Costunolide ameliorates angiotensin II-induced atrial inflammation and fibrosis by regulating mitochondrial function and oxidative stress in mice: A possible therapeutic approach for atrial fibrillation.

Atrial fibrillation (AF) is a cardiac disease characterized by disordered atrial electrical activity. Atrial inflammation and fibrosis are involved in AF progression. Costunolide (COS) is a sesquiterpene lactone containing anti-inflammatory and anti-fibrotic activities. This study aims to explore the underlying mechanisms by which COS protects against AF. Male C57BL/6 mice (8- to 10-week-old) were infused with angiotensin (Ang) II for 3 weeks. Meanwhile, different doses of COS (COS-L: 10 mg/kg, COS-H: 20 mg/kg) were administered to mice by intragastric treatment. The results showed irregular and rapid heart rates in Ang II-treated mice. Moreover, the levels of inflammatory cytokines and fibrotic factors were elevated in mice. COS triggered a reduction of Ang II-induced inflammation and fibrosis, which conferred a protective effect. Mechanistically, mitochondrial dysfunction with mitochondrial respiration inhibition and aberrant ATP levels were observed after Ang II treatment. Moreover, Ang-II-induced excessive reactive oxygen species caused oxidative stress, which was further aggravated by inhibiting Nrf2 nuclear translocation. Importantly, COS diminished these Ang-II-mediated effects in mice. In conclusion, COS attenuated inflammation and fibrosis in Ang-II-treated mice by alleviating mitochondrial dysfunction and oxidative stress. Our findings represent a potential therapeutic option for AF treatment.

Network pharmacology- and molecular simulation-based exploration of therapeutic targets and mechanisms of heparin for the treatment of sepsis/COVID-19.

Critically infected patients with COVID-19 (coronavirus disease 2019) are prone to develop sepsis-related coagulopathy as a result of a robust immune response. The mechanism underlying the relationship between sepsis and COVID-19 is largely unknown. LMWH (low molecular weight heparin) exhibits both anti-inflammatory and anti-coagulating properties that result in a better prognosis of severely ill patients with COVID-19 co-associated with sepsis-induced coagulopathy or with a higher D-dimer value. Heparin-associated molecular targets and their mechanism of action in sepsis/COVID-19 are not well understood. In this work, we characterize the pharmacological targets, biological functions and therapeutic actions of heparin in sepsis/COVID-19 from the perspective of network pharmacology. A total of 38 potential targets for heparin action against sepsis/COVID-19 and 8 core pharmacological targets were identified, including IL6, KNG1, CXCL8, ALB, VEGFA, F2, IL10 and TNF. Moreover, enrichment analysis showed that heparin could help in treating sepsis/COVID-19 through immunomodulation, inhibition of the inflammatory response, regulation of angiogenesis and antiviral activity. The pharmacological effects of heparin against these targets were further confirmed by molecular docking and simulation analysis, suggesting that heparin exerts effective binding capacity by targeting the essential residues in sepsis/COVID-19. Prospective clinical practice evaluations may consider the use of these key prognostic indicators for the treatment of sepsis/COVID-19.Communicated by Ramaswamy H. Sarma.

Case report: A 9-year systematic treatment failure of a pulmonary tuberculosis patient.

Objective: To explore the reasons of failure in a case of pulmonary tuberculosis (PTB) after 9 years systematic treatment. Methods: We extracted the patients' treatment history, drug susceptibility testing (DST), Computed tomography (CT) images, and sequenced the isolated strains by whole gene sequencing (WGS). Results: Although most results of the phenotypical DSTs were consistent with the genotype DST, the occurrence of gene resistance to amikacin (AMK), capreomycin (CAP), moxifloxacin (MFX) was earlier than the phenotypical DST. Based on the continuously reversed results of phenotypical DSTs, CT images in different stages and WGS, it can be confirmed that the patient was infected with two different strains of Mycobacterium tuberculosis (M.TB). Moreover, severe cavities may be another factor leading to treatment failure. Conclusion: Given the suggestive effect of genotype DST is earlier than the phenotypical DST, so genotype DST can play a better guiding role in patients with MDR-TB. Additionally, for patients who have not been cured for a long time, medication should be more cautious and the role of WGS in drug resistance surveillance should be fully utilized.

