女性亚健康与肝的关系研究
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摘要
亚健康是指人的身心处于疾病与健康之间的一种健康低质状态,虽然机体无明确的疾病,但在身体、心理、适应能力上出现种种不适的感觉和症状,从而呈现活力和对外界适应力降低的一种状态。亚健康状态主要由于生活节奏加快、竞争激烈、环境恶化等因素造成的长期心理压力,导致慢性疲劳和心情压抑、免疫功能降低,从而出现的一系列偏离健康的症状。
     亚健康的发生与肝的功能失调密切相关。中医学认为肝通过对气机的疏泄和调节进而影响情志的变化,对脏腑、气血津液起着重要的调节作用,正常的疏泄功能是保证肝脏本身功能和其他脏腑功能协调有序的重要条件,是维持机体健康状态极为重要的一环,在亚健康状态中起着主导性的调节作用。肝的主要生理功能有调畅气机、调节五脏生理功能、调畅情志、促进脾胃的运化、疏利胆汁、调节女子月经与男子排精、抵抗外邪侵入,藏血调血。肝疏泄有度则气机调畅,气血调和,经络通利,脏腑组织功能正常,病无由生,人体就健康,反之,则疾病丛生。亚健康状态的常见症状如疲劳、抑郁和失眠等都与肝关系密切。因此肝在亚健康状态中起着极为重要的调节作用,在治疗上应重视调治肝脏。
     成年女性亚健康状态与肝脏功能关系密切。亚健康女性常见的症状群如情绪的虑、忧郁、烦躁、睡眠障碍等各种慢性心理应激症状,以及月经的异常等多属于肝失疏泄、肝郁气滞等证,紧密联系于中医理论之“肝”。研究结果表明中医的肝与神经-内分泌-免疫网络的关系密切。从基础实验研究我们可以得知,调肝方药关键作用的机理都表现为神经、内分泌、免疫等许多相关指标的变化。因此,女性亚健康状态可以从“肝”调治,其现代医学基础可能是通过调整神经-内分泌-免疫网络系统功能实现的。
     综上所述,探讨中医的肝与成年女性的亚健康状态及其防治之间的联系具有重要的意义。因此,本课题以“女性亚健康与肝的关系”为切入点进行深入研究。本文分为文献综述与临床研究两部分。
     1文献综述
     1.1亚健康概述
     1.1.1亚健康概念
     亚健康是是指机体无明显的疾病,却呈现活力降低,适应力不同程度减退的一种状态。二十世纪80年代中期,前苏联学者布赫曼首先将介于第一种状态(健康态)和第二种状态(疾病态)之间的状态称为“第三状态”。
     1.1.2亚健康成因
     亚健康是由于心理、生理、社会三方面因素导致机体的神经系统、内分泌系统、免疫系统整体协调失调、功能紊乱而致。导致亚健康的原因可以归结为:①压力过大,身心状态失衡;②饮食结构不合理,饮食习惯不健康;③作息不规律,生活方式欠科学;④环境污染严重,生存空间狭小;⑤情感生活质量下降,人际关系紧张,社会适应低下;⑥不良情绪,不良性格的影响。
     1.1.3临床表现
     世界卫生组织(WH0)提出,亚健康状态最典型的表现为疲劳,而与疲劳相伴的则是心理及生理的双重不适,在心理上主要表现为精神不佳、情绪低落、反应迟钝、失眠多梦或嗜睡困倦、注意力不集中、健忘、烦躁、虑、易惊、肩背疼痛、关节肌肉疼痛等;在躯体上主要表现为者自觉头晕头重、胸闷、乏力倦怠、食欲不振、心悸、自汗、肩背疼痛、关节肌肉疼痛等。
     1.2中医对亚健康病因的认识
     中医认为健康是人与自然、社会环境协调以及自身阴阳脏腑之间的一种动态平衡结果,如果阴阳失衡、脏腑失调即可产生疾病。疾病的发生主要是由于饮食不节、七情内伤、劳逸失度、年老体衰、外感六淫邪毒等原因,导致机体气血阴阳失调,气机升降失常,气血津液、脏腑经络功能紊乱,或内生五邪,或耗伤正气,从而致病。
     1.3肝与亚健康关系
     1.3.1肝的生理功能
     1.3.1.1调畅气机,调节五脏生理功能
     气的升降出入运动是机体脏腑、经络、器官等机能活动正常开展的前提条件。肝气主升、主动,是气机疏通、畅达、的重要因素。
     1.3.1.2调畅情志
     肝通过调畅全身气机、促进血液运行,从而调节情志活动。气机疏畅,气血调和则心情舒畅,情志活动正常;肝失疏泄,气机不畅,或心情抑郁,精神压抑;或急躁易怒。
