OBJECTIVE:To promote the normative management of clinical off-label drug use. METHODS:The degree of devi-ation from the drug instructions and the risk degree were comprehensively considered,and the off-label drug use were classified in-to three different situations for classifying approval and informed consent classifying;situation and effects after classifying were evaluated. RESULTS:The classifying included occasional or small amount off-label use on dosage and drugs solvent (the first), regular off-label use on route or administration(the second)and super-indications drug use with contraindications(the third). The approval was classified as follows as confirmed with signature by doctor,approved by medical department,approved by pharmaceu-tical committee and ethics committee accordingly;informed consent classifying were signing informed consent,informing and re-cording in medical record,informing orally. Off-label drug use approval process was officially initiated from Feb. 2014 to Jun. 2016 in our hospital,51 off-label drug use applications from 13 clinical departments were received,with 16 items belonging to the second situation,35 items belonging to the third. Finally 42 applications were approved and 9 were not. No relevant new/serious ad-verse drug reactions/ events occurred in process of the approved off-label drug use. And no off-label drug use not approved was found to continue to be used in our hospital. CONCLUSIONS:Classification management methods for off-label drug use in our hos-pital have shown high operability,improved the off-label drug use behavior of physicians.

Objective:To explore the content and model for clinical pharmacists to carry out pharmaceutical care on elderly pa-tients with atrial fibrillation combined with other diseases treated by warfarin. Methods:One case of an elderly atrial fibrillation patient complicated with coronary artery disease and urinary tract infection suffering elevated INR after the use of warfarin was applied as the example. The pharmaceutical care was carried out by clinical pharmacists including analyzing the causes of elevated INR and assisting the doctor to develop the individualized pharmaceutical care plan. Results: After the adjustment of warfarin dose and the other drugs combined with medical education, bleeding and thromboembolic events did not occur during the hospitalization, and finally, satisfactory effect of anticoagulation therapy was achieved. Conclusion: The implementation of pharmaceutical care on anticoagulation in atrial fi-brillation patients with various diseases is helpful to improve the compliance in patients, avoid the occurrence of adverse drug reactions and guarantee the effectiveness and safety of warfarin.

OBJECTIVE:To investigate the efficacy and mechanism of ademetionine for treating hyper-unconjugated bilirubinemia in neonate rats.METHODS:The model of hyper-unconjugated bilirubinemia was established in 95 neonate SD rats by subcutaneously injection of phenylhydrazine hydrochloride,then the rats were randomly assigned to model control group(treated with normal saline),therapeutic control group(phenobarbital/nikethamide)and the therapeutic group(s-adenosyl-1-methionine)q.d for 7 days all by intraperitoneal injection.Blood samples were taken at different time for the analysis of the hepatic BUGT activity and serum bilirubin.RESULTS:In therapeutic control group compared with the model control group,the serum unconjugated bilirubin was lower,and the hepatic BUGT activity of therapeutic was higher(P

OBJECTIVE: To explore the relationship of cathepsin L (CatL) with coronary heart disease (CHD), severity of coronary stenosis and risk factors of CHD. METHODS: A total of 137 CHD patients and 48 controls were included in the study, to determined the serum levels of CatL, high sensitive C reactive protein (hs-CRP), fasting glucose (FBS), total cholesterol, triglyceride, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C), apolipoprotein A1(Apo-A1) and apolipoprotein B. All the subjects were invited for a coronary angiography, using the sum of the Gensini scores to assess the severity of coronary artery stenosis. RESULTS: Serum CatL levels were significantly higher in CHD patients (5.63 +/= 0.12 microg/L) than non-CHD subjects (3.93 +/= 0.22 microg/L, P<0.01). CatL was an independent risk factor of CHD in Logistic regression analysis [Exp(B)=2.341, 95%CI 1.567 approximately 3.496, P<0.01]. Serum CatL levels were associated positively with the Gensini scores(r=0.228, P<0.01); In fact, CatL was an independent correlator of Gensini scores (P<0.05). CatL inversely associated with HDL-C (r=-0.228, P<0.01) and ApoA1(r=-0.187, P<0.05), and positively with FBS(r=0.161, P<0.05). CONCLUSION CatL is involved in the pathogenesis of CHD. Serum CatL levels could reflect the severity of coronary luminal narrowings. CatL might participate in glucose and lipid metabolic disorders.
Case-Control Studies ; Cathepsin L ; blood ; Coronary Disease ; blood ; pathology ; Female ; Humans ; Logistic Models ; Male ; Middle Aged ; Risk Factors

