Objective To conduct in vitro transdermal test on triamcinolone acetonide spray solution, and investigate the effects of ethanol and propylene glycol alone or in combination on the in vitro transdermal function of triamcinolone acetonide spray solution. Methods Rabbit abdominal skin was selected, and the in vitro penetration test of triamcinolone acetonide spray solution was carried out by Franz diffusion cell method, and the content of triamcinolone acetonide was determined by HPLC. The rate of transdermal absorption was compared. Results The transdermal absorption rate of the combined use of ethanol and propylene glycol was significantly higher than that of the single use (P<0.05), and the order of promoting the penetration of triamcinolone acetonide spray solution when ethanol and propylene glycol were combined by 10% ethanol + 25% propylene glycol >10% ethanol + 20% propylene glycol >15% ethanol + 25% propylene glycol >15% ethanol + 20% propylene glycol. Conclusion The combination of 10% ethanol and 25% propylene glycol could optimize the transdermal function of triamcinolone acetonide spray solution.

Anxiety disorders,dopaminergic neurons and ventral tegmental area(VTA)are related closely.VTA dopaminergic neurons play an important role in the regulation of anxiety.Numerous research results in animals indicated that the VTA dopaminergic neurons,involving in multiple neural pathways,respectively regulate anxiety-like behavior in physiological or pathological condition.Dopamine,the main neurotransmitters in VTA regulates anxiety through dopamine D1 and D2 receptors.In addition,the VTA glutamate,GABA and acetylcholine also play directly or indirectly roles in regulating anxiety.The clinical imaging research showed that the integrity of dopaminergic VTA structural of anxiety disorder group is lower than healthy control.Current researches of VTA dopamine neurons involving in the regulation of anxiety-like behavior is developing at a high speed and deserving further exploration,which will further elucidate the pathogenesis and provide new ideas for prevention and treatment of anxiety disorders.

Curcuminoids are rare diketone compounds in plants and can be found in the rhizome of Curcuma longa as well as other Zingiberaceae and Araceae. Curcuminoids have been widely used in food and medical area owing to the yellow colors, as well as the antioxidant and many other pharmacological activities. Curcuminoids are a mixture of compounds containing curcumin, demethoxycurcumin and bisdemethoxycurcumin, which have distinct benzene ring substituents. Currently, curcuminoids are exclusively produced through plant extraction, which do not satisfy the meeting of the market demand. Empowered with new synthetic biology tools and metabolic engineering strategies, there is renewed interest in production of curcuminoids using microorganisms. Heterologous production of curcuminoids has been achieved using Escherichia coli, Yarrowia lipolytica, Pseudomonas putida and Aspergillus oryzae via engineering of curcuminoids biosynthesis pathway. In this review, we first describe the biological activities and various applications of curcuminoids. Next, we summarize the biosynthetic pathway of curcuminoids in Curcuma longa and discuss the catalytic mechanisms of curcumin synthases. Then, we thoroughly explore recent advances in the use of distinct microorganisms for the production of curcuminoids with a special focus on metabolic engineering strategies. Finally, we prospect the microbial production of curcuminoids by highlighting some promising techniques and approaches.
Antioxidants ; Biosynthetic Pathways/genetics* ; Curcumin ; Diarylheptanoids ; Metabolic Engineering ; Plant Extracts

This article retrieves, sorts out, and analyzes the status quo of the application of the fatigue scale in the respiratory rehabilitation of patients with chronic obstructive pulmonary disease (COPD) , aiming to arouse the attention of clinical medical staff and researchers to the fatigue problem in the respiratory rehabilitation of COPD patients, and provide a reference for the selection of fatigue evaluation scale for COPD patients in respiratory rehabilitation.

