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

Table of Content

    Volume 23 Issue 7
    26 July 2018
    Effects of dihydromyricetin on wear-particle-induced osteolysis in murine calvarial model
    HUANG Donghui, ZHENG Hangsheng
    2018, 23(7):  721-727.  doi:10.12092/j.issn.1009-2501.2018.07.001
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    AIM: To investigate the effects of dihydromyricetin (DMY) on wear-particle-induced osteolysis in murine calvarial model. METHODS: Thirty male C57BL/J6 mice were randomly divided into the sham group, the control group, and the DMY group (10 in each group). Except for the mice from the sham group, mice from the control group and DMY group received 30 mg Ti particles into calvaria to induce osteolysis in murine calvarial model. Mice from the DMY group were gavage-fed daily with DMY of 500 mg/kg, while mice from the sham group and control group were gavage-fed daily with saline. Calvaria and vein blood samples from each group were harvested for further micro-CT and pathological analysis at the 14th after the surgery. RESULTS:Micro-CT showed that the severity of osteolysis was significantly reduced in DMY group. And the BMD of the samples in DMY group was significantly higher than that of the control group(P<0.05). By the HE and TRAP staining analysis, less osteoclasts were found in the samples in DMY group. In addition, the application of DMY also decreased the serum TNF-α, IL-1β, and RANKL level yet improved OPG level as compared with the positive control group(P<0.05). DMY could significantly inhibit the differentiation of RANKL-induced osteoclast by in vitro cell culture experiments.CONCLUSION: DMY can inhibit the wear-particle-induced osteolysis in murine calvarial model.

    Effects of bufalin on radiosensitivity of esophageal cancer Kyse150 cell line
    FANG Weiyang, LI Yue, SHENG Lei, CUI Zhenzhen, ZHONG Fei, TONG Zhuting
    2018, 23(7):  728-733.  doi:10.12092/j.issn.1009-2501.2018.07.002
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    AIM: To investigate the radio-sensitivity effect of bufalin in Kyse150 cell line. METHODS: CCK-8 method was used to determine the IC50 value of bufalin in Kyse150 cell line. The linear-quadratic (L-Q) curve was fitted according to the results of cloning formation and calculated the survival fraction of 2Gy (SF2) and sensitization enhancement ratio (SER). Annexin V-FITC/PI double staining and Western blot were used to detect the effect of bufalin on apoptosis of esophageal cancer Kyse150 cell line. The effect of different bufalin doses on Kyse150 cell line radiosenstivity was detected by cloning formation assay. RESULTS: CCK-8 results showed that the IC50 value of bufalin in the Kyse150 cell line was 129.1 nmol/L (95% CI: 105.2-158.6). The L-Q curve fitted by colony formation assay showed that bufalin can significantly reduce the colony forming efficiency of cells after radiotherapy, and the sensitization enhancement ratio of bufalin in Kyse150 cell line was 1.463. Annexin V-FITC/PI double staining and Western blot results showed that bufalin can improve radiation-induced apoptosis, and showed that bufalin has a dose-dependent effect on radiosensitization of esophageal cancer Kyse150 cell line. CONCLUSION:Bufalin can enhance the radiosensitivity effect of the Kyse150 cell line in a dose-dependent manner.

    Involvement of lateral septum GABAA receptors in the regulation of anxiety-like behaviors in hemiparkinsonian rats
    CHANG Yongli, WANG Chunlei, YUAN Li, GUO Xiaoshu, HAN Lingna
    2018, 23(7):  734-742.  doi:10.12092/j.issn.1009-2501.2018.07.003
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    AIM: To investigate the role of GABAA receptors in the lateral septum (LS) in the regulation of anxiety-like behaviors in hemiparkinsonian rats. METHODS: A total of 167 rats were randomly divided into sham-operated group (n=85) and medial forebrain bundle (MFB) lesioned group (n=82). The open field and elevated plus maze (EPM) test were performed to study the influence of MFB lesion and intra-LS injection of GABAA agonist muscimol (0.2, 0.4 or 0.8 μg/rat) and antagonist picrotoxin (0.1, 0.2 or 0.4 μg/rat) on anxiety-like behaviors. Changes of monoamine levels in limbic related brain regions were observed by high performance liquid chromatography with electrochemical detection. RESULTS: Compared with sham-operated group, the MFB lesioned group induced anxiety-like behaviors. The dopamine (DA) levels in LS, amygdala and ventral hippocampus (vHip) were significantly decreased compared with sham-opreated group. Compared with the rats treated with vehicle in the same group, the intra-injection of muscimol in LS induced or aggravated the anxiety-like behaviors in two groups, and decreased DA and 5-hydroxytryptamine (5-HT) levels in three brain regions. In contrast, the administration of picrotoxin improved anxiety-like behaviors, and increased 5-HT in three brain regions and DA in amygdala and vHip. However, the doses producing the behavioral effects in the lesioned rats were higher than those in sham-operated rats. CONCLUSION: GABAA receptors in the LS are involved in the regulation of anxiety-like behaveiors, which is attributable to changes in dopamine, 5-HT levels in the limbic-related brain regions after activation and blockade of GABAA receptors.

