Vitamin C (VC) is one of nine water-soluble vitamins. VC is known as ascorbic acid (AA), which is a reduced form of VC. AA plays some essential roles in the human body: (1) protecting skin against UV damage; (2) preventing hyperpigmentation of the skin; (3) improving skin inflammation and reducing photocarcinogenesis; (4) increasing collagen fiber; (5) reducing oxidative stress; and (6) immuno-modulating effects. AA deficiency affects collagen and vessels structure, wound healing and hemostasis, and scurvy. VC and AA are essential for life. We hope development of new medicines using VC or AA because of few adverse side effects of VC and AA.

The up regulation of anti-tumor responses by immune-checkpoint blockade is a new approach for the treatment of advanced solid malignant tumors. There are some demerits to this therapy that require an evaluation of eligibility and efficacy, balanced against adverse effects and cost. Treatment for patients without immune checkpoint receptors or ligands remains an issue of concern. The cost of this therapy is huge and is further increased when treatment is required for adverse effects. The appropriate use of immune checkpoint therapy requires careful consideration.

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Background:Pigmented nevi develop at approx. 6 months after birth, and the number of pigmented nevi often increases until middle age. Pigmented nevi evolve with age and finally disappear. Materials and methods:We studied 300 nevi of 78 male and 222 female Japanese patients. We analyzed the patients' histopathological findings, the locations of their nevi, and their gender and age. We divided the nevi into three groups (1. all three histopathological-group, 2. junctional and compound group, 3. compound and intradermal group) based on their locations and pathological findings. Sun-exposed areas were the head, face, neck, limbs and hands. Other areas were classified as the non-sun-exposed areas.Results: There were 41 junctional nevi, 73 compound nevi, and 186 intradermal nevi. The number of pigmented nevi peaked at middle age. The average age of the patients with intradermal nevi was significantly (P<0.05) older than those of the patients with junctional or compound nevi. The peaks in the numbers of junctional (30's) and compound nevi (20's) were lower than that of intradermal nevi. All three histopathologicalgroups were observed on the face and back. The junctional and compound nevi groups were observed on the hands, feet and soles. The compound and intradermal nevi groups were observed at the head, neck, chest, upper limb, abdomen, lumbar and buttock.The face had the largest number of compound nevi and intradermal nevi; 28 and 93 cases, respectively. Junctional nevi were observed more commonly in the non-sun-exposed areas compared to the sun-exposed areas, whereas for the compound and intradermal nevi, the number of nevi at the sun-exposed areas was larger than that in the non-sun-exposed areas. The number of nevi arising at sun-exposed areas was greater than that at non-sunexposed areas in all generations. Conclusions:Pigmented nevi often appear as junctional nevi and then migrate or evolve with age.

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