Chinese Journal of Clinical Pharmacology and Therapeutics

Effect of gap junction in ischemic post-conditioning on cerebral ischemic-reperfusion injury in rats and its associated mechanism

JIAO Hao, TONG Xu-hui, DONG Shu-ying, GU Yu-chen, YU Bin-bin, YU Li

2014, 19(8): 841-845.

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AIM: To investigate the effect of gap junction in ischemic post-conditioning on cerebral ischemic-reperfusion injury in rats. METHODS: Sixty adult male SD rats were randomly divided into sham group, I/R group, IPO group, I/R+CBX group and IPO+CBX group. Thread occlusion method was used to make MCAO model. Neurological scores of rat were evaluated by Longa' score. Infarct volume of brain tissue was measured by TTC staining. Histopathology of cerebral tissue was detected by HE staining. The expressions of Cx43 and PKC protein were detected by Western Blot. RESULTS: In I/R group, neurological deficit scores decreased, cerebral infarction area increased and histopathology changed significantly, while similar changes did not found in sham group. IPO has protective effect on I/R injury. Similarly, CBX increased the protection of IPO on I/R injury obviously. Results of Western Blot showed, in I/R group, Cx43 protein increased significantly and PKC decreased compared to the sham group (P<0.01). Meanwhile, in IPO group Cx43 protein decreased extremely and PKC increased compared to I/R group. Similarly, in IPO+CBX group Cx43 protein decreased significantly and PKC increased compared to IPO group. CONCLUSION: IPO has protective effect on I/R injury through the gap junction, which may be associated with the change of PKC protein.

Experimental study on small molecule drug kartogenin protecting endplate cartilage degeneration

ZHENG Quan, XU Hong-guang, WANG Jing, XIONG Shou-liang, WANG Hong, ZHANG Xiao-ling

2014, 19(8): 846-850.

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AIM: To observe the effect of small molecule drug kartogenin (KGN) on promoting extracellular matrix secretion in endplate cartilage, and explore its protective role in the endplate cartilage or intervertebral disc degeneration. METHODS: Established an in vitro organ culture model of rat intervertebral disc, punctured the annulus and cultured in vitro. The rats were divided into three groups: control group, degeneration group and KGN treated group. The change of histomorphology in intervertebral disc tissue was assessed by HE staining, the extracellular matrix of endplate cartilage was observed by safranin O-fast green staining. The expressions of type Ⅱ collagen, proteoglycans and SOX-9 in the three groups were detected by Real time-PCR. The expressions of typeⅡCollagen and SOX-9 protein were measured by western blot.RESULTS: HE staining indicated that the nucleus disappeared and the endplate cartilage tended to thin in the degeneration group, and the disc structure is more complete after KGN treated; safranin O- fast green staining showed that the secretion of extracellular matrix were increased in the KGN treated group. Realtime-PCR showed type Ⅱcollagen, aggrecan, and SOX-9 mRNA levels were significantly reduced in the degeneration group, and the cartilage-related gene increased after KGN treated; Western blot results showed similar changes. CONCLUSION: Small molecule drug KGN can promote the extracellular matrix secretion in the endplate cartilage in order to protect the endplate cartilage and intervertebral disc degeneration.

L-Securinine induced the human non small cell lung cancer A549 cell autophagy and its molecular mechanism

ZHANG Gang, CHEN Dong-yun, CHENG Jing, JI Zhao-ning

2014, 19(8): 851-855.

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AIM: To explore the mechanism of L-securinine induced autophagy of human non small cell lung cancer A549 cell autophagy. METHODS: A549 cell lines were cultured in vitro and L-securinine at different concentrations (6.25,12.5,25,50,100,200 μmol/L) was added 24 h after cell lines were transferred. Then the plates were cultured for 24, 36 and 48 h. CCK-8 method was used to detect the antitumor effect of human non small cell lung cancer A549 in vitro. Inverted microscope was used to observe A549 cells treated with L-securinine morphological changes. The A549 cells were treated with different concentrations (0, 20 μmol/L) of L-securinine for 24 h.Then autophagy was analyzed by fluorescence microscope following staining with monodansylcadaverine (MDC). The mRNA levels of Beclin-1 were detected using real-time RT-PCR pre and post-treatment of L-securinine. RESULTS: The generation depression effects of A549 cells cultured in vitro were detected by CCK-8 method (P<0.05), and there were dosage-time dependent relationships. The morphology of cells become small and round, the process of cell division got less were observed. L-securinine-treated cells exhibited higher fluorescent density and more MDC-labeled particles in A549 cells compared with the control group. Beclin-1 expression enhanced with L-securinine concentration increased. CONCLUSION: L-securinine has an anti-tumor effect against human non small cell lung cancer A549 cell. The L-securinine can induce striking autophagy in A549 cell in vitro. The autophagy induced by L-securinine is related with upregulating the expression of autophagy gene Beclin-1.