    Inhibition of articular cartilage degeneration by atorvastatin calcium via STAT1-caspase-3 signaling axis in rats with knee osteoarthritis
    HUANG Lijia, HUANG Yang, KONG Jinsong, ZHENG Xin, GONG Xiaokang, RUAN Jianwei, WANG Haibao
    2018, 23(7):  743-748.  doi:10.12092/j.issn.1009-2501.2018.07.004
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    AIM: To investigate the effect of atorvastatin calcium on the expression of STAT1, caspase-3 and on degeneration of articular cartilage in the knee osteoarthritis (KOA) rats. METHODS: SD rats were randomly divided into normal control group, model group and atorvastatin calcium treatment group. KOA rat model was established by Hulth method. After 8 weeks of experiment, the expression of TNF-α and IL-1β in serum of rats were detected by ELISA, X-ray examination was used to detect knee joint, articular cartilage HE staining were used for pathological observation, cartilage tissue p-STAT1 and cleaved caspase-3 protein expression levels were observed by immunohistochemistry and western blot.RESULTS:The levels of serum TNF-α and IL-1β in model group were significantly higher than those in normal group (P<0.01), while those in atorvastatin calcium group were lower than those in model group (P<0.01). Compared with the model group, the X-ray findings of atorvastatin calcium treatment group showed improvement of knee joint space, articular cartilage destruction and osteophyte formation. Atorvastatin calcium could significantly reduce the pathological changes of knee joint. Compared with model group, Mankin's score of articular cartilage in atorvastatin calcium treatment group decreased significantly (P<0.01). The expression of p-STAT1 and cleaved caspase-3 protein in articular cartilage of model group was significantly higher than that of normal group (P<0.01), while that of atorvastatin calcium group was lower than that of model group (P<0.01), and the correlation analysis showed that there was a linear positive correlation between p-STAT1 and cleaved caspase-3 (r=0.986, P<0.01).CONCLUSION:Atorvastatin inhibits the inflammation of the knee joint via STAT1-caspase-3 signal axis, thereby improving the degeneration of KOA articular cartilage.

    Regulative effects of miR-150 on CYP3A4
    LIU Li, PENG Jinfu, GUO Chengxian, YANG Xiding, LI Haigang, YANG Guoping
    2018, 23(7):  749-754.  doi:10.12092/j.issn.1009-2501.2018.07.005
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    AIM: To explore the role of miR-150 in the regulation of CYP3A4 and the underlying mechanism. METHODS: CYP3A4 mRNA and protein expression were tested by RT-PCR and Western blot when the Chang liver cells were stimulated by FFA containing fatty acids free 1% BSA. Bioinformatics miRNA databases were used to identify CYP3A4-related miRNAs and the wild-type CYP3A4 3′-UTR plasmids were constructed, miR-150 and reporter plasmid were co-transfected into the Chang liver cells to test the expression ratio of the reported fluorescence and the correction fluorescence. Then the miR-150 mimic were transfected into the Chang liver cells, while miRNA inhibitor were transfected into the steatosis cells. RT-PCR and Western blot were used to detect CYP3A4 mRNA and protein expression. RESULTS: The CYP3A4 mRNA and protein level were statistically significantly decreased(P<0.05), while the mature miR-150 levels were increased (P<0.05)when the Chang liver cells were stimulated after 24 h by 1 mmol/L FFA. CYP3A4 was found to be the target gene of miR-150 with a bioinformatics analysis. Then CYP3A4 mRNA level was significantly decreased (P<0.05). Meanwhile, the expression level of CYP3A4 protein also decreased when the miR-150 mimic were transfected into the Chang liver cells. But CYP3A4 mRNA expression has no statistical significance (P=0.071) in miR-150 inhibitor group. CONCLUSION: The miR-150 can combine with CYP3A4 3′-UTR directly, and can further regulate the expression of CYP3A4 mRNA.

