OBJECTIVETo explore metabolite profiling changes in serum of rats with pi-qi deficiency syndrome (PQDS) and pi-yang deficiency syndrome (PYDS) based on liquid chromatograph-mass spectrometer (LC-MS) technique, and to explore the essence of Pi-deficiency syndrome (PDS) from small molecule metabolite level.

METHODSTotally 21 male SD rats of SPF grade were randomly divided into three groups, the normal control group, the PQDS group, and the PYDS group, 7 in each group. Rats in the PQDS group overate for 1 day and fasted for 2 days. They drank freely and then swam to be exhausted in water at 35 degrees C - 37 degrees C for 15 successive days. The PYDS model was established by the same method for PQDS rats plus drenching 20% Folium sennae water extract (2 mL/100 g), once in the morning and once in the evening for one successive week. After modeling, models were evaluated according to rat general state, changes in body weight and rectal temperature. Serum metabonomic profiles were detected using LC-MS technique. Difference in inter-group metabolite spectrograms was analyzed using orthogonal partial least squares discriminant analysis (OPLS-DA). Potential biomarkers related to syndrome types in rat serum were selected via the parameter of variable importance in the projection (VIP).

RESULTSThe weight of rats in the PQDS group and the PYDS group decreased more significantly after modeling. The difference in prepost weight was statistically significant from that of the normal control group (P < 0.01). It was more obviously lowered in the PYDS group than in the PQDS group (P < 0.05). Compared with the normal control group, the rectal temperature of rats in the PYDS group and the PQDS group decreased (P < 0.05, P < 0.01). It decresed more in the PYDS group than in the PQDS group (P < 0.05, P < 0.01). Compared with the normal control group, levels of PC(19:0)/PE(22:0), PC(17:0)/PE(20:0), capric acid, oleic acid, stearic acid, succinic acid, fumaric acid, malic acid, glucose increased; arachidonic acid, linolenic acid, lauric acid, androsterone, 4-heptanone, dihydroxyacetonephosphate (DHAP) (6:0), and uridine decreased in the PYDS group and the PQDS group. Compared with the PQDS group, levels of PC(22:1), PC (22:6), PE (18:0)/PC (15:0), retinol, and deoxycytidine increased significantly in the PYDS group; PC (18:1), PC(19 :3), PC (20:3), PC (17:0)/PE (20:0), PC (19:1)/PE (22:1), PC (19:0)/PE (22:0), PC (17:1)/PE (20: 1), PC (16:1)/PE (19:1), cholic acid, hippuric acid, furoic acid, undecanedicarboxylic acid, palmitoleic acid, hydroxy stearic acid, eicosatrienoic acid, phenylalanine, tyrosine, glutamic acid, serine, carbamoyl aspartic acid, palmitoyl carnitine, tetradecanoyl carnitine, acetylcarnitine, and linoleylcarnitine decreased more significantly in the PYDS group.

CONCLUSIONSComparative contents of various serum metabolites changed significantly in PQDS and PYQS model groups. Some potential small molecular biomarkers related to PDS were preliminarily identified. These results might provide some data reference for exploring scientific connotation and pathological mechanisms of PDS.

Animals ; Biomarkers ; blood ; Chromatography, Liquid ; Discriminant Analysis ; Disease Models, Animal ; Drugs, Chinese Herbal ; Least-Squares Analysis ; Male ; Mass Spectrometry ; Metabolome ; Metabolomics ; Qi ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Yang Deficiency ; blood

