An LC-MS/MS method was developed to investigate the pharmacokinetic parameters in healthy Chi-nese volunteers following single and multiple oral administration of dimemorfan phosphate. In the Single-dose study,two-period and crossover study was conducted in 12 healthy volunteers,which were administered with single-dose of 10 mg or 40 mg of dimemorfan phosphate. And another 12 volunteers were administered with 20 mg. The values of AUC0-48 h,t1/2,and cmax were (11. 81 ±14. 46),(52. 60 ±96. 01 )and (34. 70 ±29. 59)ng. h/mL,(12. 11 ±2. 54),(12. 16 ±2. 01)and (12. 77 ±1. 27)h,and (0. 9653 ±0. 8178),(3. 150 ±3. 451)and (2. 167 ±1. 650)ng/mL for 10 mg,40 mg and 20 mg oral administration. The same 12 healthy volunteers as the group of single-dose of 20mg were participated in multiple-dose study,which were administered dimemorfan phos-phate 20 mg,three-time a day until the day-8,showed AUC0-48 h,t1/2,and cmax were (115. 9 ±135. 2)ng.h/mL, (11. 22 ±1. 61)h,and (7. 418 ±7. 010)ng/mL. The accumulation parameter Rcmax and RAUC was (3. 14 ±1. 34) and (3. 38 ±1. 22),respectively. Dose proportional of cmax and AUC was not concluded ranging from 10 mg to 40 mg after confidence interval criteria method. An accumulation was occurred after multiple -dose administra-tion with the consequence. And the results demonstrated significant individual difference.

The effect of realgar nanoparticles (NPs) on endogenous small molecules in rat kidney was analyzed by mass spectrometry-based metabolomics.The relationship between the changes of metabolites and the nephrotoxicity of realgar NPs was also discussed to provide a basis for the further toxicity study and the clinical application of realgar NPs.SD rats were randomly divided into seven groups,including control group,three doses (40,200,1 000 mg/kg) of relegar and realgar NPs groups,respectly.After 28 days of continuous intragastric administration,all rats were sacrificed and their serum and kidney samples were collected.The toxic effect of realgar NPs on kidney tissues were examined by biochemical analysis and histopathologic examination,which revealed a dosedependent nephrotoxicity induced by realgar NPs.The LC-MS and GC-MS analysis were performed for the subsequent metabolomics study.A series of 32 metabolites were found to be altered significandy in the kindey of realgar NPs treated rats,and might serve as potential nephrotoxicity biomarkers.The results of metabolic pathway analysis indicated that the nephrotoxicity of realgar NPs might be associated with the disorders of the amino acids and phosphatidic acid metabolism.

Objective To analyse the clinical efficacy of combined therapy of super-pulsed CO2 laser and traditional Chinese medicine on the prevention and treatment of post-traumatic hypertrophic scar, and to discuss effective comprehensive therapy for hypertrophic scars. Methods 108 cases of early post-traumatic hypertrophic scar were divided randomly into three groups with 36 cases each: combined treatment group of super-pulsed CO2 laser and traditional Chinese medicine (combined group), Chinese medicine treatment group (Chinese medicine group) and simple laser-treated group (laser group). They were regularly treated for 6 months and followed up for longer than 1 year. Clinical effects were evaluated according to scar property and subjective symptoms in patients. Results The total effective rate was 97.2 % and 86.1% in combined group and Chinese medicine group that were higher than 61.1 % in laser group. Obviously effective rate of the three methods were 55. 6 %, 27.8 % and 11. 1 %, respectively, and the difference of obviously effective rate between combined group and other two groups was significally different. Conclusion The method combined with super-pulsed CO2 laser and traditional Chinese medicine for prevention and treatment of post-traumatic hypertrophic scar has advantages of high obviously effective rate, long-term and stable effects, less complication, and it can achieve satisfactory cosmetic effects.