Objective By taking usage of bioinformatics screening methods,this medical research aimed at exploring how the miRNAs in endothelial progenitor cell exosomes relate to the regulation of angiogenesis.Methods miRNAs in endothelial progenitor cells exosomes and angiogenesis-related miRNA was intersected from the existing database to obtain the candidates of miRNA molecules related to angiogenesis in endothelial progenitor exosomes.Results 160 and 50 miRNAs in endothelial progenitor cell candidates were obtained through experimental data analysis and literature searching respectively.600 candidates of angiogenesis-related miRNAs were obtained through literature searching;the top 20 with the highest frequency were selected out.Finally,9 miRNA candidates (miR-126,miR-21,miR-221,miR-92a,miR-199a,miR-210,miR-214,miR-155,miR-146a) that may be highly expressed in endothelial progenitor exosomes and associated with angiogenesis were obtained for the following research.Conclusions Based on data analysis and literature searching,bioinformatics could screen out the target miRNAs for follow-up studies easily and reliably,it is worthy to be widely applied and popularized.

OBJECTIVE： To study the long-term toxicity of Liqi sanjie extractum in rats after intragastric administration， and to provide reference for safety evaluation before clinical practice. METHODS： A total of 160 rats were randomly divided into control group （normal saline） and Liqi sanjie extractum low-dose， medium-dose and high-dose groups （7.828 0， 15.656 0， 31.312 0 g/kg， calculated by crude drug）， with 40 rats in each group. They were given relevant medicine intragastrically once a day from Monday to Saturday. The experimental period was 120 days， and the recovery period was 30 days after the end of the experiment. General information of rats was observed， and body weight and feed consumption of rats were measured once a week. At the 61st day of administration， the end of administration and the end of recovery period， 10， 20 and 10 rats were collected from each group to observe their hematology， blood biochemistry， organ coefficient and histopathology changes. RESULTS： From 61st day to 120th day of administration， the rats of Liqi sanjie extractum high-dose group had hair loss and erection， and recovered after withdrawal of medicine. During medication， the body weight of mice in Liqi sanjie extractum low-dose and medium-dose groups increased faster than control group， while the body weight of rats in Liqi sanjie extractum high-dose group increased slower than control group. Compared with control group， the feed consumption of Liqi sanjie extractum low-dose group increased， while those of Liqi sanjie extractum medium-dose and high-dose groups decreased； the rats were recovered after drug withdrawal. On the 61st day of administration and after the end of administration， some hematological indexes， blood biochemical indexes and organ coefficients of rats in administration group were significantly different from those of control group （P＜0.05 or P＜0.01）. The hematology， blood biochemistry and organ coefficients of rats were basically recovered after the end of the recovery period. The number of erythrocyte， hematocrit， standard deviation of erythrocyte width， albumin， globulin ratio and potassium K+ levels in Liqi sanjie extractum low-dose group were significantly lower than those in control group （P＜0.05 or P＜0.01）. The absolute value of intermediate cells in blood of rats in Liqi sanjie extractum medium-dose group was significantly higher than that of control group （P＜0.05）， and the mean hemoglobin concentration， K+ and uterine coefficient in blood were significantly lower than those of control group （P＜0.05）. The number of white blood cells， absolute value of lymphocyte， absolute value of intermediate cells， the percentage of intermediate cells， prothrombin time and spleen coefficient in Liqi sanjie extractum high-dose group were significantly higher than those in the control group （P＜0.05 or P＜0.01）. Mean hemoglobin concentration， granulocyte percentage， albumin， alkaline phosphatase and K+ were significantly lower than those in the control group （P＜0.05 or P＜0.01）. No abnormalities in systemic autopsy and histopathology were noticed in rats. CONCLUSIONS： Long-term intragastric administration of Liqi sanjie extractum can cause certain toxic reactions in rats， and low dose of Liqi sanjie extractum causes less and lighter toxic reactions which can be automatically recovered after drug withdrawal. It can provide reference for the determination of clinical safe dose.

