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@#To explore the effects and molecular mechanism of icariin on the vascular function of mice with type 1 diabetes induced by alloxan, type 1 diabetic mice model was established by intraperitoneal injection with 200 mg/kg alloxan.After oral administration with icariin (60, 120 mg/kg) daily for 2 weeks, blood glucose, body weight, food intake and water intake were detected.To evaluate the impact of icariin on the function of isolated vascular ring contraction and relaxation, thoracic aortas of mice were removed and the Ach-induced vascular ring relaxation, Phe-induced vascular ring contraction, SNP-induced vascular ring relaxation and KCl-induced vascular ring contraction response were detected.To further confirm the mechanism of icariin to improve vascular function, human umbilical vein endothelial cells (HUVECs) were induced by high glucose (HG) in vitro.Western blot was used to detect the effect of icariin on eNOS, p-eNOS, p38 MAPK and p-p38 MAPK expressions in HG-induced human umbilical vein endothelial cells (HUVECs).The results indicated that icariin significantly ameliorated the weight loss and dampened the increase in water intake of the diabetic mice.Meanwhile, icariin had a certain ameliorative effect on blood glucose and food intake without significant difference.The results of isolated thoracic aortas vascular rings contraction and vasodilation function indicated that icariin significantly improved Phe-induced vascular contraction and Ach‐induced vascular relaxation.Meanwhile, icariin had a certain ameliorative effect on KCl-induced vascular contraction response without significant difference.However, no significant change was observed on endothelium‐independent vascular rings relaxation response induced by SNP after treatment with icariin.Results of Western blot showed that icariin inhibited the expression of p-p38 MAPK and induced expression of p-eNOS in the high glucose-induced HUVECs cell model.Therefore, icariin may attenuate alloxan-induced type 1 diabetic mice vascular diastolic function by inhibiting expression of p-p38 MAPK and inducing expression of p-eNOS.
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@#The metabolic reprogramming in cancer cells has recently attracted more and more attention from researchers. Lipid metabolism is involved in many cell processes such as cell growth, apoptosis, exercise, membrane homeostasis, chemotherapy response and drug resistance. This article summerizes the advances in research on fatty acids, cholesterol and phospholipid metabolism in non-small cell lung cancer, which may provide new ideas for the prevention, early diagnosis and treatment of non-small cell lung cancer.
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OBJECTIVE:To investigate clinical efficacy and safety of linezolid in the treatment of intracranial infection after neurosurgery operation. METHODS:Medical information of 39 intracranial infection patients receiving linezolid in Xijing Hospital of Air Force Medical University during Jul. 1st,2015-Aug. 29th,2016 were analyzed retrospectively. The clinical efficacy andsafety of linezolid in the treatment of intracranial infection after neurosurgery operation were evaluated according to indexes of intracranial infection patient,such as symptoms,signs,lab indexes test and bacterial culture results. RESULTS:Total response rate of 39 intracranial infection patients after neurosurgery operation was 79.49％ after linezolid treatment. After treatment,the patients' body temperature,white blood cell,neutrophil absolute value,white blood cell in cerebrospinal fluid and cerebrospinal fluid protein level were all significantly lower than before treatment,with statistical significance(P<0.05). Of 39 patients,cerebrospinal fluid of 27 patients were cultured before treatment,and 8 cases(29.6％)of which were positive,among which there were 6 cases (75.0％) of Gram-positive bacteria such as Staphylococcus and Enterococcus. No obvious ADR related to linezolid was found in patients. CONCLUSIONS:Linezolid can effectively control the intracranial infection caused by Gram-positive bacteria such as Staphylococcus and Enterococcus with good safety.
