OBJECTIVE:To determine plasma concentration of caffeine,dapsone and chlorzoxazone in rats,and to calculate pharmacokinetic parameters. METHODS:6 rats were given the mixture of caffeine,dapsone and chlorzoxazone intragastrically, 1.5,2 and 3 mg/kg,respectively. 0.2-0.3 ml blood were collected before medication and 0.5,1,2,3,4,6,8,12,24 h after medication.The plasma sample was treated with solid phase extraction. The plasma concentration of caffeine,dapsone and chlorzoxa-zone were determined by HPLC using N-(2-Hydroxyethyl) phthalimide as internal standard. The pharmacokinetic parameters were calculated using DAS 2.0 software. RESULTS:The linear ranges of caffeine,dapsone and chlorzoxazone were all 0.2-30 μg/ml (r were 0.996 4,0.996 1,0.998 8,respectively). The limit of quantitation were 0.2 μg/ml. The recoveries of low-concentration, medium-concentration and high concentration were(84.8±3.6)%-(111.4±10.2)%(RSD were 4.3%-9.8%,n=3),(107.0±13.3)%-(113.5±8.1)%(RSD were 7.1%-14.0%,n=3),(104.2±10.8)%-(111.1±12.2)%(RSD were 8.0%-11.0%,n=3). Pharmacoki-netic parameters were as follows as tmax(1.70±0.99),(1.50±1.00),(1.92±0.80)h;t1/2(0.73±0.22),(2.77±1.35),(2.78±2.34) h;cmax (2.60 ± 0.50),(5.78 ± 1.19),(9.76 ± 1.37) mg/L;AUC0-t (8.43 ± 0.79),(20.68 ± 1.91),(26.71 ± 2.45) mg·h/L(n=6). CONCLUSIONS:The method is simple,sensitive and accurate,and can be used for the plasma concentration determination and pharmacokinetic study of caffeine,dapson and chlorzoxazone.

Objective To evaluate the safety and efficacy of clinical application of three-dimensional printing technology (3D printing) in Orthopedics.Methods The safety and effectiveness of clinical application of three-dimensional printing technology in Orthopedics were analyzed by systematic review of non-control studies.Results Non-control studies showed that cortical perforation rate of screws was 3.83％ (calculated by the number of screw).Complication rate was 2.13％,surgical infection rate was 0.28％,prosthesis problematic rate was 0.79％,the average operation time was 139.23 minutes,and some results of the indicators for safety and effectiveness were similar between studies with and without control groups.Conclusion Although 3D printing application in Orthopedics has some clinical value,and its extension needs economic assessment.

Objective To assess the effect of clinical application of three-dimensional printing technology (3D printing) in Orthopedics.Methods Comparing the effect of clinical application of three-dimensional printing technology with traditional Standardized technology,through using a systematic review and Meta Analysis.Results Meta analysis of 25 studies included in the research showed that application of 3D printing reduced operation time by 26 minutes,decreased intraoperative blood loss by 77 ml,and increased accuracy rate or success rate of screw implanting(increased by 2.10 times compared with tradit onal standardized technology).Conclusion The application of 3D printing in Orthopedics has good short-term effect But its deVelopment in clinical application should be cautious.

Objective To study onclinical researches of 3D printing technology in Orthopedics.Methods Through literature search,107 literatures were included and systematically reviewed,and the status of clinical researches of 3D printing technology in orthopedics was described.Results The clinical researches of 3D printing technology in Orthopedics were mainly focused on males and adults population conducted from 2007 to 2012.3D printing technology frequently used in Orthopedics were reduction and internal fixation,deformity correction,pedicle screw placement,tumor resection,revision and reconstruction,and knee replacement.Conclusion 3D printing technology in Orthopedics is still at an initial stage of clinical development.

Adult ; Aged ; Aged, 80 and over ; DNA Primers ; Female ; Humans ; Lymphoma ; genetics ; Male ; Middle Aged ; Mutation ; Myeloid Differentiation Factor 88 ; genetics ; Polymerase Chain Reaction

Objective To detect the serum anti‐sialic acid glycoprotein receptor antibody (anti‐ASGPR) levels in the patients with chronic hepatitis B(CHB) ,chronic hepatitis C (CHC)and healthy people ,and to observe the relationship between anti‐ASGPR and the disease development in the patients with hepatitis .Methods Totally 60 patients with hepatitis B virus (HBV) infection(30 cases of CHB and 30 cases of CHB cirrhosis) and 60 patients with hepatitis C virus (HCV) infection(30 cases of CHC and 30 cases of CHC cirrhosis) were selected with 60 persons undergoing the physical examination as the control group .The anti‐ASGPR and ALT levels in all research subjects were detected with ELISA .Results (1)The anti‐ASGPR level in the HBV and HCV infection groups was significantly higher compared with the control group ,and the difference was statistically significant(P<0 .01) .The an‐ti‐ASGPR level in the CHB cirrhosis group was significantly higher than that in the CHB group ,and the difference was statistically significant(P<0 .05) .The anti‐ASGPR level in the CHC cirrhosis group was significantly higher than that in the CHC group ,and the difference was statistically significant(P<0 .05) .No correlation between anti‐ASGPR and ALT was found .(2) The anti‐ASG‐PR level in the CHC group was significantly higher than that in the CHB group ,and the difference was statistically significant(P<0 .01) .Conclusion The detection of anti‐ASGPR is helpful for clinical differential diagnosis and has an important significance for the treatment and prognosis .

ve To investigate the effects of selenium and zinc on the absorption, excretion and accumu-lation of fluoride in rats. Methods The contents of fluoride in serum, excrement, urine and bone were determined in Wistar rats drinking distilled water containing 100 mg/L NaF and orally perfused jointly with 0.1 mg/(kg? d) Na2SeO3 and/or 14.8 mg/(kg?d) ZnSO4 one time per two days continuously for 90 days. Results Na2SeO3 and/or ZnSO4 could increase the concentration of fluoride in urine, decrease the concentration of fluoride in serum and the content of fluoride in bone of rats. Exposure to ZnSO4 and joint exposure to Na2SeO3 and ZnSO4 could increase the content of fluoride in excrement. Conclusion ZnSO4 could inhibit the absorption of fluoride in intestine, Na2SeO3 and /or ZnSO4 could promote the excretion of urine fluoride and restrain the accumulation of fluoride in bone of rats.

