Objective To evaluate the relationship between plasma substance P (SP) and calcitonin gene-related peptide (CGRP) concentrations and intraoperative cardiovascular events in diabetic patients.Methods Twenty-two patients of either sex with type 2 diabetes mellitus and 22 non-diabetic patients of either sex,of American Society of Anesthesiologists physical status Ⅰ or Ⅱ,aged 50-77 yr,undergoing elective knee arthroplasty under neuraxial anesthesia,served as diabetes mellitus group (group DM) and non-diabetes mellitus group (group NDM),respectively.The patients of either group were further divided into 2 subgroups (n =11 each) according to whether or not the patients had cardiovascular diseases before operation:no cardiovascular disease subgroups (NDM-NCVD subgroup and DM-NCVD subgroup) and cardiovascular disease subgroups (NDM-CVD subgroup and DM-CVD subgroup).The plasma SP and CGRP concentrations were dertermined by enzyme-linked immunosorbent assay at 30 min before operation and at the end of operation.The plasma cardiac troponin Ⅰ (cTnI) concentrations were measrued by enzyme-linked immunosorbent assay at 30 min before operation and 24 h after operation.The development of intraoperative cardiovascular events was recorded.Results Compared with group NDM,the incidence of intraoperative cardiovascular events and plasma cTnI concentrations at each time point were significantly increased,and the plasma concentrations of SP and CGRP were decreased in group DM (P＜0.05).Compared with group DM-NCVD,the incidence of intraoperative cardiovascular events and plasma cTnI concen trations at each time point were significantly increased,and the plasma concentrations of SP and CGRP were decreased in group DM-CVD (P＜0.05).Conclusion The development of intraoperative cardiovascular events is related to the decrease in plasma concentrations of SP and CGRP in diabetic patients.

Objective: To explore the in vitro inhibition effect of Zuojin pills on 6 cytochrome P450 isoenzymes ( CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6 and CYP3A4) in human liver microsomes. Methods:The water extract of Zuojin pills, Cop-tidis Rhizoma and Euodiae Fructus was respectively incubated with human liver microsomes in the presence of seven probe substrates of CYP450 isoenzymes, and seven metabolites of cytochrome P450 probe substrate ( paracetamol/CYP1A2, 6α-hydroxypaclitaxel/CYP2C8, 4-hydroxydiclofenac/CYP2C9, 4-hydroxymephenytoin/CYP2C19, dextrorphan/CYP2D6, 6β-hydroxytestosterone/CYP3A4 and 1-hydroxymidazolam/CYP3A4) were simultaneously measured by LC-MS/MS, and the inhibitory effects were evaluated with IC50 value. Results:The IC50 value of Zuojin pills on CYP2D6, CYP1A2 and CYP3A4_T was 11. 6, 77. 4 and 97. 0 μg·ml-1 , respec-tively. The other IC50 values were from 334 to 690μg·ml-1 on CYP2C8, CYP2C9, CYP2C19 and CYP3A4_M isoenzymes. The IC50 value of Coptidis Rhizoma on CYP2D6, CYP1A2 and CYP3A4_T was 5. 8, 36. 8 and 59. 2 μg·ml-1 , respectively. The other IC50 values were from 163 to 476 μg·ml-1 on CYP2C8, CYP2C9, CYP2C19 and CYP3A4_M isoenzymes. The IC50 value of Euodiae Fructus on CYPs was over 107 μg·ml-1 . Conclusion:Zuojin pills shows notable inhibitory effect on CYP2D6, and weak inhibitory effects on CYP1A2 and CYP3A4_T. Coptidis Rhizoma has similar effects on CYPs and may be the main herbal medicine in the formu-la. Therefore, much attention should be paid to the combination of Zuojin pills and the drugs metabolized by human CYP2D6 in clin-ics.

OBJECTIVE: To prepare ethacridine lactate solution and to evaluate its quality.METHODS: The solution was prepared with ethacridine lactate as principal components and sterilized by steam sterilization.HPLC method was used for the determination of ethacridine.Calesil ODS column was used with mobile phase consisted of methanol-acetonitrile-0.05% sodium laurysulfonate (pH=3.0,20 ∶ 20 ∶ 60) at detection wavelength of 270 nm.The column temperature was set at 30 ℃ and injection volume was 10 ?L.The effect of sterilization on the content of preparation was determined.RESULTS: The preparation assumed as yellow transparent solution.The linear range of ethacridine was 5～50 ?g?mL-1(r=0.999 9) with an average recovery of 101.47% (RSD=1.32%,n=9).The content of ethacridine in the solution was not changed after sterilization.CONCLUSION: The quality of prepared ethacridine lactate solution is up to the standard.

