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.

Objective: A prognostic risk model for lung adenocarcinoma patients was established based on the cancer genome atlas(TCGA) database to explore the prognostic performance of autophagy related gene risk model for lung adenocarcinoma patients and its correlation with immune microenvironment． Methods: Clinical information and transcriptome data of lung adenocarcinoma patients were downloaded and extracted from TCGA database，and 232 autophagy-related genes were screened from the human autophagy database．cox regression analysis was used to screen out four autophagy genes independently associated with prognosis．The prognostic prediction model of lung adenocarcinoma was constructed by risk score ，and the performance of prediction model was evaluated by ROC curve．The relationship between risk scores and tumor immune microenvironment was explored using ESTIMATE ( estimation of stromal and immune cells in malignant tumour tissues using expression data) and CIBERSORT algo- rithms. Results: Thirty differentially expressed autophagy-related genes were identified in lung adenocarcinoma， of which four autophagy genes (BIRC5，ERO1A，ITGB4，NLRC4 ) could predict the prognosis of the patients. Grouped by risk score，the Kaplan-Meier analysis demonstrated that the survival rate of high-risk group was signifi- cantly lower than that of low-risk group(P＜0. 000 1) ．The ROC curve proved the accuracy of the model in predic- ting the prognosis of lung adenocarcinoma ( AUC = 0. 757 ) ．The ESTIMATE and CIBERSORT analyses revealed that the risk scoring model was associated with multiple immune cells and immune infiltrates in the tumor microenvi- ronment． Conclusion Compared with clinical data，the autophagy gene prognostic risk model can better predict the prognosis of patients with lung adenocarcinoma．In the high-risk group，CD4 + memory quiescent cells can im- prove prognosis in lung adenocarcinoma patients.

Objective: To construct nomogram to predict the risk of bone metastasis in patients with non-small cell lung cancer(NSCLC). Methods: The clinical data of NSCLC patients diagnosed in the hospital were retrospectively analyzed, including the occurrence of bone metastasis, age, gender, pathological type, smoking status, PS score, TN stage, metastasis of other sites before bone metastasis, carcinoembryonic antigen(CEA) level, alpha fetoprotein(AFP) level, serum calcium(Ca2+), serum phosphorus(P), alkaline phosphatase(ALP) level, which were determined by univariate and multivariate logistic regression analysis. Receiver operating characteristic curve(ROC) and decision curve analysis were used, DCA was used to verify the accuracy and clinical benefit of the model, and nomogram was used to visualize the model. Results: Area under the ROC curve(AUC) showed that in the modeling group(n=138) and the validation group(n=92), the AUC value predicted by combined indicators(age, gender, pathological type, CEA, ALP)(modeling group=0.792, validation group=0.629) was higher than that predicted by single indicator. Conclusion The prediction model constructed in this study has good effect and can provide reference for clinical screening of high-risk patients with bone metastasis of NSCLC.

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.

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.

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.

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.

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.

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.

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.