AIM: To determine the concentration of nisoldipine in human plasma by HPLC-MS method and investigate the pharmacokinetics of sustained and immediate-release preparations. METHODS: A C 18 column was used to separate nisoldipine from plasma with the mobile phase of a mixture of methanol-water-acetic acid (7525 0.1) at a flow rate of 1.0 ml?min -1. MS: atmospheric pressure electronic spray ionization (AP-ESI) and ion mass spectral (m/z) of 411 were selected to quantify nisoldipine. Internal standard (IS): atmospheric pressure electronic spray ionization and m/z of 441 for nimodipine. RESULTS: The linear range of the standard curve of nisoldipine was 0.2- 50 ?g?L -1 and the determination limit was 0.15 ?g?L -1. The recovery rate was more than 70%, and intra-day relative standard deviation (RSD) and inter-day RSD were less than 10%. After being given a single dose of 10 mg nisoldipine sustained release tablet, sustained release capsule and normal tablet, the half life(t 1/2 /h) were 6.08? 1.48, 7.06? 1.80 and 3.70? 0.25, the time to peak concentration (T peak /h) were 5.4? 0.7, 5.8? 0.4 and 2.0? 0.2, the peak concentration (C max / ?g?L -1) were 3.43? 0.55, 3.71? 0.24 and 9.18? 3.78, the area under time- concentration curve (AUC 0-t / ?g?h -1?L -1) were 31.10? 5.00, 33.63? 7.16 and 32.72? 5.09. But after being given multiple doses of nisoldipine, C max/ ?g?L -1 were 5.20? 0.27, 3.91? 0.22 and 5.30? 1.04, C min / ?g?L -1 were 0.72? 0.10, 0.77? 0.07 and 0.53? 0.07, DF were 175.00%? 16.34%, 177.10%? 18.43% and 247.92%? 57.71% respectively. The bioavailability of sustained- release tablet and capsule were 96%?12% and 102%?9% respectively. CONCLUSION: The determination of concentration of nisoldipine in human plasma by HPLC-MS method is sensitive and accurate. It can be used for the investigation of the bioavailability and pharmacokinetic of nisoldipine.

AIM: To establish a sensitive HPLC method for determining the concentrations of paeonol in human plasma and to evaluate its pharmacokinetic characteristics. METHODS: A single oral dose of 160 mg paeonol capsules was given to 24 Chinese healthy volunteers. Paeonol was separated on a XB-C18 column with tetrahydrofuran-methanol-water-phosphonic acid (6∶60∶34∶0.1, V∶V) as mobile phase. The plasma concentrations of paeonol were determined and its pharmacokinetic parameters were calculated and evaluated using DAS 2.0. RESULTS: The linear range of the paeonol was 10-500 ng/mL and the determination limit was 10 ng/mL. The main pharmacokinetic parameters, as Cmax, tmax, t1/2,AUC0-3, AUC0-∞ after a single dose of paeonol capsules were (116±46)ng/mL,(1.02±0.13) h,(1.03±0.35) h, (174±45) ng/mL, (217±56) ng/mL,respectively. CONCLUSION: The HPLC method for determining paeonol concentration in plasma is rapid, sensitive and suitable for pharmacokinetic studies.

In order to improve the efficacy of vibration expectoration and prevent secondary injury in patients with chest trauma,the body surface marking method was used in vibration expectoration.The exact injured locations and areas were identified via CT ot X-ray results.Then,the restricted and focused areas of expectoration were marked with red and green colors,which could guide the machines to avoid the fracture sites,reduce pain,prevent secondary injury and administrate effective expectoration in the areas of sputum and atelectasis.However,the dynamic CT or X-ray results must be used for reference to ensure the accuracy of the body surface marking.

Objective To observe the therapeutic efficacy of the Chinese medical herb decoction qu yin tang combined with narrow-band ultraviolet B (NB-UVB) phototherapy on psoriasis vulgaris, and to investigate its influ-ence on osteopontin (OPN) and vascular endothelial growth factor (VEGF) in serum. Methods Sixty patients with psoriasis were randomly divided into a treatment group and a control group. The treatment group was treated with qu yin tang and NB-UVB; the control group was treated with qu yin tang only. The levels of OPN and VEGF in serum were detected in both groups before and after treatment using an enzyme-linked immunosorbent assay (ELISA). Twenty healthy persons' serum samples were taken as controls. At the same time, any changes in psoriasis area and severity index (PASI) scores in the two groups were recorded and compared. Results After 8 weeks of treatment, PASI scores and levels of OPN and VEGF had been reduced significantly in both groups, and there was a significant difference between the treatment group and the control group. Conclusions Chinese medical herbs combined with NB-UVB phototherapy is a safe and effective method for the treatment of psoriasis. The results suggested that OPN and VEGF may play an important role in the pathogenesis of psoirasis vulgaris.

