BACKGROUND:Studies have shown that atorvastatin can up-regulate the expression of heme oxygenase-1 and enhance the anti-inflammation and anti-oxidative damage ability of cells.However,whether atorvastatin can regulate macrophage polarization,inhibit inflammation and reduce cholesterol accumulation by inducing heme oxygenase-1 expression remains unclear. OBJECTIVE:To investigate the effect of atorvastatin on polarization,inflammation and cholesterol content of oxidized low-density lipoprotein stimulated RAW264.7 macrophages by inducing heme oxygenase-1 expression and its related mechanism. METHODS:Firstly,RAW264.7 cells were randomly divided into six groups and incubated with different concentrations of atorvastatin for 24 hours.The expression of heme oxygenase-1 protein and cell activity were detected to explore the optimal dose of atorvastatin for subsequent studies.RAW264.7 cells were randomly divided into control group,atorvastatin group and heme oxygenase-1 inhibition group.Cells were preincubated with pure medium,atorvastatin 20 μmol/L and atorvastatin 20 μmol/L + zinc protoporphyrin IX 10 μmol/L for 24 hours,and then oxidized low-density lipoprotein 50 mg/L was added for 48 hours.The polarization of macrophages was detected by flow cytometry.The secretion of inflammatory factors such as transforming growth factor β,interleukin 10,interleukin 1β,and tumor necrosis factor α was detected by ELISA.The expression levels of heme oxygenase-1,LC3II,LC3I,P62,PPARγ and ABCA1 were detected by western blot assay.The intracellular cholesterol content was measured with the oxidose method and the accumulation degree of intracellular lipid droplets was evaluated by oil red O staining. RESULTS AND CONCLUSION:(1)Atorvastatin could induce the expression of heme oxygenase-1 protein in macrophages in a dose-dependent manner.(2)Oxidized low-density lipoprotein could induce macrophages to polarize towards M1,secrete proinflammatory factors,and increase the accumulation of intracellular cholesterol.(3)Compared with the control group,the heme oxygenase-1 protein expression of macrophages was increased after atorvastatin intervention,and the cells turned to M2-type polarization and mainly secreted anti-inflammatory factors such as transforming growth factor-β and interleukin-10.PPARγ,ABCA1,LC3II/I and other signal molecules reflecting cholesterol efflux and autophagy increased,and the contents of intracellular cholesterol and lipid droplets decreased significantly(P<0.05).(4)The heme oxygenase-1 inhibition group treated with zinc protoporphyrin IX significantly reversed the above changes in the atorvastatin group.(5)The results have shown that atorvastatin may promote the polarization of macrophages stimulated by oxidized low-density lipoprotein to M2 type and inhibit inflammation by up-regulating the expression of heme oxygenase-1 and by up-regulating PPARγ/ABCA1 signaling pathway and enhancing autophagy.Atorvastatin can increase the outflow of intracellular cholesterol and reduce the accumulation of intracellular lipids.

The training of clinical pharmacists in pain specialists often focuses on the education of professional knowledge,while neglecting the important role of ethics in the teaching process.Ethical elements such as the patient's right to informed consent,privacy,health,autonomy have not received sufficient attention in the teaching process.This training model poses a potential threat to patients'rights and interests and may bring ethical risks to pharmacists.To improve teaching quality and avoid risks,lecturers and trainees should deeply understand and respect the various rights of patients,safeguard their right to health from infringement,and ensure that privacy is fully protected.In addition,the patient's right to informed consent should be implemented to allow them to make autonomous choices based on a full understanding of the treatment plan,and humanistic care should be strengthened so that patients can feel the warmth and care from the pharmacists.Through the implementation of ethical measures,the paper aims to provide useful inspirations and references for the teaching work of clinical pharmacists in pain specialists,thereby promoting clinical pharmacists to achieve comprehensive improvement in professional skills and ethical literacy,and better serving the majority of pain patients.

OBJECTIVETo investigate the expression patterns of ZEB2 and C-myc in epithelial ovarian cancer (EOC) and the associations between their expressions and the pathological features of EOC.

METHODSThe expressions of ZEB2 and C-myc proteins were detected immunohistochemically in 191 cervical cancer tissues and 13 normal ovarian tissues. The relationship between ZEB2 and C-myc protein expressions and the clinicopathological features of EOC was evaluated.

RESULTSZEB2 positive expression ratea in EOC tissues and normal ovarian tissues were 49.2% (94/191) and 30.8% (4/13), respectively (P=0.007), and C-myc positive expression rates in the two tissues were 53.9% (103/191) and 15.4% (2/13), respectively (P=0.001). A high expression of ZEB2 was positively correlated with the pathological type of the tumor (P=0.003), FIGO stage (P=0.028), T stage (P=0.002), and N stage (P=0.04), and a high expression of C-myc was positively correlated with FIGO stage (P=0.035), histological grade (P=0.039), and T stage (P=0.002). C-myc and ZEB2 expressions were positively correlated in EOC (P<0.001), and their co-expression in EOC was significantly correlated with T stage (R=0.358, P<0.001) and FIGO stage (P=0.008).

