Integrated transcriptome and metabolome analysis revealed that HaMYB1 modulates anthocyanin accumulation to deepen sunflower flower color.

KEY MESSAGE: HanMYB1 was found to play positive roles in the modulation of anthocyanins metabolism based on the integrative analysis of different color cultivars and the related molecular genetic analyses. As a high value ornamental and edible crop with various colors, sunflowers (Helianthus annuus L.) provide an ideal system to understand the formation of flower color. Anthocyanins are major pigments in higher plants, which is associated with development of flower colors and ability of oxidation resistance. Here, we performed an integrative analysis of the transcriptome and flavonoid metabolome in five sunflower cultivars with different flower colors. According to differentially expressed genes and differentially accumulated flavonoids, these cultivars could be grouped into yellow and red. The results showed that more anthocyanins were accumulated in the red group flowers, especially the chrysanthemin. Some anthocyanins biosynthesis-related genes like UFGT (UDP-glycose flavonoid glycosyltransferase) also expressed more in the red group flowers. A MYB transcriptional factor, HanMYB1, was found to play vital positive roles in the modulation of anthocyanins metabolism by the integrative analysis. Overexpressed HanMYB1 in tobacco could deepen the flower color, increase the accumulation of anthocyanins and directly active the express of UFGT genes. Our findings indicated that the MYB transcriptional factors provide new insight into the dynamic regulation of the anthocyanin biosynthesis in facilitating sunflower color formation and anthocyanin accumulation.

Comprehensive mRNA and microRNA analysis revealed the effect and response strategy of freshwater fish, grass carp (Ctenopharyngodon idella) under geosmin exposure.

Geosmin is an environmental pollutant that causes off-flavor in water and aquatic products. The high occurrence of geosmin contamination in aquatic systems and aquaculture raises public awareness, however, few studies have investigated the response pathways of geosmin stress on freshwater fish. In this research, grass carp were exposed to 50 µg/L geosmin for 96 h, liver tissue was sequenced and validated using real-time qPCR. In total of 528 up-regulated genes and 488 down-regulated genes were observed, includes cytochrome P450 and uridine diphosphate (UDP)-glucuronosyltransferase related genes. KEGG analysis showed that chemical carcinogenesis-DNA adducts, metabolism of xenobiotics by cytochrome P450, drug metabolism-cytochrome P450 pathway was enriched. Common genes from the target genes of microRNAs and differential expression genes are enriched in metabolism of xenobiotics cytochrome P450 pathway. Two miRNAs (dre-miR-146a and miR-212-3p) down regulated their target genes (LOC127510138 and adh5, respectively) which are enriched cytochrome P450 related pathway. The results present that geosmin is genetoxic to grass carp and indicate that cytochrome P450 system and UDP-glucuronosyltransferase play essential roles in biotransformation of geosmin. MicroRNAs regulate the biotransformation of geosmin by targeting specific genes, which contributes to the development of strategies to manage its negative impacts in both natural and artificial environments.

[Pharmacovigilance guidelines for clinical application of traditional Chinese medicine injections].

In 2019, the newly revised Drug Administration Law of the People's Republic of China was issued and implemented,clearly proposing that China should establish a pharmacovigilance system. As a new traditional Chinese medicine(TCM) dosage form created in China, TCM injections have been widely used in clinic, and its pharmacovigilance has attracted much attention. In response to this situation, the project team convened a group of clinical, pharmaceutical and evidence-based medicine experts from all over the country to form an expert group, which formulated the Pharmacovigilance guidelines for clinical application of traditional Chinese medicine injections in strict accordance with the requirements of the group standards of the Chinese Association of Chinese Medicine.From the perspective of clinical application and considering the key elements of pharmacovigilance for clinical application of TCM injections, the guidelines put forward suggestions on the decision making of pharmacovigilance for clinical application of TCM injections from four key links, namely the monitoring and reporting, signal recognition, risk assessment and risk control, according to China's pharmacovigilance regulations and learning from foreign pharmacovigilance guidelines.

Dexmedetomidine alleviates acute postoperative anxiety in rats by suppressing the NF-ĸB pathway.