    Effects of CD40 pathway on the biological behavior of pancreatic cancer cells
    ZHANG Guifeng, CAI Jiaqin, CUI Tongjian, LIU Zhenhua, XU Zhixian
    2018, 23(7):  755-760.  doi:10.12092/j.issn.1009-2501.2018.07.006
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    AIM: To study the effect of CD40L on the biological characteristics and stenness of pancreatic cancer cells. METHODS: The effect of different concentrations of sCD40L (0, 1, 2, 4 μg/mL) on the proliferation of human pancreatic cancer cell line panc02 was analyzed by CCK-8 live cell counting assay. Apoptosis was detected by Annexin V/PI double staining; migrational ability was detected by Cell Scratch Assays. Q-PCR was used to detect the levels of c-Myc, OCT-4 and Sox-2 after panc02 treatment for 4 h/mL sCD40L. A Balb/c nude mouse model of pancreatic cancer was established and randomly divided into two groups: control group (normal saline) and sCD40L (10 mg/kg) group. They were injected intraperitoneally with sCD40L 10 mg/kg and an equal volume of saline for three times a day. Tumor volume was measured using vernier calipers at 0, 7th, 14th, 21st, and 28th day. RESULTS: Compared with the control group, the growth and migration of panc02 decreased significantly after sCD40L treatment (1, 2, 4 μg/mL for 96 h), and apoptosis was promoted in a dose-dependent manner (P<0.01). sCD40L (4 μg/mL) significantly inhibited the expression of c-Myc, OCT-4, Sox-2 of panc02 (P<0.01). In the nude mice tumor-bearing experiment, compared with the control group, sCD40L significantly inhibited the tumor volume at 28th day (P<0.01, 252±13 vs. 189±9). CONCLUSION: Activation of CD40 pathway inhibits proliferation, migration and apoptosis of pancreatic cancer cells as well as the proliferation of pancreatic cancer cell lines in vivo. This effect may be related to the change of stemness in pancreatic cancer cell lines.

    Changes of Sonic Hedgehog signaling pathway in the stomach mucosa of rats in the formation process of gastric precancerous lesions
    LIU Qingsheng, YU Jianshun, CAI Danli, YAN Maoxiang, WANG Xiaoqi, SANG Yi
    2018, 23(7):  761-769.  doi:10.12092/j.issn.1009-2501.2018.07.007
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    AIM: To investigate the changes of Sonic Hedgehog signaling pathway in the stomach mucosa of rats in the formation process of gastric precancerous lesions. METHODS: Seventy-two suckling rats in half genders were randomly and equally divided into normal group and model group. The rats in the model group were given 0.1 mL MNNG at the dosage of 800 mg/L by gavage per day for 10 days, while the rats in the normal group were given normal saline. Twelve rats in each group were sacrificed at the end of the 10th, 22th and 34th week, respectively. Histopathologic changes of the gastric mucosa were observed by HE staining; the levels of Shh, Ptch1, Smo, Gli1, Gli2, Gli3, SuFu, CyclinD1, CyclinE1, c-Myc and β-actin mRNA in the gastric mucosa were determined by Realtime-PCR; the expressions of Shh, Ptch1, Smo, Gli1, SuFu, CyclinD1, CyclinE1, c-Myc, p-c-Myc protein were detected by Western Blot. RESULTS:With the development of the atrophy and dysplasia of gastric mucosa, the levels of Shh, Smo, Gli1, CyclinD1, CyclinE1 and c-Myc mRNA increased and those of Ptch1 and SuFu mRNA decreased; the expressions of Shh, Smo, Gli1, CyclinD1, CyclinE1, p-c-Myc protein showed an increase trend while the expressions of Ptch1 and SuFu protein decreased. CONCLUSION: Shh signaling is activated in the formation process of gastric precancerous lesions, which indicates Shh signaling pathway participates in the development and progression of gastric precancerous lesions.