Objective To investigate the differential metabolites of lymph node metastasis in pancreatic ductal carcinoma (PDAC) and provide new ideas for the pathogenesis, early diagnosis and treatment of metastatic pancreatic cancer. Methods Forty serum specimens of patients with pancreatic ductal carcinoma were collected and divided into lymph node metastasis group (18 cases) and non-metastasis group (22 cases). Thirty-one serum specimens were also collected from the healthy control group. Liquid chromatographytandem mass spectrometry was used to analyze the differential metabolites and metabolic pathways between patients with PDAC and healthy controls as well as between lymph node metastasis and non-metastasis groups. Results Principal component analysis and partial least squares-discriminant analysis revealed statistically significant differences in metabolites and metabolic pathways between patients with PDAC and the healthy controls and between lymph node metastasis and non-metastasis groups. The differences in profiles were also statistically significant. Seventy-six different metabolites and 11 metabolic pathways were screened between patients with PDAC and the healthy controls, among which phenylalanine metabolism and histidine metabolism were the two most influential metabolic pathways. Four different metabolites were screened between lymph node metastasis and non-metastasis groups, and the expression of ethopropazine and phenylalanine were upregulated but the expression of tetrahydrodeoxycorticosterone and oxprenolol were downregulated. Conclusion Metabolites are significantly altered in the lymph node metastasis group of patients with PDAC compared with the non-metastasis group. Ethopropazine, phenylalanine, tetrahydrodeoxy corticosterone, and oxprenolol are potential biomarkers of lymph node metastasis in patients with PDAC.

Objective:This study aims to explore the pathogenic roles of protein S-nitrosylation modification in the development of severe acute pancreatitis, and provide new insights into the molecular mechanisms driving acute pancreatitis development.Methods:Thirty two Sprague Dawley (SD) rats were randomly divided into sham operation group, mild acute pancreatitis (MAP) group, severe acute pancreatitis (SAP) group and SAP + N-nitro-L-arginine methyl ester (L-NAME) group (treated with nitric oxide synthase inhibitor), 8 rats in each group. All rats were sacrificed to take blood from heart and pancreatic tissues 24 h after model construction. Total protein S-nitrosylation modification level in pancreatic tissues was quantitated by the biotin-switch method, followed by histological evaluation via hematoxylin and eosin (HE) staining. The serum endotoxin, D-lactic acid, diamine oxidase, interleukin-6 and tumor necrosis factor-ɑ(TNF-ɑ), amylase, alanine aminotransferase, urea nitrogen and calcium ions in rat were detected. Pearson correlation analysis was used to analyze the correlation between each index and protein S-nitrosylation.Results:Compared with the sham operation group, the modification level of protein S-nitrosylation in pancreatic tissue of MAP group increased significantly ( P<0.05); Compared with MAP group, the modification level of protein S-nitrosylation in pancreatic tissue of SAP group increased significantly ( P<0.05); Compared with SAP group, the modification level of protein S-nitrosylation in pancreatic tissue of SAP + L-NAME group decreased significantly ( P<0.05). HE staining showed that the degree of pancreatic necrosis and inflammatory cell infiltration in SAP + L-NAME group were significantly weaker than those in SAP group. The concentrations of serum endotoxin, diamine oxidase, D-lactic acid, IL-6 and TNF-ɑ, amylase, alanine aminotransferase, and urea nitrogen in the MAP group were significantly higher than those in the sham operation group (all P<0.05); The above indexes in SAP group were significantly higher than those in MAP group and sham operation group (all P<0.05); The above indexes in SAP + L-NAME group were significantly lower than those in SAP group (all P<0.05). The serum IL-6 and TNF-ɑ levels in rats with acute pancreatitis were positively correlated with protein S-nitrosylation in pancreatic tissue (all P<0.05). Conclusions:Protein S-nitrosylation modification plays essential roles in the development and progression of severe acute pancreatitis.

OBJECTIVE： To provide reference for rational use of estradiol （E2） preparation in clinic. METHODS： The medical records of outpatients receiving assisted reproductive technology （ART） and E2 preparation [Estradiol valerate tablets （EV）， Complex packing estradiol tablets/estradiol and dydrogesterone tablets （EP）， Estradiol gel （EG）] were collected from the reproductive medicine center of a hospital during Jan. 2016-Mar. 2017. Taking drug instruction as standard， the rationality of medical records was evaluated from aspects of indication， route of administration， contraindication， usage and dosage， treatment course， etc. At the same time， these patients were followed up by telephone or outpatient service， and their pregnancy outcomes and ADR were summarized. RESULTS： A total of 12 646 prescriptions were collected， and 7 222， 3 912， 181 and 1 331 prescriptions used EV， EP， EG and EV+EP， respectively. The types of off-label use included over-indication， over-route and over-contraindication， and the rates of off-label use rates were 100％， 11.73％ and 43.60％， respectively. A total of 5 868 ART patients were involved； 439 patients received fresh embryo transplantation， and 5 429 patients received frozen-thawed embryo transplantation， involving 720 and 11 926 prescriptions， respectively. The rates of off-label use of above E2 preparations were 100％ （except for fresh embryo transplantation patients using EG）. As of Feb. 2018， the infant-holding rates of ART patients using EV， EP， EG and EV+EP were 85.29％， 85.37％， 86.36％ and 85.45％， respectively. No relevant ADR and neonatal birth defect was found. CONCLUSIONS： The phenomenon of off-label use of E2 preparations is widespread in the reproductive medicine center of the hospital. Although there is no indication of related safety risks， evidence-based evaluation should be carried out by enlarging the sample size in clinical practice， and careful use.

