OBJECTIVE: To evaluate and optimize the treatment regimen of cephalosporins based on Monte Carlo simulation and the pharmacokinetics /pharmacodynamics (PK/PD) model. METHODS: The treatment regimens of cefradine, cefuroxime, ceftriaxone and cefepime are 0.75 g qid, 1 g qid, 2 g bid and 2 g tid. And a total of 903 strains from eight species were collected. The minimum inhibitory concentration (MIC) was measured by trace broth dilution method. Monte Carlo simulation was used to simulate the regimens against Escherichia coli, Bacillus, Klebsiella pneumoniae, Acinetobacter baumannii, Citrobacter, Staphylococcus aureus, Streptococcus pneumoniae, Pseudomonas aeruginosa. Then, the cumulative fraction of response (CFR) was calculated. RESULTS: Cefhradine and cefuroximes' rates of resistance were higher (47.31% - 100%), the cumulative reaction scores(CFR) were all less than 90%. Cefuroxime has desirable regimen for Escherichia coli, Klebsiella pneumoniae, Citrobacter and Streptococcus pneumoniae. Cefepime has at least one dose regimen's CFR for more than 90%, and cephalosporins is consistent with time-dependent drug characteristics. CONCLUSION: For the treatment of infectious diseases, the choice of cephalosporins should be used to follow the principles of antibiotics. Target therapy should be used to test the pathogen susceptibility test, according to the value of MIC to simulate the corresponding dosing regimen, to achieve individualized administration.

Objective To investigate the effects of midazolam on hypoxic-ischemic (HI) brain injury in neonatal piglets.Methods Twenty-four newborn male piglets 3-7 days old weighing 1.8-3,0 kg were randomly divided into 3 groups ( n = 8 each): sham group (group S), HI + normal saline group (group HI-S) and HI + midasolam group (group HI-M). The animals of group HI-S and HI-M were subjected to 7 min of hypoxia, producing asphyxic cardiac arrest, followed by cardiopulmonary resuscitation. At 3 h after restoration of spontaneous circulation (ROSC), animals received i.v. infusion of fentanyl at a rate of 10-30 μg·kg-1·h-1 and pancuroniumat a rate of 0.1-0.2 mg·kg-1·h-1 from 3 h after ROSC to 24 h after ROSC to maintain the anesthesia. In addition, midazolam at a rate of 0.05 mg·kg-1·h-1 wee infused simultaneously until 24 h after ROSC in HI-M group, while the equal volume of normal saline was infused instead in group HI-S and S. Arterial blood samples were taken before hypoxia (baseline), and at 37 min of hypoxia, 5 min of air inspiration, 5 min of asphyxia and 6, 12, and 24 h after ROSC for blood gas analysis, and MAP was monitored at the each time point. Neurological behavior was assessed and scored (NBS) at 48, 72, 96 and 240 h after ROSC. Brains were removed at 10 h after ROSC, the remaining viable neurons in putamen and candate nucleus were counted and the density of viable neurons was determined using light microscopic examination. Results PaO2 was significantly decreased during hypoxia-eephyxia, and PaCO2 was significantly increased, while pH value and MAP were significantly decreased at 5 min of asphyxia in group HI-S and HI-M compared with group S and the baseline (P < 0.05).There were no significant differences in MAP and arterial blood gas analysis at the each time point between group HI-S and HI-M ( P > 0.05). The density of viable neurons in putamen and caudate nucleus was significantly lower, and NBS at 48-96 h after BOSC significantly higher in group HI-S and HI-M than in group S ( P < 0.05). The density of viable neurons in putamen and caudate nucleus was significantly higher and NBS at 72 and 96 h after ROSC significantly lower in group HI-M than in group HI-S ( P < 0.05). Conclusion Midazolam used at the early stage of cardiopulmonary resuscitation can attenuate HI brain injury in neonatal piglets.