     1.3.1.3促进血和津液的运行
     肝调畅全身气机,促进血液运行和津液的输布代谢,使血液运行畅达而不瘀滞,促进津液输布代谢正常而无聚湿成水、生痰化饮之患。
     1.3.1.4促进脾胃的运化
     脾主升清,胃主降浊,脾胃运化功能正常与否的重要环节在于脾胃之间气机的升降平衡协调。肝的疏泄功能正常,有利于中脾胃气机正常的升降平衡。
     1.3.1.5疏利胆汁
     胆汁为肝之余气所化,其生成、分泌、排泄均受肝主疏泄功能的控制和调节。
     1.3.1.6调节女子月经与男子排精
     男子排精、女子排卵是肾主封藏和肝主疏泄功能协同作用的结果。
     1.3.1.7抵抗外邪侵入,和调表里营卫
     肝脏具有升发元气、推动激发人体生命活动、鼓舞正气、抵抗外邪、护卫机体等重要功能。
     1.3.1.8藏血调血
     肝贮藏一定的血液,可以制约肝的阳气,防止肝阳过亢,维护肝脏正常的疏泄功能并防止出血。另一方面可以调节人体血量的分配。
     1.3.2肝功能失调的表现
     ①肝主藏血司疏泄,喜条达而恶抑郁,若肝气疏泄不及,气机不畅,则肝气郁结,出现情志抑郁或虑,善叹息,胸胁、两乳、少腹部位胀满甚或疼痛等。②肝郁化火,肝火犯肺,可出现胸胁胀痛,咳嗽,咯血;肝疏泄太过,肝气上逆,甚至气逼血升,出现急躁易怒,面红目赤,失眠多梦,头目眩晕,呕血,女子月经先期或崩漏等。③肝气横逆,肝胃不和,出现脘腹胀满,口苦,纳呆,呕逆,嗳气,便秘或泄泻,甚或黄疸等。④肝气疏泄太过,肾气不固,出现遗精滑泄,遗尿,大便失禁等。⑤肝血不足,外不能应抗邪之需极易外感,内不能灌注形体、九窍、经络、诸脏,筋骨,使其失于滋养,则见视物昏花,爪甲枯脆,肢体麻木不仁或疼痛、屈伸不利,女子月经不调等。⑥肝阴不足,则眩晕耳鸣,双目干涩,迎风流泪,腰膝酸软等肝肾阴精亏耗的虚证。
     1.4中医对女性生理病理特点的认识
     1.4.1生理方面
     在女性生理方面,中医尤以肝、肾、脾胃为要。肝在女子生理过程中发挥重要作用,《临证指南医案》提出的“女子以肝为先天”被后世医家推崇。《素问·上古天真论》中强调了人的生长发育衰老与肾的密切关系,也指出其它脏腑、经络对女性的生长发育的重要作用。徐春甫的《古今医统大全》说明脾胃在女性生理中亦有重要影响。
     1.4.2病理方面
     肾精亏损,可致肝阴不足,反之,肝阴不足,亦可引起肾精亏损。同时,肝火太盛亦可下劫肾阴,而致肾阴不足。因此,妇女的一般疾病常与肝肾虚损直接相关,其中,肝脏功能的正常与否起着非常关键的作用。
     1.5女性亚健康状态与肝脏功能关系研究概况
     从这些研究我们可以得知,肝主疏泄,肝郁气滞,调肝方药等各种作用的机理都表现为神经、内分泌、免疫等许多相关指标的变化,与神经-内分泌-免疫(NIM)网络关系非常密切。
     2女性亚健康状况调查与肝关系的临床研究
     2.1研究内容
     研究对象为2011年6月~2011年12月在美年上海、北京、天津、成都分体检中心体检的28~50岁女性,且经年度体检无明显疾病或有明确诊断但所患疾病与目前状态没有直接因果关系。诊断标准根据亚健康的定义,参考中华中医药学会亚健康专业委员会制定的《亚健康的中医临床研究指导原则(试行)》和相关文献研究,制定亚健康状态的判断参考标准,包括三个方面。
     纳入标准应符合①女性,年龄在28~50岁;②愿意接受调查并签署知情同意书者。排除标准包括①不符合纳入标准者;②患有心脑血管疾病、糖尿病、肿瘤等重大疾病;③不愿意合作者。
     2.2研究方法
     调查工具选择中国中医科学院临床评价中心研制的“亚健康状态调查问卷”。
     调查内容包括人口学资料、状况检查、临床检查。人口学资料包括姓名、年龄、婚姻状况、最高学历、职业、既往患病情况等。状况检查包括精力状况、躯体状况、心理状况、社会环境状况、生活状况、工作状况及女性情况等。临床检查内容包括有①一般情况,内、外科情况等。②妇科专科查体情况。③常规检验:血常规、尿常规、便常规、血生化检验(包括肝功能、肾功能、血糖、血脂等)。
