Pseudoxanthoma treatment flexibility, elastic pseudoxanthoma should be treated

Pseudoxanthoma

flexibility to consider before treatment? 1 primary prevention of genetic disease prevention, in addition to the entire population from the perspective of good epidemiological survey, carrier detection, genetic care for people and environment monitoring, guidance to carry out marriage and childbearing, efforts to reduce the incidence of genetic disease in populations improve the quality of the population, the targeted individuals, must take effective preventive measures to avoid the birth of offspring genetic diseases (ie, the implementation of eugenics), and the occurrence of genetic variation, taking the usual measures include: pre-marital checks, genetic counseling, prenatal care and early treatment of genetic diseases. (1) pre-marital check: pre-marital check (ie, marriage, health), it is to ensure that both men and women happy married life, an important part of the health of future generations. Focus on pre-marital check: ① investigation of genetic diseases, including both men and women asked in detail about the health of their family members, past medical history and treatment, particularly with or without congenital malformations, genetic history and the history of Inbreeding. Family should be carried out necessary investigations, blood examination, chromosome or genetic diagnosis, detection of carriers to; ② comprehensive physical examination, mainly for acute infectious diseases, tuberculosis, or severe heart, liver, kidney disease, chronic urinary tract inflammation can be a serious threat to the health of the individual or spouse diseases, and the womans severe anemia, diabetes can affect the fetus detection of the disease and to mobilize only after the marriage by the cure; ③ examination of male and female reproductive organs, and the detection genital abnormalities, hermaphroditism and other diseases, so very early to take measures. (2) Genetic Counseling: Genetic counseling (genetic counselling) by clinicians from the genetically inherited disease as willing to answer questions about their relatives the cause of genetic diseases, genetic methods, diagnosis, treatment and prognosis and other issues, it is estimated Patients suffering from a disease of children and then the probability, and to make recommendations and guidance for patients and their relatives reference. The significance of genetic counseling: ① reduce the patients body and mental pain and reduce the psychological stress of patients and their relatives to help them properly treat genetic diseases, to understand the probability of disease, to adopt appropriate preventive and treatment measures; ② reduce the population of genetic disease rate, reduce the frequency of harmful genes, and reduce transmission opportunities. ① classification and content of genetic counseling: A. premarital counseling: both men and women before marriage or their relatives in the party that has a genetic disease, when asked whether to get married? Incidence of the disease among offspring how? B. prenatal consultation : the couple in the party or his relatives have a genetic disease or congenital malformation, asking future generations of similar diseases; if for some kind of genetic disease or congenital malformations, when asked to stop having the situation and how to prevent future generations suffering childs birth. Suffered from a disease during pregnancy, taking certain drugs or exposure to toxic substances or radiation, ask the fetus possible. C. General Genetic Counseling: In addition to the above situation, but also asked whether Inbreeding? Individual disease prevention and control measures has been the emergence of certain symptoms or signs of suspected genetic disease who want to explain. Although the consultants age, occupation, level of knowledge base and varied culture, what he wanted and not the same requirement, but the basic content of genetic counseling can be summarized as the following four areas: a. whether the diagnosis of genetic diseases; b. answer a variety of issues, including prevention and treatment and prognosis; c. calculate the risk of relapse rate; d. discuss countermeasures. To accomplish these, genetic counseling programs typically include: a. by history and family, physical examination and necessary laboratory examinations and analysis of specific genetic testing to determine whether the genetic disease, the manner in which genetic; b. estimated by genetic methods and characteristics of the risk of relapse rate; c. through talks, discussion, for the prevention, treatment strategies and marriage, fertility guidance. ② recurrence risk ratio estimates: A. The recurrence risk of human genetic diseases, according to their degree of risk can be divided into three categories: a. General risk: risk of disease is more than 1:20. Often refers to environmental factors (such as pregnant women infected with rubella in early pregnancy, etc.) caused by the disease, its future on behalf of individuals with the disease, generally had no effect, similar to the expected risk-risk