OBJECTIVE： To investigate the improvement effects of Liqi sanjie granule on liver-qi stagnation model rats. METHODS： According to the weight， totally 80 rats were randomly divided into blank control group （normal saline）， model control group （normal saline）， Xiaoyao pill control group （positive control a， 750 mg/kg ，calculated by crude drug）， Xiaojin pill control group （positive control b， 200 mg/kg， calculated by pill weight）， Liqi sanjie pill control group （prototype control， 1 957 mg， calculated by crude drug） and Liqi sanjie granule low-dose， medium-dose and high-dose groups （978.5， 1 957， 3 914 mg/kg， calculated by crude drug）， with 10 rats in each group. Each group was given medicine 20 mL/kg intragastrically once a day， for consecutive 21 d. 1 h after per medication， liver-qi stagnation model was established in those groups by binding method except for blank control group. The syrup preference of rats was determined by designing syrup preference test. Rattail suspension test was adopted to determine the hanging immobility time and struggling times of mice. Open-field behavior test was used to determine total behavior score so as to judge the extent of liver-qi stagnation and effect of the drug in rats. RESULTS： Compared with blank control group， hanging immobility time of model control group was significantly prolonged， the syrup preference and the total behavior score of open field test were decreased significantly， with statistical significance （P＜0.05 or P＜0.01）. Compared with model control group， the struggling times of rats were increased significantly in Xiaojin pill control group， Liqi sanjie pill control group and Liqi sanjie granule medium-dose group （P＜0.05 or P＜0.01）； the hanging immobility time of Xiaoyao pill control group， Xiaojin pill control group， Liqi sanjie pill control group， Liqi sanjie granule low-dose and medium-dose groups were shortened significantly； syrup preference and total behavior score of open-field behavior test were increased significantly （P＜0.05 or P＜0.01）. Compared with Liqi sanjie pill control group， the struggling times of rats were decreased significantly and hanging immobility time were prolonged significantly only in Liqi sanjie granule high-dose group （P＜0.05 or P＜0.01）； there was no statistical significance in above indexes of rats in Liqi sanjie granule low-dose and medium-dose groups （P＞0.05）. CONCLUSIONS： Liqi sanjie granule can significantly improve liver-qi stagnation caused by binding method， and the effects of low-dose and medium-dose Liqi sanjie granule are similar to those of Liqi sanjie pill.

Objective To compare two different regimens of ultrasound-guided Continuous ad-ductor canal block (CACB)for postoperative analgesia and early ambulation after total knee arthro-plasty (TKA).Methods Sixty-seven patients scheduled for unilateral TKA undergoing spinal anes-thesia,13 males and 54 females,aged 18-85 years,BMI 18-30 kg/m2,ASA physical status Ⅰ-Ⅲ, were randomly divided into the continuous infusion group A (n=34)and the intermittent boluses group B (n=33).After the operations,ultrasound-guided CACB were administered and 20 ml of 0.2% ropivacaine was given as the loading dose.From then on,patients in both groups used electronic analgesic pumps containing 240 ml of 0.2% ropivacaine for postoperative analgesia.5 ml/h of 0.2% ropivacaine was continuously infused for 48 hours in the group A.5 ml of 0.2% ropivacaine was automated injected every 60 minutes in the group B.All infusion pumps were setted at a bolus dose of 5 ml,with a lock time of 30 minutes.The total consumptions of analgestic pum solution and dezoine, quadriceps muscle strength, active range of knee flexion, ambulation distance and occurrences of adverse reactions such as nausea and vomiting,dizziness,drowsiness,extravasating and errhysis were recorded at different time points postoperatively.Results The total consumptions of analgestic pum solution at 12,24 h postoperatively of group B were significantly reduced than that of group A (P<0.05).The 48 h total dezoine consumption of group B was significantly reduced than group A (P<0.05).Active range of knee flexion at 24,48 h and ambulation distance at 48,72 h of group B were significantly higher than group A (P<0.05).There was no statistical difference in quadriceps muscle strength between group A and group B.The incidence of nausea and vomiting in group A was significantly higher than that in group B,and there were no statistical difference in other adverse reactions between group A and group B.Conclusion Compared with the continuous infusion group,the intermittent bolus group for CACB after TKA can provide better analgesic effect and de-crease opioid use postoperatively,with little effect on motor nerve,promoting early ambulation.