Objective To screen the high specific and sensitive monitoring indications in the diagnosis of intestinal barrier dysfunction.Methods A total of 70 critical patients with intestinal barrier dysfunction and acute physiology and chronic health evaluation (APACHE) Ⅱ score≥8 and over the same period 41 patients without intestinal barrier dysfunction and APACHE Ⅱ score≤6 were recruited.The general information,histories,symptoms,physical signs,24 hours urine output and the condition of mechanical ventilation treatment were recorded.The venous blood was taken for bacteria culture,white blood cell counting,creatinine level,diamine oxidase (DAO) activity,D-lactic acid,intestinal fatty acid binding protein (IFABP) and endotoxin level testing.The urine was taken for urinary IFABP level testing.Twenty-four hours urine was reserved for 24 hours total urinary IFABP testing.The factors which might influence intestinal barrier dysfunction were analyzed by univariate analysis and multivariate analysis.The measurement data were analyzed by t test and the count data were analyzed by x2 test.The factors were screened according to receiver operating characteristic (ROC) curve.Results The factors related with intestinal barrier dysfunction were white blood cell counting (OR=3.971,P=0.046),plasma endotoxin level (OR=7.857,P=0.005)and 24 hours total urinary IFABP (OR=11.154,P=0.001).The areas under the ROC curve (AUC)of plasma endotoxin level and 24 hours total urinary IFABP were 0.852 and 0.820 respectively (both P＜0.01).The critical value was 8.0 pg/ml and 17.12 ng respectively.The sensitivity was 97.8％ and 84.4％.The specificity was 66.7％ and 72.7％.Conclusion Once critical patients presented certain gastrointestinal symptoms and physical signs with plasma endotoxin level ＞8.0 pg/ml and or 24 hours total urinary IFABP ＞17.12 ng,which might indicate intestinal barrier dysfunction.

Objective Recent studies in neonatal animals have shown that even slightly decreasing in brain or core temperature could ameliorate the damage resulting from hypoxic-ischemia insults. But the influence of hypothermia which had been used after the end of hypoxia-ischemia of the model hypoxia-ischemia brain damage(HIBD)was unknown. This research wanted to investigate whether hypothermia of defferent begin time after HIBD still could protect the brain in neonatal rats. Methods Pericranial temperatures were adjusted to 31 C in neonatal rats immediately or 2h after the end of hypoxia-ischemia(HI),the number of apoptosis cells in HIBD rats' brain had been counted,rat pups' storing food ability had been observed. Results Apoptosis increased obviously when rat pups were 8 days old, while hypothermia reduced apoptosis ,and postponed apoptosis expression in group that 31 C hypothermia was used immediately or 1h after the end of HI,and hypothermia improved the rat pups' storing food ability. This effect was more obviously in the group that hypothermia was used immediately after the HI than in the group that hypothermia was used 1h after the HI. But the protective effect was not clear in the group that hypothermia was used 2 h after the HI. Conclusion Hypothermia which was used within 1h after the end of HI could protect the HIBD neonatal rat pups brain, this effect was more obviously in the hypothermia be used early after the end of HI group than in the hypothermia be used late after the end of HI group.