    Lycopene protects against CCl4-induced acute hepatic injury via inhibiting endoplasmic reticulum stress
    LIAO Xiaoling,WU Liang,LIN Zongze,YE Jian
    2018, 23(7):  770-775.  doi:10.12092/j.issn.1009-2501.2018.07.008
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    AIM: To investigate the effects and mechanism of lycopene on endoplasmic reticulum stress (ERS) in CCl4-induced acute liver injury mice. METHODS: The mice were treated with lycopene (i.g.) and acute hepatic injury was induced by carbon tetrachloride (CCl4, i.p.). The activity of lactic dehydrogenase (LDH) in liver tissue was measured by kit. The apoptosis was measured by TUNEL assay. Western blot was performed for proteins. RESULTS: Lycopene decreased the activity LDH (P<0.01) significantly. Meanwhile, lycopene inhibited apoptosis makedly (P<0.05). In addition, pretreatment with lycopene inhibited the expressions of glucose regulated protein 78kda (GRP78), activating trnsfection factor-6 (ATF-6), inositol requiring enzyme (p-IRE-1α), eukaryotic initiation factor-2α (p-eIF-2α) and caspase-12 (P<0.05). Furthermore, the ratio of p-Akt/Akt was down-regulated by lycopene (P<0.05). CONCLUSION: Lycopene alleviates CCl4-induced liver injury by inhibiting ER stress, and the mechanism might be associated with the activation of PI3K/Akt signaling pathway.

    GC-MS-based a carrier gas purge experimental device to test the electronic smoke nicotine concentration
    ZHANG Yongxue, HE Qing, ZHANG Xiaoyu, ZHANG Wenxin, ZHAO Qingzhong, WANG Zhiwei, GAO Shan
    2018, 23(7):  776-781.  doi:10.12092/j.issn.1009-2501.2018.07.009
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    AIM: To establish an experimental device to test the nicotine concentration of cigarette smoke. METHODS: The nicotine concentration and peak area linear equation were established by GC-MS. It was used to determine the different flow rates of air for the carrier gas purge of liquid nicotine formation of aerosol nicotine concentration. Serum cotinine concentration in rats was determined by ELISA. RESULTS: In the range of 0.226 0 to 2.269 7 μg/mL, the nicotine peak area showed a good linear relationship with its mass concentration, and the correlation coefficient (r2=0.993 7).The average recoveries were 97.2%, 113.7%, and 108.1%, respectively, with standard gaseous nicotine concentrations of 0.567 4, 1.134 8, and 1.702 3 μg/mL, respectively. The relative standard deviations (RSD) were 6.1% and 20.8%,16.9%,respectively (n=3).The retention time of standard and e-cigarette nicotine was 13.41 min. Fragment quantification ion m/z 84.03 and auxiliary quantification ion m/z 133.03 appeared. The specificity of the method was good. Electronic cigarette smoke nicotine concentration was 0.584 μg/mL. Conditions: 25 ℃ nicotine liquid height of 20 cm, air flow 1.1 L/min, the experimental device aerosol nicotine concentration and electronic cigarette smoke matched. Compared with the control group (2.05±0.83) ng/mL, the serum cotinine concentration in the nicotine group was significantly higher(5.31±0.62) ng/mL (P<0.01). CONCLUSION: An experimental device is established to test the nicotine concentration of the electronic cigarette smoke,which can infect rats with nicotine.

