OBJECTIVE To establish a method for simultaneous determination of venetoclax， busulfan and voriconazole in plasma of patients with acute myeloid leukemia （AML）， and apply it clinically. METHODS Plasma samples were subjected to protein precipitation using acetonitrile and subsequently analyzed by liquid chromatography-tandem mass spectrometry （LC-MS/MS） using venetoclax-D 8 ， busulfan-D 8 and posaconazole as internal standards. The separation was performed on a Phenomenex Kinetex ® C 18 column with a mobile phase composed of 0.1% formic acid solution （2 mmol/L ammonium acetate）-0.1% formic acid in acetonitrile （gradient elution） at a flow rate of 0.8 mL/min. The column temperature was set at 40 ℃， the sample size was 5 μL， and the total run time was 3.10 min. An electrospray ionization source was employed， and positive ion scanning was conducted using multiple reaction monitoring mode. The ion pairs used for quantitative analysis included m/z 868.4→636.3 （venetoclax）， m/z 264.1→151.1 （busulfan）， and m/z 350.1→224.0 （voriconazole）. The above LC-MS/MS method was adopted to determine plasma concentrations of venetoclax and voriconazole in 10 AML patients， as well as plasma concentration of busulfan in 5 patients undergoing conditioning treatment for allogeneic hematopoietic stem cell transplantation. RESULTS The linear ranges of venetoclax， busulfan and voriconazole were 50-10 000， 15-3 000 and 50-10 000 ng/mL， respectively （ R 2 ≥0.999 0）， with lower limits of quantification of 50， 15 and 50 ng/mL， respectively. The RSDs of intra-day and inter-day precision tests for all three analytes were all less than 10%， with accuracy （relative errors） ranging from －10.00% to 12.96%. The average extraction recovery ranged from 92.54% to 100.95%， and the average matrix effect was 89.98%-101.49%. Dilution reliability covered all dilution factors used in the test samples， and the absolute values of relative errors in stability tests were all≤16.25%. The plasma concentrations of venetoclax， busulfan and voriconazole in enrolled patients were 496.20-4 250.45， 233.48-2 002.28 and 475.51-5 710.18 ng/mL， respectively. CONCLUSIONS The LC-MS/MS method established in this study is rapid， sensitive and easy to operate， and can be used for the therapeutic drug monitoring of venetoclax， busulfan and voriconazole.

Objective: To understand the growth and development levels of four physical measurements in children aged 3-6 years in China, so as to provide a reference for child nutrition improvement and health promotion. Methods: A stratified random sampling method was used to collect physical measurement data from 120 kindergartens 25 842 children aged 3-6 years across 24 provinces and cities in seven natural geographical regions of North China, Northeast China, East China, Central China, South China, Southwest China and Northwest China from 2020 to 2023. The development levels of head circumference, chest circumference, waist circumference, and hip circumference were evaluated using a grading method. The analysis of gender and age differences was conducted using Mann-Whitney U- test and Kruskal-Wallis test, and the comparison of abnormal detection rates for different genders was conducted using Chi square test. Results: The distribution range of children aged 3-6 was 51.74(50.08, 53.33) cm in terms of head circumference, 55.73(52.09, 59.04) cm in terms of chest circumference, 53.04(48.92, 56.40) cm in terms of waist circumference, and 59.36(56.30, 62.32) cm in terms of hip circumference. The detection rate of abnormal head circumference in boys and girls aged 3-6 years old was relatively high (19.71%-42.02%), and the detection rate of abnormal physical circumference development levels in boys was higher than that in girls of all ages ( χ 2=5.63-83.35, P <0.05). The detection rate of abnormal hip circumference (4.89%-6.53%) and chest circumference (4.51%-6.38%) in boys and girls aged 3-6 was relatively low, and there was no statistically significant difference in the abnormal rate between different ages and genders ( χ 2=0.00-1.61, 0.00-3.71, P >0.05). The detection rate of abnormal waist circumference in boys and girls aged 3-6 was relatively high (13.70%-42.45%), and the detection rate of abnormal waist circumference in girls was higher than that in boys aged 4-6 groups ( χ 2=10.49-58.18, P < 0.05). Conclusions The overall physical development of children aged 3-6 years in China is improving, but the abnormal detection rates for head circumference and waist circumference are relatively high. Child healthcare should focus on preventing and treating abdominal obesity, with differentiated health intervention strategies based on different age groups and genders.

