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Intrinsic breast cancer molecular subtyping (IBCMS) provides significant prognostic information for patients with breast cancer and helps determine treatment. This study compared IBCMS methods on various gene-expression platforms in PALOMA-2 and PALLET trials. PALOMA-2 tumor samples were profiled using EdgeSeq and nanostring and subtyped with AIMS, PAM50, and research-use-only (ruo)Prosigna. PALLET tumor biopsies were profiled using mRNA sequencing and subtyped with AIMS and PAM50. In PALOMA-2 (n = 222), a 54% agreement was observed between results from AIMS and gold-standard ruoProsigna, with AIMS assigning 67% basal-like to HER2-enriched. In PALLET (n = 224), a 69% agreement was observed between results from PAM50 and AIMS. Different IBCMS methods may lead to different results and could misguide treatment selection; hence, a standardized clinical PAM50 assay and computational approach should be used.Trial number: NCT01740427.

Abstract Background Post-stroke cognitive impairment (PSCI) not only increases patient mortality and disability, but also adversely affects motor function and the ability to perform routine daily activities. Current therapeutic approaches for, PSCI lack specificity, primarily relying on and medication and traditional cognitive therapy supplemented by a limited array of tools. Both transcranial direct current stimulation (tDCS) and virtual reality (VR) training have demonstrated efficacy in improving cognitive performance among PSCI patients. Previous findings across various conditions suggest that implementing a therapeutic protocol combining tDCS and VR (tDCS - VR) may yield superior in isolation. Despite this, to our knowledge, no clinical investigation combining tDCS and VR for PSCI rehabilitation has been conducted. Thus, the purpose of this study is to explore the effects of tDCS - VR on PSCI rehabilitation. Methods This 4-week, single-center randomized clinical trial protocol will recruit 200 patients who were randomly assigned to one of four groups: Group A (tDCS + VR), Group B (tDCS + sham VR), Group C (sham tDCS + VR), Group D (sham tDCS + sham VR). All four groups will receive conventional cognitive rehabilitation training. The primary outcome measurement utilizes the Mini-Mental State Examination (MMSE). Secondary outcome measures include the Montreal Cognitive Assessment, Frontal Assessment Battery, Clock Drawing Test, Digital Span Test, Logic Memory Test, and Modified Barthel Index. Additionally, S-YYZ-01 apparatus for diagnosis and treating language disorders assesses subjects’ speech function. Pre- and post-four-week intervention assessments are conducted for all outcome measures. Functional near-infrared spectroscopy (fNIRS) is employed to observe changes in oxygenated hemoglobin (HbO), deoxy-hemoglobin (HbR), and total hemoglobin (HbT) in the cerebral cortex. Discussion Our hypothesis posits that the tDCS - VR therapy, in opposed to individual tDCS or VR interventions, could enhance cognitive function, speech ability and daily living skills in PSCI patients while concurrently augmenting frontal cortical activity. This randomized study aims to provide a robust theoretical foundation supported by scientific evidence for the practical implementation of the tDCS - VR combination as a secure and efficient PSCI rehabilitation approach. Trial registration Chictr.org.cn Identifier: ChiCTR2300070580. Registered on 17th April 2023.

Abstract Pedunculoside and rotundic acid, the most abundant components in plants of the genus Ilex L. (Aquifoliaceae), exhibit biological and pharmacological significance in the treatment of cardiovascular diseases. However, there have been few studies on their metabolism. This study performed a systematic metabolism study of pedunculoside and rotundic acid and evaluated their potential for herb–drug interaction. Pedunculoside or rotundic acid was incubated with human liver microsomes and recombinant human metabolic enzymes, and analyzed using LC‐Q‐TOF/MS and LC–MS/MS. Pedunculoside was found to be the most stable in human liver microsomes, whereas rotundic acid was easily metabolized. Eight pedunculoside metabolites and six rotundic acid metabolites were detected and tentatively identified through hydroxylation, glucuronidation, acetylation, and glucose conjugation. Hydroxylation of pedunculoside is mainly catalyzed by CYP3A4/5 and partly by CYP2C8. Hydroxylation of rotundic acid is almost exclusively catalyzed by CYP3A4/5, and its glucuronidation reaction is mediated by UGT1A4. Neither pedunculoside nor rotundic acid showed CYP inhibition (IC50 values > 50 μM) with the probe substrates of major CYP isoforms during incubation with human liver microsomes. This study is the first investigation into the in vitro metabolism of pedunculoside and rotundic acid using human liver microsomes. It also aims to assess their potential as perpetrators of drug–drug interactions involving CYP enzymes. The comprehensive metabolism and drug interaction studies of pedunculoside and rotundic acid enable us to evaluate and manage potential risks with their use in pharmacotherapy.