    Determination of apatinib in tumor patients' plasma by liquid chromatography tandem mass spectrometry and its application
    LI Li, LI He, LIU Xing'e, WEI Nan
    2018, 23(7):  790-795.  doi:10.12092/j.issn.1009-2501.2018.07.011
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    AIM: To establish a rapid, accurate liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of apatinib in tumor patients and apply this method to analyze the clinical samples. METHODS: Sorafenib was employed as the internal standard. The analyte and internal standard were extracted from plasma by protein precipitation with acetonitrile and separated on Eclipse Plus C18 column (2.1 mm×100 mm, 3.5 μm) , mobile phase consisted of acetonitrile-10 mmol/L ammonium acetate (85∶15, V/V, containing 0.1% formic acid) at the flow rate of 0.25 mL/min. Electrospray ionization (ESI) source was applied and operated in the positive multiple reaction monitoring (MRM) mode.The MS/MS ion transitions monitored were m/z 398.1→m/z 212.0 and m/z 465.3→m/z 270.1 for apatinib and internal standard, respectively. After methodology validation, this method was applied for the clinical analysis of apatinib in plasma from tumor patients.RESULTS:Chromatograms showed no endogenous interfering peaks with blank samples. The standard curves were demonstrated to be liner in the range of 2.0-2 000 μg/L (r=0.996 8). The RSD of inter-day (n=5) and intra-day (n=3) for four different concentration levels were less than 15%, The average recoveries were between 78.0% and 87.8%.The internal standard normalized matrix effect 92.4% and 107.3%. CONCLUSION: The method is specific, sensitive and suitable for clinical determination of apatinib in tumor patients plasma efficiently.

    Clinical effect of entecavir combined with probiotics on treatment of patients with hepatitis B cirrhosis
    ZENG Chuanli, HU Airong, HU Yaoren, YUAN Gang, ZHU Dedong, SHI Xiaojun
    2018, 23(7):  796-801.  doi:10.12092/j.issn.1009-2501.2018.07.012
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    AIM: To observe the clinical efficacy of nucleoside antiviral drugs (entecavir) combined with probiotics (Bifid triple viable capsules) in the treatment of patients with hepatitis B cirrhosis. METHODS: One hundred and sixty patients with cirrhosis caused by hepatitis B virus infection admitted to our department of hepatology from July 2014 to January 2017 were randomly divided into control group and observation group, with 80 cases in each group. The two groups were treated with basic liver protection, and the control group was treated with entecavir 0.5 mg/times/day orally, while the observation group was given extra Bifidobacterium triple viable capsules 2 times a day, 2-4 capsules per time. All patients received continuous treatment for 6 months, during which the clinical signs, the liver region B ultrasound, liver function, the liver fiber 4 items and the peripheral blood T cell subgroup level of two groups were observed. RESULTS: Compared with before treatment, ALT, AST, TBIL, blood ammonia and endotoxin, liver fibrosis and immune response index, the diameter of portal vein and spleen thickness were significantly improved after treatment (P<0.05); also, compared with control group, those indexes of the observation group improved more significantly (P<0.05); comparison of the complications after treatment had no significant difference. CONCLUSION: Entecavir combined with Bifidobacterium triple viable capsule can improve the intestinal homeostasis, further reduce liver fibrosis and improve liver function in patients with viral hepatitis B cirrhosis.

    Influence of genetic variation of KDR on clinical outcomes of advanced NSCLC treated by first line bevacizumab regimens
    WANG Haixia, LIU Xingan, HOU Jiyuan, GONG Zhe, SHAN Guoyong
    2018, 23(7):  802-808.  doi:10.12092/j.issn.1009-2501.2018.07.013
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    AIM: To investigate the association between KDR gene polymorphism and the efficacy of bevacizumab in patients with advanced non-small cell lung cancer. METHODS: A total of 135 patients with advanced non-small cell lung cancer who were treated by bevacizumab based first line regimens were included in this study. Peripheral blood and the biopsy tissue specimens of the NSCLC patients were collected for the genotyping of genetic variation and KDR gene expression, respectively. The univariate analysis of genotypes and prognosis was carried out by Kaplan-Meier survival analysis, and multivariate analysis was adjusted by Cox regression analysis. RESULTS: Among the polymorphisms analyzed, only V297I was of clinical significance. Located in the coding region, the prevalence rates of V297I in KDR among the study population were as follows: CC genotype 99 cases (73.33%), CT genotype 33 cases (24.44%), TT genotype 3 cases (2.23%), and minor allele frequency of V297I was 0.14. The distribution of three genotypes was in accordance with Hardy-Weinberg Equilibrium (P=0.898). TT and CT genotype patients were merged in the comparison of clinical outcomes. The analysis of patients with different genotypes found that the overall response rate (ORR) of CT/TT genotypes were 41.67% and 47.67% (P=0.549), respectively. And the median progression free survival (mPFS) of patients with CT/TT genotype and CC genotype were 6.2 and 8.6 months, respectively, which was statistically significant (P=0.003). In terms of overall survival (OS), the median overall survival (mOS) of the two genotypes were 18.9 and 21.5 (P=0.017), respectively. Adjusted in multivariate Cox regression analysis of PFS, CT/TT genotypes were an independent factor for PFS (HR=1.95,P=0.019). Additionally, among the 68 biopsy tissue specimens, gene expression analysis was conducted. And the results showed that the expression of KDR in cancer tissues of the patients with CT/TT genotypes were significantly higher than those of the CC genotype patients (P<0.01). CONCLUSION: Among non-small cell lung cancer patients treated by bevacizumab, the polymorphism V297I of KDR may impact the clinical outcomes of first line bevacizumab treatment by influencing the mRNA expression of KDR.

