{"paper_id":"452791c0-9756-48c1-809f-1220f006c063","body_text":"The Therapeutic Effect of Quyu Jiedu Xiaozheng Tang \nCombined with Diqu Progesterone Tablets on \nEndometriosis and Its Effect on Serum MIF and TGF- Β \nImpact Of 1 \nTian Lihua1,a, Liu Jiale1, Wang Chen1, Chen Mengjie2,*, Yao Jia2 \n1Shaanxi University of Chinese Medicine, Xianyang, Shaanxi, 712046, China \n2Xi'an Traditional Chinese Medicine Hospital, Xi'an, Shaanxi, 710021, China \na1510932239@qq.com \n*Corresponding author: mengjie8369@163.com \nKeywords: Apply Quyu Jiedu Xiaozheng Tang and Diqu Progesterone Tablets to treat \nendometriosis, and pay attention to the patient's serum MIF and TGF before and after \ntreatment- β value change of 1 \nAbstract: To observe the clinical efficacy of Quyu Jiedu Xiaozheng Tang combined with \nDiqu Progesterone Tablets in the treatment of patients with endometriosis, and to analyze \nthe serum MIF and TGF of patients - β the impact of 1 . 60 EM p atients were selected and \nrandomly divided into a traditional Chinese medicine group, a combination of traditional \nChinese and Western medicine group, and a western medicine group, with 20 cases each. \nThe traditional Chinese medicine group was given oral Q uyu Jiedu Xiaozheng Tang; The \nWestern medicine group was given oral Dafu Tong (Diqu Progesterone Tablets); The \ncombination of traditional Chinese and Western medicine group was given a combined oral \nadministration of Quyu Jiedu Xiaozheng Tang and Diqu Prog esterone Tablets. After three \nconsecutive months of treatment, the clinical efficacy and total effective rate of the three \ngroups of patients were compared. Enzyme linked immunosorbent assay (ELISA) was used \nto detect the levels of macrophage migration inh ibitory factor (MIF) and transforming \ngrowth factor (TGF) in the serum of the three groups of patients before and after treatment- \nβ 1 level.\n The total effective rate (95%) of clinical efficacy in the combination of traditional \nChinese and Western medicine group is better than that in the traditional Chinese medicine \ngroup (90%) and the western medicine group (90%); After treatment, the serum MIF levels \nof the three groups of patients were significantly reduced compared to before treatment, and \nP (0.033) in the combination of Chinese and Western medicine group was lower than P (0.036) \nin the traditional Chinese medicine group and P (0.036) in the we stern medicine group; \nSerum TGF of the three groups after treatment - β All levels were significantly lower than \nbefore treatment, and P (0.035) in the combination of traditional Chinese and Western \nmedicine group was lower than P (0.043) in the traditional  Chinese medicine group and P \n(0.042) in the western medicine group. The P -values are all<0.05, indicating significant \nsignificance in the experiment. Conclusion: Quyu Jiedu Xiaozheng Tang combined with \nDiqu Progesterone Tablets can effectively alleviate t he clinical symptoms of patients with \nendometriosis, and can reduce the serum MIF and TGF of patients - β At the first level, the \nclinical effect of combining traditional Chinese and Western medicine in treating EM is more \nsignificant than that of tradition al Chinese medicine and Western medicine alone. Its \nMEDS Chinese Medicine (2023) \nClausius Scientific Press, Canada\nDOI: 10.23977/medcm.2023.051026 \nISSN 2616-1753 Vol. 5 Num. 10\n192\n\nmechanism of action may be related to the regulation of macrophage migration inhibitory \nfactor MIF and transforming growth factor TGF- β 1. Related. \n1. Introduction \nEndometriosis (EM), also known as endom etriosis, refers to an estrogen dependent disease in \nwhich active endometrial tissue (stroma and glands) implants, grows, and repeatedly damages areas \noutside the endometrium and myometrium of the uterus. It is a common, frequently occurring, and \ndifficult disease in gynecology[1]. According to comprehensive literature reports, about 2% -10% of \nwomen of childbearing age suffer from EM, with infertility accounting for up to 50%[2]. The etiology \nand pathogenesis of this disease are not yet fully understood, and inflammatory reactions and immune \nsystem abnormalities