Research On Traditional Chinese Medicine Diagnosis And Syndrome Differentiation-classification Of Precocious Puberty Based On Delphi Method

ObjectiveBasic materials and historic evidences used for designing expert questionnaires of "Traditional Chinese Medicine (TCM) guidelines of diagnosis and treatment for precocious puberty" were offered by metrology analyzing domestic literatures of TCM treatment for precocious puberty in recent 30 years. Clinical firsthand information and realistic evidences for expert questionnaires were provided by clinical investigation. Following principles of Delphi method, expert questionnaires were designed and delivered, and questionnaires retrieved were statistically analyzed, in order to form first draft of scientific, objective and systemic "TCM guidelines of diagnosis and treatment for precocious puberty".MethodsPART 1:Metrology Analyzing Literatures of TCM Treatments for Precocious Puberty in Recent 30 YearsUsing "precocious puberty", "gynecomastia" as subject Headings, literatures of TCM treatments for precocious puberty were searched in China journal full-text database of China National Knowledge Infrastructure (CNKI). Internalizing and precluding standards were enacted. Internalized literatures were preliminary assessed following the methods of evidence based medicine for the purpose of selecting evidence of higher class. Distribution of methods of treatment and laws of syndrome differentiation and medication were metrology analyzed.PART 2:Clinical Investigation for TCM Syndromes in 109 Girls of Precocious Puberty and Early PubertyQuestionnaire for classifying and quantifying TCM symptoms of girls of precocious puberty was designed. Internalizing and precluding standards were enacted. General conditions, test items, classified and quantified TCM symptoms, and correlation factors of precocious puberty for girls of precocious puberty and early puberty were clinically investigated. And TCM syndromes for all the girls were differentiated and classified by the panel of experts in our department. Syndrome differentiation principles were enacted according to the main syndrome, first accompanied syndrome and second accompanied syndrome. statistical software of SPSS 16.0 were used in:①comparison with relevant conditions of the two groups classified by the age of onset;②correlation analysis or partial correlation analysis on age of onset, degree of mammillary nucleus and test items;③practical prevalence and score of TCM symptoms and manifestation of tongue and pulse;④analysis on frequency distribution of different syndromes, comparison with diagnostic integrations of different syndromes, correlation analysis or partial correlation analysis on scores for different syndromes, according to results of syndrome differentiation.PART 3:Research on TCM Standards of Diagnosis and Treatment for Precocious Puberty Based on Delphi MethodBased on the anterior two parts, expert questionnaires for "TCM guidelines of diagnosis and treatment for precocious puberty" was designed. Forty to fifty five selected experts with titles of senior professional posts and a certain degree of celebrity, who had been engaged in pediatrics for at least 10 years, were investigated by designed questionnaire. They appraised items in the questionnaire by different grades, and gave literal suggestion and opinions for modifying. Following principles of Delphi method, retrieved questionnaires were appraised by indexes of concentration degree and coordination degree from experts' opinions.ResultsResults of PART11. General Conditions In total,3428 patients were treated,75 decoctions and 120 traditional Chinese drugs were included in 74 internalized literatures. The total absolute frequency for traditional Chinese drugs was 752 times.2. Methods of Treatment Distribution Classified by different methods of treatment,65 literatures (87.84%) using decoctions,21 literatures (28.38%) using ready made patent drugs,9 literatures (12.16%) using integrated TCM and western medicin,4 literatures (5.41%) associated by TCM external therapy,1 literature (1.35%) associated by dietary therapy. Ranking