Objective To assess the effects of health management on high-risk diabetic populations.Methods A total of 307 diabetic high-risk adults from 6 communities of Tianjin were recruited by using diabetes risk screening technology.Three-month intensive health management and nine-month follow-up were conducted in this participants.Paired t test for continuous variables and paired contingency table x2 test were used for data analysis.Results Energy intake (1989.8 vs.1766.4 kcal,t =6.84,P ＜0.05),effective exercises (120.4 vs.157.5 kcal,t =-5.00,P ＜ 0.05),body weight (73.0 vs.71.5 kg,t =6.92,P ＜0.05),systolic blood pressure (130.4 vs.124.6 mm Hg (1 mm Hg =0.133 kPa),t =8.36,P ＜0.05),diastolic blood pressure (81.8 vs.78.4 mm Hg,t =7.40,P ＜ 0.05),serum total cholesterol (5.21 vs.5.08 mmol/L,t =2.73,P ＜ 0.05),fasting plasma glucose (6.4 vs.5.8 mmol/L,t =16.37,P ＜ 0.05)and 2 h postprandial blood glucose (7.7 vs.6.9 mmol/L,t =9.67,P ＜ 0.05) were significantly improved after the intervention.Conclusions Community-based health management may provide an effective way to prevent and control the risk factors of diabetes.

Objective To assess the efficacy of 308 nm excimer laser irradiation for the treatment of guinea pig model of vitiligo and its immunoregulatory effect on Treg cell and Th17 cell.Methods Vitiligo was induced in guinea pigs by hydroquinone bleaching,and they were randomly divided into an experimental group and a control group.There was also a normal control group.The experimental group was treated with a 308 nm excimer laser at the nidus of vitiligo; the two control groups were given no intervention.After 8 weeks of treatment,leukasmus of the different groups were compared.The mRNA expression of Foxp3 and IL-17 were measured by real-time fluorescence quantitative (RTFQ-PCR) and the expression of Foxp3 and IL-17 in the lesions were measured by immunohistochemistry staining.Results The effectiveness rate was 100％ in the experiment group.The results of RTFQ-PCR showed that the mRNA expression of Foxp3 in the experimental group and the vitiligo control group was significantly higher than the healthy control group (all P ＜ 0.05),being 0.33 ± 0.03 and 0.02 ±0.07 respectively,as was the mRNA expression of IL-17,being 0.21 ± 0.05 and 0.94 ± 0.06 accordingly; and the mRNA expression of IL-17 in the experimental group was significantly lower than the vitiligo control group(P ＜ 0.05).The immunohistochemical staining showed that Foxp3 and IL-17 protein was scattered in the lesions of the experimental group,while they were crowded in those of the vitiligo control group.Conclusion Laser irradiation might contribute to a therapeutic effect on vitiligo through modulating the balance of Treg and Th17 cells,at least in guinea pigs.

The aim of this study is to establish an HPLC method for simultaneous determinations of mifepristone and its metabolites, mono-demethylated mifepristone, di-demethylated mifepristone and C-hydroxylated mifepristone in plasma and to evaluate the pharmacokinetic characteristics of mifepristone tablet. Twenty healthy female Chinese subjects were recruited and a series of blood samples were collected before and after 0.25, 0.5, 1.0, 1.5, 2.0, 4.0, 8.0, 12.0, 24.0, 48.0, 72.0 and 96.0 hours administration by a single oral dose of 75 mg mifepristone tablet. Mifepristone and its three metabolites were extracted from plasma using ethyl acetate and determined by high performance liquid chromatography. The main pharmacokinetic parameters of mifepristone and its metabolites, including Cmax, tmax, MRT, t(1/2), V, CL, AUC(0-96 h) and AUC(0-infinity), were calculated by Drug and Statistical Software Version 2.0. The simple, accurate and stable method allows the sensitive determinations ofmifepristone and its metabolites in human plasma up to 4 days after oral administration of 75 mg mifepristone tablet and the clinical applications of their pharmacokinetic studies.