    Effects of soluble human leukocyte antigen G on the standardized treatment of hepatitis C patients
    ZHOU Yong, YING Li, XU Jiajia, DING Shixiong, HU Airong, GAO Guosheng
    2018, 23(7):  809-813.  doi:10.12092/j.issn.1009-2501.2018.07.014
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    AIM: To investigate the effect of soluble human leukocyte antigen G (sHLA-G) on the efficacy of pegylated interferon combined with ribavirin in the treatment of chronic hepatitis C (CHC). METHODS: A total of 63 CHC patients from October 2013 to October 2015 were enrolled. The genotype of hepatitis C virus (HCV), HCV RNA and sHLA-G were detected by gene chip, RT-PCR and ELISA method accordingly. All patients received a subcutaneous injection of pegylated interferon combined with oral ribavirin. The factors affecting the sustained virological response (SVR) were observed and analyzed. RESULTS: The proportion of female and non-genotype 1 in SVR group was significantly higher than that in non-sustained virological response (NSVR) group (female:70.59% vs.44.83%, χ2=4.285; non-genotype 1:82.76% vs.55.88%, χ2=5.217, P<0.05); other baseline indexes presented no significant difference (P>0.05). The level of plasma sHLA-G before treatment in NSVR group was significantly higher than that in SVR group[1.85(1.49-16.00) ng/L vs.1.53(1.36-2.80) ng/L; U=329.00, P<0.05]. After multivariable logistic regression analysis, sHLA-G and HCV genotypes were the independent influencing factors associated with the outcome of treatment with Exp(B)(95% CI) were 0.922(0.868-0.978) and 14.204(1.898-106.289), respectively. CONCLUSION: sHLA-G exhibits an important effect on the standardized treatment of hepatitis C patients, and patients with low sHLA-G level are more likely to achieve a sustained virological response.

    Effects of dapagliflozin on intima-medial thickness of carotid artery in type 2 diabetic mellitus patients
    YE Shengkai, WEN Jie, LIU Weiping, REN Xia, CHEN Haiying, DU Ying, LI Xue, ZHANG Ru, YU Li, ZHANG Biying
    2018, 23(7):  814-819.  doi:10.12092/j.issn.1009-2501.2018.07.015
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    AIM: To assess the effects of dapagliflozin on intima-medial thickness(IMT) of carotid artery in type 2 diabetic mellitus patients. METHODS: A total of 113 patients of type 2 diabetic mellitus were divided into dapagliflozin group (58 cases) and control group (55 cases).All patients were recruited in this randomized trial. Based on the intervention of life style,all patients undertook oral aspirin 0.1 g/d and atorvastatin 20 mg/d. The dapagliflozin group was given dapagliflozin 10 mg every day, while the control group was given other oral antidiabetic drug with/without insulin therapy. Course of treatment was 24 weeks. The various biochemical indices and carotid artery IMT were detected and the data were analyzed and compared between the two groups. RESULTS: In the dapagliflozin group, the IMT decreased after dapagliflozin therapy (P<0.01).In the control group, the distinction of IMT had not statistical significant between before and after therapy (P>0.05).There were significant differences in carotid artery IMT between the two groups after therapy (P<0.01), while there was no statistically significant difference between decreased blood sugar and blood pressure level (P>0.05). CONCLUSION: Dapagliflozin can decrease the IMT in patients with type 2 diabetic mellitus, which is closely related to cardiovascular benefit in patients with type 2 diabetic mellitus.