absolute frequency of ready made patent drugs from many to few, there were "Zhi Bai Di Huang Wan" (10 times) "Xiao Yao San" (7 times), "Da Bu Yin Wan" (6 times), "Liu Wei Di Huang Wan" (4 times), "Ru Pi Xiao", "Gan Lu Xiao Du Dan", "Gui Pi Wan", "Xiao Jin Dan" (1 time). The associated western medicine was megestrol except depogeston in one literature. For associated TCM external therapy, there were pressing on ear acupoint, wiping medicine wine and ointment application.3. Distribution for Patterns of Syndromes Precocious puberty had 3 syndromes, including syndrome of hyperactivity of fire due to yin deficiency (SyndromeⅠfor short in below contents), syndrome of depressed liver qi transforming into fire (SyndromeⅡfor short in below contents) and syndrome of endoretention of damp heat (SyndromeⅢfor short in below contents). That conclusion could be drawn from synthetizing all the internalized literatures. SyndromeⅠincluded 36 decoctions (occupying 48.00% in total),60 traditional Chinese drugs (305 times for absolute frequency).SyndromeⅡincluded 13 decoctions (17.33%),53 traditional Chinese drugs(132 times for absolute frequency). SyndromeⅢincluded 4 decoctions(5.33%), 25 traditional Chinese drugs (40 times for frequency). SyndromeⅠcombined with SyndromeⅡor SyndromeⅢ, Combined Syndrome for short in below contents, included 22 decoctions(29.33%),82 traditional Chinese drugs(275 times for absolute frequency).4. Traditional Chinese Drugs with High Frequency for Different Syndromes SyndromeⅠhad 9 traditional Chinese drugs with frequency higher than>3% ,204 times for accumulative absolute frequency and 66.88% for frequency. These traditional Chinese drugs in turn were Rhizoma Anemarrhenae, Radix Rehmanniae, Cortex Phellodendri Amurensis, Carapax et Plastrum Testudinis, Cortex Moutan Radicis, Rhizoma Alismatis, Spica Prunellae Vulgaris, Radix Scrophulariae, and Radix Gentianae. SyndromeⅡhad 13 traditional Chinese drugs with frequency higher than>3%,76 times for accumulative absolute frequency and 57.58% for frequency. These traditional Chinese drugs in turn were Radix Bupleuri Chinensis, Radix Paeoniae Alba, Radix Angelicae Sinensis, Spica Prunellae Vulgaris, Fructus Gradeniae, Radix Glycyrrhizae, Radix Scutellariae Baicalensis, Rhizoma Cyperi, Cortex Moutan Radicis, Herba Menthae Haplocalycis, Rhizoma Atractylodis, poria, and Fructus Hordei Germinatus. Combined Syndrome had 7 traditional Chinese drugs with frequency higher than>3%,88 times for accumulative absolute frequency and 32.00% for frequency. These traditional Chinese drugs in turn were Spica Prunellae Vulgaris, Cortex Phellodendri Amurensis, Radix Bupleuri Chinensis, Radix Rehmanniae, Rhizoma Anemarrhenae, Cortex Moutan Radicis, and poria.Results of PART 2 1. Correlation Analysis and Partial Correlation Aanalysis①The age of onset had significant positive correlation with height, age and bone age of first visit(r=0.688,0.880,0.998, respectively, all intimate correlativity), had negative correlation with weight of first visit and course of this disease (r=-0.233,-0.193, respectively, no intimate correlativity), and had significant negative correlation with advanced degree of bone age(r=-0.997, intimate correlativity).②The average degree of mammillary nucleus had positive correlation with serous level of follicle stimulating hormone (FSH), height of first visit, and uterus volume (r=0.328,0.220,0.379,respectively).③The uterus volume had significant positive correlation with average ovary volume and serous FSH level (r=0.308,0.434, respectively).④The average ovary volume had positive correlation with serous level of luteinizing hormone (LH) and height of first visit (r=0.333,0.433, respectively), and had significant negative correlation with weight of first visit (r=0.661, intimate correlativity).