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

Table of Content

    Volume 23 Issue 1
    26 January 2018
    Therapeutic time window of effectiveness for idazoxan ameliorating brain damage of rats with experimental autoimmune encephalomyelitis
    LI Fang, ZHENG Liupu, WENG Jianlong, GUO Tao, SONG Xingwei, ZHENG Rongyuan
    2018, 23(1):  1-7.  doi:10.12092/j.issn.1009-2501.2018.01.001
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    AIM: To investigate the effective therapeutic time window of idazoxan in rats with experimental autoimmune encephalomyelitis (EAE). METHODS: Fifty SD rats were randomly divided into four groups: (1) Control group (n=8), which was given no treatment, but raised in the same condition as the experimental groups. (2) EAE-NS group (n=14), which received saline rather than idazoxan; (3) EAE-idazoxan 1-7 d group (n=14), which idazoxan was given at 2 mg/kg through i.p. (b.i.d.) from the first day of immunization to the 7th day; (4) EAE-idazoxan 8-14 d group (n=14), which received 2 mg/kg idazoxan through i.p. (b.i.d.) from the 8th day of immunization to the 14th day. Rat's behavioral changes were measured twice daily after immunizations until they were killed at 15th day after immunization to collect the cerebrum and the lumbar spinal cord.  HE staining and luxol fast blue (LFB) staining was performed on the tissue sections to show tissue damage, infiltration of inflammatory cells and demyelination. Immunohistochemistry was used to determine the expression of Iba1 and GFAP in the spinal cord.RESULTS:Idazoxan improved neurological behaviours: EAE-idazoxan 8-14 d group significantly reduced the daily clinical scores and cumulative neurobehavioral scores compared with the EAE-NS group (P<0.05). Idazoxan reduced EAE histopathology: Inflammatory cell entry into the brain and spinal cord was significantly reduced in EAE-idazoxan 8-14 d group compared with the EAE-NS group (P<0.05). Demyelinationin the brain and spinal cord was also reduced in EAE-idazoxan 8-14 d group based on LFB staining when compared with EAE-NS group (P<0.05). Idazoxan reduced Iba1 expression: EAE induced significant increase in the number of Iba1 expressing cells in the brain and reduce astrocytic(GFAP) activation. Compared with the EAE-NS group, the number of Iba1 positive cells EAE-idazoxan 8-14 d Group was significantly reduced (P<0.01). ELISA analysis showed that the expressions of IL-17 (P<0.01) decreased and IL-10 increased significantly in the CNS in EAE-idazoxan 8-14 d group rats compared with EAE-NS group rats. CONCLUSION: The effective therapeutic time window for idazoxan is in the period of disease onset of EAE disease progression. The protective effect of idazoxan on EAE is associated with the attenuated microglial activation and shifting the balance of inflammatory cytokines.

    Effects of limoninon on LPS-induced acute lung injury in mice
    WANG Di, ZHANG Huanhuan, FANG Jie, ZHONG Yushen, YU Chenhuan
    2018, 23(1):  8-12.  doi:10.12092/j.issn.1009-2501.2018.01.002
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    AIM: To investigate the effects of limonin (LM) on lipopolysaccharides (LPS)-induced acute lung injury (ALI) in mice. METHODS: Forty ICR male mice were divided randomly by weight into 4 groups: normal group, model group, dexamethasone (Dex)-treated group and LM-treated group. Each group had ten mice. Dex and LM were intraperitoneally injected at the dose of 10 mg/kg, respectively. Two hours after drug administration, except the mice in normal group treated with same vehicle, others were intracheally injected with LPS (5 mg/kg). Six hours after LPS challenge, mice were sacrificed and lung tissues were obtained for calculating the pulmonary index and wet/dry mass (W/D) ratio. The sections were stained with hematoxylin and eosin (HE) for histological analysis. The levels of TNF-alfa, IL-1beta, and IL-6 in serum were determined by ELISA. Myeloperoxidase (MPO) in serum were determined by chromatometry. The mRNA expressions of TNF-alfa, IL-1beta and IL-6 were determined by RT-PCR while TLR4 and NF-kB p65 protein by Western blot analysis. RESULTS: Compared with normal group, mice in model group had obvious increase of lung indexes and W/D ratios, which were accompanied by marked inflammatory cell infiltration, alveolar congestion and edema in lung; the levels of TNF-alfa, IL-1beta, IL-6 and MPO in serum as well as their mRNA expressions in the lung of ALI mice were also increased (P<0.01). Compared with model group, lung indexes and W/D ratios were decreased in LM-treated group while histological changes were improved; the levels of TNF-alfa, IL-1beta, and IL-6 in serum (P<0.01) and their mRNA expressions, and the expressions of TLR4 and NF-kB p65 protein in lung tissues were also significantly decreased (P<0.01). CONCLUSION: LM protects against LPS-induced ALI via regulating TLR4/NF-kB pathway and inhibiting expression of inflammatory cytokines in mice.