     ④胸透、心电图、腹部B超、乳腺B超及盆腔B超。
     本研究所用资料系选用流行病学的横断面调查方法,使用统一设计的女性健康状况调查表进行调查,问卷由自填部分和访谈部分组成。本课题质量控制以各地分体检中心为单位,由经过课题组统一培训的调查员,现场发放问卷,当场回收并核查问卷。
     对于本研究合格问卷的判断,需要对填写后的问卷进行再次筛选,并符合以下要求者视为合格问卷:①一般信息中除地址和联系方式外的项目必须填写。②全部问题的缺失和遗漏不超过5%。
     2.3数据录入与统计分析
     本研究采用EpiData3.02软件作为数据录入软件建立数据库。
     录入人员需先参加录入手册的学习,再作录入练习,正式数据采用不同人员异地双录入的方式进行。对于数据资料,需对正正式数据逐项核查、修正至录入数据完全一致。统计学分析运用SPSS软件进行。
     3.结果3.1一般情况:共发放问卷650份,回收644份,其中634份为合格问卷,剔除问卷10人,2人因年龄原因,4人因重大疾病,4人因条目缺失。问卷合格率为97.54%。问卷的平均完成时间约为30分钟。
     3.2研究对象的人口学特征:在年龄分布上,亚健康女性人群中,28~35岁占第一位,居于第二位和第三位的分别是35~42岁年龄段和42~49岁年龄段,而49岁以上占的比例最少。在职业分布上,业健康女性人群中,行政管理人员占第一位,医务人员占第二位,再次是行政事务人员。在婚姻状况上,亚健康女性人群中,已婚人员占比率最大,明显高于未婚和离异的人员;其次是未婚人员,再次是离异人员。在文化程度上,亚健康女性人群中,大专学历占第一位,其次是大学本科学历,再次是中专学历。
     3.3女性亚健康症状:女性业健康临床症状分布方面,社会环境状况的亚健康症状表现最多,为16个,其次为生活状况10个,再次为躯体状况9个,情志状况8个,精力状况5个,禀赋状况没有。社会环境的分值在女性亚健康的所有症状分值中最高。生活状况分布方面,性生活和饮食因素的分值最高,10个症状中,5个为睡眠状况。躯体症状分布方面,疲乏及休息后不能缓解在躯体症状中是最主要的症状,其次是头昏、眼睛干涩酸胀及咽干。8个情志状况的分值中有6个在3分以上,分值较高。精力状况分布方面,表现为亚健康女性普遍对自身的工作能力和日常生活不满意,且工作及休闲的精力欠缺。
     3.4女性情况:未绝经与绝经人数分布情况,绝经的亚健康人群中,年龄小于49岁的人员比率多于年龄大于等于49岁的女性;在未绝经的亚健康人群中,年龄小于49岁的人员比率明显多于年龄大于等于49岁的女性。在亚健康女性人群中,月经异常的女性占很大的比率,明显大于月经正常的女性;在月经异常的女性中,月经周期和量异常的比率基本相等。在月经周期异常及量异常的亚健康女性中,年龄小于35岁的女性都占最大的比率,其次是35岁-42岁之间的人群,大于42岁的人数最少。亚健康女性中经前乳房胀痛占76.81%;经前乳房中度、重度和极重度胀痛的占31.55%,年龄小于35岁的人群占绝大部分,且科技或工程研究人员、企事业负责人及行政事务人员的人群比例最高。
     3.5女性亚健康舌象和脉象:亚健康人群中,舌体正常的人占多数,属于第一位;舌体偏胖的人占第二位;舌体偏瘦的人最少,占第三位。舌质偏淡的人占第一位,舌质红的人占第二位,舌质紫暗的人占第三位。脉象方面,细脉的人群占第一位,其次是弦脉,滑脉占第三位。
     3.6女性亚健康人群的中医证候分布:634例女性亚健康中辨证结果共计46种证候,其中分布集中的频数在10次以上者有9种,根据其在总例数中出现的频次及频率高低排序,分别为肝气郁结证(182次,28.70%),肝郁脾虚证(176次,27.76%),肝肾阴虚证(70次,11.04%),脾虚湿阻证(56次,8.8%),肝火炽盛证(38次,6.0%)脾肾阳虚证(22次,3.47%),心肾不交证(14次,2.21%),气血两虚证(12次,1.89%),气虚证(10次,1.58%)。肝气郁结和肝郁脾虚证两者之和所占的比例高达56.47%.