Objective To analyze CYP17A1 gene mutation in a patient with 46,XY disordered sex development and to explore the possible influence on the phenotype of the patient.Methods Eight exons of CYP17AI gene in the patient and her parents were amplified and directly sequenced.In order to construct Mini-gene system,PCR fragments containing wildtype and mutant splicing sites were inserted in expression vector,and then transfected into cells.RT-PCR was used to observe the influence of splicing site mutation.Wildtype and aberrant splicing CYP17A1 cDNA expression plasmids were constructed and transfected into cells respectively,and CYP17A1 enzyme activity was tested in vitro.Results Mutation analysis revealed compound heterozygous CYP17A1 mutations,with Y329fs in one allele and a synonymous substitution( c.1263G＞A:GCG＞GCA) in another allele.In vitro analysis showed that the synonymous substitution induced a novel splicing site,which resulted in aberrant splicing of CYP17A1 mRNA and lacked six or seven amino acids after 415 in splicing product.In vitro transfection and enzyme activity experiment showed that the aberrant splicing product abolished the enzyme activity completely.However,this mutation did not completely influence splicing.The patient also had a part of normal splicing product,which was a coincidence to the phenotype of the patient.Conclusion This is the first description of an exonic splicing mutation in CYP17A1 relevant to the 17ot-hydroxylase deficiency phenotype.The functional study of the aberrant splicing variant has been initiated.

BACKGROUND:Resistance training and weight-bearing exercise are recommended modes for patients with osteoporosis to improve bone health.High-intensity interval training is a high-impact weight-bearing exercise with obvious time-efficient characteristics;however,little attention has been paid to its impact on bones. OBJECTIVE:To observe the effect of high-intensity interval training on the bone health of ovariectomized rat models. METHODS:Thirty-six female Sprague-Dawley rats were randomly divided into sham group,model group and model exercise group(n=12 per group).Bilateral ovariectomy was used to prepare an osteoporosis rat model in the latter two groups.Six weeks after modeling,the model exercise group was subjected to a high-intensity interval training on an electric treadmill at 90%peak running speed for 2 minutes and 50%peak running speed for 1 minute as one session,a total of nine sessions,3 days per week,for 6 weeks.Rats in the sham and model groups were raised quietly in the mouse cage during the same period.The relevant indexes were tested 48-72 hours after the final training. RESULTS AND CONCLUSION:Compared with the sham group,bone mineral density,maximal load,stiffness,elasticity,trabecular volume fraction,and trabecular number decreased(P<0.05),while trabecular separation increased(P<0.05);the level of irisin in the serum,gastrocnemius and femur decreased(P<0.05);the expression of peroxisome proliferator-activated receptor γ coactivator-1α protein and fibronectin type Ⅲ domain-containing protein 5 mRNA and protein in the gastrocnemius muscle decreased(P<0.05);the expression of type I collagen,Osterix,and Runx2 mRNA in the femur decreased(P<0.05);and the expression of anti-tartrate acid phosphatase,receptor activator of nuclear factor κB ligand,and osteoclast-associated receptor mRNA increased in the model group(P<0.05).Compared with the model group,bone mineral density,fracture load,maximal load,stiffness,elasticity,average trabecular thickness,and trabecular number increased(P<0.05),and trabecular separation decreased(P<0.05);the level of irisin in the serum,gastrocnemius and femur increased(P<0.05);the expression of peroxisome proliferator-activated receptor γ coactivator-1α protein and fibronectin type Ⅲ domain-containing protein 5 mRNA and protein in gastrocnemius increased(P<0.05);the expression of type I collagen,Osterix,and Runx2 mRNA in the femur increased(P<0.05);and the expression of anti-tartrate acid phosphatase,receptor activator of nuclear factor κB ligand,and osteoclast-associated receptor mRNA decreased in the model exercise group(P<0.05).To conclude,short-term high-intensity interval training may improve bone health of ovariectomized rats through up-regulating the irisin level.

Randomized controlled trials (RCT) have long been considered the gold standard for assessing clinical efficacy. However, RCT are inappropriate for some diseases due to related ethical issues and costs, such as rare diseases that are seriously life-threatening but without adequate treatment. Using real world data (RWD) as external control for RCT could make recruitment less complicated and reduce time and cost. This paper introduces common application scenarios, data sources, study design, basic principles, and statistical methods of RWD as an external control based on the latest guidelines related to RWD and combined with our team's previous research experience. This study could provide references for scholars and sponsors who want to conduct RWD research.