groups. b. Mild risk: incidence probability 1:10 ~ 1:20. Often refers to multi-gene recurrence risk of genetic disease, according to the heritability of the disease, such as a comprehensive analysis of the threshold calculation. c. a high degree of risk: risk of disease is 1:1 to 1:10. All single-gene genetic disease (autosomal dominant genetic disease, recessive genetic disease, X sex-linked genetic disease) and one of the parents has a balanced translocation of chromosomes, fall into this category. B. genetic disease recurrence risk ratio estimates: methods with different genetic diseases and genetic information may be different known. In the single-gene estimates of recurrence risk. The presumption against sub-genotype and genotype were not presumed to be estimated both cases. a. genotype has been presumed by: autosomal dominant cause of patients are heterozygous, if the exon was 100% for patients with one parent, the child is 50% probability of disease, if it has one or several fertility patients recurrence risk is still 50%, both parents are patient, the childs risk of recurrence was 75%, none of the patients children, parents are generally not sick. Mutations in individual risk of recurrence was 50% children, their fellow group is equal to the natural incidence of the mutation rate. If the explicit failure, the probability of their children get sick K / 2 (K is penetrance, that concept to the actual prevalence of the number and percentage of expected value). Autosomal recessive genetic disease: risk of offspring with parents close the case (Table 1). If Inbreeding increased risk for children. X sex-linked dominant genetic disease: male patients with normal women marry, their children, normal male, female incidence. Men marry women with normal and 50% of the children of their own disease. X sex-linked recessive genetic disease: male, 50% of patients with possible onset brother, his sister is not the disease, but 50% of carriers, our compatriots in the overall incidence rate of 25%; their children are generally not ill, but her daughter is carriers, female offspring of patients with 100% incidence in boys, daughters are carriers. Male patients and female carriers of marriage, their children from each of the 50% incidence. Carriers and normal women marry men, the incidence of children, half of boys, girls, half of the carriers. Y sex-linked genetic disease: the general performance of father to son, son Chuan Sun, only male disease. b. genotypes were not presumed: If one or both parents unknown genotype, the estimated incidence of children born on or after the children the risk of recurrence is much more complex. Because delayed penetrance genetic disease, heterozygotes to a certain age before onset. A healthy child may be completely normal, it could be a disease of heterozygotes has not been to estimate the recurrence risk, it must be presumed that it is the probability of heterozygotes. Recessive genetic disease in the family, the phenotype of normal parents, gave birth to normal children, we can not conclude that they are not genetic carriers, because, even if the parents are heterozygous, the probability of children with normal birth 3 / 4. Of course, the more they give birth to normal children, the smaller the chances are heterozygous. In this case, the estimated risk of relapse, according to the performance of previous generations and the next generation model, experimental results do check with the law of inverse probability (Bayes law) to project. Multi-gene genetic diseases more pairs were co-dominant; the role of each gene a small, but with cumulative effect, and, in addition to the genetic basis of external, environmental factors in the incidence of multi-gene genetic diseases play a larger role . Different multi-gene genetic disease in varying degrees, the incidence thresholds are different, the projected risk of relapse rates, more complex. In general, the relatively high heritability (70% to 80%) of multi-gene diseases, if the population incidence rate of 0.1% to 1%, the incidence of first-degree relatives of patients groups, the incidence is similar to the square root. In addition. Should also consider several issues, are examples. Incidence of cleft lip in our group was 0.17%, the heritability of 76%, the incidence of first-degree relatives of patients was 4%, close to the square root of 0.17%; when 1 2 the couple gave birth to children with cleft lip, the recurrence risk ratio the corresponding increase in the incidence rate of 4% to 10%; if seriously ill patients, the incidence rate risk will be higher than the light condition, the side of the incidence of first-degree relatives of patients with cleft lip was 2.6%, while both sides of the cleft lip and cleft palate persons, the risk of recurrence rate of up to 5.6%, while the incidence of gender differences, the gender of a low incidence of first-degree relatives of patients with a high incidence of recurrence risk rate than the sex of first-degree relatives of patients with risk of relapse rate is high; congenital malformations in newborns in 1% to 2%, when such deformities