    Oxymatrine inhibits invasion and metastasis of triple-negative breast cancer cells by regulating epithelial mesenchymal transition
    CAI Jiaqin, WEI Xiaoxia, HUANG Xuhui, ZHUANG Jie, SUN Hong
    2018, 23(1):  13-17.  doi:10.12092/j.issn.1009-2501.2018.01.003
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    AIM: To study the inhibitory effects of oxymatrine on growth and migration of human triple-negative breast cancer MDA-MB-231 cell.  METHODS: CCK-8 assay was used to detect the inhibitory effects of oxymatrine on the growth of MDA-MB-231 cells. Inhibitory effect of oxymatrine on cell cycle of MDA-MB-231 cells was detected by flow cytometry (FCM). Effect of oxymatrine on migration of MDA-MB-231 cells was detected by scratch experimental. RESULTS: Compared with the control group, the growth of MDA-MB-231 cells decreased significantly in a time- and dose-dependent manner after oxymatrine treatment (2, 4, 6, 8, 10, 20 mg/mL for 24, 48 and 72 h). Oxymatrine significantly increased the number of cells in G0/G1 phase and decreased the number of cells in S and G2/M phase(P<0.05). Transwell showed that oxymatrine treated MDA-MB-231 cells for 12 h significantly inhibited the invasion of MDA-MB-231. The high concentration of oxymatrine significantly up-regulated the expression of E-cadherin and inhibited the expression of Snail-2 mRNA (P<0.01). CONCLUSION: Oxymatrine exerts its antitumor effect by inhibiting the growth and invasion of MDA-MB-231 cells, which plays a potential role on anti-tumor growth and metastasis.

    Radio sensitizing effect of double PI3K/mTOR inhibitor NVPBEZ235 on Hela cells of cervical cancer
    ZHENG Yingao, LI Shengze, ZHANG Lei, GUO Xiangrui, BAO Jiaqian, WU Tao, LIU Jian
    2018, 23(1):  18-23.  doi:10.12092/j.issn.1009-2501.2018.01.004
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    AIM: To investigate the effect that external irradiation of dual PI3K/mTOR inhibitors NVPBEZ235 on cervical cancer Hela cells. METHODS: Cervical cancer Hela cells treated with different concentrations of NVPBEZ235 and the radiotherapy (irradiation, IR) were examined for cell viability using MTT assay and colony forming ability. The cycle arrest of cervical cancer cells combined drug with IR was analyzed by using the flow cytometry. RESULTS: Compared with the control group, NVPBEZ235 can inhibit human cervical carcinoma cell in vitro (P<0.05). The combined use of NVPBEZ235 significantly enhanced the inhibitory effect of IR (P<0.05) in Hela cells. In vitro, NVPBEZ235 and IR, which had synergistic effect, can block cell cycle to G2/M period by the combined effect which was significantly greater than the effect of one single drug (P<0.05). CONCLUSION: 20% IC50 NVPBEZ235 can promote the cell's radiation sensitivity, inhibit the proliferation of cells, and thereby, increase its radio sensitivity to cervical cancer cells.

    Anti-aging effects of Kangshuailing ointment and its mechanism
    LUO Shengyong, DENG Xuefeng, LIU Peng, LI Chengwang, LI Rui
    2018, 23(1):  24-28.  doi:10.12092/j.issn.1009-2501.2018.01.005
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    AIM: To observe the anti-aging effects of Kangshuailing ointment and the possible mechanisms.  METHODS: ICR mice were randomly divided into six groups: normal group, model group, positive group, Kangshuailing ointment 1.3, 2.6, 5.2 g/kg group. Aging model was induced by subcutaneously injecting mice with 5% D-galactose. Mice of each group receiced daily administration by gavage for 6 weeks. Thymus index and spleen index were calculated; LPO, LF contents and MAO-B activity in brain tissue were detected by ELISA method; MDA contents, SOD and GSH-Px activities in blood serum were examined by spectrophotometry method; the pathology change of brain tissues were observed using light microscope. RESULTS: Compared with model group, Kangshuailing ointment could significantly increase the thymus and spleen index, reduce the LPO and LF contents, and increase MAO-B activity in brain tissue, remarkably decrease the MDA contents and increase the SOD and GSH-Px activities in blood serum. In addition, Kangshuailing ointment could markedly relieve the pathological lesions induced with D-galactose in brain. CONCLUSION: Kangshuailing ointment has obvious anti-aging effect on aging mice, which may be related to the antioxidation.

