OBJECTIVE:To discuss the significance of therapeutic drug monitoring(TDM)for rational administration of anti-epileptic drugs and to probe into the cognition of clinic staff on TDM.METHODS:Access database of antiepileptic drugs was established to analyze the TDM data of antiepileptic drugs used from 2001 to 2006.RESULTS:The TDM cases of anti-epileptic drugs increased year by year.The proportions of effective concentration,high blood drug concentration and low blood drug concentration derived from TDM data showed that it is quite necessary to conduct blood drug concentration monitoring.But the lack of individual medication information has hindered the development of patients' individualized medication of anti-epileptic drugs.CONCLUSION:The application of TDM is increasingly widespread;however,the joint efforts of physicians and pharmacists are still needed to ensure individualized medication of anti-epileptic drugs.

OBJECTIVE:To evaluate the uncertainty of the determination of clopidogrel active metabolite derivative(CAMD) in human plasma by LC-MS/MS. METHODS:The course of CAMD determination in human plasma by LC-MS/MS were analyzed to evaluate the uncertainty caused by evaluate repeatability,weighing,standard solution preparation,biological sample prepara-tion,recovery,instrument precision and calibration curve fitting in CAMD assay;the uncertainty were calculated and expanded. RESULTS:The expanded uncertainty for low(0.107 ng/ml),medium(4.467 ng/ml)and high(155.667 ng/ml)levels of CAMD were 0.010 2 ng/ml,0.188 ng/ml and 6.413 ng/ml,respectively(k=2,P=95%). CONCLUSIONS:The uncertainty of the CAMD determination in human plasma by LC-MS/MS at low concentration is mainly caused by calibration curve fitting;at medium and high concentrations is mainly caused by biological sample preparation,extraction procedure,standard solution preparation and in-strument precision.

Objective:To investigate dermoscopic features of childhood vulvar lichen sclerosus.Methods:From January 2019 to May 2021, 79 female children with vulvar lichen sclerosus were collected from Kunming Children′s Hospital, and their dermoscopic features at first and return visits were analyzed retrospectively.Results:Among the 79 female children with vulvar lichen sclerosus, their age ranged from 2.4 to 12 years, the age at onset was 5.6 ± 2.12 years, the course of disease was 14.23 ± 12.36 months, and 30 children received regular follow-up and treatment. Among 329 skin lesions at the first visit, characteristic vascular shapes were observed in 149 (45.3%) , including linear vessels in 129, punctate vessels in 25, coiled vessels in 19, and hairpin-like vessels in 12; degenerative structures and pigment abnormalities were seen in 207 (62.92%) , including bluish-gray pigmented structures in 136, brown pigmented structures in 51, pepper-like patterns in 15, etc.; yellowish-white structureless areas were found in 280 (85.1%) , follicular keratotic plugs in 97 (29.5%) , and reddish-violet globules and patches in 66 (20%) . Among 238 skin lesions at the return visit, characteristic vascular shapes were observed in 100 (42%) , including linear vessels in 87, dendritic vessels in 21 and punctate vessels in 4, and no hairpin-like vessels were observed; degenerative structures and pigment abnormalities were seen in 154 (64.70%) , including brown pigmented structures in 93, bluish-gray pigmented structures in 57, and pepper-like patterns in 4; yellowish-white structureless areas were found in 165 (69.3%) , follicular keratotic plugs in 62 (26.1%) , and reddish-violet globules and patches in 8 (3.4%) . The prevalence rates of bluish-gray pigmented structures, yellowish-white structureless areas, reddish-violet globules and patches, punctate vessels, hairpin-like vessels, and coiled vessels in the skin lesions were all significantly lower at the return visit than at the first visit (all P < 0.05) , while the prevalence rate of the brown pigmented structure was significantly higher at the return visit than at the first visit ( P < 0.05) . Conclusion:Under a dermoscope, yellowish-white structureless areas are a highly specific characteristic of childhood vulvar lichen sclerosus, and therapeutic effect can be monitored by observing changes in dermoscopic features, including brown pigmented structures, bluish-gray pigmented structures, yellowish-white structureless areas, reddish-violet globules and patches, and vascular structures. Dermoscopy shows favorable application value in auxiliary diagnosis and follow-up observation of childhood vulvar lichen sclerosus.