     3.7女性亚健康的脏腑定位及证候要素提取:根据因子分析统计方法,将症状进行证候要素的提取。选取特征根值大于1的共因子共10个,进行证候要素分析。因子1脏腑定位在肝,其证候要素为郁证。因子2脏腑定位在心和肝,其证候要素为虚和郁证。因子3脏腑定位在大肠,证候要素为热证。因子4脏腑定位在心和肝,证候要素为气虚和郁证。因子5脏腑定位在脾,证候要素为气虚证。因子6脏腑定位在肝,证候要素为阴虚证。因子7脏腑定位在肝,证候要素为热和郁证。因子8脏腑定位在肝和肾,证候要素为血虚和瘀证。因子9脏腑定位在心,证候要素为阴虚证。因子10脏腑定位在小肠,证候要素为热证。女性亚健康人群不适症状的脏腑定位在肝、心、脾、肾、大肠和小肠。其中尤以定位在肝最多,其次为心。证候要素最多为郁证,其次为虚证(气、血、阴)和热证,再次为瘀证。
     3.8血流变学检测指标结果:女性亚健康组与正常范围比较,全血粘度值、血浆粘度与红细胞压积与均明显升高。这些异常的变化,发生在临床出现症状或体征之前,即亚健康状态。
     4结论
     通过研究得出以下结论:
     4.1肝失疏泄是女性亚健康主要病机之一。
     4.2气机不利、藏血失司是女性亚健康月经异常的病机特点。
     4.3肝气郁结证和肝郁脾虚证是女性亚健康的主要证候。
     4.4由郁致虚、由气及血与由肝及心脾肾功能失调是女性亚健康的证候演变趋势。
     4.5血行滞涩是女性亚健康的常见病理变化。
Sub-health is a conception of modern medicine, in which a person's body and mind, between illness and health, is in inferior state. People suffering from sub-health have various uncomfortable feelings and symptoms in body and mind, but don't get specific diseases. These will result in vigor and ability to changeable society reduced. The sub-health state of modern society mainly refers to a series of sub-healthy symptoms which be caused by chronic depression and declining immune function raised by quickening pace of life、fierce competition deterioration of environment, which leading to long-term psychological stress.
     The occurrence of sub-health has closely relationship with liver. Liver can affect minds and push fluid and humor through activating and regulate qi. Liver palys an important role in harmonizing both viscera-bowels, qi-blood and fluid-humor. Liver is also an important part to maintain body's healthy state. To sum up, the happening of sub-health mostly depends on whether liver function well. The main physiological function of liver is as follows:to regulate qi movement and the function of five viscera, to adjust minds,to activate blood and fluid-humor's movement, to promote the transportation and transformation of spleen and stomach, to smooth bile, to regulate women's menstruation and emission of men, to harmonize qi movement of viscera and bowels, to regulate waterways of triple energizers, to defend invasion of external pathogen, to harmonize the exterior-interior and nutrient-defense and to store and regulate blood. If liver can be smoothed appropriately, the qi and blood will become harmony, the meridians and collaterals will be dredged and activated and the viscera and bowel's function will be normal. Then the body of human will be healthy. If not, abundant disease will occur. The main symptoms of sub-health have closely relationship with liver, such as lassitude of spirit, depression and inability to sleep. So liver's function is the predominant condition which decides whether sub-health will occur. We should emphasize on the treatment of liver.