    Effects of volatile oil of the angelica on the proliferation and apoptosis of human lung adenocarcinoma cell GLC-82
    ZHANG Yanxia, LIN Xingyao, AN Fangyu, ZHANG Zhengshun, CHEN Shaoyi, ZHOU Jiawei, ZHANG Yanying
    2018, 23(1):  29-33.  doi:10.12092/j.issn.1009-2501.2018.01.006
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    AIM: To investigate the cytotoxic effect and apoptosis of volatile oil of the angelica on human lung adenocarcinoma cell GLC-82. METHODS: MTT colorimetric assay was used to investigate the cytotoxic effect of human lung adenocarcinoma cell GLC-82. The cell apoptosis was analyzed by flow cytometry. AO/BE fluorescent staining was applied to observe the cell apoptosis. RESULTS: The GLC-82 cell was inhibited by volatile oil of the angelica in a concentration-dependent manner; the IC50 was 113.03 μg/mL. The result of flow cytometry indicated volatile oil of the angelica could induce apoptosis and necrosis of GLC-82 cell, and the rates of apoptosis and necrosis were increased by the increase of drug concentration. The results of AO/BE fluorescent staining method indicated the rate of apoptosis and necrosis increased in drug group along with the increase of drug concentration. CONCLUSION: Volatile oil can induce the apoptosis of GLC-82 cell.

    Effects of pinocembrin on mRNA expression of genes related to endoplasmic reticulum stress-mediated apoptosis in acute injury induced by focal cerebral ischemia-reperfusion
    WU Caixia, DU Guanhua
    2018, 23(1):  34-40.  doi:10.12092/j.issn.1009-2501.2018.01.007
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    AIM: To investigate the effects of pinocembrin on mRNA expression of several genes related to endoplasmic reticulum stress-mediated apoptosis in acute injury induced by focal cerebral ischemia-reperfusion. METHODS: Fifty male Sprague-Dawley rats, weighing 260-280 g were divided into five groups: sham operation group; I/R group; I/R + pinocembrin (1, 3 and 10 mg/kg) group. Focal cerebral I/R model was established by occlusion of the middle cerebral artery(MCAO) for 2 h followed by 6 h reperfusion. Pinocembrin was administered intravenously at different doses at the onset of reperfusion. The mRNA expression of gene GRP78, CHOP, ATF4, XBP-1 was then detected by RT-PCR method in penumbra cortex, respectively. RESULTS: Pinocembrin significantly modulated the levels of mRNA expression of these genes by increasing GRP78 and attenuating CHOP expression along with ATF4, and XBP-1 (P<0.05 or P<0.01). CONCLUSION: Pinocembrin can protect against I/R injury, and the possible mechanism might be attributed to its regulation of mRNA expression of genes related to endoplasmic reticulum stress-mediated apoptosis in penumbra area.

    Effects of procyanidins on TLR4/NF-κB signaling pathway in rats with acute gouty arthritis
    LUO Fei, MEI Yan
    2018, 23(1):  41-46.  doi:10.12092/j.issn.1009-2501.2018.01.008
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    AIM: To observe the effect of procyanidins on acute gouty arthritis SD rats and to explore its possible mechanism. METHODS:SD rats were randomly  divided into six groups: the normal group, the model group, low dose group (30 mg/kg), middle dose group (60 mg/kg), high dose group (90 mg/kg) and colchicine positive control group (0.3 mg/kg). Administration group and control group were given the corresponding dose of drugs by intragastric administration, the normal and model groups were given the same volume of saline. Model of acute gouty arthritis was established by injecting sodium urate into ankle joint cavity. At the fixed time point, joint swelling and mechanical pain threshold were determined, the gait was observed. The levels of IL-1beta, IL-6 and TNF-alfa in serum were measured by ELISA; the protein expression of TLR4 and NF-kB in synovial tissue was measured by Western blot.  RESULTS: Procyanidins can relieve swelling of the ankle, improve gait changes and pain changes in rats. At the same time, procyanidins can inhibit the expression of TLR4 and NF-kB protein in SD rats with acute gouty arthritis, down-regulate the levels of IL-1beta, IL-6 and TNF-alfa in serum. CONCLUSION: Proanthocyanidins exhibit a certain effect on SD rats with acute gouty arthritis. The mechanism may be related to the inhibition of TLR4/NF-kB signaling pathway, thereby inhibiting IL-1beta and other inflammatory factors.