Evidence suggests that surgical procedures can effect the central nervous system and lead to changes in mood and behavior, rarely understood about the role of acute inflammation in promoting acute anxiety postoperatively. This study was designed to explore the possible mechanism of dexmedetomidine (DEX, a2-adrenergic receptor agonist) for reducing acute postoperative anxiety, which may be related to the activation of nuclear factor kappa B (NF-κB) and downstream signal pathway in the hippocampus. Experiments were conducted with rat, the elevated plus-maze and open field test were performed to evaluate anxiety-like behavior. Inhibit DEX with Atipamezole (AT, α2-adrenergic receptor antagonist) and inhibit NF-κB with Pyrrolidinedithiocarbamate (PDTC, inhibit phosphorylation of IκB, prevent the activation of NF-κB), the level of interleukin-6 (IL-6), IL-1ß, IL-10 and Tumor necrosis factor-α (TNF-α); the nuclear translocation of NF-κB in the hippocampus and anxiety-like behavior were measured. Rats exhibited anxiety-like behavior at 6h and 12h after surgery. Preoperative administration of DEX significantly alleviated postoperative anxiety-like behavior. DEX premedication inhibited the nuclear translocation of NF-κB alleviate acute postoperative anxiety. These findings are the first to show that acute postoperative anxiety may be related to NF-κB nuclear translocation in the hippocampus in rats, which can be alleviated by DEX premedication.

Applying core lexicon analysis in patients with anomic aphasia: Based on Mandarin AphasiaBank.

BACKGROUND: Patients with anomic aphasia experience difficulties in narrative processing. General discourse measures are time consuming and require necessary skills. Core lexicon analysis has been proposed as an effort-saving approach but has not been developed in Mandarin discourse. AIMS: This exploratory study was aimed (1) to apply core lexicon analysis in Mandarin patients with anomic aphasia at the discourse level and (2) to verify the problems with core words among people with anomic aphasia. METHODS & PROCEDURE: The core nouns and verbs were extracted from narrative language samples from 88 healthy participants. The production of core words for 12 anomic aphasia and 12 age- and education-matched controls were then calculated and compared. The correlation between the percentages and the Aphasia Quotients of the revised Western Aphasia Battery was analyzed as well. OUTCOMES & RESULTS: The core nouns and verbs were successfully extracted. Patients with anomic aphasia produced fewer core words than healthy people, and the percentages differed significantly in different tasks as well as word classes. There was no correlation between the core lexicon use and the severity of aphasia in patients with anomic aphasia. CONCLUSIONS & IMPLICATIONS: Core lexicon analysis may potentially serve as a clinician-friendly manner of quantifying core words produced at the discourse level in Mandarin patients with anomic aphasia. WHAT THIS PAPER ADDS: What is already known on the subject Discourse analyses in aphasia assessment and treatment have increasingly garnered attention. Core lexicon analysis based on English AphasiaBank has been reported in recent years. It is correlated with microlinguistic and macrolinguistic measures in aphasia narratives. Nevertheless, the application based on Mandarin AphasiaBank is still under development in healthy individuals and patients with anomic aphasia. What this paper adds to existing knowledge A Mandarin core lexicon set was developed for different tasks. The feasibility of core lexicon analysis to evaluate the corpus of patients with anomic aphasia was preliminarily discussed and the speech performance of patients and healthy people was then compared to provide a reference for the evaluation and treatment of clinical aphasia corpus. What are the potential or actual clinical implications of this work? The purpose of this exploratory study was to consider the potential use of core lexicon analysis to evaluate core word production in narrative discourse. Moreover, normative and aphasia data were provided for comparison to develop clinical use for Mandarin patients with anomic aphasia.

Fabrication of highly efficient hydroxyapatite microtubes for uranium sequestration and immobilization.

