Objective To evaluate the bioequivalence and safety of ezetimibe tablets in healthy Chinese subjects.Methods The study was designed as a single-center,randomized,open-label,two-period,two-way crossover,single-dose trail.Subjects who met the enrollment criteria were randomized into fasting administration group and postprandial administration group and received a single oral dose of 10 mg of the subject presparation of ezetimibe tablets or the reference presparation per cycle.The blood concentrations of ezetimibe and ezetimibe-glucuronide conjugate were measured by high-performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS),and the bioequivalence of the 2 preparations was evaluated using the WinNonlin 7.0 software.Pharmacokinetic parameters were calculated to evaluate the bioequivalence of the 2 preparations.The occurrence of all adverse events was also recorded to evaluate the safety.Results The main pharmacokinetic parameters of total ezetimibe in the plasma of the test and the reference after a single fasted administration:Cmax were(118.79±35.30)and(180.79±51.78)nmol·mL-1;tmax were 1.40 and 1.04 h;t1/2 were(15.33±5.57)and(17.38±7.24)h;AUC0-t were(1 523.90±371.21)and(1 690.99±553.40)nmol·mL-1·h;AUC0-∞ were(1 608.70±441.28),(1 807.15±630.00)nmol·mL-1·h.The main pharmacokinetic parameters of total ezetimibe in plasma of test and reference after a single meal:Cmax were(269.18±82.94)and(273.93±87.78)nmol·mL-1;Tmax were 1.15 and 1.08 h;t1/2 were(22.53±16.33)and(16.02±5.84)h;AUC0_twere(1 463.37±366.03),(1 263.96±271.01)nmol·mL-1·h;AUC0-∞ were(1 639.01±466.53),(1 349.97±281.39)nmol·mL-1·h.The main pharmacokinetic parameters Cmax,AUC0-tand AUC0-∞ of the two preparations were analyzed by variance analysis after logarithmic transformation.In the fasting administration group,the 90％CI of the log-transformed geometric mean ratios were within the bioequivalent range for the remaining parameters in the fasting dosing group,except for the Cmax of ezetimibe and total ezetimibe,which were below the lower bioequivalent range.The Cmax of ezetimibe,ezetimibe-glucuronide,and total ezetimibe in the postprandial dosing group was within the equivalence range,and the 90％CI of the remaining parameters were not within the equivalence range for bioequivalence.Conclusion This test can not determine whether the test preparation and the reference preparation of ezetimibe tablets have bioequivalence,and further clinical trials are needed to verify it.

BACKGROUND: A deep learning model (DLM) that enables non-invasive hypokalemia screening from an electrocardiogram (ECG) may improve the detection of this life-threatening condition. This study aimed to develop and evaluate the performance of a DLM for the detection of hypokalemia from the ECGs of emergency patients. METHODS: We used a total of 9908 ECG data from emergency patients who were admitted at the Second Affiliated Hospital of Nanchang University, Jiangxi, China, from September 2017 to October 2020. The DLM was trained using 12 ECG leads (lead I, II, III, aVR, aVL, aVF, and V1-6) to detect patients with serum potassium concentrations <3.5 mmol/L and was validated using retrospective data from the Jiangling branch of the Second Affiliated Hospital of Nanchang University. The blood draw was completed within 10 min before and after the ECG examination, and there was no new or ongoing infusion during this period. RESULTS: We used 6904 ECGs and 1726 ECGs as development and internal validation data sets, respectively. In addition, 1278 ECGs from the Jiangling branch of the Second Affiliated Hospital of Nanchang University were used as external validation data sets. Using 12 ECG leads (leads I, II, III, aVR, aVL, aVF, and V1-6), the area under the receiver operating characteristic curve (AUC) of the DLM was 0.80 (95% confidence interval [CI]: 0.77-0.82) for the internal validation data set. Using an optimal operating point yielded a sensitivity of 71.4% and a specificity of 77.1%. Using the same 12 ECG leads, the external validation data set resulted in an AUC for the DLM of 0.77 (95% CI: 0.75-0.79). Using an optimal operating point yielded a sensitivity of 70.0% and a specificity of 69.1%. CONCLUSIONS In this study, using 12 ECG leads, a DLM detected hypokalemia in emergency patients with an AUC of 0.77 to 0.80. Artificial intelligence could be used to analyze an ECG to quickly screen for hypokalemia.
Artificial Intelligence ; Deep Learning ; Electrocardiography ; Humans ; Hypokalemia/diagnosis* ; Retrospective Studies