TNFα activation and TGFß blockage act synergistically for smooth muscle cell calcification in patients with venous thrombosis via TGFß/ERK pathway.

Venous calcification has been observed in post-thrombotic syndrome (PTS) patients; yet, the cell types and possible mechanisms regulating this process are still unclear. We evaluated the calcium deposition within the venous wall, the cell type involved in the calcified remodelling of the venous wall after thrombosis and explored possible mechanisms in vitro. Calcium deposition was found in human specimens of superficial thrombotic veins and was co-localized with VSMCs markers αSMA and TAGLN (also known as SM22α). Besides, the expression of osteogenesis-related genes was dramatically changed in superficial thrombotic veins. Moreover, the inhibition of the TGFß signalling pathway after TNFα treatment effectively induced the expression of osteogenic phenotype markers, the calcium salt deposits and the obvious phosphorylation of ERK1/2 and JNK2 in the VSMCs calcification model. Supplementing TGFß2 or blocking the activation of the ERK/MAPK signalling pathway prevented the transformation of VSMCs into osteoblast-like cells in vitro. Taken together, VSMCs have an important role in venous calcification after thrombosis. Supplementing TGFß2 or inhibiting the ERK/MAPK signalling pathway can reduce the appearance of VSMCs osteogenic phenotype. Our findings may present a novel therapeutic approach to prevent of vascular calcification after venous thrombosis.

Bio-additives Derived from Ricinoleic Acid and Choline with Improved Tribological Properties in Lithium Base Grease.

In this study, bio-based ionic liquid prepared from ricinoleic acid and choline was firstly used as additive in lithium base grease. The characterization and tribological performance of the prepared ionic liquid ([cho][ricinoleic]) as additive in grease were studied compared with the traditional ionic liquid such as L-P104. All the concentrations showed promising friction-reducing and anti-wear properties, though a 3% concentration has superior lubricating properties than others. Furthermore, [cho][ricinoleic]) can greatly enhance the lubrication capability of lithium base greaseunder different frequency and load at room temperature. Although L-P104 showed good lubricating performance than [cho][ricinoleic] at 150°C, the chosen formulation (1.5% [cho][ricinoleic] + 1.5% L-P104) could have better synergism at high and room temperature, which could be a good supplement to ionic liquid as grease additive. Thin films formed according to the results of SEM and XPS were attributed to be the main account for the preferable tribological properties of [cho][ricinoleic] in lithium base grease.

Selenium Vacancies and Synergistic Effect of Near- and Far-Field-Enabled Ultrasensitive Surface-Enhanced Raman-Scattering-Active Substrates for Malaria Detection.

Defect engineering with the active control of defect states brings remarkable enhancement on surface-enhanced Raman scattering (SERS) by magnifying semiconductor-molecule interaction. Such light-trapping architectures can increase the light path length, which promotes photon-analytes interactions and further improves the SERS sensitivity. However, by far the reported semiconductor SERS-active substrates based on these strategies are often nonuniform and commonly in the form of isolated laminates or random clusters, which limit their reliability and stability for practical applications. Herein, we develop self-grown single-crystalline "V-shape" SnSe2-x (SnSe1.5, SnSe1.75, SnSe2) nanoflake arrays (SnSe2-x NFAs) with controlled selenium vacancies over large-area (10 cm × 10 cm) for ultrahigh-sensitivity SERS. First-principles density functional theory (DFT) is used to calculate the band gap and the electronic density of states (DOS). Based on the Herzberg-Teller theory regarding the vibronic coupling, the results of theoretical calculation reveal that the downshift of band edge and high DOS of SnSe1.75 can effectively enhance the vibronic coupling within the SnSe1.75-R6G system, which in turn enhances the photoinduced charge transfer resonance and contributes to the SERS activity with a remarkable enhancement factor of 1.68 × 107. Furthermore, we propose and demonstrate ultrasensitive (10-15 M for R6G), uniform, and reliable SERS substrates by forming SnSe1.75 NFAs/Au heterostructures via a facile Au evaporation process. We attribute the superior performance of our SnSe1.75 NFAs/Au heterostructures to the following reasons: (1) selenium vacancies and (2) synergistic effect of the near and far fields. In addition, we successfully build a detection platform to achieve rapid (∼15 min for the whole process), antibody-free, in situ, and reliable early malaria detection (100% detection rate for 10 samples with 160 points) in whole blood, and molecular hemozoin (<100/mL) can be detected. Our approach not only provides an efficient technique to obtain large-area, uniform, and reliable SERS-active substrates but also offers a substantial impact on addressing practical issues in many application scenarios such as the detection of insect-borne infectious diseases.