Uranium-containing wastewater is a common by-product of uranium mining. Phosphate and phosphate minerals can interact with uranyl ions [U(VI)], impeding the migration of these ions by forming relatively stable uranium-containing crystalline phase(s). In this study, hydroxyapatite microtubes (HAP-T) were fabricated to sequester uranyl ions from simulated radioactive wastewater. HAP-T had excellent adsorption and stability properties; over 98.76% of U(VI) could be sequestrated by 0.25 g/L HAP-T within 5 min at pH = 4.0. The isotherms and kinetics data could be suitably reflected by the Freundlich and the pseudo second-order kinetic models, respectively. The maximum adsorption capacity of HAP-T was 356.42 mg/g. The adsorption ability of HAP-T for U(VI) was inhibited when Mg2+ or SO42- ions or fulvic acid (FA) substances existed in the simulated radioactive wastewater. The inhibition by FA was attributed to its negative charges, which caused competition between FA and HAP-T for uranium sequestration. The primary mechanisms of U(VI) sequestration by HAP-T were electrostatic interactions and surface complexation. The effectiveness of HAP-T, HAP-B (bio-hydroxyapatite synthesized from fish bone), and HAP-C (commercially available synthesized hydroxyapatite) for uranium immobilization was compared; HAP-T was more effective than HAP-B or HAP-C in immobilizing uranium. HAP-T, which has a micron-sized tubular structure, is likely less mobile in groundwater than are HAP-B and HAP-C, which have nanoscale granular structures. In conclusion, HAP-T can be used to sequester and immobilize uranyl ions.

Simultaneous bilateral fallopian tubal pregnancy of a laparoscopic definite spontaneous unilateral ovulation: a case report.

BACKGROUND: Bilateral simultaneous fallopian tubal pregnancy is one of the rarest forms of ectopic pregnancy. Due to the lack of unique features and clinical presentation to distinguish bilateral from unilateral ectopic pregnancy, challenges the diagnosis. CASE REPORT: A 27-year-old Asian woman presented with pelvic pain and vaginal bleeding. Pelvic transvaginal ultrasound showed fluid in Douglas Pouch and posterior fornix puncture revealed unclotted blood. Laparoscopic examination unveiled bilateral ectopic pregnancy with two corpus luteum visible in the right ovary, suggesting a double spontaneous unilateral ovulation. Bilateral fallopian tube fenestration and embryo extraction were performed to preserve fertility. CONCLUSION: Diagnosis of bilateral tubal pregnancy is difficult during preoperative ultrasound examination and careful examination during laparoscopic inspection of the whole pelvic cavity to avoid missed diagnosis.

Effect of neuromuscular block on surgical conditions during short-duration paediatric laparoscopic surgery involving a supraglottic airway.

BACKGROUND: Use of an LMA ProSeal™ laryngeal mask airway (P-LMA; Teleflex) with no neuromuscular block is considered a safe alternative to tracheal intubation in short-duration paediatric laparoscopic surgery. However, few studies have evaluated surgical conditions of short-duration paediatric laparoscopic surgery using this anaesthetic technique. We assessed surgical conditions for paediatric laparoscopic inguinal hernia repair using P-LMA with and without neuromuscular block. METHODS: Sixty-six patients undergoing laparoscopic inguinal hernia repair were randomised to receive a neuromuscular block (train-of-four 1-2 twitches) using rocuronium or no neuromuscular block with the P-LMA. All operations were performed by the same surgeon who determined the surgical conditions using the Leiden-surgical rating scale (L-SRS). Secondary outcomes included perioperative data, haemodynamics, and adverse events. RESULTS: Neuromuscular block improved surgical conditions compared with no neuromuscular block: mean (standard deviation) L-SRS 4.1 (0.5) vs 3.5 (0.6), respectively (P<0.0001). Mean rocuronium dose in the neuromuscular block group was 12.7 (4.4-29.7) mg or 0.7 (0.6-0.8) mg kg-1. The insufflation Ppeak was higher in the no neuromuscular block group than in the neuromuscular block group: mean (standard deviation) Ppeak 17.9 (1.8) cm H2O vs 16.2 (1.9) cm H2O, respectively (P=0.0004). Fifteen children (45.5%) in the no neuromuscular block group had adverse events during the surgery and anaesthesia vs four children (12.1%) in the neuromuscular block group (P=0.006). CONCLUSIONS: Neuromuscular block significantly improved surgical conditions and reduced the incidence of adverse events during surgery and anaesthesia when an LMA Proseal™ was used in short-duration paediatric laparoscopic surgery. CLINICAL TRIAL REGISTRATION: ChiCTR2000038529.

