm and stasis,and can reduce blood sugar,blood lipid,BMI level and relieve clinical symptoms of patients, and so worth promotion.

Use of evidence-based pharmacotherapy for secondary prevention of coronary heart disease: a Chinese medicine hospital versus a general hospital / 中国结合医学杂志

<p><b>OBJECTIVE</b>To determine differences in adherence to secondary prevention guidelines (pharmacological interventions) among coronary heart disease (CHD) patients between a Chinese medicine (CM) hospital and a general hospital in a Chinese city.</p><p><b>METHODS</b>Medical records of 200 patients consecutively discharged from the CM hospital and the general hospital for CHD were reviewed to determine the proportions of eligible patients who received antiplatelet agents, β-blockers, angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) and statins at discharge. The effects of patient characteristics and hospital type on the use of these medicines were estimated using logistic regression models.</p><p><b>RESULTS</b>Patients discharged from the CM hospitals were older; more likely females; had greater history of hyperlipidemia, cerebrovascular diseases and less smoker (P<0.01 or P<0.05). They were less likely to receive coronary angiography and percutaneous coronary intervention, and had a longer length of stay than those discharged from the general hospital (P<0.01 or P<0.05). There were no significant differences in antiplatelet agents (96% vs. 100%, P=0.121) or statins (97.9% vs. 100%, P=0.149) use between the CM hospital and the general hospital. In multivariable analyses that adjusted for patient characteristics and hospital type, there was no significant difference in use of β-blockers between the CM hospital and the general hospital. In contrast, patients discharged from the CM hospital were less likely to receive ACE inhibitors/ARBs compared with those discharged from the general hospital (odds ratio: 0.3, 95% confidence interval: 0.105-0.854).</p><p><b>CONCLUSION</b>In this study, the CM hospital provides the same quality of care in CHD for prescribing evidence-based medications at discharge compared with another general hospital except for ACE inhibitors/ARBs use.</p>

A prospective study to evaluate the efficacy of an intracardiac electrogram-based atrioventricular and interventricular intervals optimization method in cardiac resynchronization therapy / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Cardiac resynchronization therapy (CRT) with biventricular pacing improves cardiac function, functional capacity and quality of life in selected patients with heart failure. The current study aimed to evaluate the efficacy of the intracardiac electrogram (IEGM)-based optimization method, QuickOpt(TM), in Chinese patients treated with CRT.</p><p><b>METHODS</b>Aortic time velocity integrals (AVTI) achieved at the sensed atrioventricular (AV), paced AV and interventricular (VV) interval settings recommended by both QuickOpt(TM) and standard echocardiographic optimization were measured in 101 patients. Consistency and the strength of the relationship between the two timing cycle optimization methods were assessed by intra-class correlation coefficient (ICC).</p><p><b>RESULTS</b>The ICC showed good agreement and correlation with what the AVTI achieved at the optimal sensed AV (ICC = 0.9683 (0.9535 - 0.9785)), paced AV (ICC = 0.9642 (0.9475 - 0.9757)) and VV (ICC = 0.9730 (0.9602 - 0.9817)) interval settings determined by the two optimization methods. The average time required by echocardiographic optimization and by QuickOpt(TM) were (78.32 ± 32.40) minutes and (1.98 ± 1.64) minutes respectively (P < 0.0001).</p><p><b>CONCLUSION</b>The QuickOpt(TM) algorithm provides a quicker, simpler and reliable alternative to the standard method for timing cycle optimization.</p>

Effects of dietary chitosan and Bacillus subtilis on the growth performance, non-specific immunity and disease resistance of cobia, Rachycentron canadum.

The present study was performed to investigate the effects of various levels of dietary Bacillus subtilis and chitosan on the growth performance, non-specific immunity and protection against Vibrio harveyi infection in cobia, Rachycentron canadum. Fish were fed with the control diet and six different experimental diets containing three graded levels of B. subtilis at 2 × 10(10) CFU g(-1) (0.0, 1.0, 2.0 g kg(-1) diet) for each of two levels of chitosan (3.0 and 6.0 g kg(-1) diet). The results of 8 weeks feeding trial showed that the survival rate ranged from 81.3% to 84.0% with no significant difference (P > 0.05). The SGR (%) in the fish fed with dietary treatments was significantly higher than that of the control fish except diet 6 group with 2.0 g kg(-1)B. subtilis and 3.0 g kg(-1) chitosan. The serum lysozyme activities were significantly higher in 6.0 g kg(-1) chitosan groups and no significant differences were observed among B. subtilis levels. The serum ACP activities were significantly higher in 3.0 g kg(-1) chitosan groups at 0.0 and 1.0 g kg(-1)B. subtilis levels; at low chitosan level, the cobia fed diets with 1.0 g kg(-1)B. subtilis had significantly higher serum ACP activity, but at high chitosan level, the cobia fed diets with 2.0 g kg(-1)B. subtilis had significantly higher serum ACP activity. The phagocytosis and respiratory burst activity in the fish fed with dietary treatments was significantly higher than that of the control fish except diet 3 group with 6.0 g kg(-1) chitosan. Moreover, fish fed the diet containing 2.0 g kg(-1)B. subtilis and 6.0 g kg(-1) chitosan had significantly higher post-challenge survival on the 7th day following V. harveyi infection and post-challenge survival showed clearly the synergistic effect of chitosan and B. subtilis. Based on these results, the combination of 1.0 g kg(-1)B. subtilis and 6.0 g kg(-1) chitosan is optimal for the growth, innate immunity and disease resistance of cobia with an 8-week oral administration.

A novel GAP460 biopolymer for use as a carrier in drug-delivery applications.

We synthesized a new non-toxic biopolymer (GAP460) containing γ,L-glutamic acid and aspartate (Asp). Conjugates of GAP460 and cisplatin exhibited a drug-carrying capacity of nearly 40%, 3-times higher than γ-PGA and dramatically decreasing the amount of biopolymer required for high-dose delivery. Treatment with GAP460-cisplatin conjugate (PACC) not only effectively inhibited tumor growth in nude mice, but also resulted in extended survival and lower nephrotoxicity, suggesting that GAP460 could be used as an effective carrier for drug delivery and that PACC may have potential therapeutic applications in the clinical treatment of cancer.