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Objective To study the dose-time-toxicity relationship of hepatotoxicity in mice with multiple administration of Paracetamol Tablets (PT),Compound Paracetamol and Amantadine Hydrochloride Tablets (CPAH),Compound Dextromethorphan Hydrobromide Tablets (CDH),and Chaiqin Qingning capsules (CQC).Methods Mice were randomly divided into control,PT,CPAH,CDH,and CQC high,medium,and low dose groups.The acetaminophen contents of high,medium,and low doses were 266.24,425.98,and 681.57 mg/kg in PT,CPAH,and CDH groups,and the doses of CQC group were 1437.70,2300.31,and 3 680.50 mg/kg,ig administration,once daily for 5 d.General state and toxicity of mice were observed.The changes of ALT,AST,AKP,TBIL,and ALB levels in serum and organ indexes of liver,spleen,thymus,and kidney were tested on day 1,3,7,11,and 14 after multiple administration.Results CQC with the dosage range of 1 437.70-3 680.50 mg/kg to mice within 14 d,has not yet induced the increase of AST,ALT,AKP,TBIL,and ALB levels and changes of organ indexes of liver,thymus spleen,and kidney compared with normal control (P ＞ 0.05).PT,CPAH,and CDH with repeated dose of 425.98-681.57 mg/kg could induce significant increase of the levels ofALT,AST,AKP,and TBIL which reached the peak on day 1 (P ＜ 0.05),and then gradually decreased on day 3-14.The level of ALB significant decreased on day 1-11 (P ＜ 0.05),and then gradually recovered on day 11-14.The liver index significant increased on day 1-3 (P ＜ 0.05),and recovered on day 7-14.Conclusion Multiple administration of CQC could not induce liver injury in mice within 14 d,while multiple administration ofPT,CPAH,and CDH could induce hepatotocixity in mice with a certain dose,and show an obvious dose-time-toxicity relationship.
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Objective To study the time-toxicity and dose-toxicity relationship of hepatotoxicity induced by Paracetamol Tablets (PT),Compound Paracetamol and Amantadine Hydrochloride Tablets (CPAH),Compound Dextromethorphan Hydrobromide Tablets (CDH),and Chaiqin Qingning Capsules (CQC) with single dose in mice.Methods In the Time-Toxicity relationship study,Kunming mice were randomly divided into control,PT,CPAH,CDH,and CQC group,and mice of.each drug administration group were randomly divided into nine subgroups according to the time (1,2,4,8,12,24,48,72 and 96 h after administration) of blood collection.The acetaminophen contents in PT,CPAH,and CDH groups were 425.98 mg/kg,and the dose of CQC group was 3 680.50 mg/kg.In the Dosage-Time relationship study,mice were randomly divided into control,PT,CPAH,CDH,and CQC high,medium and low dose group.The acetaminophen contents of high,medium,and low dose were 266.24,425.98,and 681.57 mg/kg in PT,CPAH,and CDH group,and the dose of CQC group was 1437.70,2300.31,and 3680.50 mg/kg,10 mice in each group,sex in half.Blood was collected 12 h after administration.Animal behavior was observed every day,blood and organs were collected at the corresponding time points,serum alanine aminotransferase (ALT),aspartate aminotransferase (AST),and alkaline phosphatase (ALP) level were detected,and the organs index of spleen and thymus,liver were calculated.Results There were no significant changes of ALT,AST,ALP,and organs index after once ig administration of CQC at dosage of 1437.70 mg/kg to 3680.50 mg/kg in mice.The study on time-toxicity relationship indicated that,after once administration of PT,CPAH,and CDH at 425.98 mg/kg,mice showed toxic symptom such as hypokinesia,dry hair and so on,12 h was the most obvious,24 ～ 72 h disappeared.The level of ALT,AST,and ALP in serum increased and reached to the peak at 12 h and then restored near normality after 72,24,and 24 h in PT,CPAH,and CDH group.Their organ index of liver,spleen and thymus all had no significant changes.The study on the dosage-toxicity relationship indicated that,there were no significant changes of animal behavior,ALT,AST,ALP,and organs index after once ig administration of PT,CPAH,and CDH at 266.24 mg/kg.Obvious liver injury can be induced by the three drugs with dosage of 425.98 to 681.57 mg/kg and the level of ALT,AST,and ALP increased significantly with the increase of dosage.Their liver index increased significantly with dosage of 681.57 mg/kg,but the organs index of spleen,thymus had no significant changes.Conclusion There was no hepatotoxicity after once ig administration of CQC with dosage of 3680.50 mg/kg in mice.Mice were once ig administration ofPT,CPAH,and CDH with a large dose,may induce acute liver injury and show obvious time-toxicity and dose-toxicity relationships.