ObjectiveTo observe the efficacy and safety of pelvic floor magnetic stimulation (PFMS) combined with mirabegron in female patients with refractory overactive bladder (OAB) symptoms.Patients and methodsA total of 160 female patients with refractory OAB symptoms were prospectively randomized into two groups. Eighty cases in the combination group accepted PFMS and mirabegron therapy and 80 cases as control only accepted mirabegron therapy (The clinical trial registry number: ChiCTR2200070171). The lower urinary tract symptoms, OAB questionnaire (OAB-q) health-related quality of life (HRQol), symptom bother score and OABSS between two groups were compared at the 1st, 2nd and 4th week ends.ResultsAll of 160 patients were randomly assigned to two groups, of which 80 patients were included in the combination group and 80 in the mirabegron group. The incidences of LUTS, including urgency, frequent urination, and incontinence episodes, in the 2nd week and the 4th week after combination treatment were significantly lower than those in the mirabegron group (p 0.05). With respect to secondary variables, the OAB-q HRQol score in the combination group was statistically superior in comparison with that in the mirabegron group between the 2nd week and the 4th week (p

Background: Ginsenoside Rg1 has been studied to improve systemic inflammatory injury induced by sepsis, but its mechanism is not fully understood. The objective of this study was to explore the potential molecular mechanism by which Rg1 ameliorates septic intestinal barrier function impairment. Results: Rg1 administration or miR-30e-5p upregulation alleviated LPS-induced apoptosis of Caco2 cells, decreased LDH and inflammatory cytokines levels, enhanced cell proliferation, promoted tight junction protein expression, and inhibited p65 phosphorylation. These beneficial effects of Rg1 were compensated by miR-30e-5p knockdown or FBXO11 overexpression. Animal studies have also yielded consistent results. Mechanistically, Rg1 performed this role by upregulating miR-30e-5p and inhibiting FBXO11 expression. Conclusions: Rg1 protects intestinal barrier function in sepsis by regulating the miR-30e-5p/FBXO11 axis. These data provide new insights into the development of targeted agents for septic intestinal injury and the understanding of Rg1's therapeutic mechanisms. How to cite:: Zhu W, Fan D, Zhou Z, et al. Ginsenoside protects intestinal barrier function and improves epithelium injury in sepsis by regulating the miR-30e-5p/FBXO11 axis. Electron J Biotechnol 2023;66. https://doi.org/10.1016/j.ejbt.2023.07.001.

Purpose: This study aims to investigate the potential of Oregon grape root extracts to modulate the activity of P-glycoprotein.Methods: We performed 3H-CsA or 3H-digoxin transport experiments in the absence or presence of two sources of Oregon grape root extracts (E1 and E2), berberine or berbamine in Caco-2 and MDCKII-MDR1 cells. In addition, real time quantitative polymerase chain reaction (RT-PCR) was performed in Caco-2 and LS-180 cells to investigate the mechanism of modulating P-glycoprotein.Results: Our results showed that in Caco-2 cells, Oregon grape root extracts (E1 and E2) (0.1–1 mg/mL) inhibited the efflux of CsA and digoxin in a dose-dependent manner. However, 0.05 mg/mL E1 significantly increased the absorption of digoxin. Ten µM berberine and 30 µM berbamine significantly reduced the efflux of CsA, while no measurable effect of berberine was observed with digoxin. In the MDCKII-MDR1 cells, 10 µM berberine and 30 µM berbamine inhibited the efflux of CsA and digoxin. Lastly, in real time RT-PCR study, Oregon grape root extract (0.1 mg/mL) up-regulated mRNA levels of human MDR1 in Caco-2 and LS-180 cells at 24 h.Conclusion: Our study showed that Oregon grape root extracts modulated P-glycoprotein, thereby may affect the bioavailability of drugs that are substrates of P-glycoprotein.

AbstractObjective To investigate the predictive value of serum d-serine level for hearing impairment (HI) in uremic patients.Methods In this study, 30 uremic patients with HI and 30 with normal hearing were selected. The basic conditions, biochemical indicators, and serum serine levels of the two groups were compared to analyze the influencing factors of HI.Results The age and d-serine levels were higher in the HI group, while the l-serine level was lower than uremia in the normal hearing group. Logistic regression analysis showed that d-serine level ≥10 μM and older age increased the risk of HI. The area of the receiver operating characteristic (ROC) curve drawn by the prediction probability of HI was 0.838, indicating that age, d-serine, and l-serine had predictive diagnostic values for HI (p