Objective To improve the cellular uptake efficiency and the therapeutic effect through the structural modification of paclitaxel(PTX)and the preparation of corresponding liposomes.Methods The prodrug of paclitaxel,PTX-PA,was prepared by esterification reaction,and the quantitative detection method of PTX-PA was established.Next,the optimal formulation and preparation of PTX-PA/Lip was obtained through single factor screening based on their appearance,particle size,and encapsulation efficiency.Results The PTX-PA was successfully synthesized,and the established HPLC quantitative analysis method for PTX-PA met the methodological requirements.After the optimal preparation and formulation research through single factor screening,the particle size of optimized PTX-PA/Lip was(62.75±1.81)nm with a PDI of(0.076±0.02),while the drug encapsulation rate reached more than 90%.Conclusion This research successfully prepared palmitic acid modified paclitaxel liposomes based on nanotechnology,enhancing the drug delivery efficiency of paclitaxel and laying the foundation for the pharmacodynamics research of PTX-PA.

Objective To introduce an improved method of continuous intradermal suture,and to evaluate its clinical efficacy for the closure of surgical incisions.Methods Eighty-two patients were enrolled in this study,including 37 cases of nevus,10 cases of basal cell carcinoma,16 cases of sebaceous cyst,6 cases of lipoma,8 cases of seborrheic keratosis,3 cases of dermatofibroma and 2 cases of depressed scar.All the patients were managed by simple surgical excision with the shortest length of postoperative incisions being 0.8 cm and the longest length being 12 cm.An improved method of continuous intradermal suture was used for the closure of all the postoperative incisions.Specifically,an absorbable thread with a small triangle needle in both ends was inserted through and pulled out from the dermal layer at one side of the incision,and then inserted through and pulled out from the dermal layer at the opposite side of the incision,which was repeated until the incision was entirely closed.Results Among the 82 patients,80 achieved primary healing,and 2 developed erythematous painful swelling at the incision site 2 days after the operation,which disappeared after symptomatic treatment for 5 days.During 3-6 months of follow-up,the incisions closed leaving a flat and smooth surface in 78 patients,and proliferative scar formed in 4 patients,which was obviously improved after local injection with glucocorticoids.No disruption of incisions was observed.Conclusion The improved method of continuous intradermal suture can be applied to the closure of skin defects in the face,neck,trunk and extremities with a favorable healing outcome and cosmetic result.

Objective To compare the effects of two skin sampling methods (negative pressure suction blister and skin shaving) on the physical status of autologous epidermal keratinocytes transplanted to patients with vitiligo. Methods Skin samples were obtained from the normal skin of 32 patients with stable vitiligo by suction blister under negative pressure and skin shaving alone or in combination. Immunohistochemistry was performed to examine the expression of proliferating cell nuclear antigen (PCNA) and caspase-3 in these samples.Skin tissues resected from 15 normal human subjects served as the control. Results There was an expression of PCNA and caspase-3 at different degrees in all the skin tissues obtained by the two sampling methods from the 32 patients. Most PCNA-positive cells were focally distributed at the basal layer in epidermis obtained from suction blisters, and a few PCNA-positive cells were observed in the middle and lower part of the prickle cell layer of epidermis from shaved skin. There was a significant difference in the percentage of PCNA-positive cells between the epidermis from suction blisters and shaved skin as well as between the epidermis from suction blisters and normal control skin (x2 = 10.99, 14.08, both P < 0.05), but not between the epidermis from shaved skin and normal control skin (x2 = 1.31, P > 0.05). The expression of caspase-3 was predominantly located in the cytoplasm of keratinocytes in the basal layer as well as middle and lower part of prick cell layer, and no difference was observed in the percentage of caspase-3-expressing keratinocytes between the epidermis from shaved skin, suction blisters and normal control skin (x2 = 1.41, 2.89, 1.91, all P > 0.05). Conclusions The proliferation activity of epidermal cells seems important to the survival of grafted skin, and compared to the suction blister technique, skin shaving appears to have less influence on the proliferation of keratinocytes.