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Objective To study the antipyretic effect of Paracetamol Tablets,Compound Paracetamol and Amantadine Hydrochloride Tablets,Compound Dextromethorphan Hydrobromide Tablets,and Chaiqin Qingning Capsules on the fever model induced by LPS and dry yeast in rats.Methods Fever was induced by ip injecting LPS (100 μg/kg) or sc injecting dry yeast (20％) in rats.We observed the changes of temperature of the rats after administration of Paracetamol Tablets,Compound Paracetamol and Amantadine Hydrochloride Tablets,Compound Dextromethorphan Hydrobromide Tablets (the acetaminophen contents were 205.67,102.83,and 51.42 mg/kg)and Chaiqin Qingning Capsules (1110.60,555.30,and 277.65 mg/kg).Maximum temperature rise height (△T) and temperature response index (TRI) were calculated,and the curve of average rise in temperature was drawn.Results Each dose group of Paracetamol Tablets,Compound Paracetamol and Amantadine Hydrochloride Tablets,Compound Dextromethorphan Hydrobromide Tablets,and Chaiqin Qingning Capsules had obvious antipyretic effect on the fever model induced by LPS and dry yeast in rats,and there was a certain dose-effect relationship.Conclusion Paracetamol Tablets,Compound Paracetamol and Amantadine Hydrochloride Tablets,Compound Dextromethorphan Hydrobromide Tablets,and Chaiqin Qingning Capsules has certain antipyretic effect on LPS and dry yeast fever model in rats,and on the whole,the Western medicine acts rapid but continue for a short time,while the traditional Chinese medicine acts slow but continues for a long time.
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A liquid chromatography-quadrupole-time-of-flight mass spectrometer(LC-Q/TOF-MS) based urinary metabolomic approach was employed to assess the toxicity-alleviation effect of Huangqi oral solution(HOs) on cisplatin-exposed rats and explore its possible mechanisms. Rat toxicity model was developed by multiple intraperitoneal injection of low-dose cisplatin, while HOs was orally administrated to rats simultaneously for 16 consecutive days to attenuate or reduce the cisplatin-induced toxicity. 24-hour urine samples on day 18 were collected and analyzed using LC-Q/TOF-MS to obtain the dataset of urinary metabolites. Principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA) were employed to assess the quality of the dataset and screen the potential toxicity-alleviation biomarkers. The serum level of rat creatinine and urea nitrogen on day 20 was determined, and the results showed that successive administration of HOs significantly reduced the cisplatin-induced increase of creatinine and urea nitrogen. PCA cluster analysis clearly demonstrated that HOs could partly improve the CDDP-induced abnormality of metabolic profiling. 35 urinary metabolites were finally screened as the potential biomarkers associated with the toxicity-attenuation effect of HOs, according to the combination of the analysis results of OPLS-DA, t-test and fold change analysis. Further metabolic pathway analysis revealed that HOs could restore the metabolic disorders of amino acid, energy and nucleotide, thereby exerted its toxicity-alleviation effect.
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To investigate the effect of estrogen receptor (ER) agonist 17β-estradiol and G protein-coupled estrogen receptor 1 (GPER) agonist fulvestrant on masangial cell fibrogenesis under protein kinase C (PKC),we quantified type Ⅳ collagen (COL4A1),fibronectin (FN1),connective tissue growth factor (CTGF) and transforming growth factor-β1 (TGFβ1) gene transcription and semi-quantified phosphorylation of Akt signal upon Phorbol 12-myristate 13-acetate stimulation (which increased COL4A1,FN1,CTGF and TGFβ1 gene transcription to 2.5-0.5,1.4 ±0.2,26 ± 11 and 1.9 ±0.3 times compared with baseline,P ＜0.05) when incubated with the two drugs.It was found that 17β-estradiol and fulvestrant down-regulated COL4A1,FN1,CTGF and TGFβ1 genes transcription (P ＜0.05) and Akt signaling under PKC activation via ER and GPER.ER and GPER agonists are beneficial in protecting the mesangial cells from fibrogenic stimuli by inhibiting PKC signaling and excessive extracellular matrix production.
