OBJECTIVE: To review systematically the association of dipeptidyl peptidase-4 inhibitors on pancreatitis and/or pancreatic cancer risk in type-2 diabetes mellitus. METHODS: Databases including The Cochrane Library, PubMed, Embase, Clinical Trials. gov, CNKI, WanFang Data and CBM, were searched electronically for randomized controlled trials (RCTs) of DPP-4 inhibitors in pancreatitis and pancreatic cancer risk in T2DM patients up to June 2017. Two reviewers independently screened literatures according to the inclusion and exclusion criteria, extracted data, and assessed the methodological quality of the included studies. Then Metaanalysis was performed using Rev Man 5.3 software. RESULTS: A total of 39 RCTs involving 65 189 patients were included. The results of Meta-analysis showed that there were no significant differences between the DPP-4 inhibitors group and the control group in the pancreatitis and/or pancreatic cancer adverse events (RR = 0.92, 95%CI 0.69 to 1.23, P = 0.59), pancreatitis (RR = 1.05, 95% CI 0.76 to 1.4, P = 0.79) and pancreatic cancer (RR = 0.62, 95%CI (0.35, 1.08), P = 0.09). Subgroup analyses showed there were no significant differences of acute pancreatitis events between DPP-4 inhibitors group and the control group (RR = 1.42, 95%CI 0.82 to 2.47, P = 0.21). CONCLUSION: The present Meta-analysis of RCTs data does not suggest that DPP-4 inhibitors are associated with pancreatitis and/or pancreatic cancer. Long-term clinical studies are required to further prove this conclusion.

OBJECTIVE: To explore the clinical regularities and risk factor of abnormal liver function associated with LMWH in pulmonary thromboembolism patients. METHODS: Clinical date of pulmonary thromboembolism patients in use of LMWH was collected and analyzed from January 2008 to December 2016. RESULTS: 97 cases were enrolled. Of them, there were 76 cases were assessed as probable or possible. Single factor analysis showed the the levels of Scr (P=0.000), ALT (P=0.000), AST (P=0.000), γ-GGT (P=0.000), ALP (P=0.023), co-infection (P=0.024) and Ccr (P=0.026) had statistically significant difference. Multivariate analysis indicated that co-infection (OR=1.982, P=0.022) and high level of Scr (OR=1.045, P=0.000) were the independent risk factors of abnormal liver function associated with LMWH in PTE. CONCLUSION: The incidence of abnormal liver function due to LMWH in PTE patients is high. With high level of Scr and/or co-infection patients are high-risk persons of abnormal liver function. It is necessary to dynamically evaluate the liver function during hospitalization. Symptomatic treatment can be significant if the liver function become abnormal.

In order to obtain the phase I clinical trial data safely and accurately , the subjects management is very important .The purpose of this paper is to introduce the subjects management model during recruitment , screening and observation and discuss the phase I subjects management strategy , according to the author ’ s practical experience and the working model of phase I clinical trials in hospital .

OBJECTIVE: To systematically review the safety and efficacy of dexamethasone intravitreal implant (DEX) in secondary macular edema (ME) patients. METHODS: Multiple databases were searched electronically for randomized controlled trials (RCTs) of DEX in secondary ME patients up to April 2019. Two reviewers independently screened literatures according to the inclusion and exclusion criteria, extracted data, and assessed the methodological quality of the included studies. Then Meta-analysis was performed using Rev Man 5.3 software. RESULTS: A total of nine randomized controlled trials involving 1 530 patients were included. There were 737 patients in the experimental group and 793 patients in the control group. DEX was retrieved. Anti-vascular endothelial growth factor (anti-VEGF) or sham injection were used to treat the patients in the control group. The efficacy analysis results showed that the improvement rate of best corrected visual acuity (BCVA) in DEX group was significant higher than the control group in retinal vein occlusion (RVO) patients [MD=-10.59, 95%CI: -13.96--7.23,P=0.01]. The CST/CRT decrease in DEX was significant lower than control group in diabetic macular edema(DME) patients [MD=-63.60, 95%CI: -114.83--12.37,P=0.01], but higher than the control group in RVO [MD=-114.89, 95%CI: -48.68--181.09,P=0.00]. The safty analysis results showed that the incidence of serious adverse events (SAEs) in DEX was significant higher than control group [9.36% (28/299) : 5.23%(19/363), RR=1.94, 95%CI: 1.05-3.59, P=0.04]in RVO. The cataractin DEX was significant higher in RVO [4.87%(22/452) : 0.97% (5/513), RR=5.06, 95%CI: 1.96-13.06, P=0.00] than the control group. CONCLUSION: DEX has better efficacy than anti-VEGF in DME patients. DEX is similar in efficacy but inferior in safety to anti-VEGF in patients with ME secondary to RVO.