    Mechanism of ethanolic extract of root of Anacyclus pyrethrum on two models of inflammation
    HUANG Hai, LIU Changjiang, JIN Xiaoyue
    2018, 23(1):  47-50.  doi:10.12092/j.issn.1009-2501.2018.01.009
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    AIM: To study the effects of ethanolic extract of root of Anacyclus pyrethrum (EERAP) on two models of inflammation.  METHODS: Fifty mice were randomly divided into Control group (received water), EERAP groups of high dose (640 mg/kg), middle dose (320 mg/kg), low dose (160 mg/kg) and Aspirin (120 mg/kg) group. Two models of inflammation were established through mice induced by xylene and RAW264.7 cells induced by lipopolysaccharide (LPS). The anti-inflammatory and antioxidant activity mechanisms were investigated by detecting the contents of malondialdehyde (MDA) in inflammatory tissue, the activity of SOD in serum, while NF-kB and TNF-alfa in RAW264.7 cells. RESULTS: Compared with the control group, different concentrations of EERAP had significant inhibition on the auricle swelling and capillary permeability (P<0.01), and increased the activity of SOD and MDA in serum in mice in vivo (P<0.01), while reduced the contents of TNF-alfa and NF-kB in RAW264.7 cells in vitro. CONCLUSION: The anti-inflammatory and antioxidant activity mechanism of EERAP might be related to the reduction of MDA and NF-kB, and the elevation of SOD and NF-kB.

    Expression of absent in melanoma 2 in acute pancreatitis of mice model
    YANG Feiyun, ZHU Xiuying, ZHANG Jianxin, YANG Yaqin
    2018, 23(1):  51-54.  doi:10.12092/j.issn.1009-2501.2018.01.010
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    AIM: To explore the expression of absent in melanoma 2 (AIM2) in pancreas in acute pancreatitis (AP).  METHODS: Caerulein was used to set AP mice model, which were then divided into the control group and the AP group. Q-PCR and Western blot were used to detect AIM2, IL-1beta and IL-18 mRNA and protein expression in peripheral blood mononuclear cells (PBMCs). ELISA method was used to detect the concentration of IL-1beta and IL-18 in culture supernatants of PBMCs. RESULTS: Q-PCR and Western blot showed that compared with the control group, the expression of AIM2, IL-1β and IL-18 mRNA and protein in PBMCs AP group increased significantly (P<0.01). ELISA test results showed that compared with the control group, the concentration of IL-1beta and IL-18 from culture supernatants of PBMCs in AP group increased significantly (P<0.01). CONCLUSION: The higher expression of AIM2 in PBMCs of AP showed activation of the AIM2 inflammasome in PBMCs results in exacerbated IL-1beta and IL-18 production. Therefore, AIM2 might be a potential therapeutic target in clinical AP treatment.

    Antagonistic effects of nisoldipine on the contractile response of human uterine artery
    DU Meisu, YANG Bo, LIU Xueqin, WEI Guohui, ZHANG Xinxia, HAN Zongqi, GUO Minying
    2018, 23(1):  55-58.  doi:10.12092/j.issn.1009-2501.2018.01.011
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    AIM: To study the effects of nisoldipine on the contractile response of isolated human uterine artery induced by potassium chloride (KCl) and phenylephrine (PHE).  METHODS: Isolated artery experiment was conducted to observe the antagonistic effects of nisoldipine on the contraction induced by KCl and PHE in isolated human uterine arterial rings in the calciferous and calcium-free K-H solution. RESULTS: In the calciferous K-H solution, the contractile response of isolated human uterine artery induced by KCl (50 mmol/L, 80 mmol/L) and PHE[(1×10-6)mol/L, (5×10-6)mol/L)] were inhibited by nisoldipine. The IC50 were[(7.52±1.33)×10-9 mol/L,(2.75±0.53)×10-7 mol/L ] and  [(6.17±1.21)×10-8 mol/L,(1.51±0.49)×10-6 mol/L], respectively. In the calcium-free K-H solution, nisoldipine showed no effect. CONCLUSION: The contractile response of isolated human uterine artery can be inhibited by nisoldipine.

