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.

Objective: Compare and analyze the results of the domestic Lanyi AH600 glycated hemoglobin analyzer and other different detection systems to understand the comparability of the detection results of different detectors, and establish the best cut point of Lanyi AH600 determination of haemoglobin A1c (HbA1c) in the diagnosis of diabetes. Methods: Multi center cohort study was adopted. The clinical laboratory departments of 18 medical institutions independently collected test samples from their respective hospitals from March to April 2022, and independently completed comparative analysis of the evaluated instrument (Lanyi AH600) and the reference instrument HbA1c. The reference instruments include four different brands of glycosylated hemoglobin meters, including Arkray, Bio-Rad, DOSOH, and Huizhong. Scatter plot was used to calculate the correlation between the results of different detection systems, and the regression equation was calculated. The consistency analysis between the results of different detection systems was evaluated by Bland Altman method. Consistency judgment principles: (1) When the 95% limits of agreement (95% LoA) of the measurement difference was within 0.4% HbA1c and the measurement score was≥80 points, the comparison consistency was good; (2) When the measurement difference of 95% LoA exceeded 0.4% HbA1c, and the measurement score was≥80 points, the comparison consistency was relatively good; (3) The measurement score was less than 80 points, the comparison consistency was poor. The difference between the results of different detection systems was tested by paired sample T test or Wilcoxon paired sign rank sum test; The best cut-off point of diabetes was analyzed by receiver operating characteristic curve (ROC). Results: The correlation coefficient R² of results between Lanyi AH600 and the reference instrument in 16 hospitals is≥0.99; The Bland Altman consistency analysis showed that the difference of 95% LoA in Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180) was -0.486%-0.325%, and the measurement score was 94.6 points (473/500); The difference of 95% LoA in the Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant II) was -0.727%-0.612%, and the measurement score was 89.8 points; The difference of 95% LoA in the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT) was -0.231%-0.461%, and the measurement score was 96.6 points; The difference of 95% LoA in the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT) was -0.469%-0.479%, and the measurement score was 91.9 points. The other 14 hospitals, Lanyi AH600, were compared with 4 reference instrument brands, the difference of 95% LoA was less than 0.4% HbA1c, and the scores were all greater than 95 points. The results of paired sample T test or Wilcoxon paired sign rank sum test showed that there was no statistically significant difference between Lanyi AH600 and the reference instrument Arkray HA8180 (Z=1.665,P=0.096), with no statistical difference. The mean difference between the measured values of the two instruments was 0.004%. The comparison data of Lanyi AH600 and the reference instrument of all other institutions had significant differences (all P<0.001), however, it was necessary to consider whether it was within the clinical acceptable range in combination with the results of the Bland-Altman consistency analysis. The ROC curve of HbA1c detected by Lanyi AH600 in 985 patients with diabetes and 3 423 patients with non-diabetes was analyzed, the area under curve (AUC) was 0.877, the standard error was 0.007, and the 95% confidence interval 95%CI was (0.864, 0.891), which was statistically significant (P<0.001). The maximum value of Youden index was 0.634, and the corresponding HbA1c cut point was 6.235%. The sensitivity and specificity of diabetes diagnosis were 76.2% and 87.2%, respectively. Conclusion: Among the hospitals and instruments currently included in this study, among these four hospitals included Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180), Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant Ⅱ), the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT), and the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT), the comparison between Lanyi AH600 and the reference instruments showed relatively good consistency, while the other 14 hospitals involved four different brands of reference instruments: Arkray, Bio-Rad, DOSOH, and Huizhong, Lanyi AH600 had good consistency with its comparison. The best cut point of the domestic Lanyi AH600 for detecting HbA1c in the diagnosis of diabetes is 6.235%.
Pregnancy ; Child ; Humans ; Female ; Glycated Hemoglobin ; Cohort Studies ; Diabetes Mellitus/diagnosis* ; Sensitivity and Specificity ; ROC Curve

Objective: To examine the application value of 3D Slicer software assisted domestic frameless stereotactic robot in biopsy of intracranial lesions. Methods: A retrospective analysis was performed on 80 patients who admitted consecutively and underwent intracerebral lesions biopsy with the domestic frameless stereotactic robot at Department of Neurosurgery, Aerospace Central Hospital from January 2019 to December 2021. There were 36 males and 44 females, with a mean age of (38.5±18.0) years (range: 6 to 71 years). Before surgery only enhanced T1-weighted three-dimensional magnetization prepared gradient echo sequences and diffusion tensor imaging scans were performed. Self-reconstruction of intracranial lesions, cerebral cortex and blood vessels was carried out using 3D Slicer software system after the DICOM format imaging data of 80 patients were collected. These imaging data were merged to the workstation of the domestic frameless stereotactic robot for preoperative surgical planning and the surgical puncture path was designed to avoid blood vessels in the brain functional area, cerebral cortex and sulcus. Results: All frameless stereotactic biopsy were successfully performed. Postoperative pathological diagnosis included 50 cases of diffuse astrocytic and oligodendroglioma, 15 cases of lymphoma, 5 cases of metastatic tumors, 5 cases of inflammatory demyelinating disease, 2 cases of inflammatory granuloma, 1 case of hemangioma, 1 case of acute lymphoblastic leukemia intracranial invasion and 1 case of seminoma. The positive diagnosis rate was 100% (80/80). Postoperative imaging confirmed that the puncture path and target were accurately implemented according to the preoperative planning, and the target error was (1.32±0.44) mm (range: 0.55 to 1.99 mm). One case of puncture-related bleeding occurred at the target after surgery and improved after treatment. Conclusion: The three-dimensional multimodal images reconstructed by the 3D Slicer software before operation could help the surgeons make the preoperative planning and reduce the risk of stereotactic brain biopsy.
Male ; Female ; Humans ; Child ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Aged ; Brain Neoplasms/pathology* ; Diffusion Tensor Imaging ; Retrospective Studies ; Robotics ; Biopsy ; Software ; Stereotaxic Techniques