OBJECTIVE Diabetes-induced endothelial cell (EC) dysfunction and neovasculariza-tion impairment constitute vascular complications with limited treatment regimens.Transcription factor FOXO1 is a key angiogenic regulator and plays a pathologic role in progression of diabetes.The pres-ent study was designed to determine the involvement of FOXO1 in impaired EC function and post-isch-emic neovascularization in diabetes and investigate underlying mechanisms.RESULTS We found that FOXO1-selective inhibitor AS1842856 improved blood flow recovery and capillary density in ischemic hindlimb,and rescued the delay of wound closure with a concomitant augmentation of mean perfusion rate in diabetic mice. In vitro,treatment with AS1842856 or FOXO1 siRNA abrogated high glucose-in-duced apoptosis and ameliorated capillary tube formation in human umbilical vein endothelial cells(HU-VECs). FOXO1 inhibition relieved alterations in mitochondrial networks and significantly suppressed the over production of mitochondrial reactive oxygen species(mtROS)induced by high glucose in ECs. Expression of dynamin-relatedprotein-1 (Drp1) and phosphorylation at Ser616, a protein required for mitochondrial fission, were enhanced by hyperglycemia, which could be neutralized by FOXO1 inhibition. Moreover, the transcription of Rho-associated coiled-coil containing protein kinase 1 (ROCK1), which phosphorylates Drp1 at Ser616, was shown by luciferase assay to be directly regulated by FOXO1. CONCLUSION These findings suggested that FOXO1 is critical to preserve mitochondrial quantity and func-tion in ECs,and FOXO1 may serve as a therapeutic target for microvascular complications of diabetes.

Objective:To explore the learning experience of the medical massive open online course (MOOC) teaching design standard system constructed by the research group in the early stage.Methods:In this study, the questionnaire was adapted from four dimensions: academic analysis, curriculum content design, teaching process design, and teaching evaluation design, including 519 students majoring in clinical medicine of a university who had studied MOOC cases like "Ultra-early Diagnosis and Treatment of Acute Cerebral Infarction" based on the system. SPSS 25.0 was used for statistical analysis.Results:The system had a high degree of recognition in all dimensions, with 64.5% of academic analysis, 57.6% of content design, 54.5% of teaching design process, and 59.3% of teaching evaluation design.Conclusion:The study has found that the medical MOOC teaching design system has good learning experience effect. According to the data feedback, the key teaching design points such as the core factors of learning experience analysis and the suitability of teaching content in the practical operation of teaching design has been explored, providing the practical basis and method reference for the design of medical MOOC teaching design.

Objective:To explore the seizure recurrence and prognosis of epilepsy in relapse after anti-epileptic drugs (AEDs) withdrawal, and the influencing factors for these conditions.Methods:From December 2009 to August 2018, patients from the Affiliated Brain Hospital of Nanjing Medical University who relapsed after AEDs withdrawal were collected and followed up for at least 18 months. The seizure recurrence and prognosis of these patients were prospectively observed. The Kaplan-Meier method was used for survival analysis. The associated risk factors of the second relapse in the enrolled patients were analyzed by multivariate Cox analysis. The included patients were divided into good prognosis group and poor prognosis group according to whether they had achieved seizure freedom for at least one year after the first relapse. A multivariate Cox regression model was used to analyze the independent risk factors affecting their prognosis.Results:A total of 56 patients with epilepsy in relapse after AEDS withdrawal were collected. The average follow-up period was 46.23 months (18-120 months) from the initial time of seizure recurrence, and 21 patients (37.5%) had the second seizure recurrence. The relapsing risk in patients who continued to be observed without adding AEDs was higher than those who were treated immediately with drugs [9/16 vs 30.0% (12/40)], but without statistically significant difference (χ2=2.220, P=0.071). The results of univariate analysis showed that focal seizures, seizure frequency more than once per month before remission and poly-drug therapy before AEDs withdrawal were associated with high risk of the second relapse. Poly-drug therapy was an independent risk factor for the second relapse by multivariate Cox analysis ( HR=3.383, 95% CI 1.257-9.105). Of the 56 patients with epilepsy in relapse after AEDs withdrawal, 47 patients (83.9%) had a good prognosis without seizure for at least one year, and of 33 patients who were followed up for three years or more, 26 (78.8%) had no seizure for at least two years. Between the group retreated immediately after the first recurrence and the group without immediate treatment [87.5% (35/40) vs 12/16],there were no statistically significant differences on the proportions of good prognosis (χ2=2.333, P=0.258). Univariate analysis showed that the course of epilepsy>6 months before initial treatment, the frequency of seizures>1/month before remission, symptomatic epilepsy and poly-drug therapy were associated with the poor prognosis. However, none of independent risk factors was found for the poor prognosis through the multivariate analysis. Conclusions:The prognosis of patients with epilepsy in relapse after AEDs withdrawal is well, and about 2/3 patients with epilepsy in relapse after AEDs withdrawal have no more seizure recurrences. The poly-drug therapy before AEDs withdrawal may be an independent risk factor for the second seizure relapse.