⑤Others:Serous LH level and FSH level were significant positive correlated (r =0.661). Height and weight of first visit were significant positive correlated (r =0.659). Bone age of first visit had significant positive correlation with advanced degree of bone age (r=0.931, extremely intimate correlativity). Course of this disease had significant positive correlation with bone age of first visit (r=0.991), and had significant negative correlation with advanced degree of bone age (r=-0.988).2. Investigation on TCM Symptoms and Manifestation of Tongue and Pulse: The 9 symptoms which was common in clinic and with relatively heavy synthetic degree ranked in order were:enjoying fat and sugar, being afraid of heat, burning sensation of five centres, agitation and tantrum, increase of ocular discharge, fetid breath, night sweat, less urine, spargosis and pain, especially the 3 symptoms ahead, which were mainly among middle to severe degree. Red tip of tongue was the most common tongue manifestation (67.89% for actuality prevalence). More than half of involved girls (55.96% for exactly) had thick or greasy fur, with degrees of mild to middle. The most common pulse manifestations were slippery pulse, string-like pulse, and soggy weak pulse, with mild degree for ninety percent of these pulse manifestations.3. Diagnosis on Syndrome Differentiation①Diagnostic Rate of Principal Syndrome:Syndrome I was the most common diagnosis for principal syndrome, occupied 80.73% in 109 girls. Next comes SyndromeⅡ, occupied 19.27%. None of girls were diagnosed as SyndromeⅢfor principal syndrome.②Diagnostic Integrations of Different Syndromes:The diagnostic integrations of 3 syndromes were with significant statistical differences. Average ranks for each syndrome from most to least were:SyndromeⅠ(528.18), SyndromeⅡ(395.85), SyndromeⅢ(148.47)③Combined Syndrome:86.24% of girls were diagnosed as Syndrome I and SyndromeⅡat the same time, but these two syndromes were different on diagnosis as principal syndrome or accompanied symptoms. Exactly speaking,81 girls were diagnosed as SyndromeⅠaccompanied by Syndrome②, and the rest 13 girls were diagnosed as SyndromeⅡaccompanied by SyndromeⅠ.Results of PART 31. Forty nine questionnaires in reply were received in second round of investigation. The active index of experts was 90.74%.2. Diagnosis of Precocious Puberty2.1 Clinical Manifestation:including①anticipation of secondary sex characters: 1) following appearances in girls:mammoplasia, increase of vaginal secretions, development of lip of pudendum, chromatosis on areola of breast and lip of pudendum, appearance of pubic hairs and axillary hairs, menstrual onset, acne; 2) following appearances in boys:testis enlargement, penis thickening, increase and chromatosis of scrotum skinfold, appearance of pubic hairs and axillary hairs, appearance of beard and laryngeal prominence, change of voice, erection of penis, night seminal emission, acne, mammoplasia;②accelerated linear growth. Mean (x) of these 21 items were between 1.00 and 2.00, with rank sum (Sum)≥50.00% of full score, percentage of unimportance (R)=≤15.22%. Majority of experts agreed that these items were important in diagnosis of precocious puberty.2.2 Laboratory Examination:including 1)gonadotropin releasing hormone (GnRH) stimulation test; 2)serous sex hormone level including:luteinizing hormone, follicle stimulating hormone, estradiol, prolactin, testosterone; 3)B-mode ultrasound for uterus, ovaries, mammary glands in girls, for testis, scrotum in boys; 4)bone age; 5)bone density; 6)vagina cast-off cells test; 7) serous thyroid gland functions; 8) insulin-like growth factor-1 (IGF-1), insulin-like growth factor binding protein (IGFBP3),9)plain magnetic resonance imaging (MRI) scan of hypothalamus and pituitary gland to exclude organic disease; 10) B-mode ultrasound or CT scan to exclude hyperplasia or space-occupying disease in adrenal glands, x of these 16 items were between 1.00 and 2.00, with Sum≥50.00% of full score, R≤16.67%. These items were relatively important laboratory examinations.2.3 History Collection & Differential Diagnosis of Central Precocious Puberty: History collection including:exposure to exogenous hormones, birth history, gestation history of mothers, developmental history of family members. Differential diagnosis of central precocious puberty including:adrenal cortex neoplasms, ovarian or testicular neoplasms, congenital adrenal hyperplasia, and polyostotic fibrous