Neonatal Fentanyl analgesia decrease spinal Fos expression in young rats

LIN Xi, HUANG Yi-jian, WU Bin, ZHANG Xiao-yan

2014, 19(8): 856-860.

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AIM: To investigate the mechanism of blocking visceral hyperalgesia by Fentanyl analgesia in neonatal period through observeing the Fos expression of lumbosacral spinal dorsal horn in visceral hyperalgesia rats. METHODS: Colorectal irritation (CI) stimulation in neonatal period was used to establish the model of visceral hypersensitivity in young rats.32 neonatal rats were divided into four groups by 2×2 factorial design with each 8. Group A₁B₁ was imposed on CI at neonatal period and imposed on fentanyl intraperitoneal injection before CI stimulation; Group A₁B₂ was imposed on CI at neonatal period and administration saline before CI; Group A₂B₁ was not imposed on CI at neonatal period and imposed on fentanyl intraperitoneal injection; Group A₂B₂ was not imposed on CI at neonatal period and not imposed on fentanyl intraperitoneal injection. Then, conventionally breeding till the young period (6-week age), rats were sampled the spinal cord from L6 to S2, the semi-quantity analysis of staining density and the cell numbers of Fos-like immunoreactivity(FLI) of spinal cord were made through immunohisrochemical coloration and computer image analyzing system. RESULTS: The number of FLI and integral opticaldensity of FLI significantly decreased in lumbosacral spinal dorsal horn by neonatal Fentanyl analgesia. The spinal Fos expression in young rats were affected both by CI at neonatal period and neonatal fentanyl analgesia. Futhermore, there were interaction effects between the two factors. CONCLUSION: Neonatal fentanyl analgesia before CI can decrease spinal Fos expression and visceral hypersensitivity in young rats.

Interference of shRNA on Keap1 in prostate cancer PC3 cell mediated by lentivirus

WANG Tan-heng, WU Xin-li, LIU Xiao-pin

2014, 19(8): 861-865.

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AIM: To construct the shRNA interference lentivirus vector for Keap1 and evaluate the interference effects in human prostate cancer PC3 cell mediated by lentivirus. METHODS: Bioinformatics methods were used to design RNAi sequences for Keap1. A lentiviral vector was applied for construction of Keap1 shRNA vectors, which was expressed in E. coli packaged by 293T cells. Transfection efficiency and titer were measured by dilution method according to the green fluorescent protein (GFP) tracer. Real-time fluorescence quantitative method was applied to compare interfere effects of target sequences.RESULTS: Four Keap1 targeting sequences were constructed completely and the corresponding Keap1 shRNA lentiviral vectors were screened for efficiency. One shRNA lentiviral vector with best efficiency was screened by transient transfection (interference efficiency reached 80%) and the working condition was established as well.CONCLUSION: shRNA lentiviral vectors for Keap1 was constructed and screened successfully in PC3 cells, which effectively inhibit the expression of Keap1.

Effects of recombinant human insulin-like growth factor-Ι on the expression of matrix metalloproteinases and interstitial degradation of myocardial infarction rats

WEI You-quan, CAO Heng

2014, 19(8): 866-871.