OBJECTIVES: To investigate the sleep patterns and characteristics of infants and young children and the association between sleep patterns and breastfeeding. METHODS: A general information questionnaire, Brief Infant Sleep Questionnaire (BISQ), and a questionnaire on feeding were used to investigate the sleep quality and feeding patterns of 1 148 infants and young children aged 7-35 months. The K-means clustering method was used to identify sleep patterns and characteristics. A multivariate logistic regression analysis was used to investigate the association between sleep patterns and breastfeeding. RESULTS: Three typical sleep patterns were identified for the 1 148 infants and young children aged 7-35 months: early bedtime and long sleep time; short sleep latency and moderate sleep time; late bedtime, prolonged sleep latency, and insufficient sleep time. The third pattern showed sleep disorders. The multivariate logistic regression analysis showed that compared with formula feeding, exclusive breastfeeding within 6 months after birth reduced the risk of sleep disorder patterns by 69% (OR=0.31, 95%CI: 0.11-0.81). The risk of sleep disorder patterns was reduced by 40% (OR=0.60, 95%CI: 0.38-0.96) in the infants receiving breastfeeding for 4-6 months compared with those receiving breastfeeding for 1-3 months. CONCLUSIONS There are different sleep patterns in infants and young children, and breastfeeding can reduce the development of sleep disorder patterns.
Infant ; Child ; Female ; Humans ; Child, Preschool ; Breast Feeding ; Surveys and Questionnaires ; Sleep Wake Disorders ; Sleep ; Cluster Analysis

To investigate the effect and mechanism of psoralen on calvarial osteoblasts injuries caused by tricalcium phosphate (TCP) wear particles in vitro. Primary osteoblasts were obtained from the calvaria of neonatal SD rat by the series of digestion and were identified with ALP staining. Calvarial osteoblasts were treated with TCP wear particles for 48 h to establish the in vitro model of osteoblasts injuries. The rat osteoblasts were randomly divided into control group, TCP wear particles (0.1 mg/ml) group, psoralen treated (at the concentrations of 10, 10, 10 mol/L) groups. WST assay and the flow cytometry were used to detect the cell viability of osteoblasts and apoptosis, respectively. Chemical colorimetry was performed to examine ALP activity of osteobalsts. When the osteoblasts were treated for 14 day, mineral nodules formation was observed with alizarin red S staining. Western blot was applied to examine protein expressions of glucose regulated protein78/94(GRP78/94), inositol dependent enzyme 1 alpha (IREα), spliced X-box binding protein 1 (XBP1s) and phosphorylated c-Jun N-terminal kinase (p-JNK) in calvarial osteoblasts. Compared with control group, the cell viability of osteoblasts, ALP activity and mineral nodules formation in TCP group were decreased significantly (P＜0.05), while the percentage of apoptosis and protein expressions of GRP78/94, IRE1α, XBP1 and p-JNK were obviously increased in calvarial osteoblasts (P＜0.05). Compared with TCP group, the injuries of calvarial osteoblasts and cell apoptosis in psoralen treated groups were obviously decreased (P＜0.05), and the expression levels of GRP78/94, IRE1α, XBP1 and p-JNK were down-regulated remarkably (P＜0.05). Psoralen prevents osteoblasts injuries caused by TCP wear particles through IRE1α-XBP1s-JNK signaling pathway activation.

Objective To investigate whether elevated baseline levels of high sensitivity C-Reactive Protein (hsCRP) and neutrophil (NE) are associated with an increased risk of breast cancer in Kailuan female cohort. Methods Females from Kailuan cohort (2006-2007) were included in this study. Information on check-up, hsCRP and NE were collected at baseline for all subjects. Multivariable Cox proportional hazards regression models were used to calculate hazard ratios (HR) and 95% confidence intervals (95%CI) of association between baseline hsCRP and NE values and breast cancer risk. Results By December 31, 2015, a total of 18 866 participants were enrolled in this study. During the follow-up, 183 new cases of breast cancer were observed. All participants were divided into three groups according to the level of hsCRP (<1 mg/L, 1-3 mg/L and >3 mg/L). The cumulative incidence of breast cancer were 829/105, 1 211/105 and 1 495/105 in these 3 groups, respectively ( 2=12.08， P=0.002). Compared with participants with lower hsCRP levels (<1 mg/L), individuals with the highest hsCRP (>3 mg/L) levels had significantly increased risk of breast cancer (HR=1.71,95%CI: 1.18-2.47, P=0.005), howerver, we didn’t find the statistically significant association between NE level (<3.70×109/Lvs. ≥3.70×109/L) and the risk of brease cancer (P>0.05). Conclusions Elevated levels of hsCRP at baseline might increase the risk of breast cancer in females.

