Objective To establish the topotecan(TPT)-resistant cell line of human oophoroma (SKOV3/TPT), and to investigate its biological features. Methods To simulate the condition in clinical chemotherapy, drug resistant SKOV3/TPT cell line of human oophoroma was established by challenging SKOV3 with a large dose of TPT (2160ng/ml). Drug sensitivity was assessed by MTT assay. Light microscopy, electronic microscopy, trypan blue staining rejection, and cell counting were employed to determine the biological features of the cell line. Flow cytometry (FCM) was used to study the cell cycle distribution, the accumulation of intracellular drug, and the expression of P glucoprotein (Pgp). Results SKOV3/TPT cells were established successfully, and the resistance index (RI) was 10.67. They showed an obvious cross-resistance to CPT-11, MX and VCR, but still sensitive to taxol, cis-platin, VP16, MTX and 5-Fluorouracil. Comparing with the parent cells, their morphology was unchanged, but multiplication time was prolonged. The apoptosis rate and the proportion of G2+M phase cells of resistant cells were significantly higher than that of their parent cells (P

Objective To investigate the therapeutic effect of Shenmai injection(SMI)on neonatal hypoxic-ischemic encephalopathy(HIE)and it's possible mechanism.Methods 45 neonates with HIE were randomly divided into the SMI treatment group and routine treatment group.At the basic of routine treatment,the SMI treatment group was treated with 10 ml SMI added into 10% GS 30~50 ml via injecting into veins once a day for 7~10 d.The levels of serum S-100?,NSE were measured at 1 d,3 d,6 d after treatment.The development quotients(DQ)was evaluated at 3-month-old infants.Results Compared with routine treatment group,symptoms of nervous system in SMI treatment group were recovered obviously faster,the hospitalization time was shorter(all P

Autoimmune hepatitis (AIH) is the first liver disease which has proved responsive to gluc()orticoids,and the standard therapeutic method is hormone combined with azathioprine.Given that some patients fail to reach the standard of immunosuppressive therapy,and the long-term use of immunosuppressive therapy has many adverse effects,it is necessary to reasonably use anti-inflammatory and liver-protecting drugs to minimize the dose of immunosuppressants,control liver inflammation,reduce the damage of liver cells,and delay the progression of the disease.This paper reviews the advances in the application of anti-inflammatory and liver-protecting drugs in the treatment of AIH,in order to help clinicians make rational decisions.

Objective To explore the effects of ultraviolet on DNA damage in keratinocytes and to observe the protective role of resveratrol for the cells. Methods Comet assay was employed to evaluate the damage after radiation with different doses of UV rays (UVA, UVB and UVC) of 0, 10, 30, 50, 70 and 90 mJ/cm2, and the effects after pretreatment with various concentrations of resveratrol under irradiation with 30 mJ/cm2. Results UVA irradiation (0 ~ 90 mJ/cm2) had no significant effects on HaCaT cells. However, TailDNA%, TailLength, CometLength, TailMoment and OliveTailMoment showed both UVB and UVC induced DNA damage in a dose-de-pentent manner. UVC was more harmful than UVB at the same dose. Conclusions The DNA breakage induced by UVB and UVC is dose-dependent. As compared with UVB, UVC is more harmful to HaCaT cells. Resveratrol exerts a protective effect in HaCaT cells irradiated by UVB or UVC.

Objective To explore the mechanism of insulin resistance regulated by fibroblast growth factor 21 (FGF21)and identify its role in oxidative stress.Methods High-fat diet-induced obese mice were treated with FGF21 ,and hepatic oxidative stress markers such as iNOS and insulin signaling molecules such as IRS-1 and Akt were assessed by Western blot and co-immunoprecipitation.Meanwhile,liver steatosis was assessed in liver sections stained with oil red O.Results Obese mice in FGF21 group showed reduced body weight,blood glucose and serum insulin levels,and improved insulin sensitivity as measured by glucose tolerance testing (GTT)and insulin tolerance testing (ITT)compared with obese mice in vehicle group.Meanwhile,FGF21 treatment in obese mice decreased protein expressions of iNOS and TNF-α,and increased insulin-stimulated IRS-1 tyrosine phosphorylation and Akt Ser-473 phosphorylation,indicating that FGF21 inhibited hepatic oxidative stress and restored impaired insulin signaling.Additionally,we found significantly reduced lipid accumulation in liver sections stained with oil red O in FGF21-treated obese mice.Conclusion Our results support the notion that FGF21 is an important regulator of insulin resistance and that FGF21 may reduce lipid accumulation in the liver,restore hepatic insulin signaling and improve insulin sensitivity in obese mice,at least in part,by inhibiting hepatic oxidative stress.Therefore,FGF21 has a potential value in clinical application.