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AIM: To examine the effect of recombinant human insulin-like growth factor-I(rhIGF-I) on the expression of matrix metalloproteinases (MMPs) and interstitial degradation of myocardium in postinfarction rats. METHODS: Seven-week old male Sprague-Dawley (SD) rats were intraperitoneally injected with isoprenaline to establish myocardial infarction (MI) model. Forty-eight rats showed clear ECG evidence of infarction and were assigned randomly to IGF-I group (rhIGF-I 50 μg·kg^-1·d^-1, i.v.), Oct group (Octreotide 50 μg·kg^-1·d^-1, i.v.) or MI group (normal sodium 5 mL·kg^-1·d^-1, i.v.). Each group was divided into two subgroups (n=8, respectively) according to the treatment days, 2 or 14 days when the rats were sacrificed. Another 8 normal SD rats were selected as the control group. Transthoracic echocardiograms were performed to examine the thickness of anterior wall (LVAW) and posterior wall (LVPW) of left ventricle, left ventricular end-systolic diameter (LVESD), left ventricular end-diastolic diameter (LVEDD), and fractional shortening (FS) as well. The levels of MMP-2, MMP-9, TIMP-1 in myocardium were quantified with immunohistochemistry. Tissue homogenate myocardium hydroxyproline concentration was determined by pepsis method.RESULTS: Compared with the MI group, the expressions of MMP-2 and MMP-9 in rhIGF-I group were decreased, and the expression of TIMP-1 in the infarcted areas was increased;the degradation of myocardium collagen were decreased and the LVEDD and LVESD were decreased, the FS was increased; the expressions of MMP-2 and MMP-9 in Oct group were increased, the degradation of myocardium collagen was aggravated, the LVAW was decreased, the LVEDD, LVESD were increased, the FS was decreased.CONCLUSION: rhIGF-I administered to rats after MI is associated with decreased activities of MMPs, substantial increase of expression of TIMP-1, and leads to attenuate interstitial degradation of myocardium and may improve ventricular remodeling.

Effect of endomorphin-1 on the left ventricular function in anesthetized rats

CHENG Xiang-yang, ZONG Qiao-feng, HU Jie, GAO Qin, LI Zheng-hong

2014, 19(8): 872-876.

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AIM: To observe the effects of intravenous and intracerebroventricular injection of endomorphin-1(EM-1) on the left ventricular function in anesthetized rats and to assess its mechanism. METHODS: The left ventricular function was observed by inserting a catheter from right carotid artery into left ventricle after iv or civ injection of EM-1 in anesthetized rats.The effects of iv or civ of various blockers, naloxone, cyprodime and atropine, on the left ventricular function caused by EM-1 were observed. The level of NO and T-NOS in serum and myocardial were measured.RESULTS: EM-1 was shown to decrease left ventricular function dose-dependently. The decrease in left ventricular function was blocked by naloxone and cyprodime. Pretreatment with iv or civ atropine attenuated the decrease response. Intravenous injection of EM-1 produce NO content and NOS activity in serum were much higher than those in control group (P<0.05). While NO content and NOS activity in myocardium were no more than those in control group. Intracerebroventricular injection of EM-1 produced NO content and NOS activity in serum and myocardium were no more than those in control group. CONCLUSION: iv or civ administration of EM-1 produces depressor on the left ventricular function in anesthetized rats, which is mediated by opioid receptor, associated with the Mcholinoceptor.

N-isoquinoline-3-carbonyl-L-Leucine-benzylester as a new agent of inhibiting esophageal carcinoma proliferation

YANG Guo-dong, ZHANG Xiao-ying, FENG Zhi-song, HE Guo-bin, JIANG Yi-min

2014, 19(8): 877-881.

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AIM: To determine whether N-isoquinoline-3-carbonyl-L-Leucine-benzylester(IQ-L-OBzl)inhibited the growth of human esophageal cancer cell in vitro and in vivo. METHODS: MTT assays were performed to assess the proliferation of esophageal carcinoma cell lines. The model of esophageal carcinoma in nude mice was established, then the weight of tumor tissue was measured, the growth inhibition rates of tumor were calculated and the WBC were counted on peripheral blood of the mice. Intracellular reactive oxygen species(ROS)were detected by flow cytometry analysis. RESULTS: The IC₅₀ of IQ-L-OBzl inhibiting esophageal carcinoma cell lines(Eca-109 and EC-9706)proliferation were (405.06±23.49) nmol/L and (485.79±48.47) nmol/L. The best growth inhibition rate was (42.42±7.47) %. The growth inhibition rate and the weight of tumor exhibited dose-dependent manner. The ROS level of IQ-L-OBzl was (98.68±13.19) MFI, higher than that in control groups (P<0.05). CONCLUSION: IQ-L-OBzl has anti-esophageal carcinoma ability in vitro and in vivo, and this ability have related to ROS without significant side effects on WBC.

Effect of ABCG2 genetic polymorphism on atorvastatin modifying serum lipids

WU Ji-chu, OUYANG Ze-wei, LUO Can-xiang

2014, 19(8): 882-884.