CONCLUSIONZEB2 and C-myc can promote the progression, invasion and metastasis of EOC, and their combined detection may assist in early diagnosis of EOC.

Disease Progression ; Female ; Homeodomain Proteins ; genetics ; metabolism ; Humans ; Neoplasms, Glandular and Epithelial ; genetics ; metabolism ; Ovarian Neoplasms ; genetics ; metabolism ; Prognosis ; Proto-Oncogene Proteins c-myc ; genetics ; metabolism ; Repressor Proteins ; genetics ; metabolism ; Zinc Finger E-box Binding Homeobox 2

OBJECTIVE:To provide some references for rational application of intravenous infusion drugs to ensure the safety of drug use. METHODS:Statistical analysis was made to irrational prescriptions intercepted by the pharmacy intravenous admixture service of our hospital from 2009 to 2013. RESULTS:There were 5,802 groups of irrational prescriptions from 2009 to 2013,accounting for 0.12% of total prescriptions. For the irrationality,the top three reasons were improper solvent dosage, drug overdose and improper solvent selection in order,and the involved types of drugs were mainly antimicrobial agents,anti-neoplastic drugs,common drugs and parenteral nutrition drugs (arranged from more to less). Under the pharmacist’s interven-tion,the percentage of irrational prescriptions of intravenous drugs reduced from 0.169 4% in 2009 to 0.082 8% in 2013. The decrease in the irrational prescriptions involving with improper administration was the most significant,followed by those related to drug overdose,frequency,prescribing errors errors improper solvent dosage,incompatibility and improper solvent. CONCLU-SIONS:Pharmacists’intervention can effectively reduce the irrational prescriptions and significantly promote rational use of in-travenous drugs.

Objective To investigate the expression patterns of ZEB2 and C-myc in epithelial ovarian cancer (EOC) and the associations between their expressions and the pathological features of EOC. Methods The expressions of ZEB2 and C-myc proteins were detected immunohistochemically in 191 cervical cancer tissues and 13 normal ovarian tissues. The relationship between ZEB2 and C-myc protein expressions and the clinicopathological features of EOC was evaluated. Results ZEB2 positive expression ratea in EOC tissues and normal ovarian tissues were 49.2% (94/191) and 30.8% (4/13), respectively (P=0.007), and C-myc positive expression rates in the two tissues were 53.9%(103/191) and 15.4%(2/13), respectively (P=0.001). A high expression of ZEB2 was positively correlated with the pathological type of the tumor (P=0.003), FIGO stage (P=0.028), T stage (P=0.002), and N stage (P=0.04), and a high expression of C-myc was positively correlated with FIGO stage (P=0.035), histological grade (P=0.039), and T stage (P=0.002). C-myc and ZEB2 expressions were positively correlated in EOC (P<0.001), and their co-expression in EOC was significantly correlated with T stage (R=0.358, P<0.001) and FIGO stage (P=0.008). Conclusion ZEB2 and C-myc can promote the progression, invasion and metastasis of EOC, and their combined detection may assist in early diagnosis of EOC.

Objective To investigate the expression patterns of ZEB2 and C-myc in epithelial ovarian cancer (EOC) and the associations between their expressions and the pathological features of EOC. Methods The expressions of ZEB2 and C-myc proteins were detected immunohistochemically in 191 cervical cancer tissues and 13 normal ovarian tissues. The relationship between ZEB2 and C-myc protein expressions and the clinicopathological features of EOC was evaluated. Results ZEB2 positive expression ratea in EOC tissues and normal ovarian tissues were 49.2% (94/191) and 30.8% (4/13), respectively (P=0.007), and C-myc positive expression rates in the two tissues were 53.9%(103/191) and 15.4%(2/13), respectively (P=0.001). A high expression of ZEB2 was positively correlated with the pathological type of the tumor (P=0.003), FIGO stage (P=0.028), T stage (P=0.002), and N stage (P=0.04), and a high expression of C-myc was positively correlated with FIGO stage (P=0.035), histological grade (P=0.039), and T stage (P=0.002). C-myc and ZEB2 expressions were positively correlated in EOC (P<0.001), and their co-expression in EOC was significantly correlated with T stage (R=0.358, P<0.001) and FIGO stage (P=0.008). Conclusion ZEB2 and C-myc can promote the progression, invasion and metastasis of EOC, and their combined detection may assist in early diagnosis of EOC.