In order to reveal the molecular mechanism of blue labeled genic male sterility (BM-type GMS) and utilize the heterosis of BM-type GMS, we used the anthers of white-seed plants WS (sterile) and light blue seed plants WF (normal fertility) as experimental materials to analyze the differences in gene expression between them by transcriptome technology. And we also verified the genes expressed in anthocyanin synthesis in this study. Compared with WF, a total of 2352 differentially expressed genes were detected in WS. According to GO functional annotation, these genes could be divided into 3 categories and 43 subgroups. They are mainly involved in biosynthesis, phenylpropane metabolism, L-phenylalanine catabolism, membrane components, plasma membrane, cytoplasm, ATP binding, protein serine/threonine kinase activity, etc. KEGG pathway analysis showed that there were 159 genes enriched in the phenylpropanoid biosynthesis pathway, followed by the phenylalanine pathway, including 136 differentially expressed genes. Other genes are also involved a variety of amino acid metabolism, purine metabolism, pyrimidine metabolism and sugar metabolism pathway. Related to anthocyanin metabolism, several structural genes of key enzymes were differentially expressed, and most of them were up-regulated in WF, while only Flavanone 3-hydroxylase (F3H) and colorless anthocyanin dioxygenase (ANS) were down-regulated. Quantitative real-time PCR showed that the expression of 10 genes related to anthocyanin metabolism had the same trend as that in transcriptome sequencing data. Sequence homology analysis showed that the two selected transcription factors (DN48762c2g1 and DN25944c0g1) are clustered into the same cluster as the transcription factors regulating anthocyanin biosynthesis in maize, rice and Arabidopsis thaliana, which might be candidate genes for the blue aleurone layer of light blue seed plants in wheat. And fluorescence quantitative analysis showed that the expression level of DN48762c2g1 and DN25944c0g1 in WF was significantly higher than that in WS. In conclusion, the genes related to the anthocyanin biosynthesis pathway are not only related to the blue grain trait, but also may be involved in the anther abortion of BM-type GMS.

Objective To investigate the levels of serum Vitamin D(VD) from preconception to pregnancy in Jiading district of Shanghai, and explore the risk factors of VD concentration deficiency in the second and third trimester of pregnancy. Methods A total of 94 women who planned to have antenatal care and delivery in Maternal and Child Health Hospital of Jiading district of Shanghai from September 2016 to December 2018 were recruited as the study participants. Chemiluminescent immunoassay (CLIA) was used to examine the concentration of women’s serum VD from preconception to pregnancy. A total of 282 serum samples were detected. Results The prevalence of VD deficiency among 94 women from preconception to pregnancy were 40.4%,57.4% and 48.9% respectively. Results of the mixed linear model showed that women who had dyed or permed hair within the past 1 year had significantly lower serum VD levels during pregnancy (P<0.05), and women who often drank milk and ate deep-sea fish during pregnancy had higher VD levels during pregnancy (P<0.05). Conclusions VD deficiency was common among women in Jiading district of Shanghai, and it should be emphasized to supplement VD before and during pregnancy.

Objective:To explore the characteristics of eye tracking movement on circumscribed interests in preschool children with autism spectrum disorder (ASD), providing some reference for behavior correction and rehabilitation training.Methods:Fifty ASD children and fifty-two age-matched typically developing children(TDC) were investigated by the childhood autism rating scale(CARS), the autism diagnostic observation schedule(ADOS), the autism diagnostic interview-revised (ADI-R) and Gesell Developmental Schedule, (GDS). Eye movement during the visual search task was captured by the Tobii Pro X3-120 eye tracker.All data were analyzed by the IBM SPSS Statistics 20.0.Eye movement patterns were compared between TDC and ASD children using the independent-sample t test, and the correlations were then analyzed between abnormal eye movement characteristics and their core syndrome. Results:The total scores of CARS, ADOS and ADI-R in ASD group were 34.13±4.59, 14.44±2.59 and 39.91±12.11 respectively.During passive viewing of complex non-social picture arrays, ASD and TDC group explored total number of images were 9.28±2.72 and 12.67±2.45.The fixation time per image explored in ASD and TDC group were (0.67±0.37)ms and (0.54±0.15)ms.Moreover, the number of discrete fixations per image explored in ASD and TDC group was 2.80±1.00 and 2.48±0.48.Compared with the TDC group, ASD children demonstrated circumscribed attention ( t=6.610, P<0.01) with more perseveration ( t=-2.363, P=0.021) and detail-orientation ( t=-2.360, P=0.021). Exploration was negatively correlated with the total score of ADOS ( r=-0.480, P<0.01), CARS ( r=-0.487, P<0.01), communication score of ADOS( r=-0.290, P=0.041), social score of ADOS( r=-0.491, P<0.01), game score of ADOS( r=-0.397, P=0.004)and communication score of ADI-R( r=-0.331, P=0.025)in the ASD group. Conclusion:Compared with TDC, the eye movement pattern shows the circumscribed interests of ASD children, who not only explore fewer objects but also demonstrate circumscribed attention with more perseveration and detail-orientation.Moreover, the more severe the symptoms of ASD children, the fewer objects the children explore and the more stereotyped the circumscribed interest.