dysplasia. x of these 9 items were between 1.00 and 2.00, with Sum≥50.00% of full score, R≤8.16%, coefficient of variability (CV)≤45.18%. Majority of experts agreed that these items were important in diagnosis of precocious puberty.3. Syndrome Classification of Precocious Puberty:Majority of experts agreed that SyndromeⅠwas the most important syndrome in all the syndromes of precocious puberty. SyndromeⅡalso was one of the principal syndromes in precocious puberty. Partial experts considered that SyndromeⅢwas less important in syndrome classification of precocious puberty, which was not a common syndrome in clinic.4. Treatment of Precocious Puberty Based on Syndrome Differentiation4.1 Syndrome of Hyperactivity of Fire Due to Yin Deficiency (SyndromeⅠ)①Main Points of Syndrome Differentiation:Mammoplasia, increase of vaginal secretions, development of lip of pudendum, chromatosis on areola of breast and lip of pudendum, appearance of pubic hairs and axillary hairs, menstrual onset, enlargement of testis, penis thickening, appearance of beard and laryngeal prominence, increase and chromatosis of scrotum skinfold, change of voice, erection of penis, night seminal emission, burning sensation of five centres, tidal fever, being afraid of heat, night sweat, less urine, constipation, agitation and tantrum, thirsty or dry mouth, vermilion of the lip, trophonema of labiaoris, reddened complexion, hectic cheek, red tongue, thin tongue, few fur or exfoliative fur, frequent pulse, and fine pulse were included. x of these 30 items were between 1.00 and 2.00, with Sum≥50.00% of full score, R between 0.00% and 25.53%. Experts considered these items were very important in Syndrome I differentiation.②Major Therapeutic Principle:"Nourishing kidney yin, clearing ministerial fire" and "nourishing yin to lessen fire" were included. x of these items were between 1.00 and 2.00, with Sum≥50.00% of full score, R≤19.15%. Experts agreed that these were important therapeutic principle for Syndrome I, especially the former.③Major Prescriptions:x of "Zhi Bai Di Huang Wan Jia Jian", "Da Bu Yin Wan Jia Jian" and "Zhi Bai Di Huang Wan combined with Da Bu Yin Wan Jia Jian" were between 1.00 and 2.00, with Sum≥50.00% of full score, R between 0.00% and 10.87%. Experts considered that these three prescriptions were important prescriptions for SyndromeⅠ, especially the former one.④Important Traditional Chinese Drugs:Rhizoma Anemarrhenae, Radix Rehmanniae, Cortex Phellodendri Amurensis, Carapax et Plastrum Testudinis, Cortex Moutan Radicis, Rhizoma Alismatis, Radix Scrophulariae, Spica Prunellae Vulgaris, Radix Gentianae, Radix Rehmanniae preparata, Fructus Macrocarpii, Rhizoma Dioscoreae Oppositae, Radix Paeoniae Alba, Radix Glycyrrhizae, Fructus Hordei Germinatus, Poria, Concha Ostreae and Fructus Lycii were included. x of these 18 traditional Chinese drugs were between 1.00 and 2.00, with Sum≥50.00% of full score, R between 0.00% and 33.33%. Experts considered they were the important traditional Chinese drugs to treat SyndromeⅠ.4.2 Syndrome of Depressed Liver Qi Transforming into Fire (SyndromeⅡ)①Main Points of Syndrome Differentiation:Mammoplasia, foul turbidity of vaginal secretions, development of lip of pudendum, chromatosis on areola of breast and lip of pudendum, appearance of pubic hairs and axillary hairs, menstrual onset, enlargement of testis, penis thickening, appearance of beard and laryngeal prominence, increase and chromatosis of scrotum skinfold, change of voice, erection of penis, night seminal emission, being afraid of heat, less urine, constipation, agitation and tantrum, emotional depression, belching and sighing, oppression and gas pain in chest, spargosis and pain, insomnia, dreaminess, dizziness, conjunctival congestion, gas pain in oculuses, dessication and unsmooth in oculuses, bitter taste in mouth, fetid breath, thirsty or dry mouth, trophonema of labiaoris, reddened complexion, acne, red tongue, red margin of tongue, frequent pulse, and string-like pulse were included. x of these 37 items were between 1.00 and 2.00, with Sum≥50.00% of full score, R between 0.00% and 26.67%. Experts considered these items were important in SyndromeⅡdifferentiation.