α-Hederagenin (H), derived from Hedera nepalensis var.sinensis, is a pentacyclic oleane-type triterpenoid that exhibits clear cytotoxicity to different tumor cell lines.In this study,a series of novel C-28 derivatives of hederagenin (H) were designed and synthesized in attempt to develop potent tumor resistance reverse activities agents. Previous research showed that H6 displayed robust reverse activity for paclitaxel resistance in KBV cells. Importantly, Co-treatment of paclitaxel with H6 significantly reduced the tumor weight to 42%. Pleasingly, H6 enhanced the efficacy of paclitaxel against KBV cancer cell-derived xenograft tumors in nude mice.Mechanism studies had found that H6 activated permeability glycoprotein(P-gp)ATPase,reduced intracellular ATP levels and inhibited efflux of P-gp substrates,thus enhancing the antitumor activity of paclitaxel on KBV cells.Molecular docking analysis of homology P-gp and H6 then conducted using the Surflex-Dock module.H6 showed a high binding affinity docking score with a total score of 5.4148,much higher than that of H(0.1414).The nov-el C-28 derivatives of H was synthesized from H6 via three-step reaction. The reversal activity of all synthesized H derivatives were tested using the MTT assay.The results showed that the derivatives of nitrogen groups at C-28 displayed same even potent activity than parent compound H6.In addition,its underlying mechanism of action and in vivo activity are in explore.

BACKGROUNDTarget-controlled infusion (TCI) has been recently developed and successfully implemented in clinical practice. The current study was to estimate the population pharmacokinetics of rocuronium TCI in adult patients using nonlinear mixed-effects model (NONMEM), and to investigate the influence of relevant factors in adult patients.

METHODSFourteen ASA I-II patients undergoing elective laparoscopy operation with general anesthesia were included. After induction, all patients received rocuronium by TCI system. The beginning target plasma concentration (Cpt) was 2.0 µg/ml, then increased Cpt according to the neuromuscular transmission monitoring. The endpoint of Cpt was determined when the T₁ scale was blocked by 90% - 95%. TCI rocuronium was stopped 30 minutes before the end of the operation. Arterial blood was drawn before anesthesia at 0, 2, 4, 6, 8, 10, 15, 20, 30, 45, 60, 120, 180, 240 and 360 minutes after the infusion of rocuronium was stopped for the analysis of plasma concentrations of rocuronium by liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). The population pharmacokinetics analysis was performed using NONMEM program.

RESULTSThe pharmacokinetics of TCI rocuronium in adult patients was best described by a three-compartment model. Pharmacokinetic parameters were clearance (CL)₁ = 0.205 L/min, CL₂ = 0.324 L/min, CL₃ = 0.0292 L/min, volumes of distribution (V)₁ = 4.00 L, V₂ = 2.28 L, V₃ = 4.26 L, Vdss = 10.54 L. Both age and weight as covariates affected the pharmacokinetic parameters. V₁ and CL₁ were negatively correlated with patient age. CL₁ was positively correlated with weight.

CONCLUSIONSNo pharmacokinetic change was noted when rocuronium was administered via TCI. Both age and weight as covariates affected the pharmacokinetic parameters.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Androstanols ; administration & dosage ; pharmacokinetics ; Female ; Humans ; Infusion Pumps ; Male ; Middle Aged ; Young Adult

Objective:To review the experience of closure of the left-main-bronchial stump fistula using endoscopic liner cutter staplers through the right thoracic approach and I stage or staged treatment for the left pyothorax.Methods:6 patients with the left-main-bronchial stump fistula after left pneumonectomy combined with pyothorax were treated by closing the left-main-bronchial stump using endoscopic liner cutter staplers through the right thoracic approach, and pleura was used to cover the distal and proximal incisional margin of the stump respectively. The thoracic T-tube drainage was used in the I stage or staged treatment for the left pyothorax.Results:All patients were survived without recurrence of the bronchopleural fistula. 4 patients were observed to have no recurrence of pyothorax when 1 patient had recurrence of pyothorax and was treated with intermittent T-tube drainage.1 patient operated with left-thoracic fenestration in the past was treated with drainage waiting for secondary operation.Conclusion:The right thoracic approach seemed to be a safer and more effective method than the transsternal transpericardial approach in cases with the left-main-bronchial stump fistula combined with pyothorax. The use of endoscopic liner cutter staplers reduced the risk of bleeding, infection and recurrence of fistula. The T-tube drainage in the I stage or staged treatment for the left pyothorax was considered to be an easier way for treatment.