    Bridging method of adjusted significance levels α' in the target region concerning superiority design for normal data distribution in MRCT
    SHANG Feng, YU Chengkai, YANG Peng
    2018, 23(1):  59-64.  doi:10.12092/j.issn.1009-2501.2018.01.012
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    AIM: To explore the feasibility to adjust the significance levels α' in the target region as the basis of data in normal distribution for the primary efficacy endpoint, the reasonable value of adjusted significance levels α' and reasonable proportions of sample size in target region,and to make a reference for new drug approvals of Multi-Regional Clinical Trial (MRCT) in target region.  METHODS: By using Monte Carlo simulation, we studied the conditional false positive rate (CFPR) and conditional power (CP) changing with the proportions K of the sample size in target region by adopting different significance levels given that the treatment effect was shown to be significant under the significance level α=0.05 based on different sized MRCTs. RESULTS:Simulations results showed that CFPR and CP increased with the increasing significance level α' and the bigger K, the bigger CFPR. In addition, CFPR could be well controlled under 0.5 if K was no more than 30% and α' is no more than 0.5. Though f values 1.0, CP still kept low and was no more than 0.76 when K was no more than 15%. If f could be more than 0.8, CP would exceed 0.70 when K valued 20%. If f can be more than 0.8, CP will exceed 0.75 when K values 25%. When K valued 30%, CP would exceed 0.80 as long as f≥ 0.7. Lastly, even though f valued only 0.5, CP would exceed 0.80 when K valued 50%. CONCLUSION: The method in this study is easy to understand and operate, and have a better performance especially when f≥0.7.

    Markov model to assess long-term effects of teneligliptin in treatment of type 2 diabetes mellitus
    ZHANG Chunyan, FAN Xiaodong, QIN Yuan, KONG Wenqiang, ZHOU Chunyang, DU Biao
    2018, 23(1):  65-72.  doi:10.12092/j.issn.1009-2501.2018.01.013
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    AIM: To investigate the long-term efficacy and safety of teneligliptin as dipeptidyl -peptidase Ⅳ(DPP-4) inhibitor for type 2 diabetes mellitus and estimate the long-term efficacy.  METHODS: Search the literature in databases of PubMed, The Cochrane Library, Embase, CNKI, Wan Fang, CQVIP and so on. Randomized controlled trials (RCT) of teneligliptin for the treatment of T2DM were collected with time limit from establishment to June, 2017. References and related professional magazine were also retrieved manually. Two researchers independently screened these literatures according to the inclusion and exclusion criteria, extracted basic information and assessed the methodological quality of included studies. Meta-analysis of the indexes was performed by using RevMan 5.3. Evaluate the long-term efficacy by establishing a new Markov model. RESULTS: Five RCTs were collected, including 903 diabetic patients. The results of meta-analysis showed teneligliptin can effectively reduce the main index HbA1c [SMD=-0.87, 95%CI(-0.99,-0.76), P<0.000 01] and FPG[SMD=-0.71, 95%CI (-0.85,-0.58), P<0.000 01], increase the secondary index HOMA-beta [SMD=0.46, 95%CI (0.33,0.60), P<0.000 01] than placebo group. And there was significant difference between them (P<0.05). And Markov model showed teneligliptin can decrease the numbers of death. CONCLUSION: As the new kind of hypoglycemic agent, dipeptidyl peptidase-Ⅳ (DPP-4) inhibitor teneligliptin can reduce the blood glucose effectively with no increased risk of hypoglycemia, protect the beta-cell function of type 2 diabetic mellitus and decrease the rate of diabetes complications and death.

    Rapid and sensitive determination of amoxicillin in human plasma by LC-MS/MS and the bioavailability of two amoxicillin capsules
    NAN Feng, XU Nan, CHEN Zhihui, XIANG Jin, LIANG Maozhi, TAO Zeting, YE Wei
    2018, 23(1):  73-77.  doi:10.12092/j.issn.1009-2501.2018.01.014
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    AIM: To establish a rapid and sensitive LC-MS/MS method for determination of amoxicillin in human plasma and to study the bioavailability of two amoxicillin capsules.  METHODS: Shimadzu LCMS-8060 series LC-MS/MS was used. Amoxicillin(m/z 366.00/114.00)and d4-amoxicillin (internal standard, m/z 370.10/114.05) were monitored by ESI in MRM model. The analysts were eluted on Waters ACQUITY BEH C18 column ( 2.1×50 mm,1.7 μm) according to gradient elution program. The plasma samples were mixed with internal standard, then precipitated protein by methanol, the supernatants were detected. RESULTS: The linear, accuracy, precision, LLOQ, extraction recovery, specificity, matrix effect, stability of our method all met the guiding principles and criteria of CFDA. Compared with the literature reports, our method was simple, rapid, sensitive and had better chromatographic peaks. CONCLUSION: The method is rapid, sensitive and suitable for the determination of amoxicillin in human plasma. The test capsule is bioequivalence to the reference capsule.

