Objective To observe the dynamic changes of cardiac lymphangiogenesis in Doxorubicin(DOX)-induced dilated cardiomyopathy(DCM)model mice,and to study the the protective mechanism of Kuoxin Decoction.Methods The DCM mouse model was established by intraperitoneal injection of DOX,and the dynamic observation was performed every week.On this basis,60 C57BL/6 mice were randomly divided into 6 groups(n=10):control group,Model group,L-KXD,M-KXD and H-KXD groups and Captopril group.After successful modeling,the KXD and the positive control drug Captopril were administered continuously for 28 days.Echocardiography was used to detect cardiac function in mice,HE staining and Masson staining were used to observe pathological and morphological changes of the heart,Whole-mount immunofluorescent staining was used to detect the expression of LYVE-1 and Podoplanin in epicardial lymphatic vessels,Western blot was used to detect the expression of VEGFR-3 protein,and qPCR was used to detect the expression of VEGFR-3 mRNA.Results DCM mice induced by DOX showed significant cardiac function decline from the third week(DOX:15 mg·kg-1,P<0.05),and significant ventricular remodeling at the fifth week(DOX:15 mg·kg-1,P<0.01);The lymphatic vessel area of the mouse heart decreased significantly from the fourth week(DOX:20 mg·kg-1,P<0.0001),and the expression of VEGFR-3 decreased significantly from the third week(DOX:15 mg·kg-1,P<0.01).Conclusion KXD can improve ventricular remodeling and cardiac function in DOX-induced DCM mice,promote cardiac lymphangiogenesis,and upregulate the expression of VEGFR-3 at protein and mRNA levels,with a better effect than captopril.DOX-induced cardiac lymphangiogenesis in DCM mice leads to severe myocardial fibrosis and weakened cardiac function,which gradually worsens with the accumulation of modeling time and dose.KXD can promote cardiac lymphangiogenesis and improve cardiac function in DOX-induced DCM mice.The mechanism may be related to the up-regulation of VEGFR-3 expression.

Surgery is still the first choice for the curation of early gallbladder cancer, and the surgical strategy is selected based on anatomic position of primary tumor, accurate preoperative stage, and strict indication assessment in order to achieve the optimal curative effect. However, most patients are in advanced stage or with distant metastasis at the first diagnosis, and the recurrence rate and 5-year survival rate are not satisfied even if they receive curative resection. Subsequently, it is urgent for the employment of more treatment strategies in the process management of gallbladder cancer patients, such as neoadjuvant therapy, postoperative therapy and first-line or second-line treatment of local advanced and metastatic patients. In recent years, application of molecular targeted agents and immunotherapy have brought greater hope and laid a vaster prospect for the treatment of gallbladder cancer. However, there is still lack of evidence-based medicine data on the prognostic results, and further researches are needed. By integrating the domestic and abroad new research achievements, the authors systematically summarize the current status and future trend on the management of gallbladder cancer, and hope to provide a macroscopic and systemic treatment chart, including necessary details.