are believed to be closely related to it. Professor Zhang Xiaofeng believes that \nthe traditional Chinese medicine etiology and pathogenesis of EM are \"stasis, turbidity, and dampness \ntoxin intertwined\", so he developed his own Quyu Jiedu Xiaozheng Tang [3]. This prescription mainly \nuses insect like drugs to clear meridians and collaterals, detoxify and relieve pain, and is \nsupplemented by tonifying qi and tonifying the body, as well as promoting deto xification and going \nout. It has achieved good therapeutic effects in clinical treatment of endometriosis. This study aims \nto observe the clinical efficacy of Quyu Jiedu Xiaozheng Tang combined with Diqu Progesterone \nTablets in the treatment of endometriosis patients, and analyze the effects of serum MIF and TGF on \npatients with endometriosis- \nβ. The impact of 1 provides a basis for its clinical application. \n2. Clinical data \n2.1 General Information: \nSixty outpatient patients who were diagnosed with \"endometriosis\" at Xi'an Traditional Chinese \nMedicine Hospital from March 2022 to October 2022 and diagnosed with \"stasis, turbidity, and \ndampness toxin intertwined\" were selected. Age range from 18 to 45 years, with an average age of \n33.33 ±  5.66 years; The course of the disease is 0.4-6 years, with an average of 2.09 ±  1.24 years; \n2.2 Diagnostic criteria: \nDiagnostic criteria for Western medicine: \nAccording to the diagnosis and treatment guidelines published in the Chinese Journal of Obstetrics \nand Gynecol ogy in 2021 [1];The 2018 version of the \"Chinese Expert Consensus on Long term \nManagement of Endometriosis\" [4];In 2015, the \"Diagnosis and Treatment Guidelines for \nEndometriosis\" was released by the Endometriosis Collaborative Group of the Obstetrics and \nGynecology Branch of the Chinese Medical Association [5];Diagnosis and treatment standards \npublished by the Obs tetrics and Gynecology Professional Committee of the Chinese Society of \nIntegrated Traditional and Western Medicine in 1991 [6].Based on the above relevant literature, the \nproposed standards are as follows:(1) The patient has a history of or has no painful  menstruation, or \nhas mild dysmenorrhea, with or without a history of uterine cavity surgery;(2) ①The patient's \ndysmenorrhea gradually worsens; ②The symptoms of discomfort in the abdomen and lumbosacral \nregion of the patient during menstruation gradually worsen;③The patient has periodic rectal irritation \nsymptoms, which gradually worsen;④When the doctor examined the patient's body, it was found that \n193\n\nthere were tender nodules in the posterior fornix, uterosacral ligament, or uterine isthmus; ⑤The \npatient's ultrasound showed a lump of adhesions in the appendix accompanied by a nodular sensation \nof the capsule, and the fallopian tube was unobstructed;⑥The patient showed significant changes in \nthe size of the aforementioned lump in the attachment before and after menstruation (But the patient \ndid not use anti-inflammatory drugs. ).Any combination of points ①, ②, and ③, as well as points \n④, ⑤, and ⑥, can be considered as a clinical diagnosis. \nDiagnostic criteria for traditional Chinese medicine: \nThe endometriosis sy ndrome treated with \"Quyu Jiedu Xiaozheng Tang\" belongs to the \n\"combination of blood stasis, turbidity, and dampness toxin\". Referring to the relevant chapters on \n\"excessive menstruation\" and \"dysmenorrhea\" in the tenth edition of \"Traditional Chinese Medi cine \nGynecology\" published by China Traditional Chinese Medicine Press [7] and \"Diagnosis of \nTraditional Chinese Medicine\" (the third edition of the new century), the specific standards are as \nfollows: \nThe main symptom of the patient is abdominal pain befo re or during menstruation, and the pain \nrefuses to press. \nTongue coating and pulse condition: The tongue is purple dark or red in color, with \nvisible ecchymosis and spots on the tongue body, and varicose and blood stasis in the sublingual veins; \nThe tongue coating is greasy, and the pulse is smooth, or (or) astringent. Combined with tongue and \npulse, the main symptom is essential, and if the secondary symptom meets two or more