Electroacupuncture modulates the intestinal microecology to improve intestinal motility in spinal cord injury rats.

Spinal cord injury (SCI) is a disease involving gastrointestinal disorders. The underlying mechanisms of the potential protective effects of electroacupuncture (EA) and 5-hydroxytryptamine (5-HT) system on SCI remain unknown. We investigated whether EA improves gut microbial dysbiosis in SCI and regulates the 5-HT system. 16S rDNA gene sequencing was applied to investigate alterations in the gut microbiome of the rats. Faecal metabolites and the expression of the 5-HT system were detected. EA and faecal microbiota transplantation (FMT) treatment facilitated intestinal transmission functional recovery and restored the colon morphology of SCI rats. The composition of the intestinal microbiota, including numbers of phylum Proteobacteria, class Clostridia, order Bacteroidales, and genus Dorea, were amplified in SCI rats, and EA and FMT significantly reshaped the intestinal microbiota. SCI resulted in disturbed metabolic conditions in rats, and the EA and FMT group showed increased amounts of catechin compared with SCI rats. SCI inhibited 5-HT system expression in the colon, which was significantly reversed by EA and FMT treatment. Therefore, EA may ameliorate SCI by modulating microbiota and metabolites and regulate the 5-HT system. Our study provides new insights into the pathogenesis and therapy of SCI from the perspective of microbiota and 5-HT regulation.

Full-length transcriptome analysis and identification of genes involved in asarinin and aristolochic acid biosynthesis in medicinal plant Asarum sieboldii.

Asarum sieboldii, a well-known traditional Chinese medicinal herb, is used for curing inflammation and ache. It contains both the bioactive ingredient asarinin and the toxic compound aristolochic acid. To address further breeding demand, genes involved in the biosynthetic pathways of asarinin and aristolochic acid should be explored. Therefore, the full-length transcriptome of A. sieboldii was sequenced using PacBio Iso-Seq to determine the candidate transcripts that encode the biosynthetic enzymes of asarinin and aristolochic acid. In this study, 63 023 full-length transcripts were generated with an average length of 1371 bp from roots, stems, and leaves, of which 49 593 transcripts (78.69%) were annotated against public databases. Furthermore, 555 alternative splicing (AS) events, 10 869 long noncoding RNAs (lncRNAs) as well as their 11 291 target genes, and 17 909 simple sequence repeats (SSRs) were identified. The data also revealed 97 candidate transcripts related to asarinin metabolism, of which six novel genes that encoded enzymes involved in asarinin biosynthesis were initially reported. In addition, 56 transcripts related to aristolochic acid biosynthesis were also identified, including CYP81B. In summary, these transcriptome data provide a useful resource to study gene function and genetic engineering in A. sieboldii.

Design, synthesis and evaluation of a baicalin and berberine hybrid compound as therapeutic agent for ulcerative colitis.