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AIM: To study the correlation between ABCG2 genetic polymorphism and the lipid-lowering effect of atorvastatin. METHODS: Ninety-one aged patients with hypercholesterolemia were enrolled. Atorvastatin (10 mg/d) was given for treatment during 8 weeks.All patients'serum level of TC, TG, LDL-C and HDL-C before and after the 8 weeks' treatment was tested. Pyrosequencing was technique was adopted to analyze ABCG2 gene of the patients. RESULTS: Atorvastatin may significantly decrease the plasma levels of LDL-C in different polymorphisms (P<0.01). And the plasma levels of LDL-C in CA and AA genotype patients decline than CC genotype patients (P<0.05). Atorvastatin may significantly reduce the TC and TG plasma levels in patients with CA and AA genotype patients (P<0.05). CONCLUSION: ABCG2 genetic polymorphism may influence atorvastatin treatment.

Retrospective analysis of 119 cases with severe drug eruption

WANG Lin, QIU Xiao-yan

2014, 19(8): 885-889.

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AIM: To investigate the common sensitize medicines and prevention of severe drug eruption and appreciate causal link between the drug and the reaction. METHODS: A retrospective study over a period of 7 years (January 2006 to December 2012) was carried out in the hospital to record severe cutaneous ADRs of 119 hospitalized patients.RESULTS: Antibacterials were the most common causative drugs(43,30.1%).Carbamazepine(32,26.9%) and allopurinol(23,19.3%) were the commonest initiating drugs.SJS accounted for the highest proportion,TEN accounted for the most dangerous.Two cases died of respiratory failure.CONCLUSION: Prone to cause severe drug eruption drug, strengthening pharmaceutical care during clinical use. abnormal timely withdrawal and giving sufficient corticosteroids treatment early to control the incidence of complications.

Epidural anesthesia compared with combined spinal epidural anesthesia for femoral head replacement in the elderly: a systematic review

LUO Xue-mei, YAN Si-min, GE Wei-hong

2014, 19(8): 890-897.

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AIM: To systematically evaluate the effects of epidural anesthesia (EA) and combined spinal epidural anesthesia (CSEA) in femoral head replacement in elderly persons using meta-analysis. METHODS: Literature was retrieved in electronic databases covering PubMed, EMbase, CNKI and WanFang Data from established dates to July, 2013. Two reviewers independently screened studies according to the inclusion and exclusion criteria, extracted data and evaluated the methodological quality of the included studies. Then meta-analysis was performed using the software RevMan 5.2.RESULTS: Eighteen published randomized controlled trials involving a total of 1653 patients were suitable for inclusion in the review. The results of meta-analysis revealed that, the onset, duration time of motor-block time, and the sensory regressive time of CSEA were significantly shorter in femoral head replacement than that of EA. As the duration of anesthesia of CSEA was longer than that of EA, the number of patients needed extra anesthesia of CSEA was less. Moreover, the incidence rate of hypotension, bradycardia, shivering and an episode of oxygen desaturation in femoral head replacement with CSEA was lower than that with EA. CONCLUSION: The current evidence shows that, compared with EA, CSEA in elderly is superior in anesthetic efficacy, and is good at femoral head replacement.

Assessing the agreement of quantitative data by Bland-Altman method and realizing it with SAS Macro

NI Ping, CHEN Hui, TU Jiao, XU Lin yong

2014, 19(8): 898-903.

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AIM: To explore the application of Bland-Altman in quantitative data consistency evaluation,and realize it with SAS macro. METHODS: According to the principle of Bland-Altman method and the steps of the consistency analysis, we wrote SAS macro command.RESULTS: The SAS macro could use the Bland-Altman method to evaluate the consistency of quantitative data, and output graph and table results of analysis into word, save a lot of time for clinical trial statistics. CONCLUSION: Consistency evaluation of quantitative data should use the Bland-Altman method, the SAS macro provided great convenience for the method, contributed to its popularization and application.

Effect site concentration of propofol for loss of consciousness under remifentanil target-controlled infusion

LU Zhi-hong, DONG Hui, LIU Ming-fu, FENG Da-peng, DONG Hai-long

2014, 19(8): 904-906.