②Major Therapeutic Principle:"Dispersing stagnated liver qi for relieving qi stagnation, clearing heart fire" and "soothing the liver and purge fire, relieving qi depression and remove mass" were included. All x of these items were between 1.00 and 2.00, with Sum≥50.00% of full score, R≤24.44%. Experts considered that these were important therapeutic principle for SyndromeⅡ,especially the former.③Major Prescriptions:x of "Dan Zhi Xiao Yao San Jia Jian" and "Long Dan Xie Gan Tang Jia Jian" were between 1.00 and 2.00, with Sum≥50.00% of full score, R≤13.33%. These two prescriptions were important prescriptions for SyndromeⅡ, especially the former.④Important Traditional Chinese Drugs:Radix Bupleuri Chinensis, Radix Gentianae, Spica Prunellae Vulgaris, Radix Paeoniae Alba, Fructus Gradeniae, Radix Rehmanniae, Radix Angelicae Sinensis, Radix Scutellariae Baicalensis, Cortex Moutan Radicis, Radix Glycyrrhizae, Semen Plantaginis, Rhizoma Alismatis, Rhizoma Atractylodis, Poria, Rhizoma Cyperi, Pericarpium Citri Reticulatae, Rhizoma Chanxiong and Fructus Aurantii Submaturus were included. x of these 18 traditional Chinese drugs were between 1.00 and 2.00, with Sum≥50.00% of full score, R between 0.00% and 31.25%. Experts considered they were the important traditional Chinese drugs to treat SyndromeⅡ.4.3 Syndrome of Endoretention of Damp Heat (SyndromeⅢ)①Main Points of Syndrome Differentiation:Mammoplasia, vaginal secretions more than normal, development of lip of pudendum, chromatosis on areola of breast and lip of pudendum, appearance of pubic hairs and axillary hairs, menstrual onset, enlargement of testis, penis thickening, appearance of beard and laryngeal prominence, increase and chromatosis of scrotum skinfold, change of voice, erection of penis, dull fever, being afraid of heat, less urine, endless sloppy stool, cerebaria, dizziness, oppression in chest, increase of ocular discharge, sticking and greasy in mouth, trophonema of labiaoris, sallow complexion, acne, sore and ulcer in skin, obesity, weary and heavy limbs, weary and acratia, anorexia, polyphagia of fat and sugar, nauseated and vomit sputum, gastric and abdominal distension afterfood, yellow foul morbid leucorrhea, red tongue, hypertrophied tongue, greasy fur, thick fur, and slippery pulse were included. x of these 40 items were between 1.00 and 2.00, with Sum≥50.00% of full score, R between 0.00% and 29.55%. Experts considered these items were important in SyndromeⅢdifferentiation.②Major Therapeutic Principle:"Clearing heat and drying dampness, dissipating phlegm and remove mass" and "fortifying the spleen and drying dampness, dissipating phlegm and purging fire" were included. x of these items were between 1.00 and 2.00, with Sum≥50.00% of full score, R≤22.73%. Experts agreed that these were important therapeutic principle for SyndromeⅢ, especially the former.③Major Prescriptions:x of "Er Chen Tang Jia Jian" and "Er Chen Tang combined with Zhi Bai Di Huang Wan Jia Jian" were between 1.00 and 2.00, with Sum≥50.00% of full score, R≤9.09%. Experts agreed that these two prescriptions were important prescriptions for SyndromeⅢ, especially the former.④Important Traditional Chinese Drugs:Rhizoma Pinelliae, Pericarpium Citri Reticulatae, poria, Fructus Aurantii Submaturus, Rhizoma Atractylodis Lanceae, Fructus et Semen Trichosanthis, Semen Plantaginis, Rhizoma Alismatis, Radix Scutellariae Baicalensis, Cortex Phellodendri Amurensis, Rhizoma Anemarrhenae, Radix Rehmanniae, Rhizoma Atractylodis, Rhizoma Dioscoreae Oppositae, Radix Paeoniae Alba, Radix Bupleuri Chinensis, Thallus Sargassi Pallidi, Thallus Laminariae Japonicae, Pericarpium Citri Reticulatae Viride, Semen Litchi, Cortex Moutan Radicis, Pseudobulbus Cremastrae seu Pleiones, Rhizoma Acori Tatarinowii, Talcum and Semen Coicis were included. x of these 25 traditional Chinese drugs were between 1.00 and 2.00, with Sum≥50.00% of full score, R between 0.00% and 35.56%. Experts considered they were the important traditional Chinese drugs to treat SyndromeⅢ.5. Ready Made Patent Drugs Commonly Used in