BACKGROUND: Human epididymis secretory protein 4 (HE4) is a new ovarian cancer biomarker. The factors influencing HE4 levels are not clear, and the reference data in China are limited. Here, we aim to evaluate the effects of menopause and age on HE4 levels and to provide a possible reference value for HE4 in healthy Chinese people. METHODS: A total of 2493 healthy females aged 40 years or older were recruited from March 2013 to March 2017 with the cooperation of four medical institutions across Beijing, China. The serum levels of HE4 and cancer antigen 125 (CA125) were measured by enzyme-linked immunosorbent assay. The Wilcoxon rank-sum test of variance and a stratified analysis were used to analyze the relationships among age, menopausal status, and levels of HE4 or CA125. Confidence intervals (5%-95%) were determined for reference ranges in different populations. RESULTS: There was a statistically significant difference in median HE4 levels between the post-menopausal (n = 2168) and pre-menopausal groups (n = 325) (36.46 vs. 24.04 pmol/L, Z = -14.41, P < 0.001). HE4 increased significantly with age in the post-menopausal groups (H = 408.18, P < 0.001) but not in the pre-menopausal subjects (Z = -0.43, P = 0.67). The upper 95th percentile of HE4 levels were 44.63 pmol/L for pre-menopausal women, 78.17 pmol/L for post-menopausal women, and 73.3 pmol/L for all women. In the post-menopausal population, the HE4 reference ranges were 13.15 to 47.31, 14.31 to 58.04, 17.06 to 73.51, 24.50 to 115.25, and 35.71 to 212.37 pmol/L for different age groups from forty divided by decade. The CA125 level was affected mainly by menopausal status and not age. CONCLUSIONS Menopausal status and age were both important factors influencing the level of HE4, and age affected HE4 levels mainly in post-menopausal women. The HE4 level was higher in the post-menopausal population than in the pre-menopausal population and increased with age.

Objective: To study and create the algorithm for the diversity (AD) of extensible markup language (XML) tree map, and provide a new tool for the identification of Artemisiae Annuae Herba. Method: According to the literature research, the key information of Artemisiae Annuae Herba was selected from the macroscopic, mesoscopic and microscopic information, etc. Based on the key information, the relevant upper standards of domestic and foreign professional fields were cited to assign the unique identification independent of language for each data element, and the coding rules of relevant data elements were established. The digital coding technology was applied to the flexible structure editor, and the tree map was created, which could be returned as the 5^th version of hypertext markup language (HTML5) or XML format. Based on the diversity related algorithms, the authors innovatively developed the AD of XML tree map of Artemisiae Annuae Herba, which took into account both of topology and semantics, and the expression model of related mathematical functions of Artemisiae Annuae Herba was established. By comparing the calculation results with the reality, the algorithm model was debugged continuously until the convergence of the core-culvert algorithm model. Result: Through the research on AD, the diversity between two XML tree maps could be calculated, and the discrimination or identification model of Artemisiae Annuae Herba also could be finally optimized and established. After calculation and analysis of the tested tree maps, the effective rate of the model was 100%. Conclusion: In this study, the establishment of the AD of XML tree map can effectively assist in the identification of Artemisiae Annuae Herba, which provides certain technical support and theoretical guidance for the research on intelligent application of traditional Chinese medicine.