    Influence of genetic variation of TNFAIP3 on prognosis among esophageal squamous cell carcinoma patients
    SHAN Yan, LI Zhigang
    2018, 23(7):  820-824.  doi:10.12092/j.issn.1009-2501.2018.07.016
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    AIM: To investigate the influence of genetic variation of tumor necrosis factor alpha induced protein 3 (TNFAIP3) on prognosis among esophageal squamous cell carcinoma patients. METHODS: A total of 175 patients underwent complete surgical resection of esophageal squamous cell carcinoma were included in this study. 5 mL peripheral blood specimen of the patient was collected. Genomic DNA were extracted and genotype of rs583522 were analyzed. The association between genotype and baseline clinical characteristics and prognosis were analyzed. RESULTS: Wild type AA genotypes showed advanced tumor stages compared with those of homozygous G-allele carriers (P<0.001). Patients with an AA genotype were significantly more likely to experience relapse (P=0.022). Survival analysis revealed a significant difference in overall survival between different genotype groups (P=0.017). CONCLUSION: rs583522 genotypes can be used as biomarkers to evaluate the prognosis of patients with esophageal squamous carcinoma.

    Advances in research on the mechanism of general anesthesia by specific manipulation of neuron activities
    XU Wei, QU Weimin, HONG Zongyuan
    2018, 23(7):  825-829.  doi:10.12092/j.issn.1009-2501.2018.07.017
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    Manipulation of the neuron activity is an important method in the research of general anesthetics. Traditional methods mainly involve electrical stimulation and local administrations of drugs into brain nuclei/lesion of nuclei, etc. have many shortcomings such as extended targets, poor spatial and time accuracy, and non-specific cell types. In recent years, novel strategies such as optogenetics and chemogenetics for controlling the activities of specific neurons were established, which are of high precisions on time and space scales, and of great significance to explore the retailed mechanisms of general anesthetics. This review summarized the principles and progresses of optogenetics and chemogenetics in the mechanism research of general anesthetics.

    Recent advances of nanocarriers targeting tumor-associated macrophages in tumor therapy
    ZHAO Xiaobin, YU Chenhuan, XIA Aixiao, YU Wenying, YU Bing
    2018, 23(7):  830-835.  doi:10.12092/j.issn.1009-2501.2018.07.018
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    It is well known that tumor-associated macrophages (TAMs) play a vital role in the occurrence, development and metastasis of many tumors. Increasing evidences show that TAMs may be a promising target for tumor therapy and play an important role in future targeted treatment. Therefore, the design of TAMs-targeting nanocarriers which are able to achieve appropriate intratumoral biodistribution so as to effectively inhibit the growth of tumor has become a hot spot in recent years. In this review, the advantages of nanocarriers targeting TAMs are described. Since TAMs display a number of upregulated surface proteins (mannose receptor, folate receptor, cluster of differentiation 163, cluster of differentiation 11b, etc.), specific targeting using targeting ligands coupled to nanocarriers are discussed in the review, which may improve the ability of anti-tumor drug targeting TAMs.

    Progress in the treatment of dermatomyositis
    LU Xiaohong,WANG Peiguang
    2018, 23(7):  836-840.  doi:10.12092/j.issn.1009-2501.2018.07.019
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    Dermatomyositis is an autoimmune disease that mainly affects the skin and muscles. Systemic glucocorticoids is currently the first-line therapy of this disease. Combination of immunosuppressants helps to improve clinical efficacy and reduce the dosage of glucocorticoid, such as methotrexate, azathioprine, leflunomide, tacrolimus and mycophenolate mofetil. For some refractory cases without any response to the treatments of glucocorticoids and immunosuppressants, biologic agents (such as rituximab, abatacept, tocilizumab, infliximab), intravenous immunoglobulin, or plasma exchange are recommended. However, it is necessary to further demonstrate the clinical efficacy of some immunosuppressants and biologic agents on dermatomyositis in a lot of larger clinical trials.