have been born a childhood once again the risk of pregnancy rate of occurrence of such malformations that increase with the number of patients and has increased. Most child patients of the parental chromosome karyotypes were normal, the germ cells arise in the course of future generations caused by the incidence of chromosomal abnormalities. These patients the risk of suffering from the disease fellow and then rate the same as the general population; advanced maternal age or history of significant exposure to mutagenic factors, parents, relapse risk rate can be significantly increased; abnormal number of chromosomes (eg, 13,18,21 and other chromosome trisomy syndrome), if one parent is chimeric karyotype, the regeneration rate of children can be estimated by the risk of P = [X / (2-X)] ÷ K (P for the hazard rate, X is the percentage of three-body cells, K is the coefficient, usually 2), chromosome structural aberrations due to the risk of disease recurrence rate calculations to be based on different types of distortion, analyze the possible separation of the exchange form, the last under the law of separation law analysis and exchange of gametes can be estimated. ③ to propose a solution and answer questions: genetic counseling work in the detailed understanding of history and family situation, analysis of the genetic approach and estimated risk of relapse rate, the patients and their families want to be answers to questions, the treatment of genetic disease, prevention issues such as countermeasures, and to give the marriage, birth and other guidance. To effectively serve to prevent the occurrence of genetic disease, the role of the benefit of mankind. (3) Prenatal diagnosis: Prenatal diagnosis (prenatal diagnosis), also known as intrauterine diagnosis (intrauterine diagnosis) or prenatal diagnosis (antenatal diagnosis) is by sex and health status during pregnancy detection in order to take the necessary measures in time to prevent genetic diseases or congenital malformations in children born. Prenatal diagnosis is biochemical genetics, cytogenetics, molecular genetics and clinical practice of combining the product of todays high-resolution banding techniques, genetic engineering and the villi absorb and develop technology to make the surface more prenatal diagnostic applications wide, more accurate test results. ① object of prenatal diagnosis: prenatal diagnosis of genetic diseases often encounter the following three categories: Category 1: chromosomal abnormalities, accounting for 0.5% of the total number of births, due to the easy diagnosis. It can account for prenatal diagnosis of cases of 1 / 4 to 1 / 2 or so; Category 2: Single-gene disorders, usually accounts for 3.5% of the total number of births, accounting for prenatal diagnosis about 10% of patients; Category 3: multi-gene disease , including children without brain, spina bifida, hydrocephalus, cleft lip and cleft palate and some congenital heart disease in some. Mainly neural tube defects, accounting for 40% of cases of prenatal diagnosis to 50%. Mastery of prenatal diagnosis indications, different countries, different hospitals some differences, the general conditions of good health care and hospitals to master a wide area. Generally accepted indications include the following few: A.35 over the age of advanced maternal age. B. There are a couple one abnormal chromosome number or structure of pregnant women. C. has given birth to a trisomy 21 syndrome or other chromosomal abnormalities in children and pregnant women there is a corresponding family history. D. families with fragile X chromosome in pregnant women. E. side is his wife or other chromosomal balanced translocation carriers of chromosomal aberrations or chimera of pregnant women. F. couples party is a genetic disease, or had given birth to children with a genetic disease of pregnant women. G. There are a couple side of neural tube defects, or open neural tube birth defects than children (no brain child, spina bifida) in pregnant women. H. There are unexplained spontaneous abortion, stillbirth, neonatal death and other medical history of pregnant women. I. early in pregnancy higher doses of radiation or who have been infected, long-term medication for pregnant women. J. excess amniotic fluid of pregnant women. K. couples party has obvious environmental carcinogenic, teratogenic, mutagenic factors, history of exposure of pregnant women. ② method of prenatal diagnosis: prenatal diagnosis by examination of different objects, can be divided into maternal and fetal screening examination. Which maternal blood screening maternal serum alpha-fetoprotein can be screened, fetal cells in maternal circulation of blood in the inspection. Usually referred to prenatal diagnosis, mainly for fetal diagnosis. It can be at different levels, use different methods. A. morphological level (phenotypic level): The main check whether fetal congenital malformations, commonly used methods are: aX-ray examination: After 16 weeks of pregnancy, fetal long bone, short bone, ossification of the ribs and so, by X diagnosis of deformities. When necessary, water-soluble