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

Table of Content

    Volume 24 Issue 3
    26 March 2019
    Detection of T lymphocyte surface costimulatory molecules and T lymphocyte subsets in peripheral blood of HBV infected patients and its clinical significance
    SUN Kaikai, HUANG Chunhong, WANG Yunyun, WU Wei, CHEN Zhi
    2019, 24(3):  241-247.  doi:10.12092/j.issn.1009-2501.2019.03.001
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    AIM: To explore the relationship between surface costimulatory molecules and T lymphocyte subsets in peripheral blood of HBV infected patients and HBV-DNA, and its role in the development of HBV infection, especially in severe liver failure(such as ACLF). METHODS: 120 cases with chronic HBV infection which were selected from the first affiliated hospital The First Affiliated Hospital,School of Medicine,Zhejiang University and Zhejiang Province Youth Hospital, 60 cases with chronic hepatitis B(CHB group), 30 cases with hepatitis B-induced livercirrhosis(LC group), 30 cases with acute-on-chronic liver failure(ACLF group). The CHB group was further divided into the HBeAg positive group(n=30) and the HBeAg negative group(n=30) , 30 healthy subjects served as control group.The peripheral blood CD+4 and CD+8T cells programmed cell death (PD-1),cytotoxic T lymphocyte associated antigen-4(CTLA-4),T cell immunoglobulin mucin-3 (Tim3),T lymphocyte (CD+3) ,T helper T cells (CD+4) and inhibition of T cells (CD+8) level were detectd by flow cytometry.The HBV-DNA load of each group was detected by PCR. Pearson was used to analyze the correlation. RESULTS: The expressions of CD+4CTLA-4 and CD+8CTLA-4 in HBV infected patients were lower than those in the control group, and the expressions of CD+4CTLA-4,CD+8CTLA-4,CD+8PD1,CD+4Tim3 and CD+8Tim3 in CHB group were all higher than those in the LC group and the ACLF group(P<0.05).The expression of CD+3,CD+4and CD+4/CD+8 in patients with HBV infection was lower than that in control group, and the expressions of CD+8 was higher in CHB group than those in LC group and ACLF group , CD+8expressions were lower than those in the LC group and ACLF group. The level of HBV-DNA in CHB group was higher than that in LC group and ACLF group.All were statistically significant (P<0.05). The expression of CD+4CTLA-4,CD+8CTLA-4,CD+3,CD+4 and CD+4/CD+8 in HBeAg-positive group was lower than that in HBeAg-negative group, while the expression of CD+4PD1,CD+8PD1,CD+4Tim3,CD+8Tim3 and CD+8 in HBeAg-positive group was higher than that in HBeAg-negative group (P<0.05).In patients infected with HBV, HBV-DNA is positively correlated with CD+8PD1, CD+8Tim3 (P<0.05), but not with CD+4CTLA-4,CD+8CTLA-4,CD+4Tim3,CD+4PD1,CD+3,CD+4 and CD+8(P>0.05).Compared with the LC group, the expression level of CD+4PD-1 in the ACLF group was increased, while the expression level of CD+8CTLA-4  was decreased. CONCLUSION: Peripheral blood T-lymphocyte surface co-stimulatory molecules and T-lymphocyte subpopulation proportion are associated with the development of HBV infection, especially the progression of severe disease (such as ACLF), which has certain clinical application value for the curative effect and prognosis of the disease.