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AIM: To determine the influence of remifentanil on effect site concentration of propofol for loss of consciousness. METHODS: Patients scheduled for general anesthesia were randomly enrolled into group RP and group P. Group RP received target controlled infusion of remifentanil until an effect site concentration of 4 ng/mL was achieved. Then propofol was infused with a target plasma concentration of 4 μg/mL. Group P received infusion of propofol of the same target concentration. The effect site concentration of propofol for the patient losing consciousness was recorded.RESULTS: For the group RP, the ECe₅₀ of propofol effect site concentration for patients losing consciousness was 0.84(0.75,0.93) μg/mL,while the ECe₉₅ value was 1.40(1.27,1.59) μg/mL. However, for the group P, the ECe₅₀ value was 1.9(1.83,1.98) μg/mL and the ECe₉₅ value was 2.8(2.72,2.94) μg/mL. There were significant differences between the two groups considering both the two values (both P<0.05). Time to LOC and propofol needed to LOC was significantly lower in the RP group, while Narcotrend index was higher. Furthermore, the decrease of MAP was more significant in the RP group (all P<0.05).CONCLUSION: Remifentanil could increase the sedative effect of propofol and decrease the effect site concentration of propofol for loss of consciousness.

Analysis on clinical efficacy in the near future of mesalazine oral combined with enema for mildly to moderately distal ulcerative colitis

LI Juan, WANG Yu-lan

2014, 19(8): 907-911.

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AIM: To observe clinical efficacy and mechanism of mesalamine oral combined with enema for mildly to moderately distal ulcerative colitis. METHODS: 40 patients with mildly to moderately distal active ulcerative colitis were randomly divided into two groups:trial group (20 cases,mesalamine oral combined with enema)and control group (20 cases, mesalamine oral only),were both treated for 4 weeks. The changes of clinical efficacy and disease activity index(Sutherland DAI)were evaluated before and after the treatment.The expression of MiR-155 in intestinal mucosa was detected by Realtime-PCR.RESULTS: After the treatment for 4 weeks,the trial group total efficiency was better than the control group (P<0.05), the descent range of DAI significantly was higher in trial group than that in control group(P<0.05), the descent range of the expression of MiR-155 in intestinal mucosa significantly was higher in trial group than that in control group(P<0.01). CONCLUSION: The clinical efficacy in the near future of mesalamine oral combined with enema for distal mildly to moderately active ulcerative colitis was superior to that of mesalamine oral only, the intestinal mucosa ulcer heal rapidly and the DAI cut down, by decreasing expression of MiR-155.

Relationship on medication compliance, antipsychotic side-effects and social support in schizophrenia outpatients

HANG Rong-hua, LI Ye-ping, WU Ming-fei, LI Rui

2014, 19(8): 912-915.

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AIM: To explore the relationship on medication compliance, antipsychotic drugs side-effects and social support in schizophrenia outpatients. METHODS: 132 schizophrenia outpatients were were evaluated with Treatment Emergent Symptom Scale(TESS), Social Support Rating Scale (SSRS) and Medication Compliance Scale. The related factors influencing the medication compliance were analyzed. RESULTS: ①The score of Medication Compliance Scale was (9.45±1.29). There were significant differences on Medication Compliance Scale score among different marital state, health insurance and working position. Score of the divorced was lower than unmarried or married patients, patients with health insurance was higher than those without medical insurance, and patients who have a job was higher than have no job. ②Compliance Scale score was significantly negative correlation with TESS (r=-0.727), significantly positive correlation with SSRS (r=0.369). ③Multi-regression showed, TESS Score forecasted compliance negatively. Score of SSRS forecasted compliance positively. CONCLUSION: Antipsychotic drugs side-effect and social support are important factors for medication compliance. Reasonable measures should be taken.

Research on the therapeutic effect and adverse reactions of combination chemotherapy with NVB and TXT on non-small cell lung cancer

BAO Zhi-jian, CHEN Dao-bao, LI Bo-ying

2014, 19(8): 916-919.