or oil-soluble contrast agent injected into the uterine cavity, the amniotic cavity imaging. b. Ultrasound: Ultrasound is a simple and minimal damage to the prenatal diagnosis. A common type of ultrasonic diagnostic apparatus with ultrasonic diagnostic apparatus, B-type ultrasonic diagnostic apparatus, ultrasonic diagnostic Doppler and M-type ultrasonic diagnostic apparatus. B-type ultrasonic diagnostic apparatus (B Ultra) with a large spot contrast, image clarity, resolution advantages. Multi-probe electronic automatic quick scan, increased scanning speed, you can directly observe the fetal heart. Fetal movement so dynamic, and video recording and analysis. For the detection of abnormal B: multiple pregnancy; placental location; gender identification; neural tube defects; visceral malformations; fetal nucleated red blood cells increase in symptoms; abnormal embryonic development; intrauterine growth retardation. c. tire Mirror: fetal lens (fetoscope) Amniocentesis is a double tube with a fiber-optic endoscope. Into the amniotic cavity, may direct observation of fetal malformations, fetal tissues can be collected and fetal blood, hair and other materials, but also to carry out some of the intrauterine treatment, pre-treatment of genetic disease, provides a new way, but this operation can be cause abortion, amnionitis, maternal immune response and other complications, so its application is subject to certain restrictions. B. chromosome level: for chromosome examination of the fetal, early diagnosis and prevention of common chromosomal disease, fragile X syndrome, chromosome breakage syndrome and chromosomal abnormalities associated with cancer, but also can predict the sex of the fetus, there conducive to the prevention of sex-linked genetic disease. Commonly used material is exfoliated cells in amniotic fluid and hair cells, usually by tissue culture, the preparation of chromosome pieces, karyotype analysis and high resolution banding and other tests, but also directly for X, Y body check. Hair cells can be used for short-term observation of cultured immediately after production. Available information indicates that villus cells and amniotic fluid cell chromosome analysis chromosome analysis results are not consistent. 21 centers in Europe examined 1401 cases concluded that: a. the abnormal chromosome hair pregnancy rate than in amniotic fluid cells high; b. the total number of chromosomal aberrations occur frequently in pregnancy than three times higher amniotic fluid cells, and found that some can not survive the three-body ( such as 14,15,16 three-body); c. rate of chromosomal abnormalities in amniotic fluid cells three times, including 45, X 10 times higher than the amniotic fluid cells; d. There are a couple of balanced chromosomal translocation. The villi are unbalanced translocation chromosome were also higher than the amniotic fluid cells; e. chromosomal abnormality found in hair cells, the risk of recurrence was 4.16%, 1.5% of amniotic fluid cells. Early pregnancy villus cells and amniotic fluid cells, the diagnosis is not entirely consistent at least suggest that in embryonic development. The role of natural selection constantly out of abnormal cells, while the other meaning is not clear. C. Enzyme levels: through the amniotic fluid and in cells, hair cells or maternal blood, urine enzyme inspection, the enzyme can be detected in many congenital disorders. D. metabolite levels: detection of specific metabolites, can be pre-diagnosis of certain inherited metabolic diseases, such as mucopolysaccharide disease. E. Gene level: the use of amniotic fluid cells, fetal cells or villus biopsy, even fetal cells in maternal blood for the material, the use of extremely sensitive and highly specific genetic diagnosis, genetic detection of child patients. In recent years, with the in vitro fertilization, the blastocyst in vitro, to take a single cell micromanipulation, artificial embryo transplantation technology, the emergence of a pre-implantation diagnosis (also known as preimplantation diagnosis). It is the application of molecular biology techniques HYUNDAI PCR, in situ hybridization sensitivity and specificity are high detection methods, analysis of IVF embryos or blastocysts by uterine lavage obtained in a single cell or several cells, the genetic composition of to clarify whether the disease gene carriers and healthy embryos into the mother to continue development. This is another development of prenatal diagnostic techniques, but is not yet mature, and not widely used. ③ amniocentesis: fertilized egg to form the amniotic cavity on day 7, generated amniotic fluid, amniotic fluid and fetal direct contact. Nutrients required for fetal development is a major supplier of one of the ways, is excreted in fetal urine, and its ingredients are able to respond to fetal growth and metabolism. Therefore, loss of amniotic fluid and amniotic fluid for prenatal diagnosis of fetal cells are the main materials, the successful application of amniocentesis, is the key to specimen collection. The following describes the main technical points