criteria, it can \nbe diagnosed. And it meets the inclusion criteria for this experiment. \n3. Methods \n3.1 Sample grouping method \nFirstly, 60 subjects were coded according to a pre designed sample size, and random numbers were \ngenerated using SPSS 22.0 statistical software through a random number generation algorithm. Based \non the corresp onding random numbers for each subject code, the included subjects were randomly \nassigned in a 1:1:1 ratio to A: 20 Chinese medicine group, B: 20 integrated Chinese and Western \nmedicine group, and C: 20 Western medicine group. \n3.2 Treatment methods\nTrad\nitional Chinese Medicine Group: Patients take orally Quyu Jiedu Xiaozheng Tang (all \ntraditional Chinese medicine are decoction, provided by the Traditional Chinese Medicine Decoction \nRoom of Xi'an Traditional Chinese Medicine Hospital).  The dosage of the med ication is 200ml per \nbag, and the patient takes one bag after breakfast and one bag after dinner. Medication instructions: \nThe patient starts taking the medication from the 3rd to 5th day after each menstrual cycle is clean. \nThey take it continuously for 6  days and rest for 1 day. One treatment cycle lasts for three months.  \nDuring this treatment period, patients should not take other medications to treat this disease, and \nshould also refrain from eating raw, cold, greasy, or irritating foods. If the patient  has a cold, stop \ntaking medication. If the patient becomes pregnant during treatment, discontinue medication \nimmediately. It is prohibited for those who are allergic to traditional Chinese medicine, and should \nbe used with caution for those with allergic constitution. \nWestern medicine group: Administer oral administration of Dafu Tong (Dedroprogesterone \nTablets) Abbott Biologicals B.V . (Netherlands), batch number: 364232. Store below 25 ℃, Starting \nfrom the 5th day of menstruation, take 10mg/dose twice a day for 20 consecutive days. Continuously \ntreat for 3 menstrual cycles. During the treatment period, it is prohibited to take other drugs with \nsimilar effects. \n194\n\nThe combination of traditional Chinese and Western medicine group: Oral administration of \ntraditional Chinese medicine and the medication method are consistent with those of the traditional \nChinese medicine group. At the same time, starting from the 5th day of menstruation, oral \nadministration of dexamethasone and progesterone tablets is the same as that of the Western medicine \ngroup. \n3.3 Observation indicators and methods\nEfficacy observation indicators: Traditional Chinese Medicine syndrome score and total effective \nrate of clinical efficacy \nLaboratory observation indicators: determination of MIF and TGF- β 1 level, and conduct analysis \nand comparison to collect venous blood. Using enzyme -linked immunosorbent assay (ELISA), \nperipheral blood from the elbow vein was extracted on an empty stomach  using coagulation \npromoting blood vessels in the early morning. After centrifugation (3500rpm, 10min, 4 ℃), the upper \nserum was carefully extracted and stored in a -80 ℃ refrigerator. Sufficient samples were collected \nbefore and after treatment. Operators need to follow MIF and TGF- β\n 1. Instructions for the reagent \nkit, follow the steps to carry out the relevant operations. \n3.4 Statistical methods\nThis study used SP\nSS22.0 statistical software to process the obtained data. \n4. Results \nAfter a three-month cycle of treatment, the patient's symptoms and signs improved. Serum samples \nwere collected before and after treatment, and MIF and TGF were measured - β 1 level and conduct \nanalysis and comparison. Table 1, Table 2, and Table 3 respectively represent the relationship between \nthe degree of illness and efficacy of the three groups of patients, as well as the serum MIF and TGF \nbefore and after treatment in the three groups of patients - β Comparison of levels (mean ± standard \ndeviation), serum MIF and TGF before and after treatment in three groups of patients- β Compare the \nP-values of 1, as follows: \nTable 1: Relationship between the degree of illness and efficacy of three groups of patients \n heal Apparent \neffect effective invalid \nApparent \nhealing rate \n(%) \nTotal \neffective \nrate (%) \nTraditional Chinese Medicine Group 2 4 12 2 30 90 \nIntegrated Traditional Chinese and Western Medicine Group 3 6 10 1 45 95 \nWestern Medicine Group 2 2 14 2 20 90 \nTable 2: Serum MIF and TGF before and after treatment in three groups of patients- β 1 level \ncomparison (mean ±  standard deviation) \ngroup \nMIF TGF-β1 \nBefore \ntreatment After treatment Before \ntreatment \nAfter \ntreatment \nTraditional Chinese Medicine Group 57.10± 5.59 51.99± 5.73 21.65± 3.93 18.82± 2.37 \nIntegrated Traditional Chinese and Western Medicine Group 50.91± 4.87 45.61± 6.44 24.65± 12.43 15.99± 3.63 \nWestern Medicine Group 57.02± 5.77 51.38± 8.05 18.39± 2.18 14.95± 4.53 \nNote: After treatment, three groups of patients obtained serum MIF and TGF - β All levels have \ndecreased, indicating clinical efficacy. All values obtained are rounded to two decimal places \n195\n\nTable 3: Serum MIF and TGF before and after treatment in three groups of patients- β Comparison \nof P-values for 1 \n Traditional Chinese \nMedicine Group \nIntegrated Traditional  \nChinese and Western \nMedicine Group \nWestern Medicine \nGroup \nMIF 0.036 0.033 0.036 \nTGF-β1 0.043 0.035 0.042 \nNote: After t -test, the P values of the three groups of patients before and after comparison were \nall<0.05, indicating that the experiment was mean ingful; From the above differences in P values, it \ncan be seen that the patients in the combination of traditional Chinese and Western medicine group \nhave serum MIF and serum TGF - β The P-value of 1 was lower than that of the traditional Chinese \nmedicine group and the Western medicine group treatment group. \nThe t-values obtained from the serum MIF test of the three groups of patients were 2.386 in the \ntraditional Chinese medicine group, 2.402 in the integrated traditional Chinese and Western medicine \ngroup, and 2.354 in the western medicine group, respectively; Serum TGF - β The t-values obtained \nfrom the 1 test were 2.256 for the traditional Chinese medicine group, 2.381 for the combination of \ntraditional Chinese and Western medicine group, and 2.282 for the \nwestern medicine group. \n5. Discussion \nAlthough endometriosis is a benign disease, it has the characteristics of cell proliferation, \ninfiltration and growth, and easy recurrence of malignant behavior. At present, the etiology and \npathogenesis have not been elucidated, and surgical treatment has a high recurrence rate and is prone \nto infertility. For EM patients who do not meet surgical indications, medication is usually used to \nsuppress ovarian function and prevent the development of endometriosis. However,  hormone based \ndrugs have significant side effects and a high recurrence rate in treating EM, as well as symptoms \nsuch as nausea, mild depression, liver and kidney dysfunction, masculinization, amenorrhea, obesity, \nand bone loss [8]. Therefore, the treatmen t methods of traditional Chinese medicine provide more \noptions for EM patients, which can improve clinical efficacy, relieve dysmenorrhea, and pregnancy \nrates, as well as reduce the incidence of adverse reactions. \nTraditional Chinese medicine believes that  the pathological basis of this disease is blood stasis, \nwhich refers to the \"blood leaving the meridians\" that stops accumulating in the uterus, Chongren, \nand obstructs the veins. Due to the obstruction of Chongren, dysmenorrhea can occur due to pain \ncaused by obstruction; Due to prolonged blood stasis, abnormal body fluid application, continued \ngrowth of phlegm and dampness, and the formation of symptoms due to blood stasis; The visible evil \nblocks Chongren and the uterus, and cannot produce sperm and lea d to secondary infertility. The \npathological feature is periodic bleeding caused by changes in ovarian hormones in ectopic lesions, \nleading to proliferation and adhesion of surrounding fibrous tissue. Therefore, the main treatment \nmethod is to promote bloo d circulation and dissipate blood stasis, supplemented by tonifying the \nkidney and tonifying qi, soothing the liver and regulating qi, warming the meridians and dispersing \ncold, softening and firming the body to dispel blood stasis, and so on.  \nCommonly used formulas and medicines include Shaofu Zhuyu Tang, Guizhi Fuling Wan, Yinjia \nWan, etc. Xiao Shan, Zhao Li [9], and others believe that \"blood stasis\" is the core of endometriosis, \nwhich is both a pathogenic factor, pathogenesis, and pathological product. Fu Youfeng et al. [10] \nbelieve that the main pathogenesis of endometriosis is the deficiency of spleen and kidney, as well as \nthe combination of dampness, turbidity, stasis, and toxin. Therefore, they established the general \nmethod of detoxifying, promoting dampness, and resolving blood stasis to eliminate symptoms. Xie \nDandan, Cao Yang, and others [11] believe that endometriosis mostly belongs to the type of qi \nstagnation and blood stasis, and advocate promoting the circulation of qi to relieve pain, promoting \n196\n\nblood circulation and resolving blood stasis. Yang Dongxia, Wang Ning, et al. [12] treated \nendometriosis based on the theory of dampness, heat, and stasis, with the treatment of clearing heat, \npromoting blood circulation, resolving blood stasis, and relieving pain. Guan Lil an and Zhou Ying \n[13] applied the method of warming yang and dispersing nodules to treat endometriosis of the type of \n\"yang deficiency and yin nodules\", and clinically used Lizhong Tang, Guizhi Fuling Wan, and \nXiaoluo Wan. Professor You Zhaoling believes t hat \"blood stasis\" is the pathological basis of \nendometriosis, and \"stasis, deficiency, and phlegm\" are the characteristics of its pathogenesis. She \nproposed a treatment method of \"tonifying and tonifying qi, promoting blood circulation to remove \nstasis, and softening and dispersing nodules\". For those with fertility requirements, treatment should \nbe combined with different therapies of the menstrual cycle [14]. Zhao Xiaoxuan, Zhang Yang, and \nothers [15] explained the mechanism of dysmenorrhea in patients w ith endometriosis from the \nperspective of \"all pain and itching ulcers belong to the heart\", emphasizing the importance of \npsychological factors, and providing new ideas for the treatment of endometriosis dysmenorrhea \npatients. \nProfessor Zhang Xiaofeng, the mentor, believes that the clinical manifestation of EM patients with \nectopic endometrium, stimulated by hormonal changes in the menstrual cycle, is called \"menstrual \nblood stasis\", which is caused by the shedding of ectopic endometrium. If there is a portion of blood \nstasis, there will be a portion of latent heat. If the blood stasis persists for a long time, it will \naccumulate into poison, which is called \"stasis toxin\"; Blood stasis does not dissipate, turning into \n\"evil blood\" and \"turbid fluid\", which then affects the application of body fluid, causing loss of water \nmetabolism and forming \"dampness toxin\"; Blood stasis, toxin, dampness, and heat are intertwined, \ncausing a lack of smooth qi flow, a lack of clear qi, a lack of turbidity, and internal obs truction of \ndampness and turbidity. This is called \"turbid toxin\". The etiology and pathogenesis of the disease \nare \"stasis, turbidity, and dampness toxin intertwined\", and the characteristic of the disease is \"when \nthe toxin is present\".  \nTherefore, the m ethod of removing blood stasis and eliminating symptoms, detoxifying and \nturbidity was established, and a self-formulated decoction for removing blood stasis, detoxifying and \neliminating symptoms was developed. The three drugs in Quyu Jiedu Tang, including Chicken Blood \nVine, Hedyotis \ndiffusa, and edible tulip, have the effects of clearing heat and detoxifying, promoting \ndampness and turbidity; Frankincense, myrrh, and dragon's blood can have the effect of promoting \nblood circulation, dispersing blood stasi s, and alleviating pain; Insects are good at moving and \nchanneling, used to detoxify centipedes, disperse knots, and clear collaterals to relieve pain; Huoxiang \nand Coix seed are fragrant and turbid, have light penetration and dampness removal, can also detoxify, \nand strengthen the spleen and stomach; Calcined corrugated, lychee kernels eliminate symptoms, \nsoften and disperse knots, promote