Precocious Puberty: including "Zhi Bai Di Huang Wan", "Dan Zhi Xiao Yao Wan", "Da Bu Yin Wan", "Xiao Yao Wan", "Chai Hu Shu Gan Wan", "Long Dan Xie Gan Wan" and "Liu Wei Di Huang Wan". x of these 7 items were between 1.00 and 2.00, with Sum≥50.00% of full score, R between 0.00% and 15.56%. Experts considered these items were important to treat Precocious Puberty, especially "Zhi Bai Di Huang Wan", "Dan Zhi Xiao Yao Wan", "Da Bu Yin Wan" and "Xiao Yao Wan", which were the major Ready Made Patent Drugs to treat precocious puberty.6. Methods of Western Medicine Combined With TCM Treatment of Precocious Puberty:including gonadotropin releasing hormone analog (GnRHa), megestrol, cyproterone and danazol. x of these 4 items were between 1.00 and 2.00, with Sum≥50.00% of full score, R between 9.30% and 26.19%. Experts considered these items were important methods of western medicine combined with TCM treatment of precocious puberty.7. Other Traditional Therapy of Precocious Puberty & Psychological and Behavior Therapy:Pasting and pressing on ear acupoint, ear acupuncture therapy, body accupunture therapy, and external traditional Chinese drugs to dissipate mammillary nucleus were included. x of these 4 items were between 1.03 and 1.10, with Sum≥50.00% of full score, R between 24.39% and 32.50%. Experts considered these items were relatively important in other traditional therapy. Explaining to family members in details the cause of this disease and the importance to treat in time considering to prognosis, comforting patients to relieve mental stress were included. x of these 2 items were≥1.50, with Sum≥50.00% of full score, with both R 0.00%, CV≤23.15%. Majority of experts agreed that these two items were important in the treatment of precocious puberty.8. Partner Treatment of Precocious Puberty:including①prevention and nursing care:for patients 1) alimentary control,2) physical exercise,3) psychological counseling,4) keeping away from poisonous substance,5) keeping away from television, movie, books and internet related to sex,6) avoiding intaking tonics if without special needs,7) avoiding intaking poultry, livestock, aquatic products which were feeded with sex hormones; for mothers 1) avoiding intaking contraceptives during lactation,2) avoiding intaking foods containing hormones during pregnancy;②requirements to control intaking following items:fast food, health care products, traditional Chinese drugs to reinforce kidney, puffing and fried food;③requirements to avoid intaking or exposure to following items:health care products, lactobin, royal jelly, contraceptive, skin care products for female, cosmetics, environmental endocrine disruptors, pollen, chick embryo and silkworm pupa. x of these items were between 1.00 and 2.00, with Sum≥50.00% of full score, R between 0.00% and 16.67%. Experts considered these items were important partner treatment of precocious puberty.Conclusions Conclusions of PART 11. Location of Precocious Puberty:Liver and kidney meridian were the most two reaching meridians for all the traditional Chinese drugs treating precocious puberty. Conjecturing from this phenomenon, the location of precocious puberty is mainly in liver and kidney.2. TCM Mechanism:The nature of 67.75% of all traditional Chinese drugs treating precocious puberty was cold and cool. This phenomenon is consistent with TCM mechanism that the majority patients of precocious puberty are prone to fire-heat, so excess syndrome of precocious puberty is syndrome of depressed liver qi transforming into fire, or syndrome of endoretention of damp heat, and deficiency syndrome of precocious puberty is syndrome of hyperactivity of fire due to yin deficiency.3. Treatment Based on Syndrome Differentiation:SyndromeⅠexisted as the most common and main syndrome in syndrome differentiation of precocious puberty, then next comes Combined Syndrome, SyndromeⅡand SyndromeⅢranked in order.4. Therapeutic Principle:Heat-clearing drugs and deficiency-reinforcing drugs were the most common used kind of drugs when treating precocious puberty, especially heat-clearing and fire-purging drugs, heat-clearing and