Structural modification of active natural compoundswhichwereoriginated fromTraditional Chinese Medicine (TCM) have showedgreat advantagesin thedevelopmentof new drugs. In TCM, "Huangqin-Huanglian" is a classic "medicine couple"thathas been used to treat intestinal diseases for thousands ofyears, while baicalinand berberine are the major active compoundsof Huangqin and Huanglianrespectively. Based onthis"medicine couple",wedesignedand synthesizeda newbaicalin and berberine hybrid compound (BBH).Its molecular structure wasconfirmedby spectroscopy.The antibacterial activity of BBH was detected in vitro.Results indicatedthat the new hybrid compound exhibited the best antibacterial activity forproteobacteria as compared with its original synthetic materials (baicalin andberberine). In vivo, the effect of BBHon ulcerative colitiswas alsoinvestigated.BBH treatment significantly ameliorated the disease symptoms andpreventedthe colon damage of ulcerative colitis. Furthermore, BBH showed asignificant anti-inflammatory effect through regulating activities of SOD, MPOandexpressions of pro-inflammatory cytokines (TNF-α, IL-1ß and IL-6) in colontissue. Data also suggested that BBH was more superior than baicalin and berberine inameliorating colonic damage. This indicated that the new hybrid compound BBHshowed enhanced efficacy in treating ulcerative colitis.

Huang-Qi San ameliorates hyperlipidemia with obesity rats via activating brown adipocytes and converting white adipocytes into brown-like adipocytes.

BACKGROUND: Brown adipose tissue (BAT) activation is a promising therapeutic target to treat hyperlipidemia with obesity. Huang-Qi San (HQS), an traditional Chinese medicine, can ameliorate hyperlipidemia with obesity, but its mechanism of action (MOA) is not understood. PURPOSE: To articulate the MOA for HQS with animal models. METHODS: The main chemical constituents of HQS were identified by high-performance liquid chromatography (HPLC) based assay. Hyperlipidemia with obesity rat models induced by high-fat diet were employed in the study. The levels of the fasting plasma glucose (FPG), triglyceride (TG), total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C) and high-density lipoprotein-cholesterol (HDL-C) were measured to evaluate the ability of HQS to ameliorate hyperlipidemia with obesity. Pathological analyses of organs were conducted with Oil Red O staining, hematoxylin-eosin (H&E) staining and transmission electron microscopy. The expression of mRNAs related to thermogenic genes, fatty acid oxidation-related genes and mitochondria biogenic genes were examined by quantitative real-time PCR. The protein expressions of uncoupling protein 1 (UCP1) were investigated by immunohistochemistry and western blot. Simultaneously, the protein expression of PR domain containing 16 (PRDM16), ATP synthase F1 subunit alpha (ATP5A) was detected by western blot. RESULTS: HQS ameliorates metabolic disorder, lipid ectopic deposition, obesity and maintained glucose homeostasis in hyperlipidemia with obesity rats. HQS can significantly increase the number of mitochondria and reduced the size of the intracellular lipid droplets in BAT, and increase the expression of BAT activation-related genes (UCP1, PGC1α, PGC1ß, Prdm16, CD137, TBX1, CPT1a, PPARα, Tfam, NRF1 and NRF2) in vivo. Furthermore, UCP1, PRDM16 and ATP5A proteins of BAT were increased. CONCLUSION: HQS can activate BAT and browning of S-WAT (subcutaneous white adipose tissue) through activating the PRDM16/PGC1α/UCP1 pathway, augmenting mitochondrial biogenesis and fatty acid oxidation to increase thermogenesis and energy expenditure, resulting in a significant amelioration of hyperlipidemia with obesity. Therefore, HQS is an effective therapeutic medicine for the treatment of hyperlipidemia with obesity.

Monoacylglycerol lipase inhibitors: modulators for lipid metabolism in cancer malignancy, neurological and metabolic disorders.

Monoacylglycerol lipase (MAGL) is a serine hydrolase that plays a crucial role catalysing the hydrolysis of monoglycerides into glycerol and fatty acids. It links the endocannabinoid and eicosanoid systems together by degradation of the abundant endocannabinoid 2-arachidaoylglycerol into arachidonic acid, the precursor of prostaglandins and other inflammatory mediators. MAGL inhibitors have been considered as important agents in many therapeutic fields, including anti-nociceptive, anxiolytic, anti-inflammatory, and even anti-cancer. Currently, ABX-1431, a first-in-class inhibitor of MAGL, is entering clinical phase 2 studies for neurological disorders and other diseases. This review summarizes the diverse (patho)physiological roles of MAGL and will provide an overview on the development of MAGL inhibitors. Although a large number of MAGL inhibitors have been reported, novel inhibitors are still required, particularly reversible ones.

