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Welcome to Chinese Journal of Clinical Pharmacology and Therapeutics,Today is Chinese

Table of Content

    Volume 22 Issue 4
    26 April 2017
    Lipoxin A4 attenuates hypoxia induced oxidative stress and apoptosis in human first trimester trophoblast cells
    HUANG Yanjun, WU Jie, JIANG Wei, WANG Xiao, HUANG Yinping
    2017, 22(4):  361-366. 
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    AIM: To investigate the effect of lipoxin A4 (LXA4) on oxidative stress and apoptosis of human first trophoblast cells induced by hypoxia.  METHODS: Primary human trophoblast cells were randomized into normoxia group, hypoxia group and hypoxia+LXA4 (1,10 and 100 nmol/L) groups. The level of ROS was determined by DCFH-DA, the activity of SOD, CAT and GPx were detected by the corresponding kits. The apoptosis rate was analyzed by flow cytometer method and the level of Bcl-2 and Bax protein were observed by Western Blot. RESULTS: Compared with normoxia group, the level of ROS and apoptosis rate increased (P<0.05) while the activity of SOD, CAT and GPx decreased (P<0.05) in hypoxia group. Compared with hypoxia group, the level of ROS and apoptosis rate decreased (P<0.05), while the activity of SOD, CAT and GPx increased (P<0.05) in hypoxia+LXA4 (1,10 and 100 nmol/L) groups. Compared with normoxia group, the level of Bcl-2 protein in hypoxia group decreased and the level of Bax protein increased (P<0.05). Compared with hypoxia group, the level of Bcl-2 protein in hypoxia+LXA4 (1,10 and 100 nmol/L) groups increased and the level of Bax protein decreased (P<0.05). CONCLUSION: Lipoxin A4 attenuates hypoxia induced oxidative stress and apoptosis in human first trophoblast cells. The regulation of Bcl-2/Bax expression may be an important mechanism of LXA4 in inhibiting apoptosis.

    Protective effect of total flavones of abelmoschl manihot on hippocampal neurons subjected to anoxia-reoxygenation injury
    WEN Jiyue, CHEN Zhiwu
    2017, 22(4):  367-372. 
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    AIM: To study the protective effect of total flavones of abelmoschl manihot (TFA) on hippocampal neurons subjected to the injury of anoxia/re-oxygenation (A/R) and its endothelium-dependent hyperpolarizing factor (EDHF) mechanism.  METHODS: The injury of primarily cultured hippocampal neurons plus with cerebral basilar artery ring was induced by hypoxia for 4 hours and re-oxygenation for 24 hours, pretreated with TFA, acetylcholine (Ach),etc. Cell viability and the lactate dehydrogenase (LDH) activity in supernatant were served as the cell damage index. The level of free calcium fluorescence intensity in the neurons was detected by laser scanning confocal microscope. RESULTS: Pretreated with TFA and cerebral artery could increase the cell viability, reduce the activity of LDH in culture medium significantly, pretreated with Ach had a similiar effect. The N -nitro-L-arginine-methyl-ester (L-NAME) and indomethacin (Indo) didn't influence the effect of Ach or TFA. Moreover, pretreated with TFA plus with cerebral artery lowered the calcium concentration in neuron (compared with model group). CONCLUSION:TFA has remarkably neuroprotective effect induced by A/R, the mechanism is partially concerned with the calcium overload inhibited by EDHF released from cerebral basilar artery ring.

    Icaritin protects the ICMT-induced degeneration of endplate chondrocytes via inhibiting Hedgehog signaling pathway
    XU Yongming, XU Hongguang, GAO Zhi, ZHANG Xiaoling
    2017, 22(4):  373-380. 
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    AIM: To investigate the effect of icaritin on degeneration of endplate chondrocytes induced by intermittent cyclic mechanical tension (ICMT) and its mechanism in vitro.  METHODS: Rat endplate chondrocytes degeneration model was established by using FX-5000T flexcell stress loading system in vitro. Three groups were erected: normal control group (NC group), ICMT group (10%intermittent cyclic mechanical tension ,10%ICMT, 0.5 Hz, 8 h/d), and ICT+ICMT group. The morphological alteration of the cells was observed with toluidine blue staining and phalloidin staining. Cell proliferation and apoptosis were detected respectively by CCK-8 and flow cytometry. The mRNA levels of chondrocyte-associated genes were detected by qRT-PCR and protein levels were determined by Western blot. RESULTS: Degeneration of endplate chondrocytes was apparently observed after mechanical stimulation. In detail, cell morphology changed from polygon to long spindle after mechanical loading. The cell proliferation rates in ICMT group and ICT+ICMT group were higher than NC group. However, there was no significant difference between ICMT group and ICT+ICMT group. The apoptosis rate of ICT+ICMT group was significantly lower than ICMT group. Interestingly, treatment with icariin effectively alleviated ICMT-induced degeneration of endplate chondrocytes, and significantly suppressed the Hedgehog signaling pathway. CONCLUSION: Icaritin can efficiently protect the ICMT-induced cartilage degeneration by inhibiting the activity of Hedgehog signaling pathway.

