OBJECTIVE: To provide reference for dealing with the problems arose from unlicensed and off-label drug uses.METHODS: The rationality of unlicensed and off-label drug uses and the possible problems induced by which were analyzed.RESULTS: The existence of unlicensed and off-label drug used has its rationality,and it also in line with the international practices,but it may cause some problems related to policy,laws and regulations and medication safety etc.CONCLUSION: The concerned department and trade association should attach great importance to unlicensed and off-label drug uses and establish a generally accepted principle and strategies to tackle the problems.

Objective To explore the effect of inhibiting Akt phosphorylation on tumor necrosis factor related apoptosis inducing ligand (TRAIL)-induced apoptosis of human non-small cell lung cancer (NSCLC) H1299 cells with wild type EGFR and KRAS.Methods The TRAIL-induced apoptosis was examined by the Annexin V-FITC/PI.The expressions of TRAIL-activated Akt phosphorylation and p-Akt were measured by Western blot.After cells were treated with LY294002, an inhibitor of PI3K-Akt pathway, Annexin V-FITC/PI and Western blot were used to analyze the alteration of TRAIL-induced apoptosis and Akt phosphorylation, respectively.Results H1299 cells were not sensitive to TRAIL-induced apoptosis.When TRAIL concentration was 100 ng/ml, the apoptosis rate of the test group was significantly higher than that of the control group [(15.06±1.29) ％ vs (3.56±0.50) ％, t =66.953, P =0.000].When TRAIL concentration was 500 ng/ml, the difference was not statistically significant compared with apoptosis rate of 100 ng/ml TRAIL group [(18.65±2.09) ％ vs (15.06±1.29) ％, t =2.423, P =0.136].The expression level of Akt phosphorylation in H1299 cells was increased by TRAIL in a time-dependent way.When cells were pretreated with LY294002, TRAIL-induced Akt phosphorylation was suppressed to baseline level.At the same time, the apoptosis rate in LY294002-treated group was significantly higher than that in TRAIL group [(41.65±4.62) ％ vs (15.82±0.61) ％, t =39.028, P =0.001].Conclusions TRAIL-induced Akt phosphorylation can antagonize TRAIL-induced apoptosis.Inhibition of Akt phosphorylation can significantly enhance the sensitivity of NSCLC H1299 cells with wild type EGFR and KRAS to TRAIL-induced apoptosis.

This article reviews the health-related home safety assessment methods for the elderly, and briefly introduces the development process of the "Person-environment fit" model from the concept, to the risk assessment method of environmental factors and then to the interactive risk assessment method of human-environment factors.Especially, this article introduces several risk assessment methods of residential environment, such as "The Enabler" human function and environmental obstacle assessment tool, the Safety Assessment of Function and the Environment for Rehabilitation(SAFER), the Safety Assessment of Function and the Environment for Rehabilitation-Health Outcome Measurement and Evaluation(SAFER-HOME), the Westmead Home Safety Assessment(WeHSA), the Home Falls and Accident Screening Tool(HOME FAST), the Cougar Home Safety Assessment(CHSA), the in-Home Occupational Performance Evaluation(I-HOPE), the In-Home Occupational Performance Evaluation for Providing Assistance(I-HOPE Assist), the In-Home Medication Management Performance Evaluation(HOME-Rx).

AIM To investigate the inhibitory effect of pycnogenol on generation of advanced glycation end products (AGEs) in vitro. METHODS Advanced glycation end products were determined by fluorospectrophotometer in the medium of 1 mol?L -1 glucose and 5% bovine albumin incubated at 37℃, 50℃, and 70℃ for different times. The inhibitory effect of pycnogenol was confirmed by the same system incubated with or without pycnogenol at different concentrations. RESULTS The rate of generation of AGEs in vitro was related with incubation time and incubation temperature. The generation of AGEs was inhibited by pycnogenol in vitro. The inhibitory rate was 10%～80% dependent on concentration and incubation time of pycnogenol. The inhibitory effect of pycnogenol on generation of AGEs was almost the same as that of Aminoguanidine at the same concentration. CONCLUSION pycnogenol could significantly inhibit generation of AGEs in vitro.