amniocentesis. A. amniocentesis indications and contraindications: all clinical and other information prompted the need for pregnant women in prenatal diagnosis are amniocentesis indications. Generally believed that the contraindications are: a. less than 12 weeks of pregnancy (uterus too small) or more than 24 weeks (cell cultures is not easy to succeed); b. indications are not clear; c. threatened abortion or missed abortion in pregnant women; d. pelvic or There intrauterine infection; e. simply because social customs were asked to predict fetal sex. B. amniocentesis time: the best 16 to 20 weeks of pregnancy. The reason is: a. large amount of amniotic fluid at this time (more than 170ml), grew faster, taking 20ml of amniotic fluid, at first small and will not cause abortion bureaucratic; b. more appropriate ratio of fetal and amniotic fluid, the fetus is small, amniotic fluid and more than around amniotic fluid with a wide, easy to puncture injuries to the fetus; c. amniotic fluid cells in the percentage of viable cells, the highest point, easy to cultivate success; d. more than skin fibroblast cells and amniotic fluid cells for enzyme-based and biochemical analysis. C. puncture method: puncture before the need to carefully make the following preparations. a. check indication, gestational age, uterine size, with or without complications. b. to make white blood cells, hemoglobin and blood examination. c. Check whether the dermatitis of the skin puncture site, infection, the situation is not conducive to puncture; d. choosing a suitable puncture site, you can use B-to help you locate the placenta and to determine whether a single tire, the puncture may also be in the B- under the guidance. e. puncture before emptying the urine of pregnant women must be. The most suitable puncture site on the 3 cross-refers to the pubic bone, the belly line next to the best house at the end of the umbilical shame, or between 2 Wang pointed below the belly button, so that the needle into the center position in the womb or just under Shaopian. Before the needle should be carefully palpation. Lumbar puncture needle using 21 long (with a needle core). General steps: disinfection of the puncture site and the surrounding skin, shop towels hole, local anesthesia, the vertical speed needle, the needle piercing the skin slow to 7 ~ 8cm deep (into the uterine cavity may have a sense of frustration), out of light yellow transparent liquid , is the amniotic fluid (Figure 1). Pumping for the first 1 ~ 2ml biochemical tests, precipitation cells can be used as sex chromatin examination, and the other pumping 15ml into a sterile test tube, used for cell culture. Table 2 lists the application of amniocentesis. D. amniocentesis in the Frequently Asked Questions: a. puncture failure: the failure rate is generally 0.5% to 1%. Possible reasons are: the uterus is too small, or the puncture site is too low, wrong to wear a urine within the bladder; abdominal wall is too thick, the needle is not deep enough; puncture to the placental site, out of the blood did not dare to continue to apply again and again into the needle. b. bloody amniotic fluid: If the beginning is out of bloody amniotic fluid, suggesting that there are some tip in the uterine wall, should the needle deep thorn out of amniotic fluid after the exchange of clean syringes apply again and again, you can smooth out clear amniotic fluid. If the amniotic fluid pumping is very smooth, and always with blood, needle puncture may cause bleeding in the matrix or the placenta walls placenta previa of pregnant women more likely to occur. c. For pregnant women and fetal injury: general rare, occasionally stabbing pregnant woman with abdominal artery, the formation of large hematoma and shock; puncture the placenta, hematoma caused the formation of the placenta after abortion; fetal skin puncture injuries, birth fetus after a little bit like pitting; hurt the fetus resulting in a lower limb necrosis reported. d. intrauterine infection: failure due to operation, the bacteria into the uterine cavity, can cause intrauterine infection and fetal death, so the operation should be extremely careful, strict sterile concept. e. abortion: general incidence is extremely low. May be due to the puncture needle outflow of amniotic fluid, bleeding leading to miscarriage. f.Rh blood problem: Rh-negative blood of pregnant women, suspected fetal Rh blood group incompatibility, it would be after puncture injection of anti-D globulin to pregnant women, if the placenta attached to the wall, you can not. g. application of amniocentesis: Table 2 lists the amniocentesis for prenatal diagnosis in the range of applications, only amniotic fluid cell cultures in the technical details and biochemical examination of amniotic fluid for further instructions. h. Note cultured amniotic fluid cells: amniotic fluid cell cultures in order to get more fetal cells in order to meet the needs of other tests. Most of amniotic epithelial cells, amniotic fluid and fetal loss of epithelial cells, to develop successful, should be noted: the cells have a certain dynamic proportion; culture