    Effects of Huanglianjiedu Decoction on vascular endothelial NO pathway in young spontaneously hypertensive rats
    GAO Yiwen, ZHANG Nan, LV Chanmei, YANG Xuanmei, YUE Guihua
    2019, 24(3):  248-253.  doi:10.12092/j.issn.1009-2501.2019.03.002
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    AIM: To study the protective effect of Huanglianjiedu Decoction (HLJD) on vascular endothelial endothelium in spontaneously hypertensive rats (SHR) and the mechanism of action of the drug.  METHODS: A total of 40 SHR rats were randomly divided into model group (SHR group), positive group (Captopril group), HLJD high dose group, and HLJD low dose group with 10 rats in each group. Simultaneously, there was 10 Wistar rats in control group. All groups were treated by gavage for 6 weeks. Systolic and diastolic blood pressure of the caudal artery was measured by noninvasive tail sleeve method. The changes of nitric oxide (NO), superoxide dismutase (SOD), angiotensin (AngII) and calmodulin (CaM) in rat serum were tested by enzyme linked immunosorbent assay (ELISA) method; the expression of RhoA, cGK, MYPT1 protein and mRNA in thoracic aorta were determined by Western blot and real-time fluorescence quantitative (PCR). RESULTS:After 6 weeks, compared with the model group, HLJD and positive group can significantly reduce the blood pressure of rats. Compare with blank group, the levels of AngII and SOD in serum of the model group were significantly increased (P<0.01), and the levels of NO and CaM were significantly lower (P<0.01). Conversely, the levels of AngII and SOD in the positive and HLJD groups were significantly decreased (P<0.01 or P<0.05), and the levels of NO and CaM were significantly increased (P<0.01 or P<0.05). HLJD could reduce the expression of RhoA and MYPT1 in the thoracic aorta of hypertension rats (P<0.05), and increase the expression of cGK in the thoracic aorta of hypertensive rats (P<0.05). CONCLUSION: HLJD can reduce the blood pressure of hypertensive rats, regulate the secretion of vascular endothelial vasopressin and affect the expression of factors such as cGK, RhoA, MYPT1. The expression of these factors is closely related to the activity of NO.

    Yunnan Baiyao ameliorates MIA-induced knee osteoarthritis pain in rats through anti-inflammatory effect
    HU Peipei, HUANG Fang
    2019, 24(3):  254-259.  doi:10.12092/j.issn.1009-2501.2019.03.003
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    AIM: To study the mechanism of Yunnan Baiyao on MIA-induced knee osteoarthritis pain of rats. METHODS: Sprague-Dawley male rats (160-220) g were randomly divided into 4 groups: Normal group (B), Control group (C) ,Yunnan Baiyao group (YB, 125 mg/kg) and Diclofenac sodium group (DF, 2.5 mg/kg). Then they were given single intra-articular injection with 2 mg MIA through the infrapatellar ligament of the right knee except for the normal group (B). The Paw withdrawal threshold (PWT) and cold pain latency of the right hind limb of each rats were collected as the baseline the day before making the animal model, followed by measuring the PWT and cold pain latency twice a week. The serum PGE2 level was determined by ELISA 35 days after administration, and the knee joint sections were observed via the microscope after H&E staining. Evaluation of drugs was estimated according to the Markin's score and the data was analyzed by SPSS18.0. RESULTS: Compared with the blank group, the mechanical pain threshold of the model group was significantly reduced (P<0.01), and the level of PGE2 in serum was increased (P<0.01). Compared with the model group, Yunnan Baiyao and diclofenac sodium can significantly increase the mechanical pain threshold of knee osteoarthritis in rats (P<0.01), reduce the serum PGE2 level of knee osteoarthritis in rats (P<0.05), and delay the cartilage injury of knee osteoarthritis.CONCLUSION:Yunnan Baiyao possibly relieves the pain of knee osteoarthritis induced by MIA through anti-inflammation.

