The in vitro studies of triptolide with CYP isoforms and P-gp indicate that triptolide has the potential to cause pharmacokinetic drug interactions with other co-administered drugs metabolized by CYP1A2 and CYP3A4. Further clinical studies are needed to evaluate the significance of this interaction.

Objectives The aim of this study was to explore the Vitamin D receptor (VDR) gene polymorphism and its association with multiple myeloma (MM) development. Methods The peripheral blood of 40 MM cases and 84 healthy controls were collected. Polymerase chain reaction (PCR) and DNA sequencing were applied to detect VDR gene polymorphism (including: FokI, BsmI, ApaI, and TaqI). SHESIS biological information software was used to analyze genotypes, alleles, linkage disequilibrium (LD), haplotype distribution, and their association with MM. Results Compared with controls, the MM group had a significantly higher frequency of the A allele in BsmI site (8.7% vs 2.4%) and C allele in the TaqI site (10.5% vs 3.6%). These two alleles were closely associated with an increased risk of MM (P = .025; P = .030). The highly rare genotypes (BsmI‐AA and TaqI‐CC) were found in one patient with MM. Conclusion VDR gene polymorphisms may be a molecular marker of MM risk.

Context: Dihydromyricetin (DHM) is the most abundant and active flavonoid component isolated from Ampelopsis grossedentata (Hand-Mazz) W.T. Wang (Vitaceae) and it possesses numerous pharmacological activities. However, whether DHM affects the activity of human liver cytochrome P450 (CYP) enzymes remains unclear. Materials and methods: The inhibitory effects of DHM on eight human liver CYP isoforms (i.e., 1A2, 3A4, 2A6, 2E1, 2D6, 2C9, 2C19 and 2C8) were investigated in vitro using human liver microsomes (HLMs). Results:The results showed that DHM could inhibit the activity of CYP3A4, CYP2E1 and CYP2D6, with IC 50 values of 14.75, 25.74 and 22.69 lM, respectively, but that other CYP isoforms were not affected. Enzyme kinetic studies showed that DHM was not only a non-competitive inhibitor of CYP3A4 but also a competitive inhibitor of CYP2E1 and CYP2D6, with Ki values of 6.06, 9.24 and 10.52 lM, respectively. In addition, DHM is a time-dependent inhibitor for CYP3A4 with K I /K inact value of 12.17/0.057 min À1 lM À1 . Discussion and conclusion: The in vitro studies of DHM with CYP isoforms indicate that DHM has the potential to cause pharmacokinetic drug interactions with other co-administered drugs metabolized by CYP3A4, CYP2E1 and CYP2D6. Further clinical studies are needed to evaluate the significance of this interaction. ARTICLE HISTORY

This study aimed to explore the proliferation and apoptosis of B-cell lymphoma cells under targeted regulation of FOXO3 by miR-155. We analyzed the differences between B-cell lymphoma cells and B lymphocytes in expressions of miR-155 and FOXO3, explored the effects of miR-155 on proliferation and apoptosis of B-cell lymphoma cells, and relevant mechanisms, and also analyzed the relationship between expressions of miR-155 and FOXO3 in 42 patients with diffuse large B-cell lymphoma (DLBCL) and clinical characteristics of them. B-cell lymphoma cells showed a higher expression of miR-155 and a low expression of FOXO3 than B lymphocytes (both P<0.05). B-cell lymphoma cells transfected with miR-155-inhibitor showed significantly decreased expression of miR-155, significantly weakened cell proliferation ability and increased cell apoptosis rate (all P<0.05), and they also showed up-regulated expression of FOXO3 (P<0.05). Dual luciferase reporter assay revealed that there were targeted binding sites between miR-155 and FOXO3. Compared with B-cell lymphoma cells transfected with miR-155-inhibitor alone, those with co-transfection showed lower expression of FOXO3, higher proliferation and lower cell apoptosis rate (all P<0.05). The expression of miR-155 in DLBCL tissues was higher than that in tumor-adjacent tissues (P<0.05), and the expressions of miR-155 and FOXO3 were closely related to the international prognostic index (IPI) and the 5-year prognosis and survival of the patients (P<0.05). miR-155 can promote the proliferation of B-cell lymphoma cells and suppress apoptosis of them by targeted inhibiting FOXO3, and both over-expression of miR-155 and low expression of FOXO3 are related to poor prognosis of DLBCL patients.

Objectives To explore the risk factors for systemic lupus erythematosus (SLE) flare and their impact on prognosis. Methods The clinical characteristics, laboratory results, and treatment plans of 121 patients with SLE flare were retrospectively analyzed. Ninety-eight SLE outpatients with sustained remission during the same period were selected as controls. Logistic multivariate regression analysis was employed to screen for risk factors for SLE flare. Results Infection, thrombocytopenia, arthritis, anti-nucleosome antibodies positive, anti-β2-glycoprotein I (IgG) antibodies positive, and patient’s self-discontinuation of medicine maintenance therapy might be risk factors for SLE flare. Patients who discontinued medicine maintenance therapy by themselves had a significantly higher rate of severe SLE flare than patients with regular medicine maintenance therapy (P = 0.033). The incidence of anemia associated with SLE (P = 0.001), serositis (P = 0.005), and pulmonary hypertension (P = 0.003) in patients who discontinued medicine maintenance therapy were significantly higher than patients with regular medicine maintenance therapy. SLE patients with regular medicine maintenance therapy for less than 3 years had a higher risk of pulmonary hypertension than those with regular medicine maintenance therapy longer than 3 years (P = 0.034). Conclusions The accompanying thrombocytopenia, arthritis, anti-nucleosome antibodies positive and anti-β2-glycoprotein I (IgG) antibodies positive at the onset of SLE may affect the prognosis of SLE. Patient’s self-discontinuation of medicine maintenance therapy is the main cause of SLE flare, which may induce severe flare in SLE patients and lead to a significantly higher incidence of pulmonary hypertension.