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OBJECTIVE:To provide reference for the establishment of clinical skills evaluation system in students majored in clinical pharmacy and pharmacy of China. METHODS:Retrieved from pharmacy OSCE literatures and the related websites,phar-macy OSCE contents and evaluation in the United States,the United Kingdom,Canada,Japan,Malaysia and other countries were introduced to provide suggestions for clinical skills evaluation system in students majored in clinical pharmacy and pharmacy of Chi-na. RESULTS & CONCLUSIONS:OSCE had widely applied in medicine,nursing and other professional clinical skills,the United States,the United Kingdom and other countries had applied OSCE into pharmacy,and confirmed its important role in assessment of clinical competence in pharmacy students. There was no uniform standard in OSCE,and OSCE examinations were slightly different in different countries and different schools. Pharmacy OSCE usually based on school courses such as pharmacotherapy,clinical pharmacokinetics,medicine information,pharmaceutical care,doctor-patient communication,identification and solving ability of clinical drug-related issues. Numerous college of pharmacy in domestic colleges and universities has added the practice-based cours-es,but evaluation system and assessment methods are poor. Almost no OSCE is applied for the assessment of pharmacy students. OSCE has short application time in pharmacy education and relatively less study,therefore,pharmacy OSCE in foreign countries should be learnt to assess clinical skills of pharmacy students,establish and improve the pharmacy OSCE that is suitable for China by combining with the pharmacy education status.
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Objective To evaluate the association between C-reactive protein (CRP) blood levels and specific survival time of non-small cell lung cancer (NSCLC) patients treated with chemotherapy.Methods Data from 96 advanced (stage ⅢB/Ⅳ) NSCLC patients were analyzed.All patients were divided into two groups based on the enrolled time as follows the initial treatment group (48 cases) and retreatment group (48 cases).According to 0.6 mg/L and 7.3 mg/L of CRP which were the 1/3 and 2/3 of CRP concentrations,respectively,the 96 patients were divided into low,intermediate and high groups.Kaplan-Meier and Cox proportional-hazard models were used to evaluate the relationship between the CRP level and survival time.Results After adjusting for age,sex,smoking history,histological type and stage of lung cancer,a significant relationship between CRP and survival time was observed (P ＜ 0.05).Such significant differences of survival time were also observed in both of the adenocarcinoma (P ＜ 0.001) and squamous with poorly differentiated (P =0.032) subtypes.On stratification analysis by chemotherapy status,the circulating CRP level in retreatment group was correlated well with survival time (P ＜ 0.001).However,the influence of circulating CRP levels on survival time in initial group did not reach statistical significance (P =0.296).For all patients,the hazard ratio with high CRP levels for NSCLC-specific survival was 1.15 (95 ％ CI 0.82-1.61) compared with that of low CRP levels.The hazard ratio for the initial treatment group and retreatment group were 0.52 (95 ％ CI 0.16-1.74) and 1.77 (95 ％ CI 0.73-4.26),respectively.Patients with high circulating CRP level also responded poorly to chemotherapy.Conclusion A high level of circulating CRP is associated with an inferior response and survival outcome in NSCLC patients treated with chemotherapy.
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Objective To explore the relevance of high density lipoprotein cholesterol (HDL-C) level and resistance of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) in advanced non-small cell lung cancer (NSCLC).Methods In a total of 87 NSCLC patients harboring EGFR mutation treated with EGFR-TKI, the correlations of pre-treatment levels of soluble HDL-C between efficacy and resistance of EGFR-TKI were analyzed by Kaplan-Meier method and Cox proportional hazard model.Results Patients with normal HDL-C (≥0.94 mmol/L) had a better disease control rate (DCR) than those with low HDL-C (＜0.94 mmol/L) [94.5 ％ (52/55) vs 65.7 ％ (21/32), P ＜ 0.001].The results of univariate analysis showed that patients with normal HDL-C had longer progress free survival (PFS) (HR =0.27, 95 ％ CI 0.164-0.444, P ＜ 0.001).The results of multivariate Cox proportional hazard model analysis with sex, pathologic histology, smoking history and mutation type showed that only HDL-C group had a significant difference (P ＜ 0.001).The same results were showed when stratified by sex and smoking history (female: P ＜ 0.001, male: P =0.002;Smoker: P ＜ 0.001, non-smoker: P =0.014).Conclusion Normal pre-treatment serum levels of HDL-C are associated with a better outcome and longer progression-free survival in NSCLC patients treated with EGFR-TKI, which may be a predictive marker for a better response.
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Endothelial dysfunction plays a crucial role in the development of arteriosclerosis (AS). Accumulating evidence suggests that endothelial dysfunction is an initiating event in the etiology of arteriosclerosis. This article reviewed the relationship between endothelial dysfunction and atherosclerosis, and the effects of therapeutic drugs especially statins on endothelial dysfunction.