Objective To establish an UPLC-MS/MS method for determinating content of three paclitaxel fatty acid esters such as paclitaxel myristate(PTX-MA),paclitaxel palmitate(PTX-PA)and paclitaxel myristate(PTX-SA)in mouse plasma,and preliminarily investigate the pharmacokinetic characteristics of their liposomes in mice.Methods Eclipse Plus C8 chromatography column(2.1 mm×50 mm,1.8 μm)was used with different proportions of 0.2%formic acid aqueous solution(A)and methanol(B)mixture as mobile phase for gradient elution at a flow rate of 0.3 ml/min.The collum temperature was 30℃.The sample injection volume was 10 μl.The triple quadrupole mass series spectrometer was used as multi-reaction monitoring(MRM).Results PTX-MA,PTX-PA and PTX-SA all exhibited a good linear relationship in the range of 5.0～500.0 ng/ml(r>0.995 0).Their RSD of precision,stability,extraction recovery rate and matrix effect test results was all less than 10%.The half-lives(t1/2)for liposomes of three paclitaxel fatty acid esters PTX-MA-L、PTX-PA-L and PTX-SA-L in mice were 14.78 h,44.49 h and 69.32 h individually,and their clearance rates(CL)were 29.06 L?kg/h,24.94 L?kg/h and 13.74 L?kg/h,respectively.Conclusion This method had high specificity,sensitivity,easy operation and good stability,which could be used for the determination of paclitaxel fatty acid esters in mouse plasma.The results of pharmacokinetic studies in mice showed that t1/2 for paclitaxel fatty acid esters were significantly prolonged,and the clearance rate were significantly reduced with the length of fatty acid carbon chains increasement,which indicated that esterification of paclitaxel with different chain length saturated fatty acids could obviously alter its in vivo pharmacokinetic properties,which provided scientific basis for the research and development of nano formulations of paclitaxel fatty acid ester prodrug.

Objective:To understand the attitudes and cognition of disease control and prevention professionals at provincial level on public health physician standardized training and provide evidence for the improvement of the standardized training and exploration of more effective training mode in China.Methods:By cluster sampling, 2 193 professionals at provincial centers for disease control and prevention (CDC) in 6 provinces, including Jiangsu and Guangdong, Shanxi and Hubei,Sichuan and Xinjiang were selected as the study subjects, the sample size was estimated to be 1 933 persons.Results:A total of 1 716 provincial-level CDC professionals were surveyed, the support rate to the standardized training was 70.7%(1 213/1 716). The level of support was negatively associated with the educational level of professionals and their specialty of public health and preventive medicine. Of 875 public health and preventive medicine professionals, 61.6%(318/516) of those with master's degree or above supported the standard training for public health physicians, which was lower than 73.1%(225/308) of those with bachelor's degree and 86.3%(44/51) of those with college degree or below. There were 14.9%(232/1 555) of the respondents suggested a two year training, and 60.4%(933/1 544) suggesting a field training mode. In terms of training content, 86.6%(1 355/1 564) suggesting "epidemiological survey and public health practice", and 76.7%(1 199/1 564) suggesting "basic theories and methodology".Conclusions:In general, the professionals of provincial CDC showed a relatively low interest in the standardized training for public health physicians and failed to reach a consensus. Besides, they were ill-informed about current training duration, method and content. Thas, the professionals at provincial CDC are suggested to be the key target-population whom should be mobilized during the training pilot period, especially the highly educated ones with relevant specialties of public health. It is suggested that public health physician standardized training should to be implemented in whole CDC system to reach full consensus based on its practical achievements and effects. It is also suggested to establish public health graduate medical education system in China.