    Analysis of regulatory issues of adverse events in drug clinical trials
    PENG Peng, YUAN Wei'an, HU Yihui, TANG Jie, JIANG Jian
    2018, 23(1):  78-82.  doi:10.12092/j.issn.1009-2501.2018.01.015
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    AIM: To investigate the issues of regulatory issues of adverse events in drug clinical trials.  METHODS: The supervisory quality of adverse events in phase Ⅱ-Ⅳ drug clinical trials and those for post-marketing drug assessment with finished clinical section from 2011 to 2016 was analyzed by referring to clinical trial materials in the institution.RESULTS:The related data of influencing factors in 5 monitoring aspects including recording integrity of adverse events for laboratory examination, consistency of records between source data and case report form, their follow-up visit and review, on-time rate of documentation, and reporting situation of serious adverse events were collected in all the adverse events in 165 drug clinical trials and 39 serious ones among the total. CONCLUSION: There are still some problems in the current safety evaluation system of drug clinical trials. It is imperative to strengthen the training of investigators and all-round process management in order to find a solution to these issues.

    Role of Th17 cells in acne pathogenesis and the correlation with severity of acne
    LU Wei, ZHOU Bingrong,TANG Yi, FAN Yibin, TAO Xiaohua
    2018, 23(1):  83-87.  doi:10.12092/j.issn.1009-2501.2018.01.016
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    AIM: To investigate the mechanism of Th17 cells in acne development and its correlation with severity.  METHODS: One hundred and thirty six cases were divided into control, mild, moderate and severe acne group according to the Pillsbury method. The expression levels of IL-17, IL-23, IL-6 and TGF-beta1 in serum were detected by ELISA. RORγt mRNA and IL-17 mRNA expression levels were detected by RT-PCR. RESULTS: The levels of IL-17 and IL-23 in serum of patients with moderate to severe acne were significantly higher than those of the control and mild acne groups (P<0.05). The levels of IL-6 and TGF-beta1 in moderate and severe acne groups were significantly higher than those of control group (P<0.05). There was no significant difference in the expression of IL-6 and TGF-beta1 between mild and moderate acne groups (P>0.05). In addition, the expressions of IL-17 mRNA and RORγt mRNA from mild to severe groups were significantly different from control group (P<0.05). And there was significant difference between the three groups (P<0.05). CONCLUSION: Th17 cells have a cascade effect in mild, moderate and severe acne groups, which can provide a new target for future treatment of severe acne.

    Application of vasopressin in laparoscopic ovarian endometriosis cyst removal
    ZHOU Xianwei, SHENG Shaoqin, HU Fengying
    2018, 23(1):  88-92.  doi:10.12092/j.issn.1009-2501.2018.01.017
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    AIM: To observe the application effect of vasopressin used in laparoscopic cystectomy of ovarian endometriosis cyst. METHODS: One hundred and four patients with ovarian endometriosis cyst were randomly divided into two groups,the observation group(the operation was using vasopressin before laparoscopic cystectomy) and control group (routine laparoscopic cystectomy) 52 cases in each group.The operation time,blood loss,cyst rupture rate,postoperative body temperature,anal exhaust time and the levels of follicle-stimulating hormone (FSH), luteinizing hormone(LH),estradiol (E2) at the preoperative and postoperative one month were observed between two groups. RESULTS: Operation time,blood loss,cyst rupture rate of observation group were less than those of control group,the difference were statistically significant (P<0.05).Compared with preoperative,the postoperative one month (7.17±1.27),three month(7.13±1.26),six month(7.12±1.32) levels of FSH in observation group were slightly higher,there was no statistically difference(P>0.05);the postoperative one month(186.67±34.16) level of E2 in observation group was slightly reduced,and three month (193.56±31.46),six month(204.79±33.48) levels of E2 were gradually rised,there was no statistically difference(P>0.05).In control group,the postoperative one month (7.91±1.16),three month(7.48±1.44),six month(7.22±1.60) level of FSH were higher than the preoperative level, the difference were statistically significant (P>0.05); and the postoperative one month(171.35±28.75),three month(179.42±27.64), six month(180.31±29.04) levels of E2 were lower than the preoperative level,although the three month and six month were slightly higher than one month,compared with preoperative there was significant difference (P<0.05). Compared with preoperative,two groups of postoperative one month,three months, six months levels of LH showed no statistically significant difference (P>0.05). CONCLUSION: Using vasopressin before laparoscopic cystectomy can shorten the operation time, decrease blood loss and cyst rupture rate,and is helpful to protect ovarian reserve function, which worth promoting in clinical.