Ultradian calcium rhythms in the paraventricular nucleus and subparaventricular zone in the hypothalamus.

The suprachiasmatic nucleus (SCN), the master circadian clock in mammals, sends major output signals to the subparaventricular zone (SPZ) and further to the paraventricular nucleus (PVN), the neural mechanism of which is largely unknown. In this study, the intracellular calcium levels were measured continuously in cultured hypothalamic slices containing the PVN, SPZ, and SCN. We detected ultradian calcium rhythms in both the SPZ-PVN and SCN regions with periods of 0.5-4.0 hours, the frequency of which depended on the local circadian rhythm in the SPZ-PVN region. The ultradian rhythms were synchronous in the entire SPZ-PVN region and a part of the SCN. Because the ultradian rhythms were not detected in the SCN-only slice, the origin of ultradian rhythm is the SPZ-PVN region. In association with an ultradian bout, a rapid increase of intracellular calcium in a millisecond order was detected, the frequency of which determined the amplitude of an ultradian bout. The synchronous ultradian rhythms were desynchronized and depressed by a sodium channel blocker tetrodotoxin, suggesting that a tetrodotoxin-sensitive network is involved in synchrony of the ultradian bouts. In contrast, the ultradian rhythm is abolished by glutamate receptor blockers, indicating the critical role of glutamatergic mechanism in ultradian rhythm generation, while a GABAA receptor blocker increased the frequency of ultradian rhythm and modified the circadian rhythm in the SCN. A GABAergic network may refine the circadian output signals. The present study provides a clue to unraveling the loci and network mechanisms of the ultradian rhythm.

Individualized surgery combined with radiotherapy and triamcinolone acetonide injection for the treatment of auricular keloids.

BACKGROUND: Although multiple methods have been proposed to treat auricular keloids, low curative effects and high recurrence rates are currently major clinical problems. Thereinto, surgery combined with radiotherapy and triamcinolone acetonide injection is considered to be the proper choice for comprehensive treatment of auricular keloids. This study aimed at evaluating the therapeutic effect of individualized surgery combined with radiotherapy for the treatment of auricular keloids. METHODS: From February 2014 to February 2017, 67 patients with 113 auricular keloids in total were enrolled in this study. According to specific conditions of lesions, the local tissue and patients' individual wishes, different surgical methods were selected to analyze the scar excision and repairment of the defect. Within 24 h after the keloid was excised, 5 MeV electron beam irradiation by the linear accelerator was used by radiotherapy with a total dose of 20 Gy at interval of 1 day for 10 consecutive times. Triamcinolone acetonide was injected immediately after surgery, and per month afterward in the following three months. RESULTS: 113 keloids in total were received treatment. The follow-up period was 24 months. Fourteen keloids (12.39%) showed subjective recurrence with a success rate of 87.61%. Wilcoxon matched-pairs rank-sum test was used to compare the differences of the 24-month postoperative VSS scores and the preoperative VSS scores. The VSS scores were as follows: 82 keloids (72.57%) scored less than 5 points (good result), 21 keloids (18.58%) scored 6 to 10 points (fair result), and only 10 keloids (8.85%) scored more than 10 points (bad result). The effective rate was 91.15%. CONCLUSIONS: Individualized surgery combined with early postoperative radiotherapy and triamcinolone acetonide injection is an ideal treatment method to ensure good auricular appearance, low incidences of complications and recurrence based on effective treatment of auricular keloids.

Remedial dosing recommendations for delayed or missed doses of valproic acid in patients with epilepsy based on Monte Carlo simulations.

