Five new megastigmanes (1-5) were isolated from a decoction of Uncaria rhynchophylla by separation techniques of column chromatography using a combination of multiple stationary phases, including macroporous adsorbent resin, MCI resin, silica gel, Sephadex LH-20, and Toyopearl HW-40F, and reversed phase HPLC. Their structures were characterized by spectroscopic data analysis of HR-ESI-MS, NMR, and CD, in combination with Mosher's mothed as well as ECD and NMR calculations. The new compounds were named uncarphyllonone A (1), uncarphyllonols A (2) and B (3), and uncarphabscisic acids A (4) and B (5). Although the structures of 3 and 4 were previously reported, the reported NMR spectroscopic data were incorrect or do not support the assigned structures in literatures. This is also the first report of discovery of new megastigmane natural products from the Uncaria genus.

Township and Village Health Services Integration Management (TVHSIM) is an essential form of China's two-tiered health service integration plan at the township and village level.Its main purpose,also one of the target goals in China's new healthcare reform,is to gradually integrate rural health services and appropriately allocate rural health resources.This study aims to assess the village doctors' satisfaction with the TVHSIM and provide scientific base to further improve TVHSIM.A cross-sectional study was carried out in which 162 village doctors from Qinghai,Inner Mongolia and Xinjiang in western China were interviewed.Descriptive analysis,independent t-test,one-way ANOVA,Spearman rank correlation and multiple linear regression were used to analyze the difference and relevance between village doctors' personal characteristics and their satisfaction with TVHSIM and six subscales.Village doctors with different years of practice,social insurance status and essential medical knowledge level showed statistically significant differences in their satisfaction levels (all P＜0.05).Age (P＜0.05) and years of practice (P＜0.01) were negatively correlated with Drug and Medical Device Management and Financing Management.Essential medical knowledge level (P＜0.05) was negatively correlated with Operations Management as well.However,social insurance status (P＜0.05) was positively correlated with Human Resources Management and Drug and Medical Device management.Gender,age and years of practice respectively had significant influence on village doctors' satisfaction with TVHSIM (P＜0.01).In conclusion,in order to further promote TVHSIM policy in rural China,a well-rounded social insurance model for village doctors is urgently needed.In addition,the development of TVHSIM is regionally imbalanced.Efficient and effective measures aiming at rationalizing gender and age structure and enhancing essential medical training should be carefully considered.

Objective: To study the feasibility of evaluating the adequacy of hemodialysis using neural calculating method. Methods: The adequacy of hemodialysis patients were evaluated using Daugirdas, TACurea and neural calculating method respectively, the results of the 3 method; were compared with the clinical assessment of the patients. Results: The coincidence rate among the 3 methods was 84.6%, coincidence rate between neural calculating method and the clinical outcome of the patients was 92.3%, which was significantly higher than that of Daugirdas method (76.9%) and of TACurea (80.8%). Conclusion: Neural calculating method has higher accuracy in assessing the adequacy of hemodialysis patients and is clinically practical.

OBJECTIVE To investigate the protective effect and potential mechanism of desmethylbellidifolin (DMB) in chronic alcoholic fatty liver disease. METHODS C57BL/6 mice were randomly divided into five groups. Control, meta?doxine and DMB group (high dose and low dose) mice were fed with Lieber-DeCarli liquid diet containing 5％alcohol for six weeks. Pair-fed group mice were fed with a liquid diet containing the same calories. After treatment, serum GOT, GPT, TG and hepatic T-CHO, TG, GSH, GSH-Px, SOD and CAT levels were measured. Ectopic liver lipid deposition was determined by oil red O and hematoxylin-eosin (HE) staining. Lipid metabolism and autophagy related genes expression were determined by real-time PCR and Western blotting. Electron microscope and laser scanning confocal microscope were used to detect autophagosome and autophagy flux. RESULTS DMB treatment markedly reduced serum TG, GOT and GPT levels in alcohol-induced mice, as well as hepatic levels of T-CHO, TG and MDA, while increased the GSH, GSH-Px, SOD and CAT levels in the liver. Oil red O and HE staining showed that the alcohol-induced lipid accumulation and hepatocyte morphology changes were significantly improved by DMB treatment. Mecha?nistically, the expression of stearoyl-CoA desaturase 1 and fatty acid synthase were significantly decreased, while lipoly?sis related hormone-sensitive lipase was elevated in mouse liver by DMB treatment. In addition, DMB could inhibit the phosphorylation of Akt and mTORC1, and activate autophagy process by inducing autophagy related genes expression, such as LC3, ATG5 and ATG7. Moreover, treatment with DMB notably increased the number of autolysosome and promote the autophagy flux, which may therefore induce the lipolysis and oxidation of lipids and prevent the alcohol-induced excessive lipid accumulation in the liver. CONCLUSION DMB exerts a protective role in alcoholic fatty liver dis?ease by regulating the Akt-mTORC1 pathway mediated autophagy activation.

