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.

OBJECTIVEIt is well documented that epilepsy can increase neurogenesis in certain brain regions and cause behavioral alternations in patients and different epileptic animal models. A series of experimental studies have demonstrated that neurogenesis is regulated by various factors including glucocorticoid (CORT), which can reduce neurogenesis. Most of studies in animal have been focused on adulthood stage, while the effect of recurrent seizures to immature brain in neonatal period has not been well established. This study was designed to investigate how the recurrent seizures occurred in the neonatal period affected the immature brain and how CORT regulated neurogenesis in immature animals.

METHODSNeonatal rats were subjected to 3 pilocarpine-induced seizures from postnatal day 1 to day 7. Then neurogenesis at different postnatal ages (i.e. P8, P12, P22, P50) was observed. Behavioral performance was tested when the rats were mature (P40), and plasma CORT levels following recurrent seizures were simultaneously monitored.

RESULTSRats with neonatal seizures had a significant reduction in the number of Bromodeoxyuridine (BrdU) labeled cells in the dentate gyrus compared with the control groups when the animals were euthanized on P8 or P12 (P<0.05); whereas there was no difference between the two groups on P22. Until P50, rats with neonatal seizures had increased number of BrdU-labeled cells compared with the control group (P<0.05). In Morris water maze task, pilocarpine-treated rats were significantly slower than the control rats at the first and second day, and there were no differences at other days. In probe trial, there was no significant difference in time spent in the goal quadrant between the two groups. Endocrine studies showed a correlation between the number of BrdU positive cells and the CORT level. Sustained increase in circulating CORT levels was observed following neonatal seizures on P8 and P12.

CONCLUSIONNeonatal recurrent seizures can biphasely modulate neurogenesis over different time windows with a down-regulation at early time and up-regulation afterwards, cause persistent deficits in cognitive functions of adults, and increase the circulating CORT levels. CORT levels are related with the morphological and behavioral consequences of recurrent seizures.

Age Factors ; Animals ; Animals, Newborn ; Critical Period (Psychology) ; Dentate Gyrus ; cytology ; growth & development ; metabolism ; Glucocorticoids ; blood ; Male ; Maze Learning ; physiology ; Neurons ; cytology ; metabolism ; Random Allocation ; Rats ; Rats, Wistar ; Seizures ; metabolism ; pathology ; physiopathology ; Stem Cells ; cytology ; metabolism

Seventeen minor triterpenoid acids (1-17) were isolated from an aqueous decoction of Uncaria rhynchophylla by a combinatory application of column chromatography using multiple stationary phases, including macroporous adsorbent resin, MCI resin, Sephadex LH-20, Toyopearl HW-40C, silica gel, and C18 reversed phase silica gel, combined with separation techniques of flash chromatography (FC) and high performance liquid chromatography (HPLC). Their structures were determined by analysis of HR-ESI-MS, UV, CD, and IR as well as 1D and 2D NMR spectroscopic data, of which eight new compounds (1-8) are named successively uncarinic acids Q-X, while the structures of 2 and 7 were confirmed by single crystal X-ray diffraction. In the in vitro assays, 27-hydroxyolean-12-en-28-oic acid (17) inhibited TGF-β-induced HSC-T6 cell activation at the concentration of 5 μmol·L^-1.

In the 21st century, natural disasters and emergencies occur frequently worldwide, which leads to the loss of hundreds of thousands of lives as well as the direct and indirect economic losses. China has a vast territory frequently struck by natural disasters. However, the reality is not optimistic. Poor organization and management during the rescue actions, the lack of large-scale, systematic medical rescue equipment were all great barriers to the outcomes. Mobile hospitals are expected to provide better health care. We were inspired by the concept of mobile hospital. Chongqing Emergency Medical Center, has set up trauma care system since 1988, in which prehospital care, intensive care, and in-hospital treatment is fully integrated. As a major advantage, such a system provided assurance of "golden hour" rescue treatment. Providing mobile intensive care and prehospital surgical service for severe trauma patients could reduce mortality significantly. Based on the civilian experiences in Chongqing Emergency Medical Center, the mobile emergency (surgical) hospital was developed.
China ; Earthquakes ; Emergency Medical Services ; Humans ; Mobile Health Units ; Relief Work ; Rescue Work

Objective To explore the changes of functional connectivity of the prefrontal cortex in chronic heroin addicts under resting-state functional MRI (fMRI). Methods Resting fMRI examination was performed on 13 chronic heroin addicts and 14 healthy volunteers. After pre-processing the resting-state fMRI data, the prefrontal cortex was selected as the seed region, with which a whole-brain voxel temporal correlation in Iow frequency fMRI fluctuations was analyzed and the changes of functional connectivity of the prefrontal lobe in both chronic heroin addicts and healthy volunteers were calculated with SPM5 software. Results Compared with that in the control group, the functional connectivity between the left prefrontal cortex and the left hippocampus, right anterior cingulate, left middle frontal gyrus, right middle frontal gyrus, right precuneus in the heroin addiction group was significantly decreased. The functional connectivity between the right prefrontal cortex and the left orbital frontal cortex, left middle frontal gyrus in thc heroin addiction group was also significantly decreased as compared with that in the control group. Conclusion Functional connectivity of prefrontal cortex in chronic heroin addicts decreases, indicating that the prefrontal cortex may be involved in the maintenance of heroin addiction and relapse after withdrawal.