Objective:To investigate the effect of Norcantharidin(NCTD)on the apoptosis of human ovarian cancer SKOV3 cells and its mechanism.Methods:Human ovarian cancer SKOV3 cells were cultured in vitro and treated with 52 μmol/L NCTD.The SKOV3 cells were divided into the control group and NCTD group(52 μmol/L).The morphological changes of SKOV3 cells were observed under an inverted microscope,and the changes of nucleus were observed under a fluorescence microscope.The changes of mitochondrial membrane potential were detected by flow cytometry after drug treatment for 24 h.Western blot was used to detect the expression levels of apoptosis-related proteins Bax,Bcl-2 and Wnt/β-catenin signaling pathway-related protein β-catenin in SKOV3 cells after drug treatment for 24 h.Result:Compared with that in the control group,NCTD inhibited the proliferation of SKOV3 cells,reduced mitochondrial membrane potential,induced apoptosis of SKOV3 cells,increased the expression of Bax protein,decreased the expression of Bcl-2 protein and β-catenin.Conclusion:NCTD-induced apoptosis of ovarian cancer SKOV3 cells may be related to the regulation of Wnt/β-catenin signaling pathway.

Recent years, the prevalence of thyroid cancer in pregnancy has increased significantly, and its diagnosis and management have also attracted attention. The diagnosis and evaluation of thyroid cancer during pregnancymay extend to non-pregnant adult. Ultrasound and ultrasound-guided fine needle aspiration biopsy are the cornerstones on the diagnosis of thyroid cancer. The main treatment of thyroid cancer during pregnancy includes surgery and active surveillance. However, the choice of optimal timing, as well as the type of surgery depends on the comprehensive evaluation of the properties and staging of the tumors. Physicians should fully communicate with patients and their families, and respect their willingness and expectation.

Graves′ disease, also known as diffuse toxic goiter, is an autoimmune disease with increased secretion of thyroid hormone. There are three effective treatments for Graves′ disease, which including anti-thyroid drugs (ATD), radioactive iodine and thyroidectomy. In general, ATD is the first choice of Graves′ disease treatment for domestic physicians, but the high recurrence rate has always been the deficiency of ATD treatment. Recurrence is mainly related to gender, age, smoking, course of disease, goiter and other factors. Among them, the reliability and applicability of single risk factor in evaluating the recurrence rate of Graves′ disease after ATD treatment are poor. The prediction model of multi-factor comprehensive score is helpful for the naive patients to choose the best treatment plan, to achieve the goal of precise treatment and to improve the remission rate of Graves′ disease drug treatment. In this paper, the reliability of risk factors for Graves′ disease recurrence after ATD treatment is evaluated, and the development and application of prediction models such as Graves′ recurrent events after therapy (GREAT) score, GREAT + score, and clinical severity score (CSS) are reviewed.

Objective: To understand the present situation of physical activity and its influencing factors, and to provide a reference for improving the level of physical activity and making the intervention measures. Methods: The method of random stratification was used to select 4 740 pre school children aged 3-6 from 17 kindergartens in 12 counties and districts of Nanchang City, The questionnaire of physical activities of young children and the questionnaire of parents of physical activities of young children were applied to conduct a survey. Results: Compared with weekday PA and MVPA, preschool children’s weekends decreased, SB increased. The differences in PA, MVPA and SB on weekdays and weekends were statistically significant( P <0.01). The proportion of PA and MVPA reaching the recommended amount during the working day of preschool children were 44.9%-59.2%, 45.4%- 61.7%.The proportion reaching the recommended amount of PA and MVPA on weekends were 24.7%-27.8%, 24.5%-29.9%, and the proportion reaching the recommended amount on weekdays was higher than that on weekends. Conclusion There is still gap between actual amount of physical activity and the recommended amount. There are different modes of activity on weekdays and weekends, and weekends are the least active periods. Parents and teachers should pay enough attention to the establishment of "social campus family" model to improve the lack of physical activity of preschool children.

