Cholangiocarcinoma (CCA) is a category of highly heterogeneous and aggressive malignancy mainly originating from bile duct epithelial cells. The median survival time of untreated CCA patients is approximately 12?24 months, and the effectiveness and durability of surgical resection and neoadjuvant chemotherapy are limited. Results of the next-generation sequencing show that dysregulation of the immune system plays an important role in the pathogenesis of CCA. It has opened up new possibilities for the study of therapies targeting the natural course of aggressive CCA, such as immune checkpoint inhibitors, adoptive cell therapy, and tumor vaccines. Based on the current status of immunotherapy for CCA, the authors review the efficacy and dilemmas of current CCA immunotherapy strategies and look forward to the future treatment prospects of CCA.

Purpose Hydrogen proton magnetic resonance imaging was used to study the brain metabolism of menstrual-related migraine(MRM)in different states,and to investigate its correlation with clinical features and estrogen and progesterone.Materials and Methods We recruited 36 patients with MRM diagnosed by neurology outpatient experts of the First Affiliated Hospital of Henan University of Science and Technology from April 2019 to August 2022,and also recruited 29 normal women with age-and education-matched.Proton magnetic resonance spectroscopy was used to assess neurochemical brain changes during interictal period(late follicular phase)and ictal period(perimenstrual phase)in them.The point resolved spectroscopic sequence was used to focus on the bilateral medial prefrontal cortex(mPFC)and bilateral thalamus.Sex hormone levels were collected on the same day of MRI acquisition.The ratios of NAA/Cr,GABA/Cr,Glx/Cr and Cho/Cr were observed.Metabolite changes and hormone levels were investigated among two groups.Furthermore,metabolite changes were investigated in a longitudinal design during the interictal period and ictal period.Results There were no significant differences in the levels of estrogen and progesterone both in the late follicular and perimenstrual periods.There were no significant differences in decline rate of them in perimenstrual periods between patients and normal people(P>0.05).During interictal period,the ratio of Cho/Cr in the region of left mPFC was lower significantly in the MRM group than that of control group(U=-2.957,P=0.003)and showed a significant negative correlation with attack frequency(r=-0.398,P=0.018).During ictal period,the women with MRM had significantly lower the ratio of GABA/Cr in the left mPFC and higher the ratio of Glx/Cr in the left thalamus compared to those of controls(U=-2.015,P=0.044;t=2.213,P=0.033).We found no significant correlations between these results and magraine characteristics(P>0.05).In addition,we found the ratio of GABA/Cr did not change(P>0.05),the ratio of Glx/Cr and Cho/Cr in right thalamus increased from interictal towards the ictal state for MRM patients(t=-2.181,P=0.038;Z=-2.414,P=0.016).Conclusion The present study suggests the existence of distinct cerebral metabolism states between MRM and control,and there are dynamic changes in cerebral metabolism with headache attacks.However,there is no significant difference in estrogen and progesterone from normal women,and its neural mechanism still needs to be further studied.