     There are few modern literature reporting the relationship between sub-health state of adult women and liver's function. These reports hold that the symptoms of sub-healthy women mostly describe chronic psychological stress, such as anxiety, depression, irritable, sleep disorders and menstrual abnormalities. Many basic studies reveal that the liver of TCM has closely relationship with neuro-endocrine-immune network. We can know from these basic experimental researches that liver's controlling conveyance and dispersion, liver qi stagnation, medicine smoothing the liver are all expressed by some changeable index related with nervous, endocrine and immune systems. Some symptoms of chronic psychological stress like anxiety, depression, irritable, sleep disorders and a series of sub-healthy symptoms due to liver not controlling of conveyance and dispersion or liver qi stagnation are also because of the nerve, endocrine and immune systems abnormal.
     Above all, to explore of the connection between the liver of TCM and adult women of health status has the vital significance. Therefore,I chose this topic. This paper is divided into two parts, literature review and clinical research.
     The Survey of Women's Sub-health State and the Clinical Research about the Relationship between Sub-health and Liver. The objects of the research are women aged28-50years, who took medical examination from June2011to December2011in branches of Meinian medical examination center set in Shanghai, Beijing, Tianjin and Chengdu. They either have no clear disease or the disease they got have no direct causality with present state. Diagnostic criteria refers to a body's state between health and illness. People who stay in sub-healthy state can't reach the standard of health, appearing vigor reduced, function and ability to adapt to society declined in a period, but don't meet the clinical or the sub-clinical diagnosis standard of related disease in moderm medicine. The entry criteria is women aged28-50, willing to accept investigation. Exclusive criteria are cardiovascular diseases, diabetes and cancer.
     The "sub-health questionnaire" developed by Liubaoyan. etc from China Academy of Chinese Medical Sciences is the survey reference tool in this research. This research choose cross-sectinal survey method of epidemiology, and made by investigators who get unified and professional training, and finished as a form of scene investigation. We take every branch of Meinian medical examination center as a unit, assign the professional investigators to send questionnaire, check the questionnaire at the same time and spot.
     We adopt EpiData3.02software as data logger. Data entried by different people in different spots, using double entry method, verified and modified item by item until the secondary input data identical. At last, we use SPSS16.0software to analyze.
     The results of research are as follows.
     1.General situation:650questionnaires were sent, among them644questionnaires were recovered and634questionnaires qualified.10questionnaires were ruled out, for2failing to meet the age range,4getting severe disease,4not completing all the item. The qualified rate of the questionnaires is97.54%.The duration of finishing the questionnaires is within30minutes.
     2.The description of demographic characteristics for the objects:in terms of the age distribution among subhealthy women, those aged28-35years take first place. On the second and third place respectively are those in35-42years and in42-49years. Those whose age above49years take the least proportion.In terms of the profession distribution among sub-healthy women:administrative management personnel occupy the first place. The medical staff take the second place. On the third place is administrative affairs personnel. The chief of enterprise and public institution take a small proportion compared with above people. In terms of the marital status among the sub-healthy women, the number of married women accounts for the largest percentage, much higher than that of unmarried and divorced women. The unmarried women take the second place, and divorced women take the third place.In terms of the cultural degree among the sub-healthy women, those with college degree take the first place, second place is the bachelor degree, the technical secondary school education take the third place..
     3. Symptoms statistics of sub-healthy women:on the aspect of distribution of clinical symptoms,16items of the sub-health symptoms caused by social environment condition take the most percentage.10items relate to living conditions.9items relate to body condition.8items of emotional state take the fourth place.5items of energy state take the fifth place. There is no item related to natural endowment conditions. The score of social environment is the highest compared with other scores. It suggests that social environment influence a woman's health life in a large extent. In the terms of distribution of living conditions, sex and food taking get the highest score. among10symptoms,5is about sleep state. In terms of distribution of somatic symptoms, fatigue even not being relieved after rest is the main symptom. Other symptoms are dizziness, dry and acid eyes and dry throat. Scores of6among8about emotional state take more than3points, which is a high score. As for distribution of energy situation, sub-healthy women generally do not satisfied with their work ability and daily life, and lack of energy during work and entertainment.