Huang-Qi San improves glucose and lipid metabolism and exerts protective effects against hepatic steatosis in high fat diet-fed rats.

Numerous researches supported that non-alcoholic fatty liver disease (NAFLD) was an emerging problem associated with increased visceral adiposity (obesity), diabetes and related metabolic disorders. Huang-Qi San (HQS) is composed of three traditional Chinese medicines (Astragali Radix, Pueraria Radix and Cortex Mori Radicis) with a weight ratio of 1:2:1. HQS has been reported to be effective in improving glucose-lipid metabolism, but its underlying mechanism on NAFLD has not been fully understood. The purpose of the present study was to assess the protective effects of HQS on obesity-induced hepatic steatosis in rats fed with high fat diet (HFD). Our data revealed that administration of HQS (1.2 and 2.4 g/kg body weight) resulted in significant reduction in body weight (BW) and organs coefficients of visceral fat. The full-Body CT scan demonstrated that HQS reduced liver fat ratio, visceral and subcutaneous fat mass in a dose-dependent manner. Additionally, HQS decreased plasma TC, TG, FFA and FABP4 levels, normalized glucose and insulin levels, and improved the glucose tolerance. Pathological examination showed that HQS alleviated hepatic steatosis and reduced the cell size of epididymal visceral adipose tissue. Hepatic lipid accumulation was also reduced by HQS treatment compared with HFD fed rats. RNA-Seq analysis combining with qPCR demonstrated that the mRNA expression of some important glucose and lipid metabolism-related genes including Acat2, Apoc4, Bhmt, Cyp3a62, Cyp51, Egln3 (Phd3), Fads1, Fads2, Gnmt, Hmgcs1 and Pemt, were significantly changed by HQS treatment. Taken together, these results suggested that HQS had beneficial effects on glucose-lipid metabolism and hepatic steatosis, and its mechanism might be related to the functions of the genes in regulating glucose and lipid metabolism.

Wrist-ankle acupuncture attenuates cancer-induced bone pain by regulating descending pain-modulating system in a rat model.

BACKGROUND: Cancer-induced bone pain (CIBP) presents a multiple-mechanism of chronic pain involving both inflammatory and neuropathic pain, and its pathogenesis is closely related to endogenous descending system of pain control. However, the action mechanism underlying the effects of wrist-ankle acupuncture (WAA) versus electroacupuncture (EA) on CIBP remains unknown. METHODS: Thirty-two Wistar rats were divided into sham, CIBP, EA-treated and WAA-treated groups. CIBP was induced in rats of the latter three groups. Time courses of weight and mechanical hyperalgesia threshold (MHT) were evaluated. After 6 days of EA or WAA treatment, the expressions of 5-hydroxytryotamine type 3A receptor (5-HT3AR) and µ-opioid receptor (MOR) in rostral ventromedial medulla (RVM) and/or spinal cord, as well as the levels of 5-HT, ß-endorphin, endomorphin-1 and endomorphin-2 in RVM and spinal cord, were detected. RESULTS: Injection of cancer cells caused decreased MHT, which was attenuated by EA or WAA (P < 0.05). WAA had a quicker analgesic effect than EA (P < 0.05). No significant difference of MOR in RVM was found among the four groups. EA or WAA counteracted the cancer-driven upregulation of 5-HT3AR and downregulation of MOR in spinal cord (P < 0.05), and upregulation of 5-HT and downregulation of endomorphin-1 in both RVM and spinal cord (P < 0.05). ß-endorphin and endomorphin-2 in RVM and spinal cord decreased in CIBP group compared with sham group (P < 0.05), but EA or WAA showed no significant effect on them, although a tendency of increasing effect was observed. CONCLUSION: WAA, similar to EA, alleviated mechanical hyperalgesia in CIBP rats by suppressing the expressions of 5-HT and 5-HT3AR, and increasing the expressions of MOR and endomorphin-1 in RVM-spinal cord pathway of the descending pain-modulating system. However, WAA produced a quicker analgesic effect than EA, the mechanisms of which need further investigation.