    Clinical features and risk factors for infecfions in multiple myeloma during chemotherapy
    WU Haibing, ZHANG Gang, HAN Bin, GUO Xiaojun, JI Zhaoning
    2018, 23(1):  93-98.  doi:10.12092/j.issn.1009-2501.2018.01.018
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    AIM: To observe the clinical characteristics of infections in multiple myeloma (MM) patients during chemotherapy in hospital, and to identify the risk factors for infection and provide the basis for prevention and control of nosocomial infections. METHODS: A retrospective study of patients with MM who underwent chemotherapy between Jan 2012 and Mar 2016 in the First Affiliated Hospital of Jiaxing University was conducted. Clinical features and risk factors for infections were analyzed. RESULTS: One hundred and fifty three patients with MM received a total of 415 courses of chemotherapies. During which 150 (36.14%) infections episodes occurred. The common infections sites were respiratory tract infection (49.25%), gastrointestinal tract infection (16.42%), urinary tract infection (13.43%) and oral infection (7.46%).Seventy-four strains of pathogenic bacteria were detected. Gram-negative bacteria were observed in 71.62% of documented pathogens, and Gram-positive bacteria were responsible for 17.57% of infections. Multivariate unconditioned logistic analysis of factors identified consistent independent risk factors for complication of diabetes mellitus(95%CI:6.572-80.650, OR=22.359, P<0.001), hospitalization time longer than 20 days(95%CI:1.785-29.169, OR=17.328, P<0.001), and high ISS stage(95%CI: 4.974-35.247, OR=12.894, P<0.001). CONCLUSION: Patients with MM tended to be infected with various species of pathogens after the chemotherapy; MM patients with complication of diabetes mellitus, hospitalization time longer than 20 days, and high ISS stage faced an increased risk of infections by multivariate analysis. It is necessary for the hospital to strengthen the risk assessment for the patients and take effective prevention and control measures for the patients complicated with diabetes, hospitalization interval longer than 20 days, or high ISS stage.

    Clinical trial of methylprednisolone and batroxobin combined with hyperbaric oxygen in the treatment of sudden deafness
    WANG Jingbo, FANG Lian, SONG Xiaoxiao, ZHOU Qinshuang
    2018, 23(1):  99-103.  doi:10.12092/j.issn.1009-2501.2018.01.019
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    AIM: To observe the clinical efficacy and safety of methylprednisolone and batroxobin combined with hyperbaric oxygen in the treatment of sudden deafness, and to explore their effect on blood coagulation function and blood vessel function.  METHODS: Ninety-two patients with sudden deafness were randomly divided into the control group and the treatment group, forty-six cases for each group. The control group were given batroxobin injection initial dose 10 BU, maintenance dose 5 BU, two days one time, intravenous plus hyperbaric oxygen therapy; and the treatment group were given methylprednisolone sodium succinate injection 40 mg, qd, intravenous plus batroxobin injection plus hyperbaric oxygen therapy. After treatment for 10 d, the clinical efficacy and occurrence of adverse drug reactions were observed. The levels of plasma prothrombin time (PT), activated partial thromboplastin time (APTT), soluble vascular cell adhesion molecule-1 (sVCAM-1), intercellular adhesion molecule-1 (ICAM-1), vascular endothelial growth factor (VEGF), superoxide dismutase (SOD), thromboxane B2 (TXB2) and vascular endothelial cadherin (VE-cadherin) were compared. RESULTS:The total effective rate in the treatment group and the control group were 97.83%(45/46) and 80.43% (37/46), respectively (P<0.05). PT of the treatment group and control group were (20.34±3.21) and (15.18±2.13) s; APTT were (51.47±4.34) and (40.01±3.56) s; sVCAM-1 were (113.35±20.76) and (172.14±21.37) μg/L; ICAM-1 were (67.12±14.35) and (95.16±14.52)μg/L; VEGF were (92.75±15.36) and (75.12±14.18) μg/L; SOD were (133.47±11.69) and (112.37±10.43) ng/L; TXB2 were (198.74±16.31) and (237.15±17.17) ng/L; VE-cadherin were (3.02±0.57) and (4.41±0.59) mg/L , respectively, the differences were all statistically significant (P<0.05). The adverse drug reactions were mainly headache, gastrointestinal discomfort, flustered, itchy skin; the incidence of adverse drug reactions in treatment group and control group were 17.39% and 15.22%, respectively (P>0.05). CONCLUSION: Methylprednisolone and batroxobin combined with hyperbaric oxygen have significantly curative effect in the treatment of sudden deafness, which improve the patient's blood coagulation function, endothelial function, repair endothelial injury, and present no increasing the adverse drug reactions.

