| Part1:A Correlation Study of Premature Ovarian Failure and Progeste rone Receptor Membrance Component 1Background:The etiology of premature ovarian failure is not clear, and genetic factors account for about 30% of all cases. Excessive follicular atresia induced by granular cell apoptosis is an important pathogenesis of premature ovarian failure. Increasing numbers of genes involved in follicle development are considered causative by gene screening, such as GDF9, FOXO3, NOBOX,FIGLA, FMR1, FMR2, BMP15, NR5A1 andPOU5F1. Although usually only 1-2% of a given ethnic cohort will show perturbation of a candidate gene, the cascade reaction of the perturbations may lead to impaired ovarian function. Therefore, further screening of candidate genes is necessary for contributing to a final targeted array.Progesterone receptor membrane component (PGRMC1) is highly expressed in the granulose and luteal cells of rodent and primate ovaries and it can regulate follicle growth by regulating expression of genes associated with apoptosis and modulating cell-cycle of granular cells. Since the ovaries from PGRMC1 conditional knock out mice have fewer antral follicles and a higher percentage of atretic follicles, besides studies in Sweden had shown between PGRMC1 and female reproductive function, we propose that PGRMC1 may be an important candidate gene for premature ovarian failure.Objective:To perform mutation screening of PGRMC1 gene in Chinese Han population in POF patients, so that to investigate the correlation between PGRMC1 gene and POF, so as to discuss the pathogenic gene for premature ovarian failure.Method:196 cases of POF patients who visited Reproductive hospital affiliated to shandong university were selected as the research objects, and 200 women with normal ovarian function as normal control. Peripheral blood of POF patients and normal control group was collected, and genomic DNA was extracted. The 3 exons of PGRMC1 were amplification by polymerase chain reaction (PCR) and direct sequencing analysis was performed.Results:One new missense mutation (C.556C> T, P.Pro186Ser) and one new SNP (C.533C> T, P. Trh177Ile) was found by direct sequencing. According to PolyPhen-2 (http://genetics.bwh.harvard.edu/pph2/), this p.Pro186Ser mutation is predicted to be benign with a score of 0.021; therefore, this mutation might not affect the activity of the protein. Meanwhile, the novel variance (C.533C> T, p. Trh177I1e) was discovered in both the women with POF and the controls. No significant difference, however, was found in frequencies between them..Conclusion:PGRMC1 may be associated with the pathogenesis of premature ovarian failure, but it is not a common cause of POF in Han population.Part2:An Analysis of the Traditional Chinese Medication Regul arity for Treating Premature Ovarian Failure Based on the Dictionary of Chinese Medicine PrescriptionsBackground:At present the treatment of premature ovarian failure is mainly hormone replacement, which has obvious side effect. Premature ovarian failure is classified as amenorrhea in traditional Chinese medicine, and it is recorded since ancient times and a lot of effective prescription remained. There is traditional advantages of traditional Chinese medicine and it should play a greater role in treatment of POF. Traditional Chinese medicine is in the organic community traditional Chinese medicine under the guidance of the theory of drug. The regularity between treatment and prescription would be found out following the cases increasing. This study is to sum up the main drugs and the main combination of drugs for POF, and then analysis the natures, flavours, channel tropism and function classification of them, so as to provide better treatment of premature ovarian failure.Objective:Using the literature analysis and statistical methodology to study the main drugs and the main combination of drugs for amenorrhea in the dictionary of Chinese medicine prescriptions, in order to explore natures, flavours, channel tropism and combination rules in them and put forward new efficient prescriptions.Method:The number, name, composition of prescription drugs of 493 prescriptions for treating amenorrhea from the dictionary of Chinese medicine prescriptions were