Impacts of government supervision on hospitalization costs for inpatients with COPD: An interrupted time series study.

To address the remaining medical misconducts after the zero-makeup drug policy (ZMDP), e.g., over-examinations, China has given the priority to government supervision on medical institutions. This study evaluated the effect of government supervision on medical costs among inpatients with chronic obstructive pulmonary disease (COPD) in Sichuan province, the first province in China where the medical supervision was conducted.A linear interrupted time series (ITS) model was employed to analyze data about 72,113 inpatients from 32 hospitals. Monthly average medicine costs, diagnostic costs, and medical services costs, nursing costs from January 2015 to June 2018 were analyzed, respectively.The average hospitalization costs fell with a monthly trend of 42.90Yuan before the implementation of supervision (P < .001), and the declining trend remained with the more dramatic rate (-158.70Yuan, P < .001) after the government audit carried out. For western medicine costs, the monthly decreasing trend remained after the implementation of supervision (-66.44Yuan, P < .001); meanwhile, the monthly upward trend was changed into a downtrend trend for traditional Chinese medicine costs (-11.80Yuan, P = .009). Additionally, the increasing monthly trend in average diagnostics costs disappeared after government supervision, and was inversed to an insignificant decreasing trend at the rate of 26.18Yuan per month. Moreover, the previous upward trends were changed into downward trends for both medical service costs and nursing costs (P = .056, -44.71Yuan; P = .007, -11.17Yuan, respectively) after the supervision carried out.Our findings reveal that government supervision in Sichuan province was applicable to curb the growth of medical costs for inpatients with COPD, which may reflect its role in restraining physicians' compensating behaviors after the ZMDP. The government medical supervision holds promise to dismiss medical misconducts in Sichuan province, the experience of which may offer implications for other regions of China as well as other low- and middle-income countries.

A novel berberine-metformin hybrid compound exerts therapeutic effects on obese type 2 diabetic rats.

In this study, we investigated the biological activities of a novel berberine-metformin hybrid compound (BMH473) as an anti-diabetic agent. BMH473 exhibited significant anti-hyperglycaemic and anti-hyperlipidaemic effects on T2DM rats. In white adipose tissue, BMH473 reduced the perirenal and epididymal adipose tissue mass and modulated the lesions in perirenal adipose tissue, by inhibiting the protein expressions of PPAR-Ɣ, C/EBP-α and SREBP-1c as well as the mRNA expressions of lipogenic genes. Moreover, BMH473 downregulated the levels of pro-inflammatory cytokines in perirenal adipose tissue through the suppression of p-NF-κB. In liver, BMH473 reduced liver ectopic fat accumulation, by regulating the protein expression levels of SREBP-1c and PPAR-α as well as the mRNA expression levels of lipogenic genes. In addition, BMH473 inhibited hepatic gluconeogenesis by promoting the phosphorylation levels of AMPK α and ACC, and down-regulating the mRNA expression levels of FBPase, G6Pase and PEPCK. Furthermore, BMH473 exhibited significant inhibitory effects on lipogenesis and lipid accumulation in 3T3-L1 adipocytes by modulating the protein expression levels of PPAR-Ɣ, C/EBP-α and SREBP-1 c as well as the mRNA expression levels of lipogenic genes. In conclusion, our results suggest that the newly synthesized BMH473 is beneficial for maintaining glucose and lipid homeostasis in type 2 diabetic rats, and exhibits better anti-hyperlipidaemic effects compared to metformin and berberine.

Design, synthesis and evaluation of novel 7H-pyrrolo[2,3-d]pyrimidin-4-amine derivatives as potent, selective and reversible Bruton's tyrosine kinase (BTK) inhibitors for the treatment of rheumatoid arthritis.