Objective To observe the protection effect of ischemic preconditioning to small intestines injury after limbs ischemia reperfusion ,and investigate the role of nitrogen monoxidum in the process .Methods 52 male Wistar rats were randomly divided in-to Sham group ,limbs ischemia-reperfusion (IR) group ,IPC + IR group and Nω-nitro-L-arginine methylester (L-NAME) group . The value of diamine oxidase (DAO) and nitrogen monoxidum (NO) in plasma and gut tissue ,the content of fluorescein isothiocya-nate lipopolysaccharide (FITC-LPS) in plasma ,and the value of cyclic guanosine monophosphate (cGMP) and malondialehyde (MDA) in gut tissue were measured ,respectively .The expression of P-selection and Caspase-3 were measured by immunohisto-chemistry .The apoptosis of intestinal cells was detected by terminal deoxynucleotidyl transferase -mediated dUTP nick end labe-ling (TUNEL) and the results were analysed quantitatively by automatic image analytical system .Results Compared with the LIR group ,the values of DAO and FITC-LPS in plasma decreased obviously in the IPC group ,and the level of NO in plasma increased obviously (P<0 .01) .The values of DAO ,NO and cGMP in gut tissue increased obviously ,the level of MDA and the expression of Caspase-3 and the apoptosis index (AI) were significantly decreased in IPC group (P<0 .01) .Compared with the IPC group ,the value of DAO and FITC-LPS were higher and the level of NO was lower in plasma of the L-NAME group (P<0 .01) .The values of DAO ,NO and cGM P in gut tissue obviously decreased ,the level of MDA significantly increased ,and the expression of Caspase-3 and the AI significantly upregulated in L-NAME group than those in IPC group (P<0 .01) .Conclusion IPC can improve the small intestine injury and the apoptosis following hind limbs ischemia reperfusion which may correlated with the increase in the level of NO .

Objective To investigate the trough and peak vancomycin plasma concentrations in steady-state following regular dosage and to improve dosing regimen based on pharmacokinetic modeling, providing reference for clinical practice in children.Methods we retrospectively analyzed pharmacokinetics of vancomycin in 50 cases admitted in our PICU who had been confirmed or suspected with gram-positive bacterial infections following regular dosage[40 mg /(kg?d)].Then we tried to optimize dosing regimens with Monte Carlo simulation to evaluate different dosing regimens of vancomycin in children.Results with regular dosage of vancomycin,mean trough concentrations of vancomycin were (1 1.02 ±4.44 )mg /L, trough concentrations higher than 15 mg /L accounted for only 12%.In the actual program,the extension of a single intravenous infusion to 3 hours after administration would result in 26% of trough concentrations dis-tributing in the range above 15 mg /L.If we increased daily dose to 50 mg /kg and 60 mg /kg with simulation, the trough concentration distribution frequency above 15 mg /L would increase from 12% to 32% and 40%. If minimum inhibitory concentration of vancomycin to pathogenic bacteria (Staphylococcus aureus )was 1 mg/L,the probabilities of target attainment for pharmacokinetic/pharmacodynamic evaluation were 51.73%, 76.54% and 87.5% for three dosages [40 mg/(kg?d),50 mg/(kg?d)and 60 mg/(kg?d)]of vancomycin, respectively.we suspected that dosage of 60 mg/(kg?d)was a good choice.with this dosage regimen,we could achieve a substantial increase in the probability of target attainment.Conclusion Following regular dosages, trough concentration distribution frequency from 15 to 20 mg /kg is low.The extension of a single intravenous infusion time can not achieve a good result.According to the result of pathogenic bacteria and anti-microbial susceptibility tests,increasing daily dosage of vancomycin to 60 mg /(kg?d)will help to improve the trough concentration and get more clinic achievements.