    Expression trend of autophagy in mice with renal interstitial fibrosis
    CHEN Xinxin, CHEN Yu, ZHENG Chenfei, ZHOU Ying, CHEN Chaosheng
    2019, 24(3):  260-265.  doi:10.12092/j.issn.1009-2501.2019.03.004
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    AIM: To observe the expression trend of autophagy at different time points after UUO surgery. METHODS: Thirty-two clean healthy male ICR mice were randomized into Sham operation (Sham) group and UUO model (UUO) group, and mice were sacrificed at 3, 7 and 14 d after UUO surgery, respectively, 8 mice for each group. Serum was collected to detect Scr, BUN, HE and Masson staining ways were applied to the renal tissue, and the formation of autophagosomes was observed by electron microscopy and the expression of LC3 protein and P62 protein in renal tissue was detected by Westernblot. RESULTS:The renal cortex thinned, tubule atrophy, interstitial fibrosis, single nuclear cell infiltration, no obvious glomerular lesions were found in the obstructed side of UUO postoperatively, and the pathological changes were most prominent on 14 d after UUO surgery. Compared with the Sham group, LC3-Ⅱbegan from 3 d, peaked on 7 d, down on 14 d; P62 was different, 3 d began to decline, 7 d reached the lowest, 14 d recovered gradually, which showed that autophagy was most significant at 7 d. Electron microscopy showed that autophagosome and phagocytic vacuoles appeared 7 days after UUO surgery.CONCLUSION: The expression of autophagy after UUO surgery had a certain time dependence, which was most significant at 7 d, and the severity of autophagy was not parallel to the pathological severity.

    Polysaccharide inhibits tumor associated fibroblasts transformation
    GU Yanling, SHENG Yongjia, WANG Jin
    2019, 24(3):  266-271.  doi:10.12092/j.issn.1009-2501.2019.03.005
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    AIM: To inveatigate the effect of polysaccharides on the transformation of bone marrow mesenchymal stem cells (MSC) into tumor associated fibroblasts induced by conditioned medium of hepatoma cells.  METHODS: The medium of human hepatoma cell HepG2(CM)was isolated, and the bone marrow mesenchymal stem cells were divided into normal group, control group and experimental group. The normal group was treated with conventional DMEM medium +10%FBS, the control group was cultured with CM+10%FBS, and the experimental group was cultured with CM+10%FBS +10 mg/L polysaccharides. The cell viability of MSC was detected by CCK-8 kit, the cell proliferation detected by BrdU labeling and flow cytometry, the apoptosis rate was detected by flow cytometry, and the cell cycle was detected by PI staining. Western blot method was used to detect the expression of α smooth muscle agonist (α-SMA), myocin (Desmin), fibroblast activation protein (FAP), thrombin sensitive protein 1 (Tsp-1), and fibroblast specific protein (FSP). The expression of α-SMA, FAP and FSP were detected by immunofluorescence staining. RESULTS:The cell viability of MSC in the control group was significantly higher than that in the normal group and the experimental group (P<0.05). There was no significant difference of the apoptosis rate among the three groups (P>0.05). In the control group, the proportion of G0/G1 phase decreased, and the proportion of S phase increased in MSC, which was significantly different from that in the normal group and the experimental group (P<0.05). The expression level of α-SMA, Desmin, FAP, Tsp-1, FSP and the expression level of TGF-β1, Smad1 and Smad2 in the control group was significantly higher than those in the normal group and the experimental group (P<0.05). The immunofluorescence results also showed that the level of α-SMA, FAP, FSP and TGF-β1, Smad1 and Smad2 in the control group was significantly higher than those in the normal group and the experimental group (P<0.05). CONCLUSION: Hepatoma cells can promote the transformation of MSC into tumor related fibroblasts, and polysaccharides can inhibit the transformation, which is one of the mechanisms of anti tumor effect of polysaccharides.

    Gene microarray Analysis of Glucocorticoid resistance-related genes in Acute Lymphoblastic Leukemia based on GEO
    ZHANG Danyang, DONG Xiaomin, ZHOU Xiaohuan, ZHANG Yue, ZHANG Juan, ZHOU Hebin
    2019, 24(3):  272-277.  doi:10.12092/j.issn.1009-2501.2019.03.006
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    AIM: To detect the differentially expressed genes associated with glucocoticoid resistance by microarray and to analyze the signal transduction pathways in acute lymphoblastic leukemia. METHODS: Downloading the gene chip data from the gene expression omnibus (GEO), R software was used to analyze the differentially expressed genes between glucocorticoid resistance samples and sensitive samples. The function of differential genes was determined by gene ontology (GO) and pathway analysis. Intergene interaction network were constructed to screen key genes. RESULTS: In total, 109 differential genes were screened out, of which 86 genes were up-regulated and 23 genes were down-regulated. GO enrichment analysis revealed  that DEGs were mainly involved in biological processes of immune response, blood coagulation, regulation of cell proliferation and apoptosis, cell migration. Pathway analysis showed that DEGs were mostly enriched in Toll like receptor cascade, MAPK pathway, NF-κB-MAP pathway and cell apoptosis. The network analyses identified the hub genes such as FOS, NFKB1, MAP2K1, IRS1, CASP3. CONCLUSION: The glucocrticoid resistance-related ALL shows differentially expressed genes, we screen out the hub genes and signal pathways of glucocrticoid resistance.