OBJECTIVE: Delayed or missed doses are unavoidable in the pharmacotherapy of epilepsy and significantly compromise the efficacy of antiepileptic drug treatment. An inappropriate remedial regimen can cause seizure relapse or serious adverse events. This study investigated the effect of delayed or missed doses on the pharmacokinetics (PK) of valproic acid (VPA) in patients with epilepsy and established remedial dosing recommendations for nonadherent patients. METHODS: Monte Carlo simulations are based on all previous population pharmacokinetic models for pediatric, adult and elderly patients with epilepsy. The following four remedial strategies were investigated for each delayed dose: A) A partial dose or a regular dose is taken immediately; a regular dose is taken at the next scheduled time. B) The delayed dose was administered immediately, followed by a partial dose at the next scheduled time. C) The delayed dose and a partial dose are taken; the next scheduled time is skipped, and the regular regimen is resumed. D) Double doses are taken when missed one dose or two doses, and the regular regimen at the subsequent scheduled time is resumed. RESULTS: The recommended remedial dose was related to the delay duration and daily dose. Remedial dosing strategies A and B were almost equivalent, whereas Strategy C was recommended when the delayed dose was close to the next scheduled dose. Strategy D was only suggested for delayed two doses. CONCLUSION: Simulations provide quantitative insight into the remedial regimens for nonadherent patients, and clinicians should select the optimal regimen for each patient based on the individual's status.

The Effects of Timing of Postoperative Radiotherapy on Hypertrophic Scar in a Rabbit Model.

BACKGROUND Hypertrophic scar is associated with excessive proliferation of fibroblasts, the accumulation of collagen fibers, and angiogenesis associated with chronic inflammation. Scar resection, combined with radiotherapy, is widely used in clinical practice, but timing remains controversial. This study aimed to investigate the association between the timing of postoperative radiotherapy and the effects on hypertrophic scar in a rabbit model. MATERIAL AND METHODS Forty New Zealand white rabbits, 8-12 months old, weighing 1.8-2.3 kg were used in the model of hypertrophic scar and underwent surgical resection with or without postoperative radiotherapy. The study groups included: Group 1, the non-resection group; Group 2, the resection and non-radiotherapy group; Group 3, the immediate postoperative radiotherapy group; Group 4, the 12-hour postoperative radiotherapy group; Group 5, the 24-hour postoperative radiotherapy group; Group 6, the 48-hour postoperative radiotherapy group; Group 7, the 72-hour postoperative radiotherapy group; and Group 8, the 120-hour postoperative radiotherapy group. The rabbit ear skin was observed after treatment, and the hypertrophic scar index (HI), fibroblast numerical area density (NA), and collagen fiber area density (AA) were determined. RESULTS The HI, NA, and AA were significantly lower after 48 hours of postoperative radiotherapy (P<0.05), with the effects occurring mainly within 24 hours. There was no difference in HI, NA, and AA between the radiotherapy and non-radiotherapy groups within 24 hours after surgery. CONCLUSIONS In a rabbit model of hypertrophic scar, surgical resection combined with radiotherapy resulted in an optimal effect within 24 hours after surgery.

Lipid droplets participate in modulating innate immune genes in Ctenopharyngodon idella kidney cells.