Objective To study the relationship between the level of serum thrombomodulin (TM ) ,radiation dose-volume factors with acute radiation pneumonitis (ARP) .Methods 54 patients with lung cancer were given the routine 3 -dimensional conformal radiation therapy(3DCRT) and chemotherpy ,20 cases received the concurrent radiochemotherapy and 34 cases were performed the the sequential chemotherapy .The serum TM level was measured with enzyme-linked immunosorbent assay(ELISA) before radio-therapy(B-RT) and at 30 Gy(M-RT) in radiotherapy .The ARP grade was evaluated according to the criteria of the Common Ter-minology Criteria for Adverse Events(CTCAE v3 .0) by the National Caner Institute(NCI) ,grade 2 or more was taken as ARP . The relationship between the serum TM level ,dose-volume factors with ARP was analyzed .Results 20 cases (37% ) had ARP .12 cases got grade 2 ARP and 8 cases had grade 3 .The occurrence rates of ARP in the minimal lethal dose (MLD) Gy <10 and >10 groups ,V5 < 50% and ≥ 50% groups ,V10 < 40% and ≥ 40% groups ,V20 < 25% and ≥ 25% groups ,V30 < 13% and ≥ 13%groups ,TM decrease group and TM increase group after 30 Gy radiation were 8% vs .62% ,7% vs .69% ,21% vs .75% ,28% vs . 56% ,15% vs .57% and 50% vs .13% respectively ,the differences had statistical significance (χ2 = 16 .83 ,22 .29 ,14 .05 ,3 .97 , 10 .08 ,6 .46 ,P<0 .05);in the ARP group and non-ARP group ,MLD ,V5 ,V10 ,V20 and V30 were (12 ± 2) vs .(9 ± 2) ,(58 ± 10) vs .(43 ± 10) ,(42 ± 8) vs .(30 ± 8) ,(23 ± 3) vs .(19 ± 6) ,(15 ± 4) vs .(11 ± 4) respectively ,the differences had statistical signifi-cance (t= -4 .96 ,-5 .27 ,-5 .70 ,-3 .37 ,-3 .61 ,P<0 .05) .Conclusion Multiple dose-volume parameters are associated with the occurrence rate of ARP .The patients with decreased serum TM level after radiotherapy are liable to develop ARP .

Objective To explore the inheritance characteristics of SCN1A gene in familial severe myoclome epilepsy in infancy.Methods The clinical information and blood of the patients and their relatives who had febrile seizure(FS)or epilepsy history were collected.Blood genome DNA were extracted.All exons of SeN1A gene were PCR amplified and screened with denaturing high Performance liquid chromatography(DHPLC)technology,and sequence analysis was performed.Results Fourteen SME patients had FS or epilepsy family history.Five were found positive history in first class relatives and 2 of them had inherited mutations of SCN1A(C.4284+2T>C and e.1216G>T):Other9 were found positive history in second class relatives and 2 of them had de novo mutations of SCN1A.Condusions SCN1A is the pathogenic gene for SME.The same muatation of SCN1A gene can be related to different clinical phenotypes.SME patients whose first class relatives with FS or epilepsy history should be taken as the focus of SCN1A inherited mutation screening.

Objective To study the sodium channel α1-subunit (SCN1A) gene in a pair of monozygotic twins with borderland severe myoclonic epilepsy in infancy (SMEB) and its characteristic of clinical manifestations. Methods The clinical features of 2 monozygotic twins were summarized. All 26 exons of SCNIA genes were screened with denaturing high performance liquid chromatography (DHPLC), and direct sequence analysis was performed on those with abnormal elution peak. Results The proband and her sister showed typical clinical features of SMEB. The same heterozygous mutations on exon 26 which caused the related amino acid change were found among them (c. 5348C > T, A1783E). Conclusion Monozygotic twins with similar clinical phenotype of SMEB have same SCN1A gene mutation.

Objective To study the SCN1A gene in a family with partial epilepsy with febrile seizures plus ( PEFS+ ) and its characteristics of inheritance. Methods The clinical features of the 2 patients and their father were summarized. All 26 exons of SCN1A gene were screened with denaturing high performance liquid chromatography (DHPLC), and direct sequence analysis was pedormed on those with abnormal elution peak. Pyrosequencing was subsequently performed in those without abnormality in direct sequence analysis. Results The proband and his sister had the phenotype of PEFS+ . The same heterozygous mutations (AS768G) on exon 26 which caused the related amino acid change (Q1923R) were found among them. Their father had frequent febrile seizures (FS) in childhood, and seizures stopped spontaneously. No abnormality was found in direct sequence but mosaic mutation in the same site was discovered with pyrosequencing (mutation quantity was 25% ). Conclusions The mutatin of SCN1A could cause partial epilepsy. PEFS+ could be inherited, the relatives carrying the affected gene may have mild clinical symptoms, possibly resulting from the low concentration of the mutated gene due to mosaic mutation.