    Protective effects of L-carnitine on diabetic nephropathy in rats
    ZHAO Shaojing, ZENG Yan, LI Zhengdong, ZHANG Hua
    2019, 24(3):  278-282.  doi:10.12092/j.issn.1009-2501.2019.03.007
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    AIM: To investigate and analysis the protective effects of L-carnitine on diabetic nephropathy in rats. METHODS: Twenty-four 8-week-old male SD rats were randomly divided into three groups of 8 rats each. The control group were received single intraperitoneal injection of normal saline (10 mL/kg), followed by intravenously injection of normal saline (1 mL/kg). The diabetic nephropathy group were received single intraperitoneal injection of streptozotocin (65 mg/kg), followed by intravenously injection of normal saline(1 mL/kg). The experimental group were received single intraperitoneal injection of streptozotocin (65 mg/kg), followed by intravenously injection of intravenous L-carnitine (50 mg/kg), 1 time/d for 14 d, and the renal function after the experiment were recorded.RESULTS:The models of diabetic nephropathy were successfully established both in the experimental group and the diabetic nephropathy group. After the experiment, the body weight of the experimental group and the control group were significantly higher than that of the diabetic nephropathy group (P<0.05). Serum creatinine and urinary protein excretion, IL-6 and TNF-α, Bcl-2 and Caspase-3 in renal tissue of the experimental group and the control group were significantly lower than those of diabetic nephropathy group (P<0.05). There was no significant difference between the experimental group and the control group (P>0.05).CONCLUSION: The application of L-carnitine in diabetic nephropathy can effectively protect renal function, inhibit the expression of Bcl-2 and Caspase-3 in kidney tissue, and promote the recovery of normal body weight.

    Association analysis of apolipoprotein E polymorphisms and weight loss among schizophrenia patients with risperidone treatment
    FAN Yao, XUE Yong, WANG Xin, CHEN Xuefei, ZHANG Xu, YAO Yingshui, SHEN Chong
    2019, 24(3):  288-295.  doi:10.12092/j.issn.1009-2501.2019.03.009
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    AIM: To explore the association between apolipoprotein E (APOE) gene polymorphisms and weight change in schizophrenia (SZ) patients induced by antipsychotic treatment. METHODS: 1 516 first-episode SZ patients treated with risperidone, aripiprazole, quetiapine, clozapine, olanzapine and perphenazine for 2 to 7 weeks were followed up. TaqMan genotyping technique was used to detect APOE gene polymorphisms. Cox regression was used to analysis the association between APOE gene variation and risk of weight change induced by drug treatment in SZ patients. RESULTS:The results showed that rs7412 increased the risk of weight loss in patients treated with risperidone, HR (95% CI) was 1.78 (1.01-3.14) with P=0.045. In patients treated with risperidone, the risk of weight loss was higher in carriers of AG/GG genotype of rs405509 than in carriers of AA genotype, HR (95% CI) was 1.75 (1.02-2.98), P value was 0.04. In SZ patients treated with other antipsychotic drugs, the associations between rs769450, rs7412 and rs405509 genotypes (additive model, dominant model and recessive model) with weight change were not found. There was no statistical association; all the P values were more than 0.05. Stratified analysis showed that there was no heterogeneity between rs7412 and rs405509 genotypes (additive model, dominant model and recessive model) and the risk of weight loss in baseline normal weight group and baseline overweight or obesity group (P>0.05). CONCLUSION: rs7412 and rs405509 of APOE increase the risk of weight loss in SZ patients treated by risperidone. Clinician should pay more attention to association between APOE gene rs7412 C>T, rs405509 A>C variations and risperidone-induced weight loss in normal body weight patients.