medium and fetal calf serum to the variety of selected, HamF10, HamF12 success rate in the culture medium high, calf serum or embryo extract containing bovine growth hormone, to promote the growth of viable cells is very important; promote early adherent amniotic fluid cells, generally adherent for 5 to 7 days, mostly when adherent epithelial cells, medium was changed after fibroblasts have large growth; attention to the factors that affect the survival of cultured cells. Cultured cells grow too fast or too slow to be considered the mother cell contamination; vitro cell culture, chromosome mutation will occur. Need to be identified; other factors: fungi, mycoplasma contamination. The use of antibiotics, blood cell contamination in amniotic fluid and cultured other conditions. i. biochemical examination of amniotic fluid: changes in biochemical composition of amniotic fluid can be a direct reflection of fetal growth and development, for its detailed biochemical analysis can provide information on many genetic diseases, such studies are now more and more. Table 3 lists some common biochemical indicators of amniotic fluid and its corresponding genetic disease. ④ the significance of prenatal diagnosis: prenatal diagnosis in the fetus before birth is suffering from a pre-clear genetic disease or congenital malformations, chromosomal analysis and by precise genetic diagnosis, but also clear whether the carriers of a genetic mutation , for the conduct of clinical disease prevention and the prevention of genetic diseases at all levels to provide the most direct basis. According to clinical data, laboratory examinations data, a population survey data and results of prenatal diagnosis, to undertake a comprehensive analysis, to take the necessary measures, such as the sick fetus selective termination of pregnancy, can be used for early treatment of genetic diseases (such as benzene, acetone aciduria) for treatment of some congenital malformations can be a simple intrauterine surgery. Prenatal diagnosis has become an important basis for eugenics methods HYUNDAI, which help limit the spread of the gene population, reduce the incidence of genetic diseases, birth control and other population genetic quality of the work plays an increasing role. With the improvement of health conditions, expanding the indications for prenatal diagnosis, but also for a large number of medical genetics research provides first-hand information. 2 Ai - swing syndrome secondary and tertiary prevention of genetic disease prevention from the perspective of science, the treatment of genetic diseases are secondary and tertiary prevention areas. The treatment of genetic diseases is the key: early detection, treatment as soon as possible. Mastery of timing of treatment are the following: ① diagnosed before birth (prenatal diagnosis), may be pre-treatment (intrauterine treatment) or immediately post-treatment. Intrauterine treatment with drug therapy, and direct treatment of pregnant women, fetuses categories. As long as the use of drugs through the placenta, maternal administration of law on the convenient, safe, easily accepted. Such as pregnant women taking biotin, vitamin B12, adrenocorticotropic hormone, digitalis, etc., can be treated separately fetal biotin-dependent carboxylase deficiency, vitamin B12-dependent metabolic acidosis, congenital adrenal hyperplasia and congenital supraventricular tachycardia. Drugs that can not pass through the placenta, can be directly injected into the amniotic cavity, so that the fetus in the amniotic fluid during the process of swallowing drugs be swallowed. Injected directly into the amniotic fluid, such as thyroid hormone to treat hereditary goiter. Fetal surgery, there are success stories; ② typically be diagnosed before symptoms appear (presymptomatic diagnosis), given as soon as possible after diagnosis treatment. For example, children with phenylketonuria after birth, infants can use the Guthrie blood spots on filter paper after 72h bacterial inhibition assay for early diagnosis, treatment given to low-phenylalanine diet, can prevent children with intellectual impairment; ③ After the symptoms have appeared was only confirmed. At this time there had been damage to organs and tissues, treatment will be limited, and poor efficacy. Can be taken to surgery (removal of organ lesions, repair replacement, etc.) and medical symptomatic therapy to improve symptoms. The treatment of genetic disease is the general principle avoid ban it, go over it, make it short, regulating metabolic balance, to prevent the onset of symptoms. (1) to correct metabolic disorders: This is the treatment of inherited metabolic diseases of the most important method, with the pathogenesis of inherited metabolic diseases and intermediate deepening understanding of the process, the scope of application of this method is also increasing. ① diet (avoid ban it): When the metabolic abnormalities caused by the body when the lack of certain essential substances through dietary supplement; piling occurs when metabolites, then the limit of this metabolite or its precursor substance