OBJECTIVE: To systematically assess the efficacy and safety of uninterrupted novel oral anticoagulation (NOAC) in patients undergoing atrial fibrillation catheter ablation. METHODS: Databases including multiple databases were searched electronically for randomized controlled trial (RCT) of NOAC in patients undergoing atrial fibrillation catheter ablation up to October, 2018. Two reviewers independently screened literatures according to the inclusion and exclusion criteria, extracted data, and assessed the methodological quality of the included studies. Then Meta-analysis was performed using Rev Man 5.3 software. RESULTS: A total of 5 RCTs involving 1 843 patients were included. Experimental group including apixaban, rivaroxaban and dabigatran; control group using warfarin. Efficacy outcome including stroke and transient ischemic attack (TIA); safety outcome was major bleeding. RESULTS were as followsthere was no significant difference between experimental group and control group in efficacy outcome; the safety of the experimental group was significantly superior to that of the control group. CONCLUSION: Compared with warfarin, uninterrupted NOACs during percutaneous atrial fibrillation catheter ablation could reduce the risk of major bleeding and would not increase the incident of stroke and TIA.

OBJECTIVETo investigate the potential of yolk sac mesenchymal stem cells in osteogenic differentiation.

METHODSMurine yolk sacs were harvested on day 8.5 postcoitus, yolk sac cells were obtained after the yolk sacs were digested by 0.1% type I collagenase for 1 hour, the non-adherent cells were removed after being cultured for 1 hour. The adherent cells were cultured in DMEM containing of 5 ng/ml bFGF and 15% FBS, and passaged when they became subconfluent. The morphologic characteristics, and AKP, BMP-2, as well as type I, III collagen of the yolk sac adherent cells were observed and tested. The attached cells were treated with 10(-8) mol/L dexamethasone, 10 mmol/L beta-glycerophosphate, and 50 micrograms/ml vitamin C at passage 4. Alternations of morphological characteristic, AKP activity, collagen of type I, III and mineralization were detected.

RESULTSPure mesenchymal stem cells which were of spindle shape, uniform in size, positive in type I, III collagen staining and weak positive in AKP activity could be induced to pleomorphism osteoblast-like cells in vitro. The cells were transformed from spindle shape to polygonal cells which were positive in type I collagen, negative in type III collagen, strong positive in BMP-2, and positive in Von Kossa's stain at week 8. The polygonal cells could form nodular structure and their AKP activity was increased. All these were coincidence with the characters of osteoblast.

CONCLUSIONYolk sac mesenchymal stem cell can be purified and induced to osteoblast in vitro.

Alkaline Phosphatase ; biosynthesis ; Animals ; Bone Morphogenetic Proteins ; biosynthesis ; Cell Differentiation ; Cells, Cultured ; Female ; Mesoderm ; cytology ; Mice ; Osteoblasts ; cytology ; Osteogenesis ; Stem Cells ; cytology ; Yolk Sac ; cytology

OBJECTIVETo investigate the intervention effect of thalidomide on paraquat-induced acute lung injury in mice and its mechanism.