In this experiment, the decoction process of famous classical formula Xiebai San was determined by optimizing the particle size of "Cuo san" and investigating the decoction process parameters, such as boiling container, water volume and duration. Xiebai San was taken as an example to explore the study method of the "Cuo san" in the famous classical formulas. The specific chromatogram of Xiebai San and the determination method of glycyrrhizin and glycyrrhizic acid in Xiebai San were established. Different particle sizes of "Cuo san" and decoction parameters were optimized based on the similarity of specific chromatogram, the specific chromatogram's peak area, the content of glycyrrhizin, the content of glycyrrhizic acid and extract yield rate.The particle size of Xiebai San powder was determined to be 2.00-4.75 mm(by four-mesh sieves). The decoction process was determined as follows: put the prescription amount into a ceramic pot, add 420 mL of water, and boil and simmer until the volume is 300 mL.The similarity of specific chromatogram was above 0.9, the specific chromatogram's peak area was larger, the content of glycyrrhizin was 0.12%, the content of glycyrrhizic acid was 0.21%,and the extract yield rate was 15.05%. The finally determined particle size of "Cuo san" can better represent the quality of Xiebai San, and is easy to prepare and suitable for industrial production.This experimental research method can comprehensively investigate the quality of Xiebai San as a whole, the content of active ingredients, and the situation of extract yield.It is a more comprehensive and objective evaluation method, and can provide experimental basis and reference for the study of other "Cuo san" famous classical formulas.
Drugs, Chinese Herbal/chemistry* ; Glycyrrhizic Acid/analysis* ; Particle Size ; Powders ; Technology, Pharmaceutical

To establish a determination method for the contents of ammonium glycyrrhetate,nardosinone,and curcumin in transdermal receptor liquid of Baimai Ointment,and investigate the percutaneous permeability of Baimai Ointment and the effects of two kinds of penetration enhancers on percutaneous absorption of three components. The contents of ammonium glycyrrhetate,nardosinone,and curcumin in transdermal receptor liquid were determined by high pressure liquid chromatography( HPLC). The vertical modified Franz diffusion cell was used to perform a transdermal experiment in vitro with the abdominal skin of mice( treated and untreated). The transdermal receptor liquid was preferably used to investigate the transdermal absorption rule of the Baimai Ointment and the effect of the penetration enhancer. The results showed that the comprehensive solubility of PEG-ET-NS( 3 ∶3 ∶4) was best among three types of receptor liquid PG-ET-NS( 3 ∶3 ∶4),PEG-ET-NS( 3 ∶3 ∶4),ET-NS( 3 ∶7). PEG-ET-NS was used as the receptor liquid for in vitro transdermal experiments. The cumulative permeation area of ammonium glycyrrhetate,nardosinone and curcumin within 24 h was 5. 73,18. 99,0. 38 μg·cm~(-2)respectively. Taking QEFand ER as comprehensive evaluation indicators of permeation performance,the comprehensive penetration-promoting performance of ammonium glycyrrhizinate: 3% PEG 400-ethanol-normal saline ≈ 1. 19 times( 3%azone) = 1. 94 times( blank); comprehensive penetration-promoting performance of nardosinone: 3% PEG 400-ethanol-normal saline≈1. 28 times( 3% azone) = 1. 37 times( blank); the comprehensive penetration performance of curcumin: 3% PEG 400-ethanol-normal saline≈1. 77 times( 3% azone) ≈3. 42 times( blank). The comprehensive penetration enhancement properties of the two penetration enhancers were as follows: 3% PEG 400-ethanol-normal saline>3%azone>blank. The transdermal absorption curve of ammonium glycyrrhetate,nardosinone and curcumin in Baimai Ointment were consistent with the zero-order equation,indicating that the transdermal absorption process was irrelevant to the concentration of three components,and its was a diffusion process. This experiment provides reference for the study of ointment transdermal preparations.
Administration, Cutaneous ; Animals ; Mice ; Ointments ; pharmacokinetics ; Permeability ; Skin ; Skin Absorption