OBJECTIVETo research the expectorant components in volatile oil from the root and rhizome of Aster tataricus.

METHODGC-MS was applied to isolate and identify the compounds. In addition, TLC was used to isolate compound, and its structure was elucidated on the basis of spectral data analysis. At the same time, its expectorant effect was observed by method of the excretion quantity of phenol red in trachea of mice.

RESULTSeven compounds were isolated and identified by GC-MS, they were (R)(-)-p-menth-1-en-4-ol (1), 2-undecanone (2), n-decanoic acid (3), (-)-spathulenol (4), hexahydrofamrnesyl acetone (5), hexadecanoic acid (6), and cis-9, cis-12-octaecadienoic acid (7). A known compound 1-acetoxy-2-ene(E)-4,6- decandiyne was isolated from the root and rhizome of A. tataricus, and it was shown to have expectorant effect.

CONCLUSION1-Acetoxy-2-ene(E) -4,6- decandiyne, a main compound in volatile oil, had been found to have expectorant effect.

Animals ; Aster Plant ; chemistry ; Drugs, Chinese Herbal ; chemistry ; isolation & purification ; pharmacology ; Expectorants ; chemistry ; isolation & purification ; pharmacology ; Gas Chromatography-Mass Spectrometry ; Magnetic Resonance Spectroscopy ; Male ; Mice ; Oils, Volatile ; chemistry ; Plant Roots ; chemistry ; Rhizome ; chemistry

OBJECTIVETo study the changes of amino acids in cerebral spinal fluid (CSF) in children with spastic or athetotic cerebral palsy (CP) by examining CSF levels of glutamic acid (Glu), gamma-aminobutyric acid (GABA) and aspartate (ASP).

METHODSCSF samples were obtained from 13 children with spastic CP, from 14 children with athetotic CP, and from 10 children without central nervous system and infectious diseases (control group). CSF levels of Glu, GABA and ASP were determined by high-performance liquid chromatography.

RESULTSCSF levels of GABA, ASP and Glu in the control group were 13.04+/-2.19, 10.21+/-0.45 and 8.41+/-2.26 micromol/L, respectively. Compared with the control group, CSF GABA levels in the spastic and the athetotic CP groups (8.02+/-2.03 and 10.01+/-2.68 micromol/L respectively) significantly decreased (P<0.01), whereas CSF levels of Glu (20.99+/-8.15 and 28.77+/-17.62 micromol/L respectively) and Asp (13.53+/-3.93 and 14.02+/-2.88 micromol/L respectively) in the spastic and the athetotic CP groups significantly increased (P<0.01). There were statistical differences in the GABA level between the spastic and the athetotic CP groups (P<0.05). In children with spastic CPCSF Glu level was positively correlated to muscle tension.

CONCLUSIONSCSF excitatory amino acid levels increased, while CSF inhibitory amino acid levels decreased in children with CP. There were differences for CSF amino acid levels in different types of CP. The changes of amino acid levels may contribute to the pathogenesis of CP.

Amino Acids ; cerebrospinal fluid ; Cerebral Palsy ; cerebrospinal fluid ; physiopathology ; Child, Preschool ; Chromatography, High Pressure Liquid ; Female ; Humans ; Male ; Muscle Tonus

Traditional Chinese medicines (TCMs), with a history of thousands of years, are widely used clinically with effective treatment. However, the drug delivery systems (DDSs) for TCMs remains major challenges due to the characteristics of multi-components including alkaloids, flavones, anthraquinones, glycosides, proteins, volatile oils and other types. Therefore, the novel preparations and technology of modern pharmaceutics is introduced to improve TCM therapeutic effects due to instability and low bioavailability of active ingredients. Salviae Miltiorrhizae Radix et Rhizoma, the radix and rhizomes of Salvia miltiorrhiza Bunge (Danshen in Chinese), is a well known Chinese herbal medicine for protecting the cardiovascular system, with active ingredients mainly including lipophilic tanshinones and hydrophilic salvianolic acids. In this review, this drug is taken as an example to present challenges and strategies in progress of DDSs for TCMs. This review would also summary the characteristics of active ingredients in it including physicochemical properties and pharmacological effects. The purpose of this review is to provide inspirations and ideas for the DDSs designed from TCMs by summarizing the advances on DDSs for both single- and multi-component from Danshen.