Objective:To investigate the risk factors for recurrence of Graves′ disease after withdrawal of antithyroid drugs (ATD).Methods:This prospective study recruited 285 patients with newly onset Graves′ disease taking ATD from 2012 to 2018 at Department of Endocrinology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine. A total of 121 patients who completed follow-up were enrolled and were divided into relapse and remission group according to whether hyperthyroidism reoccurred within 2 years after ATD with drawal. Demographics, clinical manifestations, thyroid serological characteristics, and thyroid color doppler ultrasound at baseline and withdrawal were compared between the two groups. Cox regression analysis was used to analyze the correlation between above factors and recurrence of Graves′ disease.Results:Sixty-five patients relapsed within 2 years after drug withdrawal. Patients with early recurrence were characterized by Graves′ disease genetic history and high baseline thyrotrophin receptor antibody (TRAb) levels. Family history, higher serum FT 3(≥18.1 pmol/L), FT 4(≥49.8 pmol/L), and TRAb(≥16.1 mIU/mL) levels, larger goiter(Ⅱ-Ⅲ) and thyroid volume(≥28.6 cm 3), higher peak velocity of superior thyroid artery (STA-PV; ≥0.6 m/s) before treatment, and higher TRAb(≥0.8 mIU/mL) level after ATD withdraw were risk factors for Graves′ disease recurrence. Higher 25-hydroxy vitamin D(≥14.7 ng/mL) level at baseline, as well as high level of TSH(1.4 μIU/mL) at withdrawal may reduce the risk of relapse. Conclusions:Family history of Graves′ disease, clinical manifestations, thyroid serological indicators and imaging characteristics of severe Graves′ disease before treatment all increased the risk of Graves′ disease recurrence. Patients with aforementioned factors should be actively evaluated in order to choose treatment modalities reasonably. We recommended to maintain lower TRAb titer within normal reference range and TSH level between 1.4 μIU/mL and upper limits of normal reference range at ATD withdrawal to reduce the recurrence rate of Graves′ disease.

Malignant tumors have become the main cause of human death.With the prolonged use of chemotherapeutic drugs during the treatment process,tumor cell resistance is also constantly increasing.long non-coding RNA(lncRNA)is an important mem-ber of the non-coding RNA family.Cancer susceptibility candidate 2(CASC2)is a type of long non-coding RNA,high expression of CASC2 can inhibit tumor cell development and reduce drug resistance of tumor cells by promoting apoptosis,regulating signaling path-ways,participating in cellular transmission pathways,competitively binding of miRNA,and changing the protein structure or functional status.This article will provide a comprehensive review of the regulatory effects and mechanism of lncRNA CASC2 on chemotherapy resistance in malignant tumors.

Objective:To investigate the efficacy of venetoclax-based combined regimen in treatment of adult patients with acute myeloid leukemia (AML).Methods:The data of 50 adult AML (non-acute promyelocytic leukemia) who received venetoclax-based combined regimen in the First Affiliated Hospital of Xiamen University, Dongguan People's Hospital, the First Hospital of Longyan City, Jieyang People's Hospital from December 2018 to May 2021 were retrospectively analyzed. Different doses venetoclax combined with demethylation drugs or low-dose chemotherapy regimen were used to analyze the therapeutic efficacy. The related factors influencing efficacy were analyzed by using logistic regression.Results:The composite complete remission (CR) rate of 50 AML patients was 62.0% (31/50), the overall response rate (ORR) was 76.0% (38/50); 28 patients achieved effectiveness [CR and partial remission (PR)] after the first cycle and could achieve effectiveness by 3 courses of treatment at the latest. Among 50 patients, 28 cases were newly diagnosed AML, the composite CR rate was 60.8% (17/28), ORR was 78.6% (22/28); 22 cases were recurrent and relapsed, the composite CR rate was 63.6% (14/22), ORR was 72.7% (16/22); and there was no statistically significant difference of ORR between the both groups ( χ2 = 0.23, P = 0.743). Logistic regression multivariate analysis showed age was the only independent influencing factor for the treatment effectiveness ( OR = 8.451, 95% CI 1.306-54.697, P = 0.025). The median duration time of patients receiving venetoclax treatment regimen was 4.5 months (1.1-15.0 months); 16 cases who had treatment effectiveness finally relapsed, the median time of maintaining effectiveness was 5 months (1.1-11.0 months). Additionally, the common treatment-related adverse reactions included bone marrow suppression after treatment, followed by some gastrointestinal reactions like nausea, vomiting and stomachache. In addition, no patient stopped medication for more than 1 week due to bone marrow suppression related complications. Conclusion:Venetoclax-based combined regimen shows a good short-term efficacy in treatment of AML. It is also effective and tolerable for elderly patients receiving reduced dose therapy.