    Admission Neutrophil-to-lymphocyte ratio predicts coronary lesion complexity and clinical risk in patients with unstable angina pectoris
    WANG Xiaqin, HE Fei, WANG Tong, HU Zhangle
    2019, 24(3):  296-300.  doi:10.12092/j.issn.1009-2501.2019.03.010
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    AIM: To study the association of admission neutrophil-to-lymphocyte ratio (NLR) with coronary lesion complexity and prognosis as respectively evaluated by Gensini score and GRACE(global Registry of Acute Coronary Events,GRACE) score in patients with unstable angina pectoris. METHODS: A total of 156 cases were retrospectively analyzed. All patients were assigned into 3 groups according to their NLR tertiles(low NLR,LNLR;Medium NLR, MNLR;High NLR, HNLR). Clinical characteristics, risk and angiographic complexity attached to the 3 groups were compared. RESULTS:HNLR group exhibited much higher age,rest heart rate,LDL-C and blood creatine values and percentages of smoking, hypertension, diabetes mellitus, ST depression as compared with LNLR group(all P<0.01). However,the use rate of statins in HNLR group was significantly lower than that in LNLR group (P<0.01). The GRACE risk score and Gensini score were all significantly higher in HNLR group compared to MNLR and LNLR groups (all P<0.01). Both GRACE and Gensini scores illustrated significant positive correlations with NLR. CONCLUSION:Admission NLR positively mirrors clinical risk and angiographic complexity in unstable angina patients.

    Clinical efficacy of monosialotetrahexose ganglioside combined with mouse nerve growth factor in the treatment of neonatal hypoxic ischemic encephalopathy
    JIANG Haoming,CHEN Xiang, LI Zhen, GU Chengping
    2019, 24(3):  301-306.  doi:10.12092/j.issn.1009-2501.2019.03.011
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    AIM: To investigate the clinical efficacy and safety of monosialotetrahexose ganglioside (GM1) combined with mouse nerve growth factor (NGF) in the treatment of neonatal hypoxic ischemic encephalopathy (HIE).  METHODS: A total of 122 children with HIE admitted to our hospital from January 2017 to April 2018 were enrolled in the observation group and the control group (61 cases each) according to the random number table method. The control group was given monosialotetrahexosyl ganglioside sodium (20 mg+10% GS injection 30-50 mL, once a day), while the observation group was given mouse nerve growth factor sodium (20 mg+10% GS injection 30-50 mL, once a day) + mouse nerve growth factor (18 μg + 2 mL water for injection, intramuscular injection, once a day); two groups of children were treated for 14 days. The clinical efficacy, neurological function, mental development and motor development of two groups were compared. The conscious reflex, sucking reflex, and muscle tension recovery time of two groups were recorded. The determination of insulin-like growth factor-1 (IGF-1), serum myelin basic protein (MBP), neuron specific enolase (NSE), vascular endothelial growth factor (VEGF) and S-100β levels of two groups were detected. RESULTS:The clinical effective rate was 93.44%(57/61) in the observation group and 80.33%(49/61) in the control group. The difference was statistically significant (Z=4.604, P<0.05). The neurological measurement scale (NBNA) score of the observation group at 28 days after birth was significantly higher than that of the control group (P<0.05). The mental development index (MDI) and psychomotor development index (PDI) scores of the observation group were higher than those of the control group at 3 months after birth (P<0.05). During the treatment period, the recovery time of conscious reflex, the recovery time of sucking reflex and the recovery time of muscle tension were significantly shorter in the observation group than in the control group (P<0.05). The levels of IGF-1 were increased after treatment, and the levels of MBP, NSE, VEGF and S-100β were decreased (P<0.05). The improvement of the above indicators in the observation group was better than that of the control group (P<0.05). CONCLUSION: GM1 combined with mouse nerve growth factor has a significant effect on the treatment of HIE, which can significantly improve the neurological function of children, shorten the recovery time and reduce the serum related factors.

