OBJECTIVE To investigate the intervention effect of kushenol F （KSC-F） on ulcerative colitis （UC） mice. METHODS Totally 30 male C57BL/6J mice were randomly divided into the normal group， model group， positive drug group （sulfasalazine， 703 mg/kg）， KSC-F 50 mg/kg group （KSC-F50 group）， and KSC-F 100 mg/kg group （KSC-F100 group）， with 6 mice in each group. Except for the normal group， the mice in the remaining groups were given 3% dextran sulfate sodium solution continuously for 7 days to induce UC model. Concurrently， administration groups received corresponding drug solution intragastrically， once a day， for 10 consecutive days. During the experiment， the changes in body weight and bowel movements of the mice were observed. Disease activity index scoring was performed after the last administration. The histopathological morphology of colonic tissue was examined. The levels of inflammatory factors in the serum and colon tissue were measured. Additionally， the mRNA expression of inflammatory factors， and the protein expressions of inflammation-related proteins [interleukin-1β （IL-1β）， forkhead box O1（FOXO1）， phosphoinositide 3-kinase（PI3K）， phosphorylated PI3K（p-PI3K）， p38 mitogen-activated protein kinase（p38 MAPK）， phosphorylated p38 MAPK（p-p38 MPAK） and phosphorylated protein kinase B（p- Akt）] were determined in colonic tissue. RESULTS KSC-F could alleviate weight loss and colonic tissue damage in UC mice. KSC- F reduced the levels of IL-1β， IL-6， IL-8 and tumor necrosis factor-α （TNF-α） in serum， as well as IL-1β， IL-6， IL-17 and TNF- α in colonic tissue to varying degrees and increased the levels of IL-10 in both serum and colonic tissue （P＜0.05 or P＜0.01）. Moreover， KSC-F decreased the expression levels of IL-1β， IL-17 and TNF-α mRNA， as well as p-PI3K， p-p38 MAPK， and p- Akt proteins in colonic tissue to varying degrees， and increased the expression levels of IL-10 mRNA and FOXO1 protein in colonic tissue （P＜0.05 or P＜0.01）. CONCLUSIONS KSC-F effectively alleviates UC symptoms in mice by inhibiting PI3K， Akt and p38 MAPK activation， mitigating the release of pro-inflammatory factors such as IL-1β， IL-6， TNF- α，promoting the anti-inflammatory factor IL-10 secretion， and reducing inflammation-induced colonic tissue damage.

Third space fluid(TSF) is a common complication of advanced malignancies, including malignant pleural effusion, malignant ascites, intracranial effusion, and pelvic effusion, etc. The pharmacokinetics(PK) of anti-tumor drugs in vivo are influenced by various factors, and TSF is one of the potential factors that contributes to PK variations, which may consequently affect the efficacy and safety of anti-tumor drugs. This paper aimed to comprehensively investigate PK studies related to anti-tumor drugs in patients with malignant tumors accompanied by TSF. The paper summarized the PK characteristics of common cytotoxic drugs, small molecule targeted drugs, and monoclonal antibodies in both blood and TSF.

Novel oral anticoagulants (NOAC)include direct thrombin inhibitors (ximelagatran and dabigatran etexilate ) and coagulation factor Xa inhibitors (rivaroxaban, apixaban and edoxaban ). Ximelagatran was withdrawn from the market in 2006 because of its high incidence of liver injury after listing in 2004,which has aroused concern about the hepatotoxicity of NOAC. No significant evidence of hepatotoxicity was found in pre-clinical studies on dabigatran etexilate,rivaroxaban,apixaban,or edoxaban and their risks of liver injury were low. However,pre-marketing clinical studies,post-marketing literature reports,and pharmacovigilance data showed that the incidence of NOAC-related liver injury was 0.1% to 1.0%. Reports of liver adverse events related to rivaroxaban were more than those related to apixaban and dabigatran etexilate. The patients who use NOAC have underlying diseases. Once liver injury occurs,it is more serious and the mortality is higher. Clinicians should be highly vigilant. The mechanism of NOAC-related hepatotoxicity is still unclear and further study is needed in the future.

Novel oral anticoagulants (NOAC)include direct thrombin inhibitors (ximelagatran and dabigatran etexilate ) and coagulation factor Xa inhibitors (rivaroxaban, apixaban and edoxaban ). Ximelagatran was withdrawn from the market in 2006 because of its high incidence of liver injury after listing in 2004,which has aroused concern about the hepatotoxicity of NOAC. No significant evidence of hepatotoxicity was found in pre-clinical studies on dabigatran etexilate,rivaroxaban,apixaban,or edoxaban and their risks of liver injury were low. However,pre-marketing clinical studies,post-marketing literature reports,and pharmacovigilance data showed that the incidence of NOAC-related liver injury was 0.1% to 1.0%. Reports of liver adverse events related to rivaroxaban were more than those related to apixaban and dabigatran etexilate. The patients who use NOAC have underlying diseases. Once liver injury occurs,it is more serious and the mortality is higher. Clinicians should be highly vigilant. The mechanism of NOAC-related hepatotoxicity is still unclear and further study is needed in the future.