Objective:To investigate the effect of four different limbs postures on leg loading and stability of stand-to-sit (StandTS) in hemiplegic stroke patients.Method:30 hemiplegic stroke patients and 30 healthy individuals participated in this study.The duration,mean lower limb loading,and sway of the center of gravity (COG) in mediolateral directions (COGX) were measured during StandTS at four postures.Result:There were no significant differences in duration,mean lower limb loading,and COGX between the two arm positions during StandTS in hemiplegic stroke patients (0.05＜P＜0.1).In hemiplegic stroke patients performing StandTS,there were significant differences in duration,lower limb loading,and COGX between the different foot positions (P＜0.05).When hemiplegic stroke patients placed the paretic foot posterior,the weightbearing asymmetry between lower limbs was greatly improved,compared with the asymmetry when the non-paretic foot was posterior (P＜0.05).Furthermore,when the non-paretic foot was posterior,the duration to complete the StandTS movement increased (P＜0.05),and the postural stability during StandTS improved(P＜0.05).There were no significant differences in duration,mean lower limb loading,and COGX among four different limbs positions during StandTS in healthy individuals (0.05＜P＜0.1).Conclusion:Changing the upper limb position did not affect lower limb loading and postural stability during StandTS in stroke patients.However,changing the foot position significantly influenced the lower limb loading and postural stability during StandTS in hemiplegic stroke patients.

Objective To establish the quality standard for Xuanshi Texiao Yaoshui(mainly composed of Radix Sophorae Flavescentis,Cortex Pseudolaricis,etc).Methods Radix Sophorae Flavescentis and Cortex Pseudolaricis were identified by TLC.The content of oxymatrine was determined by HPLC.Symmetry C18 column(4.6 mm? 250 mm,5 ? m)with mobile phase of methanol-water-triethylamine(40:60:0.04)was used.The detective wavelength was 220 nm.Results TLC for Radix Sophorae Flavescentis and Cortex Pseudolaricis was specific .HPLC for oxymatrine had a good separation with other components,and the linear range of oxymatrine was 0.60～ 1.80 ? g and recovery rate was 99.34 %(RSD =0.71 %).Conclusion This method can be used to control the quality of Xuanshi Texiao Yaoshui.

Objective In order to investigate the situation application of compound Danshen injection (CDI) in the treatment and to provide reference for clinical rational use.Methods Adverse drug reactions (ADR) report literatures through WANFANG DATA, VIP DATA and CNKI from 1989 to 2013 with (CDI) were retrieved the data including patient age, gender, medical history, dosage, medication time and ADR type were got and analyzed.Results One hundred and twenty-one literatures with one hundred and forty-eight ADR report cases wore retrieved. The ADR of (CDI) rate of male was higher than female. The original disease causes were cardiovascular and cerebrovascular diseases. The age, a rather elderly bunch, was not associated with the disease. The frequent onest time of adverse reaction was in 5-20 min after medication, and allergic reaction was the main adverse reaction.Conclusion The ADR of CDI should not be ignored. Patients constitution, gender, medication time and the combined application should be pay more attention to reduce the incidence of ADR and ensure the drug safety.

Objective To investigate the effects of endaravane on hypoxia-ischemia (HI)-induced brain injury in neonatal piglets. Methods Male piglets 3-7 days old weighing 2.0-3.0 kg were used in this study. Group Ⅰ 10 piglets were randomly collected as sham operation without HI. Twenty piglets with HI were randomly divided into 2 groups (n = 10 each) : group Ⅱ HI and group Ⅲ HI + endaravone. The animals were anesthetized with intraperitoneal pentobarbital sodium 50 mg/kg, tracheostomized and mechanically ventilated with 30% O_2. Right femoral artery and vein were cannulated. MAP, HR, PET CO_2, blood gases and glucose and rectal temperature were monitored. After 15 min stabilization cardiac arrest was induced by inhalation of hypoxic air (O_2 10%) for 40 min followed by inhalation of 21% O_2 for 5 min. The tracheal tube was then occluded for 7 min. Cardio-pulmonary resuscitation (CPR) was then started until recovery of spontaneous circulation (ROSC). CPR > 3 min was considered a failure. A bolus of endaravone 3 mg/kg was given iv over an hour at 30 min after CPR,followed by continuous infusion at 1.5 mg·kg~(-1)·h~(-1) for 5.5 h in group Ⅲ , while in group Ⅱ vehicle was given instead of endaravone. The neurological function of the animals was evaluated at 48, 72 and 96 h after ROSC and scored (0-154, 0 = normal, 154 = severest dysfunction). The animals were killed at 96 h after ROSC. The brains were removed for microscopic examination of striatum and cortex and determination of 8-hydroxy-2'-deoxyguanine (8-OHdG/OHG) expression in putamen by immuno-histochemistry. Results The neurological function scores were significantly higher at 48 h after ROSC and the number of viable neurons in striatum and sensory cortex were significantly lower and the expression of 8-OHdG/OHG in putamen was significantly higher in group Ⅱ than in group Ⅲ . Conclusion The antioxidant endaravone given after CPR can attenuate Hl-induced brain injury by inhibiting oxidative damage to DNA and RNA.