    Application research of tranexamic acid combined with low central venous pressure during liver transplantation
    QI Yong,ZHANG Song, LU Caide
    2019, 24(3):  307-312.  doi:10.12092/j.issn.1009-2501.2019.03.012
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    AIM: To investigate the effects of tranexamic acid(TXA) combined with low central venous pressure (LCVP)on volume management, cerebral oxygen metabolism and prognosis in patients during orthotopic liver transplantation(OLT). METHODS: Forty-eight patients subject to OLT were randomly divided into 3 groups(n=16):control group(group A);Low central venous pressure(LCVP) group(group V) and tranexamic acid(TXA) combined with controlled low central venous pressure(LCVP) group(group T).The group A was treated as a routine; The CVP was maintained in the range of 3-5 cmH2O by inhaling sevoflurane and intravenous infused nitroglycerin in group V,combined with continuous pumped dopamine at the rate of 2-10 μg·kg-1·min-1, maintaining average arterial pressure (MAP) more than 60 mmHg; The group T was given a load dose of 20 mg/kg tranexamic acid after induction of anesthesia, and 10 mg·kg-1·h-1 infusion performed till to the end of operation, the other treatment was as the same as group L.Blood samples were taken from radial artery and jugular simultaneously for blood gas analysis before operation(T1,baseline),10 min before anhepatic phase(T2),30 min after anhepatic phase(T3),30 min after graft reperfusion(T4),2 h after graft reperfusion(T5),and the end of OLT(T6).Cerebral arterial oxygen content(CaO2),jugular oxygen content(CjvO2),cerebral arterial-venous oxygen content difference(Ca-jvO2),cerebraI oxygen extraction rate(CERO2),and cerebral arterial-venous cerebral lactic acid difference(VADL) were calculated by the Fick formulae and the D-dimer was recorded.We also recorded the whole operation time,anhepatic phase time,ICU residence time, volume of blood loss and transfusion,and urine volume.RESULTS:The level of D-dimer in group C at T3, T4 was significantly higher than T1(P<0.05) , while there was no significant difference at each time point in group V and group T (P>0.05).As compared with group A,CaO2,CjvO2,Ca-jvO2,CERO2 and VADL in group V and group T were nearly not changed at different time pioints(P>0.05);but in the same group,as compared with T1 and T2,the CaO2,CjvO2,Ca-jvO2,CERO2 and SjvO2 in T3,T4 were decreased significantly(P<0.05),while VADL was increased significantly(P<0.05). As compared with group A and group V, the length of hospitalization in group T were decreased significantly (P<0.05).As compared with A group,the volume of blood loss and transfusion in group V and group T were decreased(P<0.05),and the urine increased significantly(P<0.05). CONCLUSION:Tranexamic acid combined with low central venous pressure can be used safely for liver transplantation, maintain normal oxygen metabolism, decrease volume of blood loss and transfusion,increase urine volume during OLT,and accelerate the recovery.