BACKGROUNDLittle is known about the influence of liver transplantation on the pharmacokinetics of most anesthetic drugs. The goal of this study was to study the population pharmacokinetics of remifentanil in the different phases of orthotopic liver transplantation (OLT) and the influence of relevant factors.

METHODSThirteen adult patients undergoing OLT were enrolled. A single bolus infusion of remifentanil 5 microg/kg was administered during the preanhepatic, anhepatic and neohepatic phases of OLT. Arterial blood samples of 1.5 ml were collected at 0 (baseline), 1, 2, 3, 5, 7, 10, 15, 20, 25, 30, 45, 60 and 90 minutes after drug administration. Remifentanil concentration was assayed by high-performance liquid chromatography/mass spectrometry/mass spectrometry (HPLC/MS/MS). Population pharmacokinetic modeling was performed using nonlinear mixed-effects modeling (NONMEM).

RESULTSThe pharmacokinetics of remifentanil in patients undergoing OLT was best described by a two-compartment open model. The pharmacokinetic parameters were not influenced by age, gender, operative phase, blood temperature, rehydration volume, or blood loss volume during sampling. The volume of distribution in the central compartment (V(1)) and the volume of distribution in the peripheral compartment (V(2)) were influenced by body weight.

CONCLUSIONSThe population pharmacokinetics of remifentanil in patients undergoing OLT can be well described by a two-compartment open model. The functional status of the liver does not significantly affect the pharmacokinetics of remifentanil, but the body weight is an influential factor of V(1) and V(2).

Adult ; Chromatography, High Pressure Liquid ; Female ; Humans ; Liver Transplantation ; Male ; Middle Aged ; Piperidines ; administration & dosage ; pharmacokinetics ; Tandem Mass Spectrometry

In order to establish HPLC fingerprint of Liuwei Dihuang soft capsule, and to provide certain reference for an quality control of it, the HPLC method was performed on an Agilent C18 (4.6 mm x 250 mm, 5 μm) column with acetonitrile-0.02% trifluoroacetic acid as mobile phase, gradient elution volume flow of 1.0 mL x min(-1), column temperature was 30 degrees C, detection wavelength: 0-60 min, 238 nm, 60-70 min, 210 nm. The software for chromatographic fingerprint was applied to analysis different batches of Liuwei Dihuang soft capsule samples. Sixteen mutual peaks were selected as the fingerprint peaks in 12 samples with loganin as the reference peak, and all of the detected peaks were separated effectively. Cluster analysis (HCA) and similarity analysis (SA) were done based on data of 12 samples clustering analysis of 12 batches of samples were divided into 2 categories. Including 7 for the first class, the rest was second, similarities calculated by SA were all above 0.92, indicating a good similarity between the reference and twelve batches of samples, also, the analysis results of HCA and SA basically the same. This method is simple with good precision, repeatability and stability, and provides the basis for Liuwei Dihuang soft capsule quality control.
Capsules ; analysis ; Chromatography, High Pressure Liquid ; methods ; Drugs, Chinese Herbal ; analysis ; Quality Control

Objective To investigate the expression and significance of major histocompatibility complex classⅡgene in multiple organ dysfunction syndrome.Methods Two-hit porcine model of MODS was duplicated in 18 swine that were randomly assigned into experimental group(Group M,n=9) and control group(Group C,n=9).The Group M was given compound factors including hemorrhagic shock,reperfusion injury and endotoxemia,and the Group C only underwent anesthesia and arterious/ve- nous eannula.After seven days,the animals were killed to remove splenic tissues fro extracting total RNA by Trizol method.The primer of SLA-DQA(MHC classⅡgene of swine)was designed to construct cD- NA by reverse transcription and the quantity of SLA-DQA mRNA detected with real time fluorescent quan- titative polymerase chain reaction(real time FQ-PCR).The standard curve was described by UVP com- puter image analysis system.Results The mortality of Group M was 78%(7/9),and the incidence rate of MODS was 89%(8/9).The expressing quantity of Group M was(1.376?1.006)?10~3,signifi- cantly lower than(5.330?3.053)?10~3 of Group C(P＜0.01).Conclusion Duplication of por- cine MODS model is satisfactory.Down-regulation of MHC classⅡgene may be due to control of classⅡtransactivator(CⅡTA)and release of multiple eytokine,such as TNF-?and IL-10.