AIM: To explore the role of purinergic signaling mediated by ATP in the Alzheimer ’ s disease (AD)-related colon motility disorder and its related molecular mechanisms .METHODS:(1)Clinical trials:AD patients in our hospital were collected and studied .Radioimmunoassay was used for the determination of plasma motilin (MTL), cholecystokinin (CCK), vasoactive intestinal peptide (VIP) and nitric oxide (NO), and high-performance liquid chroma-tography ( HPLC) was applied to test the level of adenosine triphosphate ( ATP) .The patients were assessed by neuropsy-chology and scored accordingly .( 2 ) In animal experiments , AD mice received Morris water maze test , and the spatial learning and memory function were evaluated .The plasma levels of MTL , CCK, VIP and NO were examined by radioimmu-noassay , and the level of ATP was measured by HPLC .Choline acetyltransferase ( ChAT ) , VIP, nitric oxide synthase ( NOS) and ATP synthase were detected by immunohistochemistry .Western blot and immunohistochemistry were used to detect the expression of P2Y receptor.(3) In vitro, organ bath was applied to observe the effect of α,β-methylene ATP (α,β-MeATP), an agonist of P2Y receptor, on both spontaneous and electrically evoked contraction of colonic smooth muscle strip, and the technique of intracellular microelectrode was applied to observe the effect of α,β-MeATP on the membrane potential of colonic smooth muscle cells .RESULTS:Compared with control group , the levels of MTL and CCK were decreased (P<0.01), and the levels of NO and ATP were increased (P<0.05 or P<0.01), while the VIP level was not changed.Mini-Mental State Examination (MMSE) score was decreased (P<0.05), Alzheimer’s Disease Assess-ment Scale-Cognitive Subscale (ADAS-Cog) score, Neuropsychiatric Inventory (NPI) score and Alzheimer’s Disease Co-operative Study-Activities of Daily Living Scale ( ADCS-ADL ) were all increased as compared with control group ( P <0.01).The 4~6 d escape latency of APP/PS1 AD mice was significantly prolonged (P<0.05), and the space explora-tion ability distinctly reduced (P<0.05).In AD mice, the levels of MTL and CCK were decreased (P<0.01), and the levels of NO and ATP were increased (P<0.05 or P<0.01), while the VIP level was not changed .The protein expres-sion of colonic ATP synthase was significantly increased (P<0.05), but the expression of ChAT, VIP and NOS was not changed.The expression of P2Y receptor was increased (P<0.01).The results of in vitro experiment displayed that α,β-MeATP, from 20 μmol/L to 100 μmol/L, inhibited the spontaneous contraction of colonic smooth muscle strip in the nor-mal mice and AD mice ( P<0.05 or P<0.01 ) , and this inhibition was reversed by Na +channel inhibitor tetrodotoxin (TTX) (P<0.05 or P<0.01).In addition, the effect of α,β-MeATP at 100μmol/L on the AD mice was more obvious than that on the normal mice (P<0.05), and this inhibition was also antagonized by TTX (P<0.05 or P<0.01), pro-minent in AD group as compared with control group (P<0.05).In 10 Hz electrically evoked contraction of colonic smooth muscle strip,α,β-MeATP inhibited both the normal and AD mice (P<0.05 or P<0.01), while the inhibition was more obvious in the AD mice at the concentration of 40μmol/L or 100μmol/L (P<0.05 or P<0.01).CONCLUSION:AD patients and AD mice are accompanied by decreased MTL and CCK levels , and enhanced NO level , thus inducing colonic motor dysfunction along with AD .Meanwhile, ATP in plasma, purinergic neurons , and P2Y receptor expression are in-creased in the AD mice .Purinergic signaling mediated by ATP inhibits colonic smooth muscle strip contraction and further paralyzes the colonic movement function in AD .

Objectives:To evaluate essential medicines accessibility from the availability, drug price level and affordability perspective in Beijing. Methods:Data was collected from a sample of a Beijing social security database on diabetes in 2013 and a field research on 4 primary healthcare institutions. The essential medicine equipping rate, medium price ratio ( MPR) and poverty-inducing effect were selected as accessibility indicators. Results:Among 21 sample drugs, the nitrendipine, magnesium sulfate, sodium nitroprusside, prazosin, phentolamine and glyburide e-quipping rates are less than 15%. The 9 sample drugs MPR varied from 1. 3 to 27. 4. The hypertension, hyper-lipemia and diabete poverty-inducing rate varied from 0. 44% to 0. 70% in urban areas, and varied from 1. 17% to 1. 88% in rural areas. Conclusion:Some essential medicines in Beijing are equipped with a very low rate, but have a high price level, and the poverty-inducing population is large. We recommend strengthening the monitoring of es-sential medicines accessibility and introducing appropriate supporting policies.