dampness-drying drugs, heat-clearing and blood-cooling drugs and yin-reinforcing drugs. These 4 kinds of drugs occupied 46.01% in total, and reflected that nourishing yin and purging fire is the main therapeutic principle to treat precocious puberty. Sweet taste and bitter taste were dominant tastes in all the treating drugs, occupied 66.28% in total. Sweet taste could reinforce deficiency, and bitter taste could clear excess, which is consistent with that the main therapeutic principle of this disease is nourishing yin and purging fire.5. Prescription and Traditional Chinese Drugs:Traditional Chinese drugs with high frequency for treating SyndromeⅠwere similar to the composition of "Zhi Bai Di Huang Wan", with coincidence rate of 62.50%. This results demonstrates that "Zhi Bai Di Huang Wan" is the major prescription for treating SyndromeⅠ. Likewise, traditional Chinese drugs with high frequency for treating SyndromeⅡwere similar to the composition of "Long Dan Xie Gan Tang", with coincidence rate of 50.00%. This result demonstrates that "Long Dan Xie Gan Tang" is the major prescription for treating SyndromeⅡ.Conclusions of PART 21. Investigation on TCM Symptoms and Manifestation of Tongue and Pulse:In 56 TCM investigated symptoms, enjoying fat and sugar was the most common in clinic and with the heaviest synthetic degree. It suggests that the onset of precocious puberty and the development of positive symptoms may be possibly relevant to excessive intake of foods with high fat, high protein and high sugar.In survey of diet structure, the proportion of meats in precocious puberty group was 30%±21%, and that in early puberty group was 40%±28%. Both proportions were about more than 1/3. Red tip of tongue was the most common tongue manifestation and more than half of surveyed girls had thick or greasy fur. This result demonstrates that the constitution or syndrome of precocious puberty patients is prone to heat property. The thick or greasy fur is one of the manifestations due to relatively higher proportion of meats in diet.2. Syndrome Differentiation Diagnosis:According to average rank, conclusion can be drawn that the most common syndrome in 109 surveyed girls was SyndromeⅠ, and next was SyndromeⅡ, but the rank of SyndromeⅢobviously lower than else syndromes, suggesting it isn't the clinically common syndrome. The status of Combined Syndrome shouldn't be ignored.Conclusions of PART 3Following principles of Delphi method, retrieved questionnaires were statistically analyzed and appraised, including diagnosis, main points of syndrome differentiation, therapeutic principle, major prescriptions, and major traditional Chinese drugs, ready made patent drugs, methods of western medicine, other traditional therapy and partner treatment. First draft of "TCM guidelines of diagnosis and treatment for precocious puberty" will be shaped through repeated communication, feedback and modification.1. Main Points of Syndrome DifferentiationMajority of experts agreed that items about developmental conditions of first and second sex characters were significant to syndrome differentiation in all 3 syndromes, especially these 3 items, including mammoplasia, penis thickening and enlargement of testis.①TCM items considered very important in differentiation of SyndromeⅠby majority of experts were:burning sensation of five centres, tidal fever, night sweat, red tongue, few fur or exfoliative fur, and frequent pulse.②TCM items considered very important in differentiation of SyndromeⅡby majority of experts were:agitation and tantrum, oppression and gas pain in chest, spargosis and pain, less urine, bitter taste in mouth, red tongue, and string-like pulse.③TCM items considered very important in differentiation of SyndromeⅢby experts were:sticking and greasy in mouth, weary and heavy limbs, polyphagia of fat and sugar, greasy fur, slippery pulse.2. Prescriptions for First Choice The prescriptions for first choice in treating 3 syndromes were:"Zhi Bai Di Huang Wan Jia Jian" for SyndromeⅠ, "Dan Zhi Xiao Yao San Jia Jian" for SyndromeⅡ, "Er Chen Tang combined with Zhi Bai Di Huang Wan Jia Jian" for SyndromeⅢ.