A series of 7H-pyrrolo[2,3-d]pyrimidine derivatives were designed and synthesized as reversible BTK inhibitors, and evaluated their kinase selectivity, anti-proliferation against the B-cell lymphoma cell lines (Ramos, Jeko-1) and cell line BTK enhanced (Daudi) in vitro. Among them, compound 28a exhibited the most excellent potency (IC50 = 3.0 nM against BTK enzyme, 8.52 µM, 11.10 µM and 7.04 µM against Ramos, Jeko-1, Daudi cells, respectively), good kinase selectivity and inhibited BTK Y223 auto-phosphorylation and PLCγ2 Tyr1217 phosphorylation. Importantly, 28a showed efficacy anti-arthritic effect on collagen-induced arthritis (CIA) model in vivo. 28a 60 mg/kg dose level once a day group displayed markedly reduced joint damage and cellular infiltration without any bone and cartilage morphology change.

Qiliqiangxin attenuates atrial structural remodeling in prolonged pacing-induced atrial fibrillation in rabbits.

Qiliqiangxin (QL) can attenuate myocardial remodeling and improve cardiac function in some cardiac diseases, including heart failure and hypertension. This study was to explore the effects and mechanism of QL on atrial structural remodeling in atrial fibrillation (AF). Twenty-one rabbits were randomly divided into a sham-operation group, pacing group (pacing with 600 beats per minute for 4 weeks), and treatment group (2.5 g/kg/day). Before pacing, the rabbits received QL-administered p.o. for 1 week. We measured atrial electrophysiological parameters in all groups to evaluate AF inducibility and the atrial effective refractory period (AERP). Echocardiography evaluated cardiac function and structure. TUNEL detection, hematoxylin and eosin (HE) staining, and Masson's trichrome staining were performed. Immunohistochemistry and western blotting (WB) were used to detect alterations in calcium channel L-type dihydropyridine receptor α2 subunit (DHPR) and fibrosis-related regulatory factors. AF inducibility was markedly decreased after QL treatment. Furthermore, we found that AERP and DHPR were reduced significantly in pacing rabbits compared with sham rabbits; treatment with QL increased DHPR and AERP compared to the pacing group. The QL group showed significantly decreased mast cell density and improved atrial ejection fraction values compared with the pacing group. Moreover, QL decreased interventricular septum thickness (IVSd) and left ventricular end-diastolic diameter (LVEDD). Compared with the sham group, the levels of TGFß1 and P-smad2/3 were significantly upregulated in the pacing group. QL reduced TGF-ß1 and P-smad2/3 levels and downstream fibrosis-related factors. Our study demonstrated that QL treatment attenuates atrial structural remodeling potentially by inhibiting TGF-ß1/P-smad2/3 signaling pathway.

[Effect of Huangqi San on AMPK/ACC/CPT1 pathway in hyperlipidemia rats].

To investigate the mechanism of the treatment of hyperlipidemia rats induced by Huangqi San. The 40 male SD rats were randomly divided into normal group, model group, Huangqi San low and high dose group (1, 2 g·kg⁻¹), and positive lipitor group (2 mg·kg⁻¹). The normal group feeds on base feed, and other groups feed on high-fat feed. After 8 weeks, the hyperlipidemia model was successful. After intervention by drugs for 13 weeks, fasting blood glucose, total cholesterol, triglycerides and LDL cholesterol content of all rats were measured. The pathological changes of liver and skeletal muscle of rats were observed in rats. Real-time PCR and Western blot were used to detect the mRNA and protein expression levels of AMPK signaling pathway in the liver and skeletal muscles (AMPK, ACC, CPT1A, SREBP2, HMGCR). The degree of FPG, TC, TG and LDL-C were the highest in the model group, and the liver and skeletal muscle pathology were the most obvious. After intervention by Huangqi San and lipitor, a significant reduction in the blood sugar blood fat, liver, and skeletal muscle injury has improved significantly, except SREBF2 and HMGCR mRNA and protein expression of this enzyme is reduced, other AMPK pathway related mRNA and protein expression increased significantly. Huangqi San effect is superior to lipitor. Huangqi San may improve hyperlipidemia by regulating the AMPK signaling pathway, increasing the oxidation of fatty acids and inhibiting cholesterol synthesis.