Potent inhibition of cytochrome P450 2D6 (CYP2D6) in human liver microsomes by fluoxetine and its major metabolite norfluoxetine was confirmed (apparent inhibition constant values, 0.2 mumol/L). Several other serotonergic agents were also found to be competitive inhibitors of this genetically polymorphic enzyme. The O-demethylation ratio of dextromethorphan that expressed CYP2D6 activity in 19 patients receiving fluoxetine fell in the region of the antimode separating the O-demethylation ratio values observed in 208 extensive metabolizers from 15 poor metabolizers of a control group of healthy subjects. Inhibition of CYP2D6 activity in patients undergoing treatment with fluoxetine or other serotonin uptake inhibitors could contribute to toxicity or attenuated response from concurrent medications that are substrates of this enzyme. Other in vitro studies indicated that CYP2D6 catalyzes the O-demethylation of oxycodone to form oxymorphone. This reaction was inhibited by fluoxetine and its normetabolite in liver microsomes from both extensive and poor metabolizer individuals, indicating that these compounds are not selective inhibitors of CYP2D6 activity.

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1. In microsomes prepared from three human livers, methadone competitively inhibited the O‐demethylation of dextromethorphan, a marker substrate for CYP2D6. The apparent Ki value of methadone ranged from 2.5 to 5 microM. 2. Two hundred and fifty‐two (252) white Caucasians, including 210 unrelated healthy volunteers and 42 opiate abusers undergoing treatment with methadone were phenotyped using dextromethorphan as the marker drug. Although the frequency of poor metabolizers was similar in both groups, the extensive metabolizers among the opiate abusers tended to have higher O‐demethylation metabolic ratios and to excrete less of the dose as dextromethorphan metabolites than control extensive metabolizer subjects. These data suggest inhibition of CYP2D6 by methadone in vivo as well. 3. Because methadone is widely used in the treatment of opiate abuse, inhibition of CYP2D6 activity in these patients might contribute to exaggerated response or unexpected toxicity from drugs that are substrates of this enzyme.

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ProblemThe aim of this prospective study was to investigate the prevalence of chronic endometritis (CE) in repeated implantation failure (RIF) patients and to determine whether intrauterine delivery of the combined administration of antibiotic and dexamethasone improves the clinical pregnancy outcome.Method of studyThe combination of hysteroscopy and histology was used to diagnose CE in the patients with RIF, and the diagnosed patients were treated with the intrauterine delivery of the combined antibiotic and dexamethasone therapy. The prevalence of CE in the RIF patients was recorded, and the therapeutic effect was also evaluated in the first IVF‐ET cycle.ResultsIn a total number of 298 patients with RIF, 109 cases (36.58%) were diagnosed as CE. Intrauterine infusion treatment resulted in CE resolution in 77.98% of patients. After the treatment, 85 cases with no signs of CE (Group 2) had a significantly higher implantation rate (31.33%) and clinical pregnancy rate (51.76%) as compared with both 126 cases without CE diagnosis (Group 1; 16.30% and 30.15%, respectively) and 24 cases with persistence of CE (Group 3; 14.89% and 25.00%, respectively). The live birth rate in the first IVF‐ET cycle following treatment in Group 2 was significantly higher than that of both Group 1 and Group 3 (all P < .05).ConclusionChronic endometritis is highly prevalent in patients with RIF. To the best of our knowledge, we for the first time reported that intrauterine delivery of the combined administration of antibiotic and dexamethasone as a treatment option of CE could achieve expected therapeutic effects and successful pregnancy outcomes.

Performance evaluation is of great importance for effective supply chain management. The foundation of efficiency evaluation is to faithfully identify the corresponding production possibility set. Although a lot of researches have been done on supply chain DEA models, the exact definition for supply chain production possibility set is still in absence. This paper defines two types of supply chain production possibility sets, which are proved to be equivalent to each other. Based upon the production possibility set, a supply chain CRS DEA model is advanced to appraise the overall technical efficiency of supply chains. The major advantage of the model lies on the fact that it can help to find out the most efficient production abilities in supply chains, by replacing or improving inefficient subsystems (supply chain members). The proposed model also directly identifies the benchmarking units for inefficient supply chains to improve their performance. A real case validates the reasonableness and acceptability of this approach.

Background Ovarian clear cell carcinoma (OCCC) is a special pathological type of epithelial ovarian carcinoma (EOC). We conducted this research to investigate the clinical characteristics and outcomes of OCCC and to provide additional supporting evidence to aid in the clinical diagnosis and management. Methods This was a retrospective study investigating the clinical characteristics and survival outcomes of 86 patients with OCCC treated at our center between January 2010 and March 2020. Survival analysis was also performed on 179 patients with OCCC obtained from the Surveillance, Epidemiology and End Results (SEER) cancer registry database. Results The median age of participants was 49.21 ± 9.91 years old, and 74.42% of them were diagnosed at early stage. The median CA125 level was 601.48 IU/mL, while 19.77% of the patients had normal CA125 levels. Sixteen patients (18.60%) had co-existing endometriosis and 8 patients (9.3%) developed venous thromboembolism (VTE). There were 5 patients received suboptimal cytoreduction. Sixty-six patients (76.74%) underwent lymphadenectomy, and only 3 (4.55%) patients had positive lymph nodes. Patients diagnosed at an early stage had higher 3-year overall survival (OS) and progression-free survival (PFS) rates than those with advanced stage OCCC. CA19–9 (P = 0.025) and ascites (P = 0.001) were significantly associated with OS, while HE4 (P = 0.027) and ascites (P = 0.001) were significantly associated with PFS. Analysis of data from the SEER database showed that positive lymph nodes is also an independent prognostic factor for OS (P = 0.001). Conclusions OCCC often presents at an early stage and young age with a mildly elevated CA125. CA19–9, HE4, massive ascites, and positive lymph node are independent prognostic factors.