Objective To establish a high-performance liquid chromatography-tandem mass spectrometry(LC-MS/MS)method for the simultaneous determination of seven vitamin Bs(VBs)in rat plasma.Methods The plasma samples were pretreated using the protein precipitation method.The chromatographic separation was achieved using an Agilent ZORBAX SB-Aq column(2.1 mm×150 mm,3.5 μm),with a mobile phase composed of 0.01%formic acid(A)and methanol(B)in a gradient elution mode.The flow rate was set at 0.3 mL·min-1 and the column temperature was maintained at 30℃.Mass spectrometric detection was performed using positive ion mode in multiple reaction monitoring.2,4,5,6-Deuteronicotinamide was used as the internal standard.Results Methodological validation results showed that the lowest limits of quantitation(LOQs)for the seven VBs ranged from 7.5 to 300 ng/mL,while the highest LOQs ranged from 1 000 to 20 000 ng·mL-1.Within a certain concentration range,all compounds showed a good linearity(r2>0.992 2).The accuracies ranged from 86.0%to 117.6%,and both intra-and inter-batch precision were less than 20%.Additionally,all analytes demonstrated extraction recoveries greater than 86.1%.No significant matrix effects were observed,and the stability was good.The established validation method was successfully applied to the pharmacokinetics study of single intragastric administration of VB solution in SD rats.Conclusion The analytical method established in this study is simple,rapid,sensitive,and exclusive for the simultaneous determination of VB in real plasma samples.This LC-MS/MS method provides a new analytical tool for further exploring the physiological and pathological effects of VB.

Objective:In order to determine the development potential of human embryos in vitro, amino acid and carnitine levels were measured in the culture medium of different grades of early human embryos. Methods:From the infertile couples who received in vitro fertilization-embryo transfer treatment in the Department of Reproductive Medicine of Linyi People′s Hospital from June 2022 to December 2022, the age of the women was defined as 25-35 years old [31.5(26.5, 33.25)] with 8-20 eggs, 126 cultured cells and embryos of the third day were randomly collected from infertile couples. They were divided into three groups according to the morphological level of the corresponding embryos: excellent, neutral and poor. Amino acids and L-carnitines levels in culture medium were detected by liquid chromatography-mass spectrometry (LC-MS). Using analysis of variance to compare differences among groups, correlation analysis, factor analysis was performed to analyze the association between the levels of amino acids and L-carnitines and development potential of early human embryos.Results:The value of Methionine/Phenylalanine was found statistically different among superior embryo (3.09±1.67), moderate embryo (4.00±1.19) and inferior embryo (4.99±2.04). The difference between the three groups was statistically different ( F=7.09, P<0.05): superior embryo vs moderate embryo ( t=-0.91, P<0.05), superior embryo vs inferior embryo ( t=-1.91, P<0.05), moderate embryo vs inferior embryo ( t=-0.99, P<0.05). Among different amino acids, Phe had the strongest positive correlation with Tyr ( r=0.99, P<0.01). Among different carnitines, C 8/C 10 has the strongest positive correlation with C 5DC+C 6OH/C 16( r=0.44, P<0.01). The weight value of leucine (isoleucine), arginine, valine/phenylalanine, glycine, tyrosine and carnitine(C 5DC+C 6OH)/C 8 calculated by the least square fitting model is 2.22, 1.99, 1.65, 1.54, 1.21 and 1.15 respectively. Conclusion:Leucine, arginine, valine/phenylalanine, glycine, tyrosine and carnitine (C 5DC+C 6OH)/C 8 in embryo culture medium were significantly correlated with the levels of early human embryos in vitro.

Objective To explore the application of A-V impulse foot pump in patients with lumbar spine surgery to prevent lower extremity deep venous thrombosis. Methods A total of 139 patients with spinal lesions who took spinal surgery treatment from April 2015 to March 2016 were divided into experimental group (69 cases) and control group (70 cases) by random digits table method. Control group was given normal nursing instruction, and the person who had negative results of B ultrasonic examination in experimental group was accepted physical therapy with A-V impulse foot pump. The patients got secondary ultrasound or CT examination who had the deep venous thrombosis symptoms and/or highly suspected deep venous thrombosis in order to further confirmed, then calculated the incidence rate of two groups with deep venous thrombosis. Results There were 4 cases of 139 patients who got deep venous thrombosis in 2-6 days of postoperative, 1 case in experimental group, 3 case in control group, compared with control group, patients who used A-V impulse foot pump had lower risk of deep venous thrombosis, but there was no significant difference (P>0.05). The operation time, body mass index were (5.00 ± 0.82) h , (30.54 ± 3.93) kg/m2 in patients with deep venous thrombosis and (3.16 ± 0.66) h, (24.90 ± 2.62) kg/m2 in patients without deep venous thrombosis, and there were significant differences(t=5.44, 4.19, P<0.01). Conclusions The application of A-V impulse foot pump has positive significance to prevent the happening of deep venous thrombosis for patients who took spinal surgery, and it is worth to be popularized and applied in clinic.

Rituximab, a chimeric human-mouse monoclonal antibody, has been used as a first-line treatment for CD20