Echinococcus granulosus is an important zoonotic parasite globally causing cystic echinococcosis (CE) in humans and animals. In this study, prevalence of CE and variation of cox1 gene sequence were analyzed with isolates E. granulosus collected from different areas in northern Xinjiang, China. The survey showed that 3.5% of sheep and 4.1% of cattle were infected with CE. Fragment of cox1 was amplified from all the positive sheep and cattle samples by PCR. In addition, 26 positive samples across the 4 areas were included. The isolates were all E. granulosus sensu stricto (s.s.) containing 15 haplotypes (Hap1-15), and clustered into 2 genotypes, G1 (90.1%, 91/101) and G3 (9.9%, 10/101). Hap1 was the most common haplotype (48.5%, 49/101). Hap9 were found in humans samples, indicating that sheep and cattle reservoir human CE. It is indicate that E. granulosus may impact on control of CE in livestock and humans in the region.
Animals ; Cattle ; China ; Cross-Sectional Studies ; Echinococcosis ; Echinococcus granulosus ; Echinococcus ; Genotype ; Haplotypes ; Humans ; Livestock ; Parasites ; Polymerase Chain Reaction ; Prevalence ; Sheep

Objective To observe the clinical efficacy of Tangzhiping Prescription on non-proliferative diabetic retinopathy (NPDR) and the effects on serum vascular epithelial growth factor (VEGF) and pigment epithelium derived factor (PEDF). Methods Totally 86 NPDR patients were randomly divided into treatment group (43 cases) and control group (43 cases). Both groups were given hypoglycemic, anti hypertensive and lipid-regulatory basic therapy. The control group was given calcium distillate capsules, 0.5 g per time, 3 times a day, orally; the treatment group was treated with Tangzhiping Prescription based on the control group, 1 dosage per day, twice a day, orally. Four weeks were set as one treatment course. Treatment for both groups lasted for three courses. Clinical efficacy and fundus efficacy of both groups were evaluated. TCM symptom scores, fundus scores, and visual condition were observed; FPG, 2 h PG, Hb A1 C, TC, TG, HDL-C and LDL-C and changes in the contents of VEGF and PEDF were detected. Results The control group and the treatment group lost 2 and 3 cases respectively. The total effective rate of clinical efficacy and total fundus efficiency of the control group were 65.00％ and 68.35％, respectively, and the treatment group were 87.50％ and 84.62％ respectively, with statistical significance (P＜0.05). Compared with before treatment, TCM symptom scores and fundus scores decreased significantly after treatment in both groups (P＜0.01); After treatment, the TCM symptom scores and fundus scores in the treatment group were lower than those in the control group (P＜0.05, P＜0.01). Compared with before treatment, visual acuity improved significantly after treatment in both groups (P＜0.05, P＜0.01). Compared with before treatment, levels of FPG, 2 h PG, Hb A1 c, TC, TG, and LDL-C decreased significantly in both groups after treatment (P＜0.01). After treatment, the levels of 2 h PG, Hb A1 c, TC, TG, and LDL-C in the treatment group were significantly lower than the control group (P＜0.05, P＜0.01). Compared with before treatment, the levels of VEGF decreased and PEDF levels increased in both groups, with statistical significance (P＜0.01). After treatment, the improvement of VEGF and PEDF in the treatment group was better than that in the control group (P＜0.05, P＜0.01); negative correlation was found between VEGF and PEDF (r=-0.320, P＜0.01). Conclusion Tangzhiping Prescription can effectively improve the clinical symptoms of patients with NPDR and slow down the progress of NPDR via reducing the blood glucose and blood lipids, and regulating the contents of VEGF and PEDF.