    MiR-200a alleviates renal interstitial fibrosis by inhibiting Wnt/β-catenin signaling pathway
    CHEN Hua, GONG Yi, ZHOU Baoshang, ZHANG Jing
    2017, 22(4):  381-386. 
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    AIM: To investigate the inhibition of miR-200a on Wnt/β-catenin signaling pathway in unilateral ureteral obstruction mouse, and the effects of miR-200a on renal interstitial fibrosis.  METHODS: Models of renal interstitial fibrosis were established by unilateral ureteral obstruction (UUO). Twenty-four six-weeks C57BL/6 male mice were randomly divided into four groups (n=6), Sham group, UUO group, UUO + miR-200a group and UUO + NC group. From day 1, UUO + miR-200a group was given miR-200a (i.v. by tail vein, 40 mg/kg), while UUO + NC group was given Negative Control (i.v. by tail vein, 40 mg/kg). Both groups were administered for three consecutive days. On day 7, HE and Masson staining were used to detect pathological changes in kidneys; RT-PCR and Western blot were used to detect mRNA and protein expressions of Wnt4, β-catenin, Fibronectin and α-SMA. RESULTS: Compared with Sham group, UUO group exhibited obvious renal tubular damage and interstitial collagen deposition; expressions of Wnt4, β-catenin, Fibronectin and α-SMA mRNAs and proteins were also increased in UUO group(P<0.05). Compared with UUO group, UUO+miR-200a group presented minor renal tubular injury and interstitial collagen deposition; expressions of Wnt4, β-catenin, Fibronectin α-SMA mRNAs and proteins were also reduced in UUO+miR-200a group(P<0.05). CONCLUSION: miR-200a can alleviate renal interstitial fibrosis by inhibiting the Wnt/β-catenin signaling pathway.

    Effect of traditional Chinese medicine Yuxia capsule on renal fibrosis in spontaneously hypertensive rats and its relationship with TGF-β1/Smads signaling pathway
    HU Kunmei, HU Haoran, SHEN Yuanyuan, LU Yining, YANG Jieren, HAN Jun
    2017, 22(4):  387-393. 
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    AIM: To observe the effect of traditional Chinese medicine Yuxia capsule(YXC) on renal fibrosis in spontaneously hypertensive rats(SHR) and its relationship with TGF-β1/Smads signaling pathway.  METHODS: Twenty-eight 14-week-old male SHR were randomized into four groups (n=7), i.e. SHR group (0.5% CMC-Na, 5 mL/kg), YXC high dose group (0.6 g/kg), middle dose group (0.3 g/kg) and low dose group (0.15 g/kg). Another 7 wistar-kyoto( WKY) rats were selected as normal group (0.5% CMC-Na, 5 mL/kg). Animals in each group were intragastrically administrated with YXC once a day for consecutive 10 weeks. Blood pressure was measured before administration and every two weeks during administration by tail cuff method. After the last administration 24 h urine was collected and the urine micro albumin (U-mALb) levels were detected. Serum levels of beta 2-microsphere protein (β2-MG), plasma and renal tissue angiotensin II (AngII) were measured. Changes of renal histology and collagen fibers were observed under HE and Masson staining. Expressions of TGF-β1, Smad4, Smad7 protein and Smad2/3 protein phosphorylation were detected in renal tissues by Western blot. RESULTS: Compared with model group, YXC significantly decreased the blood pressure of SHR, levels of U-mALb, β2-MG, plasma and renal tissue AngII (P<0.01 or P<0.05), and it significantly ameliorated the renal pathological tissue damage and the collagen fiber deposition. Expressions of TGF-β1, Smad4 proteins and phosphorylation of Smad2/3 protein level in YXC group were lower than those in model group, while Smad7 protein expression was higher(P<0.01).CONCLUSION: Traditional Chinese medicine YXC demonstrated protective effects against renal injury in a dose-dependent manner within a certain range in SHR, of which the potential mechanism may be related to decreasing the blood pressure, down-regulating AngII level and inhibiting the excessive activation of TGF-β1/Smads signaling pathway.