Lipid droplets (LDs) are increasingly being recognized as important immune modulators in mammals, in additional to their function of lipid ester deposition. However, the role of LDs in fish immunity remains poorly understood. In this study, the function of LDs in the innate immune response of Ctenopharyngodon idella kidney (CIK) cells, which are the equivalent of myeloid cells in vertebrates, was investigated. LD number and TG content significantly increased in the CIK cells following exposure to lipopolysaccharide (LPS), peptidoglycan (PGN), and polyriboinosinic-polyribocytidylic acid (Poly [I: C]) for 24 h, accompanied by increases in the relative expression of several innate immune genes. However, fatty acid compositions of the triglycerides were not changed after treatment with these three pathogenic mimics. LPS, PGN, and Poly (I: C) did not alter the relative expressions of lipogenic (FAS, SCD, and DGAT) and lipid catabolic (PPARα, ATGL, and CPT-1) genes. However, these treatments did increase the mRNA levels of lipid transportation genes (FATP/CD36, ACSL1, and ACSL4), and also decreased the non-esterified fatty acid level in the medium. To further explore the role of LDs in the immune response, CIK cells were incubated with different concentrations (0, 100, 200, 300, 400, 500 µM) of exogenous lipid mix (LM; oleic acid [OA]:linoleic acid [LA]:linolenic acid [LNA] = 2:1:1), and were then transferred to a lipid-free medium and incubated for 24 h. LD size and number increased with the increase in lipid levels, and this was accompanied by increased expression of innate immune genes, including MyD88, IRF3, and IL-1ß, which were expressed at their highest levels in 300 µM exogenous lipid mix. Interestingly, after incubating with different fatty acids (LM, OA, LA, LNA, arachidonic acid [ARA], and docosahexaenoic acid [DHA]; 300 µM), ARA and DHA were more potent in inducing LD formation and innate immune gene expression in the CIK cells. Finally, atglistatin, an ATGL inhibitor, effectively attenuated the expression of most genes upregulated by ARA or DHA, suggesting that lipolysis may be involved in the regulation of immune genes at the transcriptional level. Overall, the findings of this study demonstrate that LDs are functional organelles that could act as modulators in the innate immune response of CIK cells. Additionally, long-chain polyunsaturated fatty acid enriched LDs play a unique role in regulating this process.

Remedial dosing recommendations for delayed or missed doses of lamotrigine in pediatric patients with epilepsy using Monte Carlo simulations.

OBJECTIVE: This study investigated the effect of delayed or missed doses on the pharmacokinetics (PK) of lamotrigine (LTG) in children with epilepsy and established remedial dosing recommendations for nonadherent patients. METHODS: The Monte Carlo simulation based on a published LTG population PK model was used to assess the effect of different scenarios of nonadherence and the subsequently administered remedial regimens. The following three remedial approaches were investigated for each delayed dose: A) A partial dose was administered immediately, and the regular dose was administered at the next scheduled time. B) The delayed dose was administered immediately, followed by a partial dose at the next scheduled time. C) The delayed and partial doses were coadministered immediately, the next scheduled dose was skipped, and the regular dosing was resumed at the subsequent scheduled time. The most appropriate remedial regimen was that with the shortest deviation time from the individual therapeutic window. RESULTS: The effect of nonadherence on PK was dependent on the delay duration and daily dose, and the recommended remedial dose was related to the delay duration and concomitant antiepileptic drugs. Remedial dosing strategies A and B were almost equivalent, whereas C showed a larger PK deviation time. If one dose was missed, double doses were not recommended for the next scheduled time. CONCLUSIONS: Simulations provide quantitative insight into the remedial regimens for nonadherent patients, and clinicians should select the optimal regimen based on the status of patients.

Lipid accumulation in grass carp (Ctenopharyngodon idellus) fed faba beans (Vicia faba L.).

Feeding faba beans (Vicia faba L.) to grass carp (Ctenopharyngodon idellus) increases muscle compactness but decreases growth and motility. The lipid metabolism of grass carp was examined to assess potential effects of feeding faba beans on physiological properties using a total of 180 fish. The treatment group was fed faba beans for 120 days and a commercial diet for another 30 days. The control group received a commercial diet for 150 days. Fish were sampled every month. Weight gain was significantly lower in the treatment group than in the control. Hardness, springiness, chewiness, cohesiveness, and gumminess of the dorsal muscle increased significantly with the feeding faba beans from 30 to 120 days, which was not reversed by the subsequent feeding of commercial diet. Fat accumulation increased significantly in the treatment group as suggested by the condition factor, viscera index, hepatopancreatic index, and intraperitoneal fat index (IPFI), hepatopancreas, and muscle fat content but was not affected by subsequent feeding with the commercial diet. Serum triglyceride and total cholesterol levels were significantly reduced in the experimental diet group. In the hepatopancreas and intraperitoneal fat IPF, monounsaturated fatty acids showed significantly higher content in faba bean feeding fish, whereas polyunsaturated fatty acid content showed the reversed pattern. In the hepatopancreas, the activities of the lipogenic enzymes malate dehydrogenase and glucose 6-phosphate dehydrogenase were higher in the treatment than in the control group. Moreover, the treatment group showed lower mRNA levels of carnitine palmitoyltransferase-1. Overall, our results clearly demonstrate increasing lipid accumulation in the viscera of faba bean-fed grass carp.