intake, to to maintain balance. PKU patients with low-phenylalanine diet is a good example. In addition, also by limiting the absorption of specific substances to reduce the intake, such as phenylketonuria patients taking phenylalanine amino hydrolase capsules can be food for the transfer of phenylalanine into cinnamic acid, which is to eliminate. ② reducing substrate (they go over): due to harmful substances caused by metabolic diseases, by reducing the substrate and reduce the harmful substances and metabolic derivatives of its predecessor, the concentration, to remove or reduce its toxicity to control or improve symptoms of the disease. Main methods are: A. chelation or to promote excretion; B. Plasma exchange method and affinity binding assay; C. change the metabolic pathway; D. Surgical bypass surgery; E. metabolic inhibition. ③ product substitution (complement its lack of): When an important product of the enzymatic reaction to lack of disease, it can directly add the appropriate end product required. As for patients with pituitary dwarfism with growth hormone, for hemophilia patients with anti-hemophilia protein (clotting factor), to patients with hereditary immune deficiency corresponding immunoglobulin. (2) to correct abnormal activity: ① coenzyme supplement: Some genetic diseases, abnormal activity may be involved. A. A specific vitamin or coenzyme binding sites. B. transfer or the active coenzyme biosynthesis, leading to abnormal. Many coenzymes are all necessary for normal activity of the enzyme. So supplement coenzyme composition is induced increase in activity is an effective method, it can make the whole enzyme degradation in the cell to slow down, increase the enzyme half-life, can reduce the enzymatic reaction of the Michaelis constant (Km), the current This method has been treated with more than 25 genetic diseases. As with cobalamin (B12) treatment of a variety of anemia and methylmalonic aciduria and so on. ② enzyme induction or feedback inhibition: the level of the enzyme defect is another treatment with drugs to improve the residual activity to improve metabolism. For example, phenobarbital and related drugs can significantly stimulate the smooth endoplasmic reticulum formation, and can accelerate the endoplasmic reticulum in the synthesis of specific enzymes, including liver UDP glucuronyl transferase enzymes, for the use of phenobarbital treatment Gibert syndrome Crigler-Najjar syndrome and provides a theoretical basis. Feedback inhibition is important in the metabolism of many forms, for defects caused by an enzyme substrate or accumulation of precursors can be bypassed by other metabolic feedback inhibition to increase activity, reduce the accumulation of the substrate, feedback suppression has been the treatment of acute porphyria as a method. ③ allograft: implantation by the same individuals genetic disease gene with normal cells, tissues or organs in order to produce in the body are affected by the activity of enzymes and other gene products, for therapeutic purposes. Grafts in vivo may be affected by two mechanisms play a role. A. produce active enzyme, metabolism of in situ piling remove the original substrate. B. release of active enzyme, coenzyme, or immune activity factor into the blood, distributed to other organizations play a role in the body. Has been carried out the same kind of tissue and organ transplantation are: kidney, liver, adrenal gland, bone marrow, thymus, spleen, pancreas, and some have achieved significant results. ④ enzyme replacement therapy: patients directly to the enzyme defect corresponding normal enzyme. With enzymatic technology and cell engineering, gene engineering technology, already available in sufficient quantities, high purity of the enzyme. This enzyme must have a long half-life, low antigenicity, guidance and good features. This method is often used: A. the use of microcapsules, liposomes, red blood cells and other carriers to bubble film packaging enzymes to reduce immunogenicity, prolong half-life. B. Application of receptor-mediated molecular recognition method to improve oriented. C. for some lysosomal storage diseases, because sediment can diffuse into the blood, and to maintain homeostasis, the available "balance one remove" method to treat. (3) Gene therapy: Gene therapy is the use of gene transfer technology directly to the reproductive cells or genetic material into cells to play a genetic disease and the treatment of other diseases, new treatment methods. Gene therapy for genetic diseases is expected to correct the underlying genetic disease phenotype abnormalities. ① The basic strategy of gene therapy: the past 10 years, the flourishing of gene therapy research and put forward many new ideas, new ideas, the key strategies are: A. In situ gene correction (correction) and in situ replacement (replacement): The purpose of this strategy is in place to repair the mutant gene, without affecting the surrounding structure and function of other genes. Which in situ for gene correction of point mutations or small-scale variations, to be designated by its specific repair