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AIM: To evaluate the therapeutic effect and adverse reactions of combination chemotherapy with NVB and TXT on NSCLC , and to prove the synergistic effect of combination chemotherapy. METHODS: A total of 53 NSCLC patients were randomized into 2 groups, 26 cases of them were treated with NVB at the dose of 25 mg/m² on d 1, d 8, every 21 days. 27 cases of them were treated with NVB at the dose of 25 mg/m² on d1, d8, every 21 days and TXT were administered 75 mg/m² by infusion, with a 3-day pre-medication of corticosteroids b.i.d to reduce the incidence of severe fluid retention and hypersensitivity. RESULTS: NVB group CR, PR, SD, PD, TCR and 1-year survival rate was 0%(0/26), 30.77% (8/26), 53.85%(14/26), 15.38%(4/26), 84.6%(22/26)and 42.31%(11/26). The NVB and TXT group CR, PR, SD, PD, TCR and 1-year survival rate was 3.70%(1/27), 33.33%(9/27), 51.85%(14/27), 11.11%(3/27), 88.9%(24/27) and 51.85% (14/27). There was no statistical significance in the two groups, the common adverse event were bone marrow suppression. There was statistical significance in different two groups (P<0.05). CONCLUSION: Although the effective of combination chemotherapy with NVB and TXT may be a little better than the single NVB,the adverse reactions is more serious.

Observation on combined seretide with theophylline on the pulmonary artery pressure and right cardiac functionin in patients with stable chronic obstructive pulmonary disease

HUANG You-ming, WANG An-cai, ZHA Ri-tian

2014, 19(8): 920-925.

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AIM: To observe the effects of combined application of salmeterol and fluticasone propionate(seretide) powder for inhalation with theophylline sustained-release tablets on the variation of pulmonary artery pressure and right cardiac function in patients with stable pulmonary obstructive disease(COPD). METHODS: Retrospective analyses were performed in 128 COPD patients in their stable phase after therapy on hospitalization and long-term management on outpatient basis in our hospital from Sept. 2010 to Jun. 2012. after one year inhalation of secretide for determination and comparison of the right ventricular geometry parameters and Doppler parameters. RESULTS: Different baseline level of pulmonary artery pressure patient determined by echocardiography in the three groups of patients varied to a certain extent before and after therapy, yet the parameters showed no statistical difference in patients with normal pulmonary artery pressure(P>0.05). Significant pulmonary systolic pressure was observed in MPH group, with decreased right ventricular Tei index (P<0.05). In SPH group, the changes were seen concerning right ventricular Tei index, transverse RA of right atrium and anterior and posterior diameter of the RV, which were statistically different. Nevertheless, there was no statistical difference regarding the RVAW, MPA, RVESV, EVEDV, RVSV, PASP and RVEF. Enlarged right atrium and ventricle as well as widened inner diameter of the MPA to a certain degree were found in patients with mild, moderate to severe pulmonary artery pressure as compared with those in NPH group. The PASP in MPH group showed no correlation with the Tei index, and the RA and RV also had no significant correlation with the Tei index of right ventricle in SPH group. CONCLUSION: Combined utilization of seretide with theophylline can improve the right cardiac function of patients with stable COPD.

Evaluation of therapeutic efficiency of laparoscopic radical nephrectomy and postoperative immunotherapy with different doses of IL-2

PAN Cai-ming, HUANG Hou-bao, QIU Cheng

2014, 19(8): 926-930.

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AIM: To evaluate the therapeutic efficiency of laparoscopic radical nephrectomy and postoperative immunotherapy with different doses of IL-2. METHODS: A total of 38 patients underwent laparoscopic radical nephrectomy were enrolled. There were 33 patients with clear cell carcinoma, 2 patients with papillary renal cell carcinoma and 3 patients with granular cell carcinoma. Operative time, intraoperative bleeding, recovery time of gastrointestinal function, remove time of drainage tube, average hospital stay after operation and postoperative complications were investigated. All patients were divided into two groups according to postoperative immunotherapy with different doses of IL-2: group 1 (18 mL U/m²) and group 2 (1 mL U/m²). The therapeutic efficiency and the adverse reactions between groups were also been compared.RESULTS: A total of 38 patients underwent laparoscopic radical nephrectomy were enrolled. There were 33 patients with clear cell carcinoma, 2 patients with papillary renal cell carcinoma and 3 patients with granular cell carcinoma. Operative time, intraoperative bleeding, recovery time of gastrointestinal function, remove time of drainage tube, average hospital stay after operation and postoperative complications were investigated. All patients were divided into two groups according to postoperative immunotherapy with different doses of IL-2: group 1 (18 mL U/m²) and group 2 (1 mL U/m²). The therapeutic efficiency and the adverse reactions between groups were also been compared.CONCLUSION: Laparoscopic radical nephrectomy is safe, effective and fewer complications. Postoperative IL-2 immunotherapy can effectively delay recurrence and distant metastasis of renal cell carcinoma. The therapeutic efficiency of postoperative immunotherapy with low-dose trial of IL-2 is similar to high-dose trial of IL-2.