    Comparative study on the pharmacokinetics of baicalin and baicalein in rats after intravenous administration
    YANG Di, YUAN Tingting, GAN Shulei, CUI Yajiao, DING Ru, WU Yulin,YANG Jing
    2017, 22(4):  394-400. 
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    AIM: To compare the pharmacokinetics of baicalin(BG)and baicalein (BL) in rats by intravenous administration. METHODS: Two groups of rats (5 per group) received an intravenous administration of BG or BL at equimolar dose of 37 μmol/kg and dosing volume of 10 mL/kg. After administration, blood samples were collected in 1.5 mL heparinized polythene tubes, at 0 (pre-dose), 0.08, 0.17, 0.33, 0.5, 1, 2, 4, 6, 8,12, 24 h after dosing, simultaneous determination of baicalin and baicalein in plasma by HPLC-MS / MS. RESULTS: BG and BL could be detected in all plasma after baicalein/baicalin was administrated intravenously to rats. In BG group, the C max of BG was (24.5±18.3)nmol/mL,AUC 0-24 was (13.3±11.6)nmol·mL-1·h-1 group. In BL group , the C max of BL was (10.5±5.1)nmol/mL,AUC 0-24 was (18.2±4.9)nmol·mL-1·h-1. The rate of BG transformed into BL was 26.5% in the BG group. The rate of BL transformed into BG was 35%. CONCLUSION: The Cmax of BL in BL group was significantly higher than that of BG in BG group after intravenous administration of equimolar dose of BG/BL; however, the AUC 0-24 value was opposite. It might be caused by the higher lipophilicity, the wider distribution; the lower clearance rate of baicalein. It is suggested that baicalin and baicalein can be transformed into each other in vivo. The rate of BL transforming into BG is significantly higher than that of BG transforming into BL.

    Effects of gastrin on ERK signaling pathway in the proliferation of colorectal cancer cell line CACO2
    MAO Jiading, HU Di, WU Pei
    2017, 22(4):  401-405. 
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    AIM: To investigate the effects and mechanisms of exrtacellular-signal regulated protein kinase in gastrin-induced cell proliferation of colorectal cancer cells by using RNA interference technology.  METHODS: CCK-BR positive cell strain CACO2 was constructed lentivirus infection. Detection of gastrin receptor (CCK-BR) expression in colorectal cancer cell line CACO2 by qRT-PCR. RNA interference was used to silence the ERK1/2 gene, and the expression of total ERK protein and its phosphorylation level were analyzed. The experiment was divided into four groups: The control group, negative interference group, gastrin group and plasmid interference group. Changes of proliferation index of CACO2 cells were detected by cell cytometry. The protein of ERKl/2 and phosphorylation levels were detected by Western blot. RESULTS: After chronic viral infection, the target strip membrane protein and mRNA expression of CCK-BR were detected in the CACO2 cells. The amplified product was 185 bp. The interference plasmid was selected, the ratio of plasmid and liposome was 1∶2, the transfection efficiency was 40%-50%, and the expression level of ERK protein in the transfected plasmid was decreased. From the protein level,the constructed plasmid was observed effective. The proliferation index of the gastrin group was significantly higher than that of the plasmid interference group,the negative interference group and the blank control group, the difference was statistically significant (P<0.01). The expression of ERK1/2 protein and phosphorylation level in the four groups were significantly different (P<0.01). The protein expression and phosphorylation level of ERK1/2 in gastrin group were significantly higher than those in the plasmid interference group, the negative interference group and the blank control group, the difference was statistically significant (P<0.01). CONCLUSION: Gastrin can promote the proliferation of CACO2 cells in vitro by ERK signaling pathway. RNA interference can effectively block the phosphorylation of ERK protein in ERK signaling pathway, which is expected to provide a new approach for the treatment of colorectal cancer.

