No abstract

Seahorse is an important high-value marine fish, which has a huge trade volume in traditional Chinese medicine (TCMs), marine aquarium and souvenir market (Job et al., 2002;Lin et al., 2012).At present, there are 54 known species of seahorse, mainly distributed in tropical and temperate oceans between 50°N and 50°S (Vincent, 2010). Among them, Hippocampus kuda Bleeker is mainly distributed in the Indian Pacific coast (Lourie et al., 2004;LePage et al., 2014).

Summary Immune checkpoint inhibitors (ICPis) are novel immunotherapy drugs for a variety of cancers. Toripalimab is one of the ICPis that selectively blocks programmed death 1 (PD-1) and has been used for the treatment of malignant cancers in the hospitals of China. But with the widespread use of ICPis, some of the adverse reactions have gradually appeared. One of the most serious side effects is diabetes mellitus which is a relatively rare immune-related adverse event (irAEs) with life-threatening complications. We report a case of diabetes after the administration of toripalimab for the treatment of melanoma in southern China. To our knowledge, this is a rare case of diabetes occurring during toripalimab therapy, there is only one similar case reported in China so far. As China has a high morbidity of malignant cancer, a significant number of patients could be affected by the adverse reactions of using ICPis. Therefore, when ICPis are administrated, it is very important for clinicians to pay attention to one of the serious side effects – diabetes mellitus. Insulin therapy is often necessary after the diagnosis of ICPis-related diabetes, which has been proved as an effective method to prevent diabetic ketoacidosis (DKA) and other life-threatening complications in these patients. Learning points Toripalimab can cause the diabetes mellitus. ICPis-related diabetes is treated primarily with insulin. Immune checkpoint inhibitors cause diabetes by primarily destroying islet β cells. There is not enough evidence to demonstrate that diabetic autoantibodies are related to diabetes caused by ICPis. In addition to focusing on the efficacy of PD-1 inhibitor therapy, it is also necessary to pay attention to its adverse reactions, such as ICPis-related diabetes mellitus.

Many researchers found that there is a close connection between biological rhythm and metabolism in mammals and humans. But, it is uncertain whether there is a central and peripheral clock system in fish or not, and it is also uncertain whether there is a relationship between them. This article used the model fish, marine medaka (Oryzias melastigma) as the experimental object, and built a complete test with 2 factors and 2 levels, the photoperiod factor with Light (L): Dark (D) = 16:8 and 12:12 and the factor of feeding time with 1 h after light and 1 h before dark, to verify the existence of the clock system and explore the relationship between biological rhythm and metabolism. The results showed that: In treatment 1# with L:D = 16:8 and 1 h after light, two clock genes of Bmal1 and Per1, among the tested 6 clock genes, had obvious rhythmic expression in the brain and in the liver, and 2 metabolic genes of Elovl5 and Lpl also had obvious rhythmic oscillations in the liver. In treatment 2# with L:D = 12:12 and 1 h after light, 3 clock genes (Bmal1, Per1 and Per2) had obvious rhythmic expression in the brain and in the liver, and 5 metabolic genes (Elovl5, Lpl, Fadsd2, Tryp, Pck) also presented rhythmic oscillations in the liver. Both treatments had the same photoperiod, the treatment with feeding at 1 h before dark still had several clock genes in the brain that were rhythmical, but neither clock gene nor metabolic gene in the liver exhibited obvious rhythmic oscillations. This study showed that there were biological rhythms in marine medaka, and there was a close relationship between the biological rhythm and the lipid metabolism. According to the set 2 factors, it is found that the photoperiod could mainly affect the central clock system, and the feeding time could mainly affect the rhythmic expression of the peripheral clock and metabolic genes. The conclusion will provide a scientific and efficient breeding strategy for marine medaka.