Objective: To explore the value of parameters obtained by dual-pulse wave Doppler to predict the recurrence of atrial fibrillation (AF) after radiofrequency catheter ablation(RFCA) and the value of the technology to evaluate the left ventricular diastolic function of the AF. Methods: Sixty-seven AF patients who were subjected to ablation were selected as the case group, and 47 patients with sinus rhythm were matched as control group. The general clinical data of the case group and the control group was collected, routine ultrasound examination and dual-pulse wave Doppler examination were performed to all of them. A 24-hour Holter examination was performed at 3, 6 and 12 months after radiofrequency catheter ablation in the case group, the patients were divided into two groups with and without recurrence according to the results. Dual-pulse wave Doppler parameters included: ①the time interval between the onset of early transmitral flow velocity (E) and that of early diastolic mitral annular velocity (e′) (TE-e′); ②peak early diastolic transmitral flow velocity (E) and tissue Doppler septal (S) mitral annular early diastolic velocity (e′), peak early diastolic transmitral flow velocity (E) and tissue Doppler lateral (L) mitral annular early diastolic velocity (e′), E/e′(S) and E/e′(L). The differences between the case group and the control group, and between the recurrent and the non-recurrent group were compared. The factors influencing the recurrence of AF after RFCA were analyzed with univariate and multivariate Logistic regression. Results: ①The parameters E/e′(S), E/e′(L) and TE-e′ of case group were higher than those of control group (all P<0.05); ②During follow-up examinations after the ablation, 21 (31.34%) patients recurred. TE-e′ of the recurrence group was higher than that in the nonrecurrence group (P<0.001). The parameters E/e′(S) and E/e′(L) in the recurrence group had no difference compared with those in nonrecurrence group without recurrence(all P>0.05); ③Univariate and multivariate Logistic regression suggested that TE-e′ was an independent predictor for the recurrence of AF patients after the ablation(P=0.001). Conclusions Dual-pulse wave Doppler can evaluate left ventricular diastolic function of atrial fibrillation, TE-e′ is an independent predictor for the recurrence of AF patients after radiofrequency catheter ablation.

Aim Toresearchthemolecularmecha-nisms of adriamycin-induced cardiomyocyte apoptosis based on β-adrenoceptor signaling pathway during de-velopmentofheartfailure.Methods SeventymaleSD rats were assigned randomly into two groups:the con-trol group(CON,n=30)and the ADR-induced cardio-toxicity group (ADR,n =40 ).ADR was administered intraperitoneally in five equal injections (each contai-ning 3 mg·kg-1 )over a period of two weeks,with a total cumulative dose of 15 mg · kg-1 body weight. Age-matched rats injected with saline were used as controls.The general condition of all rats was observed, and transthoracic echocardiography was performed im-mediately following the final ADR injection,and then every other week.Serum and myocardial tissue were harvested at W2,W4 and W6 separately.The serum contents of brain natriuretic peptide(BNP)and cardiac troponin-T(cTn-T)were analyzed by euzymelinked im-munosorbent assay (ELISA ).The pathological change and apoptosis were determined by HE,Masson and ter-minal deoxyribonucleotide transferase-mediated dUTP nick end labeling (TUNEL).The protein expressions ofβ1-AR,β2-AR,PKA and CaMK Ⅱ were detectedbyWesternblot.Results FollowingthefinalADRin-jection,cardiac systolic function and SV declined, which was accompanied by marked atrophy of the heart,low levels of cardiomyocyte fibrosis and apopto-sis,significantly increased serum BNP and cTn-T and decreased β1-AR,PKA and CaMK Ⅱ protein expres-sion.However,cardiac systolic function was improved with the extension of time but remained depressed as compared to CON group.The serum BNP and cTn-T concentration kept on rising.The gradual aggravation apoptosis and concomitant fibrosis in the ADR group heart were observed following ADR withdrawal.β1-AR protein expression was continuously down-regulated,β2-AR protein expression unchanged.Expression of PKA and CaMKⅡ proteins in hearts from ADR-injec-ted rats gradually increased.Conclusion β-AR/PKA/CaMKⅡ signaling pathway mediates cardiomyo-cyte apoptosis during the progress of ADR-induced car-diac dysfunction and pathological remodeling and apop-tosis.