Abstract Heigen is the root and rhizomes of Duhaldea Nervosa Anderberg., a traditional medicine food homology herb used to treat rheumatoid arthritis in China,but the potential active components and the underlying mechanism have not been clarified. In this study, the chemical compounds and the components absorbed into the blood from Heigen were assessed using ultra-high performance liquid chromatography coupled with quadrupole Orbitrap high-resolution mass spectrometry. 72 chemical constituents were identified in Heigen, 13 blood prototypical constituents, and 9 metabolites were found in serum samples after intragastric administration of Heigen extracts to rats. Then, using network pharmacology and molecule docking, 10 compounds were assumed to be potentially key active compounds against RA, which may be via the multi-component, multi-target and multi-pathway interaction mechanism of Heigen in the treatment of RA, and also provides a pharmacological basis for the treatment of RA.

Abstract Voriconazole increases tacrolimus blood concentration significantly when coadministrated. The recommendation of reducing tacrolimus to 1/3 in voriconazole package insert seems not to be satisfactory in clinical practice. In vitro studies demonstrated that the magnitude of inhibition depends on the concentration of voriconazole, while voriconazole exposure is determined by the genotype status of CYP2C19. CYP2C19 gene polymorphism challenges the management of drug-drug interactions(DDIs) between voriconazole and tacrolimus. This work aimed to predict the impact of CYP2C19 polymorphism on the DDIs by using physiologically based pharmacokinetics (PBPK) models. The precision of the developed voriconazole and tacrolimus models was reasonable by evaluating the pharmacokinetic parameters fold error, such as AUC0-24, Cmax and tmax. Voriconazole increased tacrolimus concentration immediately in all population. The simulated duration of DDIs disappearance after voriconazole withdrawal were 146h, 90h and 66h in poor metabolizers (PMs), intermediate metabolizers (IMs) and extensive metabolizers(EMs), respectively. The developed and optimized PBPK models in this study can be applied to assit the dose adjustment for tacrolimus with and without voriconazole.

Abstract Objective: To evaluate the mid-term survival rate after tricuspid valve replacement (TVR). Methods: We retrospectively studied 110 consecutive patients who underwent TVR from January 2007 to November 2017. A survival analysis was performed with the Kaplan-Meier method and the log-rank test. Results: The median survival was 65.81 months. Mean age was 50 (range 39 to 59) years. Forty-eight patients (43.6%) were male, and 62 patients (56.4%) were female. Most of the patients (78.5%) were categorized into the New York Heart Association (NYHA) functional classes III/IV. Seventy-two patients (65.5%) had isolated TVR. Six-three patients (57.3%) had previously undergone heart surgery. The Kaplan-Meier survival rates at one year, three years, and five years were 59.0%±5%, 52.0%±6%, and 48.0%±6%, respectively. A Cox regression analysis demonstrated that the risk factors for mid-term mortality were advanced NYHA class (hazard ratio [HR] 2.430, 95% confidence interval [CI] 1.099-5.375, P=0.028), need for continuous renal replacement therapy (CRRT) treatment (HR 3.121, 95% CI 1.610-6.050, P=0.001), and need for intra-aortic balloon pump (IABP) treatment (HR 3.356, 95% CI 1.072-10.504, P=0.038). Conclusion: In TVR, impaired cardiac function before the operation and a need for CRRT or IABP treatment after the operation is independently associated with increased mid-term mortality.

OBJECTIVES: Our purpose was to examine the associations of female genital infections and certain comorbidities with infertility. METHODS: The Taiwan National Health Research Database was searched for women with a new diagnosis of infertility between 2000 and 2013. Women without a diagnosis of infertility served as a control group and were matched with the infertility cases by age (±3 years) and index year. They were divided into two groups: ≤40 years old and >40 years old. Univariate and multivariate conditional logistic regression models were employed to identify the risk factors associated with infertility. RESULTS: A total of 18,276 women with a new diagnosis of infertility and 73,104 matched controls (mean cohort age, 31±6.2 years) were included. According to the adjusted multivariate analysis, pelvic inflammatory disease involving the ovary, fallopian tube, pelvic cellular tissue, peritoneum (odds ratio (OR)=4.823), and uterus (OR=3.050) and cervical, vaginal, and vulvar inflammation (OR=7.788) were associated with an increased risk of infertility in women aged ≤40 years. In women aged >40 years, pelvic inflammatory disease of the ovary, fallopian tube, pelvic cellular tissue, and peritoneum (OR=6.028) and cervical, vaginal, and vulvar inflammation (OR=6.648) were associated with infertility. Obesity, lipid metabolism disorders, dysthyroidism, abortion (spontaneous or induced), bacterial vaginosis, endometritis, and tubo-ovarian abscess were associated with an increased risk of infertility according to the univariate analysis but not the multivariate analysis. CONCLUSIONS: Female genital tract infections, but not the comorbidities studied here, are associated with an increased risk of infertility.

The effects of Dangguibuxue Tang (DBT) on growth performance and immunity response in immunosuppressed broiler chicks were investigated in this study. 240 one-d-old broiler chicks (DaHeng S01) were randomly divided into 4 groups, 2.0% DBT-treatment (A), 0.5% DBT-treatment (B), cyclophosphamide-control (C), and control group (D). From 4 d to 7 d of age, chicks in group A, B and C were given cyclophosphamide (CY) at a dosage of 100mg/kg body weight (BW) daily by intraperitoneal injection to induce immunosuppression. Chicks in group D were given an equal volume of physiological saline daily by intraperitoneal injection and considered normal chicks. Groups A and B were supplemented with 2.0% or 0.5% of DBT in the drinking water from 8 d to 42 d of age. Groups C and D did not receive any additional medication. The results revealed that chicks from group B had lower feed:gain rate (FGR), lower total mortality, higher immunity organ indexes, higher levels of Newcastle disease (ND) antibody and infectious bursal disease (IBD) antibody, higher interleukin-2 and interleukin-6 levels, and greater lymphocyte proliferative responses to concanavalin A (ConA) during the experiment than those from group C. However, no significant difference in the immunity status in the two levels of DBT-treatment was observed. These results indicate that supplementation of 0.5% of DBT can improve both cellular immunity and humoral immunity in immunosuppressed broiler chicks.