    Proteasome inhibitors decrease IL-6 and TNF-α levels in mouse acute viral myocarditis
    ZHANG Xinmin, CHEN Peng, YE Sheng, XIA Wujie, LI Yuechun
    2017, 22(4):  406-411. 
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    AIM:To investigate the effect of proteasome inhibitor in mice with inflammatory reaction of acute viral myocarditis induced by coxsackievirus B3 virus (CVB3) infection.   METHODS: 100 male BALB/C mice were randomly divided into four groups, i.e. the normal control group, CVB3 group, CVB3 and bortezomib group, CVB3 and MG-132 group. Mice in control group were injected with blank solvent, while mice in other three groups were intraperitoneally inoculated with CVB3 to induce acute viral myocarditis. 24 h after infection, mice in treatment groups were administrated with bortezomib or MG-132 respectively for 7d continuously by intraperitoneal injection. Changes of myocardial ultra-structure, the mRNA and protein levels of IL-6 and TNF-α, the number of PMN, and the survival rate of each group were detected. RESULTS: Compared with control group, the protein levels of IL-6 and TNF-α, and the number of polymorphonuclear neutrophils (PMN) were significantly increased in CVB3 group (P<0.05). The cardiomyocytes were diffused and swelled, the myofilament was lysed, and the mitochondria was swelled and vacuolizated. The above mentioned inflammatory factors in bortezomib group and MG-132 group were significantly decreased as compared with CVB3 group (P<0.05). The damaged degree of the cardiomyocytes in treatment groups were less, and the mortality due to deadly arrhythmia were lower than that in CVB3 group. CONCLUSION: Proteasome inhibitors protect the mice from CVB3-induced acute viral myocarditis by suppressing the expression of inflammatory factors. Ubiquitin proteasome system is a potential new target therapy for viral myocarditis.

    Effect of USP22 on gemcitabine chemoresistance in human pancreatic cancer cell
    WANG Wanming, DONG Jiazhong, GUAN Shuming
    2017, 22(4):  412-417. 
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    AIM: To evaluate the potential effect of  USP22 on gemcitabine chemoresistance in pancreatic cancer cells.  METHODS: USP22 expression was detected by Western blot in pancreatic cancer cell lines PANC-1 and SW1990 treated with gemcitabine. The IC50 values of different pancreatic cancer cells to gemcitabine were detected by cell counting kit 8 (CCK-8) assays. RESULTS: USP22 expression was induced by certain dose of gemcitabine treatment in pancreatic cancer cells. CCK-8 assay demonstrated that the IC50 values in SW1990-NC group and SW1990-shUSP22 group were (1 850.96±87.37) nmol/L and (534.83±49.68) nmol/L, respectively. Furthermore, the IC50 values in SW1990-NC, SW1990/Gem-NC and SW1990/Gem-shUSP22 groups were (1 387.58±96.56) nmol/L, (29 850.96±345.78) nmol/L and (2 157.08±120.32) nmol/L, respectively. CONCLUSION: Gemcitabine treatment increases the expression of USP22 in pancreatic cancer cells. Knock-down USP22 expression could enhance the chemosensitivity to gemcitabine in pancreatic cancer cells, but also rescue the gemcitabine resistance in pancreatic cancer cells.

    Effect of Baishile capsule on expressions of BDNF,NT-3,NGF in septo-temporal axis of hippocampus of depressive rats
    MENG Pan, LIU Zhuo, ZHU Qing, ZHAO Hongqing, ZHANG Xiuli, LEI Chang, WANG Yuhong, YANG Hui
    2017, 22(4):  418-423. 
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    AIM: To investigate the effect of Baishile capsule on the expression of  neurotrophic factor including brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT-3), and nerve growth factor (NGF) in hippocampal septo-temporal axis of depressive rats.  METHODS: Sixty SD rats were randomly divided into control group, model group of depression, fluoxetine group, high (2.88 g/kg), medium (1.44 g/kg) and low (0.72 g/kg) doses of Baishile capsule. Chronic unpredictable mild stress for 21 d was used to establish depression model; sucrose preferences and forced swimming test to detect depression-like behavior in rats; Morris water maze test to evaluate learning and memory ability; immunofluorescence technique to observe the content change of neurotrophic factors (BDNF,NT-3,NGF) in hippocampal septo-temporal axis of rats. RESULTS: Compared with the control group, sucrose preference was decreased while immobility time was increased significantly (P<0.01); escape latency and latency time in target quadrant presented a significant increase (P<0.01); times of crossing the target quadrant were significantly reduced (P<0.05); BDNF, NT-3, NGF expressions were down-regulated in S1, S2, T3 and T4 parts of hippocampal septo-temporal axis in model rats (P<0.01). Compared with model group, Baishile capsule could significantly improve sucrose preference degree and decrease immobility time (P<0.05); escape latency and latency time in target quadrant were significantly shorter (P<0.05); times of crossing the target quadrant increased in rats after administration of Baishile capsule (P<0.05); BDNF, NT-3, NGF expressions increased in S2 and T3 parts of septo-temporal axis in depressive rats (P<0.05 or P<0.01). CONCLUSION: Baishile capsule could significantly improve the depression-like behavior, learning and memory ability in depressive rats, which might be associated with regulating the function of S2, T3 parts of hippocampal septo-temporal axis, and promoting the expression of neurotrophic factors.