METHODSMale ICR mice were randomly allocated to negative control group (n = 30), thalidomide control group (n = 30), paraquat poisoning group (n = 30), 50 mg/kg thalidomide treatment group (n = 30), 100 mg/kg thalidomide treatment group (n = 30), and 150 mg/kg thalidomide treatment group (n = 30). The negative control group was intraperitoneally injected with the same volume of saline; the thalidomide control group was intraperitoneally injected with thalidomide (150 mg/kg); the paraquat poisoning group was intraperitoneally injected with diluted paraquat solution (22 mg/kg); each thalidomide treatment group was intraperitoneally injected with the same volume of paraquat solution (22 mg/kg) and was injected with thalidomide (50, 100, or 150 mg/kg) 1 h later. All mice were anesthetized and sacrificed at 1, 3, or 7 d after paraquat poisoning, and their lung tissue was collected. The levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 in lung tissue were measured by double-antibody sandwich ELISA; the mRNA expression of nuclear factor-kappa B (NF-κB) was measured by RT-PCR; the protein expression of nuclear NF-kgr;B p65 was measured by Western blot. The pathological changes of lung tissue were observed under light microscope; the wet/dry ratio of the lung was calculated.

RESULTSCompared with the negative control group, the paraquat poisoning group had significantly increased levels of TNF-α, IL-1β, IL-6, NF-κB mRNA, and nuclear NF-κB p65 and wet/dry ratio of the lung (P < 0.05). Compared with the paraquat poisoning group, the thalidomide treatment groups had significantly decreased levels of TNF-α, IL-1β, IL-6, NF-κB mRNA, and nuclear NF-κB p65 and wet/dry ratios of the lung (P < 0.05), and the 150 mg/kg thalidomide treatment group showed the most significant decrease in the levels of TNF-α, IL-1β, IL-6, NF-κB mRNA, and nuclear NF-κB p65. The observation of pathological changes showed that the paraquat poisoning group had the most marked lung tissue damage at 3 d after poisoning, and the lung tissue damage was lessened in the thalidomide treatment groups.

CONCLUSIONThalidomide can reduce paraquat-induced acute lung injury and lung edema. The mechanism may include inhibition of NF-κB activation and expression and downregulation of TNF-α, IL-1β, and IL-6.

Acute Lung Injury ; chemically induced ; drug therapy ; Animals ; Cytokines ; metabolism ; Disease Models, Animal ; Male ; Mice ; Mice, Inbred ICR ; NF-kappa B p50 Subunit ; metabolism ; Paraquat ; poisoning ; Thalidomide ; pharmacology ; Transcription Factor RelA ; metabolism

OBJECTIVE: To investigate the application of dinucleotide STR locus in paternity testing. METHODS: Dinucleotide STR locus D6S261 was selected and the paternity testing blood samples were amplified using 200 random blood samples, 16 family samples and 193 paternity test samples. Data of the PCR products were collected by 3130XL Genetic Analyzer and the genetic parameters of population were calculated by PowerStats v12. RESULTS: Fifteen alleles and 50 genotypes were found and H, DP, PE and PIC were 0.850, 0.953, 0.695, and 0.820, respectively. The typing results of both family samples and paternity test samples were accord with the law of inheritance, which no mutation was discovered. CONCLUSION The genetic polymorphisms of D6S261 show good characteristics with low mutation rate and high stability. It can be an effective method to solve the indetermination caused by mutation in paternity testing if the stutter bands can be decreased.
Asian People/genetics* ; Base Sequence ; Forensic Genetics/methods* ; Gene Frequency ; Genotype ; Humans ; Microsatellite Repeats/genetics* ; Nucleotides/genetics* ; Paternity ; Polymerase Chain Reaction/methods* ; Polymorphism, Genetic