    Effects of neo-adjuvant chemotherapy combined with modified radical mastectomy on clinical effect and tumor markers in patients with breast cancer
    LUO Yong, LI Qi, HUA Tebo
    2018, 23(1):  104-109.  doi:10.12092/j.issn.1009-2501.2018.01.020
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    AIM: To investigate the effects of neo-adjuvant chemotherapy combined with modified radical mastectomy on clinical effect and tumor markers in patients with breast cancer.  METHODS: According to chemotherapy regimens, a total of 88 advanced colorectal cancer patients were divided into TE group (46 cases) and FEC group (42 cases) from August 2013 to February 2015. All patients received 4 cycles of chemotherapy (1 cycle=21 d). Changes of immune function, MMP and VEGF, adverse reaction and survival situation in two groups were observed and compared. RESULTS: Total lymphocytes, T lymphocyte, helper T lymphocyte and cytotoxic T lymphocyte of TE group had no significant difference before chemotherapy and after chemotherapy (P>0.05); T lymphocyte, and cytotoxic T lymphocyte of FEC group had no significant difference before chemotherapy and after chemotherapy (P>0.05); total lymphocytes and helper T lymphocyte of FEC group decreased significantly after chemotherapy (P<0.05); total lymphocytes and helper T lymphocyte of FEC group were significantly lower than those in TE group (P<0.05); MMP-2 and MMP-9 of two groups decreased significantly after chemotherapy (P<0.05); MMP-2 and MMP-9 of TE group were significantly lower than those in FEC group (P<0.05); VEGF-A and VEGF-B of two groups decreased significantly after chemotherapy (P<0.05); VEGF-A and VEGF-B of TE group were significantly lower than those in FEC group (P<0.05); incidence rate of adverse reactions of TE group was 4.35%, which was 16.67% of FEC group, there was no significant difference between TE group and FEC group (P>0.05); Followed up for 2 years, survival rate of TE group was 84.78%, incidence rate of adverse reactions of FEC group was 64.29%, survival rate of TE group was significantly higher than that in FEC group (P<0.05). CONCLUSION: neo-adjuvant chemotherapy combined with modified radical mastectomy has little influence on immune function and fewer adverse reactions, which can restrain MMP and VEGF, and improve survival rate in patients with breast cancer.

    Evaluation of clinical rationality of linezolid in our hospital in 2016
    XU Jia, HUANG Qi, YANG Zhiling
    2018, 23(1):  110-115.  doi:10.12092/j.issn.1009-2501.2018.01.021
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    AIM: To evaluate the clinical rationality, efficacy and safety of linezolid in our hospital in 2016 and to provide reference for its clinical application. METHODS: A retrospective study was conducted using the medical history data of patients treated with linezolid in 2016. The questionnaire was designed to compile statistics of rational use rate, to analyze the causes of irrational use, and to calculate the clinical cure rate, pathogen clearance rate and comprehensive cure rate, as well as to monitor the red blood cell, hemoglobin and platelet decline after treatment of linezolid. RESULTS: The rational use rate of linezolid was 48.1%, the irrational reasons are mainly that the indication was unreasonable and the course of treatment was unreasonable. The clinical cure rate was 40.4%, the pathogen clearance rate was 42.3%, and the comprehensive cure rate was 56.4%. The incidence of myelosuppression was 21.2% in patients whose average age was (81.4±8.7)years old, and the average course of treatment was (13.6±5.6)days. CONCLUSION: The rate of clinical rational use of linezolid needs to be improved in our hospital. The correct indication and course of treatment will improve the rational rate to a great extent. And the comprehensive curative effect is acceptable. But special attention should be paid to the occurrence of myelosuppression for the elderly patients.

    Pharmacodynamic studies evaluation of voriconazole
    ZHANG Chao
    2018, 23(1):  116-120.  doi:10.12092/j.issn.1009-2501.2018.01.022
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    Voriconazole, as a first-line antifungal treatment, has been widely used in clinics. Significant variability of voriconazole has been found and its pharmacodynamic characteristics vary in different populations. In this paper, the review and evaluation of voriconazole pharmacodynamics are presented to indicate their determined influence factors according to populations and to investigate corresponding strategy of dosage adjustment. Therapeutic drug monitoring is suggested to combine with simulations through population pharmacokinetic/phamacodynamic model to improve the accuracy of dosage adjustment.