    Effect of rHuEPO on the change of Ang-1 during acute skin wound healing in rats
    XU Shujuan, LV Dalun, CHEN Lei, DING Wei, WANG Heli, ZHANG Wei, WANG Shuai
    2017, 22(4):  424-427. 
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    AIM:To investigate the effects of recombinant human erythropoietin (rHuEPO) on Ang-1 during acute skin wound healing in rats. METHODS: 72 healthy male SD rats were selected to establish animal model of acute wounds, and were randomly divided into low dose group(50 U/mL rHuEPO), middle dose group(100 U/mL rHuEPO), high dose group (150 U/mL rHuEPO) and normal saline group (NS).Different doses of rHuEPO(external application) and saline were administered at the same time of modeling. Healing of the wound was observed in rats in each group. Skin samples 3 d,7 d,14 d after injury were collected to detect the changes of CD31 and Ang-1under immunohistochemistry staining. RESULTS: Compared with control group and low dose rHuEPO group,results of immunohistochemistry indicated higher expression of CD31and Ang-1 in high dose and middle dose rHuEPO group after 3 d and 7 d treatment (P<0.05). CONCLUSION: rHuEPO can increase the expression of Ang-1 and the angiogenesis of rats during healing, thereby accelerating wound healing process.

    Exposure-response model of Qing-e pill in menopausal syndrome patients
    WANG Chen, ZHENG Qingshan
    2017, 22(4):  428-433. 
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    AIM: To develop an exposure-response PK-PD model of Qing-e pill in Chinese menopausal syndrome (MPS)  patients so as to evaluate the efficiency of phytoestrogen and the effect of individual factors on administration.  METHODS: An exposure-response PK-PD model was established based on the clinical data of MPS patients. Related parameter and variability were thence estimated. RESULTS:The effective component-semen psoraleae (14 coumarins and flavonoids with a total content of 3.42% of the whole Qing-er pill dosage) was selected as the PK exposure. The 24 h hot flashes decreasing- rate from baseline was chosen as the PD indicator. The basic exposure-response model was a linear model. The typical values (RSE%) of model parameters (Slope and Intercept) were -56.2(10.2) and -14.6(22.2), respectively. Some other factors as body weight, course of treatment and dosage, etc. were included in the PK exposure part of the basic model. CONCLUSION: Treatment for at least 12 weeks is needed to achieve the ideal efficacy. A predicting surface model is built after simulation of different weights and courses, which indicate a negative correlation with weight but a positive correlation with drug frequency and treatment course. Therefore, specific dosage should be adjusted according to weight, and for patients presented with poor therapeutic effects, larger dose and longer course are suggested.

    Effect of difference censored rates between groups in clinical trails
    CHEN Mengkai, BAI Jianling, WEI Yongyue, HUANG Lihong, ZHAO Yang, YU Hao
    2017, 22(4):  434-438. 
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    AIM: To explore the influence on the results of survival analysis when the censored rates are different between the groups. METHODS: Monte-Carlo method was used to simulate a two-group survival data in clinical trials and to estimate the type I error and the test power of the log-rank test and Cox proportional hazards models in different scenario of different censored rates between groups. RESULTS: If censored rates were equal in both test group and control group, the type I errors were well controlled, the estimates of HR were most accurate, and the power was relatively high. If total censored rates were lower than 30%, the lower censored rate difference between two groups, the higher reliability hypothesis testing results. CONCLUSION: In clinical trials, by ensuring enough sample size, the total censored rate should be controlled within 30%, and the difference of censored rate between the two groups less than 10% was suggested.

    Correlation between detection rate of clindamycin-resistant Staphylococcus aureus and utilization of antibacterial drugs
    JIANG Cheng, LV Jiangang, LI Fangqiong, YE Zuowu, LU Chunfang, LI Gonghua
    2017, 22(4):  439-442. 
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    AIM: To provide information for reasonable clinical application of antibacterial drugs, the partial least squares (PLS) regression models were established for analyzing the correlation between detection rate of clindamycin-resistant Staphylococcus aureus (CRSA) and utilization of antibacterial drugs.  METHODS: The PLS regression models were established with the defined daily doses (DDDs) of antibacterial drugs as independent variables and the detection rates of CRSA with same and different periods as dependent variables. The lag between detection rates of CRSA and utilization of antibacterial drugs were investigated. The antibacterial drugs, which were highly correlated with the detection rate of CRSA, were screened according to the variable importance (VIP) values. RESULTS: The detection rate of CRSA lagged about two quarters behind the utilization of antibacterial drugs, and was significantly positively correlated with the DDDs of cefoperazone/sulbactam, azithromycin and cefuroxime. CONCLUSION: It was effective to employ PLS regression algorithm to simultaneously analyze the correlation between detection rate of CRSA and utilization of multiple antibacterial drugs. This research provided a new scientific tool for the investigation of CRSA.