qi circulation and relieve pain; Astragalus membranaceus can \nnourish qi and nourish the body, and promote detoxificatio n to go out; Roasted licorice is used to \nblend various herbs, while the other is to relieve pain and detoxify slowly. Patients taking Quyu Jiedu \nXiaozheng Tang can comprehensively and multi-level dissolve and eliminate evil toxins in the body, \nenabling faster elimination of evil toxins. \nMoreover, modern pharmacological research has shown that the active ingredients extracted from \nCaulis spatholobi can inhibit the occurrence of inflammatory reactions [16] and regulate a series of \nbiological processes, acting  on the treatment of endometriosis through the \"active ingredient target \npathway\" [17]. The aqueous extract of Hedyotis diffusa can reduce the levels of IL-6 and TNF-a factors \nin serum to achieve anti -inflammatory and analgesic effects  [18]. This drug can also synergistically \nregulate endometriosis with multiple components, targets, and pathways [19]. Shancigu can inhibit \ntumor cell proliferation, invasion, metastasis, and neovascularization, promote cancer cell apoptosis, \nand regulate the body's immune system [20]. The effective ingredients of frankincense and myrrh have \nclear anti-inflammatory and analgesic effects [21,22]. The flavonoid compounds in dragon's blood not \n197\n\nonly reduce inflammation and pain, but also inhibit transforming growth factor (TGF) - β 1) High \nexpression of [23]; The active ingredients of centipede may have anti -inflammatory and analgesic \neffects by inhibiting the synthesis of prostaglandins [24,25]; Litchi seed has good anti -cancer activity, \nsuch as prostate cancer, lung cancer, breast cancer, etc. [26].  \nAccording to incomplete clinical statistics, Quyu Jiedu Xiaozheng Tang has a good therapeutic \neffect on endometriosis. And through experimental research, it has been shown that the serum MIF \nand TGF of patients after treatment - β the level of 1 has decreased. Serum MIF is a key pro -\ninflammatory cytokine secreted by active macrophages accumulated in the endometrium of ectopic \ntissues. It undergoes gene expression during the secretion phase of the menstrual cycle [27], and when \nit reaches a high expression level, it may promote the development of endometriosis through \nangiogenesis [28]. Other studies have shown that serum MIF levels are higher in women with \nendometriosis caused by infertility and chronic pelvic pain [29]; Serum MIF can also activate multiple \nsignaling pathways, promoting cell proliferation, adhesion, metastasis, neovascularization, epithelial \nmesenchymal transition, and enhancing immunosuppression in gynecological malignancies such as \ncervical cancer, ovarian cancer, endometrial cancer, etc. [30]. Serum TGF in the human body- β\n By \ninducing anaerobic glycolysis and lactate secretion in endometrial stromal cells, the expression of \nmonocarboxylate transporter 4 (MCT4) is increased, further affecting endometriosis [31].  \nThere are also studies indicating that serum TGF in the human body- β 1. It may be involved in \nthe occurrence and development of endometriosis, and is related to the severity of dysmenorrhea in \npatients with endometriosis [32]; Serum TGF in the human body- β. It is also related to osteoporosis \nand breast cancer [33,34]. So the serum MIF and TGF- β the high expression of 1 in the human body, \nis closely related to the occurrence and development of endometriosis. Therefore reducing serum MIF \nand TGF - β a level of 1 through treatment ,is more conducive to the treatment of endometriosis \nand the prevention of complications or other diseases. \nAcknowledgements \n*Fund projects: Xi'an Traditional Chinese Medicine Hospital, Clinical Mechanism Study on the \nTreatment of Endometriosis with Quyu Jiedu Xiaozheng Tang ,2022yb02. \nReferences \n[1] Obstetricians and Gynecologists Branch of the Chinese Medical Association, Endometriosis Collaborative Group of \nthe Obstetrics and Gynecology Branch of the Chinese Medical Association. 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Frontiers in Genetics, 2023, 13  \n200","source_license":"CC0","license_restricted":false}