OBJECTIVE Using metabolomics to explore the essence of damp heat accumulation syndrome of infantile human cytomegalovirus hepatitis.METHODS 20 infantile HCMV hepatitis patients with damp heat accumulation syndrome and 20 healthy infants were recruited for investigation.Plasma and urine samples were analyzed using ultra-high-performance liquid chromatography-linear trap quadruple/orbitrap mass spectrometry (UHPLC-LTQ/Orbitrap-MS) to determine the alterations in metabolomic profiles of this syndrome.Orthogonal partial least squares-discriminate analysis (OPLS-DA) was applied to analyze the UHPLC-MS data obtained from these samples.The specificity and sensitivity of potential biomarkers were assessed according to the area under the receiver operator characteristic (ROC) curves.RESULTS The metabolomic analysis yielded 1076 plasma compounds and 414 urine compounds.Among them,22 plasma and 7 urine differential metabolites relating to sphingolipid,glycerophospholipid,histidine,glycerolipid,and fatty acid metabolism were identified.Sphingomyelin and triglycerides were screened as potential biomarkers and showed excellent discriminant performance.CONCLUSION This research can provide insights into the essence of HCMV hepatitis damp heat accumulation syndrome.

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.

Objective To analyze the results of malaria focus investigation and disposal in Tengchong City,Yunnan Prov-ince between 2015 and 2016,so as to provide evidences for interrupting potential malaria transmission. Methods The malaria foci were investigated and disposed according to the malaria cases reported from"China Information System for Disease Control and Prevention"in Tengchong City between 2015 and 2016. The mosquitoes were captured by mosquito-lured lamp overnight to investigate the malaria vector in local. The peripheral blood samples were collected from the local residents with a febrile history in the foci within two weeks and the accompanists of the cases,and then the rapid malaria diagnosis tests were used to screen the malaria carriers. Results Totally 145 imported malaria cases were reported in Tengchong City between 2015 and 2016,and the focus investigation and disposal rate within 7 d was 100%(145/145). A total of 16186 mosquitoes of 12 species of Anopheles were captured,among which An. sinensis was the predominant,accounting for 64.31%(10410/16186),followed by An. kun-mingensis and An. minimus,with the constituent ratios of 14.15%(2291/16186)and 11.66%(1887/16186),respectively. One person(1.96%,1/51)in the 51 accompanists of the cases was positive in the malaria rapid diagnosis test. Conclusions The malaria transmission vectors such as An. sinensis,An. kunmingensis,An. minimus etc. are still distributed in Tengchong City,and An. sinensis is the predominant species. Therefore,the relevant authorities should continue to strengthen the focus in-vestigation and disposal to interrupt the potential introduced malaria transmission by imported cases in the future.

Background: Esophageal cancer is associated with substantial disease burden in China, and data on the economic burden are fundamental for setting priorities in cancer interventions. The medical expenditure for the diagnosis and treatment of esophageal cancer in China has not been fully quantified. This study aimed to examine the medical expenditure of Chinese patients with esophageal cancer and the associated trends. Methods: From 2012 to 2014, a hospital-based multicenter retrospective survey was conducted in 37 hospitals in 13 provinces/municipalities across China as a part of the Cancer Screening Program of Urban China. For each esophageal cancer patient diagnosed between 2002 and 2011, clinical information and expense data were extracted by using structured questionnaires. All expense data were reported in Chinese Yuan (CNY; 1 CNY= 0.155 USD) based on the 2011 value and inflated using the year-specific health care consumer price index for China. Results: A total of 14,967 esophageal cancer patients were included in the analysis. It was estimated that the overall average expenditure per patient was 38,666 CNY, and an average annual increase of 6.27％ was observed from 2002 (25,111 CNY) to 2011 (46,124 CNY). The average expenditures were 34,460 CNY for stage Ⅰ, 39,302 CNY for stage Ⅱ, 40,353 CNY for stage Ⅲ, and 37,432 CNY for stage IV diseases (P < 0.01). The expenditure also differed by the therapy type, which was 38,492 CNY for surgery, 27,933 CNY for radiotherapy, and 27,805 CNY for chemotherapy (P < 0.05). Drugs contributed to 45.02％ of the overall expenditure. Conclusions: These conservative estimates suggested that medical expenditures for esophageal cancer in China substantially increased in the last 10 years, treatment for early-stage esophageal cancer costs less than that for advanced cases, and spending on drugs continued to account for a considerable proportion of the overall expenditure.