    Correlation and clinical value of PCT, SVRI, SOFA  in sepsis patients
    WANG Jian,ZHANG Wen
    2017, 22(4):  443-447. 
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    AIM: To discuss the value of the combination of serum procalcitonin concentration (PCT), systemic vascular resistance index (SVRI) and sequential organ failure assessment score (SOFA score) in the early diagnosis of patients with sepsis in the intensive care unit (ICU) ward and clinical application. METHODS: 78 patients with sepsis were divided into the high SVRI group, the normal SVRI group and the low SVRI group on the basis of the SVRI index. The records and tests included the age, the sex, the infection, concentration of serum PCT and SOFA score, cardiac index (CI), central venous pressure (CVP), mean arterial pressure (MAP), global end diastolic volume index (GEDVI) and extravascular lung water index (EVLWI) respectively. The correlations between the records were studied. RESULTS: The records of the age, gender and infection site of each group showed no statistical significance. The SOFA score, serum PCT concentration and cardiac index of low SVRI group were significantly higher than those of the normal SVRI group and the high SVRI group, respectively. There were no statistical significant of the serum PCT concentration, SOFA score and heart index difference of the high SVRI group and the normal SVRI group of patients with sepsis. The spearman analysis showed that SVRI was negatively correlated with the concentration of PCT (r=-6.38,P=0.000), and SOFA score (r=-0.527,P=0.000), respectively. It showed no significant correlation with CI (r=-0.375,P=0.000). The pearson analysis showed that PCT concentration was positively correlated with SOFA score (r=0.69,P=0.000). CONCLUSION: PCT concentration, SVRI, SOFA score were important clinical indexes in assessing the patient's condition and make the plan for that. This method is referential for clinical application.

    Effect of risk adjustment methylprednisolone intervention on the prognosis of pre-engraftment syndrome after unrelated cord blood transplantation
    HUANG Laiquan, YAN Jiawei, WEI Zhongling, DAI Yan, SU Guiping, JIANG Yizhi, SUN Zimin, HUANG Dongping
    2017, 22(4):  448-455. 
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    AIM: To retrospectively study the effect of risk adjustment methylprednisolone (MP) intervention on the prognosis of pre-engraftment syndrome (PES) and impacts on outcomes after unrelated cord blood transplantation (UCBT).  METHODS: The data of 8 patients with acute leukemia underwent single or double UCBT from November 2012 to March 2015 were analyzed in this study, including 7 single UCBT and 1 double UCBT, half of the patients were acute lymphoblastic leukemia, and the other 4 patients were acute myeloid leukemia. All the patients were received intensified myeloablative conditioning, including 7 sTBI-based conditioning and one based on Flu. Treatment with risk adjustment methylprednisolone was given to all the patients for PES intervention. And for graft-versus-host disease (GVHD) prophylaxis, a combination of cyclosporine (CsA) and mycophenolate mofetil (MMF) was given. The cohort of patients were followed-up till to August 31, 2016. RESULTS:All the patients showed PES after UCBT and the incidence of PES was 100%. When compared the maximum C-reactive protein(CRP) level, the median value during PES was significantly higher than the serum level during conditioning therapy, after PES and the onset of II-IV acute GVHD (all P<0.05, respectively), and the result of patients received different doses of MP (0.5 mg·kg-1·d-1 and 1 mg·kg-1·d-1) showed no significant difference (P>0.05). Treatments based on different doses of MP showed a good clinical effect on PES, and there was no significant difference on transplant-related complications such as cumulative incidences of neutrophil engraftment, platelet recovery, II-IV and III-IV acute GVHD (all P>0.05, respectively). What's more, all the patients experienced infections in 100 days after UCBT. The incidence of bacterial infection was 75%, and the incidence of CMV infection was 100%. But in this study, no one experienced EBV infection after UCBT. In patients received MP 0.5 mg·kg-1·d-1, the incidence of bacterial infection was 50%, but it was 100% in those received MP 1 mg·kg-1·d-1.  No significant difference was found between the 2 groups not only in infection, but also in the incidences of overall survival (OS) and relapse (P>0.05). CONCLUSION: PES seems to be common after UCBT, and MP is an effective intervention. Different doses of MP therapy based on the clinical manifestations of PES cases do not influence the results of UCBT in this cohort. Furthermore this approach can reduce patient transplant complications, improve the outcomes of UCBT and prolong the survival of patients underwent UCBT.