[Experimental factors affecting in vitro recovery of puerarin in microdialysis].

OBJECTIVE: : To analyze experimental factors affecting in vitro recovery of puerarin in microdialysis. METHODS: : Puerarin concentration in microdialysate samples was determined by high performance liquid chromatography. The methods of direct dialysis, retrodialysis and the zero-net flux were used to calculate in vitro recovery, respectively. The effects of perfusate composition, the analyte concentration, perfusate flow rate, medium temperature and stir rates of the dialysis medium on recovery were investigated. RESULTS: : There were significant differences in the recovery values among direct dialysis, retrodialysis and zero-net flux methods. The recovery for 0.9% NaCl solution, Ringer's solution, PBS and anticoagulant dextrose solution as perfusate fluid were (71.25±2.36)%,(73.48±1.41)%,(68.50±2.43)% and (74.98±1.16)%, respectively. The composition of perfusate fluid had significant influence on the recovery(P<0.01). At the same flow rate, recovery was independent of the analyte concentration. At the same concentration, the recovery was decrease with the increasing flow rate in an exponential relationship. The recovery increased with the raising temperature and stir rate of the dialysis medium, and the recovery remained stable when the stir rate reached above 200 rpm. CONCLUSIONS: : A study method for in vitro recovery of puerarin in microdialysis has been established, and the recovery of puerarin is affected by calculating methods, perfusate fluids, flow rate, medium temperature and stir rate, but not affected by analyte concentrations.

Comparative analysis of effects of dietary arachidonic acid and EPA on growth, tissue fatty acid composition, antioxidant response and lipid metabolism in juvenile grass carp, Ctenopharyngodon idellus.

Four isonitrogenous and isoenergetic purified diets containing free arachidonic acid (ARA) or EPA (control group), 0·30 % ARA, 0·30 % EPA and 0·30 % ARA+EPA (equivalent) were designed to feed juvenile grass carp (10·21 (sd 0·10) g) for 10 weeks. Only the EPA group presented better growth performance compared with the control group (P<0·05). Dietary ARA and EPA were incorporated into polar lipids more than non-polar lipids in hepatopancreas but not intraperitoneal fat (IPF) tissue. Fish fed ARA and EPA showed an increase of serum superoxide dismutase and catalase activities, and decrease of glutathione peroxidase activity and malondialdehyde contents (P<0·05). The hepatopancreatic TAG levels decreased both in ARA and EPA groups (P<0·05), accompanied by the decrease of lipoprotein lipase (LPL) activity in the ARA group (P<0·05). Fatty acid synthase (FAS), diacylglycerol O-acyltransferase and apoE gene expression in the hepatopancreas decreased in fish fed ARA and EPA, but only the ARA group exhibited increased mRNA level of adipose TAG lipase (ATGL) (P<0·05). Decreased IPF index and adipocyte sizes were found in the ARA group (P<0·05). Meanwhile, the ARA group showed decreased expression levels of adipogenic genes CCAAT enhancer-binding protein α, LPL and FAS, and increased levels of the lipid catabolic genes PPAR α, ATGL, hormone-sensitive lipase and carnitine palmitoyltransferase 1 (CPT-1) in IPF, whereas the EPA group only increased PPAR α and CPT-1 mRNA expression and showed less levels than the ARA group. Overall, dietary EPA is beneficial to the growth performance, whereas ARA is more potent in inducing lipolysis and inhibiting adipogenesis, especially in IPF. Meanwhile, dietary ARA and EPA showed the similar preference in esterification and the improvement in antioxidant response.

[Application progress of proteomic in pharmacological study of Chinese medicinal formulae].