Objective To study inhibition of litsea cubeba oil on biofilm initial formation stage of Candida albicans ,in order to provide new sight for prevention and treatment of refractory infections arising from Candida albicans biofilm .Methods Observe the inhibition effect of different concentrations litsea cubeba oil on yeast budding by serum germ tube experiments .Results 2 -5μL/mL litsea cubeba oil could thoroughly inhibit budding growth of Candida albicans ,but haven′t antiseptic effect ,the inhibition rate of 0 .25 μL/mL litsea cubeba oil on Candida albicans germ was 85 .0% .Conclusion 2-5μL/mL litsea cubeba oil could completely inhibit the budding growth of Candida albicans ,but have no antiseptic effect .0 .25 μL/mL litsea cubeba oil could hardly inhibit the growth of buds .

Prostate cancer is one of the most common male malignancies in many parts of the world and also the fifth leading cause of cancer death among men worldwide.At present,the commonly used clinical screening methods for prostate cancer are serum prostate-specific antigen(PSA)and transrectal ultrasound guided puncture biopsy.However,the above two diagnostic methods have some related problems such as over-diagnosis caused by false negative and false positive.Metabolomics is an important component of systems biol-ogy,which recognizes minor changes in certain molecular metabolites during tumorigenesis and development.This article reviewed how to use the method of metabolomics to find the metabolites of the three major sub-stances in the patients with prostate cancer and the changes of related metabolic pathways to provide the new ideas for the clinical diagnosis of prostate cancer.

OBJECTIVE To explore the mechanism Baitouweng Decoction on mice with vulvovaginal candidiasis(VVC)based on phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)-hypoxia-inducible factor-1α(HIF-1α)pathway.METHODS Female SPF-grade Kunming mice were injected subcutaneously with estradiol benzoate and vaginally inoculated with Candida albicans suspension to establish a VVC mouse model.The mice with successful modeling were randomly divided into model group,high-,me-dium-,and low-dose Baitouweng Decoction groups(23.4,11.7,and 5.85 g·kg-1),and fluconazole group(0.02 g·kg-1),with 20 mice in each group.Another 20 mice were injected with estradiol benzoate as control group.Treatment started the day after success-ful model establishment and continued for 14 days.Two hours after the last administration,the number of neutrophils in vaginal lavage fluid was examined with Papanicolaou stain.The HE staining method was used to observe the morphology of vaginal tissue.ELISA was used to measure the levels of nicotinamide adenine dinucleo-tide phosphate oxidase 2(NOX2),reactive oxygen species(ROS),su-peroxide dismutase(SOD),malondialdehyde(MDA)in the vaginal tissues.The mRNA expression levels of PI3K,AKT and HIF-1α were detected using qPCR.Western blot was employed to evaluate the protein expression of p-PI3K,PI3K,p-AKT,AKT,and HIF-1α in vaginal tissue.RESULTS Compared to the control group,the model group exhibited a significant increase in neutrophils in va-ginal lavage fluid(P<0.001);the vaginal mucosal layer was severely desquamated and a large number of inflammatory cells infiltrated.Additionally,there was an elevation in NOX2,ROS,and MDA levels in vaginal tissue(P<0.001),while SOD content decreased(P<0.001).Furthermore,the mRNA expression of PI3K,AKT and HIF-1α was reduced along with decreased protein ex-pression of p-PI3K/PI3K,p-AKT/AKT,and HIF-1α(P<0.001).In comparison to the model group,both high-dose and medi-um-dose groups treated with Baitouweng Decoction demonstrated a significant decrease in neutrophil count in lavage fluid(P<0.01,P<0.001);the condition of the vaginal mucosa improved to varying degrees.Moreover,the levels of ROS and MDA in vaginal tissue were reduced(P<0.05,P<0.01,P<0.001),the activity of NOX2 was decreased(P<0.01,P<0.001),and the activity of SOD was increased(P<0.01,P<0.001).The high-dose group showed that,the mRNA expression of PI3K,AKT,and HIF-1α in vaginal tissue was increased(P<0.001),the ratios of p-PI3K/PI3K and p-AKT/AKT,and the protein expression of HIF-1α were increased(P<0.001).CONCLUSION Baitouweng Decoction has a therapeutic effect on VVC,and its mechanism of action may be related to the PI3K/AKT-HIF-1α signal pathway.