Objective To investigate the distribution of related single nucleotide polymorphisms (SNPs) of drug transporters in healthy Chinese Han population.Methods 10 specific SNPs of 6 drug transporters,including organic anion transporting polypeptide 1B1 (OATP1B1),OATP1B3,organic cation transporter 1 (OCT1),P-glycoprotein (P-gp),multidrug resistance protein 2 (MRF2) and breast cancer resistance protein (BCRP),were determined in healthy Chinese Han volunteers by the established rapid polymerase chain reaction (PCR) methods and sequencing.Gene frequencies were calculated and compared with other populations in the 1000 genomes project.Results The minor allele frequencies of OATP1B1 388A ＞ G,OATP1B1 521T ＞ C,OATP1B3 699G ＞ A,OCT1 181C ＞ T,OCT1 1393G ＞ A,OCT1 1258delA,MDR1 3435T ＞ C,MRP2-24C ＞ T,BCRP 421C ＞ A and BCRP 376C ＞ T were 26.97％,6.25％,23.91％,0,0,0,38.47％,18.52％,31.97％ and 1.48％,respectively.By comparing the distribution of allele frequencies between test group and Mrican,the frequencies of the OATP1 B3 699G ＞ A variant alleles were 76.09％ and 35.63％,respectively;the frequencies of the MDR1 3435T ＞ C variant alleles were 61.53％ and 85.02％,respectively;the frequencies of the MRP2-24C ＞ T variant alleles were 18.52％ and 3.10％,respectively;the frequencies of the BCRP 421C ＞ A variant alleles were 31.97％ and 1.29％,respectively.And these differences were statistically significant (P ＜ 0.05).By comparing the distribution of allele frequencies between test group and American,the frequencies of the OATP1B1 388A ＞ G variant alleles were 26.97％ and 47.26％,respectively;the frequencies of the BCRP 421C ＞A variant alleles were 31.97％ and 14.12％,respectively.And these differences were statistically significant (P ＜ 0.05).By comparing the distribution of allele frequencies between test group and European,the frequencies of the OATP1B1 388A ＞ G variant alleles were 26.97％and 40.26％,respectively;the frequencies of the OATP1B1 521T ＞ C variant alleles were 6.25％ and 16.10％,respectively;the frequencies of the OCT1 181C ＞ T variant alleles were 0 and 6.26％,respectively;the frequencies of the BCRP 421C ＞ A variant alleles were 31.97％ and 9.44％,respectively.And these differences were statistically significant (P ＜ 0.05).There was no significant difference in the distribution of allele frequencies between test group and Japanese (P ＞ 0.05).Conclusion Significant differences were observed in the distributions of some SNPs between Chinese and other populations.It is important to analyze the distribution of the related genetic polymorphisms of drug transporters in Chinese people to guide rational drug use in clinical.

Objective To explore the clinical features and prognostic factor of acute drug induced liver injury (DILI) associated with low molecular weight heparin (LMWH) in pulmonary thromboembolism patients.Methods International recognized Roussel Uclaf causality assessment method 2015 (RUCAM) was taken as standard.Basic clinical date,prescriptions and laboratory of pulmonary thromboembolism (PTE) patients in use of LMWH was collected and analyzed.Results Among 92 patients with acute DILI,according to RUCAM,there were 82.61％ with quite high probability and high probability (≥6).The hepatocellular injury type accounted for 18 patients (19.57％),mixed type accounted 45 patients (48.91％) and cholestatic type of DILI accounted for 29 patients (31.52％).Basic analysis showed the levels of alanine transaminase (ALT),aspartate aminotransferase (AST),alkaline phosphatase (ALP) and total bilirubine (TBIL) had statistically significant difference among 3 groups (P ＜ 0.05).Multivariate analysis indicated that severe infection (P ＜ 0.05) and high level of serum creatinine (Scr,P ＜ 0.05) were the independent adverse prognostic factors of mixed type and hepatocellular injury type of DILI,respectively.There was no statistically significant difference in the time to apparent onset of the reaction,the time upon the top level of abnormal liver function and outcomes among the 3 groups of DILI (P ＞ 0.05).Conclusion It is necessary to dynamically evaluate the liver function during hospitalization especially patients are with severe infection and/or high level of Scr.Specific treatment can be necessary in according with the type of DILI.