Objective:To analyze the cardiopulmonary function of stable patients with pulmonary arterial hypertension (PAH), and to explore effects of the cardiopulmonary exercise testing (CPET)-based individualized moderate-intensity exercise prescription on cardiopulmonary functional reserve and exercise capacity in patients with PAH. Methods:From April, 2018 to July, 2019, 31 stable patients with PAH (PAH group) and 32 healthy counterparts (normal group) were enrolled. All subjects underwent CPET. PAH group was assessed with 6-Minute Walking Test (6MWT), and then was divided into exercise group (n = 16) and control group (n = 15). Both groups were treated with ordinary targeted drugs, while the exercise group was additionally provided with an individualized moderate-intensity exercise prescription of △50% power treadmill training, five days a week for eight weeks. CPET and 6MWT were conducted again after intervention. Results:Before intervention, body mass, body mass index (BMI), force vital capacity (FVC), forced expiratory volume in one second (FEV₁), maximum voluntary ventilation (MVV), anaerobic threshold (AT), peak heart rate (HRpeak), peak systolic blood pressure (SBPpeak), peak load power (WRpeak), peak oxygen uptake (VO₂peak), peak oxygen pulse (VO₂/HRpeak), peak cardiac output (COpeak), peak minute ventilation (VEpeak), peak end-tidal carbon dioxide (P_ETCO₂peak), peak pulse oxygen saturation (SpO₂peak) and oxygen uptake efficiency plateau (OUEP) were significantly lower (t > 2.419, P < 0.05), and the rest heart rate (HRrest), peak dead space to tidal volume ratio (V_D/V_Tpeak), minimum ventilatory equivalent for carbon dioxide (Lowest VE/VCO₂) and slope of ventilatory equivalent for carbon dioxide (VE/VCO₂ slope) were higher (|t| > 2.615, P < 0.05) in PAH group than in the normal group. After intervention, FEV₁, MVV, VO₂peak (ml/min/kg) and VO₂/HRpeak decreased in the control group (t > 2.272, P < 0.05); FVC, FEV₁, MVV, AT, SBPpeak, WRpeak, VO₂peak, VO₂/HRpeak, COpeak, VEpeak, P_ETCO₂peak, SpO₂peak and 6-Minute Walking Distance (6MWD) increased (|t| > 2.167, P < 0.05), while the average Lowest VE/VCO₂ and VE/VCO₂ slope decreased (t > 2.264, P < 0.05) in the exercise group. Compared with the control group, the FEV₁/FVC, AT, WRpeak, VO₂peak, VO₂/HRpeak, COpeak and 6MWD increased in the exercise group (|t| > 2.168, P < 0.05). Conclusion:The holistic cardiopulmonary function of stable patients with PAH decreases. CPET-based individualized moderate-intensity exercise could enhance the cardiopulmonary functional reserve and exercise capacity of patients with PAH.

OBJECTIVEInterferon-γ (IFN-γ) plays an important role in apoptosis and was shown to increase the risk of diabetes. Visfatin, an adipokine, has anti-diabetic, anti-tumor, and regulating inflammatory properties. In this study we investigated the effect of visfatin on IFN-γ-induced apoptosis in rat pancreatic β-cells.

METHODSThe RINm5F (rat insulinoma cell line) cells exposed to IFN-γ were treated with or without visfatin. The viability and apoptosis of the cells were assessed by using MTT and flow cytometry. The expressions of mRNA and protein were detected by using real-time PCR and western blot analysis.

RESULTSThe exposure of RINm5F cells to IFN-γ for 48 h led to increased apoptosis percentage of the cells. Visfatin pretreatment significantly increased the cell viability and reduced the cell apoptosis induced by IFN-γ. IFN-γ-induced increase in expression of p53 mRNA and cytochrome c protein, decrease in mRNA and protein levels of anti-apoptotic protein Bcl-2 were attenuated by visfatin pretreatment. Visfatin also increased AMPK and ERK1/2 phosphorylation and the anti-apoptotic action of visfatin was attenuated by the AMPK and ERK1/2 inhibitor.

CONCLUSIONThese results suggested that visfatin protected pancreatic islet cells against IFN-γ-induced apoptosis via mitochondria-dependent apoptotic pathway. The anti-apoptotic action of visfatin is mediated by activation of AMPK and ERK1/2 signaling molecules.

Adenylate Kinase ; metabolism ; Animals ; Apoptosis ; physiology ; Cell Line ; Cytokines ; physiology ; Flow Cytometry ; Interferon-gamma ; physiology ; Islets of Langerhans ; cytology ; MAP Kinase Signaling System ; Nicotinamide Phosphoribosyltransferase ; physiology ; Rats ; Real-Time Polymerase Chain Reaction ; Signal Transduction

Two new folate-derived analogues, named uncarophyllofolic acids A (1) and B (2), respectively, were isolated from the Uncaria rhynchophylla hook bearing stem (Gouteng in Chinese). The distinct stereochemical structures of 1 and 2 were determined by spectroscopic data analysis in combination with acidic hydrolysis and Marfey's derivatization, along with comparison of their specific rotation and Cotton effect (CE) data with those of the biogenetically related known derivatives as well as theoretical calculations of electronic circular dichroism (ECD) spectra. A plausible biosynthetic pathway of 1 and 2, associating to folate metabolism and the previously reported orychophragines A-C from Orychophragmus violaceus, is discussed.