AIM:To study the effect of mistletoe lectins on cell proliferation and apoptosis in HT-29 human colon cancer cell.METHODS:The effect of mistletoe lectins on cell viability in HT-29 cell was evaluated by MTT assay.Cell apoptosis was observed by DNA ladder analysis and Tunel.RESULTS:Mistletoe lectins(eg.,1-4 mg/L) inhibited cell growth in a dose and time dependent way in HT-29 cells.HT-29 cells apoptosis can be induced when exposed to mistletoe lectins(eg.,1-4 mg/L).CONCLUSION:Mistletoe lectins can inhibits proliferation and induces apoptosis in HT-29 cells in vitro.

To investigate whether interleukin-1β(IL-1β), tumor necrosis factor-α (TNF-α) and lipopolysaccharide (LPS) induce expression of monocyte chemoattractant protein-1 (MCP-1)mRNA and protein in calf aortic smooth muscle cells(SMCs), calf aortic SMCs were cultured by a substrate-attached explant method. The cultured SMCs were used between the third to the fifth passage. After the cells became confluent, the SMCs were exposed to 2 ng/ml IL- 1β, 20 ng/mlTNF-lα and 100 ng/ml LPS respectively, and the total RNA of SMCs which were incubated for 4h at 37℃ were extracted from the cells by using guanidinium isothiocyanate method. The expression of MCP-1 mRNA in SMCs was detected by using dot blotting analysis using a probe of γ-32p-end-labelled 35-mer oligonucleotide. After a 24-h incubation, the media conditioned by the cultured SMCs were collected. The MCP-1 protein content in the conditioned media was determined by using sandwich ELISA. The results were as follows: Dot blotting analysis showed that the cultured SMCs could express MCP-1 mRNA. After a 4-h exposure to IL-Iβ, TNF-α and LPS, the MCP-1 mRNA expression in SMCs was increased (3.6-fold, 2.3-fold and 1.6-fold, respectively).ELISA showed that the levels of MCP-1 protein in the conditioned media were also increased (2.9-fold, 1.7-fold and 1.1-fold, respectively ). The results suggest that calf aortic SMCs could express MCP-1 mRNA and protein. IL-1β and TNF-α can induce strong expression of MCP- 1mRNA and protein, and the former is more effective than the latter.

To investigate whether interleukin-1β(IL-1β), tumor necrosis factor-α (TNF-α) and lipopolysaccharide (LPS) induce expression of monocyte chemoattractant protein-1 (MCP-1)mRNA and protein in calf aortic smooth muscle cells(SMCs), calf aortic SMCs were cultured by a substrate-attached explant method. The cultured SMCs were used between the third to the fifth passage. After the cells became confluent, the SMCs were exposed to 2 ng/ml IL- 1β, 20 ng/mlTNF-lα and 100 ng/ml LPS respectively, and the total RNA of SMCs which were incubated for 4h at 37℃ were extracted from the cells by using guanidinium isothiocyanate method. The expression of MCP-1 mRNA in SMCs was detected by using dot blotting analysis using a probe of γ-32p-end-labelled 35-mer oligonucleotide. After a 24-h incubation, the media conditioned by the cultured SMCs were collected. The MCP-1 protein content in the conditioned media was determined by using sandwich ELISA. The results were as follows: Dot blotting analysis showed that the cultured SMCs could express MCP-1 mRNA. After a 4-h exposure to IL-Iβ, TNF-α and LPS, the MCP-1 mRNA expression in SMCs was increased (3.6-fold, 2.3-fold and 1.6-fold, respectively).ELISA showed that the levels of MCP-1 protein in the conditioned media were also increased (2.9-fold, 1.7-fold and 1.1-fold, respectively ). The results suggest that calf aortic SMCs could express MCP-1 mRNA and protein. IL-1β and TNF-α can induce strong expression of MCP- 1mRNA and protein, and the former is more effective than the latter.

To observe the transcriptional regulation of the two isoflavones genistein and daidzein on target genes.