OBJECTIVETo investigate the levels of cytokines related to T-helper (Th) 17 cells in serum and signal transducers in the psoriatic lesions of patients with psoriasis vulgaris of blood-heat syndrome (BHS) and blood-stasis syndrome (BSS).

METHODSSixty patients with psoriasis vulgaris were divided into the BHS and BSS groups according to the syndrome differentiation of Chinese medicine (CM). Ten healthy subjects were considered as the control group. Cytokine levels of interleukin (IL)-17, IL-23 and IL-6 in serum were determined by enzyme-linked immunosorbent assay. Expression levels of signal transducer and activator of transcription 3 (STAT3), p38-mitogen-activated protein kinase (MAPK) and STAT6 in the psoriatic lesions were determined using immunohistochemistry (IHC), Western blot, and real-time quantitative reverse transcription polymerase chain reaction, respectively.

RESULTSProduction of IL-17, IL-23 and IL-6 in the BHS group and BSS group were significantly increased compared with those in the control group (P<0.05). Levels of IL-17 and IL-23 in the BHS group were higher than those in the BSS group (P<0.05). Compared with the control group, IHC positive expressions and protein expressions of STAT3 and p38-MAPK, and the STAT3 mRNA expressions in the BHS and BSS groups were significantly higher (P<0.05 or P<0.01). The protein expression of STAT3 in the BHS group was significantly higher than that in the BSS group (P<0.05).

CONCLUSIONSCytokines in serum and signal transducers in the psoriatic lesions alter with various CM syndromes of psoriasis. The results provide scientific basis for the treatment based on syndrome differentiation of CM in treating psoriasis vulgaris.

Adult ; Female ; Gene Expression Regulation ; Humans ; Immunohistochemistry ; Interleukin-17 ; blood ; Interleukin-23 ; blood ; Interleukin-6 ; blood ; Male ; Psoriasis ; blood ; enzymology ; genetics ; immunology ; RNA, Messenger ; genetics ; metabolism ; STAT3 Transcription Factor ; genetics ; metabolism ; STAT6 Transcription Factor ; genetics ; metabolism ; Signal Transduction ; Syndrome ; Th17 Cells ; immunology ; p38 Mitogen-Activated Protein Kinases ; genetics ; metabolism

BACKGROUNDHypoxemic respiratory failure (HRF) is one of the most common causes for neonatal infants requiring aggressive respiratory support. Inhaled nitric oxide (iNO) has been established routinely as an adjunct to conventional respiratory support in developed countries. The aim of this study was to investigate effects of iNO in neonates with HRF in resource limited condition with no or limited use of surfactant, high frequency oscillatory ventilation (HFOV) and extracorporeal membrane oxygenation.

METHODSA non-randomized, open, controlled study of efficacy of iNO was conducted over 18 months. Eligible term and near-term neonates from 28 hospitals with HRF (oxygenation index > 15) were enrolled prospectively into two groups as either iNO or control. Oxygenation improvement and mortality as primary endpoint were determined in relation with dosing and timing of iNO, severity of underlying diseases, complications and burden. Intention-to-treat principle was adopted for outcome assessment. Response to iNO at 10 or 20 parts per million (ppm) was determined by oxygenation in reference to the control (between-group) and the baseline (within-group).

RESULTSCompared to 93 controls, initial dose of iNO at 10 ppm in 107 treated infants significantly improved oxygenation from first hour (P = 0.046), with more partial- and non-responders improved oxygenation with subsequent 20 ppm NO (P = 0.018). This effect persisted on days 1 and 3, and resulted in relatively lower mortalities (11.2% vs. 15%) whereas fewer were treated with surfactant (10% vs. 27%), HFOV (< 5%) or postnatal corticosteroids (< 10%) in both groups. The overall outcomes at 28 days of postnatal life in the iNO-treated was not related to perinatal asphyxia, underlying diseases, severity of hypoxemia, or complications, but to the early use of iNO. The cost of hospital stay was not significantly different in both groups.

CONCLUSIONSWith relatively limited use of surfactant and/or HFOV in neonatal HRF, significantly more responders were found in the iNO-treated patients as reflected by improved oxygenation in the first three days over the baseline level. It warrants a randomized, controlled trial for assessment of appropriate timing and long-term outcome of iNO.