    Study on the relationship between constipation, colonic mucosal inflammation, intestinal LPS and Parkinson's disease
    LIU Xiaolin, YU Meiling, XIE Jing, ZHANG Lina, XU Wenfang, YE Ming, LI Qianqian, CHEN Yuhua
    2017, 22(4):  456-460. 
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    AIM: To investigate the correlationship between intestinal symptoms (constipation), colon pathological changes, lipopolysaccharide(LPS)and Parkinson's disease(PD) so as to provide theoretical and experimental basis for the early detection of PD and its pathogenesis.  METHODS: 102 PD patients were randomly divided into three groups through constipation questionnaire and discriminant analysis. Multivariate logistic regression analysis was used to analyze the relationship between the types of constipation and age, course of disease as well as course of constipation. 6 PD patients with constipation in were performed colonoscopy, and the infiltration of lymphocytes in colonic mucosa was detected by immunohistochemistry. LPS of 78 PD patients (23 cases without constipation and 55 cases with constipation) were detected by dynamic turbidimetric limulus test. RESULTS: (1) Within the total 102 PD patients, 23 cases presented without constipation while 79 cases with constipation, among which the STC, Mixed, RED were 31 cases (39.24%), 33 cases (41.77%) and 15 cases (18.99%) , respectively. (2) The colon mucosa of 6 PD patients with constipation showed chronic inflammation and a large number of CD+4 cell infiltration.(3) There were 15 cases of PD patients with the amount of LPS more than 0.1 EU/mL, 29 cases 0.1 to 0.01 EU/mL, and 34 cases <0.01 EU/mL among the 78 cases of PD patients, and the increased LPS was related to the constipation of PD patients. CONCLUSION: Constipation, colonic mucosal inflammation, chronic low-grade inflammation-induced intestinal LPS are associated with the occurrence and development of PD.

    Effect of single and repeated intravesical instillation on prognosis after radical nephroureterectomy in upper urinary tract urothelial carcinoma
    LIAO Guodong, YU Weiwen, ZHANG Qi, LV Jia, MAO Zujie
    2017, 22(4):  461-465. 
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    AIM: To compare the effect and safety between single intravesical chemotherapy and repeated instillation intravesical after radical nephroureterectomy in upper urinary tract urothelial carcinoma (UUT-UC).  METHODS: 63 patients were enrolled after radical nephroureterectomy in upper urinary tract urothelial carcinoma from June 2010 to July 2016, and were divided into two groups according to the chemotherapy protocol. 29 patients in single intravesical group (SIG) and 34 patients in repeted instillation intravesical group (RIG). The progression-free survival, overall survival and side effects between two groups were compared.RESULTS: Follow-up was 5-60 months, media follow-up was 36.4 months. The 3-year and 5-year OS in SIG and RIG were 65.5%, 51.7% and 67.6%, 52.9%, respectively. No significant difference was observed between them(P>0.05). Meanwhile, the 3-year and 5-year PFS in SIG and RIG were 79.3%,72.4% and 85.3%,76.5%, there were significant differences between them(P<0.05). The main side effects of two groups were 1-2 grade hematologic toxicity and gastrointestinal reaction. The incidence of hematologic toxicity, digestive tract reaction, bladder spasm and cystitis in RIG were higher than SIG, there were significant difference among them(P<0.05).However, there were no significant difference between liver or kidney damage and fever(P>0.05).CONCLUSION:Using pirarubicin for intravesical instillation is safe and effective for UUT-UC patients after radical nephroureterectomy. Compared with single instillation, repeated instillation chemotherapy can reduce the recurrence rate of bladder cancer, whilst cannot improve the overall survival. Also, repeated instillation cause more severe gastrointestinal and hematologic toxic reactions.

