Crazy enough. Clinical medicine. Two internship reports of 2000 ~ 3000 words. I give 50 points! ! !
Here is an article, I hope it will help you. Present situation and prospect of clinical receptor research In the past century, endocrinologists mainly studied the structure and function of endocrine glands, the structure and function of hormones and the regulation of hormone secretion. It is found that normal or elevated hormone levels can still show that the hormone function is low, that is, "hormone resistance". With the deepening of receptor science research, it is found that this is due to the abnormal information transduction of receptors or after receptors. The change of hormone function is related to the quality and quantity of hormone, and also to the change of signal transduction protein and quantity after hormone receptor or receptor. Therefore, the focus of endocrine research has gradually shifted to the study of hormone responsiveness, that is, receptor and post-receptor signal transduction system. The development of receptor science has been nearly a century and has gone through four stages: the first stage is the concept of receptor. 1878, Langley put forward "accepting substance" and 1900, and ehrlich put forward the word "receptor" as the representative. At that time, the two basic characteristics of receptors: binding and biological effects after binding, are still the standards we continue to use now. The second stage is pharmacological research stage. Its representative is Clark's work in 1937. The third stage is the research stage of radioactive ligand binding. 1962, Jensen and Jacobson first confirmed the existence of estrogen receptor (ER) in rat uterus and vagina with tritium labeled highly radioactive estradiol (3H-E2). The greatest contribution of this stage is that the receptor can be studied as an entity, which is a milestone in the biochemical and clinical research of the receptor. At present, this method is still our basic method to study receptors. The fourth stage is the research stage of molecular biology. From the nucleotide sequence of α subunit of N- acetylcholine receptor, the amino acid sequence of α subunit of N- acetylcholine receptor is deduced, which indicates that receptor research has entered the stage of molecular biology. Since then, the research on receptors has advanced by leaps and bounds, and the primary structure and functional relationship of dozens of receptors have been clarified. Significant progress has also been made in signal transduction. At present, the research on the three-dimensional structure of receptor molecules has also begun to make gratifying progress. With the deepening of the basic research of receptor science, the research of clinical receptor science has also been deepened, and many hormone receptor diseases have been discovered, which explains why the clinical manifestations of hormone deficiency still appear when the hormone level is normal or rising. Such as testicular feminization syndrome, the testosterone level is normal, but the male organs are underdeveloped, showing a female appearance. The results showed that the mutation of androgen receptor (AR) gene resulted in structural abnormality and functional loss of AR. Domestic authors reported 7 cases, of which 2 cases were reported for the first time in the world. People are also worried about the sensitivity of hormones and drugs. Hormone, drug sensitivity and time difference are also related to receptor changes. Our study found that glucocorticoid receptor (GR) has a circadian rhythm, with a peak value of 6: 00 ~ 8: 00 and a trough value of 0:00. It reasonably explains why taking glucocorticoid once in the morning is better than taking it once. It has been reported abroad that melatonin (M) can stimulate the immune system at night, but the same dose has no such effect in the morning. It has been found that the melatonin receptor (MR) is significantly higher at 20:00 pm than at 8:00 am, and the circadian rhythm of MR leads to the time difference of the body's response to M. Lipman. It has been reported that glucocorticoid is used to treat lymphoblastic leukemia, and its curative effect is related to GR, and GR with high glucocorticoid has a good curative effect. It was effective at first, but it was invalid later. The results showed that GR decreased at this time, and the curative effect appeared after stopping the drug until GR recovered, suggesting that detection of GR can predict the curative effect of glucocorticoid. It is believed that with the deepening and expansion of receptor research, more and more mechanisms of hormone resistance and sensitivity change will be clarified. The research on the relationship between receptor and tumor is also a hot spot in the field of receptor science. Oncogenes cause tumors through their encoded oncoproteins. Cancer proteins can be growth factors or receptors, and several oncogene products have been found to have homology with receptors. For example, the cytooncogene c-erb-A is a gene that encodes a thyroid hormone receptor. The molecular structure of the receptor is abnormal, for