methods. The in situ alternative, you want to have a greater range of variation of the gene to remove and replace it with a normal gene. This strategy is the best, most direct cure of genetic variation for the method, the present study a lot of site-specific integration in mammalian cells (homologous recombination), to this strategy provides a theoretical and experimental basis, but has not really used in human trials. B. Enhanced gene (gene augmentation or gene complementation): defects in the gene itself does not change under the premise of exogenous functional gene transfer to diseased cells or individuals within the genome, their expression to compensate for the loss of gene function sick. This strategy is the most studied and most sophisticated way. C. Antisense against the abnormal gene or other gene products of gene expression within cells, play an inhibitory effect, or inhibition of gene therapy (gene inhibition therapy) or immune cells (intercellular immunity). ② gene therapy techniques in many gene therapy strategies in the most studied, most mature and used in clinical trials of gene enhancement strategy. Throughout the research process usually involves pre-clinical and clinical research, in Table 4. A. Disease choice: the current gene therapy is the preferred single-gene defect diseases. Choose the basic conditions often include: a. The genetic basis of relatively clear, the purpose of gene cloning in vitro. b. do not need fine-tuning of gene expression, and often open, the product of the higher physical level is not better. c. has a certain morbidity, harmful, yet the lack of other effective treatments are. Our earlier study of gene therapy is to carry out one of the countries, such as Fudan Xue Jinglun is based on these conditions, selection for the study of hemophilia, has achieved good results, has reached the world advanced level. Of course, these conditions are limited to the current level of research was proposed. B. the choice of target cells: target cells for gene therapy can be divided into two categories: germ cells and somatic cells. This leads to a germ cell gene therapy and somatic cell gene therapy category. If the germ cells or early embryonic cells for gene repair or replace, the genetic defect has been corrected, so that genetic diseases can not only be treated in a contemporary, but also the new genes to the next generation, but also for people to reduce a harmful gene, is ideal means to cure genetic diseases. However, due to HYUNDAI biotechnology, the theory of constraints, as well as germ cell genes involved in the operation of human society, ethical, moral and legal and other factors, for a long period of time. Only to animal testing. In 1985 the U.S. government had provided, to limit human trials of gene therapy in somatic cells. Has been used as target cells are: hematopoietic stem cells, liver cells, fibroblasts, endothelial cells, lymphocytes, etc. C. gene transfer vectors and transfer methods: transfer and build a suitable expression vector and selection of efficient gene transfer method is the key to gene therapy, commonly used carriers are: retroviral vectors, plasmid and adenovirus vectors, adeno-associated virus carrier, in addition to liposome carrier. Commonly used gene transfer methods are four types: a. chemical method: mainly calcium phosphate precipitation method. b. physical law: common conductance and microinjection. c. Membrane fusion: the liposome method is better. d. virus method: mainly refers to anti-retroviral and adenovirus-mediated gene transfer. ③ the prospect of gene therapy: the concept of gene therapy has been proposed for decades, only to nearly a decade, with the HYUNDAI molecular biology techniques (especially recombinant DNA technology) development, the concept was to be a strong theoretical support of basic and technical methods, and to put into practice. In 1990, two adenosine deaminase (ADA) deficiencies cause severe immune deficiency in patients receiving gene therapy to be successful, this study indicates that gene therapy has entered a new stage. Biomedical scientists from around the world, in national government departments and social forces of the strong support of the full swing of the gene therapy research. From development for a single genetic disease to cancer, infectious diseases and other diseases, gene regulation proposed therapy, gene suppression therapy and other new concepts, new ways. To the first half of 1994, more than 100 approved clinical trial program implementation, and some have achieved very good results. Of course, the development of gene therapy is not a long history, a lot needs to be widely used in clinical research and exploration, in particular the following issues: A. for more genetic diseases and gene expression of the molecular basis of more in-depth understanding of regulatory mechanisms This is the basis for gene therapy. B. build a more effective and safe to express and transfer the carrier. C. is more simple and effective gene transfer method was established. D. fixed-point integration, in-situ repair systems, the improvement of technology.