    Curative efficacy of ulinastatin combined with hydrocortisone in treatment of severe sepsis secondary shock and effects on serum factor levels
    XUE Hua, LU Lili, XIANG Hui, QIAN Zhenhua
    2019, 24(3):  313-317.  doi:10.12092/j.issn.1009-2501.2019.03.013
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    AIM: To study curative efficacy of ulinastatin combined with hydrocortisone in treatment of severe sepsis secondary shock and effects on serum factor levels. METHODS: 87 patients of severe sepsis secondary shock who received therapy from December 2015 to December 2017 in our hospital were selected as research objects. According to random number table, those patients were divided into the 43 cases of the control group and the 44 cases of the treatment group. The control group was treated with routine treatment, on the basis of the control group, the treatment group combined with intravenous drip of ulinastatin 200 thousand U into the 5% glucose solution 250 mL+intravenous infusion of 200 mg hydrocortisone into 5% glucose solution 250 mL, 1 times/d, they were continuous treatment for 2 weeks. The clinical efficacy, laboratory indexes, serum procalcitonin (PCT), IL-6, IL-10, mechanical ventilation time, hospitalization time, adverse drug reaction and 28 d mortality were compared between the 2 groups. RESULTS:After treatment, the total effective rate of the treatment group and the control group were 86.36%(38/44)and 67.44%(29/43)respectively, there was significant differences in comparison (P<0.05). After treatment, the systolic pressure (SBP) of the treatment group and the control group were(85.82±6.25) and (78.80±9.26)mmHg, respectively; the C reactive protein (CRP) were (34.78±4.79) and (46.76±5.93) mg/L, respectively; the white blood cell count (WBC) were (7.85±2.02) and (12.49±2.14)×109/L, respectively; the PCT were (1.50±0.22) and (2.70±0.46) ng/mL, respectively; the IL-6 were(59.13±12.73)and(82.32±18.40)pg/mL, respectively; the IL-10 were (10.04±1.25)and (14.41±1.88)pg/mL respectively; the acute physiology and chronic health evaluation (APACHEⅡ) were(10.30±1.41)and(14.51±1.68)score, there were significant differences in comparison (P<0.05). The mechanical ventilation time and hospitalization time in the treatment group were(10.02±1.65)d and(16.00±1.36)d, respectively, those in the control group were (17.58±2.54)d and(24.00±1.69)d, respectively; there were significant differences in comparison (P<0.05). During the treatment period, there were no serious adverse reactions in the 2 groups, there were 1 cases of rash in the treatment group, and there was no significant difference in the incidence of adverse reactions between the 2 groups (P>0.05). The 28 d mortality in the treatment group and the control group was 4.55%(2/44)and 20.93% (9/43), respectively, there was significant differences in comparison (P<0.05). CONCLUSION:Ulinastatin combined with hydrocortisone is well for severe sepsis secondary shock, which can effectively relieve the disease, reduce the mortality, and have less adverse drug reactions and high safety.

    Trimethylamine N-oxide and inflammatory disease
    FANG Qing, OU-YANG Dongsheng
    2019, 24(3):  318-326.  doi:10.12092/j.issn.1009-2501.2019.03.014
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    High levels of intestinal flora metabolite Trimethylamine N-oxide can promote the development of inflammatory diseases. This reviews mainly discussed the relationship between the TMAO and inflammatory diseases, such as diabetes, atherosclerosis, heart failure and the potential molecular mechanisms of TMAO-induced inflammatory diseases.

    Research progress of MRP3 and MRP4 transporters in tumor
    ZONG Sidou, ZHANG Hong
    2019, 24(3):  327-331.  doi:10.12092/j.issn.1009-2501.2019.03.015
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    The study of tumor molecular mechanism has received extensive attention and plays an increasingly important role in the diagnosis and treatment of tumor. MRP family is a transmembrane ATP binding box (ABC) transporter which plays an important role in the study of tumor molecular mechanism. As members of MRP family, MRP3 and MRP4 are novel molecular targets of tumor in recent years and have potential clinical value. Therefore, the structure of MRP3 and MRP4, the role of MRP3 and MRP4 in the diagnosis or treatment and the relevant regulation mechanisms are reviewed in this article to provide new ideas for the future research of tumor.

    Research progress of Scutellaria barbata against colorectal cancer and its metastasis mechanism
    QIAO Dawei, LI Yufang, XIAO Yun, JIANG Lishuang, BO Ping
    2019, 24(3):  332-336.  doi:10.12092/j.issn.1009-2501.2019.03.016
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    Colorectal cancer is one of the common malignant tumors in the digestive tract. Because it is difficult to eradicate and it is highly prone to metastasize, it brings difficulty in treatment. In recent years, studies have shown that traditional Chinese medicine Scutellaria barbata can be used for molecular targeted therapy of colorectal cancer and its metastasis through a variety of approaches, mainly including four aspects: signal transduction pathways, related tumor suppressor genes, telomerase activity, and body immunity. Here we review the main approaches in hope of providing referential idea for its clinical application.