Objective:To analyze the level diversifies of plasma CCL19 and CCL21 in the male drug users infected HCV.Methods: The plasma CCL19 and CCL21,anti-HCV and HCV RNA were detected by ELISA quantitation,ELISA qualitation and Real-time RT-PCR respectively.Compared with 60 healthy man,the level diversifies of plasma CCL19 and CCL21 in 391 male drug users conducted as part of HCV Surveillance Programme in Zhuhai were analyzed.Results: 180 of 391 male drug users were infected HCV and the infection rate was 46.04%.The level of plasma CCL19 and CCL21 in the male drug users[anti-HCV(-)/HCV RNA(-)] were higher than that in the healthy man (P≤0.001).The level of plasma CCL19 and CCL21 in anti-HCV(-)/HCV RNA(+) group was lower than that in the others(P≤0.05) .Compared with that in the healthy man,the level of plasma CCL19 and CCL21 in the drug abuse anti-HCV(+)/HCV RNA(-) group had significant deviation(P<0.05).Conclusion: Drug abuse can heighten the level of plasma CCL19 and CCL21 in man.Increasing the level of plasma CCL19 and CCL21 may conduce to spontaneous HCV clearance.It may prognosticate that HCV infection will be persistent and have a bad consequence when the level of plasma CCL19 and CCL21 were degraded.

Objective To investigate the improving effects of Shenshao decoction on myocardial structure and function in diabetic cardiomyopathy,and its effect on expression of TLR4/MyD88-dependent pathway signal in diabetic cardiomyopathy.Methods Diabetes mellitus was induced in 8-week-old male Wistar rats by a single intraperitoneal injection of streptozotocin.The changes of plasma myocardial enzyme (CK, LDH) and high sensitive C reactive protein (hsCRP) were measured.Cardiac function was measured by left ventricular intubation.Hematoxylin and eosin staining and electron microscopy were used to observe the changes of myocardial morphology and ultrastructure in rats.Expression of Toll-like receptor 4(TLR4), myeloid differentiation protein 88(MyD88), and nuclear factor-κB P65(NF-κB P65) were tested by immunohistochemistry.Results After 6 weeks of treatment, the left ventricular diastolic and systolic functions were obviously improved;the degrees of myocardial fibers and mitochondrial damage were obviously relieved;the content of CK, LDH and hsCRP decreased (P< 0.05), and hsCPR was positively correlated with CK and LDH (r=0.823,r=0.819,P < 0.05).The expressions of TLR4, MyD88, NF-κB P65 were significantly decreased (P< 0.05).There was no significant difference in the above mentioned indicators between the control group and control+Shenshao decoction group (P> 0.05).Conclusions Shenshao decoction can reduce the myocardial injury in diabetic cardiomyopathy and improve cardiac diastolic and systolic functions.The mechanism may be related to attenuated inflammation by TLR4/MyD88 dependent signaling pathway.

Objective To observe the clinical efficacy of needling a group of acupoints for choke plus rehabilitation training in treating post-stroke deglutition disorder.Method Ninety patients with post-stroke deglutition disorder were randomized into a treatment group and a control group, 45 cases in each group. In addition to the conventional treatment, the control group also received swallowing rehabilitation training, and the treatment group received acupuncture ata group of acupoints for chokeas the major intervention(Aqiang point, Zhiqiang point, Tunyan point, Tiyan point and Fayin point, all extra) besides the intervention given to the control group, both for 3 successive treatment courses. Before and after theintervention, the National Institute of Health Stroke Scale (NIHSS), Videofluoroscopic Study (VFSS), post-stroke swallowing scale of traditional Chinese medicine (TCM) (TCM scale for short), and the occurrence rate of relevant complications were comparedbetween the two groups.Result The total effective rate was 97.8% in the treatment group, significantly higher than 84.4% in the control group (P<0.05); the scores of NIHSS, VFSS and TCM scale in the treatment group were superior to those in the control group (P<0.05);the NIHSS, VFSS and TCM scale scores in the treatment group were superior to those in the control group after the intervention (P<0.05);24 cases in the control group presented complications versus 8 cases in the treatment group (P<0.05).Conclusion Acupuncture at the points group for chokepredominantlyplus rehabilitation training can effectively improve post-stroke deglutition disorder and reduce the occurrence of complications, with satisfactory safety and consistency.