What's the harm of long-term day-night reversals? These 8 pictures tell you.

What about doctors who work night shift for a long time? To ask doctors what they don't like most about the industry, it must be on the list to work night shifts.but there is no way. Patients need 24-hour care.especially cardiovascular and cerebrovascular diseases, such as heart failure, cerebral infarction and cerebral hemorrhage, often come quietly in the middle of the night.there is no way to avoid diseases. We can only rely on doctors to stick to their posts and escort people's lives.but who would have thought that the long-term night shift would be a stumbling block to the doctors' longevity.before we start the text, let's do a little research: next, let's get back to the point.recently, an article was published in the journal Nature communication, which proposed that chronic circadian rhythm disorder can cause breast cancer metastasis by regulating the characteristics of cancer stem cells and immune microenvironment.this study was mainly carried out in mice. The effects of chronic circadian rhythm disorder on breast cancer metastasis were studied from the aspects of tumor initiation potential, stem cell characteristics, proliferation and metastasis, tumor microenvironment, and gene expression.Figure 1 nature Chronic circadian rhythm disorder can regulate the characteristics of tumor stem cells and immune microenvironment, thus causing breast cancer metastasis in mice. The researchers divided young and middle-aged mice (6 weeks old) with spontaneous breast cancer tendency into two groups: one group simulated normal conditions, that is, 12 hours of light and 12 hours of dark environment every 24 hours; the other group, every 24 hours Reduce the dark environment by 8 hours a day for 10 weeks. The first mock exam ofshowed that the model could simulate the circadian rhythm disorder in long term shift work by evaluating the movement and body temperature of these mice.the growth of primary tumor was monitored every 2 weeks by luciferase activity imaging.at the age of 16 weeks, the mice were killed for related tests. The main results were as follows: 1. The blood glucose level of mice with chronic circadian rhythm disorder was significantly decreased, and the levels of cholesterol, triglycerides and free fatty acids were increased. At the same time, the tumor burden was heavier and the degree of malignancy was higher after tumor occurrence; 2 In mice with chronic circadian rhythm disorder, there are more disseminated and circulating cancer cells, and the probability of bone and lung metastasis is also significantly increased; 3. Chronic circadian rhythm disorder also affects the expression of light transduction genes (related to light adaptation and dark adaptation when environmental light changes); 4 Compared with normal rhythm breast cancer mice, mice with chronic circadian rhythm disorder have stronger tumor stem cell characteristics, higher expression of EMT related genes, higher efficiency of mammary bulb formation test, and greater tumor initiation potential; 5 In mice with chronic circadian rhythm disorder, the number of macrophages and regulatory T cells supporting tumor progression in tumor microenvironment increased, and invasive CD8 + T cells with inhibitory effect on tumor decreased, and tumor microenvironment showed immunosuppressive state; 6. Chronic circadian rhythm disorder also changed the cytokine chemokine network of breast cancer mice.next, let's take a detailed look at what aspects of tumor development are affected by chronic circadian rhythm disorder: 01 long term circadian rhythm disorder leads to changes in metabolic state, higher risk of cancer, heavier tumor burden, and similar body weight and peripheral blood cell count in mice with normal circadian rhythm disorder, but blood glucose level of mice with chronic circadian rhythm disorder is significantly higher The levels of total cholesterol (P = 0.027), triglycerides (P & lt; 0.0001) and free fatty acids (P = 0.012) were significantly lower (P = 0.043), and the levels of total cholesterol (P = 0.027), triglycerides (P & lt; 0.0001) and free fatty acids (P = 0.012) were increased, and some metabolic disorders appeared. Compared with normal day and night environment, mice were more prone to metabolic diseases.Fig. 2 Comparison of blood glucose, total cholesterol, triglyceride and free fatty acid levels between the normal circadian rhythm group and the circadian rhythm disorder group. In the early stage, the imaging results in vivo showed that there was no significant difference in the occurrence of tumor.after tumorigenesis, with the growth of age, the tumor volume of mice with chronic circadian rhythm disorder was larger, the burden on the body was heavier (P = 0.029), and the malignant degree was higher in terms of staging (P = 0.042).Fig. 3 Comparison of tumor burden between normal circadian rhythm group and circadian rhythm disorder group. 