To investigate the changes in bcl-2, bax expression and neuron apoptosis in the hippocampus after the blockade of cervical lymphatics, the model of lymphostatic encephalopathy was established by occluding and removing both the superficial and deep cervical lymph nodes in rats. The animals were sacrificed at 1, 2, 3, 5, 7 and 14 d after operation. H and E staining was used to observe the structure of brain tissues and TUNEL staining was used to detect in situ cell apoptosis in the hippocampus. The expression of bcl-2 and bax in the hippocampus were examined by RT-PCR. The results showed that cerebroedema appeared at day 2 and was most serious at day 5 after the blockade of cervical lymphatics. The number of TUNEL positive cells began to increase at day 2 and reached the maximum at day 5. The expression of bax began to increase at day 1 and reached the maximum at day 2. The expression of bcl-2 began to decrease at day 1 and dropped to the minimum at day 5. The items mentioned above recovered to control level at day 14. These results suggest that lymphostatic encephalopathy following the blockade of cervical lymphatics result in changes in bcl-2 and bax expression in the hippocampus and that apoptosis is the main form of neuron death.
Animals ; Apoptosis ; physiology ; Female ; Hippocampus ; metabolism ; pathology ; Lymph Node Excision ; Lymphatic System ; physiology ; Male ; Neck ; Neurons ; cytology ; Proto-Oncogene Proteins c-bcl-2 ; genetics ; metabolism ; Random Allocation ; Rats ; Rats, Wistar ; bcl-2-Associated X Protein ; genetics ; metabolism

Objective To Analyze the change trend of the incidence and mortality of breast cancer in Chinese women from 2005 to 2013 in the Chinese Cancer Registry Annual Report in order to provide references for the implement of the prophylaxis and treatment of breast cancer. Methods Extracted all the records of the incidence and mortality of breast cancer in Chinese women from 2005 to 2013, applied the Joinpoint regression model to analyze the change trend of the incidence and mortality of breast cancer in Chinese women. Results The incidence levels of breast cancer among urban women in China was higher than that in rural from 2005 to 2013, the change trend of urban incidence was stable(t=-0.2, P=0.828), the rural incidence showed an increasing trend(t=7.8, P<0.001). The peaks of urban and rural incidence were in the age group of 50- and the age group of 45- respectively.The mortality of breast cancer among urban women in China was higher than that in rural from 2005 to 2013, the change trend of urban mortality was stable(t=0.8, P=0.458), and the rising trend of rural mortality was obvious(t=3.3, P=0.014). The mortality of urban women began to rise after the age of 30, accelerating to rise after the age of 75, the mortality of rural women began to rise after the age of 30, the change tended to be stable at the age of 55-69, and began to rise after the age of 70 again. Conclusions The incidence and mortality of breast cancer among urban women in China were all higher than that in rural from 2005 to 2013, the rising trend of the incidence and mortality of breast cancer among rural women was obvious, so the prophylaxis and treatment measures of breast cancer should be actively formulated and perfected.

Etanercept has been shown to be effective for the treatment of moderate-to-severe plaque psoriasis.Since most clinical trials examined etanercept in combination with other drugs,the efficacy and safety of etanercept monotherapy for moderate-to-severe plaque psoriasis have not been well established.This prospective study enrolled 61 Chinese patients with moderate-to-severe plaque psoriasis to explore the efficacy and safety of etanercept monotherapy.These patients were treated with etanercept at a subcutaneous dose of 25 mg,twice a week,for 12 weeks.All the 61 patients completed the treatment and showed significant improvement in psoriasis area and severity index (PASI) scores.At 4,8,and 12 weeks after treatment,the response rates (PASI75) were 0％,21.31％,and 40.98％,respectively.It was concluded that etanercept monotherapy is efficacious and safe for patients with moderate-to-severe plaque psoriasis.