Chinese medicinal formulae are the important means of clinical treatment in traditional Chinese medicine. It is urgent to use modern advanced scientific and technological means to reveal the complicated mechanism of Chinese medicinal formulae because they have the function characteristics of multiple components, multiple targets and integrated regulation. The systematic and comprehensive research model of proteomic is in line with the function characteristics of Chinese medicinal formulae, and proteomic has been widely used in the study of pharmacological mechanism of Chinese medicinal formulae. The recent applications of proteomic in pharmacological study of Chinese medicinal formulae in anti-cardiovascular and cerebrovascular diseases, anti-liver disease, antidiabetic, anticancer, anti-rheumatoid arthritis and other diseases were reviewed in this paper, and then the future development direction of proteomic in pharmacological study of Chinese medicinal formulae was put forward. This review is to provide the ideas and method for proteomic research on function mechanism of Chinese medicinal formulae.

[Research progress of pharmacokinetics and pharmacodynamics of total glucosides of peony in hepatoprotective effects].

Total glucosides of peony (TGP), containing the effective components of paeoniflorin (Pae), albiflorin (Alb) and so on, are effective parts of Radix Paeoniae Alba. And it possesses extensive pharmacological actions, one of which is hepatoprotective effect. In recent years, abundant of pharmacokinetics and pharmacodynamics research of TGP in hepatoprotective effects have been performed. However, the relative medicine of TGP in hepatoprotective effect has not been developed for clinical application. In order to provide reference for the development and rational clinical application of TGP, the research progresses of pharmacokinetics and pharmacodynamics of TGP in hepatoprotective effect were summarized in this paper. Pharmacokinetics research has clarified the process of absorption, distribution, metabolism and excretion of TGP in vivo, and liver injury disease can significantly influence its metabolic processes. Pharmacodynamics studies suggested that TGP can protect against acute liver injury, non-alcoholic fatty liver diseases (NAFLD), chronic liver fibrosis and liver cancer. However, the action mechanism and in vivo process about hepatoprotective effects of TGP have not been clearly revealed. How liver injury influences the metabolism of TGP and its integrated regulation through multiple targets need to be further studied. The combined pharmacokinetics and pharmacodynamics studies should be performed in favour of medicine development and clinical application of TGP in hepatoprotective effects.

Gelsemine alleviates both neuropathic pain and sleep disturbance in partial sciatic nerve ligation mice.

AIM: Gelsemine, an alkaloid from the Chinese herb Gelsemium elegans (Gardn & Champ) Benth., is effective in mitigating chronic pain in rats. In the present study we investigated whether the alkaloid improved sleep disturbance, the most common comorbid symptoms of chronic pain, in a mouse model of neuropathic pain. METHODS: Mice were subjected to partial sciatic nerve ligation (PSNL). After the mice were injected with gelsemine or pregabalin (the positive control) intraperitoneally, mechanical allodynia and thermal hyperalgesia were assessed, and electroencephalogram (EEG)/electromyogram (EMG) recording was performed. Motor performance of the mice was assessed using rota-rod test. c-Fos expression in the brain was analyzed with immunohistochemical staining. RESULTS: In PSNL mice, gelsemine (2 and 4 mg/kg) increased the mechanical threshold for 4 h and prolonged the thermal latencies for 3 h. Furthermore, gelsemine (4 mg/kg, administered at 6:30 AM) increased non-rapid eye movement (non-REM, NREM) sleep, decreased wakefulness, but did not affect REM sleep during the first 3 h in PSNL mice. Sleep architecture analysis showed that gelsemine decreased the mean duration of wakefulness and increased the total number of episodes of NREM sleep during the first 3 h after the dosing. Gelsemine (4 mg/kg) did not impair motor coordination in PSNL mice. Immunohistochemical study showed that PSNL increased c-Fos expression in the neurons of the anterior cingulate cortex, and gelsemine (4 mg/kg) decreased c-Fos expression by 58%. Gelsemine (4 mg/kg, administered at either 6:30 AM or 8:30 PM) did not produce hypnotic effect in normal mice. Pregabalin produced similar antinociceptive and hypnotic effects, but impaired motor coordination in PSNL mice. CONCLUSION: Gelsemine is an effective agent for treatment of both neuropathic pain and sleep disturbance in PSNL mice; anterior cingulate cortex might play a role in the hypnotic effects of gelsemine.