     4. Female physiological state:In terms of distribution of premenopausal and menopausal people, women younger than49years ole are more than the those aged49and older than49among in the menopausal people. Women younger than49years old are fewer than those aged49years old and older than49years old in the premenopausal.Among the sub-healthy women, those with menstrual abnormality take up a large proportion, significantly greater than those with normal menstruation. The proportion of both period and quantity of the menstruation is almost equal among the women of menstrual abnormality. In the sub-healthy women, no matter whether menstrual period and or menstrual quantity is normal, those of less than35years old account for the biggest ratio, followed by those aged35-42years. The number of those aged42years is the least.Among all the sub-healthy women, the people who have distending pain in breast before menstruation account for76.81%. The women who have moderate, severe and very serious distending pain account for31.55%. People less than35years old account for the most part. People who works as science and technology personnel, engineering research staff, the chief of enterprise and public institution, administrative affairs personnel reach the highest proportion of the objects.
     5.The distribution of tongue manifestation and pulse condition of sub-healthy women:Subhealthy people with normal tongue body account for the majority. People with enlarged tongue body take the second place. People with thin tongue body are the least. In terms of tongue color, people with pale tongue take the first place. People with red tongue take the second place. People with dark purple tongue take the third place. As for pulse condition, the first one is people with thready pulse, the second one string-like pulse and the third one slippery pulse.
     6.The distribution of TCM syndrome among sub-healthy women:634cases of sub-healthy women can be classified as46patterns of syndrome differentitation of TCM, including concentrated nine patterns, of which frequency is five times or more. We can sort in the order according to its frequency appearing in total cases from high to low as follows:liver qi depression pattern(182times,28.70%), pattern of liver depression and spleen deficiency(176times,27.76%),liver-kidney yin deficiency pattern (70times,11.04%),pattern of spleen deficiency with dampness encumbrance (56times,8.8%), intense liver fire pattern (38times,6.0%) spleen-kidney yang deficiency pattern(22times,3.47%), heart-kidney non-interaction pattern(14times,2.21%), pattern of dual deficiency of qi and blood (12times,1.89%), qi deficiency pattern (10times,1.58%). Combine the proportion of liver qi depression pattern and pattern of liver depression and spleen deficiency, the total proportion reaches as much as56.47%.
     7. Viscera positioning and extraction for syndrome elements
     According to the statistical methods of factor analysis, we extract the syndrome elements from symptoms. We select10factors of which root value greater than1and make explanation for them. Factor1, of which viscera positioning is liver and the syndrome element is depression pattern. Factor2, of which viscera positioning is heart and liver and the syndrome elements are deficiency and depression patterns. Factor3.of which viscera positioning is large intestine and syndrome element is heat pattern. Factor4, of which viscera positioning is heart and liver, syndrome elements are qi deficiency and depression patterns. Factor5, of which viscera positioning is spleen and syndrome element is qi deficiency. Factor6, of which viscera positioning is liver and syndrome element is yin deficiency pattern. Factor7, of which viscera positioning, is liver, syndrome elements are heat and depression patterns. Factor8, of which viscera positioning is liver and kidney, syndrome elements are blood deficiency and blood stasis patterns. Factor9, of which viscera positioning is heart, syndrome element is yin deficiency pattern. Factor10,of which viscera positioning is small intestine, syndrome element is heat pattern.
     8. Blood rheology test indexes result
     Compared with the normal range, the whole blood viscosity value, plasma viscosity and hematocrit of sub-healthy women group were significantly increased. These abnormal changes happen before the clinical symptoms or signs occur. This duration is a stage that health state transform into disease state, which is called sub-health state.
     The conclusion of research are as follows.
     1.The liver is one of the main pathogenesis of female health.
     2. Negative air machine, hidden blood loss are characteristics of the pathogenesis of female sub-health menstrual abnormalities.
     3. The stagnation of Liver-qi syndrome and liver stagnation and spleen deficiency syndrome is the main syndrome of sub-health symptoms in women.
     4. By Yu to deficiency, by the gas and blood and by liver and spleen kidney dysfunction is the evolution trend of the health of the syndrome in women.
     5. The blood line obscure is a common pathological changes of female sub-health
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