Research current situation and progress on pharmacogenomics and personalized medicine of cyclosporine A

DAI Ying, ZHANG Jing, LIN Mei-qing, SONG Hong-tao

2014, 19(8): 931-936.

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Cyclosporine (CsA), as a novel potent immunosuppressant, is widely used in organ transplantation in recent years. Due to its narrow therapeutic index and individual difference, it has been greatly concerned that how CsA can be used rationally in clinic. The bioavailability and metabolic of CsA are mainly affected by drug-metabolizing enzymes CYP3A and P-glycoprotein transporter protein (P-gp), while the individual differences of gene polymorphism of CYP3A and multi-drug resistance gene (MDR1) are the molecular mechanisms of the generation of activity difference. In addition, the combination therapy, diet and other non-genetic factors are also an important reason for the therapeutic effect of CsA. This paper reviews the pharmacogenomics research of CsA combined with non-genetic factors, in order to provide reference for clinical individualized medicine so as to ensure safety and rational use of drugs on patients.

Current advancement on pharmacokinetics study of herbal injection prescription

SHEN Han-yuan, HAO Hai-ping, WANG Guang-ji

2014, 19(8): 937-942.

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The problem of medication safety about herbal injections has gained more and more attention. Pharmacokinetics is not only an important way to reveal the pharmacodynamic material basis and in vivo behavior of herbal injections, but also significant to improve the quality control standards and rational clinical use. This reveal makes a simple introduction about research status of herbal injection pharmacokinetics and indicates that the attention paid to the study is still limited. In recent years, the research of in vivo process about herbal injections could be carried out as the progress of TCM pharmacokinetics. The study of quality control, safety evaluation, process optimization and clinical rational drug use of herbal injections should use the results of the in vivo research to improve and guarantee the efficacy and safety of the injections.

Endogenous cannabinoid system and Alzheimer Disease

DONG Man-man, YANG Hong-wei

2014, 19(8): 943-947.

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Alzheimer's disease (AD) is a chronic progressing neurodegenerative disorder, and the principal neuropathological hallmark of the disease, is the extracellular β-amyloid peptide(Aβ) accumu- lation formed senile plaques, intracellular hyperphosphorylated tau formed neurofibrillary tangles, and loss of neuron with gliocyte proliferation. Recent evidence shows that endogenous cannabinoid system serve as preventive treatment for AD, based on their neuroprotective and anti-inflammatory effects. Here we summarizes several aspects of the endogenous cannabinoid protective effect of the AD, aiming at providing a new method for the treatment of AD.

Progress on the treatment of cardiovascular disease with bone marrow stem cells

ZHAO Chun-mei, WANG An-cai, WANG De-guo

2014, 19(8): 948-952.

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Bone marrow stem cells are a population of multipotent cells,including two types of hematopoietic stem cells and mesenchymal stem cells,which are widely exist in bone marrow tissue.With the capacity of self-renewal and multiple differentiation,under certain conditions,bone marrow stem cells can be induced to differentiate into a variety of cells including myocardial cells and be used as ideal seed cells for tissue and organ damage caused by aging and disease, especially for the clinical treatment of cardiovascular disease,such as myocardial infarction,ischemic heart failure,intractable angina,dilated cardiomyopathy and so on.The progress on the bone marrow stem cells for the treatment of cardiovascular disease were reviewed in this paper.

Advancement of antineoplastic activity research on heparanase drugs

ZHANG Jun, CUI Ya-fang, ZHANG Chang-zhuo, ZHANG Ya, SHAO Peng

2014, 19(8): 953-960.

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Heparanase is a glucuronic acid enzyme, it hydrolizes heparin sulfate, which is main components of cell membrane and extracellular matrix, growth factors are released to promote tumor cell invasion and metastasis. As for the antineoplastic drug targets, a series of polysaccharides, synthetic small chemical compounds and natural product compounds have been found, some of them have begin the clinical research. The crystal structures of heparanase have successfully been discovered, so it is possible to do rational drug design based on 3D protein structures. This paper introduces antineoplastic activity research advance of heparanase inhibitors in details.

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