Objective To evaluate the practicability of CHROMagar orientation medium combined with simple biochemical tests for identification of common oxidase-negtive gram-negative bacilli.Methods The CHROMagar orientation medium was used together with biochemical tests including indole test , ornithine decarboxylase test and lysine decarboxylase test for identification of common oxidase -negtive gram-negative bacilli.The sensitivity, specificity, likelihood ratio, Youden index and Kappa value of the diagnostic assays were evaluated .McNemar test was performed to evaluate facticity, accuracy and cost of the method in com-parison with the Vitek-2 system as reference method .Results The identification of oxidase-negtive gram-negative bacilli from 318 bacterial strains showed that the sensitivities and specificities of CHROMagar orien-tation mediumm in combination with simple biochemical tests to Serratia marcescens, Stenotrophomonas mal-tophilia and Acinetobacter baumannii reached 100%, and for Escherichia coli, Enterobacter aerogenes and Klebsiella pneumoiae were above 90%.The specificities for identification of Enterobacter cloacae, Klebsiella oxytoca, Citrobacter freundii and Proteus mirabilis were all above 90%, but the sensitivities were around 75%-90%.Kappa values of the assays were above 0.85, howerer, which was only 0.5947 for Citrobacter freundii.McNemar test showed that all P values were above 0.05, and cost of the assays was reduced by 90%.Conclusion CHROMagar orientation medium in combination with simple biochemical tests is a cost-effective assay for identification of common oxidase-negtive gram-negative bacilli .

Aim To investigate the inhibitory effect of Bupleurum chinense-Scutellaria baicalensis decoction(CQ)on activation of rat HSC induced by CCl4 and the mechanism.Methods Cells in logarithmic growth phase were cultured in culture medium without FBS for 24 h.After disassociated using 0.25％EDTA-trypsin,the cells were seeded into respective plates at the density of 1.5×109· L-1 and cultured overnight.The cells were divided into the following groups:control group(no treatment),model group(treated with 6 mmol·L-1 CCl4 for 24 h),CQ groups(pretreated with 6 mmol·L-1 CCl4 for 24 h and 400,500,600 mg·L-1 CQ for 24 h).Concentrations of hyaluronidase(HA),laminin(LN),procollagen Ⅲ(PCⅢ),collagen type Ⅳ(Ⅳ-C)were assayed by ELISA kits.Gene expressions of Toll-like receptor 4(TLR4)and NF-κB were examined by RT-PCR analysis.Protein expression of TLR4 and NF-κB was examined by Western blot.Results CQ could significantly inhibit cell proliferation induced by CCl4.Furthermore,CQ at 600 mg·L-1 significantly downregulated gene and protein expressions of TLR4 and NF-κB.And CQ reduced the secretion of HA,LN,PCⅢ,Ⅳ-C.Further studies disclosed that the TLR4 inhibitor TAK-242 and NF-κB inhibitor BAY 11-7082 could significantly inhibit the gene and protein expressions of NF-κB,but could not change gene and protein expression of TLR4,and reduced the secretion of HA,LN,PCⅢ,Ⅳ-C.Conclusion CQ could inhibit inflammatory responses in HSC induced by CCl4 probably by inhibiting the transcription activity and protein expression of TLR4-NF-κB,which indicates its possible therapeutic effect on liver fibrosis.

Objective To explore the clinical value of MRI in diagnosing and treating cesarean scar pregnancy (CSP).Methods A retrospective analysis was conducted on the clinical manifestations of 54 patients diagnosed with CSP between January 2009 to January 2013 in Peking University Third Hospital.Based on the patients' MRI image and other clinical datas,we did transvaginal operation on patients with CSP1,and transvaginal combined with abdominal operations on patients with CSP2.The intraoperative blood loss,operation time,postoperative hospital stay,and the length of time required for of serum hCG dropping to normal of the patients were analyzed.Results The average age of the 54 patients was (34±5) years and the average duration of gestation was (56± 16) days,all patients' vital sign were stable,the hCG level was 23-142 962 U/L before treatment.Twelve patients were diagnosed with CSP1 by MRI,and 5 of them had focus of 1-2 cm in diameter,the 5 patients' serum hCG level was 436-1 159 U/L and 23-32 days after drug administration,their hCG level returned to normal; the other 7 patients had focus of 2.0-4.4 cm in diameter,and their hCG level was 2 218-63 446 U/L,lesion resection was done on the 7 patients by hysteroscope or under B-uhrasound monitor.Forty-two patients were diagnosed with CSP2,and their focus were 1.0-7.1 cm in diameter,and serum hCG level were 23-142 962 U/L.We did bilateral uterine artery occlusion by laparoscope or laparotomy during operation for 22 patients or bilateral uterine artery embolization (UAE) before operation for 20 patients,then we did lesion resections.The blood loss during operation of CSP1 or CSP 2 was 50.1,267.2 ml; operation time was 30,128 minutes; postoperative hospital stay was 4.6,6.7 days;their serum hCG returned to normal 13-30 days after the surgery.All the 54 patients' uterus were preserved,and the patients undergoing operations were all cured without the second operation.Conclusion MRI is an effective method to conduct clinical treatment in CSP.