Taurine can effectively enhance the immune function of mice with T-cell lymphoma during chemotherapy, reduce the toxicity of chemotherapy.

Immunoassayable TRH in human ejaculate was eluted from a gel column in a form with a molecular weight larger than that of the native peptide. With reverse-phase high-performance liquid chromatography (HPLC) the same activity co-eluted with standard TRH. Incubation of ejaculates at room temperature for 8 h was associated with a time-related increase in the total immunoassayable TRH. Analysis by HPLC of ejaculates after 12 h of incubation at room temperature indicated that, whereas the levels of the peptide co-eluting with native TRH declined with time, there was a concomitant increase in the concentration of a molecular species which also cross-reacted with the TRH antiserum, but which was more hydrophobic. The latter species is presumably identical to the tetrapeptide recently described by others and which may arise from the proteolytic degradation of secretory macromolecules. Although immunological activity was present in all six fractions of split ejaculates, the bulk of the peptide was associated with the later portions, implying a major vesicular contribution. However, secretions isolated from surgical preparations of the seminal vesicles contained undetectable levels of peptide, suggesting that the ejaculation process may represent a stimulus for its appearance in the semen. This study is further support for a local involvement of TRH in male reproductive function.

BACKGROUND CD163 is a scavenger receptor specifically expressed by cells of monocyte/macrophage lineage. It is a biomarker in many clinical conditions, including coronary artery disease, anti-inflammatory response, and cancers. In breast cancer, high numbers of CD163-positive macrophages correlated with unfavorable outcome. Expression of CD163 in breast cancer was also related to early distant recurrence and poor survival. In this study we evaluated whether CD163 expression was associated with aggressive breast cancers from patients enrolled in the Clinical Breast Care Project (CBCP). METHODS Patients were enrolled into the CBCP following IRB-approved, HIPAA-compliant protocols. The study focused on 129 invasive breast cancer samples with CD163 immunohistochemistry (IHC) results. Expression of CD163, ER, PR, HER2, and Ki67 were assayed by IHC. CD163 was positive if IHC&gt;0. ER and PR were positive if there was &gt;5% nuclear staining. HER2 was negative if IHC=0 or 1+ and positive if IHC=3+. For HER2 IHC=2+, HER2 was negative if FISH was &lt;1.8 and positive if FISH was &gt;2.2. Ki67 was positive if there was ≥15% nuclear staining. For subtyping, Luminal A (LA) was ER+/HER2-/Ki67-, Luminal B1 (LB1) was ER+/HER2-/Ki67+, Luminal B2 (LB2) was ER+/HER2+, Her2+ was ER-/PR-/HER2+, and triple negative (TN) was ER-/PR-/HER2-. Associations of CD163 IHC score with age, race, and IHC subtype were examined by Wilcoxon rank-sum tests and/or Fisher's exact tests. Prognoses of CD163 in overall survival (OS), disease specific survival (DSS), disease free survival (DFS), and recurrence were studied using univariable and multivariable Cox proportional hazards regression models. CD163 score, age, race, AJCC stage, and subtype were included in the multivariable model. RESULTS CD163 IHC score displayed a significant negative correlation with age (R=-0.20, P=0.022). Patients with a CD163 score of 3+ were significantly younger than those with a score of 0 (P=0.019). CD163 score distributions were not statistically different between white and African American patients. CD163 scores of LA tumors were significantly lower than those of the tumors with all other subtypes except Her2+. Similarly, the CD163 scores of TN tumors were significantly higher than those of the tumors with all other subtypes but LB2. A higher CD163 score predicted worse DSS (HR=3.87 & P=0.0020 in univariable model; HR=4.21 & P=0.033 in multivariable model) and higher risk of recurrence (HR=2.85 & P=0.00016 in univariable model; HR=2.81 & P=0.012 in multivariable model). CONCLUSION Higher CD163 expression in breast cancer was significantly associated with younger age, the TN subtype, worse DSS, and higher risk of recurrence. These results highlight CD163 as a prognostic marker for breast cancer. The views expressed in this article are those of the author and do not reflect the official policy of the Department of Defense, or U.S. Government. Citation Format: Ru Y, Hu PT, Kovatich AJ, Hooke JA, Liu J, Kvecher L, Fantacone-Campbell JL, Deyarmin B, Kovatich AW, Cammarata F, Rui H, Davidson-Moncada J, Shriver CD, Hu H. CD163 expression is associated with young age, triple negative subtype, and poor outcome in breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-09-24.