inputted in the Excel database, and data standardization was performed Then they were inputted in the TCM inheritance auxiliary system, through the function of software integration patterns of drug use, drug frequency statistics, rule analysis, statistics of all the selected prescription drugs were performed, and then discusses the main drugs,, commonly used combination of drugs and deduce the new prescription; Finally to sum up the essence of drug laws and rules from the perspective of property theory by statistics of the 60 drugs whose frequency is greater than or equal to 16.Results:1. The main drugs for POF are as follows, Angelica sinensis, Rhizoma Chuanxiong, Radix et Rhizoma Rhei, cinnamon,Peach kernel, Radix Paeoniae Alba, radix paeoniae rubra, Radix Glycyrrhizae, Radix Achyranthis Bidentatae, radix rehmanniae, Cortex Moutan, nutgrass galingale rhizome,safflower, Atractylodes, Poria, radix rehmanniae, Rhizoma Corydalis, Radix Bupleuri, leech,zedoary turmeric, orange peel, ginseng, Radix Aucklandiae, Radix Scutellariae, gadfly,trigonous, drypaint, cassia twig, amber, green, ginger, myrrh, Fructus aurantii, turtle shell, To angelica root, Amomum villosum, astragalus, sal ammoniac, musk, trogopterus dung, pinellia, pollen Typhae, fennel,asarum, Wu Zhuyu, trumpet creeper, Ophiopogon japonicus, Radix Linderae, angelica tail, Liu Jinu, Rhizoma Anemarrhenae, hematoxylin, yam, Betel nut and motherwort,2. The most commonly used drugs are as follows, Rhizoma Chuanxiong, Peach kerne, Radix Achyranthis Bidentatae, safflower,Rhizoma Corydalis,leech,zedoary turmeric, gadfly, trigonous and myrrh, which belongs to drug for invigorating blood circulation and eliminating stasis. Angelica, red paeony root, licorice root, prepared rhizome of rehmannia, atractylodes, ginseng, turtle shell, astragalus root, dwarf lilyturf, angelica tail belongs to restoratives. nutgrass galingale rhizome, dried tangerine or orange peel, sweet, bitter orange, black, green husk belongs to qi-activating drug. Cinnamon, dried ginger, monkshood, fennel, evodia rutaecarpa which belongs to interior-warming drug and red paeony root, cortex moutan, radix rehmanniae, radix scutellariae, rhizoma anemarrhenae which belongs to heat-clearing drugs.3. Effective drug combination including rhizoma ligustici wallichii+angelica, radix paeoniae alba; Rhizoma ligustici wallichii+licorice, Chinese angelica; Rehmannia glutinosa, rhizoma ligustici wallichii and angelica; Rehmannia glutinosa+angelica sinensis, radix paeoniae alba. Radix paeoniae rubra, rhizoma ligustici wallichii and angelica; Cortex moutan, rhizoma ligustici wallichii and angelica; Licorice+Chinese angelica, root of herbaceous peony; Rhizoma ligustici wallichii+angelica+sweet attached; Radix paeoniae rubra+angelica, cinnamon; Rehmannia glutinosa, rhizoma ligustici wallichii and radix paeoniae alba, etc.4. The core drugs have XinWen, Fairbanks and GanPing characters. Liver, spleen, heart and kidney is the most related meridian. The core drugs act mainly as drug for invigorating blood circulation, restoratives, qi-activating drug, interior-warming drug and heat-clearing drugs.5. Qi stagnation and blood stasis, deficiency of qi and blood, deficiency of liver and kidney, and heart-kidney imbalance is the basic pathogenesis of premature ovarian failure.6. When the correlation is set to 8, the degree of punishment can be set to 2, the new 28 prescriptions were screened According to the professional knowledge, we can get 8 new prescriptions, which would be effective for treating Qi stagnation and blood stasis, deficiency of qi and blood, deficiency of liver and kidney, and heart-kidney imbalanceConclusion:Qi stagnation and blood stasis, deficiency of qi and blood, deficiency of liver and kidney, and heart-kidney imbalance is the basic pathogenesis of premature ovarian failure. The principle of treatment is to invigorate the circulation of blood, tonic and adjusting qi and Yin and Yang. The onset of premature ovary failure is closely associated with liver, spleen, heart, kidney, especially the liver. We should pay attention to protect liver Yin before its onset as well as have good living habits, proper diet and good mood. |
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