Objective: To discuss the relationship between lingual tonsil hypertrophy and laryngopharyngeal reflux. Methods: Ninety-two patients who received throat surgery in Nanfang Hospital between October 2015 and October 2016 were enrolled. Twenty-six healthy volunteers were recruited as normal controls. All participants were assessed with the reflux finding score(RFS) and the size of lingual tonsils were evaluated using a clinical grading system proposed by Friedman under electronic laryngoscope. The score of reflux symptom index(RSI), personal history and medical history were gathered. Biopsy specimens of lingual tonsils were taken from all participants for the immunohistochemical stain of pepsin.SPSS 19.0 software was used for statistical analysis. Results: There were 46.2% (12/26) pepsin-positive and 53.8% (14/26) pepsin-negative volunteers in normal controls. There were 87.0% (80/92) pepsin-positive and 13.0% (12/92) pepsin-negative patients in study group. The severity of lingual tonsil hypertrophy and expression intensity of pepsin in patients were significantly higher in volunteers (Z=-3.636, Z=-5.273, P<0.01). The severity of lingual tonsil hypertrophy was positively associated with the pepsin level in patients (r=0.556, P<0.01). The patients with pepsin-positive expression showed significant correlation between lingual tonsil hypertrophy and the positive rate of RSI and RFS (r=0.258, r=0.225, P<0.05). Analysis of correlated factors indicated that lingual tonsil hypertrophy was associated with smoking (χ²=8.502, P<0.05). Conclusions The expression of pepsin can be detected in lingual tonsil tissues. The lingual tonsil hypertrophy is closely related to laryngopharyngeal reflux.

OBJECTIVE To explore the role of clinical pharmacists in identifying paroxysmal spasms caused by drugs， and provide reference for rational drug use. METHODS Retrospective analysis was conducted on pharmaceutical care provided by clinical pharmacists for a patient with ceftazidime-avibactam （CZA-AVI） induced paroxysmal spasms. The clinical pharmacists identified， analyzed and summarized the clinical manifestations， risk factors and treatment methods of the nervous system toxicity caused by antibacterial drugs. According to the patient’s clinical symptoms and test results， the clinical pharmacists recommended temporarily discontinuing the use of polymyxin B and montelukast sodium， and halving the dose of CZA-AVI. The physicians did not adopt the recommendation to halve the dose of CZA-AVI， and when the patient’s neurologic toxicity did not improve， the clinical pharmacists again recommended discontinuing CZA-AVI， which was accepted by the physicians. RESULTS Clinical pharmacists analyzed the condition and checked related drugs that caused paroxysmal spasms of extremities one by one， and finally determined that CZA-AVI might be the drug that caused paroxysmal spasms of extremities in the patient. After stopping the drug， the patient’s symptoms improved and was transferred to a community hospital for rehabilitation treatment. CONCLUSIONS The dose of CZA-AVI should be adjusted according to the renal function and the neurotoxicity should be guarded against， especially for patients with advanced age， renal insufficiency， and the combined use of multiple drugs related to nephrotoxicity and neurotoxicity.

OBJECTIVE To establish evaluation criteria for rational drug use of atosiban in clinic， and to provide reference for rational drug use of atosiban in clinic. METHODS Based on the drug instructions of atosiban acetate injection and related guidelines， the experts of the Evaluation Group of Rational Drug Use formulated the evaluation criteria of rational drug use， including 5 primary indexes and 8 secondary indexes. The weight coefficients of secondary indexes were calculated by analytic hierarchy process （AHP）， and the use of atosiban acetate injection in 190 pregnant women from the Third Affiliated Hospital of Guangzhou Medical University （referred to as “our hospital”） was evaluated retrospectively by technique for order preference by similarity to an ideal solution （TOPSIS）. The evaluation results were divided into three levels including reasonable， basic reasonable and unreasonable application based on the relative approach degree. RESULTS Among 190 pregnant women， 49 （25.8%） were treated with atosiban reasonably， 39 （20.5%） were treated with atosiban basic reasonably， and 102 （53.7%） were treated with atosiban unreasonably. The evaluation results obtained by AHP-TOPSIS method were consistent with the actual situation in clinic. The main problems of the unreasonably use were super indications， unreasonable usage and dosage， over the course of treatment and the lack of proper economic consideration. CONCLUSIONS The rationality evaluation criteria of atosiban’s clinical application are established by AHP-TOPSIS method； the evaluation results obtained by this method are quantifiable， scientific and reliable. The unreasonable use of atosiban is common in our hospital， and the management should be strengthened in clinical application.