    Research progress of sensitization of chemotherapy and radiotherapy in triple-negative breast cancer
    LI Xiaoli,CAI Yongqing,ZHOU Weiying
    2019, 24(3):  337-342.  doi:10.12092/j.issn.1009-2501.2019.03.017
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    Triple-negative breast cancer refers to breast cancer with negative expression of estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 (HER2). It has the characteristics of poor prognosis, high recurrence rate, rapid invasion and metastasis, and high mortality. Chemotherapy is one of the main means of clinical treatment for triple-negative breast cancer, but with the progress of treatment, triple-negative breast cancer patients are prone to produce different degrees of drug resistance, which greatly reduces the therapeutic effect. Therefore, it is of great importance to find effective targets and preparations for sensitization. This article will review the current status of triple negative breast cancer radiotherapy and chemotherapy, the research progress of known sensitization targets and potential sensitization targets, in order to provide reference for triple negative breast cancer chemotherapy.

    Advances in drugs and genetic pharmacology for heart failure
    SHEN Lei, WANG Keke, YANG Jingke, ZHAO Juntao, MENG Xiangguang, YUAN Yiqiang
    2019, 24(3):  343-349.  doi:10.12092/j.issn.1009-2501.2019.03.018
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    Heart failure (HF) is called cardiac insufficiency and mainly manifested in abnormal changes in cardiac structure and function such as ventricular systolic and (or) diastolic dysfunction, characteristic of sympathetic nerve and renin-angiotensin-aldosterone system activation. Clinical observation has showed that there was great heterogeneity in patients with HF during drug treatment. Therefore, we should take into account not only environmental factors but also genetic ones in terms of drug use, especially the epigenetics. Recently, some reports admited that the drug response of patients with HF was partly related to epigenetic modifications such as DNA methylation, histone modifications and microRNAs. But the relevant research is still rare as yet. Therefore, this article reviews the advances of epigenetic pharmacology in the treatment of HF in recent years.

    Advances on the molecular mechanism of metformin's antitumor effect
    DING Qiuhua, SHI Daohua
    2019, 24(3):  350-354.  doi:10.12092/j.issn.1009-2501.2019.03.019
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    Metformin is a classical drug with safety and efficacy for type 2 diabetes therapies, which are widely used in hypoglycemia. According to recent study, the morbidity and mortality of malignant tumors are lower in patients. Although the mechanism is unclear, metformin might become a potential antitumor drug. Research on the related pathways serves to reveal its mechanism, which is great significance for developing novel antitumor targets and drugs. This article reviews the molecular mechanisms of metformin on inhibition of tumors in AMPK dependent and non-dependent way.

    Sodium calcium exchanger and renal ischemia reperfusion injury
    CHEN Chaohu, ZHUANG Hua, YAO Zhiqiang, HAN Dali, CHANG Cheng, MA Zhongyi, KONG Xiangbing, CAO Jinlong, LI Pan, TIAN Junqiang
    2019, 24(3):  355-360.  doi:10.12092/j.issn.1009-2501.2019.03.020
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    Sodium calcium exchanger (NCX), which is widely expressed in the plasma membrane, mitochondrial membrane and secretory vesicles in diverse kinds of cells, belongs to a type of cation translocators. NCX works in two modes, the forward mode and reverse mode. Exactly through the two-way modes, NCX can regulate intracellular Ca2+ concentration fleetly and accurately, and plays a critical role in a series of physiological processes. However, abnormal activation of the reverse mode of NCX plays a vital role in renal ischemia reperfusion injury, which can mediate the overload of cytoplasmic Ca2+, then triggers a series of harmful metabolic reactions that led to cell injury and death. Currently, phenoxyl derivatives that selectively inhibit the reverse mode of NCX have been extensively studied and become new drug targets for the treatment of renal ischemia reperfusion injury.