example, V-erb-B is a homologue of C-Erb-B (proto-oncogene, epidermal growth factor receptor (EGFR)), and the gene product is a decapitated EGFR (equivalent to the peptide chain of EGFR557- 1 158), which contains transmembrane domain and includes tyrosine protein kinase (PTK) activity. In tumor tissues, the original receptors can disappear and new receptors can be found. The significance of these changes needs further study. It is found that the occurrence and development of some tumors are regulated by some endocrine hormones, which are called endocrine hormone-dependent tumors. As a result, endocrine therapy came into being, which is the fifth largest treatment after surgery, chemotherapy, radiotherapy and biological agents. It is reported that in Europe and America, 50% of female cancers and 20% of male cancers are hormone-dependent to varying degrees, among which breast cancer is the most common hormone-dependent tumor. Estrogen antagonists can be used to treat breast cancer, progesterone can be used to treat uterine body cancer and renal cancer, and glucocorticoid can be used to treat lymphocytic leukemia and lymphoma. However, the therapeutic effect of these hormones is related to the binding amount of their receptors. With the deepening of research, more and more hormone-dependent tumors will be found, and the survival rate of patients with such tumors can be improved through endocrine therapy. With the deepening of research, it is found that the initial link of most infectious diseases is the adhesion of pathogens (including cells, viruses and protozoa) to host cells. This adhesion first depends on mutual recognition and combination, so this combination has certain specificity. Components on pathogens that recognize host cells are called ligands or adhesins. Host cells recognize the components of pathogens and become pathogen receptors. Because the study of pathogen receptors helps to understand why people are exposed to a pathogen, in the same environment, some people will get sick, and some people will not get sick, that is, only people with pathogen receptors will get sick. While studying pathogen ligands and pathogen receptors, people have also designed measures to prevent and treat infectious diseases. If the pathogen adheres and locates in the host cell, it is the first step. If it loses its adhesion ability, it loses its pathogenicity. Adhesion antibodies or receptor analogs should be used to block adhesion from binding to the receptor. Corresponding measures can also be taken to decompose pathogen adhesin, so that pathogens lose pathogenicity, thus achieving the purpose of preventing and treating diseases. With the deepening of receptor research, people pay attention to the signal transduction process after receptor. Abnormal post-receptor signal transduction is related to many diseases. Such as tumor and diabetes. Abnormal signal transduction can be hereditary, autoimmune or secondary. Among them, the relationship between information transduction protein gene mutation and diseases is one of the hot spots in current research. Genetic mutations in somatic cells can lead to tumors. Gene mutation can be divided into inactivation mutation and constitutive activation mutation. The former leads to the weakening or disappearance of signal transduction protein function, while the latter leads to the continuous activation of signal transduction protein. Due to the deletion, reduction or structural abnormality of a signal transduction protein in the signal transduction pathway, the signal transduction process can be weakened. If there is no other pathway to replace it, the target cells will be insensitive to signals, leading to ligand (hormone) resistance syndrome, such as insulin-resistant diabetes. Overexpression of a certain signal transduction protein, or gene mutation that makes it abnormally or continuously activated, can make intracellular signal transduction out of control and lead to diseases with overactive signals. The general screening method for gene mutation receptor diseases is polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP). If swimming denaturation and other changes are found, the location and nature of the mutation are determined by sequencing. Hormone resistance can occur at receptor level or post-receptor signal transduction level. For example, insulin-resistant diabetes, including Kahn's type A insulin resistance syndrome, leprechaun-like syndrome and so on. It is related to a variety of gene changes and can be caused by insulin receptor (IR) or post-receptor defects. Since 1988 reported the first IR gene mutation, 50 cases of IR abnormalities have been reported all over the world, which occurred in the synthesis and precursor processing of α subunit, β subunit and receptor of IR. The reported IR mutations are obviously heterogeneous, mainly point mutations. In short, with the popularization of molecular biology technology, more and more receptor diseases will be found. With the deepening of receptor research, it will certainly promote the development of clinical medicine and improve people's understanding of diseases.