Objective:To investigate the changes in liver function and peripheral regulatory lymphocytes before and after treatment in patients with occupational medicamentosa-like dermatitis due to trichloroethylene (OMDT) .Methods:In December 2019, 16 patients with OMDT (8 patients with erythema multiforme and 8 with erythema multiforme major) who were admitted from February 2017 to February 2019 were enrolled as subjects. Liver function parameters and percentages of peripheral regulatory lymphocytes were measured before and after treatment, and the changes in liver function and peripheral regulatory T and B lymphocytes and their correlation were analyzed.Results:Before treatment, compared with the healthy control group, the experimental group had significantly higher levels of alanine aminotransferase (ALT) , aspartate aminotransferase (AST) , total bilirubin (TBIL) , direct bilirubin (DBIL) and gamma-glutamyl transpeptidase (GGT) and significantly lower levels of total protein (TP) , albumin (ALB) and cholinesterase (CHE) ( P<0.05) . Compared with the healthy control group, the experimental group had significantly lower percentages of lymphocytes, CD4 + T cells, CD4 +CD25 + Tregs, CD19 +CD24 +CD27 + Bregs and CD4 +/CD8 + ratio, as well as a significantly higher percentage of CD8 + T cells ( P<0.05) . Before treatment, the levels of ALT, AST, GGT and DBIL were negatively correlated with the percentages of CD4 +CD25 + Tregs, CD19 +CD24 +CD27 + Bregs, CD4 + T cells and CD4 +/CD8 + ratio ( r=-0.386 to -0.809, P<0.05) and was positively correlated with the percentage of CD8 + T cells (except DBIL) ( r=0.503-0.568, P<0.05) . The levels of TP and ALB were positively correlated with the percentages of CD4 +CD25 + Tregs, CD19 +CD24 +CD27 +Bregs and CD4 + T cells ( r= 0.351-0.784, P<0.05) , ALB was negatively correlated with the percentage of CD8 + T cells ( r=-0.315, P<0.05) . CHE was positively correlated with the percentages of CD4 +CD25 + Tregs, CD19 +CD24 +CD27 +Bregs and CD4 +/CD8 + ratio ( r=0.390-0.527, P<0.05) . Conclusion:Immune dysfunction is observed in patients with OMDT, which may be caused by the imbalance of regulatory lymphocytes. And liver injury may be associated with the increase of CD8 + T cells and the reductions of percentages of CD4 + T cells, CD4 +CD25 + Tregs, CD19 +CD24 +CD27 +Bregs and CD4 +/CD8 + ratio.

Objective:To investigate the changes in liver function and peripheral regulatory lymphocytes before and after treatment in patients with occupational medicamentosa-like dermatitis due to trichloroethylene (OMDT) .Methods:In December 2019, 16 patients with OMDT (8 patients with erythema multiforme and 8 with erythema multiforme major) who were admitted from February 2017 to February 2019 were enrolled as subjects. Liver function parameters and percentages of peripheral regulatory lymphocytes were measured before and after treatment, and the changes in liver function and peripheral regulatory T and B lymphocytes and their correlation were analyzed.Results:Before treatment, compared with the healthy control group, the experimental group had significantly higher levels of alanine aminotransferase (ALT) , aspartate aminotransferase (AST) , total bilirubin (TBIL) , direct bilirubin (DBIL) and gamma-glutamyl transpeptidase (GGT) and significantly lower levels of total protein (TP) , albumin (ALB) and cholinesterase (CHE) ( P<0.05) . Compared with the healthy control group, the experimental group had significantly lower percentages of lymphocytes, CD4 + T cells, CD4 +CD25 + Tregs, CD19 +CD24 +CD27 + Bregs and CD4 +/CD8 + ratio, as well as a significantly higher percentage of CD8 + T cells ( P<0.05) . Before treatment, the levels of ALT, AST, GGT and DBIL were negatively correlated with the percentages of CD4 +CD25 + Tregs, CD19 +CD24 +CD27 + Bregs, CD4 + T cells and CD4 +/CD8 + ratio ( r=-0.386 to -0.809, P<0.05) and was positively correlated with the percentage of CD8 + T cells (except DBIL) ( r=0.503-0.568, P<0.05) . The levels of TP and ALB were positively correlated with the percentages of CD4 +CD25 + Tregs, CD19 +CD24 +CD27 +Bregs and CD4 + T cells ( r= 0.351-0.784, P<0.05) , ALB was negatively correlated with the percentage of CD8 + T cells ( r=-0.315, P<0.05) . CHE was positively correlated with the percentages of CD4 +CD25 + Tregs, CD19 +CD24 +CD27 +Bregs and CD4 +/CD8 + ratio ( r=0.390-0.527, P<0.05) . Conclusion:Immune dysfunction is observed in patients with OMDT, which may be caused by the imbalance of regulatory lymphocytes. And liver injury may be associated with the increase of CD8 + T cells and the reductions of percentages of CD4 + T cells, CD4 +CD25 + Tregs, CD19 +CD24 +CD27 +Bregs and CD4 +/CD8 + ratio.