Administration, Inhalation ; Female ; Humans ; Hypoxia ; drug therapy ; physiopathology ; Infant, Newborn ; Male ; Nitric Oxide ; administration & dosage ; therapeutic use ; Pregnancy ; Respiratory Insufficiency ; drug therapy ; physiopathology

Objective:To observe the expression levels of niemann-pick C1-like 1 (NPC1L1) and adenosine triphosphate-binding cassette transporters G8 (ABCG8) in intestine of hyperlipidemic model rats, in order to investigate the therapeutic mechanism of Shuangyu Tiaozhi decoction on hyperlipidemia. Method:A total of 40 SD rats were selected, including 8 for normal control group. The remaining 32 rats were used to establish hyperlipemic model. After modeling, the rats were randomly divided into the model group (equivalent normal saline), the high and low-dose Shuangyu Tiaozhi groups (15.6, 7.8 g·kg^-1), and the Simvastatin group (4 mg·kg^-1), with 8 in each group. They were given drugs by gavage for 8 weeks. The levels of total cholesterol (TC), triglyceride (TG) in serum and total cholesterol (TTC), free cholesterol (FTC) in liver of rats in each group were determined by biochemical and enzymatic methods. The morphological changes of liver were observed by hematoxylin-eosin (HE) staining, and the levels of expressions of NPC1L1, ABCG8 and liver X receptor-α (LXR-α) in intestine were detected by Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and Western blot. The expression of ABCG8 protein was determined by immunohistochemistry. Result:After successful replication of the hyperlipidemia model, the blood lipid level was abnormally increased, and the liver steatosis became obvious in the model group compared with the normal control group. The expression levels of NPC1L1, LXR-α and ABCG8 increased significantly (P<0.05, P<0.01). Compared with the model group, the blood lipid levels were significantly reduced in the Shuangyu Tiaozhi decoction group. The expressions of NPC1L1 and LXR-α were significantly down-regulated, but ABCG8 was obviously up-regulated in a dose-dependent manner (P<0.05, P<0.01). The results of immunohistochemistry indicated that the protein expression of ABCG8 in intestine of the model group increased significantly (P<0.01). Compared with the model group, the expression of ABCG8 in each drug-administered groups increased obviously (P<0.05, P<0.01), especially in high-dose Shuangyu Tiaozhi group (P<0.05). Conclusion:Shuangyu Tiaozhi decoction can reduce the blood lipid level of hyperlipemic rat model by reducing the absorption of cholesterol. Its mechanism may be correlated with the down-regulation of NPC1L1 expression and the up-regulation of ABCG8 expression.

Objective:To analyze and determine heavy metal content in Paridis Rhizoma from different genus and localities,in order to provide a reference for selecting cultivation areas and establishing the quality standard of Paridis Rhizoma of heavy metals content. Method:Microwave digestion method combined with inductively coupled plasma atomic emission spectrometry method (ICP-AES) method were applied to determine the contents of 6 heavy metals,i.e. As,Cu,Hg,Cd,Pb and Cr in 39 samples of Paridis Rhizoma of different genus and localities in Yunnan Province. Cluster analysis,statistical analysis and principal component analysis (PCA) were used to compare the differences of heavy metals contents in different localities and species. Result:The contents of six heavy metals in Paridis Rhizoma met the ISO international standard of Heavy Metal Limit of Traditional Chinese Medicine-traditional Chinese Medicinal Materials. Under the limited value standard of Green Trade Standards of Importing Medicinal Plants and Preparations,the over-standard rate of heavy metal As was 15.4%,the excess rate of Cd was 5.1%,and the excess rate of Pb was 2.6%. The contents of Cu and Hg conformed to relevant requirements. Cluster analysis,statistical analysis and principal component analysis showed that for the same variety,differences in producing places had significant effects on heavy metal content,while differences in species had little effects. Conclusion:The results of this study indicated that the heavy metal content of Paris planted in and around Dali basically conformed to relevant standards. The differences of heavy metal content in Paris were mainly regional differences,which provided a theoretical basis for standardizing the cultivation of medicinal materials and formulating the limit standards of heavy metals for Paridis Rhizoma.

To explore the correlation between chemical compositions (organic acids, small molecule sugars, protein and others) of traditional Chinese medicine extracts and the wall stickiness in spray drying. In this study, 55 types of most common used Chinese herbs were selected to determine the content of 7 chemical components such as citric acid and fructose from plant extraction. The status of wall stickiness was observed during the drying process. The principle component analysis (PCA-X), hierarchical clustering analysis(HCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) were then used to evaluate the correlation between each chemical compositions and wall stickiness, so as to look for the essential chemical compositions associated with the wall stickiness. All of the above 3 statistical analysis methods showed significant results in distinguishing the two groups (sticky or non-sticky). PCA-X score chart and HCA clustering scatter plot suggested that the small molecular substance was the main factor causing wall stickiness, which was then proved by the reality where some of the traditional herb extracts were in non-sticky state after drying but in sticky state after alcohol precipitation. OPLS-DA results revealed that L-malic acid, citric acid, fructose and glucose were the difference factors for the wall stickiness of the extracts. Under small molecular components, L-malic acid, citric acid, fructose and glucose were the crucial factors that directly led to the hot melt sticky wall of the herbal extracts, and macromolecular substances might ameliorate the function of wall stickiness.
Citric Acid ; Desiccation ; Discriminant Analysis ; Drugs, Chinese Herbal ; chemistry ; Fructose ; Glucose ; Least-Squares Analysis ; Malates ; Medicine, Chinese Traditional ; Plant Extracts ; chemistry ; Principal Component Analysis