02 the possibility of tumor metastasis was increased due to circadian rhythm disorder. Bone CT and bone section H & amp; E staining results showed that disseminated cancer cells increased in bone tissue of mice with chronic circadian rhythm disorder. At the same time, the probability of lung metastasis increased from 28% to 52% (P = 0.025), and the number of lung metastases also increased (P = 0.012).Fig. 4 bone metastasis and lung metastasis of mice in normal circadian rhythm group and circadian rhythm disorder group. 03 the expression of light transduction genes was changed due to circadian rhythm disorder. The genes with altered expression were mainly concentrated in the light transduction and rhodopsin mediated signal pathways (rhodopsin, GNAT1, rbp3 and Prph2). these data suggest that circadian rhythm disorders have a strong effect on gene expression related to light perception and light signal transduction, even in tissues that are not directly exposed to light (due to poor tissue permeability) or do not know how to respond to light stimulation. Fig. 5 the expression of light transduction genes in the circadian rhythm disorder group was changed. 04 the tumor in the circadian rhythm disorder environment made the tumor have stronger stem cell characteristics. The tumor of the two groups was isolated and purified, and cultured on the culture plate. Compared with the ability of forming tumor ball in the two groups, it was found that the formation efficiency of mammary bulb in the circadian rhythm disorder group was higher (P = 0.025). the tumor cells isolated from the two groups were injected into the fat pad of mouse mammary gland, and the tumor formation ability was compared. The results showed that the tumor cells in the circadian rhythm disorder group had higher tumor formation efficiency and stronger stem cell characteristics (P = 0.0003). Figure 6 Comparison of tumor formation ability of breast fat pad between normal circadian rhythm group and circadian rhythm disorder group.05 circadian rhythm disorder caused immune microenvironment to incline to immunosuppressive state. In addition to tumor cells themselves, tumor surrounding environment also changed. breast cancer mice with circadian rhythm disorder had more macrophage infiltration associated with immunosuppression. Figure 7 the number of CD11b + MHC Ⅱ low TAM in normal circadian rhythm group and circadian rhythm disorder group was lower than that in normal circadian rhythm group (P = 0.034), while infiltrating CD8 + T cells with tumor inhibitory effect increased (P = 0.019). The number of CD8 + til and CD4 + Foxp3 + Treg in normal circadian rhythm group and circadian rhythm disorder group were compared. 06 chronic circadian rhythm disorder changed the cytokine chemokine network. In primary tumor cells, the number of CXCR4 + cells was significantly increased (P = 0.0016); in tumor infiltrating cells, the number of CXCR2 + cells was also significantly increased (P = 0.013). disturbance of circadian rhythm can reduce the total number of leukocytes in the circulation by interfering with the daily activity of leukocytes, thus reducing the immune infiltration to tumor site. however, CXCR2 inhibitor sb265610 can correct the effect of long-term circadian rhythm disorder on the proliferation and metastasis of breast cancer cells. Figure 9 The expression of CXCR4 in primary tumor cells and CXCR2 in tumor infiltrating immune cells of mice in normal circadian rhythm group and circadian rhythm disorder group were summarized. Previous studies have proved that chronic circadian rhythm disorder has an impact on the incidence of breast cancer in mice [2], and this study further shows that circadian rhythm disorder not only affects the incidence of breast cancer, but also affects its diffusion and metastasis It is easy to form tumor microenvironment with immunosuppression. moreover, chronic circadian rhythm disorder has different effects on lung cancer, liver cancer [3] and intestinal chronic inflammation [4]. Br / > in 2007, the "circadian rhythm" of human cancer research institutions has been classified as "circadian rhythm disorder". doctors are often exposed to the environment full of bacteria, so it is very difficult to "get out of the mud but not contaminated". Long term reversal of day and night has also led to a sharp rise in the risk of cancer and other diseases, making life a high-risk industry. if you want to avoid these situations, of course, it's the cliche, such as adjusting work and rest, ensuring enough sleep time as much as possible. if you have cancer, you can also take the CXCR2 inhibitor sb265610 for rescue (no). However, there is no need for positive mood in literature, Chronically Alternating Light Cycles Increase Breast Cancer Risk in Mice. Curr Biol, 2015. 25(14): p. 1932-7.[3]Chan, A.B. and K.A. Lamia, Cancer, hear my battle CRY. J Pineal Res, 2020: p. e12658.[4]Pagel, R., et al., Circadian rhythm disruption impairs tissue homeostasis and exacerbates chronic inflammation in the intestine. Faseb j, 2017. 31(11): p. 4707-4719.[5]Masri, S. and P. Sassone-Corsi, The emerging link between cancer, metabolism, and circadian rhythms. Nature Medicine, 2018. 24(12): p. 1795-1803.