Objective To explore the security of exosome derived from human umbilical cord mesenchymal stem cell(huc-MSC-exosome)as a kind of biological product on clinical application.Methods huc-MSC-exosome were separated by ultea centrifuge. CD9 and CD63 expression of huc-MSC-exosome were tested by Western-blot.Nanoparticle analysis was used to detect the size and concentration of huc-MSC-exosome.Hemolytic experiment,systemic anaphylaxis and blood routine test were used to verify the self-safety of huc-MSC-exosome.Results huc-MSC-exosome expressed specific markers of exosome,CD9 and CD63.Moreover,huc-MSC-exosome cannot result in hemolysis,systemic anaphylaxis reaction and abnormality of blood routine test.Conclusion Exosome derived from human umbilical cord mesenchymal stem cell has general signs of exosomes and possesses the certainly security,which may provide the experimental evidence for huc-MSC-exosome clinical application.

Objective To explore the risk factors of lung cancer in non-smoking Chinese women and to provide evidence for lung cancer prevention and control.Methods Information was collected on case-control studies published in the journals,both nationally and internationally from January,1995 to November,2014 that reported correlations between lung cancer and risk factors.Pooled odds ratio (OR) and 95％ confidence interval (CI) of risk factors on lung cancer in non-smoking Chinese women were calculated,using the Meta-analysis method,with sensitivity and publication bias tested.Results Information on 24 case-control studies was selected including 11 946 cumulative cases and 12 596 controls.Pooled ORs (95％CI) were shown as:history of lung diseases 1.89 (1.57,2.27),history of tuberculosis 1.86 (1.53,2.27),history of chronic bronchitis 1.51 (1.04,2.19),family history of cancers 2.02 (1.67,2.44),family history of lung cancers 2.45 (1.80,3.34),passive smoking (at workplace in adult period 1.47 (1.28,1.69),at home in adulthood 1.22 (1.09,1.36),in all life's time 1.52 (1.29,1.79),kitchen smog while cooking 2.21 (1.27,2.96),position of kitchen 1.76 (1.48,2.09),and frequency of deep frying per week 2.24 (1.61,3.12) etc.respectively.Conclusion Major risk factors related to lung cancer in non-smoking Chinese women would include lung diseases,family history of cancers,and passive smoking (tobacco smog and cooking smog).Particularly,the combination of family history and the degree of cooking presented stronger correlation effects,indicating that genetic and environmental factors jointly played an important role in the development of lung cancer.

Objective:To investigate the clinical features and influencing factors of early-onset gout.Methods:Male patients with gout admitted to Department of Endocrinology and Metabolism were recruited from 2015 to 2018. Patients with gout onset before age 30 were defined as the " early-onset" group, and those with onset at 30~60 years were defined as the "late-onset" group. Clinical characteristics were compared between two groups. Factors associated with early-onset gout were analyzed.Results:A total of 1 243 male patients were enrolled in this study; 480 individuals were in the early-onset, and 763 in the late-onset groups. Compared with the late-onset group, patients with early-onset gout had higher consumption rates of sugar-sweetened beverage(28.0% vs 15.0%, P=0.001), a higher homeostasis model assessment for insulin resistance level(3.78±2.93 vs 3.10±2.39, P<0.01), and larger proportions of family histories of diabetes(30.8% vs 20.4%, P<0.01)and hypertension(51.2% vs 42.6%, P=0.003). Logistic regression analysis showed that factors associated with early-onset gout were drinking sugar-sweetened beverage( P=0.012), family history of diabetes( P=0.037). Conclusion:Early-onset gout was associated with a family history of diabetes. Patients with family histories of diabetes are more likely to have early-onset gout, which may be associated with a common genetic basis.