The vitamin K antagonist is a commonly prescribed effective oral anticoagulant with a narrow therapeutic range, and the dose requirements for different patients varied greatly. In recent years, studies on human intestinal microbiome have provided many valuable insights into disease development and drug reactions. A lot of studies indicated the potential relationship between microbiome and the vitamin K antagonist. Vitamin K is absorbed by the gut, and the intestinal bacteria are a major source of vitamin K in human body. A combined use of the vitamin K antagonist and antibiotics may result in an increase in INR, thus elevating the risk of bleeding, while vitamin K supplementation can improve stability of anticoagulation for oral vitamin K antagonist treatment. Recently, how intestinal bacteria affect the response of the vitamin K antagonist remains unclear. In this review, we reviewed the research, focusing on the physiology of vitamin K in the anticoagulation treatment, and investigated the potential pathways of intestinal bacteria affecting the reaction of the vitamin K antagonist.

Epidermal growth factor receptor (EGFR)-activating mutations are major oncogenic mechanisms in non-small cell lung cancer (NSCLC). Most patients with NSCLC with EGFR mutations benefit from targeted therapy with EGFR- tyrosine kinase inhibitors (TKIs). One of the main limitations of targeted therapy is that the tumor response is not durable, with the inevitable development of drug resistance. Previous studies demonstrated that the potential resistance mechanisms are diverse, including the presence of EGFR T790M, MET amplification, mesenchymal transformation, and anaplastic lymphoma kinase ( ALK ) rearrangement. The patient in our report was diagnosed with stage IA lung adenocarcinoma harboring the EGFR L858R mutation and underwent radical surgery. The patient received icotinib for 12 months after recurrence. Subsequent molecular analysis of the left pleural effusion indicated that LCLAT1-ALK fusion might be an underlying mechanism contributing to the acquired resistance to icotinib. Ensartinib was prescribed, but the lesion in the right lung continued to progress. Hence, a re-biopsy and molecular analysis of lesions in the right lung was performed to solve this problem. In contrast to the left pleural effusion, EGFR exon 20 T790M might have mediated the acquired resistance in lesions in the right lung of this patient. The combination of osimertinib and ensartinib has achieved a rapid partial response until now. The complexity and heterogeneity in our case may provide new insights into the resistance mechanisms of targeted therapy.

Background Dexmedetomidine (DEX) administration decreases post-operative nausea and vomiting (PONV), but it is a lack of large-scale retrospective cohort study and is unclear whether there is a dose-relationship and optimal dose for antiemetic effects between DEX and PONV. We performed a large-scale retrospective cohort study to explore the optimal dose of intraoperative DEX for antiemetic effects of PONV. Methods A total of 5,310 patients aged ≥18 who underwent elective thoracic surgery from January 2016 to March 2020 under total intravenous anesthesia (TIVA) or combined intravenous and inhalation anesthesia in Henan Provincial People's Hospital. Patients were divided into two groups, those who received DEX intraoperatively and those who did not receive DEX. Patients who received DEX after surgery were excluded. Our primary outcomes were the association, the dose-response relationship, and the optimal dose for antiemetic effects between intraoperative DEX and PONV. Results Among the 3,878 patients enrolled, 2,553 patients received DEX and 1,325 patients did not receive DEX. The incidence of PONV in patients who received DEX was 21.3%, and the incidence of PONV in patients who did not receive DEX was 46.5% ( P = 0.001). After the matched-pairs cohort consisted of 1,325 patients, the incidence of PONV in patients who received DEX was 23.6%, and the incidence of PONV in patients who did not receive DEX was 46.5% ( P = 0.001). We analyzed three different models after propensity matching to validate the stability of the prediction model between intraoperative DEX and PONV. A dose-response relationship between intraoperative DEX and PONV was observed. The optimal dose range of intraoperative DEX for antiemetic effects of PONV is 50–100 μg in elective thoracic surgery. Conclusions Intraoperative DEX was associated with a decreased incidence of PONV in the large-scale retrospective cohort study. A dose-response relationship between intraoperative DEX and PONV was observed. The optimal dose range of intraoperative DEX for antiemetic effects of PONV is 50–100 μg in elective thoracic surgery.