    Effect of paliperidone and olanzapine on patients with first-episode schizophrenia
    CUI Lijun, PAN Xin, ZHU Jielin, LI Jianhua
    2017, 22(4):  466-470. 
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    AIM: To explore the effect of paliperidone and olanzapine treating patients with first-episode schizophrenia and their influence on sugar metabolism and serum levels of brain-derived neurotrophic factor (BDNF).  METHODS: 80 patients with first-episode schizophrenia were randomly divided into paliperidone group (n=40) and olanzapine group (n=40) for an 8-week study. Positive and Negative Syndrome Scale (PANSS) was used to assess clinical efficacy, at the same time the Treatment Emergent Symptom Scale (TESS) was used to assess treatment of adverse reactions. Fasting blood sugar of the two groups  at baseline, 4th and 8th weekend were detected, and serum levels of BDNF were measured by enzyme-linked immuno sorbent assay (ELISA). RESULTS:The effective rate was similar (68.4% vs.63.1%, P>0.05 ) after 8 weeks of treatment; In both groups, the factors and total scores of PANSS at the 4th, 8th weekend were significantly lower than those at the baseline, the difference was statistically significant (P<0.05), yet positive and negative symptoms score had no statistical significant differences between two groups. Comparison between the groups, olanzapine group FBS levels at 8th weekend had increased significantly than the 4th weekend (P<0.01), and paliperidone group had no significant differences. Comparison between groups, FBS levels in olanzapine group were obviously higher than those of paliperidone groups at the 8th weekend, the difference was statistically significant (P<0.01). BDNF concentrations of two groups were significantly higher at 4th, 8th weekend than those at the baseline (P<0.01). Comparison between groups, BDNF concentration in paliperidone group was obviously higher than that of olanzapine groups at the 8th weekend, the difference was statistically significant (P<0.01). CONCLUSION: Paliperidone and olanzapine have similar clinical efficacy in treating first-episode schizophrenia, paliperidone is better than olanzapine in regulating sugar metabolism index and elevated serum concentration of BDNF.

    Relation of stress hyperglycemia and intestinal mucosal barrier function after gastrectomy of stomach neoplasms
    LEI Qiang
    2017, 22(4):  471-476. 
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    AIM: To analyze the relation between stress hyperglycemia and intestinal mucosal barrier function after gastrectomy of stomach neoplasms.  METHODS: 71 patients with gastric carcinoma and prepared for radical operation were selected, 29 of them with stress hyperglycemia after surgery were the observation group, while the others were included the control group. The fasting blood of patients before surgery and 2 h, 12 h, 24 h, 36 h, 48 h, 72 h, 120 h after surgery were extracted to detect fasting plasma glucose by blood sugar analyzer and serum D-lactic acid. Diamine oxidase (DAO) level was detected by ELISA kits. Furthermore, the urinary lactulose and mannitol ratio (L/M) was also detected at the same time. RESULTS:Both groups and times had effect on blood sugar, urine L/M, D-lactic acid and DAO level (P<0.05), and there was no interaction between (P>0.05). In terms of the trend, the blood glucose level increased after treatment, and peaked at 24 h, and the observation group was higher than the control group at 12 h, 24 h, 36 h and 72 h after surgery (P<0.05). The L/M level increased after treatment, and peaked at 72 h, and the observation group was higher than the control group at each time point after surgery (P<0.05). The serum D-lactic acid and DAO level increased after treatment, and the control group peaked at 72 h, while the observation group increased all the time, and at most time, the observation group was higher than the control group (P<0.05). Before treatment and 24h after surgery, the blood glucose levels were positively correlated with L/M, D-lactic acid and DAO levels (P<0.05); 72h after surgery, the blood glucose levels were positively correlated with L/M and DAO levels (P<0.05); 120h after surgery, there was no significant correlation between blood glucose levels and the other indexes (P> 0.05). CONCLUSION: There is certain correlation between stress hyperglycemia and intestinal mucosal barrier function injury after gastric cancer radical surgery, and it is of great significance for intestinal function recovery to monitor and control blood glucose after surgery.

    Individualized antithrombotic therapy on one patient with chronic renal insufficiency
    DANG Xiangji, ZHOU Lin, WANG Yixuan, ZENG Lu
    2017, 22(4):  477-480. 
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    AIM: To evaluate the role of clinical pharmacist in individualized antithrombotic therapy on patients with chronic renal insufficiency.  METHODS: To review clinical pharmacist participating antithrombotic therapy on one patient with chronic renal insufficiency. RESULTS:Clinical pharmacist analyzed the causes of chronic renal failure and skin hematoma formation by pharmacokinetic and pharmacodynamic characteristics of aspirin and enoxaparin, participated the adjustment of antithrombotic therapy and implemented pharmaceutical care and pharmaceutical edueation for the patlents. CONCLUSION: Clinical pharmacist focuses on individualized medication of special crowd which could be the entry points for pharmaceutical care, avoid adverse reactions and ensure the reasonable, safety, effec, and economy of drug in patients.